{ "Contributors": [ "BC4-chem" ], "Source": [ "BC4-Chem" ], "URL": [ "https://github.com/cambridgeltl/MTL-Bioinformatics-2016/tree/master/data" ], "Categories": [ "Named Entity Recognition" ], "Definition": [ "Given a sentence, you need to recognize the name of the chemical. There might be several correct answers. If it does not exist, you need to output \"There is no related enetity.\"." ], "Reasoning": [], "Input_language": [ "English" ], "Output_language": [ "English" ], "Instruction_language": [ "English" ], "Domains": [ "Medical Knowledge" ], "Positive Examples": [], "Negative Examples": [], "Instances": [ { "input": "DPP6 as a candidate gene for neuroleptic - induced tardive dyskinesia.", "output": "There is no related enetity." }, { "input": "We implemented a two - step approach to detect potential predictor gene variants for neuroleptic - induced tardive dyskinesia ( TD ) in schizophrenic subjects.", "output": "There is no related enetity." }, { "input": "First, we screened associations by using a genome - wide ( Illumina HumanHapCNV370 ) SNP array in 61 Japanese schizophrenia patients with treatment - resistant TD and 61 Japanese schizophrenia patients without TD.", "output": "There is no related enetity." }, { "input": "Next, we performed a replication analysis in 36 treatment - resistant TD and 138 non - TD subjects.", "output": "There is no related enetity." }, { "input": "An association of an SNP in the DPP6 ( dipeptidyl peptidase - like protein - 6 ) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample ( allelic P = 0. 008 in the replication sample, allelic P = 4. 6 x 10 ( - 6 ), odds ratio 2. 32 in the combined sample ).", "output": "There is no related enetity." }, { "input": "The SNP is located in intron - 1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex.", "output": "There is no related enetity." }, { "input": "Chronic administration of haloperidol increased Dpp6 expression in mouse brains.", "output": "haloperidol." }, { "input": "DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons.", "output": "There is no related enetity." }, { "input": "The findings of this study indicate that an altered response of Kv4 / DPP6 to long - term neuroleptic administration is involved in neuroleptic - induced TD.", "output": "There is no related enetity." }, { "input": "Nanosilver effects on growth parameters in experimental aflatoxicosis in broiler chickens.", "output": "There is no related enetity." }, { "input": "Aflatoxicosis is a cause of economic losses in broiler production.", "output": "There is no related enetity." }, { "input": "In this study, the effect of one commercial nanocompound, Nanocid ( Nano Nasb Pars Co., Iran ) was evaluated in reduction of aflatoxin effects on the growth and performance indices in broiler chickens suffering from experimental aflatoxicosis.", "output": "aflatoxin." }, { "input": "For this, a total of 300 one - day - old broiler chicks ( Ross strain ) were randomly divided into 4 groups with 3 replicates of 15 chicks in each separated pen during the 28 - day experiment.", "output": "There is no related enetity." }, { "input": "Treatment groups including group A: chickens fed basal diet, group B: chickens fed 3 ppm productive aflatoxin in basal diet, group C: chickens fed basal diet plus 2500 ppm Nanocid, and group D: chickens fed 3 ppm productive aflatoxin and 2500 ppm Nanocid, in basal diet.", "output": "aflatoxin, aflatoxin." }, { "input": "Data on body weight, body weight gain ( BWG ), feed intake, and feed conversion ratio ( FCR ) were recorded at weekly intervals.", "output": "There is no related enetity." }, { "input": "Also cumulative data were assessed.", "output": "There is no related enetity." }, { "input": "Results showed, although supplement of Nanocid to conventional diet had no effect on performance but addition of Nanocid to diet containing 3 ppm aflatoxin increased significantly the cumulative BWG, cumulative feed consumption and decreased FCR in the last 2 weeks of experimental period.", "output": "aflatoxin." }, { "input": "The improvement in these performance indices by supplement of Nanocid to diet containing aflatoxin showed the ability of Nanocid to diminish the inhibitory effects of aflatoxin.", "output": "aflatoxin, aflatoxin." }, { "input": "The influence of the intensity of smoking and years of work in the metallurgy on pro - oxidant / antioxidant balance in the blood of smelters.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate the effect of cigarette smoking and occupational exposure to heavy metals on the degree of pro - oxidant / antioxidant imbalance in smelters.", "output": "There is no related enetity." }, { "input": "The investigations were performed on the blood and urine of 400 subjects: 300 male copper smelters and 100 nonexposed male subjects.", "output": "copper." }, { "input": "Biological material was divided into three groups: nonsmokers, those who smoked less than 20 cigarettes a day and those who smoked more than 20 cigarettes a day.", "output": "There is no related enetity." }, { "input": "The results showed a significant increase in the concentration of lead, cadmium and arsenic in the blood and urine of smelters, while smoking more than 20 cigarettes a day caused a further increase in the concentration of these metals.", "output": "cadmium, arsenic." }, { "input": "The level of malondialdehyde was approximately twofold higher in the plasma of the smelters compared to the control group.", "output": "malondialdehyde." }, { "input": "We have observed a disturbance in the level of antioxidants in erythrocyte lysate manifested by an increase in metallothionein and glutathione concentrations as well as superoxide dismutase and glutathione peroxidase activities and the decrease in glutathione S - transferase activity.", "output": "glutathione, superoxide, glutathione, glutathione, S." }, { "input": "Cigarette smoking, years of work in metallurgy and age of smelters were additional factors significantly affecting the pro - oxidant / antioxidant balance.", "output": "There is no related enetity." }, { "input": "Mercury induces the expression of cyclooxygenase - 2 and inducible nitric oxide synthase.", "output": "Mercury, nitric oxide." }, { "input": "Nuclear factor - kappa B ( NF - kappa B ) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses.", "output": "There is no related enetity." }, { "input": "NF - kappa B activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase - 2 ( COX - 2 ), and inducible nitric oxide synthase ( iNOS ).", "output": "nitric oxide." }, { "input": "The divalent heavy metal mercury has been used for thousands of years.", "output": "mercury." }, { "input": "Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world.", "output": "mercury." }, { "input": "However, the underlying toxic mechanism is not clearly identified.", "output": "There is no related enetity." }, { "input": "Here, we report biochemical evidence that mercury alone induces NF - kappa B activation, resulting in the induced expression of COX - 2 and iNOS.", "output": "mercury." }, { "input": "The results suggest that mercury can induce inflammatory diseases by lowering host defense.", "output": "mercury." }, { "input": "Toxic effects of chromium on tannery workers at Sialkot ( Pakistan ).", "output": "chromium." }, { "input": "Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure.", "output": "Chromium." }, { "input": "Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan.", "output": "chromium." }, { "input": "A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included.", "output": "There is no related enetity." }, { "input": "Blood complete counts, high - sensitive C - reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures.", "output": "malondialdehyde." }, { "input": "Chromium levels in blood ( BCr ) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst - 200.", "output": "Chromium, graphite." }, { "input": "Results revealed that all the workers were male with average age of 33 years and 15 ( 13 % ) had skin rashes, 14 ( 12 % ) had chronic bronchitis, 10 ( 8 % ) had gastritis and 4 ( 3 % ) conjunctivitis.", "output": "There is no related enetity." }, { "input": "The tannery workers had significantly raised median ( interquartile range ) of BCr 569 ( 377 - 726 ) nmol / L as compared to 318 ( 245 - 397 ) nmol / L in the control ( p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Sixty - five ( 54 % ) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry.", "output": "There is no related enetity." }, { "input": "The urinary chromium excretion was significantly high in workers 131 ( 46 - 312 ) nmol / L as compared to 13 ( 3 - 26 ) nmol / L in controls ( p < 0. 01 ).", "output": "chromium." }, { "input": "The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems.", "output": "There is no related enetity." }, { "input": "It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot.", "output": "chromium." }, { "input": "They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.", "output": "chromium." }, { "input": "Fish, contaminants and human health: quantifying and weighing benefits and risks.", "output": "There is no related enetity." }, { "input": "This paper describes a quantitative risk - benefit assessment of fish consumption.", "output": "There is no related enetity." }, { "input": "We compare the net health effect expressed in DALYs of two scenarios.", "output": "There is no related enetity." }, { "input": "The reference scenario is the current fish intake of the Dutch population, which is less than what is recommended by the health authorities.", "output": "There is no related enetity." }, { "input": "The alternative scenario describes the health effects if the population consumes 200g of fish per week, which is close to the recommendation.", "output": "There is no related enetity." }, { "input": "All health effects due to fish consumption for which there is convincing evidence are incorporated in the assessment.", "output": "There is no related enetity." }, { "input": "The QALIBRA software ( www. qalibra. eu ) is used to simulate the two scenarios.", "output": "There is no related enetity." }, { "input": "The results show there is a net benefit for the population if it consumes 200g of fish each week.", "output": "There is no related enetity." }, { "input": "Protective effect of honey against cigarette smoke induced - impaired sexual behavior and fertility of male rats.", "output": "There is no related enetity." }, { "input": "Cigarette smoking is associated with sexual dysfunction and impaired fertility in males.", "output": "There is no related enetity." }, { "input": "The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke ( CS ) on sexual behavior and fertility of male rats.", "output": "There is no related enetity." }, { "input": "Thirty - two adult Sprague - Dawley rats were randomly divided into four groups ( 8 rats / group ) as control, honey ( H ), CS and H plus CS ( H + CS ) groups.", "output": "There is no related enetity." }, { "input": "Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey ( 1. 2 g / kg body weight / day ) by oral gavage.", "output": "There is no related enetity." }, { "input": "Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times / day.", "output": "There is no related enetity." }, { "input": "From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies.", "output": "There is no related enetity." }, { "input": "Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS.", "output": "There is no related enetity." }, { "input": "Thus, honey has a protective effect against CS - induced impaired sexual behavior and fertility in male rats.", "output": "There is no related enetity." }, { "input": "Allelopathic activity studies of Mikania scandens.", "output": "There is no related enetity." }, { "input": "Preliminary investigation of a number of plant extracts for allelopathic activity using seed germination inhibition bioassay showed a promising activity of the water extract of the aerial parts of Mikania scandens.", "output": "There is no related enetity." }, { "input": "Activity - guided fractionation of the M. scandens extract led to the isolation of the highly allelopathic active compound mikanolide, with minimum inhibitory concentration of 0. 083 micro M mL ( - 1 ).", "output": "mikanolide." }, { "input": "As M. scandens is a highly abundant invasive plant in Sri Lanka and other South Asian countries, this plant could be developed as an environment friendly natural herbicide, either in crude form as shredded plant material or as pure mikanolide, which is the major constituent ( ~ 0. 02 % ) in the plant.", "output": "mikanolide." }, { "input": "Detection of polycyclic aromatic hydrocarbons in different types of processed foods.", "output": "polycyclic aromatic hydrocarbons." }, { "input": "Polycyclic aromatic hydrocarbons ( PCAHs ), particularly those with a high molecular weight, have been classified as probable carcinogens to humans.", "output": "Polycyclic aromatic hydrocarbons, PCAHs." }, { "input": "The aim of the present study is to determine the levels of PCAHs in samples of meat, fish, chicken, fried potato, and toasted bread, which will be thermally processed using conventional and microwave ovens.", "output": "PCAHs." }, { "input": "Different samples will be collected and analyzed for five PCAHs including pyrene, benzo ( a ) anthracene, benzo ( e ) pyrene, benzoflouroanthene, and benzo ( a ) pyrene.", "output": "PCAHs, pyrene, benzo ( a ) anthracene, benzo ( e ) pyrene, benzoflouroanthene, benzo ( a ) pyrene." }, { "input": "The analytical method involves saponification with methanolic potassium hydroxide, extraction with cyclohexane, and determination by high - performance liquid chromatography.", "output": "methanolic potassium hydroxide, cyclohexane." }, { "input": "The obtained results showed that there is a variation in the detected PCAHs in different foodstuffs.", "output": "PCAHs." }, { "input": "Fried potato processed by conventional oven or microwave oven showed none of the selected studied PCAHs.", "output": "PCAHs." }, { "input": "It was found that, chicken showed higher content levels of total PCAHs than the meat and fish.", "output": "PCAHs." }, { "input": "Data are the highest mean concentrations of fluoranthene and benzo ( a ) pyrene but within low limit.", "output": "fluoranthene, benzo ( a ) pyrene." }, { "input": "The obtained results were compared with international permissible levels to avoid pollution, which may cause hazardous effects on individual and society.", "output": "There is no related enetity." }, { "input": "Effect of Thiovit ( R ) Jet on the structure of thoracic microtrichia / trichomes in Drosophila melanogaster.", "output": "Thiovit." }, { "input": "Widely used fungicides and pesticides are known to have profound effect on several nontarget organisms, which is a cause of concern.", "output": "There is no related enetity." }, { "input": "The present study aims to demonstrate the effect of a fungicide, Thiovit ( (R) ) Jet on the structure of epidermal microtrichia ( trichome ) of the dorsal thorax in Drosophila melanogaster.", "output": "Thiovit." }, { "input": "External morphology and structural variations of thoracic appendages have been extensively studied using scanning electron microscope from flies treated with different concentrations of Thiovit Jet ( 20, 30, 40 or 200 mu g / ml ).", "output": "Thiovit." }, { "input": "Similar to the effect of other fungicides like captan and captafol which are reported to produce somatic mutations in the same organism, the present study successfully demonstrates variation in the trichome / microtrichia structure of the dorsal thorax of D. melanogaster.", "output": "captan, captafol." }, { "input": "Structural variations were observed to be associated with different concentrations of Thiovit Jet ( 30, 40 and 200 mu g / ml ), but the maximum notable change was found with 40 mu g / ml treatment.", "output": "Thiovit." }, { "input": "The gross abnormality in the trichome structure may be due to mutation in proteins associated with normal cuticular deposition.", "output": "There is no related enetity." }, { "input": "Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants.", "output": "There is no related enetity." }, { "input": "Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments.", "output": "There is no related enetity." }, { "input": "A large number of plants in Morocco were used in folk medicine to treat immune - related disorders.", "output": "There is no related enetity." }, { "input": "The objective of this study is to evaluate the immunomodulatory activity of protein extracts ( PEs ) of 14 Moroccan medicinal plants.", "output": "There is no related enetity." }, { "input": "This activity was tested on the proliferation of immune cells.", "output": "There is no related enetity." }, { "input": "The prepared total and PEs of the plant samples were tested using MTT ( 3 - ( 4, 5 - dimethylthiazol - 2yl ) - 2, 5 - diphenyltetrazolium bromide ) assay on the splenocytes with or without stimulation by concanavalin - A ( Con - A ), a mitogenic agent used as positive control.", "output": "MTT, 3 - ( 4 , 5 - dimethylthiazol - 2yl ) - 2 , 5 - diphenyltetrazolium bromide." }, { "input": "The results of this study indicated different activity spectra.", "output": "There is no related enetity." }, { "input": "Three groups of activities were observed.", "output": "There is no related enetity." }, { "input": "The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity.", "output": "There is no related enetity." }, { "input": "The second group that showed a significant immunostimulatory activity was represented by Aristolochia longa, Datura stramonium, Marrubium vulgare, Sinapis nigra, Delphynium staphysagria, Lepidium sativum, Ammi visnaga and Tetraclinis articulata.", "output": "There is no related enetity." }, { "input": "The rest of the plant extracts did not alter the proliferation induced by Con - A.", "output": "There is no related enetity." }, { "input": "This result was more important for the PE than for the total extract.", "output": "There is no related enetity." }, { "input": "In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use.", "output": "There is no related enetity." }, { "input": "The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy.", "output": "There is no related enetity." }, { "input": "Determination of three steroidal saponins from Ophiopogon japonicus ( Liliaceae ) via high - performance liquid chromatography with mass spectrometry.", "output": "steroidal saponins." }, { "input": "A simple and accurate analytical method was developed for simultaneous quantification of three steroidal saponins in the roots of Ophiopogon japonicus via high - performance liquid chromatography ( HPLC ) with mass spectrometry ( MS ) in this study.", "output": "steroidal saponins." }, { "input": "Separation was performed on a Tigerkin C ( 18 ) column and detection was performed by mass spectrometry.", "output": "There is no related enetity." }, { "input": "A mobile phase consisted of 0. 02 % formic acid in water ( v / v ) and 0. 02 % formic acid in acetonitrile ( v / v ) was used with a flow rate of 0. 5 mL min ( - 1 ).", "output": "formic acid, formic acid, acetonitrile." }, { "input": "The quantitative HPLC - MS method was validated for linearity, precision, repeatability, stability, recovery, limits of detection and quantification.", "output": "There is no related enetity." }, { "input": "This developed method provides good linearity ( r > 0. 9993 ), intra - and inter - day precisions ( RSD < 4. 18 % ), repeatability ( RSD < 5. 05 % ), stability ( RSD < 2. 08 % ) and recovery ( 93. 82 - 102. 84 % ) for three steroidal saponins.", "output": "steroidal saponins." }, { "input": "It could be considered as a suitable quality control method for O. japonicus.", "output": "There is no related enetity." }, { "input": "Three new steroidal glycosides from roots of Reineckia carnea.", "output": "steroidal glycosides." }, { "input": "Two new spirostanols and a new furostanol, reinocarnoside A ( 1 ), B ( 2 ) and C ( 3 ), were isolated from the roots of Reineckia carnea, together with two known compounds, ( 25S ) - 1 beta, 3 beta, 4 beta - trihydroxyspirostan - 5 beta - yl - O - beta - D - glucopyranoside ( 4 ), kitigenin - 5 beta - O - beta - D - glucopyranoside ( 5 ).", "output": "spirostanols, furostanol, reinocarnoside A ( 1 ) , B ( 2 ) and C ( 3 ), ( 25S ) - 1 beta , 3 beta , 4 beta - trihydroxyspirostan - 5 beta - yl - O - beta - D - glucopyranoside, kitigenin - 5 beta - O - beta - D - glucopyranoside." }, { "input": "The structures of three new compounds were elucidated by spectroscopic methods including 1 - D NMR, 2 - D NMR and MS spectrums, and their anticancer activities were evaluated by MTT method.", "output": "MTT." }, { "input": "Seasonal variation in biomarkers in blue mussel ( Mytilus edulis ), Icelandic scallop ( Chlamys islandica ) and Atlantic cod ( Gadus morhua ): implications for environmental monitoring in the Barents Sea.", "output": "There is no related enetity." }, { "input": "In the Barents Sea, the limited data on biological relevant indicators and their responses to various anthropogenic stressors have hindered the development of a consistent scientific basis for selecting indicator species and developing practical procedures for environmental monitoring.", "output": "There is no related enetity." }, { "input": "Accordingly, the main aim of the present study was to develop a common set of baseline values for contaminants and biomarkers in three species, and to identify their strengths and limitations in monitoring of the Barents Sea.", "output": "There is no related enetity." }, { "input": "Blue mussel ( Mytilus edulis ), Icelandic scallop ( Chlamys islandica ) and Atlantic cod ( Gadus morhua ) were sampled from a north Norwegian fjord in March, June, September and December 2010.", "output": "There is no related enetity." }, { "input": "Digestive glands from the bivalve species and liver from Atlantic cod were analysed for biomarkers of oxidative stress ( catalase [ CAT ], glutathione peroxidase [ GPX ], glutathione - S - transferase activities [ GST ], lipid peroxidation as thiobarbituric reactive substances [ TBARS ] and total oxyradical scavenging capacity [ TOSC ] ), biotransformation ( ethoxyresorufine - O - deethylase activity [ EROD ] ) and general stress ( lysosomal membrane stability [ LMS ] ).", "output": "glutathione, glutathione, S, thiobarbituric, ethoxyresorufine, O." }, { "input": "Concentrations of polycyclic aromatic hydrocarbons ( PAHs ) and metals in the bivalves and PAH metabolites in fish bile were quantified.", "output": "polycyclic aromatic hydrocarbons, PAHs, PAH." }, { "input": "Finally, energy reserves ( total lipids, proteins and carbohydrates ) and electron transport system ( ETS ) activity in the digestive gland of the bivalves and liver of Atlantic cod provided background information for reproductive cycle and general physiological status of the organisms.", "output": "There is no related enetity." }, { "input": "Blue mussel and Icelandic scallop showed very similar trends in biological cycle, biomarker expression and seasonality.", "output": "There is no related enetity." }, { "input": "Biomarker baselines in Atlantic cod showed weaker seasonal variability.", "output": "There is no related enetity." }, { "input": "However, important biological events may have been undetected due to the large time intervals between sampling occasions.", "output": "There is no related enetity." }, { "input": "Physiological biomarkers such as energy reserves and ETS activity were recommended as complementary parameters to the commonly used stress biomarkers, as they provided valuable information on the physiological status of the studied organisms.", "output": "There is no related enetity." }, { "input": "Interpretation of the seasonality in oxidative stress biomarkers was in general difficult but TOSC and lipid peroxidation were preferred over the antioxidant enzyme activities.", "output": "There is no related enetity." }, { "input": "This study is the first reporting seasonal baseline in these three species in a sub - Arctic location.", "output": "There is no related enetity." }, { "input": "Overall, the Icelandic scallop was considered the most adequate organism for environmental monitoring in the Barents Sea due to the interpretability of the biomarker data as well as its abundance, ease to handle and wide distribution from the southern Barents Sea to Svalbard.", "output": "There is no related enetity." }, { "input": "Drought episode modulates the response of river biofilms to triclosan.", "output": "triclosan." }, { "input": "The consequences of global change on rivers include altered flow regime, and entrance of compounds that may be toxic to biota.", "output": "There is no related enetity." }, { "input": "When water is scarce, a reduced dilution capacity may amplify the effects of chemical pollution.", "output": "There is no related enetity." }, { "input": "Therefore, studying the response of natural communities to compromised water flow and to toxicants is critical for assessing how global change may affect river ecosystems.", "output": "There is no related enetity." }, { "input": "This work aims to investigate how an episode of drought might influence the response of river biofilms to pulses of triclosan ( TCS ).", "output": "triclosan, TCS." }, { "input": "The objectives were to assess the separate and combined effects of simulated drought ( achieved through drastic flow alteration ) and of TCS exposure on biofilms growing in artificial channels.", "output": "TCS." }, { "input": "Thus, three - week - old biofilms were studied under four conditions: Control ( normal water flow ); Simulated Drought ( 1 week reduced flow + 2 days interrupted flow ); TCS only ( normal water flow plus a 48 - h pulse of TCS ); and Simulated Drought + TCS.", "output": "TCS, TCS, TCS." }, { "input": "All channels were then left for 2 weeks under steady flow conditions, and their responses and recovery were studied.", "output": "There is no related enetity." }, { "input": "Several descriptors of biofilms were analyzed before and after each step.", "output": "There is no related enetity." }, { "input": "Flow reduction and subsequent interruption were found to provoke an increase in extracellular phosphatase activity, bacterial mortality and green algae biomass.", "output": "There is no related enetity." }, { "input": "The TCS pulses severely affected biofilms: they drastically reduced photosynthetic efficiency, the viability of bacteria and diatoms, and phosphate uptake.", "output": "TCS, phosphate." }, { "input": "Latent consequences evidenced significant combined effects caused by the two stressors.", "output": "There is no related enetity." }, { "input": "The biofilms exposed only to TCS recovered far better than those subjected to both altered flow and subsequent TCS exposure: the latter suffered more persistent consequences, indicating that simulated drought amplified the toxicity of this compound.", "output": "TCS, TCS." }, { "input": "This finding has implications for river ecosystems, as it suggests that the toxicity of pollutants to biofilms may be exacerbated following a drought.", "output": "There is no related enetity." }, { "input": "Determination of chemical composition and genotoxic effects of essential oil obtained from Nepeta nuda on Zea mays seedlings.", "output": "There is no related enetity." }, { "input": "We aimed to determine the genotoxic potential of essential oil ( EO ) obtained from Nepeta nuda.", "output": "There is no related enetity." }, { "input": "The chemical content of EO was measured via gas chromatography / mass spectrometry.", "output": "There is no related enetity." }, { "input": "The most abundant contents were 4a alpha, 7 beta, 7a alpha - nepetalactone ( 18. 10 % ), germacrene ( 15. 68 % ) and elemol ( 14. 38 % ).", "output": "4a alpha , 7 beta , 7a alpha - nepetalactone, germacrene, elemol." }, { "input": "For genotoxic effects of EO, Zea mays ' seeds were exposed to four different concentrations of this oil.", "output": "There is no related enetity." }, { "input": "Inhibition of root and stem growth were observed with an increase in EO concentrations.", "output": "There is no related enetity." }, { "input": "Randomly amplified polymorphic DNA ( RAPD ) method was used to determine the genotoxic effects of EO.", "output": "There is no related enetity." }, { "input": "Some changes occurred in RAPD profiles of germinated EO - treated seeds.", "output": "There is no related enetity." }, { "input": "Even though total soluble protein quantity vary, the data observed from the protein profiles of sodium dodecyl sulphate - polyacrylamide gel electrophoresis ( SDS - PAGE ) showed that there was a little differentiation between band profiles of treated samples and control group.", "output": "sodium dodecyl sulphate, polyacrylamide, SDS." }, { "input": "We concluded that the basis of interactions between plants, like allelopathy, may be related with genotoxic effects of EO.", "output": "There is no related enetity." }, { "input": "Lethality, accumulation and toxicokinetics of aluminum in some tissues of male albino rats.", "output": "aluminum." }, { "input": "In the present work, the lethality percentiles including median lethal doses ( LD50 ), accumulation, distribution and toxicokinetics of aluminum in the liver, kidney, intestine, brain and serum of male albino rats, following a single oral administration were studied throughout 1, 3, 7, 14 and 28 days.", "output": "aluminum." }, { "input": "The estimated LD50 at 24 h was 3. 45 g Al / kg body weight ( b. wt. ).", "output": "Al." }, { "input": "The utilized dose of Al was 1 / 50 LD50 ( 0. 07 g Al / kg b. wt. ).", "output": "Al, Al." }, { "input": "Aluminum residues, in Al - treated rats, were significantly decreased in response to the experimental periods and were negatively correlated with time.", "output": "Aluminum, Al." }, { "input": "In addition, the hepatic, renal, intestinal, brain and serum Al contents were significantly higher than the corresponding controls at all experimental periods, except the brain that showed significant depletion when compared with its corresponding control after 28 days.", "output": "Al." }, { "input": "Kinetically, the highest average of Al area under concentration - time curves ( AUCtotal, mu g / g day ) and area under moment concentration - time curves ( AUMCtotal, micro g / g day ( 2 ) ) recorded in the brain followed by kidney, serum, intestine and liver.", "output": "Al." }, { "input": "The longest elimination half - life time ( t 1 / 2, day ) and the mean residence time ( MRT, day ) were recorded in the brain followed by the liver, kidney, serum and intestine.", "output": "There is no related enetity." }, { "input": "On the other hand, the slowest clearance rates ( Cls, L / day ) of Al, in order, were recorded in brain, kidney, serum, intestine and the liver.", "output": "There is no related enetity." }, { "input": "The elimination rate constant ( Lz, day ( - ) ( 1 ) ) of Al from the brain was less than that in the intestine and serum was less than that in the liver and kidney.", "output": "Al." }, { "input": "The computed maximum concentrations ( C max ) of Al in the intestine > kidney > serum > brain > liver were recorded after 3, 3. 8, 2. 2, 5. 4 and 3. 8 days, respectively.", "output": "Al." }, { "input": "The computed starting concentration ( C 0, mu g ) of Al in serum was higher than its level in the intestine followed by the brain, kidney and liver.", "output": "Al." }, { "input": "RETRACTED: Biochemical changes in the Beluga Huso huso exposed to acute crude diesel oil.", "output": "There is no related enetity." }, { "input": "RETRACTED.", "output": "There is no related enetity." }, { "input": "Potential tumor - suppressive role of monoglyceride lipase in human colorectal cancer.", "output": "monoglyceride." }, { "input": "Human monoglyceride lipase ( MGL ) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy.", "output": "monoglyceride." }, { "input": "In this study, we investigated the regulation and function of MGL in human cancer ( s ) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers.", "output": "There is no related enetity." }, { "input": "Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells.", "output": "There is no related enetity." }, { "input": "MGL was found to reside in the core surface of a cellular organelle named ' lipid body '.", "output": "There is no related enetity." }, { "input": "Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol ( 3, 4, 5 ) P3, phosphoinositol ( 3, 5 ) P2, phosphoinositol ( 3, 4 ) P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI ( 3, 4, 5 ) P3 was found to be the strongest.", "output": "phosphatidic acid, phosphoinositol ( 3 , 4 , 5 ) P3, phosphoinositol ( 3 , 5 ) P2, phosphoinositol ( 3 , 4 ) P2, phosphoinositides, phosphoinositides, PI ( 3 , 4 , 5 ) P3." }, { "input": "In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation.", "output": "There is no related enetity." }, { "input": "Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol - 3 kinase / Akt signaling and tumor cell growth.", "output": "phosphatidylinositol." }, { "input": "Chemical constituents of the hemiparasitic plant Phoradendron brachystachyum DC Nutt ( Viscaceae ).", "output": "There is no related enetity." }, { "input": "Phoradendron brachystachyum is a hemiparasitic plant widely distributed in M e xico that belongs to the Viscaceae family.", "output": "There is no related enetity." }, { "input": "It has been commonly used in folk medicine as a substitute for the European mistletoe.", "output": "There is no related enetity." }, { "input": "In this chemical study, morolic acid was isolated as the major component ( 47. 54 % of the total composition of acetone extract ) of this plant.", "output": "morolic acid, acetone." }, { "input": "In addition, 19 known compounds were identified: beta - sitosteryl and stigmasteryl linoleates, beta - sitosterol, stigmasterol, triacontanol, squalene, alpha - and beta - amyrin, lupeol, lupenone, betulin aldehyde, betulon aldehyde, oleanolic aldehyde, betulinic acid, betulonic acid, moronic acid, morolic acid, oleanolic acid, flavonoids acacetin and acacetin 7 - methyl ether.", "output": "beta - sitosteryl and stigmasteryl linoleates, beta - sitosterol, stigmasterol, triacontanol, squalene , alpha - and beta - amyrin, lupeol, lupenone, betulin aldehyde, betulon aldehyde, oleanolic aldehyde, betulinic acid, betulonic acid, moronic acid, morolic acid, oleanolic acid, flavonoids, acacetin, acacetin 7 - methyl ether." }, { "input": "There have been no previous reports in the literature on the chemical composition of this potential natural source of hypoglycaemic and antihypertensive compounds.", "output": "There is no related enetity." }, { "input": "MNK kinases facilitate c - myc IRES activity in rapamycin - treated multiple myeloma cells.", "output": "rapamycin." }, { "input": "When mTOR inhibitor rapalogs prevent cap - dependent translation of cell - cycle proteins like c - myc, continuing tumor cell growth depends on cap - independent translation, which is mediated by internal ribosome entry sites ( IRESes ) located in the 5 ' - UTR ( untranslated region ) of transcripts.", "output": "There is no related enetity." }, { "input": "To investigate if rapalog - induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma ( MM ) cells.", "output": "There is no related enetity." }, { "input": "Rapamycin ( RAP ) - activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen - activated protein kinase - dependent mechanism.", "output": "Rapamycin, RAP." }, { "input": "Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog - induced upregulation of c - myc IRES activity.", "output": "There is no related enetity." }, { "input": "Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated.", "output": "RAP." }, { "input": "In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation.", "output": "There is no related enetity." }, { "input": "In a RAP - resistant MM cell lines as well as a resistant primary MM specimen, co - exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP - induced cytoreduction.", "output": "RAP, RAP." }, { "input": "Studies in MNK - null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP - induced myc IRES stimulation.", "output": "RAP." }, { "input": "These results indicate that MNK kinase activity has a critical role in the fail - safe mechanism of IRES - dependent translation when mTOR is inhibited.", "output": "There is no related enetity." }, { "input": "As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors.", "output": "RAP." }, { "input": "Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug - resistant non - small cell lung cancer cells.", "output": "There is no related enetity." }, { "input": "The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers.", "output": "There is no related enetity." }, { "input": "Previously, we demonstrated acquisition of epithelial - mesenchymal transition, a feature highly reminiscent of cancer stem - like cells, in gefitinib - resistant A549 cells ( A549 / GR ).", "output": "gefitinib." }, { "input": "Here, we show that A549 / GR cells contain a high proportion of CXCR4 + cells that are responsible for having high potential of self - renewal activity in vitro and tumorigenicity in vivo.", "output": "There is no related enetity." }, { "input": "A549 / GR cells exhibited strong sphere - forming activity and high CXCR4 expression and SDF - 1 alpha secretion compared with parent cells.", "output": "There is no related enetity." }, { "input": "Pharmacological inhibition ( AMD3100 ) and / or siRNA transfection targeting CXCR4 significantly suppressed sphere - forming activity in A549 and A549 / GR cells, and in various non - small cell lung cancer ( NSCLC ) cell lines.", "output": "There is no related enetity." }, { "input": "A549 / GR cells showed enhanced Akt, mTOR and STAT3 ( Y705 ) phosphorylation.", "output": "There is no related enetity." }, { "input": "Pharmacological inhibition of phosphatidyl inositol 3 - kinase or transfection with wild - type PTEN suppressed phosphorylation of Akt, mTOR and STAT3 ( Y705 ), sphere formation, and CXCR4 expression in A549 / GR cells, whereas mutant PTEN enhanced these events.", "output": "phosphatidyl inositol." }, { "input": "Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere formation, but not CXCR4 expression, indicating that STAT3 is a downstream effector of CXCR4 - mediated signaling.", "output": "WP1066." }, { "input": "FACS - sorted CXCR4 + A549 / GR cells formed many large spheres, had self - renewal capacity, demonstrated radiation resistance in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4 - cells.", "output": "There is no related enetity." }, { "input": "Lentiviral - transduction of CXCR4 enhanced sphere formation and tumorigenicity in H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities in A549 / GR cells.", "output": "There is no related enetity." }, { "input": "Our data indicate that CXCR4 + NSCLC cells are strong candidates for tumorigenic stem - like cancer cells that maintain stemness through a CXCR4 - medated STAT3 pathway and provide a potential therapeutic target for eliminating these malignant cells in NSCLC.", "output": "There is no related enetity." }, { "input": "Role of excipients in successful development of self - emulsifying / microemulsifying drug delivery system ( SEDDS / SMEDDS ).", "output": "There is no related enetity." }, { "input": "The oral delivery of hydrophobic drug presents a major challenge because of the low aqueous solubility of such compounds.", "output": "There is no related enetity." }, { "input": "Self - emulsifying / microemulsifying drug delivery system ( SEDDS / SMEDDS ), which are isotropic mixtures of oils, surfactants, solvents and co - solvents / surfactants, can be used for the design of formulations in order to improve the oral absorption of highly lipophilic drug compounds.", "output": "There is no related enetity." }, { "input": "The efficiency of oral absorption of said drug from such type of formulation depends on many formulation - related parameters, such as surfactant concentration, oil / surfactant ratio, polarity of the emulsion, droplet size and charge, all of which in essence determine the self - emulsification ability.", "output": "There is no related enetity." }, { "input": "Thus, only very specific pharmaceutical excipient combinations will lead to efficient self - emulsifying systems.", "output": "There is no related enetity." }, { "input": "With the growing interest in this field, there is an increasing need for guidelines in excipient selection to obtain effective delivery system with improved bioavailability.", "output": "There is no related enetity." }, { "input": "The aim of this review is to present the recent approaches in selecting the most appropriate lipid system ( s ); methods for its characterization and role of various excipients for improved delivery of dosage form.", "output": "There is no related enetity." }, { "input": "Chemical composition and antibacterial activity of the essential oil from Mentha requienii Bentham.", "output": "There is no related enetity." }, { "input": "The chemical composition of essential oil obtained by hydrodistillation of the fresh aerial parts of Mentha requienii Bentham ( Lamiaceae ) collected on the Gennargentu Mountains ( Sardinia, Italy ) has been investigated by gas chromatography and gas chromatography - mass spectrometry.", "output": "There is no related enetity." }, { "input": "The main constituents that resulted were pulegone ( 78 % ), menthone ( 0. 5 % ), isomenthone ( 18 % ), isopulegone ( 1. 3 % ) and limonene ( 1. 76 % ).", "output": "pulegone, menthone, isomenthone, isopulegone, limonene." }, { "input": "In vitro antifungal activity is evaluated in order to identify new means that could be helpful in the prevention of contamination in indoor environments.", "output": "There is no related enetity." }, { "input": "Carbon sources and medium pH affects the growth of Withania somnifera ( L. ) Dunal adventitious roots and withanolide A production.", "output": "Carbon, withanolide A." }, { "input": "This work deals with optimisation of adventitious root suspension culture of Withania somnifera ( L. ) Dunal ( Solanaceae ) for the production of biomass and withanolide A and we investigated the effect of carbon source and the initial medium pH on growth and production of withanolide A in adventitious root cultures of Withania somnifera.", "output": "withanolide A, carbon, withanolide A." }, { "input": "A 2 % sucrose concentration was found to be best for both biomass ( 113. 58 g L ( - 1 ) fresh weight ( FW ) and 11. 33 g L ( - 1 ) dry weight ( DW ) ) and secondary metabolite accumulation ( 8. 93 mg g ( - 1 ) DW ) in the tested range of concentration ( 1 - 8 % ).", "output": "sucrose." }, { "input": "The biomass of adventitious roots was optimal when the initial medium pH was 5. 8 ( 113. 26 g L ( - 1 ) FW and 11. 33 g L ( - 1 ) DW ) but the withanolide A production was highest at the medium pH level of 5. 5 ( 9. 09 mg g ( - 1 ) DW ).", "output": "withanolide A." }, { "input": "Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets.", "output": "nimesulide." }, { "input": "The purpose of this study was to compare the in vitro release and the in vivo pharmacokinetics of bilayer tablets with the conventional dispersible tablets of nimesulide.", "output": "nimesulide." }, { "input": "The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high - performance liquid chromatography - MS / MS.", "output": "nimesulide." }, { "input": "The pharmacokinetic parameters were calculated using a noncompartmental model.", "output": "There is no related enetity." }, { "input": "The bilayer tablets showed a biphasic in vitro release pattern with initial burst release and sustained release following the quasi - Fickian diffusion - based release mechanism.", "output": "There is no related enetity." }, { "input": "The C ( max ), t ( max ), mean residence time ( MRT ), and area under the curve from 0 to 36 h were 10. 8 +/- 4. 2 mu g / mL, 2. 3 +/- 1. 0 h, 6. 7 +/- 2. 1 h, 81. 5 +/- 26. 7 mu g. h / mL for the bilayer tablets and 14. 8 +/- 5. 8 mu g / mL, 2. 7 +/- 0. 8 h, 5. 6 +/- 0. 9 h, 95. 4 +/- 44. 2 mu g. h / mL for the dispersible tablets.", "output": "There is no related enetity." }, { "input": "Compared with the dispersible tablets, the bilayer tablets have lower C ( max ), similar t ( max ), and longer MRT.", "output": "There is no related enetity." }, { "input": "The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics.", "output": "There is no related enetity." }, { "input": "This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern.", "output": "There is no related enetity." }, { "input": "Injectable PLA - based in situ forming implants for controlled release of Ivermectin a BCS Class II drug: solvent selection based on physico - chemical characterization.", "output": "PLA, Ivermectin." }, { "input": "In situ forming implants ( ISI ) prepared from biodegradable polymers such as poly ( D, L - lactide ) ( PLA ) and biocompatible solvents can be used to obtain sustained drug release after parenteral administration.", "output": "poly ( D , L - lactide ), PLA." }, { "input": "The aim of this work was to study the effect of several biocompatible solvents with different physico - chemical properties on the release of ivermectin ( IVM ), an antiparasitic BCS II drug, from in situ forming PLA - based implants.", "output": "ivermectin, IVM, PLA." }, { "input": "The solvents evaluated were N - methyl - 2 - pyrrolidone ( NMP ), 2 - pyrrolidone ( 2P ), triacetine ( TA ) and benzyl benzoate ( BB ).", "output": "N - methyl - 2 - pyrrolidone, NMP, 2 - pyrrolidone, triacetine, benzyl benzoate." }, { "input": "Hansen ' s solubility parameters of solvents were used to explain polymer / solvent interactions leading to different rheological behaviours.", "output": "There is no related enetity." }, { "input": "The stability of the polymer and drug in the solvents were also evaluated by size exclusion and high performance liquid chromatography, respectively.", "output": "There is no related enetity." }, { "input": "The two major factors determining the rate of IVM release from ISI were miscibility of the solvent with water and the viscosity of the polymer solutions.", "output": "IVM." }, { "input": "In general, the release rate increased with increasing water miscibility of the solvent and decreasing viscosity in the following order NMP > 2P > TA > BB.", "output": "NMP." }, { "input": "Scanning electron microscopy revealed a relationship between the rate of IVM release and the surface porosity of the implants, release being higher as implant porosity increased.", "output": "IVM." }, { "input": "Finally, drug and polymer stability in the solvents followed the same trends, increasing when polymer - solvent affinities and water content in solvents decreased.", "output": "There is no related enetity." }, { "input": "IVM degradation was accelerated by the acid environment generated by the degradation of the polymer but the drug did not affect PLA stability.", "output": "IVM, PLA." }, { "input": "Toxic effects of 50 Hz electromagnetic field on memory consolidation in male and female mice.", "output": "There is no related enetity." }, { "input": "In this study, the effect of exposure to an 8 mT, 50 Hz extremely low - frequency electromagnetic field ( ELF EMF ) on memory consolidation of adult male and female mice was studied.", "output": "There is no related enetity." }, { "input": "For this purpose male and female mice were randomly distributed among six groups ( n = 10 in each group ).", "output": "There is no related enetity." }, { "input": "Using passive avoidance task, despite its natural tendency, mouse learns to stay on a small platform to avoidant electric shock.", "output": "There is no related enetity." }, { "input": "Immediately after the learning session, laboratory animals in the experimental groups were placed in an 8 mT, 50 Hz sinusoidal EMF for 4 h.", "output": "There is no related enetity." }, { "input": "The second male and female groups were sham exposed ( exposure device off ) and the third groups were considered as the controls.", "output": "There is no related enetity." }, { "input": "Twenty - four hours after the learning session, the animals were placed on small platform again and step - down latency was measured as the memory consolidation index.", "output": "There is no related enetity." }, { "input": "Significant ( p < 0. 05 ) decreases were determined among groups in memory function and results showed that exposure to an 8 mT, 50 Hz EMF for 4 h has devastating effects on memory consolidation in male and female mice.", "output": "There is no related enetity." }, { "input": "9, 10 - seco - 9, 19 - cyclolanostane triterpene from Salix caprea L.", "output": "9 , 10 - seco - 9 , 19 - cyclolanostane, triterpene." }, { "input": "( goat willow ).", "output": "There is no related enetity." }, { "input": "Chemical investigation of low polar solvent extract of Salix caprea through chromatographic techniques led to the isolation of new triterpene as 1 alpha, 3 beta, 25 - trihydroxy - 9 ( 11 ) - ene - 16 - one - 9, 10 - seco - 9, 19 - cyclolanostane ( 1 ) along with fatty alcohols.", "output": "triterpene, 1 alpha , 3 beta , 25 - trihydroxy - 9 ( 11 ) - ene - 16 - one - 9 , 10 - seco - 9 , 19 - cyclolanostane, fatty alcohols." }, { "input": "The structure of compound 1 was established by IR, HRESI / MS and NMR including 1D and 2D experiments.", "output": "There is no related enetity." }, { "input": "The compound 1 showed moderate in vitro antiplasmodial activity.", "output": "There is no related enetity." }, { "input": "Chemical constituents of Euphorbia hyberna L.", "output": "There is no related enetity." }, { "input": "( Euphorbiaceae ).", "output": "There is no related enetity." }, { "input": "Chemical investigation of the aerial part and the roots of Euphorbia hyberna L. subs.", "output": "There is no related enetity." }, { "input": "hyberna. resulted in the isolation and identification of four triterpenoids ( 3 beta - O - octadecanoyllupeol ( 1 ), glut - 5 - en - 3 beta - ol ( 2 ), 24 - methylenecicloartan - 3 beta - ol ( 3 ) and cicloart - 23 - ene - 3 beta, 25 - diol ( 6 ) ) along with the phenolic compounds ellagic acid ( 4 ) and 3, 3 ' - di - O - methylellagic acid ( 7 ).", "output": "triterpenoids, 3 beta - O - octadecanoyllupeol, glut - 5 - en - 3 beta - ol, 24 - methylenecicloartan - 3 beta - ol, cicloart - 23 - ene - 3 beta , 25 - diol, ellagic acid, 3 , 3 ' - di - O - methylellagic acid." }, { "input": "Although these are all known compounds, this is the first report of their isolation from this plant.", "output": "There is no related enetity." }, { "input": "Their structures were elucidated on the basis of spectral methods, including 2D NMR experiences, and confirmed by comparing with the literature data.", "output": "There is no related enetity." }, { "input": "Structure elucidation of a new natural diketopiperazine from a Microbispora aerata strain isolated from Livingston Island, Antarctica.", "output": "diketopiperazine." }, { "input": "A new natural diketopiperazine ( 1 ) was obtained from the culture broth of Microbispora aerata strain imbas - 11A, isolated from penguin excrements collected on the Antarctic Livingston Island.", "output": "diketopiperazine." }, { "input": "Compound 1 was purified consecutively by solvent extraction, silica gel column chromatography and preparative HPLC.", "output": "There is no related enetity." }, { "input": "The structure of the compound was elucidated by 1D and 2D NMR experiments and mass spectrometric investigations.", "output": "There is no related enetity." }, { "input": "The absolute configuration of compound 1 was determined by amino acid analysis and NOESY correlations.", "output": "amino acid." }, { "input": "A low antiproliferative and cytotoxic effect of trans - cyclo - ( D - tryptophanyl - L - tyrosyl ) ( 1 ) was determined with L - 929 mouse fibroblast cells, K - 562 human leukemia cells and HeLa human cervix carcinoma.", "output": "trans - cyclo - ( D - tryptophanyl - L - tyrosyl )." }, { "input": "Trans - cyclo - ( D - tryptophanyl - L - tyrosyl ) ( 1 ) did not show antimicrobial activity at a concentration of 50 micro g per disc against Bacillus subtilis, Staphylococcus aureus, Streptomyces viridochromogenes, Escherichia coli, Candida albicans and Mucor miehei.", "output": "Trans - cyclo - ( D - tryptophanyl - L - tyrosyl )." }, { "input": "Comparative chemical composition and in vitro antioxidant activities of essential oil isolated from the leaves of Cinnamomum tamala and Pimenta dioica.", "output": "There is no related enetity." }, { "input": "Cinnamomum tamala Nees and Eberm ( tejpat ) and Pimenta dioica ( L. ) Merr ( pimento ) leaves are commonly used for flavouring food and widely used in pharmaceutical preparations because of their hypoglycemic, carminative and stimulant properties.", "output": "There is no related enetity." }, { "input": "In this study, we compared the chemical composition and antioxidant activities of tejpat and pimento essential oils by employing various in vitro methods.", "output": "There is no related enetity." }, { "input": "GC and GC - MS analyses were done to find out the chemical composition, and the main constituent identified in tejpat and pimento leaf oils was eugenol.", "output": "eugenol." }, { "input": "Both the oils showed significant radical scavenging activity against DPPH and superoxide radicals with a potent metal chelating activity and were compared with that of standard compound, eugenol.", "output": "DPPH, superoxide, eugenol." }, { "input": "Among the two oils, tejpat oil showed better activity in terms of antioxidative potential.", "output": "There is no related enetity." }, { "input": "Antioxidant and lipoxygenase inhibiting new iridoid glucosides from Caryopteris odorata.", "output": "iridoid glucosides." }, { "input": "The phytochemical investigation of the ethylacetate - soluble fraction of Caryopteris odorata ( Ham. ex Roxb. ) led to the isolation of four new iridoid glucosides ( 1 - 4 ): 8 - O - trans - cinnamoyl caryoptoside ( 1 ), 8 - O - trans - cinnamoyl shanzhiside methylester ( 2 ), 8 - O - trans - cinnamoyl mussaenoside ( 3 ) and 8 - O - cafeoyl massenoside ( 4 ).", "output": "ethylacetate, iridoid glucosides, 8 - O - trans - cinnamoyl caryoptoside, 8 - O - trans - cinnamoyl shanzhiside methylester, 8 - O - trans - cinnamoyl mussaenoside, 8 - O - cafeoyl massenoside." }, { "input": "The structures of these compounds were determined by FAB - MS, IR, 1D and 2D - NMR spectroscopy and by comparing with the published data of the closely related compounds.", "output": "There is no related enetity." }, { "input": "The antioxidant potential of the isolated iridoids ( 1 - 4 ) was evaluated relative to conventionally used standards and these molecules exhibited good antioxidant potential.", "output": "iridoids." }, { "input": "Moreover, their inhibitory potential was also screened against three enzymes, namely acetyl cholinesterase, butyrylcholinesterase and lipoxygenase.", "output": "acetyl." }, { "input": "These iridoid glucosides were found to be inactive against acetyl and butyrylcholinesterases but active against lipoxygenase.", "output": "iridoid glucosides, acetyl." }, { "input": "Minor cell - death defects but reduced tumor latency in mice lacking the BH3 - only proteins Bad and Bmf.", "output": "There is no related enetity." }, { "input": "Proapoptotic Bcl - 2 family members of the Bcl - 2 homology ( BH ) 3 - only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress.", "output": "There is no related enetity." }, { "input": "On the basis of the biochemical experiments as well as genetic studies in mice, the BH3 - only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose - or trophic factor - deprivation, glucocorticoids, or histone deacetylase inhibition, as well as suppression of B - cell lymphomagenesis upon aberrant expression of c - Myc.", "output": "glucose." }, { "input": "To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes.", "output": "There is no related enetity." }, { "input": "Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture.", "output": "There is no related enetity." }, { "input": "Only spontaneous cell death of thymocytes kept in low glucose or that of pre - B cells deprived of cytokines was significantly delayed when both genes were lacking.", "output": "glucose." }, { "input": "Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B - cell lineage.", "output": "There is no related enetity." }, { "input": "Long - term follow - up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking.", "output": "There is no related enetity." }, { "input": "Together our study suggests that Bad and Bmf co - regulate lymphocyte homeostasis and limit spontaneous transformation by mechanisms that may not exclusively be linked to the induction of lymphocyte apoptosis.", "output": "There is no related enetity." }, { "input": "Differentiating the roles of mGlu2 and mGlu3 receptors using LY541850, an mGlu2 agonist / mGlu3 antagonist.", "output": "LY541850." }, { "input": "Despite the potential therapeutic relevance of group II metabotropic glutamate ( mGlu ) receptors, there has been a lack of pharmacological tools for separating the roles of mGlu2 and mGlu3 receptor subtypes.", "output": "glutamate." }, { "input": "LY541850 was claimed from human mGlu receptors expressed in non - neuronal cells to be a selective orthosteric mGlu2 agonist and mGlu3 antagonist.", "output": "LY541850." }, { "input": "We have verified this pharmacological profile of LY541850 in hippocampal slices.", "output": "LY541850." }, { "input": "Field excitatory post - synaptic potentials ( fEPSPs ) evoked by stimulation of the temporo - ammonic path ( TAP ) input to CA1 stratum lacunosum moleculare ( SLM ) were inhibited by LY541850 in mGlu3 - / - mice ( EC ( 50 ) 38 nM ) and wild - type littermates ( EC ( 50 ) 42 nM ) to a similar extent but were not significantly affected in mGlu2 - / - mice.", "output": "LY541850." }, { "input": "The group II agonist, DCG - IV, inhibited the fEPSP in all three genotypes.", "output": "There is no related enetity." }, { "input": "Co - application of DCG - IV and LY541850 in mGlu3 - / - and wild - type littermates resulted in an additive effect, whereas in mGlu2 - / - mice, LY541850 reversed the inhibitory action of DCG - IV.", "output": "LY541850, LY541850." }, { "input": "These results confirm the selective mGlu2 agonist and mGlu3 antagonist actions of LY541850.", "output": "LY541850." }, { "input": "A similar profile of activity was seen in medial perforant path synapse to the dentate gyrus.", "output": "There is no related enetity." }, { "input": "Systemic administration of LY541850 to wild - type mice, reduced the increase in locomotor activity following both phencyclidine and amphetamine administration.", "output": "LY541850, phencyclidine, amphetamine." }, { "input": "These data support the hypothesis that mGlu2 receptors mediate the antipsychotic effects of mixed group II agonists.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Antiproliferative and antiangiogenic properties of horse chestnut extract.", "output": "There is no related enetity." }, { "input": "This study was designed to examine the in vitro antiproliferative effect of the horse chestnut extract ( HCE ) on cancer cell lines.", "output": "There is no related enetity." }, { "input": "Furthermore, we have investigated the in vitro effect of HCE on some angiogenic events by using human umbilical vein endothelial cells.", "output": "There is no related enetity." }, { "input": "The cell proliferation was evaluated by 3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 - diphenyltetrazolium bromide assay and anchorage - independent growth by colony - forming assay.", "output": "3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide." }, { "input": "To understand the growth inhibitory effects, carcinoma cell lines ( Jurkat, CEM, HeLa, and MCF - 7 ) were treated with various concentrations of HCE.", "output": "There is no related enetity." }, { "input": "Incubation of Jurkat, CEM, HeLa, and MCF - 7 cancer cells with HCE at 125 micro g / mL for 72 h caused 93. 7 %, 32. 3 %, 20. 4 % and 40. 4 % reduction in cell survival.", "output": "There is no related enetity." }, { "input": "Colony - forming assay also confirmed growth - inhibitory effects of the compound studied.", "output": "There is no related enetity." }, { "input": "In HeLa HCE - treated cells, we found a significant increase in cells having sub - G ( 0 ) / G ( 1 ) DNA content which is considered to be a marker of apoptotic cell death.", "output": "There is no related enetity." }, { "input": "Apoptosis was also further confirmed by DNA fragmentation analysis. Furthermore, HCE inhibited migration of human umbilical vein endothelial cells as well as decreased secretion of matrix metalloproteinase and vascular endothelial growth factor. In conclusion, the present study has assessed the in vitro antiproliferative / antiangiogenic potential of HCE.", "output": "There is no related enetity." }, { "input": "These results generate a rationale for in vivo efficacy studies with horse chestnut in preclinical cancer models.", "output": "There is no related enetity." }, { "input": "Synthesis of 4 - hydroxy - 3, 4 - dialkyl - 2, 6 - diaryl - piperidine derivatives as potent antimicrobial agent.", "output": "4 - hydroxy - 3 , 4 - dialkyl - 2 , 6 - diaryl - piperidine." }, { "input": "A series of 4 - hydroxy - 3, 4 - dialkyl - 2, 6 - diaryl - piperidine ( 7 - 12 ) have been synthesised by reduction of 3 - alkyl - 2, 6 - diarylpiperidin - 4 - one using the Grignard reagent.", "output": "4 - hydroxy - 3 , 4 - dialkyl - 2 , 6 - diaryl - piperidine, 3 - alkyl - 2 , 6 - diarylpiperidin - 4 - one, Grignard reagent." }, { "input": "Structural assignments and conformational analysis of the compounds were established based on the spectral studies.", "output": "There is no related enetity." }, { "input": "All the piperdin - 4 - ol derivatives ( 7 - 12 ) were assayed for antibacterial, antifungal and anthelmintic activities and they exhibited significant results.", "output": "piperdin - 4 - ol." }, { "input": "Phytochemical analysis of Gymnema sylvestre and evaluation of its antimicrobial activity.", "output": "There is no related enetity." }, { "input": "Gymnema sylvestre ( CS 149 ), known to be a rich source of saponins and other valuable phytochemicals, has been analysed for antimicrobial activity.", "output": "saponins." }, { "input": "The chloroform extracts of aerial and root parts of G. sylvestre exhibited higher antimicrobial activity as compared to diethyl ether and acetone.", "output": "chloroform, diethyl ether, acetone." }, { "input": "The root extracts of chloroform have shown competitive minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0. 04 - 1. 28 mg mL ( - 1 ) and 0. 08 - 2. 56 mg / mL, respectively, towards the pathogens.", "output": "chloroform." }, { "input": "The GC - MS analysis of chloroform extracts has shown the presence of compounds like eicosane, oleic acid, stigmasterol and vitamin E.", "output": "chloroform, eicosane, oleic acid, stigmasterol, vitamin E." }, { "input": "Plant proteins, minerals and trace elements of Eurycoma longifolia ( Tongkat Ali ).", "output": "There is no related enetity." }, { "input": "A water extraction method has been used to extract plant proteins from the roots of Eurycoma longifolia harvested from Perak and Pahang, Malaysia.", "output": "There is no related enetity." }, { "input": "On the basis of the spectroscopic Bradford assay, Tongkat Ali Perak and Pahang contained 0. 3868 and 0. 9573 mg mL ( - 1 ) of crude protein, respectively.", "output": "There is no related enetity." }, { "input": "The crude proteins were separated by one dimensional 15 % sodium dodecyl sulphate polyacrylamide gel electrophoresis into two ( 49. 8 and 5. 5 kD ) and four ( 49. 8, 24. 7, 21. 1 and 5. 5 kD ) protein spots for Tongkat Ali Perak and Pahang, respectively.", "output": "sodium dodecyl sulphate polyacrylamide." }, { "input": "Isoleucine was present in the highest concentration significantly.", "output": "Isoleucine." }, { "input": "Both plant samples showed differences in the mineral and trace element profiles, but the minerals calcium, magnesium and potassium were present in the highest concentration.", "output": "calcium, magnesium, potassium." }, { "input": "The highly concerned toxic metals such as arsenic and lead were not detected.", "output": "arsenic." }, { "input": "In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet - O Delta N89 beta - catenin system.", "output": "There is no related enetity." }, { "input": "Although significant progress has been made in understanding the importance of Wnt signaling in the initiation of colorectal cancer, less is known about responses that accompany the reversal of oncogenic Wnt signaling.", "output": "There is no related enetity." }, { "input": "The aim of this study was to analyze in vivo and in vitro responses to an ' ideal ' Wnt pathway inhibitor as a model for the therapeutic targeting of the pathway.", "output": "There is no related enetity." }, { "input": "A tetracycline - inducible transgenic mouse model expressing truncated beta - catenin ( Delta N89 beta - catenin ) that exhibited a strong intestinal hyperplasia was analyzed during the removal of oncogenic beta - catenin expression both in 3D ' crypt culture ' and in vivo.", "output": "tetracycline." }, { "input": "Oncogenic Wnt signaling was rapidly and completely reversed.", "output": "There is no related enetity." }, { "input": "The strongest inhibition of Wnt target gene expression occurred within 24 h of doxycycline removal at which time the target genes Ascl2, Axin2 and C - myc were downregulated to levels below that in the control intestine.", "output": "There is no related enetity." }, { "input": "In vitro, the small molecule Wnt inhibitor CCT036477 induced a response within 4 h of treatment.", "output": "There is no related enetity." }, { "input": "By 7 days following doxycycline withdrawal, gene expression, cell proliferation and tissue morphology were undistinguishable from control animals. In conclusion, these results demonstrate that the reversal of Wnt signaling by inhibitors should ideally be studied within hours of treatment.", "output": "doxycycline." }, { "input": "The reversible system described, involving medium throughput in vitro approaches and rapid in vivo responses, should allow the rapid advance of early stage compounds into efficacy models that are more usually considered later in the drug discovery pipeline.", "output": "There is no related enetity." }, { "input": "miR - 143 regulates hexokinase 2 expression in cancer cells.", "output": "There is no related enetity." }, { "input": "Tumor cells activate pathways that facilitate and stimulate glycolysis even in the presence of adequate levels of oxygen in order to satisfy their continuous need of molecules, such as nucleotides, ATP and fatty acids, necessary to support their rapid proliferation.", "output": "oxygen, ATP, fatty acids." }, { "input": "Accordingly, a variety of human tumors are characterized by elevated expression levels of the hexokinase 2 isoform ( HK2 ).", "output": "There is no related enetity." }, { "input": "Although different molecular mechanisms, including genetic and epigenetic mechanisms, have been suggested to account for the altered expression of HK2 in tumors, the potential role of microRNAs ( miRNAs ) in the regulation of HK2 expression has not been evaluated.", "output": "There is no related enetity." }, { "input": "Here, we report that miR - 143 inhibits HK2 expression via a conserved miR - 143 recognition motif located in the 3 ' - untranslated region ( 3 ' UTR ) of HK2 mRNA.", "output": "There is no related enetity." }, { "input": "We demonstrate that miR143 inhibits HK2 expression both in primary keratinocytes and in head and neck squamous cell carcinoma ( HNSCC ) - derived cell lines.", "output": "There is no related enetity." }, { "input": "Importantly, we found that miR - 143 inversely correlates with HK2 expression in HNSCC - derived cell lines and in primary tumors.", "output": "There is no related enetity." }, { "input": "We also report that the miRNA - dependent regulation of hexokinase expression is not limited to HK2 as miR - 138 targets HK1 via a specific recognition motif located in its 3 ' UTR.", "output": "There is no related enetity." }, { "input": "All these data unveil a new miRNA - dependent mechanism of regulation of hexokinase expression potentially important in the regulation of glucose metabolism of cancer cells.", "output": "glucose." }, { "input": "Glaucogenin E, a new C21 steroid from Cynanchum stauntonii.", "output": "Glaucogenin E, C21, steroid." }, { "input": "Glaucogenin E ( 1 ), a new C ( 21 ) steroid sapogenin, along with three known ones ( 2 - 4 ) were isolated from the rhizomes of Cynanchum stauntonii ( Decne. ) Schltr.", "output": "Glaucogenin E, C ( 21 ), steroid." }, { "input": "ex Levl.", "output": "There is no related enetity." }, { "input": "Their structures were established mainly by the spectroscopic analysis, including 2D NMR.", "output": "There is no related enetity." }, { "input": "All the isolated compounds were evaluated for their cytotoxicity against human cancer cell lines HeLa, Bel - 7402, SGC - 7901 and BGC - 823.", "output": "There is no related enetity." }, { "input": "RP - HPLC method for the simultaneous quantitation of boeravinone E and boeravinone B in Boerhaavia diffusa extract and its formulation.", "output": "boeravinone E, boeravinone B." }, { "input": "A high - performance liquid chromatography method was developed and validated for the simultaneous quantitation of two major rotenoids, boeravinone E and boeravinone B, in Boerhaavia diffusa extract and its formulation.", "output": "rotenoids, boeravinone E, boeravinone B." }, { "input": "Chromatographic separation was carried out on an Inertsil ODS - 3 column by using gradient mobile phase containing 0. 1 % v / v orthophosphoric acid in water and acetonitrile.", "output": "orthophosphoric acid, acetonitrile." }, { "input": "The detection was carried out at 276 nm.", "output": "There is no related enetity." }, { "input": "The method was validated for specificity, precision, accuracy and robustness.", "output": "There is no related enetity." }, { "input": "The linearity ( r ( 2 ) = 0. 9989 and 0. 9991 ) was found to be in the range of 7. 26 - 35. 75 micro g mL ( - 1 ) and 2. 20 - 11. 00 micro g mL ( - 1 ) for boeravinone E and B, respectively.", "output": "boeravinone E and B." }, { "input": "The percent recovery observed from the extract sample was 95. 22 - 95. 83.", "output": "There is no related enetity." }, { "input": "Screening of ecotoxicological, qualitative and reproductive variables in male European sea bass Dicentrarchus labrax ( L. ) reared in three different fish farms: Facility location and typology.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate the influence of both facility location and typology of fish farm on some ecotoxicological, qualitative and reproductive variables in European sea bass Dicentrarchus labrax L.", "output": "There is no related enetity." }, { "input": "Several variables were investigated: gonado - somatic index ( GSI ), liver - somatic index ( LSI ); 7 - ethoxyresorufin - O - deethylase ( EROD ), benzo ( a ) pyrene monooxygenase and acetylcholinesterase activities; glutathione ( GSH ), testosterone, 17 beta - estradiol, total lipid, phospholipid ( PL ) and triglyceride contents.", "output": "7 - ethoxyresorufin, O, benzo ( a ) pyrene, glutathione, GSH, testosterone, 17 beta - estradiol, triglyceride." }, { "input": "In addition, the histological sections of gonads were examined.", "output": "There is no related enetity." }, { "input": "Results suggest that LSI, EROD activity, GSI, GSH, PL, hormone levels and gonad morphology were influenced by different facility locations and typologies of fish farm.", "output": "GSH." }, { "input": "Evaluation of the physicochemical and biopharmaceutical properties of fluoro - indomethacin.", "output": "fluoro - indomethacin." }, { "input": "Drug nanocarriers have shown great potential in therapy and as diagnostic probes, e. g. in imaging of cancer and inflammation.", "output": "There is no related enetity." }, { "input": "Imaging can be applied to localize the carrier or the drug itself in the body and / or tissues.", "output": "There is no related enetity." }, { "input": "In this particular case it is important that drug molecules have the characteristics for possible detection, e. g. after modification with positron emission tomography compliant radioisotopes, without affecting their pharmacological behavior.", "output": "There is no related enetity." }, { "input": "In order to easily and efficiently follow the ADME profile of the drug after loaded into nanocarriers, the drug can be radiolabelled with, e. g. 18F - label, in order to assess its biodistribution after enteral and parenteral administration in rats.", "output": "18F." }, { "input": "However, this is only possible if the derivative compound behaves similarly to the parent drug compound.", "output": "There is no related enetity." }, { "input": "In this study, indomethacin ( a poorly water - soluble drug ) was chosen as a model compound and aimed to evaluate the physicochemical and biopharmaceutical properties of an analog of indomethacin ( IMC ), fluoro - indomethacin ( F - IMC ).", "output": "indomethacin, indomethacin, IMC, fluoro - indomethacin, F - IMC." }, { "input": "Although some of the physicochemical and biopharmaceutical properties of IMC are already known, in order to establish a feasible comparison between IMC and F - IMC, the behavior of the former was also investigated in the same conditions as for F - IMC.", "output": "IMC, IMC, F - IMC, F - IMC." }, { "input": "In this context, both IMC and F - IMC were thermally and morphologically studied.", "output": "IMC, F - IMC." }, { "input": "Furthermore, the following properties were also studied for both compounds: pKa and logP, solubility and dissolution profiles at physiological pH values, and toxicity at different concentrations in Caco - 2 cells.", "output": "There is no related enetity." }, { "input": "Finally, the transport across Caco - 2 monolayers of the IMC and F - IMC at physiological pH range was also investigated.", "output": "IMC, F - IMC." }, { "input": "The results obtained showed similar values in pKalogP, solubility, dissolution, cytotoxicity, and permeability for both compounds.", "output": "There is no related enetity." }, { "input": "Thus, there might be strong evidence that both IMC and F - IMC should have a similar ADME behavior and profiles in vivo.", "output": "IMC, F - IMC." }, { "input": "The results provide fundamental tools and ideas for further research with nanocarriers of 18F - IMC.", "output": "18F - IMC." }, { "input": "New furostanol saponins from the rhizomes of Tupistra chinensis.", "output": "furostanol, saponins." }, { "input": "Three new furostanol saponins ( 1 - 3 ), including a polyhydroxyl saponin, were isolated from the rhizomes of Tupistra chinensis.", "output": "furostanol, saponins, polyhydroxyl, saponin." }, { "input": "The structures of these compounds were identified by NMR, MS spectral data and chemical methods.", "output": "There is no related enetity." }, { "input": "mGlu5R promotes glutamate AMPA receptor phosphorylation via activation of PKA / DARPP - 32 signaling in striatopallidal medium spiny neurons.", "output": "glutamate, AMPA." }, { "input": "Group I metabotropic glutamate receptors ( mGluRs ), which comprise mGlu1Rs and mGlu5Rs, are enriched in striatal medium spiny neurons ( MSNs ), where they modulate glutamatergic transmission.", "output": "glutamate." }, { "input": "Here, we have examined the effect of group I mGluRs on the regulation of the state of phosphorylation of the GluA1 subunit of the AMPA glutamate receptor.", "output": "AMPA, glutamate." }, { "input": "We found that incubation of mouse striatal slices with the group I mGluR agonist ( R, S ) - 3, 5 - dihydroxyphenylglycine ( DHPG ) promotes GluA1 phosphorylation at the cAMP - dependent protein kinase ( PKA ) site, Ser845.", "output": "( R , S ) - 3 , 5 - dihydroxyphenylglycine, DHPG, cAMP, Ser845." }, { "input": "This effect is prevented by 2 - methyl - 6 - ( phenylethynyl ) pyridine hydrochloride ( MPEP ), a selective mGlu5R antagonist.", "output": "2 - methyl - 6 - ( phenylethynyl ) pyridine hydrochloride, MPEP." }, { "input": "The increase in GluA1 phosphorylation produced by DHPG is also prevented by blockade of adenosine A2A receptors ( A2ARs ), which are known to promote cAMP signaling specifically in striatopallidal MSNs, as well as by enzymatic degradation of endogenous adenosine, achieved with adenosine deaminase.", "output": "DHPG, adenosine, cAMP, adenosine, adenosine." }, { "input": "The ability of DHPG to increase PKA - dependent phosphorylation of GluA1 depends on concomitant activation of the dopamine - and cAMP - regulated phosphoprotein of 32kDa ( DARPP - 32 ).", "output": "DHPG, dopamine, cAMP." }, { "input": "Thus, inactivation of the PKA phosphorylation site of DARPP - 32 abolishes the effect of DHPG.", "output": "DHPG." }, { "input": "Moreover, cell - specific knock out of DARPP - 32 in striatopallidal, but not in striatonigral, MSNs prevents the increase in Ser845 phosphorylation induced by DHPG.", "output": "Ser845, DHPG." }, { "input": "These results indicate that activation of mGlu5Rs promotes PKA / DARPP - 32 - dependent phosphorylation of downstream target proteins in striatopallidal MSNs and that this effect is exerted via potentiation of tonic A2AR transmission.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407.", "output": "rebamipide, poloxamer 407." }, { "input": "This study was conducted primarily to improve the solubility of rebamipide, a poorly water - soluble anti - ulcer drug, using novel ternary solid dispersion ( SD ) systems and secondly to evaluate the effect of solubility enhancement on its pharmacokinetic ( PK ) and pharmacodynamic ( PD ) profile.", "output": "rebamipide." }, { "input": "After dissolving the three components in aqueous medium, ternary SD containing the drug, sodium hydroxide ( NaOH ) and PVP - VA 64 was achieved by spray drying method, which was used as primary SD.", "output": "sodium hydroxide, NaOH." }, { "input": "Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co - grinding, physical mixing, melting or spray drying.", "output": "Poloxamer 407." }, { "input": "SD was then characterized by dissolution test, differential scanning calorimetry ( DSC ), powder X - ray diffraction ( PXRD ) and Fourier transform infrared spectroscopy ( FT - IR ).", "output": "There is no related enetity." }, { "input": "The spray dried SD of poloxamer 407 together with primary SD displayed highest dissolution rate of the drug of about 70 % after 2 h.", "output": "poloxamer 407." }, { "input": "DSC, PXRD and FT - IR characterized the amorphous state and molecular dispersion of the drug in the SD.", "output": "There is no related enetity." }, { "input": "PK and PD studies in Sprague - Dawley rats revealed that the bioavailability of the drug using optimal SD was about twofold higher than that of reference product, and the irritation area of stomach was significantly reduced in the ulcer - induced rat model using optimal SD as compared to the reference product.", "output": "There is no related enetity." }, { "input": "Chitin synthase inhibitors as antifungal agents.", "output": "There is no related enetity." }, { "input": "Increased risk of fungal diseases in immunocompromised patients, emerging fungal pathogens, limited repertoire of antifungal drugs and resistance development against the drugs demands for development of new and effective antifungal agents.", "output": "There is no related enetity." }, { "input": "With greater knowledge of fungal metabolism efforts are being made to inhibit specific enzymes involved in different biochemical pathways for the development of antifungal drugs.", "output": "There is no related enetity." }, { "input": "Chitin synthase is one such promising target as it is absent in plants and mammals.", "output": "There is no related enetity." }, { "input": "Nikkomycin Z, a chitin synthase inhibitor is under clinical development.", "output": "Nikkomycin Z." }, { "input": "Chitin synthesis in fungi, chitin synthase as a target for antifungal agent development, different chitin synthase inhibitors isolated from natural sources, randomly synthesized and modified from nikkomycin and polyoxin are discussed in this review.", "output": "nikkomycin, polyoxin." }, { "input": "Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic.", "output": "venlafaxine, pregabalin, carbon dioxide." }, { "input": "Previous studies have shown that subjective and objective symptoms of anxiety induced by 7. 5 % CO ( 2 ) inhalation can be attenuated by anxiolytics such as lorazepam and, to a lesser extent, paroxetine.", "output": "CO ( 2 ), lorazepam, paroxetine." }, { "input": "Venlafaxine and pregabalin, two other licensed treatments for Generalised Anxiety Disorder, were used to further investigate the 7. 5 % and 35 % CO ( 2 ) models of anxiety in healthy volunteers.", "output": "Venlafaxine, pregabalin, CO ( 2 )." }, { "input": "Fifty - four participants were randomised to receive either placebo, venlafaxine or pregabalin.", "output": "venlafaxine, pregabalin." }, { "input": "Study treatments were dosed incrementally over a three week period, to reach daily doses of 150 mg venlafaxine and 200mg pregabalin by the CO ( 2 ) challenge test day.", "output": "venlafaxine, pregabalin, CO ( 2 )." }, { "input": "Participants inhaled air 7. 5 % CO ( 2 ) for 20 minutes ( single - blind presentation ), and a non - blinded single vital capacity of 35 % CO ( 2 ).", "output": "CO ( 2 ), CO ( 2 )." }, { "input": "Subjective ratings were recorded before and after each inhalation.", "output": "There is no related enetity." }, { "input": "Both 7. 5 % and 35 % CO ( 2 ) inhalations produced the expected effects of increased ratings of symptoms of panic and anxiety, with increased blood pressure and heart rate.", "output": "CO ( 2 )." }, { "input": "No significant treatment effects were found, although there were trends towards a reduction in feeling tense and nervous by both drugs compared with placebo during the 7. 5 % CO ( 2 ) challenge, and a reduction in alertness generally in the venlafaxine group compared with the pregabalin group.", "output": "CO ( 2 ), venlafaxine, pregabalin." }, { "input": "In contrast with the clear anxiolytic effects of benzodiazepines reported in several previous CO ( 2 ) studies, these findings suggest that the anxiogenic effects of CO ( 2 ) challenges are not significantly influenced by these serotonergic and GABAergic anxiolytics.", "output": "benzodiazepines, CO ( 2 ), CO ( 2 )." }, { "input": "This may be due to a lack of sensitivity of the CO ( 2 ) challenges in healthy volunteers to these drug types.", "output": "CO ( 2 )." }, { "input": "Microwave - assisted synthesis of N - isobutyl - 4, 5 - epoxy - 2 ( E ) - decenamide.", "output": "N - isobutyl - 4 , 5 - epoxy - 2 ( E ) - decenamide." }, { "input": "A new and efficient synthesis of a naturally occurring amide alkaloid, N - isobutyl - 4, 5 - epoxy - 2 ( E ) - decenamide isolated from the roots of Piper nigrum has been described involving a total of nine steps.", "output": "amide, N - isobutyl - 4 , 5 - epoxy - 2 ( E ) - decenamide." }, { "input": "Octanal and 2 - bromoacetic acid have been used as the starting materials.", "output": "Octanal, 2 - bromoacetic acid." }, { "input": "Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal - epithelial transition in breast cancer cells.", "output": "There is no related enetity." }, { "input": "The epithelial - mesenchymal transition ( EMT ) correlates with disruption of cell - cell adhesion, loss of cell polarity and development of epithelial cell malignancy.", "output": "There is no related enetity." }, { "input": "Identifying novel molecules that inhibit EMT has profound potential for developing mechanism - based therapeutics.", "output": "There is no related enetity." }, { "input": "We previously demonstrated that the endoplasmic reticulum protein 29 ( ERp29 ) is a novel factor that can drive mesenchymal - epithelial transition ( MET ) and induce cell growth arrest in MDA - MB - 231 cells.", "output": "There is no related enetity." }, { "input": "Here, we show that ERp29 is an important molecule in establishing epithelial cell integrity during the MET.", "output": "There is no related enetity." }, { "input": "We demonstrate that ERp29 regulates MET in a cell context - dependent manner.", "output": "There is no related enetity." }, { "input": "ERp29 overexpression induced a complete MET in mesenchymal MDA - MB - 231 cells through downregulating the expression of transcriptional repressors ( for example, Slug, Snai1, ZEB2 and Twist ) of E - cadherin.", "output": "There is no related enetity." }, { "input": "In contrast, overexpression of ERp29 induces incomplete MET in basal - like BT549 cells in which the expression of EMT - related markers ( for example, vimentin; cytokeratin 19 ( CK19 ) and E - cadherin ) and the transcriptional repressors of E - cadherin were not altered.", "output": "There is no related enetity." }, { "input": "However, ERp29 overexpression in both cell - types resulted in loss of filamentous stress fibers, formation of cortical actin and restoration of an epithelial phenotype.", "output": "There is no related enetity." }, { "input": "Mechanistic studies revealed that overexpression of ERp29 in both cell - types upregulated the expression of TJ proteins ( zonula - occludens - 1 ( ZO - 1 ) and occludin ) and the core apical - basal polarity proteins ( Par3 and Scribble ) at the membrane to enhance cell - cell contact and cell polarization.", "output": "There is no related enetity." }, { "input": "Knockdown of ERp29 in the epithelial MCF - 7 cells decreased the expression of these proteins, leading to the disruption of cell - cell adhesion.", "output": "There is no related enetity." }, { "input": "Taken together, ERp29 is a novel molecule that regulates MET and epithelial cell integrity in breast cancer cells.", "output": "There is no related enetity." }, { "input": "The metabotropic glutamate receptor 8 agonist ( S ) - 3, 4 - DCPG reverses motor deficits in prolonged but not acute models of Parkinson ' s disease.", "output": "glutamate, ( S ) - 3 , 4 - DCPG." }, { "input": "Metabotropic glutamate receptors ( mGlus ) are 7 Transmembrane Spanning Receptors ( 7TMs ) that are differentially expressed throughout the brain and modulate synaptic transmission at both excitatory and inhibitory synapses.", "output": "glutamate." }, { "input": "Recently, mGlus have been implicated as therapeutic targets for many disorders of the central nervous system, including Parkinson ' s disease ( PD ).", "output": "There is no related enetity." }, { "input": "Previous studies have shown that nonselective agonists of group III mGlus have antiparkinsonian effects in several animal models of PD, suggesting that these receptors represent promising targets for treating the motor symptoms of PD.", "output": "There is no related enetity." }, { "input": "However, the relative contributions of different group III mGlu subtypes to these effects have not been fully elucidated.", "output": "There is no related enetity." }, { "input": "Here we report that intracerebroventricular ( icv ) administration of the mGlu ( 8 ) - selective agonist ( S ) - 3, 4 - dicarboxyphenylglycine ( DCPG [ 2. 5, 10, or 30 nmol ] ) does not alleviate motor deficits caused by acute ( 2 h ) treatment with haloperidol or reserpine.", "output": "( S ) - 3 , 4 - dicarboxyphenylglycine, DCPG, haloperidol, reserpine." }, { "input": "However, following prolonged pretreatment with haloperidol ( three doses evenly spaced over 18 - 20 h ) or reserpine ( 18 - 20 h ), DCPG robustly reverses haloperidol - induced catalepsy and reserpine - induced akinesia.", "output": "haloperidol, reserpine, DCPG, haloperidol, reserpine." }, { "input": "Furthermore, DCPG ( 10 nmol, icv ) reverses the long - lasting catalepsy induced by 20 h pretreatment with the decanoate salt of haloperidol.", "output": "DCPG, decanoate salt, haloperidol." }, { "input": "Finally, icv administration of DCPG ameliorates forelimb use asymmetry caused by unilateral 6 - hydroxydopamine lesion of substantia nigra dopamine neurons.", "output": "DCPG, 6 - hydroxydopamine, dopamine." }, { "input": "These findings suggest that mGlu ( 8 ) may partially mediate the antiparkinsonian effects of group III mGlu agonists in animal models of PD in which dopamine depletion or blockade of D ( 2 ) - like dopamine receptors is prolonged and indicate that selective activation of mGlu ( 8 ) may represent a novel therapeutic strategy for alleviating the motor symptoms of PD.", "output": "dopamine, dopamine." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "The brain GABA - benzodiazepine receptor alpha - 5 subtype in autism spectrum disorder: a pilot [ ( 11 ) C ] Ro15 - 4513 positron emission tomography study.", "output": "GABA, benzodiazepine, [ ( 11 ) C ] Ro15 - 4513." }, { "input": "GABA ( gamma - amino - butyric - acid ) is the primary inhibitory neurotransmitter in the human brain.", "output": "GABA, gamma - amino - butyric - acid." }, { "input": "It has been proposed that the symptoms of autism spectrum disorders ( ASDs ) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABAA receptors.", "output": "GABA." }, { "input": "However, this hypothesis has not been directly tested in living adults with ASD.", "output": "There is no related enetity." }, { "input": "In this preliminary investigation, we used Positron Emission Tomography ( PET ) with the benzodiazepine receptor PET ligand [ ( 11 ) C ] Ro15 - 4513 to measure alpha 1 and alpha 5 subtypes of the GABAA receptor levels in the brain of three adult males with well - characterized high - functioning ASD compared with three healthy matched volunteers.", "output": "benzodiazepine, [ ( 11 ) C ] Ro15 - 4513." }, { "input": "We found significantly lower [ ( 11 ) C ] Ro15 - 4513 binding throughout the brain of participants with ASD ( p < 0. 0001 ) compared with controls.", "output": "[ ( 11 ) C ] Ro15 - 4513." }, { "input": "Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally.", "output": "There is no related enetity." }, { "input": "Further analysis suggested that these results were driven by lower levels of the GABAA alpha 5 subtype.", "output": "There is no related enetity." }, { "input": "These results provide initial evidence of a GABAA alpha 5 deficit in ASD and support further investigations of the GABA system in this disorder.", "output": "GABA." }, { "input": "This article is part of the Special Issue entitled ' Neurodevelopmental Disorders '.", "output": "There is no related enetity." }, { "input": "Tomentomimulol and mimulone B: Two new C - geranylated flavonoids from Paulownia tomentosa fruits.", "output": "Tomentomimulol, mimulone B, C - geranylated flavonoids." }, { "input": "Two new discovered C - geranylated flavonoids tomentomimulol ( 1 ) and mimulone B ( 2 ) were isolated from the methanol extract of Paulownia tomentosa ( Thunb ).", "output": "C - geranylated flavonoids, tomentomimulol, mimulone B, methanol." }, { "input": "Steud.", "output": "There is no related enetity." }, { "input": "( Paulowniaceae ) fruits by exhaustive chromatographic separation together with one known compound tanariflavanone D ( 3 ).", "output": "tanariflavanone D." }, { "input": "The identification of compounds and structure elucidation was carried out using 1D and 2D NMR experiments, as well as mass spectroscopy, ultra - violet, infra red and CD experiments.", "output": "There is no related enetity." }, { "input": "A new cyclododeca [ d ] oxazole derivative from Streptomyces spp.", "output": "cyclododeca [ d ] oxazole." }, { "input": "CIBYL1.", "output": "There is no related enetity." }, { "input": "A novel secondary metabolite, N - trans - cinnamoyl 2 - amino - 3a, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 13a - dodecahydrocyclododeca [ d ] oxazole ( 1 ), was isolated from Streptomyces spp.", "output": "N - trans - cinnamoyl 2 - amino - 3a , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 13a - dodecahydrocyclododeca [ d ] oxazole." }, { "input": "CIBYL1, along with five known compounds, pimprinine ( 2 ), ( 3R, 4S, 5R, 6R ) - 3, 4, 5, 6 - tetrahydro - 4 - hydroxy - 3, 5, 6 - trimethyl - 2H - pyran - 2 - one ( 3 ), indolyl - 3 - carboxylic acid ( 4 ), 2 - phenylacetamide ( 5 ) and di ( 1H - pyrrol - 2 - yl ) methanone ( 6 ).", "output": "pimprinine, ( 3R , 4S , 5R , 6R ) - 3 , 4 , 5 , 6 - tetrahydro - 4 - hydroxy - 3 , 5 , 6 - trimethyl - 2H - pyran - 2 - one, indolyl - 3 - carboxylic acid, 2 - phenylacetamide, di ( 1H - pyrrol - 2 - yl ) methanone." }, { "input": "The structures of these metabolites were elucidated on the basis of extensive analysis of spectroscopic data, including OR, IR, HRMS, 1D and 2D NMR data and chemical derivation.", "output": "There is no related enetity." }, { "input": "Negative allosteric modulation of metabotropic glutamate receptor 5 results in broad spectrum activity relevant to treatment resistant depression.", "output": "glutamate." }, { "input": "Evidence suggests that 30 - 50 % of patients suffering from major depressive disorder ( MDD ) are classified as suffering from treatment resistant depression ( TRD ) as they have an inadequate response to standard antidepressants.", "output": "There is no related enetity." }, { "input": "A key feature of this patient population is the increased incidence of co - morbid symptoms like anxiety and pain.", "output": "There is no related enetity." }, { "input": "Recognizing that current standards of care are largely focused on monoaminergic mechanisms of action ( MOAs ), innovative approaches to drug discovery for TRD are targeting glutamate hyperfunction.", "output": "glutamate." }, { "input": "Here we describe the in vitro and in vivo profile of GRN - 529, a novel negative allosteric modulator ( NAM ) of metabotropic glutamate receptor 5 ( mGluR5 ).", "output": "GRN - 529, glutamate." }, { "input": "In cell based pharmacology assays, GRN - 529 is a high affinity ( Ki 5. 4 nM ), potent ( IC50 3. 1 nM ) and selective ( > 1000 - fold selective vs mGluR1 ) mGluR5 NAM.", "output": "GRN - 529." }, { "input": "Acute administration of GRN - 529 ( 0. 1 - 30 mg / kg p. o. ) had dose - dependent efficacy across a therapeutically relevant battery of animal models, comprising depression ( decreased immobility time in tail suspension and forced swim tests ) and 2 of the co - morbid symptoms overrepresented in TRD, namely anxiety ( attenuation of stress - induced hyperthermia, and increased punished crossings in the four plate test ) and pain ( reversal of hyperalgesia due to sciatic nerve ligation or inflammation ).", "output": "GRN - 529." }, { "input": "The potential side effect liability of GRN - 529 was also assessed using preclinical models: GRN - 529 had no effect on rat sexual behavior or motor co - ordination ( rotarod ), however it impaired cognition in mice ( social odor recognition ).", "output": "GRN - 529, GRN - 529." }, { "input": "Efficacy and side effects of GRN - 529 were compared to standard of care agents ( antidepressant, anxiolytic or analgesics ) and the tool mGluR5 NAM, MTEP.", "output": "GRN - 529, MTEP." }, { "input": "To assess the relationship between target occupancy and efficacy, ex vivo receptor occupancy was measured in parallel with efficacy testing.", "output": "There is no related enetity." }, { "input": "This revealed a strong correlation between target engagement, exposure and efficacy across behavioral endpoints, which supports the potential translational value of PET imaging to dose selection in patients.", "output": "There is no related enetity." }, { "input": "Collectively this broad spectrum profile of efficacy of GRN - 529 supports our hypothesis that negative allosteric modulation of mGluR5 could represent an innovative therapeutic approach to the treatment of TRD.", "output": "GRN - 529." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "There is no related enetity." }, { "input": "Variation in the volatile oil composition of Eucalyptus citriodora produced by hydrodistillation and supercritical fluid extraction techniques.", "output": "There is no related enetity." }, { "input": "This work reports variations in the yields and quality of volatiles produced from Eucalyptus citriodora leaves by different hydrodistillation ( HD ) and supercritical carbon dioxide extraction ( SCE ) techniques.", "output": "carbon dioxide." }, { "input": "HD techniques ( 1. 5 % ) produced higher yields compared to SCE ( 0. 7 % ).", "output": "There is no related enetity." }, { "input": "Citronellal, the major component, was maximum in the extract produced by SCE ( 79 % ) followed by oil produced by water - steam distillation ( WSD ) ( 72. 6 % ) and water distillation ( WD ) ( 62. 4 % ) techniques.", "output": "Citronellal." }, { "input": "Chemical composition of glycoside - bound volatiles produced by acid hydrolysis during HD was found to be very different from free volatiles, although in a minor quantity.", "output": "There is no related enetity." }, { "input": "The extent of artefact formation and release of aglycones was more profound in the bound volatile oil produced by WD than WSD.", "output": "There is no related enetity." }, { "input": "Highest oxygenated monoterpenes were found in SCE and WSD ( 93 % each ) followed by WD ( 91. 4 % ).", "output": "oxygenated monoterpenes." }, { "input": "Although the SCE produced lower yields than the HD techniques, its extract is superior in quality in terms of higher concentration of citronellal.", "output": "citronellal." }, { "input": "Sex, stroke, and inflammation: the potential for estrogen - mediated immunoprotection in stroke.", "output": "estrogen." }, { "input": "Stroke is the third leading cause of death and the primary cause of disability in the developed world.", "output": "There is no related enetity." }, { "input": "Experimental and clinical data indicate that stroke is a sexually dimorphic disease, with males demonstrating an enhanced intrinsic sensitivity to ischemic damage throughout most of their lifespan.", "output": "There is no related enetity." }, { "input": "The neuroprotective role of estrogen in the female brain is well established, however, estrogen exposure can also be deleterious, especially in older women.", "output": "estrogen, estrogen." }, { "input": "The mechanisms for this remain unclear.", "output": "There is no related enetity." }, { "input": "Our current understanding is based on studies examining estrogen as it relates to neuronal injury, yet cerebral ischemia also induces a robust sterile inflammatory response involving local and systemic immune cells.", "output": "estrogen." }, { "input": "Despite the potent anti - inflammatory effects of estrogen, few studies have investigated the contribution of estrogen to sex differences in the inflammatory response to stroke.", "output": "estrogen, estrogen." }, { "input": "This review examines the potential role for estrogen - mediated immunoprotection in ischemic injury.", "output": "estrogen." }, { "input": "Development of self - microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride.", "output": "berberine hydrochloride." }, { "input": "The purpose of this study was to develop a self - microemulsifying drug delivery system ( SMEDDS ) to improve the oral bioavailability of Berberine hydrochloride ( BBH ), an important bioactive compound from Chinese Medicines with poor water solubility.", "output": "Berberine hydrochloride, BBH." }, { "input": "Pseudoternary phase diagrams were constructed using oil, surfactant and co - surfactant types to identify the efficient self - microemulsification region.", "output": "There is no related enetity." }, { "input": "SMEDDS was characterized by morphological observation, droplet size, zeta - potential determination, stability, in vitro release and in vivo bioavailability study.", "output": "There is no related enetity." }, { "input": "The optimal formulation with the best self - microemulsifying and solubilization ability consisted of 40 % ( w / w ) of ethyl linoleate and oleic acid ( 2: 1 ), 35 % ( w / w ) Tween - 80 and 25 % ( w / w ) glycerol.", "output": "ethyl linoleate, oleic acid, Tween - 80, glycerol." }, { "input": "The SMEDDS of BBH could exhibit good stability.", "output": "BBH." }, { "input": "In vitro release test showed a complete release of BBH from SMEDDS was in 5 h.", "output": "BBH." }, { "input": "In vivo results indicated that the peak plasma concentration ( C ( max ) ) and the area under the curve ( AUC ( 0 --> 12 h ) ) of SMEDDS of BBH were higher than the commercial tablet by 163. 4 % and 154. 2 %, respectively.", "output": "BBH." }, { "input": "The relative bioavailability of SMEDDS of BBH was enhanced about 2. 42 - fold compared with the commercial tablet in rats.", "output": "BBH." }, { "input": "The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.", "output": "BBH." }, { "input": "Neuroendocrine aspects of catamenial epilepsy.", "output": "There is no related enetity." }, { "input": "This review describes the neuroendocrinological aspects of catamenial epilepsy, a menstrual cycle - related seizure disorder in women with epilepsy.", "output": "There is no related enetity." }, { "input": "Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period.", "output": "There is no related enetity." }, { "input": "Three types of catamenial seizures ( perimenstrual, periovulatory and inadequate luteal ) have been identified.", "output": "There is no related enetity." }, { "input": "The molecular pathophysiology of catamenial epilepsy remains unclear.", "output": "There is no related enetity." }, { "input": "Cyclical changes in the circulating levels of estrogens and progesterone ( P ) play a central role in the development of catamenial epilepsy.", "output": "estrogens, progesterone." }, { "input": "Endogenous neurosteroids such as allopregnanolone ( AP ) and allotetrahydrodeoxycorticosterone ( THDOC ) that modulate seizure susceptibility could play a critical role in catamenial epilepsy.", "output": "allopregnanolone, allotetrahydrodeoxycorticosterone, THDOC." }, { "input": "In addition, plasticity in GABA - A receptor subunits could play a role in the enhanced seizure susceptibility in catamenial epilepsy.", "output": "GABA." }, { "input": "P - derived neurosteroids such as AP and THDOC potentiate synaptic GABA - A receptor function and also activate extrasynaptic GABA - A receptors in the hippocampus and thus may represent endogenous regulators of catamenial seizure susceptibility.", "output": "THDOC, GABA, GABA." }, { "input": "Experimental studies have shown that neurosteroids confer greater seizure protection in animal models of catamenial epilepsy, especially without evident tolerance to their actions during chronic therapy.", "output": "There is no related enetity." }, { "input": "In the recently completed NIH - sponsored, placebo controlled phase 3 clinical trial, P therapy proved to be beneficial only in women with perimenstrual catamenial epilepsy but not in non - catamenial subjects.", "output": "There is no related enetity." }, { "input": "Neurosteroid analogs with favorable profile may be useful in the treatment of catamenial epilepsy.", "output": "There is no related enetity." }, { "input": "The high affinity IgE receptor ( Fc epsilon RI ) expression and function in airway smooth muscle.", "output": "There is no related enetity." }, { "input": "The airway smooth muscle ( ASM ) is no longer considered as merely a contractile apparatus and passive recipient of growth factors, neurotransmitters and inflammatory mediators signal but a critical player in the perpetuation and modulation of airway inflammation and remodeling.", "output": "There is no related enetity." }, { "input": "In recent years, a molecular link between ASM and IgE has been established through Fc epsilon receptors ( Fc epsilon Rs ) in modulating the phenotype and function of these cells.", "output": "There is no related enetity." }, { "input": "Particularly, the expression of high affinity IgE receptor ( Fc epsilon RI ) has been noted in primary human ASM cells in vitro and in vivo within bronchial biopsies of allergic asthmatic subjects.", "output": "There is no related enetity." }, { "input": "The activation of Fc epsilon RI on ASM cells suggests a critical yet almost completely ignored network which may modulate ASM cell function in allergic asthma.", "output": "There is no related enetity." }, { "input": "This review is intended to provide a historical perspective of IgE effects on ASM and highlights the recent updates in the expression and function of Fc epsilon RI, and to present future perspectives of activation of this pathway in ASM cells.", "output": "There is no related enetity." }, { "input": "miR - 34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme.", "output": "There is no related enetity." }, { "input": "Chromosome 1p36. 23 is frequently deleted in glioblastoma multiforme ( GBM ).", "output": "There is no related enetity." }, { "input": "miR - 34a localizes in this region.", "output": "There is no related enetity." }, { "input": "Our experiments found that miR - 34a was often deleted and epidermal growth factor receptor ( EGFR ) was frequently amplified in genomic DNA of 55 GBMs using single - nucleotide polymorphism DNA microarray.", "output": "There is no related enetity." }, { "input": "Notably, we found that the mean survival time was significantly shortened for patients whose GBMs had both EGFR amplification and miR - 34a deletion.", "output": "There is no related enetity." }, { "input": "Expression of miR - 34a was significantly lower in GBM samples compared with normal brain tissue.", "output": "There is no related enetity." }, { "input": "Forced expression of miR - 34a in GBM cells decreased their ability to migrate and profoundly decreased their levels of cyclin - A1, - B1, - D1, and - D3, as well as cyclin - dependent kinase and increased expression of cyclin kinase inhibitor proteins ( p21, p27 ).", "output": "There is no related enetity." }, { "input": "Also, human GBM cells ( U251 ) stable overexpressing mir - 34a formed smaller tumors when growing as xenografts in immunodeficient mice compared with wild - type U251 GBM cells.", "output": "There is no related enetity." }, { "input": "Furthermore, the protein expression of EGFR decreased in the cells with forced overexpression of miR - 34a.", "output": "There is no related enetity." }, { "input": "Additional studies showed that mir - 34a targeted Yin Yang - 1 ( YY1 ) and YY1 is a transcription factor that can stimulate the expression of EGFR.", "output": "There is no related enetity." }, { "input": "Thus, our data suggest that miR - 34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell - cycle proteins and EGFR.", "output": "There is no related enetity." }, { "input": "Moreover, we discovered for the first time that both deletion of miR - 34a and amplification of EGFR were associated with significantly decreased overall survival of GBM patients.", "output": "There is no related enetity." }, { "input": "Fatty acid composition of the edible sea cucumber Athyonidium chilensis.", "output": "Fatty acid." }, { "input": "The edible sea cucumber Athyonidium chilensis is a fishery resource of high commercial value in Chile, but no information on its lipid and fatty acid composition has been previously reported.", "output": "fatty acid." }, { "input": "Phospholipids were the major lipid contents of the ethanolic extracts of tubules, internal organs and body wall of A. chilensis.", "output": "There is no related enetity." }, { "input": "Saturated fatty acids predominated in tubule phospholipids ( 40. 69 % ), while in internal organs and body wall phospholipids, the monounsaturated fatty acids were in higher amounts ( 41. 99 % and 37. 94 %, respectively ).", "output": "Saturated fatty acids, monounsaturated fatty acids." }, { "input": "The main polyunsaturated fatty acids in phospholipids were C20: 2 omega - 6, arachidonic ( C20: 4 omega - 6 ) and eicosapentaenoic ( C20: 5 omega - 3 ) acids.", "output": "polyunsaturated fatty acids, arachidonic ( C20 : 4 omega - 6 ) and eicosapentaenoic ( C20 : 5 omega - 3 ) acids." }, { "input": "These results demonstrate for the first time that A. chilensis is a valuable food for human consumption in terms of fatty acids.", "output": "fatty acids." }, { "input": "The antioxidant activity of allylpyrocatechol is mediated via decreased generation of free radicals along with escalation of antioxidant mechanisms.", "output": "allylpyrocatechol." }, { "input": "Allylpyrocatechol ( APC ) is responsible for the antiinflammatory activity exhibited by the methanolic extract of leaves of Piper betle.", "output": "Allylpyrocatechol, APC." }, { "input": "As antiinflammatory compounds may display antioxidant properties and vice versa, we investigated the antioxidant effect of APC.", "output": "APC." }, { "input": "APC effectively reduced phorbol - myristate - acetate - induced generation of reactive oxygen species and superoxide in murine peritoneal macrophages as well as inhibited Escherichia - coli - induced phagocytic activity of macrophages.", "output": "APC, phorbol, myristate, acetate, oxygen, superoxide." }, { "input": "Furthermore, pBluescript SK ( + ) plasmid DNA damage induced by addition of sodium ascorbate was attenuated by APC as it inhibited transformation of the supercoiled form to a relaxed form.", "output": "sodium ascorbate, APC." }, { "input": "In addition, APC increased the enzymatic ( catalase ) and nonenzymatic ( GSH ) antioxidant components of murine macrophages.", "output": "APC, GSH." }, { "input": "Taken together, APC exhibited an antioxidant activity which was mediated both via decreased generation of free radicals along with increase in cellular antioxidants.", "output": "APC." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Effects of Crataegus microphylla on vascular dysfunction in streptozotocin - induced diabetic rats.", "output": "streptozotocin." }, { "input": "Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease.", "output": "There is no related enetity." }, { "input": "In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla ( CM ) extract in diabetic rats induced with streptozotocin ( STZ, intraperitoneal, 65 mg / kg ) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase ( iNOS ), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action.", "output": "streptozotocin, STZ, nitric oxide." }, { "input": "Starting at 4 weeks of diabetes, CM extract ( 100 mg / kg ) was administrated to diabetic rats for 4 weeks.", "output": "There is no related enetity." }, { "input": "In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor - alpha ( TNF - alpha ) and interleukin - 6 ( IL - 6 ), total nitrite - nitrate, and malondialdehite levels were increased in diabetic rats compared with controls.", "output": "acetylcholine, noradrenaline, nitrite, nitrate, malondialdehite." }, { "input": "Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats.", "output": "There is no related enetity." }, { "input": "In comparison, pretreatment of the aorta of diabetic rats with N - [ 3 ( aminomethyl ) benzyl ] - acetamidine, dihydrochloride ( 10 ( - 5 ) M ), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity.", "output": "N - [ 3 ( aminomethyl ) benzyl ] - acetamidine, dihydrochloride." }, { "input": "These results suggest that chronic in vivo treatment of CM preserves endothelium - dependent relaxation and vascular contraction in STZ - induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF - alpha and IL - 6 and by preventing lipid peroxidation.", "output": "STZ." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Investigation into the genotoxicity of water extracts from hypoxis species and a commercially available hypoxis preparation.", "output": "There is no related enetity." }, { "input": "We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species ( Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata ) and a commercial preparation thereof using the neutral red uptake ( NRU ) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells.", "output": "There is no related enetity." }, { "input": "The relative cytotoxicity of these samples was established by determining their NI50 values ( 50 % inhibition of NRU ), and these results were used for dose - finding in genotoxicity tests.", "output": "There is no related enetity." }, { "input": "None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "A new pyrimidinedione derivative from the gorgonian coral Verrucella umbraculum.", "output": "pyrimidinedione." }, { "input": "A new pyrimidinedione derivative, 9 - acetyl - 1, 3, 7 - trimethyl - pyrimidinedione ( 1 ), was isolated from the gorgonian coral Verrucella umbraculum, together with two known compounds, caffeine ( 2 ) and 1, 3 - dimethylpyrimidine - 2, 4 ( 1H, 3H ) - dione ( 3 ).", "output": "pyrimidinedione, 9 - acetyl - 1 , 3 , 7 - trimethyl - pyrimidinedione, caffeine, 1 , 3 - dimethylpyrimidine - 2 , 4 ( 1H , 3H ) - dione." }, { "input": "The structure of 1 was elucidated by the aid of 1D, 2D NMR and MS experiments.", "output": "There is no related enetity." }, { "input": "The structures of the known compounds were identified by comparison of their spectroscopic data with those reported in the literature.", "output": "There is no related enetity." }, { "input": "MicroRNA regulation of lipid metabolism.", "output": "There is no related enetity." }, { "input": "MicroRNAs are structural components of an epigenetic mechanism of post - transcriptional regulation of messenger RNA translation.", "output": "There is no related enetity." }, { "input": "Recently, there is significant interest in the application of microRNA as a blood - based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics.", "output": "There is no related enetity." }, { "input": "The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis.", "output": "There is no related enetity." }, { "input": "Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial.", "output": "curcuminoids." }, { "input": "Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity.", "output": "There is no related enetity." }, { "input": "Curcumin is a bioactive phytochemical with well - known antioxidant, anti - inflammatory, and cardioprotective properties.", "output": "Curcumin." }, { "input": "The present study investigated the hypolipidemic activity of curcumin in obese individuals.", "output": "curcumin." }, { "input": "Participants ( n = 30 ) were treated with curcuminoids ( 1 g / day ), or placebo in a randomized, double - blind, placebo - controlled, crossover trial.", "output": "curcuminoids." }, { "input": "Serum concentrations of total cholesterol, triglycerides, low - density lipoprotein cholesterol and high - density lipoprotein cholesterol, together with anthropometric parameters and high - sensitivity C - reactive protein were measured before and after each treatment period.", "output": "cholesterol, triglycerides, cholesterol, cholesterol." }, { "input": "Anthropometric parameters including weight, BMI, waist circumference, hip circumference, arm circumference, and body fat remained statistically unchanged by the end of trial ( p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "As for the lipid profile parameters, serum triglycerides were significantly reduced following curcumin supplementation ( p = 0. 009 ).", "output": "triglycerides, curcumin." }, { "input": "However, curcuminoids were not found to affect serum levels of total cholesterol, low - density lipoprotein cholesterol, high - density lipoprotein cholesterol, and high - sensitivity C - reactive protein ( p > 0. 05 ).", "output": "curcuminoids, cholesterol, cholesterol, cholesterol." }, { "input": "In summary, the findings of the present study indicated that curcuminoid supplementation ( 1 g / day for 30 days ) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat.", "output": "triglycerides." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Promotion of DNA repair by nuclear IKK beta phosphorylation of ATM in response to genotoxic stimuli.", "output": "There is no related enetity." }, { "input": "Ataxia - telangiectasia mutated ( ATM ) is one of the key molecules involved in the cellular response to DNA damage.", "output": "There is no related enetity." }, { "input": "A portion of activated ATM is exported from the nucleus into the cytoplasm, where it activates the I kappa B kinase / nuclear factor kappa B ( IKK / NF - kappa B ) signaling pathway.", "output": "There is no related enetity." }, { "input": "It has been thought that activated IKK beta, which is a critical kinase for NF - kappa B activation, generally resides in the cytoplasm and phosphorylates cytoplasmic downstream molecules, such as I kappa B alpha.", "output": "There is no related enetity." }, { "input": "Here, we identified a new role for IKK beta during the response to DNA damage.", "output": "There is no related enetity." }, { "input": "ATM phosphorylation in response to alkylating agents consisted of two phases: the early phase ( up to 3 h ) and late phase ( after 6 h ).", "output": "There is no related enetity." }, { "input": "A portion of the activated IKK beta generated during the DNA damage response was found to translocate into the nucleus and directly phosphorylate ATM in the late phase.", "output": "There is no related enetity." }, { "input": "Furthermore, the phosphorylation of ATM by nuclear IKK beta was suggested to promote DNA repair.", "output": "There is no related enetity." }, { "input": "In parallel, activated IKK beta induced classical NF - kappa B activation and was involved in anti - apoptosis.", "output": "There is no related enetity." }, { "input": "Our findings define the function of IKK beta during the response to DNA damage, which promotes cell survival and DNA repair, and maintains cellular homeostasis.", "output": "There is no related enetity." }, { "input": "The Grainyhead transcription factor Grhl3 / Get1 suppresses miR - 21 expression and tumorigenesis in skin: modulation of the miR - 21 target MSH2 by RNA - binding protein DND1.", "output": "There is no related enetity." }, { "input": "Epidermal differentiation and stratification, crucial for barrier formation, are regulated by a complex interplay of transcription factors, including the evolutionarily conserved Grainyhead - like 3 ( Grhl3 / Get1 ); Grhl3 - deleted mice exhibit impaired epidermal differentiation and decreased expression of multiple differentiation genes.", "output": "There is no related enetity." }, { "input": "To test whether Grhl3 regulates epidermal genes indirectly by controlling the expression of specific microRNAs ( miRs ), we performed miR profiling and identified 11 miRs that are differentially regulated in Grhl3 ( - / - ) skin, one of which is miR - 21, previously shown to be upregulated in diseased skin, including in psoriasis and squamous cell skin cancer.", "output": "There is no related enetity." }, { "input": "We found that miR - 21 is normally expressed in the post - mitotic suprabasal layers of the epidermis, overlapping with Grhl3.", "output": "There is no related enetity." }, { "input": "The miR - 21 promoter is bound and repressed by Grhl3 indicating that these two factors are involved in a regulatory loop maintaining homeostasis in the epidermis.", "output": "There is no related enetity." }, { "input": "Although miR - 21 overexpression in normal keratinocytes had mild effects on the expression of several known miR - 21 targets, an enhanced downregulation of the miR - 21 tumor - related targets, including MSH2, was observed in Ras - transformed keratinocytes.", "output": "There is no related enetity." }, { "input": "The increased sensitivity of transformed keratinocytes to miR - 21 ' s effects occurs in part through downregulation of the RNA - binding protein DND1 during the transformation process.", "output": "There is no related enetity." }, { "input": "Additionally, we observed increased tumorigenesis in mice subcutaneously injected with transformed keratinocytes lacking Grhl3.", "output": "There is no related enetity." }, { "input": "These findings indicate that decreased Grhl3 expression contributes to tumor progression and upregulation of the oncomir miR - 21 in squamous cell carcinoma of the skin.", "output": "There is no related enetity." }, { "input": "The first total synthesis of apigenin 7 - O - beta - D - cellobiosyl - 4 ' - O - beta - D - glucopyranoside isolated from Salvia uliginosa.", "output": "apigenin 7 - O - beta - D - cellobiosyl - 4 ' - O - beta - D - glucopyranoside." }, { "input": "The first total synthesis of apigenin 7 - O - beta - D - cellobioside ( 5 ) and apigenin 7 - O - beta - D - cellobiosyl - 4 ' - O - beta - D - glucopyranoside ( 8 ), which were isolated from petals of Salvia patens and Salvia uliginosa, were achieved in four and six steps and 76 % and 57 %, respectively, overall yield, from naringenin ( 1 ).", "output": "apigenin 7 - O - beta - D - cellobioside, apigenin 7 - O - beta - D - cellobiosyl - 4 ' - O - beta - D - glucopyranoside, naringenin." }, { "input": "The total synthesis contained two - glycosylation, acetylation, oxidation, selective deacetylation and deprotection steps.", "output": "There is no related enetity." }, { "input": "Although this route contained six steps, the targeted compounds were obtained with higher yields and easier purifications than other synthetic methods.", "output": "There is no related enetity." }, { "input": "Cytotoxicity of semisynthetic acetal triterpenes from one - pot vicinal diol cleavage following by lactolization: Reaction promoted by NaIO4 / SiO2 gel in THF.", "output": "acetal triterpenes, vicinal diol, NaIO4, SiO2, THF." }, { "input": "In situ C - C bond cleavage of vicinal diol following by the lactolisation resulted from separated treatment of Arjunolic acid ( 1 ), 24 - hydroxytormentic acid ( 2 ) and 3 - O - beta - D - glucopyranosylsitosterol ( 3 ) with sodium periodate and silica gel in dried THF according to the strategic position of hydroxyl functions in the molecule.", "output": "C - C, vicinal diol, Arjunolic acid, 24 - hydroxytormentic acid, 3 - O - beta - D - glucopyranosylsitosterol, sodium periodate, silica gel, THF, hydroxyl." }, { "input": "The reaction led to a lactol pentacyclic triterpenes 1A, 2A and a bicyclotriacetal of beta - sitosterol 3A.", "output": "lactol pentacyclic triterpenes, bicyclotriacetal of beta - sitosterol." }, { "input": "These products were further acetylated and the cytotoxicity of all molecules was evaluated against human fibrosarcoma HT1080 cancer cells lines.", "output": "There is no related enetity." }, { "input": "Tea tree oil - induced transcriptional alterations in Staphylococcus aureus.", "output": "There is no related enetity." }, { "input": "Tea tree oil ( TTO ) is a steam distillate of Melaleuca alternifolia that demonstrates broad - spectrum antibacterial activity.", "output": "There is no related enetity." }, { "input": "This study was designed to document how TTO challenge influences the Staphylococcus aureus transcriptome.", "output": "There is no related enetity." }, { "input": "Overall, bioinformatic analyses ( S. aureus microarray meta - database ) revealed that both ethanol and TTO induce related transcriptional alterations.", "output": "There is no related enetity." }, { "input": "TTO challenge led to the down - regulation of genes involved with energy - intensive transcription and translation, and altered the regulation of genes involved with heat shock ( e. g. clpC, clpL, ctsR, dnaK, groES, groEL, grpE and hrcA ) and cell wall metabolism ( e. g. cwrA, isaA, sle1, vraSR and vraX ).", "output": "There is no related enetity." }, { "input": "Inactivation of the heat shock gene dnaK or vraSR which encodes a two - component regulatory system that responds to peptidoglycan biosynthesis inhibition led to an increase in TTO susceptibility which demonstrates a protective role for these genes in the S. aureus TTO response.", "output": "There is no related enetity." }, { "input": "A gene ( mmpL ) encoding a putative resistance, nodulation and cell division efflux pump was also highly induced by TTO.", "output": "There is no related enetity." }, { "input": "The principal antimicrobial TTO terpene, terpinen - 4 - ol, altered ten genes in a transcriptional direction analogous to TTO.", "output": "terpene, terpinen - 4 - ol." }, { "input": "Collectively, this study provides additional insight into the response of a bacterial pathogen to the antimicrobial terpene mixture TTO.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Acute effects of methiocarb on oxidative damage and the protective effects of vitamin E and taurine in the liver and kidney of Wistar rats.", "output": "methiocarb, vitamin E, taurine." }, { "input": "Methiocarb ( MC ) is a widely used carbamate pesticide in agriculture and health programs.", "output": "Methiocarb, carbamate." }, { "input": "Although the main molecular mechanism of carbamate toxicity involves acetylcholinesterase inhibition, studies have also implicated the induction of oxidative stress.", "output": "carbamate." }, { "input": "Therefore, the present study was aimed to evaluate the effect of acute MC exposure on lipid peroxidation, antioxidant defense systems, histological changes in Wistar rats and the protective effect of pretreatment with vitamin E and taurine.", "output": "vitamin E, taurine." }, { "input": "A total of 48 rats were randomly divided into six groups.", "output": "There is no related enetity." }, { "input": "Rats in group I were given corn oil, while those in group III were dosed with vitamin E ( 100 mg / kg body weight ( b. w. ) ) and in group V were dosed with taurine ( 50 mg / kg b. w. ).", "output": "vitamin E, taurine." }, { "input": "Rats in group II were administered with MC only ( 25 mg / kg b. w., 1 / 4 of median lethal dose ( LD ( 50 ) ) ), while those in groups IV and VI were pretreated with vitamin E ( 100 mg / kg b. w. ) and taurine ( 50 mg / kg b. w. ) for 20 days, respectively, and then exposed to MC ( 25 mg / kg b. w. ).", "output": "vitamin E, taurine." }, { "input": "The rats administered with MC showed significant increase in the levels of malondialdehyde in the liver and kidney as an index of lipid peroxidation.", "output": "malondialdehyde." }, { "input": "Levels of glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were significantly increased, while activity of glutathione reductase remained unchanged in both the tissues after MC treatment.", "output": "glutathione, superoxide, glutathione, glutathione." }, { "input": "Mild degenerative histological changes were observed in liver tissue, while the changes in kidney tissue were more severe then liver after MC treatment.", "output": "There is no related enetity." }, { "input": "Pretreatment with vitamin E and taurine resulted in a significant decrease in the lipid peroxidation and alleviating effects on antioxidant defense systems in both the tissues, while protective effects on the histological changes were shown only in kidney when compared with liver.", "output": "vitamin E, taurine." }, { "input": "In conclusion, the study has demonstrated that the acute MC exposure in Wistar rats caused oxidative damage on liver and kidney, which were partly ameliorated by the pretreatment of vitamin E and taurine.", "output": "vitamin E, taurine." }, { "input": "Recent advances in medicinal chemistry of sulfonamides.", "output": "sulfonamides." }, { "input": "Rational design as anti - tumoral, anti - bacterial and anti - inflammatory agents.", "output": "There is no related enetity." }, { "input": "Now - a - days, cancer is becoming one of the major problems of public health in the world.", "output": "There is no related enetity." }, { "input": "Pharmacology treatment is a way to increase quality and long life.", "output": "There is no related enetity." }, { "input": "Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors.", "output": "sulfonamide." }, { "input": "In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti - tumoral, antibacterial and anti - inflammatory agents.", "output": "sulfonamides." }, { "input": "We show strategy design, structure - activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.", "output": "sulfonamide, sulfonamides." }, { "input": "Flax terpenoid pathway as a source of health promoting compounds.", "output": "terpenoid." }, { "input": "Flax is an important crop plant grown mainly for its fiber and seeds, which are also rich in omega - 3 fatty acids and valuable antioxidants derived from the terpenoid pathways including carotenoids, tocochromanols and sterols.", "output": "omega - 3 fatty acids, terpenoid, tocochromanols, sterols." }, { "input": "Many of those components found in flax have been recently shown to positively influence human health.", "output": "There is no related enetity." }, { "input": "Although terpenes vary greatly in their chemical structure, mainly two mechanisms of their biological activity can be considered: direct antioxidation, and a recently explored one, connected to specific receptor and cell signaling pathway activation.", "output": "terpenes." }, { "input": "Recent studies show that many of the health promoting agents derived from flax act through both of the mentioned mechanisms, resulting in synergistic physiological effects.", "output": "There is no related enetity." }, { "input": "The work summarizes the two mechanisms, focusing mainly on the one involving cell signaling, as a promising target for medicine and pharmacotherapy.", "output": "There is no related enetity." }, { "input": "Direct Effects of Vaccinium myrtillus L.", "output": "There is no related enetity." }, { "input": "Fruit Extracts on Rat Heart Mitochondrial Functions.", "output": "There is no related enetity." }, { "input": "In this study, the direct influence of bilberry ( Vaccinium myrtillus ) fruit extracts ( aqueous and ethanolic ) rich in anthocyanins on the oxidative phosphorylation of isolated rat heart mitochondria was investigated in vitro.", "output": "anthocyanins." }, { "input": "Higher concentrations of bilberry extracts concentration - dependently inhibited mitochondrial state 3 respiration ( by 23 % - 61 % ) with pyruvate plus malate, mildly ( by 1. 2 - to 1. 3 - fold ) uncoupled the oxidative phosphorylation, and increased ( by 30 % - 87 % ) the state 4 respiration rate in the presence of exogenous cytochrome c.", "output": "pyruvate, malate." }, { "input": "Succinate oxidation was less affected.", "output": "Succinate." }, { "input": "Pure anthocyanins, the main components of used extracts, malvidin - 3 - glucoside, malvidin - 3 - galactoside, and cyanidin - 3 - galactoside, had no effect on oxidation of pyruvate plus malate.", "output": "anthocyanins, malvidin - 3 - glucoside, malvidin - 3 - galactoside, cyanidin - 3 - galactoside, pyruvate, malate." }, { "input": "A statistically significant decrease in H2 O2 production by mitochondria was found in the presence of bilberry fruit extracts.", "output": "H2 O2." }, { "input": "Our findings show that bilberry fruit anthocyanin - rich extracts possess direct effects on rat heart mitochondrial function in vitro.", "output": "anthocyanin." }, { "input": "These findings give the first insights into the mechanism ( s ) of their action on cellular energy metabolism.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Ethanol extract of Magnolia officinalis prevents lipopolysaccharide - induced memory deficiency via its antineuroinflammatory and antiamyloidogenic effects.", "output": "Ethanol." }, { "input": "Magnolia bark contains several compounds such as magnolol, honokiol, 4 - O - methylhonokiol, obovatol, and other neolignan compounds.", "output": "magnolol, honokiol, 4 - O - methylhonokiol, obovatol, neolignan." }, { "input": "These compounds have been reported to have various beneficial effects in various diseases.", "output": "There is no related enetity." }, { "input": "There is sufficient possibility that ethanol extract of Magnolia officinalis is more effective in amyloidogenesis via synergism of these ingredients.", "output": "ethanol." }, { "input": "Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer ' s disease ( AD ).", "output": "There is no related enetity." }, { "input": "We investigated whether the ethanol extract of M. officinalis ( 10 mg / kg in 0. 05 % ethanol ) prevents memory dysfunction and amyloidogenesis in AD mouse model by intraperitoneal lipopolysaccharide ( LPS, 250 micro g / kg / day for seven times ) injection.", "output": "ethanol, ethanol." }, { "input": "We found that ethanol extract of M. officinalis prevented LPS - induced memory deficiency as well as inhibited the LPS - induced elevation of inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase 2, and activation of astrocytes and microglia.", "output": "ethanol, nitric oxide." }, { "input": "In particular, administration of M. officinalis ethanol extract inhibited LPS - induced amyloidogenesis, which resulted in the inhibition of amyloid precursor protein, beta - site amyloid - precursor - protein - cleaving enzyme 1 and C99.", "output": "ethanol." }, { "input": "Thus, this study shows that ethanol extract of M. officinalis prevents LPS - induced memory impairment as well as amyloidogenesis via inhibition of neuroinflammation and suggests that ethanol extract of M. officinalis might be a useful intervention for neuroinflammation - associated diseases such as AD.", "output": "ethanol, ethanol." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Metabotropic glutamate receptor 4 in the basal ganglia of parkinsonian monkeys: ultrastructural localization and electrophysiological effects of activation in the striatopallidal complex.", "output": "glutamate." }, { "input": "Group III metabotropic glutamate receptors ( mGluR4, 7, 8 ) are widely distributed in the basal ganglia.", "output": "glutamate." }, { "input": "Injection of group III mGluR agonists into the striatopallidal complex alleviates parkinsonian symptoms in 6 - hydroxydopamine - treated rats.", "output": "6 - hydroxydopamine." }, { "input": "In vitro rodent studies have suggested that this may be partly due to modulation of synaptic transmission at striatopallidal and corticostriatal synapses through mGluR4 activation.", "output": "There is no related enetity." }, { "input": "However, the in vivo electrophysiological effects of group III mGluRs activation upon basal ganglia neurons activity in nonhuman primates remain unknown.", "output": "There is no related enetity." }, { "input": "Thus, in order to examine the anatomical substrates and physiological effects of group III mGluRs activation upon striatal and pallidal neurons in monkeys, we used electron microscopy immunohistochemistry to localize mGluR4, combined with local administration of the group III mGluR agonist L - AP4, or the mGluR4 positive allosteric modulator VU0155041, to assess the effects of group III mGluR activation on the firing rate and pattern of striatal and pallidal neurons in 1 - methyl - 4 - phenyl - 1, 2, 3, 6 - tetrahydropyridine ( MPTP ) - treated parkinsonian monkeys.", "output": "L - AP4, VU0155041, 1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine, MPTP." }, { "input": "At the ultrastructural level, striatal mGluR4 immunoreactivity was localized in pre - ( 60 % ) and post - synaptic ( 30 % ) elements, while in the GPe, mGluR4 was mainly expressed pre - synaptically ( 90 % ).", "output": "There is no related enetity." }, { "input": "In the putamen, terminals expressing mGluR4 were evenly split between putative excitatory and inhibitory terminals, while in the GPe, most labeled terminals displayed the ultrastructural features of striatal - like inhibitory terminals, though putative excitatory boutons were also labeled.", "output": "There is no related enetity." }, { "input": "No significant difference was found between normal and parkinsonian monkeys.", "output": "There is no related enetity." }, { "input": "Extracellular recordings in awake MPTP - treated monkeys revealed that local microinjections of small volumes of L - AP4 resulted in increased firing rates in one half of striatal cells and one third of pallidal cells, while a significant number of neurons in both structures showed either opposite effects, or did not display any significant rate changes following L - AP4 application.", "output": "MPTP, L - AP4, L - AP4." }, { "input": "VU0155041 administration had little effect on firing rates.", "output": "VU0155041." }, { "input": "Both compounds also had subtle effects on bursting and oscillatory properties, acting to increase the irregularity of firing.", "output": "There is no related enetity." }, { "input": "The occurrence of pauses in firing was reduced in the majority ( 80 % ) of GPe neurons after L - AP4 injection.", "output": "L - AP4." }, { "input": "Our findings indicate that glutamate can mediate multifarious physiological effects upon striatal and pallidal neurons through activation of pre - synaptic group III mGluRs at inhibitory and excitatory synapses in parkinsonian monkeys.", "output": "glutamate." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Learning to forget: manipulating extinction and reconsolidation processes to treat addiction.", "output": "There is no related enetity." }, { "input": "Finding effective long - lasting treatments for drug addiction has been an elusive goal.", "output": "There is no related enetity." }, { "input": "Consequently, researchers are beginning to investigate novel treatment strategies including manipulations of drug - associated memories.", "output": "There is no related enetity." }, { "input": "When environmental stimuli ( cues ) become associated with drug use, they become powerful motivators of continued drug use and relapse after abstinence.", "output": "There is no related enetity." }, { "input": "Reducing the strength of these cue - drug memories could decrease the number of factors that induce craving and relapse to aid in the treatment of addiction.", "output": "There is no related enetity." }, { "input": "Enhancing the consolidation of extinction learning and / or disrupting cue - drug memory reconsolidation are two strategies that have been proposed to reduce the strength of cues in motivating drug - seeking and drug - taking behavior.", "output": "There is no related enetity." }, { "input": "Here, we review the latest basic and clinical research elucidating the mechanisms underlying consolidation of extinction and reconsolidation of cue - drug memories in the hopes of developing pharmacological tools that exploit these signaling systems to treat addiction.", "output": "There is no related enetity." }, { "input": "Syntheses and antibacterial activity of Schiff bases from 16 - isopropyl - 5, 9 - dimethyltetracyclo [ 10. 2. 2. 0 ( 1, 10 ). 0 ( 4, 9 ) ] hexadec - 15 - ene - 5, 14 - dicarboxylic acid.", "output": "Schiff bases, 16 - isopropyl - 5 , 9 - dimethyltetracyclo [ 10 . 2 . 2 . 0 ( 1 , 10 ) . 0 ( 4 , 9 ) ] hexadec - 15 - ene - 5 , 14 - dicarboxylic acid." }, { "input": "16 - Isopropyl - 5, 9 - dimethyltetracyclo [ 10. 2. 2. 0 ( 1, 10 ). 0 ( 4, 9 ) ] hexadec - 15 - ene - 5, 14 - dicarboxylic acid ( 1b ) was prepared from rosin through a Diels - Alder addition reaction.", "output": "16 - Isopropyl - 5 , 9 - dimethyltetracyclo [ 10 . 2 . 2 . 0 ( 1 , 10 ) . 0 ( 4 , 9 ) ] hexadec - 15 - ene - 5 , 14 - dicarboxylic acid." }, { "input": "Then, a group of Schiff bases derived from 1b was synthesised.", "output": "Schiff bases." }, { "input": "Their structures were characterised by IR, ( 1 ) H - NMR, MS and elemental analysis.", "output": "( 1 ) H." }, { "input": "The antibacterial activities of these newly synthesised Schiff bases were also investigated.", "output": "Schiff bases." }, { "input": "The results show that these compounds possess antibacterial activities against Staphylococcus aureus and Escherichia coli.", "output": "There is no related enetity." }, { "input": "Among them, compounds 5a, 5b and 5c, exhibit remarkable antibacterial activity against E. coli.", "output": "There is no related enetity." }, { "input": "TGF - beta and NF - kappa B signal pathway cross - talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers.", "output": "There is no related enetity." }, { "input": "Transforming growth factor - beta ( TGF - beta ) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma ( HNSCC ).", "output": "There is no related enetity." }, { "input": "Attenuation of canonical TGF - beta signaling enhances de novo tumor development, whereas TGF - beta overexpression and signaling paradoxically promotes malignant progression.", "output": "There is no related enetity." }, { "input": "We recently observed that TGF - beta - induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor - kappa B ( NF - kappa B ), a transcription factor, which promotes malignant progression in HNSCC.", "output": "There is no related enetity." }, { "input": "However, what role cross - talk between components of the TGF - beta and NF - kappa B pathways plays in altered activation of these pathways has not been established.", "output": "There is no related enetity." }, { "input": "Here, we show TGF - beta receptor II and TGF - beta - activated kinase 1 ( TAK1 ) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF - kappa B family member RELA ( p65 ).", "output": "There is no related enetity." }, { "input": "Further, TGF - beta 1 treatment induced sequential phosphorylation of TAK1, IKK, I kappa B alpha and RELA in human HNSCC lines.", "output": "There is no related enetity." }, { "input": "TAK1 enhances TGF - beta - induced NF - kappa B activation, as TAK1 siRNA knockdown decreased TGF - beta 1 - induced phosphorylation of IKK, I kappa B and RELA, degradation of I kappa B alpha, RELA nuclear translocation and DNA binding, and NF - kappa B - induced reporter and target gene transcription.", "output": "There is no related enetity." }, { "input": "Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion.", "output": "There is no related enetity." }, { "input": "Celastrol, a TAK1 inhibitor and anti - inflammatory compound used in traditional Chinese medicine, also decreased TGF - beta 1 - induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF - beta 1 - and tumor necrosis factor - alpha ( TNF - alpha ) - induced NF - kappa B reporter gene activity.", "output": "Celastrol." }, { "input": "Celastrol also inhibited cell proliferation, while increasing sub - G0 DNA fragmentation and Annexin V markers of apoptosis.", "output": "Celastrol." }, { "input": "Furthermore, TGF - beta and RELA activation promoted SMAD7 expression.", "output": "There is no related enetity." }, { "input": "In turn, SMAD7 preferentially suppressed TGF - beta - induced SMAD and NF - kappa B reporters when compared with constitutive or TNF - alpha - induced NF - kappa B reporter gene activation.", "output": "There is no related enetity." }, { "input": "Thus, cross - talk by TGF - beta via TAK1 and NF - kappa B promotes the malignant phenotype of HNSCC.", "output": "There is no related enetity." }, { "input": "Moreover, NF - kappa B may contribute to the downstream attenuation of canonical TGF - beta signaling through increased SMAD7 expression.", "output": "There is no related enetity." }, { "input": "Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro - oncogenic TGF - beta - NF - kappa B signal pathway.", "output": "Celastrol." }, { "input": "Insulin resistance is not necessarily an essential element of metabolic syndrome.", "output": "There is no related enetity." }, { "input": "Type 2 diabetes is frequently associated with metabolic syndrome ( MetS ).", "output": "There is no related enetity." }, { "input": "Insulin resistance ( IR ) is thought to be the underlying pathophysiology of MetS.", "output": "There is no related enetity." }, { "input": "The purpose of this study is to examine the association of MetS with IR and beta cell function.", "output": "There is no related enetity." }, { "input": "This is a cross - sectional study in NHANES 1999 - 2000 participants who were at least 18 years old, including 911 non - Hispanic whites ( NHW ), 398 non - Hispanic blacks ( NHB ), and 595 Mexican - Americans ( MA ).", "output": "There is no related enetity." }, { "input": "MetS was defined based on the revised ATP III.", "output": "There is no related enetity." }, { "input": "IR and beta cell function were calculated using homeostasis model assessment ( HOMA - IR and HOMA - B ).", "output": "There is no related enetity." }, { "input": "The high - risk tertile was defined as the highest HOMA - IR and lowest HOMA - B.", "output": "There is no related enetity." }, { "input": "The odds ratio ( OR ) was calculated against the other two tertiles.", "output": "There is no related enetity." }, { "input": "The relationship of HOAM - IR and HOMA - B with the components of MetS was also examined.", "output": "There is no related enetity." }, { "input": "IR was a risk factor of MetS in all three ethnic groups ( OR 4. 17 - 12. 01, P < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Fasting glucose, triglycerides, and HDL cholesterol were associated with IR ( P < 0. 001 ) and correlated with HOMA - IR ( P < 0. 001 ), while inconsistent results were noted in blood pressure and waist circumference among three racial / ethnic groups.", "output": "glucose, triglycerides, cholesterol." }, { "input": "However, in the MetS subjects, 32 % of NHW, 28 % of NHB, and 44 % of MA were not in the IR tertile and in the IR subjects, 25 % of NHW, 36 % NHB, and 30 % of MA did not have MetS.", "output": "There is no related enetity." }, { "input": "No relationship was found between beta cell function and MetS.", "output": "There is no related enetity." }, { "input": "Although IR is a risk factor for MetS, IR is neither necessary nor required for MetS.", "output": "There is no related enetity." }, { "input": "An in vitro Study on the DNA Damaging Effects of Phytochemicals Partially Isolated from an Extract of Glinus lotoides.", "output": "There is no related enetity." }, { "input": "An extract of Glinus lotoides, a medicinal plant used in Africa and Asia for various therapeutic purposes, was recently shown to cause DNA damage in vitro.", "output": "There is no related enetity." }, { "input": "To further explore the potential genotoxicity of this plant, fractionation of the crude extract was performed using reverse phase solid - phase extraction and a stepwise gradient elution of methanol in water.", "output": "methanol." }, { "input": "Four fractions were collected and subsequently analysed for their DNA damaging effects in mouse lymphoma cells using an alkaline version of the comet assay.", "output": "There is no related enetity." }, { "input": "To identify potential genotoxic and non - genotoxic principles, each fraction was then subjected to liquid chromatography coupled to mass spectrometry, LC - MS / MS.", "output": "There is no related enetity." }, { "input": "1D and 2D nuclear magnetic resonance analyses were used to confirm the identity of some saponins.", "output": "saponins." }, { "input": "Although fractions containing a mixture of flavonoids and oleanane - type saponins or oleanane - type saponins alone produced no DNA damage, those containing hopane - type saponins exhibited a pronounced DNA damaging effect without affecting the viability of the cells.", "output": "flavonoids, oleanane, saponins, oleanane, saponins, hopane, saponins." }, { "input": "To conclude, even if this study presents evidence that hopane - type of saponins are endowed with a DNA damaging ability, further studies are needed before individual saponins can be cited as a culprit for the previously reported genotoxicity of the crude extract of G. lotoides.", "output": "hopane, saponins, saponins." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Chronic treatment with myo - inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice.", "output": "myo - inositol." }, { "input": "Type 2 diabetes is a complex disease characterized by a state of insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue or liver.", "output": "There is no related enetity." }, { "input": "Some inositol isomers have been reported to possess insulin - mimetic activity and to be efficient in lowering blood glucose level.", "output": "inositol." }, { "input": "The aim of the present study was to assess in mice the metabolic effects of a chronic treatment with myo - inositol, the most common stereoisomer of inositol.", "output": "myo - inositol, inositol." }, { "input": "Mice given myo - inositol treatment ( 0. 9 or 1. 2 mg g ( - 1 ) day ( - 1 ), 15 days, orally or intraperitoneally ) exhibited an improved glucose tolerance due to a greater insulin sensitivity.", "output": "myo - inositol, glucose." }, { "input": "Mice treated with myo - inositol exhibited a decreased white adipose tissue accretion ( - 33 %, P <. 005 ) compared with controls.", "output": "myo - inositol." }, { "input": "The decrease in white adipose tissue deposition was due to a decrease in adipose cell volume ( - 33 %, P <. 05 ), while no change was noticed in total adipocyte number.", "output": "There is no related enetity." }, { "input": "In skeletal muscle, in vivo as well as ex vivo myo - inositol treatment increased protein kinase B / Akt phosphorylation under baseline and insulin - stimulated conditions, suggesting a synergistic action of myo - inositol treatment and insulin on proteins of the insulin signalling pathway.", "output": "myo - inositol, myo - inositol." }, { "input": "Myo - inositol could therefore constitute a viable nutritional strategy for the prevention and / or treatment of insulin resistance and type 2 diabetes.", "output": "Myo - inositol." }, { "input": "Molecular mechanisms that desensitize metabotropic glutamate receptor signaling: an overview.", "output": "glutamate." }, { "input": "The purpose of the present article is to review our actual knowledge on the desensitization of metabotropic glutamate receptors based on the literature available so far, with the attempt to emphasize all converging data and to give a possible explanation to those evidences that still remain controversial.", "output": "glutamate." }, { "input": "1.", "output": "There is no related enetity." }, { "input": "We review our knowledge on the regulation of mGlu receptors based on the available literature 2.", "output": "There is no related enetity." }, { "input": "We report converging data and we comment on issues that still remain controversial.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Azole interactions with multidrug therapy in pediatric oncology.", "output": "Azole." }, { "input": "Patients with cancer receive multidrug therapy.", "output": "There is no related enetity." }, { "input": "Antineoplastic agents and supportive care drugs are often administered together, leading to potential drug - drug interactions.", "output": "There is no related enetity." }, { "input": "These interactions may have significant clinical implications in terms of toxicity or a decrease in the efficacy of the treatment administered.", "output": "There is no related enetity." }, { "input": "Here, we focus on the role of azoles and their main pharmacokinetic interactions with the principal classes of drugs used in pediatric oncology.", "output": "azoles." }, { "input": "The co - administration of azoles and antineoplastic agents, corticosteroids, immunosuppressants, antacids, antiemetics, antiepileptic drugs and analgesics was investigated, and a practical guide on the management of these drugs when administered together is provided.", "output": "azoles, corticosteroids." }, { "input": "Bioremoval of heavy metals from industrial effluent by fixed - bed column of red macroalgae.", "output": "There is no related enetity." }, { "input": "Three different species of nonliving red algal biomass Laurancia obtusa, Geldiella acerosa and Hypnea sp. were used to build three types of fixed - bed column for the removal of toxic heavy metal ions such as Cu ( 2 + ), Zn ( 2 + ), Mn ( 2 + ) and Ni ( 2 + ) from industrial effluent.", "output": "Cu ( 2 + ), Zn ( 2 + ), Mn ( 2 + ), Ni ( 2 + )." }, { "input": "In general, the highest efficiency of metal ion bioremoval was recorded for algal column of L. obtusa followed by G. acerosa and the lowest one was recorded for Hypnea sp., with mean removal values of 94 %, 85 % and 71 %, respectively.", "output": "There is no related enetity." }, { "input": "The obtained results showed that biological treatments of industrial effluents with these algal columns, using standard algal biotest, Pseudokirchneriella subcapitata, were capable of reducing effluent toxicities from 75 % to 15 %, respectively.", "output": "There is no related enetity." }, { "input": "Red algal column may be considered as an inexpensive and efficient alternative treatment for conventional removal technology, for sequestering heavy metal ions from industrial effluents.", "output": "There is no related enetity." }, { "input": "Nuclear Receptors in atherosclerosis: a superfamily with many ' Goodfellas '.", "output": "There is no related enetity." }, { "input": "Nuclear Receptors form a superfamily of 48 transcription factors that exhibit a plethora of functions in steroid hormone signaling, regulation of metabolism, circadian rhythm and cellular differentiation.", "output": "There is no related enetity." }, { "input": "In this review, we describe our current knowledge on the role of Nuclear Receptors in atherosclerosis, which is a multifactorial disease of the vessel wall.", "output": "There is no related enetity." }, { "input": "Various cell types are involved in this chronic inflammatory pathology in which multiple cellular processes and numerous genes are dysregulated.", "output": "There is no related enetity." }, { "input": "Systemic risk factors for atherosclerosis are among others adverse blood lipid profiles, enhanced circulating cytokine levels, as well as increased blood pressure.", "output": "There is no related enetity." }, { "input": "Since many Nuclear Receptors modulate lipid profiles or regulate blood pressure they indirectly affect atherosclerosis.", "output": "There is no related enetity." }, { "input": "In the present review, we focus on the functional involvement of Nuclear Receptors within the atherosclerotic vessel wall, more specifically on their modulation of cellular functions in endothelial cells, smooth muscle cells and macrophages.", "output": "There is no related enetity." }, { "input": "Collectively, this overview shows that most of the Nuclear Receptors are athero - protective in atherosclerotic lesions.", "output": "There is no related enetity." }, { "input": "Enzyme replacement therapy for mucopolysaccharidosis VI: long - term cardiac effects of galsulfase ( Naglazyme (R) ) therapy.", "output": "There is no related enetity." }, { "input": "Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI ( MPS VI ).", "output": "There is no related enetity." }, { "input": "Cardiac ultrasound was performed to investigate these findings in subjects during long - term enzyme replacement therapy ( ERT ) with recombinant human arylsulfatase B ( rhASB, rhN - acetylgalactosamine 4 - sulfatase, galsulfase, Naglazyme (R) ).", "output": "rhN - acetylgalactosamine." }, { "input": "Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg / kg during phase 1 / 2, phase 2, and phase 3 trials of rhASB.", "output": "There is no related enetity." }, { "input": "At baseline, mitral and aortic valve obstruction was present and was significantly greater in those >= 12 years of age.", "output": "There is no related enetity." }, { "input": "Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those < 12 years.", "output": "There is no related enetity." }, { "input": "Left ventricular hypertrophy, with averaged z - scores ranging from 1. 6 - 1. 9 SD greater than normal, was present for ages both < 12 and >= 12 years.", "output": "There is no related enetity." }, { "input": "After 96 weeks of ERT, ventricular septal hypertrophy regressed in those < 12 years.", "output": "There is no related enetity." }, { "input": "For those >= 12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically.", "output": "There is no related enetity." }, { "input": "Obstructive gradients across mitral and aortic valves remained unchanged.", "output": "There is no related enetity." }, { "input": "The results suggest that long - term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those < 12 years of age.", "output": "There is no related enetity." }, { "input": "Preformulation and formulation of newly synthesized QNT3 - 18 for development of a skin whitening agent.", "output": "QNT3 - 18." }, { "input": "New molecules having the structure of ( E ) - 2 - ( 4 - tert - butylbenzylidene ) hydrazinecarbothioamide ( QNT3 - 18 ) or 4 - tert - butylphenylthiourea ( QNT3 - 20 ) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation.", "output": "( E ) - 2 - ( 4 - tert - butylbenzylidene ) hydrazinecarbothioamide, QNT3 - 18, 4 - tert - butylphenylthiourea, QNT3 - 20." }, { "input": "Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies.", "output": "There is no related enetity." }, { "input": "QNT3 - 18 or QNT3 - 20 showed a strong single endothermic peak at 159. 34 degrees C with 10. 79 mu m - sized or at 150. 69 degrees C with 9. 0 mu m - sized aggregated particles, respectively.", "output": "QNT3 - 18, QNT3 - 20." }, { "input": "Both QNT3 - 18 and QNT3 - 20 did not show cytotoxicity at effective concentration range ( 0. 4 micro M ) against keratinocyte cells and QNT3 - 18 was more retained than QNT3 - 20 in the skin instead of permeating through the skin.", "output": "QNT3 - 18, QNT3 - 20, QNT3 - 18, QNT3 - 20." }, { "input": "QNT3 - 18 or QNT3 - 20 was practically insoluble in water; the aqueous solubility was 3. 8 +/- 0. 37 or 130. 6 +/- 2. 52 mu g / mL, respectively.", "output": "QNT3 - 18, QNT3 - 20." }, { "input": "Also, the partition coefficient value ( log P ) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3. 9 or 2. 6, respectively.", "output": "octanol." }, { "input": "The skin retention amount of QNT3 - 18 was 1. 7 - fold higher than that of QNT3 - 20.", "output": "QNT3 - 18, QNT3 - 20." }, { "input": "When the optimal SLN cream ( J3 formulation ) containing 4 mu M QNT3 - 18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3 - 18 quickly recovered to normal compared to skin treated with SLN cream without QNT3 - 18.", "output": "QNT3 - 18, QNT3 - 18, QNT3 - 18." }, { "input": "Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3 - 18 might be appropriate carriers for skin whitening agents.", "output": "QNT3 - 18." }, { "input": "Formulas used by tibetan doctors at men - tsee - khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to identify formulas used at Men - Tsee - Khang ( Tibetan Medical and Astrological Institute ), India, for the treatment of neuropsychiatric disorders and to compare the Tibetan usage of particular ingredients with pharmacological data from the scientific database.", "output": "There is no related enetity." }, { "input": "Using ethnographic methods, five doctors were selected and interviewed.", "output": "There is no related enetity." }, { "input": "A correlation was observed between central nervous system disorders and rLung, one of the three humors in Tibetan medicine, which imbalance is the source of mental disorders, and ten multi - ingredient formulas used to treat the imbalance of this particular humor were identified.", "output": "There is no related enetity." }, { "input": "These formulas utilize 61 ingredients; among them were 48 plant species.", "output": "There is no related enetity." }, { "input": "Each formula treats several symptoms related to rLung imbalance, so the plants may have therapeutic uses distinct from those of the formulas in which they are included.", "output": "There is no related enetity." }, { "input": "Myristica fragrans, nutmeg, is contained in 100 % of the formulas, and its seeds exhibit stimulant and depressant actions affecting the central nervous system.", "output": "There is no related enetity." }, { "input": "Preclinical and clinical data from the scientific literature indicate that all of the formulas include ingredients with neuropsychiatric action and corroborate the therapeutic use of 75. 6 % of the plants.", "output": "There is no related enetity." }, { "input": "These findings indicate a level of congruence between the therapeutic uses of particular plant species in Tibetan and Western medicines.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Effect of tetrabrombisphenol A on induction of apoptosis in the testes and changes in expression of selected testicular genes in CD1 mice.", "output": "tetrabrombisphenol A." }, { "input": "Tetrabromobisphenol A ( TBBPA ) is a substance widely used in industry as a flame retardant.", "output": "Tetrabromobisphenol A, TBBPA." }, { "input": "TBBPA was found in the environment and was detected even in the human body.", "output": "TBBPA." }, { "input": "The effect of this chemical was observed in different cell lines in vitro and it is supposed that TBBPA may affect various hormonal systems in vivo.", "output": "TBBPA." }, { "input": "In this study we examined the effect of TBBPA on the reproductive parameters of two generations of outbred mice in vivo.", "output": "TBBPA." }, { "input": "Experimental and control animals of F1 generation were bred in various conditions to enable evaluation of the possible trans - generational effect.", "output": "There is no related enetity." }, { "input": "An increased incidence of apoptosis in the testes and changes in the morphometry of seminiferous tubules was detected in the experimental animals.", "output": "There is no related enetity." }, { "input": "In addition, changes in the expression pattern of selected genes encoding proteins that play an important role during spermatogenesis were observed.", "output": "There is no related enetity." }, { "input": "In contrast, sperm quality and reproduction were not affected by TBBPA.", "output": "TBBPA." }, { "input": "Mild Mitochondrial Depolarization is Involved in a Neuroprotective Mechanism of Citrus sunki Peel Extract.", "output": "There is no related enetity." }, { "input": "Mitochondrial membrane potential ( increment Psi m ) contributes to determining a driving force for calcium to enter the mitochondria.", "output": "calcium." }, { "input": "It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis.", "output": "There is no related enetity." }, { "input": "Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults.", "output": "calcium." }, { "input": "In the present study, using both real - time recording and flow cytometric analyses of increment Psi m, we demonstrated that ethanolic peel extract of Citrus sunki Hort.", "output": "There is no related enetity." }, { "input": "ex Tanaka ( CPE ) and its active compounds are capable of inducing a mild mitochondrial depolarization.", "output": "There is no related enetity." }, { "input": "Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on increment Psi m.", "output": "Polymethoxylated flavones, nobiletin, tangeretin." }, { "input": "Neuronal viability was significantly increased in a dose - dependent manner by CPE treatment in H2 O2 - stimulated HT - 22 cells as an in vitro neuronal insult model.", "output": "H2 O2." }, { "input": "CPE treatment significantly inhibited H2 O2 - induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti - poly ( ADP - ribose ) polymerase ( PARP ) cleavage.", "output": "H2 O2, poly ( ADP - ribose )." }, { "input": "CPE treatment significantly blocked mitochondrial calcium overload in H2 O2 - stimulated HT - 22 neurons as indicated by rhod - 2 acetoxymethyl ester.", "output": "H2 O2, acetoxymethyl ester." }, { "input": "Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Dendritic cell migration assay: a potential prediction model for identification of contact allergens.", "output": "There is no related enetity." }, { "input": "This manuscript describes methodology and a prediction model for the MUTZ - LC migration assay.", "output": "There is no related enetity." }, { "input": "The assay represents the physiological change in Langerhans cell ( LC ) behavior after exposure to a sensitizing chemical, resulting in LC migration from the epidermis to the dermis.", "output": "There is no related enetity." }, { "input": "MUTZ - LC are derived from the commercially available MUTZ - 3 cell line.", "output": "There is no related enetity." }, { "input": "Upon exposure to a sensitizer MUTZ - LC migrate preferentially towards CXCL12 whereas upon exposure to a non - sensitizer MUTZ - LC migrate towards CCL5.", "output": "There is no related enetity." }, { "input": "A CXCL12 / CCL5 ratio > 1. 10 in 2 / 3 independent experiments is indicative of a sensitizer, whereas a CXCL12 / CCL5 ratio <= 1. 10 is indicative of a non - sensitizer.", "output": "There is no related enetity." }, { "input": "At non cytotoxic chemical concentrations 9 sensitizers ( 2, 4 - dinitrochlorobenzene, paraphenylendiamine, cinnamaldehyde, isoeugenol, nickel - sulfate, tetramethylthiuram disulfide, eugenol, cinnamic - alcohol, ammonium - hexachloroplatinate ) were distinguished from 4 non sensitizers ( sodium lauryl sulfate, salicylic acid, phenol, octanoic acid ).", "output": "2 , 4 - dinitrochlorobenzene, paraphenylendiamine, cinnamaldehyde, isoeugenol, nickel - sulfate, tetramethylthiuram disulfide, eugenol, cinnamic - alcohol, ammonium - hexachloroplatinate, sodium lauryl sulfate, salicylic acid, phenol, octanoic acid." }, { "input": "Critical points in assay performance are ( i ) MUTZ - 3 passage number after thawing ( p6 - p40 ); ( ii ) cell viability ( > 80 % ); ( iii ) standard curve to optimize correlation of fluorescence with cell number; and ( iv ) optimization of the concentration of rhCXCL12 and rhCCL5 in transwell.", "output": "There is no related enetity." }, { "input": "The protocol has been tested in three European laboratories and results suggest that it may provide working conditions for performing the DC migration assay which is aimed at distinguishing sensitizers from non sensitizers.", "output": "There is no related enetity." }, { "input": "Non - invasive brain stimulation in neurological diseases.", "output": "There is no related enetity." }, { "input": "Non - invasive brain stimulation has shown its potential to modulate brain plasticity in humans.", "output": "There is no related enetity." }, { "input": "Endeavour has been made to utilize brain stimulation in neurological diseases to enhance adaptive processes and prevent potential maladaptive ones.", "output": "There is no related enetity." }, { "input": "In stroke for instance both sensorimotor and higher cognitive impairment, such as aphasia and neglect, has been addressed to facilitate functional recovery.", "output": "There is no related enetity." }, { "input": "In Parkinson ' s disease, brain stimulation has been evaluated to improve motor and non - motor symptoms.", "output": "There is no related enetity." }, { "input": "In the present review we provide an update of the field of transcranial magnetic stimulation ( TMS ) and transcranial direct current stimulation ( tDCS ) as non - invasive brain stimulation techniques to improve motor and higher cognitive functions in patients suffering from stroke and Parkinson ' s disease.", "output": "There is no related enetity." }, { "input": "Rather than attempting to be comprehensive in regard of the reviewed scientific field, this article may be considered as a present day ' s framework of the application of non - invasive brain stimulation on selected examples of common neurological diseases.", "output": "There is no related enetity." }, { "input": "At the end we will briefly discuss open controversies and future directions of the field which has to be addressed in upcoming studies.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Angiotensin - Converting Enzyme Inhibitory Activity and Antioxidant Properties of Nepeta crassifolia Boiss & Buhse and Nepeta binaludensis Jamzad.", "output": "There is no related enetity." }, { "input": "This article reports phytochemical and biological studies on Nepeta binaludensis and Nepeta crassifolia.", "output": "There is no related enetity." }, { "input": "Both species were investigated for their angiotensin - converting enzyme ( ACE ) inhibitory activity and antioxidant properties through three in vitro models [ 2, 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ), 2, 2 ' - azino - bis ( 3 - ethylbenzothiazoline - 6 - sulphonic acid ) ( ABTS ) and ferric reducing antioxidant power ( FRAP ) assay ].", "output": "2 , 2 - diphenyl - 1 - picrylhydrazyl, DPPH, 2 , 2 ' - azino - bis ( 3 - ethylbenzothiazoline - 6 - sulphonic acid ), ABTS." }, { "input": "Aerial parts were extracted with methanol and partitioned between water and subsequently n - hexane, ethyl acetate and n - butanol.", "output": "methanol, n - hexane, ethyl acetate, n - butanol." }, { "input": "N. binaludensis methanol extract exerted significantly higher reducing power ( 1. 9 mu M Fe ( II ) / g ) than did the positive control butylhydroxytoluene ( 63. 2 mu M Fe ( II ) / g ) in FRAP assay.", "output": "methanol, Fe ( II ), butylhydroxytoluene, Fe ( II )." }, { "input": "The highest DPPH radical scavenging activity was found for N. crassifolia, with IC50 values of 9. 6 and 12. 1 micro g / mL for ethyl acetate and n - butanol fractions, respectively.", "output": "DPPH, ethyl acetate, n - butanol." }, { "input": "n - Butanol fraction of both species showed the highest ACE inhibitory activity, with IC50 values of 59. 3 and 81. 7 micro g / mL for N. binaludensis and N. crassifolia, respectively.", "output": "n - Butanol." }, { "input": "Phytochemical investigations resulted in the isolation of ursolic acid, oleanolic acid, apigenin, luteolin and ixoroside.", "output": "ursolic acid, oleanolic acid, apigenin, luteolin, ixoroside." }, { "input": "Apigenin - 7 - O - glucoside, 8 - hydroxycirsimaritin and cirsimaritin were furthermore identified in N. crassifolia ethyl acetate - soluble fraction.", "output": "Apigenin - 7 - O - glucoside, 8 - hydroxycirsimaritin, cirsimaritin, ethyl acetate." }, { "input": "Nepetanudoside B was isolated from the n - butanol fraction of N. binaludensis.", "output": "Nepetanudoside B, n - butanol." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Differences in the structure of anthocyanins from the two amphibious plants, Lobelia cardinalis and Nesaea crassicaulis.", "output": "anthocyanins." }, { "input": "The foliar anthocyanin profiles of two amphibious plants, Nesaea crassicaulis and Lobelia cardinalis were analysed for the first time.", "output": "anthocyanin." }, { "input": "N. crassicaulis produced very simple anthocyanins, achieving the highest concentrations when grown submerged.", "output": "anthocyanins." }, { "input": "In contrast, L. cardinalis produced leaves with a high content of very complex, acylated anthocyanins, especially when growing emergent.", "output": "acylated anthocyanins." }, { "input": "Anthocyanins were separated by high performance liquid chromatography.", "output": "Anthocyanins." }, { "input": "Nesaea crassicaulis anthocyanins were identified according to their fragment mass spectra and ultra - visible - violet spectral characteristics and 1D and 2D NMR spectra as - 3, 5 - di - O - beta - glucosides of delphinidin, cyanidin, petunidin, malvidin and peonidin as well as cyanidine and peonidin - 3 - O - beta - glucoside.", "output": "anthocyanins, - 3 , 5 - di - O - beta - glucosides of delphinidin, cyanidin, petunidin, malvidin, peonidin, cyanidine, peonidin - 3 - O - beta - glucoside." }, { "input": "In L. cardinalis cyanidin - 3 - O - [ 6 - O - ( 4 - O - E - p - coumaroyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside was the major anthocyanin and contributed more than 98 % of total anthocyanin content.", "output": "cyanidin - 3 - O - [ 6 - O - ( 4 - O - E - p - coumaroyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside, anthocyanin, anthocyanin." }, { "input": "The remaining 2 % was made up by cyanidin - 3 - O - [ 6 - O - ( 4 - O - E - caffeoyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside and pelargonidin - 3 - O - [ 6 - O - ( 4 - O - E - p - coumaroyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside.", "output": "cyanidin - 3 - O - [ 6 - O - ( 4 - O - E - caffeoyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside, pelargonidin - 3 - O - [ 6 - O - ( 4 - O - E - p - coumaroyl - O - alpha - rhamnopyranosyl ) - beta - glucopyrano ] - 5 - O - beta - glucopyranoside." }, { "input": "An optogenetic approach in epilepsy.", "output": "There is no related enetity." }, { "input": "Optogenetic tools comprise a variety of different light - sensitive proteins from single - cell organisms that can be expressed in mammalian neurons and effectively control their excitability.", "output": "There is no related enetity." }, { "input": "Two main classes of optogenetic tools allow to either depolarize or hyperpolarize, and respectively generate or inhibit action potentials in selective populations of neurons.", "output": "There is no related enetity." }, { "input": "This opens unprecedented possibilities for delineating the role of certain neuronal populations in brain processing and diseases.", "output": "There is no related enetity." }, { "input": "Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy.", "output": "There is no related enetity." }, { "input": "Expression of the inhibitory halorhodopsin NpHR in hippocampal principal cells has been recently used as a tool to effectively control chemically and electrically induced epileptiform activity in slice preparations, and to reduce in vivo spiking induced by tetanus toxin injection in the motor cortex.", "output": "There is no related enetity." }, { "input": "In this review we give a comprehensive summary of what has been achieved so far in the field of epilepsy using optogenetics, and discuss some of the possible strategies that could be envisaged in the future.", "output": "There is no related enetity." }, { "input": "We also point out some of the challenges and pitfalls in relation to possible outcomes of using optogenetics for controlling network excitability, and associated brain diseases.", "output": "There is no related enetity." }, { "input": "This article is part of the Special Issue entitled ' New Targets and Approaches to the Treatment of Epilepsy '.", "output": "There is no related enetity." }, { "input": "Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG / Rij rats.", "output": "VU0360172." }, { "input": "Absence epilepsy is generated by the cortico - thalamo - cortical network, which undergoes a finely tuned regulation by metabotropic glutamate ( mGlu ) receptors.", "output": "There is no related enetity." }, { "input": "We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges ( SWDs ) in the WAG / Rij rat model of absence epilepsy, whereas activation of mGlu2 / 3 and mGlu4 receptors produces the opposite effect.", "output": "There is no related enetity." }, { "input": "Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico - thalamo - cortical network.", "output": "There is no related enetity." }, { "input": "We used presymptomatic and symptomatic WAG / Rij rats and aged - matched ACI rats.", "output": "There is no related enetity." }, { "input": "WAG / Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5 - receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex.", "output": "polyphosphoinositide." }, { "input": "Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre - symptomatic WAG / Rij rats.", "output": "There is no related enetity." }, { "input": "SWDs in symptomatic WAG / Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP ( 10 or 30 mg / kg, i. p. ), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 ( 3 or 10 mg / kg, s. c. ), without affecting motor behaviour.", "output": "MTEP, VU0360172." }, { "input": "The effect of VU0360172 was prevented by co - treatment with MTEP.", "output": "VU0360172, MTEP." }, { "input": "These findings suggest that changes in mGlu5 receptors might lie at the core of the absence - seizure prone phenotype of WAG / Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "Neonatal exposure to low dose corticosterone persistently modulates hippocampal mineralocorticoid receptor expression and improves locomotor / exploratory behaviour in a mouse model of Rett syndrome.", "output": "corticosterone." }, { "input": "Rett syndrome ( RTT ) is a pervasive neurodevelopmental disorder, primarily affecting girls.", "output": "There is no related enetity." }, { "input": "RTT causes a wide variety of debilitating symptoms and no cure currently exists.", "output": "There is no related enetity." }, { "input": "Mouse models bearing mutations in the Mecp2 gene recapitulate most physiological and behavioural RTT - related abnormalities.", "output": "There is no related enetity." }, { "input": "Stimulating neonatal environments ( e. g. brief maternal separations or maternal low - dose corticosterone supplementation ) reduce stress and fear responses at adulthood.", "output": "corticosterone." }, { "input": "The present study investigated whether impacting early in development the hypothalamic - pituitary - adrenal axis, by exposing Mecp2 - 308 mutant pups to a low dose of corticosterone ( 50 micro g / ml, during the 1st week of life ) may contrast RTT - related abnormalities in neuroendocrine regulation and behavioural adaptation at adulthood.", "output": "corticosterone." }, { "input": "In line with previous reports, when fully symptomatic, MeCP2 - 308 mice showed a reduction in the regular nocturnal hyperactivity in the home - cage and increased anxiety - like behaviours and plasma corticosterone ( CORT ) levels in response to restraint stress.", "output": "corticosterone, CORT." }, { "input": "An abnormal elevation in mRNA levels of mineralocorticoid receptors ( MR ) and BDNF gene was also evident in the hippocampus of fully symptomatic mutant mice.", "output": "There is no related enetity." }, { "input": "Neonatal CORT modulated MR gene expression and behavioural reactivity towards a novel object, also restoring wt - like levels of locomotor / exploratory behaviour in mutant mice.", "output": "CORT." }, { "input": "Enhanced sensitivity to the neonatal treatment ( in terms of increase in GR and MR mRNA levels ), was also evident in the hippocampus of MeCP2 - 308 mice compared to wt littermates.", "output": "There is no related enetity." }, { "input": "Present results corroborate the hypothesis that targeting the glucocorticoid system may prove valid in contrasting at least some of the RTT - related symptoms and provide evidence that pharmacological interventions during critical early time windows can persistently improve the behavioural phenotype of RTT mice.", "output": "There is no related enetity." }, { "input": "Current data also support the emerging role played by Mecp2 in mediating the epigenetic programming induced by early life events and indicate that, in the absence of functional MeCP2, programming of the central nervous system in response to early environmental stimuli is abnormally regulated.", "output": "There is no related enetity." }, { "input": "This article is part of the Special Issue entitled ' Neurodevelopmental Disorders '.", "output": "There is no related enetity." }, { "input": "Isolation, characterisation and biological evaluation of a phenoxazine, a natural dyestuff isolated from leaves of Peristrophe bivalvis.", "output": "phenoxazine." }, { "input": "Peristrophe bivalvis ( L. ) Merr.", "output": "There is no related enetity." }, { "input": "( Acanthaceae ) is a wild growing and cultivated plant used for dyeing of foods by the ethnic minorities of Vietnam.", "output": "There is no related enetity." }, { "input": "The major component of the colour aqueous extract ( CAE ) of its leaves was identified as peristrophine by spectral analysis, especially the 2D NMR spectra ( HSQC, HMBC and NOESY ).", "output": "peristrophine." }, { "input": "Considering the widespread utilisation of the decoction of this plant for food dyeing, we evaluated the acute oral toxicity of the CAE.", "output": "There is no related enetity." }, { "input": "Based on the results in an acute toxicity study in mice, the LD50 value of the CAE was determined as 9100 +/- 290 mg kg ( - 1 ) body weight.", "output": "There is no related enetity." }, { "input": "Additionally, in vitro cytotoxic assay showed an inhibition of peristrophine against Hepatocellular carcinoma ( HepG2, IC503. 90 micro g mL ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "CAE and peristrophine ( 1 ) have also been tested for their ability to affect the cell number of the OCI acute myeloid leukaemia cell line.", "output": "peristrophine." }, { "input": "CAE and peristrophine significantly decreased the OCI cell number at different concentrations and times of treatment.", "output": "peristrophine." }, { "input": "Bearberry identification by a multidisciplinary study on commercial raw materials.", "output": "There is no related enetity." }, { "input": "Herbal species different from the official bearberry, Arctostaphylos uva - ursi, are sold through conventional markets and also through non - controlled Internet websites, putting consumer safety at risk owing to the lack of quality control.", "output": "There is no related enetity." }, { "input": "Recently, Arctostaphylos pungens has become one of the most used species as a raw material for herbal medicines and dietary supplements in the place of official bearberry, a plant used for the treatment of various urinary disorders.", "output": "There is no related enetity." }, { "input": "A fingerprint identification based on an integrated application of different analytical techniques ( HPTLC, NMR, HPLC - DAD and LC - ESI - MS ) is here described to distinguish A. uva - ursi from A. pungens.", "output": "There is no related enetity." }, { "input": "The HPTLC and HPLC - DAD fingerprints resulted the simplest methods to differentiate the two species, whereas LC - ESI - MS was more useful to quantify arbutin, the main component of bearberry, and to evaluate its different content in the two species.", "output": "arbutin." }, { "input": "This multidisciplinary study showed for the first time a specific phytochemical fingerprint of the new species A. pungens.", "output": "There is no related enetity." }, { "input": "Lipid biomarkers of oxidative stress in a genetic mouse model of Smith - Lemli - Opitz syndrome.", "output": "There is no related enetity." }, { "input": "7 - Dehydrocholesterol ( 7 - DHC ) accumulates in tissues and fluids of patients with Smith - Lemli - Opitz syndrome ( SLOS ), which is caused by mutations in the gene encoding 3 beta - hydroxysterol - Delta ( 7 ) - reductase ( DHCR7 ).", "output": "7 - Dehydrocholesterol, 7 - DHC, 3 beta - hydroxysterol." }, { "input": "We recently reported that 7 - DHC is the most reactive lipid molecule toward free radical oxidation ( lipid peroxidation ) and 14 oxysterols have been identified as products of oxidation of 7 - DHC in solution.", "output": "7 - DHC, oxysterols, 7 - DHC." }, { "input": "As the high oxidizability of 7 - DHC may lead to systemic oxidative stress in SLOS patients, we report here lipid biomarkers of oxidative stress in a Dhcr7 - KO mouse model of SLOS, including oxysterols, isoprostanes ( IsoPs ), and neuroprostanes ( NeuroPs ) that are formed from the oxidation of 7 - DHC, arachidonic acid and docosahexaenoic acid, respectively.", "output": "7 - DHC, oxysterols, isoprostanes, IsoPs, neuroprostanes, NeuroPs, 7 - DHC, arachidonic acid, docosahexaenoic acid." }, { "input": "In addition to a previously described oxysterol, 3 beta, 5 alpha - dihydroxycholest - 7 - en - 6 - one ( DHCEO ), we provide evidence for the chemical structures of three new oxysterols in the brain and / or liver tissue of Dhcr7 - KO mice, two of which were quantified.", "output": "oxysterol, 3 beta , 5 alpha - dihydroxycholest - 7 - en - 6 - one, DHCEO, oxysterols." }, { "input": "We find that levels of IsoPs and NeuroPs are also elevated in brain and / or liver tissues of Dhcr7 - KO mice relative to matching WT mice.", "output": "IsoPs, NeuroPs." }, { "input": "While IsoPs and NeuroPs have been established as a reliable measurement of lipid peroxidation and oxidative stress in vivo, we show that in this genetic SLOS mouse model, 7 - DHC - derived oxysterols are present at much higher levels than IsoPs and NeuroPs and thus are better markers of lipid oxidation and related oxidative stress.", "output": "IsoPs, NeuroPs, 7 - DHC, oxysterols, IsoPs, NeuroPs." }, { "input": "Cytotoxic constituents from the fungus Daldinia concentrica ( Xylariaceae ).", "output": "There is no related enetity." }, { "input": "Phytochemical study on the methanol extract of the fruit bodies of Vietnamese fungus Daldinia concentrica has led to the isolation and structural elucidation of three cytotoxic constituents, 6, 8 - dihydroxy - 3 - methyl - 3, 4 - dihydroisocoumarin ( 1 ), ( 22R ) - hydroxylanosta - 7, 9 ( 11 ), 24 - trien - 3 - one ( 2 ) and ergosterol ( 3 ).", "output": "methanol, 6 , 8 - dihydroxy - 3 - methyl - 3 , 4 - dihydroisocoumarin, ( 22R ) - hydroxylanosta - 7 , 9 ( 11 ) , 24 - trien - 3 - one, ergosterol." }, { "input": "Their structures were elucidated by 2D - NMR and FT - ICR - MS.", "output": "There is no related enetity." }, { "input": "All the three compounds showed moderate cytotoxicity against four cancer cells, KB ( a human epidermal carcinoma ), MCF7 ( human breast carcinoma ), SK - LU - 1 ( human lung carcinoma ) and HepG2 ( hepatocellular carcinoma ).", "output": "There is no related enetity." }, { "input": "In addition, the isocoumarin ( 1 ) inhibited the growth of Staphylococcus aureus with the IC50 value of 87. 81 micro g mL ( - 1 ).", "output": "isocoumarin." }, { "input": "Transfer of a two - tiered keratinocyte assay: IL - 18 production by NCTC2544 to determine the skin sensitizing capacity and epidermal equivalent assay to determine sensitizer potency.", "output": "There is no related enetity." }, { "input": "At present, the identification of potentially sensitizing chemicals is carried out using animal models.", "output": "There is no related enetity." }, { "input": "However, it is very important from ethical, safety and economic point of view to have biological markers to discriminate allergy and irritation events, and to be able to classify sensitizers according to their potency, without the use of animals.", "output": "There is no related enetity." }, { "input": "Within the Sens - it - iv EU Frame Programme 6 funded Integrated Project ( LSHB - CT - 2005 - 018681 ), a number of in vitro, human cell based assays were developed which, when optimized and used in an integrated testing strategy, may be able to distinguish sensitizers from non - sensitizers.", "output": "There is no related enetity." }, { "input": "This study describes two of these assays, which when used in a tiered strategy, may be able to identify contact sensitizers and also to quantify sensitizer potency.", "output": "There is no related enetity." }, { "input": "Tier 1 is the human keratinocyte NCTC2544 IL - 18 assay and tier 2 is the Epidermal Equivalent potency assay.", "output": "There is no related enetity." }, { "input": "The aim of this study is to show the transferability of the two - tiered approach with training chemicals: 3 sensitizers ( DNCB, resorcinol, pPD ) and 1 non sensitizer ( lactic acid ) in tier 1 and 2 sensitizers with different potency in tier 2 ( DNCB; extreme and resorcinol; moderate ).", "output": "DNCB, resorcinol, pPD, lactic acid, DNCB, resorcinol." }, { "input": "The chemicals were tested in a non - coded fashion.", "output": "There is no related enetity." }, { "input": "Here we describe the transferability to na i ve laboratories, the establishment of the standard operating procedure, critical points, acceptance criteria and project management.", "output": "There is no related enetity." }, { "input": "Both assays were successfully transferred to laboratories that had not performed the assays previously.", "output": "There is no related enetity." }, { "input": "The two tiered approach may offer an unique opportunity to provide an alternative method to the Local Lymph Node Assay ( LLNA ).", "output": "There is no related enetity." }, { "input": "These assays are both based on the use of human keratinocytes, which have been shown over the last two decades, to play a key role in all phases of skin sensitization.", "output": "There is no related enetity." }, { "input": "D - Serine facilitates the effectiveness of extinction to reduce drug - primed reinstatement of cocaine - induced conditioned place preference.", "output": "D - Serine, cocaine." }, { "input": "Addiction is a disease that is characterized by compulsive drug - seeking and use despite negative health and social consequences.", "output": "There is no related enetity." }, { "input": "One obstacle in treating addiction is a high susceptibility for relapse which persists despite prolonged periods of abstinence.", "output": "There is no related enetity." }, { "input": "Relapse can be triggered by drug predictive stimuli such as environmental context and drug associated cues, as well as the addictive drug itself.", "output": "There is no related enetity." }, { "input": "The conditioned place preference ( CPP ) behavioral model is a useful paradigm for studying the ability of these drug predictive stimuli to reinstate drug - seeking behavior.", "output": "There is no related enetity." }, { "input": "The present study investigated the dose - dependent effects of D - serine ( 10 mg / kg, 30 mg / kg and 100 mg / kg ) on extinction training and drug - primed reinstatement in cocaine - conditioned rats.", "output": "D - serine, cocaine." }, { "input": "In the first experiment, D - serine had no effect on the acquisition or development of cocaine - induced locomotor sensitization or CPP.", "output": "D - serine, cocaine." }, { "input": "In the second experiment, D - serine treatment resulted in significantly decreased time spent in the drug - paired compartment following completion of an extinction protocol.", "output": "D - serine." }, { "input": "A cocaine - primed reinstatement test indicated that the combination of extinction training along with D - serine treatment resulted in a significant reduction of drug - seeking behavior.", "output": "cocaine, D - serine." }, { "input": "The third experiment assessed D - serine ' s long - term effects to diminish drug - primed reinstatement.", "output": "D - serine." }, { "input": "D - serine treatment given during extinction was effective in reducing drug - seeking for more than four weeks of abstinence after the last cocaine exposure.", "output": "D - serine, cocaine." }, { "input": "These findings demonstrate that D - serine may be an effective adjunct therapeutic agent along with cognitive behavioral therapy for the treatment of cocaine addiction.", "output": "D - serine, cocaine." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "What should we do about student use of cognitive enhancers?", "output": "There is no related enetity." }, { "input": "An analysis of current evidence.", "output": "There is no related enetity." }, { "input": "This article reviews current data on the use of cognition enhancers as study aids in the student population.", "output": "There is no related enetity." }, { "input": "It identifies gaps and uncertainties in the knowledge required to make a balanced assessment of the need for some form of regulation.", "output": "There is no related enetity." }, { "input": "The review highlights the weak evidence on the prevalence of use of such drugs, especially outside the US, and the ambiguous evidence for their efficacy in a healthy population.", "output": "There is no related enetity." }, { "input": "Risks are well documented for the commonly used drugs, but poorly appreciated by users.", "output": "There is no related enetity." }, { "input": "These include not only the side - effects of the drugs themselves, but risks associated with on - line purchase, which offers no guarantees of authenticity and which for some drugs is illegal.", "output": "There is no related enetity." }, { "input": "The case for urgent action to regulate use is often linked to the belief that new and more effective drugs are likely to appear in the near future.", "output": "There is no related enetity." }, { "input": "The evidence for this is weak.", "output": "There is no related enetity." }, { "input": "However, drugs are not the only possible route to neuroenhancement and action is needed to collect more data on the impact of existing drugs, as well as new technologies, in order to guide society in making a proportionate response to the issue.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Hippocampal long - term depression mediates spatial reversal learning in the Morris water maze.", "output": "There is no related enetity." }, { "input": "Synaptic plasticity at hippocampal excitatory synapses has been proposed as the cellular mechanism underlying spatial learning and memory.", "output": "There is no related enetity." }, { "input": "However, most previous studies have focused on the role of long - term potentiation ( LTP ) in learning and memory, and much less is known about the role of long - term depression ( LTD ).", "output": "There is no related enetity." }, { "input": "Here, we report that hippocampal - dependent spatial learning in the Morris water maze facilitated hippocampal CA1 LTD induction in vivo.", "output": "There is no related enetity." }, { "input": "The LTD can be blocked by systemic application of the selective GluN2B antagonist Ro25 - 6981 ( 6 mg / kg, i. p. ) or a synthetic peptide Tat - GluA2 ( 3Y ) ( 3 mu mol / kg, i. p. ) that interferes with the endocytosis of AMPA receptors.", "output": "Ro25 - 6981, AMPA." }, { "input": "In addition, systemic or intrahippocampal administration of these two mechanistically and structurally distinct inhibitors impaired spatial reversal learning of a novel target location, when the hidden platform was moved to the quadrant opposite the initial target location.", "output": "There is no related enetity." }, { "input": "Notably, acute elevated - platform stress, which facilitates hippocampal LTD induction, enhanced both acquisition and retrieval of spatial reversal memory.", "output": "There is no related enetity." }, { "input": "The present study demonstrates that reversal learning is impaired by blocking hippocampal LTD, and enhanced by facilitating hippocampal LTD, suggesting that hippocampal LTD may be necessary and sufficient to mediate new information processing.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "The p53 isoform, Delta 133p53 alpha, stimulates angiogenesis and tumour progression.", "output": "There is no related enetity." }, { "input": "The tumour suppressor p53, involved in DNA repair, cell cycle arrest and apoptosis, also inhibits blood vessel formation, that is, angiogenesis, a process strongly contributing to tumour development.", "output": "There is no related enetity." }, { "input": "The p53 gene expresses 12 different proteins ( isoforms ), including TAp53 ( p53 ( or p53 alpha ), p53 beta and p53 gamma ) and Delta 133p53 isoforms ( Delta 133p53 alpha, Delta 133p53 beta and Delta 133p53 gamma ).", "output": "There is no related enetity." }, { "input": "The Delta 133p53 alpha isoform was shown to modulate p53 transcriptional activity and is overexpressed in various human tumours.", "output": "There is no related enetity." }, { "input": "However, its role in tumour progression is still unexplored.", "output": "There is no related enetity." }, { "input": "In the present study, we examined the involvement of Delta 133p53 isoforms in tumoural angiogenesis and tumour growth in the highly angiogenic human glioblastoma U87.", "output": "There is no related enetity." }, { "input": "Our data show that conditioned media from U87 cells depleted for Delta 133p53 isoforms block endothelial cell migration and tubulogenesis without affecting endothelial cell proliferation in vitro.", "output": "There is no related enetity." }, { "input": "The Delta 133p53 depletion in U2OS osteosarcoma cells resulted in a similar angiogenesis blockade.", "output": "There is no related enetity." }, { "input": "Furthermore, using conditioned media from U87 cells ectopically expressing each Delta 133p53 isoform, we determined that Delta 133p53 alpha and Delta 133p53 gamma but not Delta 133p53 beta, stimulate angiogenesis.", "output": "There is no related enetity." }, { "input": "Our in vivo data using the chicken chorio - allantoic membrane and mice xenografts establish that angiogenesis and growth of glioblastoma U87 tumours are inhibited upon depletion of Delta 133p53 isoforms.", "output": "There is no related enetity." }, { "input": "By TaqMan low - density array, we show that alteration of expression ratio of Delta 133p53 and TAp53 isoforms differentially regulates angiogenic gene expression with Delta 133p53 isoforms inducing pro - angiogenic gene expression and repressing anti - angiogenic gene expression.", "output": "There is no related enetity." }, { "input": "The Hedgehog processing pathway is required for NSCLC growth and survival.", "output": "There is no related enetity." }, { "input": "Considerable interest has been generated from the results of recent clinical trials using smoothened ( SMO ) antagonists to inhibit the growth of hedgehog ( HH ) signaling - dependent tumors.", "output": "There is no related enetity." }, { "input": "This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function.", "output": "There is no related enetity." }, { "input": "Here, we demonstrate that HH - dependent non - small cell lung carcinoma ( NSCLC ) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing.", "output": "There is no related enetity." }, { "input": "Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH - processing proteins, skinny hedgehog ( SKN ) or dispatched - 1 ( DISP - 1 ), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death.", "output": "There is no related enetity." }, { "input": "Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects.", "output": "There is no related enetity." }, { "input": "The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts.", "output": "There is no related enetity." }, { "input": "Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently overexpressed in NSCLC and that higher DISP - 1 expression is associated with an unfavorable clinical outcome.", "output": "There is no related enetity." }, { "input": "Our results show a critical role for HH processing in HH - dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand - dependent cancers.", "output": "There is no related enetity." }, { "input": "The Inhibitory Effect of 20 ( S ) - Protopanaxatriol ( ppt ) Towards UGT1A1 and UGT2B7.", "output": "20 ( S ) - Protopanaxatriol, ppt." }, { "input": "Ginseng, a commonly used natural product, has been frequently reported to induce herb - drug interaction with many clinical drugs.", "output": "There is no related enetity." }, { "input": "The intestinal bacterial metabolites of ginsenosides have been widely regarded as the substance basis for ginseng - drug interactions.", "output": "ginsenosides." }, { "input": "To date, little is known about the inhibitory effect of intestinal bacterial metabolites of ginsenosides towards UDP - glucuronosyltransferases ( UGTs ).", "output": "ginsenosides, UDP." }, { "input": "In vitro investigation of the inhibition of 20 ( S ) - protopanaxatriol ( ppt ) towards UGT1A1 and UGT2B7 was carried out.", "output": "20 ( S ) - protopanaxatriol, ppt." }, { "input": "The results showed that ppt exhibited strong noncompetitive inhibition towards UGT1A1 and competitive inhibition towards UGT2B7.", "output": "There is no related enetity." }, { "input": "The inhibition kinetic parameters ( Ki ) were calculated to be 8. 8 and 2. 2 mu M for UGT1A1 and UGT2B7, respectively.", "output": "There is no related enetity." }, { "input": "Using the maximum plasma concentration of ppt, the alteration of area under the concentration - time curve was calculated to be 20 % and 70 % respectively for UGT1A1 - mediated and UGT2B7 - mediated metabolism.", "output": "There is no related enetity." }, { "input": "However, given that the varied contribution of these two UGT isoforms towards drug metabolism and the influence of herb complexity and individual difference, the explanation of these results should be paid more caution.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "A pathogenetic link between non - alcoholic fatty liver disease and celiac disease.", "output": "There is no related enetity." }, { "input": "Non - alcoholic fatty liver disease ( NAFLD ) has recently been recognized as the leading cause of the abnormalities in the liver function tests in the Western countries.", "output": "There is no related enetity." }, { "input": "Celiac disease ( CD ) is a permanent immunological intolerance to gluten proteins in genetically predisposed individuals.", "output": "There is no related enetity." }, { "input": "CD has been reported in 4 - 13 % of the cases with steatohepatitis, although the pathogenesis of the liver steatosis in CD patients is unclear.", "output": "There is no related enetity." }, { "input": "Based on the literature data, it can be concluded that the inclusion of serological markers of CD should be a part of the general workup in the patients with steatosis when other causes of the liver disease are excluded and in the patients with NAFLD when metabolic risk factors are not evident.", "output": "There is no related enetity." }, { "input": "Role of metabotropic glutamate receptors in persistent forms of hippocampal plasticity and learning.", "output": "glutamate." }, { "input": "Storage and processing of information at the synaptic level is enabled by the ability of synapses to persistently alter their efficacy.", "output": "There is no related enetity." }, { "input": "This phenomenon, known as synaptic plasticity, is believed to underlie multiple forms of long - term memory in the mammalian brain.", "output": "There is no related enetity." }, { "input": "It has become apparent that the metabotropic glutamate ( mGlu ) receptor is critically required for both persistent forms of memory and persistent synaptic plasticity.", "output": "glutamate." }, { "input": "Persistent forms of synaptic plasticity comprise long - term potentiation ( LTP ) and long - term depression ( LTD ) that last at least for 4 h but can be followed in vivo for days and weeks.", "output": "There is no related enetity." }, { "input": "These types of plasticity are believed to be analogous to forms of memory that persist for similar time - spans.", "output": "There is no related enetity." }, { "input": "The mGlu receptors are delineated into three distinct groups based on their G - protein coupling and agonist affinity and also exercise distinct roles in the way they regulate both long - term plasticity and long - term hippocampus - dependent memory.", "output": "There is no related enetity." }, { "input": "Here, the mGlu receptors will be reviewed both in general, and in the particular context of their role in persistent ( > 4 h ) forms of hippocampus - dependent synaptic plasticity and memory, as well as forms of synaptic plasticity that have been shown to be directly regulated by memory events.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "The response to sulpiride in social anxiety disorder: D2 receptor function.", "output": "sulpiride." }, { "input": "Some previous studies have suggested that patients with social anxiety disorder ( SAD ) have a hypoactive central dopaminergic system.", "output": "There is no related enetity." }, { "input": "Supporting this there have been reports from neuroimaging studies of reduced striatal D2 receptor binding in subjects with SAD.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate D2 receptor sensitivity in patients with SAD compared with a group of matched, healthy controls using a neuroendocrine challenge with the selective D2 antagonist, sulpiride.", "output": "sulpiride." }, { "input": "D2 receptor function was assessed in 23 subjects with generalized SAD and 23 matched, healthy controls using a challenge with 400 mg of a selective D2 antagonist, sulpiride in a randomized, placebo - controlled, crossover design.", "output": "sulpiride." }, { "input": "Response to sulpiride was measured by the change in prolactin level and changes in self - rated measures of social anxiety, mood and the ability to experience pleasure.", "output": "sulpiride." }, { "input": "There was no significant difference in prolactin response to sulpiride between the two groups.", "output": "sulpiride." }, { "input": "Sulpiride resulted in no effect in either the SAD or healthy control group on measures of social anxiety, mood or the ability to experience pleasure.", "output": "Sulpiride." }, { "input": "Contrary to our hypothesis, in this study we found no evidence of reduced D2 receptor function in subjects with SAD compared with healthy controls.", "output": "There is no related enetity." }, { "input": "AMPK signalling and the control of substrate use in the heart.", "output": "There is no related enetity." }, { "input": "All mammalian cells rely on adenosine triphosphate ( ATP ) to maintain function and for survival.", "output": "adenosine triphosphate, ATP." }, { "input": "The heart has the highest basal ATP demand of any organ due to the necessity for continuous contraction.", "output": "ATP." }, { "input": "As such, the ability of the cardiomyocyte to monitor cellular energy status and adapt the supply of substrates to match the energy demand is crucial.", "output": "There is no related enetity." }, { "input": "One important serine / threonine protein kinase that monitors cellular energy status in the heart is adenosine monophosphate activated protein kinase ( AMPK ).", "output": "serine, threonine, adenosine monophosphate." }, { "input": "AMPK is also a key enzyme that controls multiple catabolic and anabolic biochemical pathways in the heart and indirectly plays a crucial role in regulating cardiac function in both physiological and pathophysiological conditions.", "output": "There is no related enetity." }, { "input": "Herein, we review the involvement of AMPK in myocardial fatty acid and glucose transport and utilization, as it relates to basal cardiac function.", "output": "fatty acid, glucose." }, { "input": "We also assess the literature amassed on cardiac AMPK and discuss the controversies surrounding the role of AMPK in physiological and pathophysiological processes in the heart.", "output": "There is no related enetity." }, { "input": "The work reviewed herein also emphasizes areas that require further investigation for the purpose of eventually translating this information into improved patient care.", "output": "There is no related enetity." }, { "input": "Predictors and mediators of add - on mirtazapine - induced cognitive enhancement in schizophrenia - - a path model investigation.", "output": "mirtazapine." }, { "input": "We aimed to evaluate predictors and mediators of enhancing effect of adjunctive mirtazapine on cognition in schizophrenia.", "output": "mirtazapine." }, { "input": "Patients with difficult - to - treat schizophrenia received either mirtazapine ( n = 19 ) or placebo ( n = 18 ) in a double - blind fashion for six weeks.", "output": "mirtazapine." }, { "input": "Mirtazapine outperformed placebo on the Block Design and Stroop Dots.", "output": "Mirtazapine." }, { "input": "In the present subsidiary study, factors underlying this difference were explored with Path Analysis.", "output": "There is no related enetity." }, { "input": "Add - on mirtazapine had an independent enhancing effect on the Block Design - measured visuo - spatial functioning.", "output": "mirtazapine." }, { "input": "Further, this effect was mediated via changes in positive, depressive and parkinsonism symptoms, but not in negative symptoms.", "output": "There is no related enetity." }, { "input": "This effect was predicted by higher doses of FGAs, longer duration of illness and lower initial Block Design scores.", "output": "There is no related enetity." }, { "input": "Path Analysis model fit was good.", "output": "There is no related enetity." }, { "input": "Mirtazapine may have direct and indirect favorable effects on visuo - spatial functioning, but further research is needed.", "output": "Mirtazapine." }, { "input": "Path analysis may be a feasible statistical method for further research of neurocognition in psychopharmacological interventions in schizophrenia.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Dietary flaxseed oil supplementation ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.", "output": "cisplatin." }, { "input": "Cisplatin ( CP; cis - diamminedichloroplatinum II ) is a drug widely used against different types of solid tumors.", "output": "Cisplatin, cis - diamminedichloroplatinum II." }, { "input": "Patients receiving CP, however, experience very profound and long lasting gastrointestinal symptoms.", "output": "There is no related enetity." }, { "input": "Recently, omega - 3 polyunsaturated fatty acid - enriched flaxseed / flaxseed oil ( FXO ) has shown numerous health benefits.", "output": "omega - 3 polyunsaturated fatty acid." }, { "input": "The present study was undertaken to investigate whether FXO can prevent CP - induced adverse biochemical changes in the small intestine of rats.", "output": "There is no related enetity." }, { "input": "A single intraperitoneal dose of CP ( 6 mg / kg body weight ) was administered to male Wistar rats fed with control diet ( CP group ) and FXO diet ( CPFXO group ).", "output": "There is no related enetity." }, { "input": "Administration of CP led to a significant decline in the specific activities of brush border membrane enzymes both in the mucosal homogenates and in the isolated membrane vesicles.", "output": "There is no related enetity." }, { "input": "Lipid peroxidation and total sulfhydryl groups were altered upon CP treatment, indicating the generation of oxidative stress.", "output": "sulfhydryl." }, { "input": "The activities of SOD, catalase and glutathione peroxidase also decreased in CP - treated rats.", "output": "glutathione." }, { "input": "In contrast, dietary supplementation of FXO prior to and following CP treatment significantly attenuated the CP - induced changes in all these parameters.", "output": "There is no related enetity." }, { "input": "FXO feeding markedly enhanced resistance to CP - elicited adverse gastrointestinal effects.", "output": "There is no related enetity." }, { "input": "The results suggest that FXO owing to its intrinsic biochemical / antioxidant properties is an effective agent in reducing the adverse effects of CP on intestine.", "output": "There is no related enetity." }, { "input": "Anion binding in water at lanthanide centres: from structure and selectivity to signalling and sensing.", "output": "lanthanide." }, { "input": "Reversible anion binding at lanthanide centres in aqueous media has emerged as an effective means of signalling and sensing the presence of selected anions.", "output": "lanthanide." }, { "input": "The constitution and configuration of a wide range of anion adducts has been defined by X - ray analyses and NMR methods, and both chelating and monodentate binding modes characterised.", "output": "There is no related enetity." }, { "input": "Variation of the lanthanide ion modulates charge density, and ligand modification allows alteration of both the peripheral electrostatic gradient and the local steric demand at the metal centre.", "output": "lanthanide." }, { "input": "Thus, selectivity for a target anion can be engineered, and the affinity constant modulated to target the desired concentration range.", "output": "There is no related enetity." }, { "input": "Changes in anion concentration can be monitored rapidly, accurately and with high spatial resolution using optical emission spectroscopy and microscopy, facilitating the measurement of anions such as bicarbonate, lactate, citrate and urate in a variety of bio - fluids.", "output": "bicarbonate, lactate, citrate, urate." }, { "input": "Flavonoid constituents and biological screening of Astragalus bombycinus Boiss.", "output": "Flavonoid." }, { "input": "Two new flavonoid compounds were isolated from Astragalus bombycinus Boiss. and identified as quercetin - 3, 7 - di - O - beta - glucopyranoside 4 ' - O - alpha - rhamnopyranoside and 5, 2 ', 4 ' - trihydroxy - flavone - 8 - C - alpha - arabinopyranoside - 7 - O - beta - glucopyranoside.", "output": "flavonoid, quercetin - 3 , 7 - di - O - beta - glucopyranoside 4 ' - O - alpha - rhamnopyranoside, 5 , 2 ' , 4 ' - trihydroxy - flavone - 8 - C - alpha - arabinopyranoside - 7 - O - beta - glucopyranoside." }, { "input": "In addition, apigenin, apigenin - 7 - O - beta - glucopyranoside, apigenin 7 - O - gentobioside, luteolin, luteolin - 7 - O - beta - glucopyranoside, quercetin - 3, 7 - di - O - beta - glucopyranoside, quercetin - 3 - O - beta - glucopyranoside - 7 - O - alpha - rhamnopyranoside and daidzein were also isolated and identified.", "output": "apigenin, apigenin - 7 - O - beta - glucopyranoside, apigenin 7 - O - gentobioside, luteolin, luteolin - 7 - O - beta - glucopyranoside, quercetin - 3 , 7 - di - O - beta - glucopyranoside, quercetin - 3 - O - beta - glucopyranoside - 7 - O - alpha - rhamnopyranoside, daidzein." }, { "input": "The structure elucidation of the isolated compounds was performed by chromatographic, chemical and spectroscopic methods.", "output": "There is no related enetity." }, { "input": "Antioxidant and cytotoxic activities were also determined for the four consecutive extracts of the plant.", "output": "There is no related enetity." }, { "input": "Bioactive alkaloids produced by Pseudomonas brassicacearum subsp.", "output": "There is no related enetity." }, { "input": "Neoaurantiaca, an endophytic bacterium from Salvia miltiorrhiza.", "output": "There is no related enetity." }, { "input": "Eleven compounds were isolated from the culture of an endophytic bacterium Pseudomonas brassicacearum subsp.", "output": "There is no related enetity." }, { "input": "Neoaurantiaca in Salvia miltiorrhiza Bunge.", "output": "There is no related enetity." }, { "input": "Their structures were elucidated by spectroscopic methods as cyclo - ( Gly - L - Ala ) ( 1 ), cyclo - ( L - Ala - L - Ala ) ( 2 ), cyclo - ( L - Pro - Gly ) ( 3 ), cyclo - ( L - Pro - L - Ser ) ( 4 ), cyclo - ( L - Ala - trans - 4 - hydroxy - L - Pro ) ( 5 ), cyclo - ( L - Val - L - Pro ) ( 6 ), cyclo - ( Gly - L - Tyr ) ( 7 ), cyclo - ( L - Ala - L - Tyr ) ( 8 ), cyclo - ( L - Tyr - trans - 4 - hydroxy - L - Pro ) ( 9 ), 3 - methylhydantoin ( 10 ) and 2 - piperidinone ( 11 ).", "output": "cyclo - ( Gly - L - Ala ), cyclo - ( L - Ala - L - Ala ), cyclo - ( L - Pro - Gly ), cyclo - ( L - Pro - L - Ser ), cyclo - ( L - Ala - trans - 4 - hydroxy - L - Pro ), cyclo - ( L - Val - L - Pro ), cyclo - ( Gly - L - Tyr ), cyclo - ( L - Ala - L - Tyr ), cyclo - ( L - Tyr - trans - 4 - hydroxy - L - Pro ), 3 - methylhydantoin, 2 - piperidinone." }, { "input": "All these compounds were isolated from this bacterium for the first time.", "output": "There is no related enetity." }, { "input": "The brine shrimp lethality, antifungal and antibacterial activities of these compounds were evaluated.", "output": "There is no related enetity." }, { "input": "The results indicated that some cyclodipeptides may play an important role in plant - bacteria interactions.", "output": "cyclodipeptides." }, { "input": "Correlation between iodide dosimetry and terephthalic acid dosimetry to evaluate the reactive radical production due to the acoustic cavitation activity.", "output": "iodide, terephthalic acid." }, { "input": "Acoustic cavitation plays an important role in sonochemical processes and the rate of sonochemical reaction is influenced by sonication parameters.", "output": "There is no related enetity." }, { "input": "There are several methods to evaluate cavitation activity such as chemical dosimetry.", "output": "There is no related enetity." }, { "input": "In this study, to comparison between iodide dosimetry and terephthalic acid dosimetry, efficacy of sonication parameters in reactive radical production has been considered by iodide and terephthalic acid dosimetries.", "output": "iodide, terephthalic acid, iodide, terephthalic acid." }, { "input": "For this purpose, efficacy of different exposure parameters on cavitations production by 1 MHz ultrasound has been studied.", "output": "There is no related enetity." }, { "input": "The absorbance of KI dosimeter was measured by spectrophotometer and the fluorescence of terephthalic acid dosimeter was measured using spectrofluorometer after sonication.", "output": "KI, terephthalic acid." }, { "input": "The result of experiments related to sonication time and intensity showed that with increasing time of sonication or intensity, the absorbance is increased.", "output": "There is no related enetity." }, { "input": "It has been shown that the absorbance for continuous mode is remarkably higher than for pulsing mode ( p - value < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Also results show that with increasing the duty cycles of pulsed field, the inertial cavitation activity is increased.", "output": "There is no related enetity." }, { "input": "With compensation of sonication time or intensity in different duty cycles, no significant absorbance difference were observed unless 20 % duty cycle.", "output": "There is no related enetity." }, { "input": "A significant correlation between the absorbance and fluorescence intensities ( count ) at different intensity ( R = 0. 971 ), different sonication time ( R = 0. 999 ) and different duty cycle ( R = 0. 967 ) were observed ( p - value < 0. 05 ).", "output": "There is no related enetity." }, { "input": "It is concluded that the sonication parameters having important influences on reactive radical production.", "output": "There is no related enetity." }, { "input": "These results suggest that there is a correlation between iodide dosimetry and terephthalic acid dosimetry to examine the acoustic cavitation activity in ultrasound field.", "output": "iodide, terephthalic acid." }, { "input": "Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil.", "output": "modafinil." }, { "input": "Multiple sclerosis ( MS ) is a multifocal demyelinating disease of the central nervous system, leading to chronic disability.", "output": "There is no related enetity." }, { "input": "Fatigue is a common and distressing symptom of MS which is unrelated to its clinical form, stage of development, the degree of disability, or the lesion load on magnetic resonance imaging.", "output": "There is no related enetity." }, { "input": "Fatigue in MS is associated with excessive daytime sleepiness and autonomic dysfunction.", "output": "There is no related enetity." }, { "input": "Recently it has been reported that the wakefulness - promoting drug modafinil may relieve fatigue in MS patients and ameliorate the associated cognitive difficulties.", "output": "modafinil." }, { "input": "However, it is not clear to what extent the anti - fatigue effect of modafinil may be related to its alerting and sympathetic activating effects.", "output": "modafinil." }, { "input": "We addressed this question by comparing three groups of subjects, MS patients with fatigue, MS patients without fatigue and healthy controls, matched for age and sex, on measures of alertness ( self - ratings on the Epworth and Stanford Sleepiness Scales and on a battery of visual analogue scales; critical flicker fusion frequency; Pupillographic Sleepiness Test; choice reaction time ) and autonomic function ( systolic and diastolic blood pressure, heart rate, pupil diameter ), and by examining the effect of a single dose ( 200 mg ) of modafinil on these measures.", "output": "modafinil." }, { "input": "MS patients with fatigue, compared with healthy controls, had reduced level of alertness on all the tests used; MS patients without fatigue did not differ from healthy controls.", "output": "There is no related enetity." }, { "input": "MS patients with fatigue had a reduced level of cardiovascular sympathetic activation compared to the other two groups.", "output": "There is no related enetity." }, { "input": "Modafinil displayed alerting and sympathomimetic effects in all three groups of subjects.", "output": "Modafinil." }, { "input": "As fatigue in MS is associated with reduced levels of alertness and sympathetic activity, modafinil may exert its anti - fatigue effect in MS by correcting these deficiencies.", "output": "modafinil." }, { "input": "The anti - fatigue effect of modafinil may reflect the activation of the noradrenergic locus coeruleus ( LC ), since there is evidence that this wakefulness - promoting nucleus is damaged in MS, and that modafinil, probably via the dopaminergic system, can stimulate the LC.", "output": "modafinil, modafinil." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey.", "output": "There is no related enetity." }, { "input": "Metabotropic glutamate ( mGlu ) receptors modulate pain from within the midbrain periaqueductal grey ( PAG ).", "output": "glutamate." }, { "input": "In the present study, the postsynaptic mGlu receptor mediated effects on rat PAG neurons were examined using whole - cell patch - clamp recordings in brain slices.", "output": "There is no related enetity." }, { "input": "The selective group I agonist DHPG ( 10 mu M ) produced an inward current in all PAG neurons tested which was associated with a near parallel shift in the current - voltage relationship.", "output": "DHPG." }, { "input": "By contrast, the group II and III mGlu receptor agonists DCG - IV ( 1 mu M ) and l - AP4 ( 3 mu M ) produced an outward current in only 10 - 20 % of PAG neurons tested.", "output": "There is no related enetity." }, { "input": "The DHPG induced current was concentration dependent ( EC ( 50 ) = 1. 4 mu M ), was reduced by the mGlu1 antagonist CPCCOEt ( 100 mu M ), and was further reduced by CPCCOEt in combination with the mGlu5 antagonist MPEP ( 10 mu M ).", "output": "DHPG, CPCCOEt, CPCCOEt, antagonist MPEP." }, { "input": "The glutamate transport blocker TBOA ( 30 mu M ) also produced an inward current, however, this was largely abolished by CNQX ( 10 mu M ) plus AP5 ( 25 mu M ).", "output": "glutamate, TBOA, CNQX, AP5." }, { "input": "Slow EPSCs were evoked following train, but not single shock stimulation, which were enhanced by TBOA ( 30 mu M ).", "output": "TBOA." }, { "input": "The TBOA enhancement of slow EPSCs was abolished by MPEP plus CPCCOEt.", "output": "TBOA, MPEP, CPCCOEt." }, { "input": "These findings indicate that endogenously released glutamate, under conditions in which neurotransmitter spill - over is enhanced, activates group I mGlu receptors to produce excitatory currents within PAG.", "output": "glutamate." }, { "input": "Thus, postsynaptic group I mGlu receptors have the potential to directly modulate the analgesic, behavioural and autonomic functions of the PAG.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "Glutamate." }, { "input": "GLP - 1 receptor activated insulin secretion from pancreatic beta - cells: mechanism and glucose dependence.", "output": "glucose." }, { "input": "The major goal in the treatment of type 2 diabetes mellitus is to control the hyperglycaemia characteristic of the disease.", "output": "There is no related enetity." }, { "input": "However, treatment with common therapies such as insulin or insulinotrophic sulphonylureas ( SU ), while effective in reducing hyperglycaemia, may impose a greater risk of hypoglycaemia, as neither therapy is self - regulated by ambient blood glucose concentrations.", "output": "glucose." }, { "input": "Hypoglycaemia has been associated with adverse physical and psychological outcomes and may contribute to negative cardiovascular events; hence minimization of hypoglycaemia risk is clinically advantageous.", "output": "There is no related enetity." }, { "input": "Stimulation of insulin secretion from pancreatic beta - cells by glucagon - like peptide 1 receptor ( GLP - 1R ) agonists is known to be glucose - dependent.", "output": "glucose." }, { "input": "GLP - 1R agonists potentiate glucose - stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations.", "output": "glucose, glucose." }, { "input": "This ' glucose - regulated ' activity of GLP - 1R agonists makes them useful and potentially safer therapeutics for overall glucose control compared to non - regulated therapies; hyperglycaemia can be reduced with minimal hypoglycaemia.", "output": "glucose, glucose." }, { "input": "While the inherent mechanism of action of GLP - 1R agonists mediates their glucose dependence, studies in rats suggest that SUs may uncouple this dependence.", "output": "glucose." }, { "input": "This hypothesis is supported by clinical studies showing that the majority of events of hypoglycaemia in patients treated with GLP - 1R agonists occur in patients treated with a concomitant SU.", "output": "There is no related enetity." }, { "input": "This review aims to discuss the current understanding of the mechanisms by which GLP - 1R signalling promotes insulin secretion from pancreatic beta - cells via a glucose - dependent process.", "output": "glucose." }, { "input": "New long - chain aliphatic compounds from Peperomia dindygulensis.", "output": "There is no related enetity." }, { "input": "Three long - chain aliphatic compounds, including one new polyketide derivative, dindygulerione C ( 1 ), one new octaketide derivative, dindygulerione D ( 2 ) and one new acylresorcinol derivative dindyguleranone ( 3 ) were isolated from the whole plant of the Chinese anticancer folk medicine Peperomia dindygulensis Miq.", "output": "polyketide, dindygulerione C, octaketide, dindygulerione D, acylresorcinol, dindyguleranone." }, { "input": "( Piperaceae ).", "output": "There is no related enetity." }, { "input": "Dindygulerione C is an unprecedented example of a N - containing polyketide.", "output": "Dindygulerione C, polyketide." }, { "input": "The chemical structures and configurations of 1 - 3 were elucidated as ( - ) - ( 4S ) - 2 - [ ( Z ) - 1 ' - ( 6 '', 7 '' - dihydroxyphenethyl - amino ) octadec - 11 ' - enylidene ] - 4 - hydroxycyclohexane - 1, 3 - dione ( 1 ), ( + ) - 2 - heptadecyl - 4 - hydroxy - 3, 4, 7, 8 - tetrahydro - 2H - chromen - 5 ( 6H ) - one ( 2 ) and 2 - ( 1, 3 - dihydroxyphenyl ) - octacosan - 1 ' - one ( 3 ), respectively, by comparing with the literature data and extensive spectroscopic methods, including 2 - D NMR and circular dichroism spectroscopic analysis.", "output": "( - ) - ( 4S ) - 2 - [ ( Z ) - 1 ' - ( 6 '' , 7 '' - dihydroxyphenethyl - amino ) octadec - 11 ' - enylidene ] - 4 - hydroxycyclohexane - 1 , 3 - dione, ( + ) - 2 - heptadecyl - 4 - hydroxy - 3 , 4 , 7 , 8 - tetrahydro - 2H - chromen - 5 ( 6H ) - one, 2 - ( 1 , 3 - dihydroxyphenyl ) - octacosan - 1 ' - one." }, { "input": "The cytotoxicity of 1 - 3 was evaluated against Hep3B and HepG2 liver cancer cell lines.", "output": "There is no related enetity." }, { "input": "Hydrothermally mixed hydroxyapatite - multiwall carbon nanotubes composite coatings on biomedical alloys by electrophoretic deposition.", "output": "hydroxyapatite, carbon." }, { "input": "Hydroxyapatite ( HA ) coatings have been used to improve biological and mechanical fixation of metallic prosthesis.", "output": "Hydroxyapatite." }, { "input": "Because of extraordinary features of carbon nanotubes ( CNTs ), they have a lot of facilities, such as extremely strong nanoreinforcement materials for composites.", "output": "carbon." }, { "input": "HA powders were synthesized and mixed with multiwalled carbon nanotubes ( MWCNTs ) by a hydrothermal process.", "output": "carbon." }, { "input": "Calcium acetate ( Ca ( CH ( 3 ) COO ) ( 2 ) ) and phosphoric acid ( H ( 3 ) PO ( 4 ) ) were used as starting materials for synthesizing nano - HA powders.", "output": "Calcium acetate, Ca ( CH ( 3 ) COO ) ( 2 ), phosphoric acid, H ( 3 ) PO ( 4 )." }, { "input": "HA - MWCNTs were treated together hydrothermally at 200 degrees C for 2 h to synthesize nano - HA powders mixed homogeneously with MWCNTs.", "output": "There is no related enetity." }, { "input": "Cathodic deposits were obtained on Ti - based alloys using suspensions containing nano - HA and MWCNTs dispersed in n - butanol solvent.", "output": "Ti, n - butanol." }, { "input": "It was shown that MWCNTs interacted with HA powders during hydrothermal processing, and therefore, they can easily be dispersed within aqueous - based suspensions.", "output": "There is no related enetity." }, { "input": "It was also shown that hydrothermal surface modification of MWCNTs with functional groups was achievable, which was a significant step toward eliminating nonwetting surface behavior of MWCNTs, resulting in obtaining homogeneous dispersion of them in liquids.", "output": "There is no related enetity." }, { "input": "Quality assessment and scavenging activity of Siamese neem flower extract.", "output": "There is no related enetity." }, { "input": "Young leaves and flowers of Siamese neem tree ( Azadirachta indica A. Juss. var. siamensis Valeton ) are commonly consumed as a bitter tonic vegetable.", "output": "There is no related enetity." }, { "input": "Active antioxidant components in the flowers are rutin and quercetin flavonoids.", "output": "rutin, quercetin, flavonoids." }, { "input": "The aqueous extracts of young flowers collected from 14 different locations in Thailand were quantitatively analysed using high - performance liquid chromatography for the contents of rutin and quercetin, and were determined for the loss on drying, heavy metals and pesticide residues, microbial contamination, solubility, chromatographic fingerprints and acute toxicity.", "output": "rutin, quercetin." }, { "input": "The extracts contained rutin and quercetin in the ranges from 388 to 1178 mg % dry weight ( average 772 mg % ), and 1 to 10 mg % dry weight ( average 5 mg % ), respectively.", "output": "rutin, quercetin." }, { "input": "EC50 of the scavenging activity of all extracts was found in the range of 27 - 133 micro g mL ( - 1 ).", "output": "There is no related enetity." }, { "input": "Loss on drying of the extracts was less than 7 % w / w and no sign of toxicity ( LD50 > 5 g kg ( - 1 ) ) was found.", "output": "There is no related enetity." }, { "input": "Polyphenol distribution in plant organs of tomato introgression lines.", "output": "Polyphenol." }, { "input": "The content of total polyphenols, chlorogenic, caffeic ( CaA ) and ferulic acids, and rutin, was investigated in plant organs of three introgression lines ( IL7 - 3, IL10 - 1 and IL12 - 4 ) of Solanum pennellii in Solanum lycopersicum cv M82 and compared with that of cropped parental.", "output": "polyphenols, chlorogenic, caffeic, CaA, ferulic acids, rutin." }, { "input": "Such study aims to evidence factors associated to the introgressions that can affect polyphenol distribution in plant.", "output": "polyphenol." }, { "input": "Among genotypes few differences in polyphenols were recorded on fresh weight basis.", "output": "polyphenols." }, { "input": "IL7 - 3 showed higher total polyphenols in fruits and lower rutin in leaves than the other genotypes.", "output": "polyphenols, rutin." }, { "input": "IL12 - 4 showed an increasing trend of total polyphenol concentration in fresh vegetative organs; however, this seems to depend on the lower water content rather than on a higher polyphenol biosynthesis in the genotype.", "output": "polyphenol, polyphenol." }, { "input": "IL10 - 1 sowed higher CaA and lignin contents in leaves.", "output": "CaA." }, { "input": "Such differences agree with the morphological and physiological traits of the genotypes.", "output": "There is no related enetity." }, { "input": "The potential impact of strawberry on human health.", "output": "There is no related enetity." }, { "input": "The strawberry ( Fragaria X ananassa, Duch. ) represents a relevant source of micronutrients, such as minerals, vitamin C, folate and phenolic substances, most of which are natural antioxidants and contribute to the high nutritional quality of the fruit.", "output": "vitamin C, folate, phenolic." }, { "input": "All these compounds are essential for health and, in particular, strawberry phenolics are best known for their antioxidant and anti - inflammatory action, and possess directly and indirectly antimicrobial, anti - allergy and anti - hypertensive properties, as well as the capacity to inhibit the activities of some physiological enzymes and receptor properties.", "output": "There is no related enetity." }, { "input": "The main objective of this article is to review and update the current knowledge on the potential impact of the strawberry on human health, with particular attention on compounds and their possible mechanisms of action.", "output": "There is no related enetity." }, { "input": "Urinary excretion of parabens in pregnant Japanese women.", "output": "parabens." }, { "input": "Urinary excretion of free and total ( free plus conjugated ) forms of methyl, ethyl, n - propyl and n - butyl parabens ( MP, EP, PP and BP, respectively ) and their metabolite p - hydroxybenzoic acid were measured for 111 pregnant Japanese women.", "output": "methyl , ethyl , n - propyl and n - butyl parabens, p - hydroxybenzoic acid." }, { "input": "Frequent detection of parabens and their metabolite indicated that exposure takes place daily for pregnant Japanese women.", "output": "parabens." }, { "input": "The estrogenic potency of PP was 20 times higher than those of the other 3 parabens for the present subjects when both abundance in the urine and the relative estrogenic activity of each compound was considered.", "output": "There is no related enetity." }, { "input": "Detection of free parabens suggested dermal exposure, probably from their inclusion in personal care products.", "output": "There is no related enetity." }, { "input": "No statistical association was found between the anogenital index ( birth weight - adjusted AGD ) of male offspring and the concentrations of any parabens in the urine of the mothers suggesting that the parabens were not apparently estrogenically active at the exposure level of the present subjects.", "output": "parabens, parabens." }, { "input": "The influence of the genetic and non - genetic factors on bone mineral density and osteoporotic fractures in Chinese women.", "output": "There is no related enetity." }, { "input": "To investigate the effects of genetic and non - genetic factors on bone mineral densities ( BMDs ) and osteoporotic fractures.", "output": "There is no related enetity." }, { "input": "This was a cross - sectional study to investigate the relationships between 18 SNPs and non - genetic factors with BMDs and osteoporotic fractures in 1012 Chinese Han women.", "output": "There is no related enetity." }, { "input": "Five SNPs in genes GPR177, CTNNB1, MEF2C, SOX6, and TNFRSF11B were associated with L1 - 4 or total hip BMDs.", "output": "There is no related enetity." }, { "input": "rs11898505 in SPTBN1 gene was associated with osteoporotic fractures.", "output": "There is no related enetity." }, { "input": "Subjects carrying the largest number of risk alleles ( highest 10 % ) not only had lower BMD values as compared to those carrying the least number of risk alleles ( lowest 10 % ), they also had a higher risk of fracture [ P = 0. 002, OR = 2. 252, 95 % CI ( 1. 136, 4. 463 ) ].", "output": "There is no related enetity." }, { "input": "Results from multivariate stepwise regression analysis revealed that age [ P < 0. 001, OR = 1. 038, 95 % CI ( 1. 018, 1. 058 ) ], number of falls in a year [ P < 0. 001, OR = 2. 347, 95 % CI ( 1. 459, 3. 774 ) ], the G risk allele in rs11898505 [ P = 0. 023, OR = 1. 559, 95 % CI ( 1. 062, 2. 290 ) ], and the L1 - 4 BMD [ P = 0. 017, OR = 0. 286, 95 % CI ( 0. 102, 0. 798 ) ] were associated with the occurrence of osteoporotic fractures.", "output": "There is no related enetity." }, { "input": "Genetic ( rs11898505 ) and non - genetic factors ( age, number of falls in a year and L1 - 4 BMD ) could work in concert to contribute to the risk of osteoporotic fractures.", "output": "There is no related enetity." }, { "input": "Flavonoids and antioxidant activity of flowers of Mexican Crataegus spp.", "output": "Flavonoids." }, { "input": "Flavonoids and antioxidant activity of extracts of flowers from some Mexican accessions of Crataegus were studied using six accessions with the purpose of contributing to the knowledge of the nutraceutical properties of the accessions of the Germplasm Bank of the Universidad Autonoma Chapingo.", "output": "Flavonoids." }, { "input": "Flavonoids were identified by HPLC - MS.", "output": "Flavonoids." }, { "input": "Among the flavonoids, the quercetin 3 - O - glucoside ( 3 ), quercetin 3 - O - rhamnoside ( 4 ), quercetin 3 - O - rhamnosyl - ( 1 --> 6 ) - glucoside ( 2 ) and quercetin 3 - O - rhamnosyl - ( 1 --> 2 ) - [ rhamnosyl - ( 1 --> 6 ) ] - glucoside ( 1 ) were assigned.", "output": "flavonoids, quercetin 3 - O - glucoside, quercetin 3 - O - rhamnoside, quercetin 3 - O - rhamnosyl - ( 1 --> 6 ) - glucoside, quercetin 3 - O - rhamnosyl - ( 1 --> 2 ) - [ rhamnosyl - ( 1 --> 6 ) ] - glucoside." }, { "input": "Flavonoid content and radical scavenging activity explain some of the medicinal properties attributed to flowers of Mexican hawthorns.", "output": "Flavonoid." }, { "input": "Antioxidant activity of Buglossoides purpureocaerulea ( L. ) I. M.", "output": "There is no related enetity." }, { "input": "Johnst. extracts.", "output": "There is no related enetity." }, { "input": "Buglossoides purpureocaerulea is a little - known plant used in the folk tradition for the preparation of a decoction in Sud, Italy, where it is appreciated for its beneficial effects on liver diseases.", "output": "There is no related enetity." }, { "input": "These properties may be due to the presence of antioxidant compounds.", "output": "There is no related enetity." }, { "input": "This study presents the phenolic characterisation and the antioxidant activity ( AA ) of B. purpureocaerulea extracts obtained by decoction, ethanol infusion and ethanol and methanol macerations.", "output": "ethanol, ethanol, methanol." }, { "input": "Total phenols ranged between 69 and 100 mg g ( - 1 ) dry weight ( DW ).", "output": "There is no related enetity." }, { "input": "The main compounds were: rosmarinic acid, caffeic acid, lithospermic acid and salvianolic acid C.", "output": "rosmarinic acid, caffeic acid, lithospermic acid, salvianolic acid C." }, { "input": "The extracts showed a good AA, particularly high for the decoction ( 142 - 283 micro mol TE g ( - 1 ) DW; TE, Trolox equivalent ) and ethanol maceration extract ( 214 - 364 micro mol TE g ( - 1 ) DW ) when determined by DPPH and ferric reducing antioxidant power test, respectively.", "output": "Trolox, ethanol, DPPH, ferric." }, { "input": "Live - birth rates after HP - hMG stimulation in the long GnRH agonist protocol: association with mid - follicular hCG and progesterone concentrations, but not with LH concentrations.", "output": "progesterone." }, { "input": "The aim of this retrospective study was to investigate the impact of endogenous and exogenous luteinizing hormone ( LH ) activity on treatment outcome, when taking into consideration potential confounding variables.", "output": "There is no related enetity." }, { "input": "Data were derived from IVF patients ( n = 358 ) stimulated with highly purified menotrophin ( HP - hMG ) in a long gonadotrophin - releasing hormone ( GnRH ) agonist protocol.", "output": "There is no related enetity." }, { "input": "Simple retrospective logistic regression analysis showed that the mid - follicular exogenous concentrations of human chorionic gonadotrophin ( hCG ) ( p = 0. 027 ), provided by the HP - hMG preparation, and female age ( p = 0. 009 ) were significantly associated with live - birth rate, while the mid - follicular progesterone concentration ( p = 0. 075 ), the estradiol concentration on last stimulation day ( p = 0. 075 ) and number of embryos transferred ( p = 0. 071 ) were borderline significant.", "output": "progesterone, estradiol." }, { "input": "Endogenous LH was not associated with live - birth rate; neither at start of stimulation ( p = 0. 123 ), nor in the mid - follicular phase ( p = 0. 933 ) or on the last day of stimulation ( p = 0. 589 ).", "output": "There is no related enetity." }, { "input": "In the multiple regression analysis of life birth, mid - follicular hCG ( p = 0. 016 ) was identified as a positive predictor, and age ( p = 0. 004 ) and mid - follicular progesterone ( p = 0. 029 ) as negative predictors.", "output": "progesterone." }, { "input": "In conclusion, mid - follicular concentrations of exogenous hCG and progesterone, but not endogenous LH, are associated with live - birth rate in IVF patients treated with HP - hMG in a long GnRH agonist cycle.", "output": "progesterone." }, { "input": "Development and characterization of composite YSZ - PEI electrophoretically deposited membrane for Li - ion battery.", "output": "PEI, Li." }, { "input": "In this work, the electrophoretic - deposition ( EPD ) method was used to fabricate pristine and composite ceramic - polymer membranes for application in planar and 3D microbattery configurations.", "output": "There is no related enetity." }, { "input": "The major focus was on the effect of polyethyleneimine additive on the morphology, composition, and electrochemical properties of the membrane.", "output": "polyethyleneimine." }, { "input": "The ionic conductivity, cycleability, and charge / discharge behavior of planar LiFePO ( 4 ) / Li cells comprising composite porous YSZ - based membrane with impregnated LiPF ( 6 ) EC: DEC electrolyte were found to be similar to the cells with commercial Celgard membrane.", "output": "LiFePO ( 4 ), Li, LiPF ( 6 )." }, { "input": "Conformal EPD coating of the electrode materials by a thin - film ceramic separator is advantageous for high - power operation and safety of batteries.", "output": "There is no related enetity." }, { "input": "Dose response analysis of monophthalates in the murine embryonic stem cell test assessed by cardiomyocyte differentiation and gene expression.", "output": "monophthalates." }, { "input": "The embryonic stem cell test ( EST ) is based on compound - induced inhibition of cardiomyocyte differentiation of pluripotent stem cells.", "output": "There is no related enetity." }, { "input": "We examined the use of transcriptomics to assess concentration - effect relationships and performed potency ranking within a chemical class.", "output": "There is no related enetity." }, { "input": "Three embryotoxic phthalate monoesters, monobutyl phthalate ( MBuP ), monobenzyl phthalate ( MBzP ) and mono - ( 2 - ethylhexyl ) phthalate ( MEHP ) and the non - embryotoxic monomethyl phthalate ( MMP ) were studied for their effects on gene expression.", "output": "phthalate monoesters, monobutyl phthalate, MBuP, monobenzyl phthalate, MBzP, mono - ( 2 - ethylhexyl ) phthalate, MEHP, monomethyl phthalate, MMP." }, { "input": "Effects on gene expression were observed at concentrations that did not inhibit cardiomyocyte differentiation or induce cytotoxicity.", "output": "There is no related enetity." }, { "input": "The embryotoxic phthalate monoesters altered the expression of 668 commonly expressed genes in a concentration - dependent fashion.", "output": "phthalate monoesters." }, { "input": "The same potency ranking was observed for morphology and gene expression ( MEHP > MBzP > MBuP > MMP ).", "output": "MEHP, MBzP, MBuP, MMP." }, { "input": "These results indicate that integrating transcriptomics provides a sensitive method to measure the dose - dependent effects of phthalate monoester exposure and enables potency ranking based on a common mode of action within a class of compounds.", "output": "phthalate monoester." }, { "input": "Transcriptomic approaches may improve the applicability of the EST, in terms of sensitivity and specificity.", "output": "There is no related enetity." }, { "input": "The antioxidant and anticancer effects of wild carrot oil extract.", "output": "There is no related enetity." }, { "input": "Daucus carota L. ssp.", "output": "There is no related enetity." }, { "input": "carota ( Apiacea ) is used in traditional medicine in Lebanon and in different regions throughout the world.", "output": "There is no related enetity." }, { "input": "The present study investigates the in vitro anticancer activities of Daucus carota oil extract ( DCOE ) on four human cancer cell lines as well as its in vitro antioxidant activity.", "output": "There is no related enetity." }, { "input": "DCOE was extracted from the dried umbels with 50: 50 acetone - methanol.", "output": "acetone, methanol." }, { "input": "The oil extract was analyzed by gas chromatography - mass spectrometry and screened for its antioxidant properties in vitro using 1, 1 - diphenyl - 2 - picryl hydrazyl free radical scavenging assay ( DPPH ), ferrous ion chelating assay ( FIC ) and the ferric reducing antioxidant power assay ( FRAP ).", "output": "1 , 1 - diphenyl - 2 - picryl hydrazyl, DPPH, ferrous, ferric." }, { "input": "The anticancer activity of the oil extract against human colon ( HT - 29, Caco - 2 ) and breast ( MCF - 7, MDA - MB - 231 ) cancer cell lines was evaluated using the trypan blue exclusion method and the WST - 1 cell proliferation assay.", "output": "trypan blue." }, { "input": "DCOE exhibited antioxidant activity in all assays used.", "output": "There is no related enetity." }, { "input": "The FRAP value was 164 +/- 5. 5 micro mol FeSO4 / g, and the IC50 values for DPPH and FIC assays were 2. 1 +/- 0. 03 mg / ml and 0. 43 +/- 0. 02 mg / ml, respectively.", "output": "FeSO4, DPPH." }, { "input": "Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation.", "output": "There is no related enetity." }, { "input": "The effect of DCOE on the cell lines exhibited time and dose - dependent responses.", "output": "There is no related enetity." }, { "input": "The present study established that DCOE possesses both antioxidant and promising anticancer activities.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models.", "output": "Saponin." }, { "input": "In this study, the in vivo effects of a purified saponin mixture ( PSM ), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol ( PC ) and carbon tetrachloride ( CCl4 ).", "output": "saponin, paracetamol, carbon tetrachloride, CCl4." }, { "input": "The effects of PSM were compared with silymarin.", "output": "silymarin." }, { "input": "Male Wistar rats were challenged orally with 20 % CCl4 or PC ( 2 g / kg ) four days after being pre - treated with PSM ( 100 mg / kg ) or silymarin ( 200 mg / kg ).", "output": "CCl4, silymarin." }, { "input": "A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase ( LDH ) activities and glutathione ( GSH ) levels and an increase of malondialdehyde ( MDA ) quantity was observed after CCl4 and PC administration alone.", "output": "aspartate, alanine, lactate, glutathione, GSH, malondialdehyde, MDA, CCl4." }, { "input": "PSM pre - treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH.", "output": "MDA, GSH." }, { "input": "Biotransformation phase I enzymes were also assessed in both models.", "output": "There is no related enetity." }, { "input": "In the CCl4 hepatotoxicity model, pre - treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine - N - demethylase and aniline 4 - hydroxylase activity and cytochrome P450, compared to the CCl4 only group.", "output": "CCl4, silymarin, ethylmorphine, N, aniline, CCl4." }, { "input": "Neither silymarin nor PSM influenced PC biotransformation.", "output": "silymarin." }, { "input": "Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl4 and PC - induced liver damage comparable to that of silymarin.", "output": "CCl4, silymarin." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Influence of low ultrasound intensity on the degradation of dextran catalyzed by dextranase.", "output": "There is no related enetity." }, { "input": "In our current research work, the effect of ultrasound irradiation on the enzymatic activity and enzymatic hydrolysis kinetic parameters of dextran catalysis by dextranase were investigated.", "output": "There is no related enetity." }, { "input": "Furthermore, the effects of ultrasound irradiation on the structure of dextranase were investigated with the aid of fluorescence spectroscopy and circular dichroism ( CD ) spectroscopy.", "output": "There is no related enetity." }, { "input": "The maximum activity of dextranase was observed when the sample was treated with ultrasound at 25 kHz, 40 W for 15 min, under which the enzyme activity increased by 13. 43 % compared the routine thermal incubation at 50 degrees C.", "output": "There is no related enetity." }, { "input": "Experimental Kinetics results, demonstrated that, both the V ( max ) and K ( M ) values of dextranase increased with ultrasound - treated compared with the incubation at 50 degrees C.", "output": "There is no related enetity." }, { "input": "Likewise, both the catalytic and specificity constants were higher under the effects of an ultrasonic field, indicating that, the substrate is converted into the product at an increased rate when compared with the incubation at 50 degrees C.", "output": "There is no related enetity." }, { "input": "On the other hand, fluorescence and CD spectra reflected that the ultrasound irradiation had increased the number of tryptophan on dextranase surface with increased alpha - helix by 15. 74 % and reduced random coil by 5. 41 % upon ultrasound - treated dextranase protein compared to the control, which were helpful for the improvement of its activity.", "output": "tryptophan." }, { "input": "Atomoxetine modulates spontaneous and sensory - evoked discharge of locus coeruleus noradrenergic neurons.", "output": "Atomoxetine." }, { "input": "Atomoxetine ( ATM ) is a potent norepinephrine ( NE ) uptake inhibitor and increases both NE and dopamine synaptic levels in prefrontal cortex, where it is thought to exert its beneficial effects on attention and impulsivity.", "output": "Atomoxetine, ATM, norepinephrine." }, { "input": "At the behavioral level, ATM has been shown to cause improvements on the measures of executive functions, such as response inhibition, working memory and attentional set shifting across different species.", "output": "ATM." }, { "input": "However, the exact mechanism of action for ATM ' s effects on cognition is still not clear.", "output": "ATM." }, { "input": "One possible target for the cognitive enhancing effects of ATM is the noradrenergic locus coeruleus ( LC ), the only source of NE to key forebrain areas such as cerebral cortex and hippocampus.", "output": "ATM." }, { "input": "Although it is known that ATM increases NE availability overall by blocking reuptake of NE, the effects of this agent on impulse activity of LC neurons have not been reported.", "output": "ATM." }, { "input": "Here, the effect of ATM ( 0. 1 - 1 mg / kg, ip ) on NE - LC neurons was investigated by recording extracellular activity of LC neurons in isoflurane - anesthetized rats.", "output": "ATM, isoflurane." }, { "input": "ATM caused a significant decrease of the tonic activity of LC single - units, although leaving intact the sensory - evoked excitatory component of LC phasic response.", "output": "ATM." }, { "input": "Moreover, the magnitude of the inhibitory component of LC response to paw stimulation was increased after 1 mg / kg of ATM and its duration was prolonged at 0. 3 mg / kg.", "output": "ATM." }, { "input": "Together, these effects of ATM produced an increase in the phasic - to - tonic ratio of LC phasic response to sensory stimulation.", "output": "ATM." }, { "input": "ATM also modulated the average sensory - evoked local field potential ( LFP ) and spike - field coherence in LC depending on the dose tested.", "output": "ATM." }, { "input": "The lower dose ( 0. 1 mg / kg ) significantly decreased early positive and negative components of the sensory - evoked LFP response.", "output": "There is no related enetity." }, { "input": "Higher doses ( 0. 3 - 1 mg / kg ) initially increased and then decreased the amplitude of components of the evoked fields, whereas the spike - field coherence was enhanced by 1 mg / kg ATM across frequency bands.", "output": "ATM." }, { "input": "Finally, coherence between LC fields and EEG signals was generally increased by 1 mg / kg ATM, whereas 0. 1 and 0. 3 mg / kg respectively decreased and increased coherence values in specific frequency bands.", "output": "ATM." }, { "input": "Taken together these results suggest that ATM effects on LC neuronal activity are dose - dependent, with different doses affecting different aspects of LC firing.", "output": "ATM." }, { "input": "This modulation of activity of LC - NE neurons may play a role in the cognitive effects of ATM.", "output": "ATM." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Could maternal exposure to the antidepressants fluoxetine and St.", "output": "fluoxetine." }, { "input": "John ' s Wort induce long - term reproductive effects on male rats?", "output": "There is no related enetity." }, { "input": "Based on the limited number of studies that have investigated the adverse effects of maternal treatment with antidepressants on the development of male descendents, this study was carried out in rat in order to evaluate if maternal exposure to fluoxetine ( FLX ) or St.", "output": "fluoxetine, FLX." }, { "input": "John ' s Wort ( SJW ) could disrupt the development of male offspring.", "output": "There is no related enetity." }, { "input": "The dams were treated daily, by gavage, with 7. 5 mg / kg of FLX or 100 mg / kg SJW during pregnancy and lactation.", "output": "FLX." }, { "input": "The reproductive and behavior parameters were analyzed in male pups.", "output": "There is no related enetity." }, { "input": "Results showed decreases in the weight of the full seminal vesicle and in the number of spermatozoa.", "output": "There is no related enetity." }, { "input": "Moreover, FLX - exposed pups presented reduced seminiferous epithelium height and diameter of seminiferous tubules.", "output": "FLX." }, { "input": "The present study shows that maternal exposure to FLX, but not SJW could interfere on reproductive parameters in adult male rats.", "output": "FLX." }, { "input": "Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke.", "output": "There is no related enetity." }, { "input": "Embryonic stem cells ( ESCs ) provide a valuable in vitro model for testing toxicity of chemicals and environmental contaminants including cigarette smoke.", "output": "There is no related enetity." }, { "input": "Mouse ESCs were acutely or chronically exposed to smoke components, cigarette smoke condensate ( CSC ), or cadmium, an abundant component of CSC, and then evaluated for their self - renewal, apoptosis, DNA damage and telomere function.", "output": "cadmium." }, { "input": "Acute exposure of ESCs to high dose of CSC or cadmium increased DNA damage and apoptosis.", "output": "cadmium." }, { "input": "Yet, ESCs exhibited a remarkable capacity to recover following absence of exposure.", "output": "There is no related enetity." }, { "input": "Chronic exposure of ESCs to low dose of CSC or cadmium resulted in shorter telomeres and DNA damage.", "output": "cadmium." }, { "input": "Together, acute exposure of ESCs to CSC or cadmium causes immediate cell death and reduces pluripotency, while chronic exposure of ESCs to CSC or cadmium leads to DNA damage and telomere shortening.", "output": "cadmium, cadmium." }, { "input": "Notably, a sub - proportion of ESCs during passages is selected to resist to smoke - induced oxidative damage to telomeres.", "output": "There is no related enetity." }, { "input": "Electrophoretic deposition of the thiophene - based copolymer and its composites with C60.", "output": "thiophene, C60." }, { "input": "Electrophoretic deposition is a useful and efficient technique to deposit conjugated polymers, if suitable suspension of the target polymer is obtained.", "output": "There is no related enetity." }, { "input": "Unfortunately, neither general theory nor universal procedure for the preparation of a suspension suitable for electrophoretic deposition has seemed to be established yet.", "output": "There is no related enetity." }, { "input": "Thus, accumulation of individual knowledge is still important in this area.", "output": "There is no related enetity." }, { "input": "Here, the preparation of suspensions of a thiophene - based polymer poly ( 3 - octylthiophene - 2, 5 - diyl - co - 3 - decyloxythiophene - 2, 5 - diyl ) ( POT - co - DOT ) and their application to the electrophoretic deposition have been reported.", "output": "thiophene, poly ( 3 - octylthiophene - 2 , 5 - diyl - co - 3 - decyloxythiophene - 2 , 5 - diyl ), POT - co - DOT." }, { "input": "The suspensions of POT - co - DOT with various good / poor solvents ratios were easily obtained by mixing a toluene solution of the polymer and acetonitrile.", "output": "POT - co - DOT, toluene, acetonitrile." }, { "input": "The composition of the dispersion medium significantly affects the surface morphology of the film prepared by the electrophoretic deposition in the suspension.", "output": "There is no related enetity." }, { "input": "Composite films consisting of POT - co - DOT and C ( 60 ) have also been successfully prepared by electrophoretic deposition.", "output": "POT - co - DOT, C ( 60 )." }, { "input": "Because the optical absorption peak at 333 nm in C ( 60 ) showed neither significant broadening nor a red shift, C ( 60 ) molecules were expected to be well - dispersed in the composite films.", "output": "C ( 60 ), C ( 60 )." }, { "input": "A photovoltaic device with a composite film prepared from a POT - co - DOT / C ( 60 ) = 2: 1 suspension showed 10 times larger short - circuit current density and 5 times larger power conversion efficiency than a device with pure POT - co - DOT, although further work is required to improve the device performance.", "output": "POT - co - DOT, C ( 60 ), POT - co - DOT." }, { "input": "Structural requirements for effective oximes - Evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes.", "output": "oximes, oximes." }, { "input": "Treatment of poisoning by various organophosphorus ( OP ) nerve agents with established acetylcholinesterase ( AChE ) reactivators ( oximes ) is insufficient.", "output": "organophosphorus, oximes." }, { "input": "In consequence, extensive research programs have been undertaken in various countries in the past decades to identify more effective oximes.", "output": "oximes." }, { "input": "The efficacy of new compounds has been investigated with different in vitro and in vivo models which hamper the comparison of results from different laboratories.", "output": "There is no related enetity." }, { "input": "The crucial mechanism of action of oximes is the reactivation of phosphylated AChE.", "output": "oximes." }, { "input": "The kinetic properties of these compounds can be quantified in vitro with isolated AChE from different origin.", "output": "There is no related enetity." }, { "input": "It was tempting to evaluate the reactivation kinetics of a series of oximes with various OP inhibitors performed under identical experimental conditions in order to get insight into structural requirements for adequate affinity and reactivity towards inhibited AChE.", "output": "oximes." }, { "input": "The determination of reactivation rate constants with bispyridinium oximes having different linkers, bearing oxime group ( s ) at different positions and having in part additional substituents revealed that ( a ) the reactivating potency was dependent on the position of the oxime groups and of additional substituents, ( b ) small modifications of the oxime structure had an in part marked effect on the kinetic properties and ( c ) no single oxime had an adequate reactivating potency with AChE inhibited by structurally different OP.", "output": "bispyridinium oximes, oxime, oxime, oxime, oxime." }, { "input": "These and previous studies underline the necessity to investigate in detail the kinetic properties of novel oximes and that the identification of a single oxime being effective against a broad range of structurally different OP will remain a major challenge.", "output": "oximes, oxime." }, { "input": "Evaluation of seven drug metabolisms and clearances by cryopreserved human primary hepatocytes cultivated in microfluidic biochips.", "output": "There is no related enetity." }, { "input": "We present characterization of the metabolic performance of human cryopreserved hepatocytes cultivated in a platform of parallelized microfluidic biochips.", "output": "There is no related enetity." }, { "input": "The RTqPCR analysis revealed that the mRNA levels of the cytochromes P450 ( CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 ) were reduced after the adhesion period ( when compared to the post - thawing step ).", "output": "There is no related enetity." }, { "input": "The microfluidic perfusion played a part in stabilizing and partially recovering the levels of the HNF4 alpha, PXR, OAPT2, CYP 1A2, 2B6, 2C19 and 3A4 mRNA on contrary to non - perfused cultures.", "output": "There is no related enetity." }, { "input": "Fluorescein diacetate staining and P - gp mRNA level illustrated the hepatocytes ' polarity in the biochips.", "output": "Fluorescein diacetate." }, { "input": "Drug metabolism was assessed using midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen and repaglinide as probes.", "output": "midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen, repaglinide." }, { "input": "Metabolite detection and quantification revealed that CYP1A2 ( via the detection of paraxanthine ), CYP3A4 ( via 1 - OH - midazolam, and omeprazole sulfone detection ), CYP2C8 ( via hydroxyl - repaglinide detection ), CYP2C19 ( via hydroxy - omeprazole detection ) and CYP2D6 ( via dextrorphan detection ) were functional in our microfluidic configurations.", "output": "paraxanthine, 1 - OH - midazolam, omeprazole sulfone, hydroxyl - repaglinide, hydroxy - omeprazole, dextrorphan." }, { "input": "Furthermore, the RTqPCR analysis showed that the drugs acted as inductors leading to overexpression of mRNA levels when compared to post - thawing values ( such as for HNF4 alpha, PXR and CYP3A4 by dextromethorpahn and omeprazole ).", "output": "dextromethorpahn, omeprazole." }, { "input": "Finally, intrinsic in vitro biochip clearances were extracted using a PBPK model for predictions.", "output": "There is no related enetity." }, { "input": "The biochip predictions were compared to literature in vitro data and in vivo situations.", "output": "There is no related enetity." }, { "input": "Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung.", "output": "Vitamin A." }, { "input": "Partial reversibility by retinoic acid.", "output": "retinoic acid." }, { "input": "Vitamin A is essential for lung development and pulmonary cell differentiation.", "output": "Vitamin A." }, { "input": "Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances.", "output": "There is no related enetity." }, { "input": "Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form.", "output": "retinoids, retinoic acid, vitamin A." }, { "input": "This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all - trans - retinoic acid.", "output": "vitamin A, all - trans - retinoic acid." }, { "input": "Male weanling pups were fed a retinol - adequate / - deficient diet until 60 days old.", "output": "retinol." }, { "input": "A subgroup of vitamin - A - deficient pups received daily intraperitoneal all - trans - retinoic acid injections for 10 days.", "output": "vitamin - A, all - trans - retinoic acid." }, { "input": "Collagen IV and laminin chain composition were modified in vitamin - A - deficient rats.", "output": "vitamin - A." }, { "input": "The protein and mRNA contents of chains alpha 1 ( IV ), alpha 3 ( IV ) and alpha 4 ( IV ) increased; those of chains alpha 2 ( IV ) and alpha 5 ( IV ) remained unchanged; and the protein and mRNA contents of laminin chains alpha 5, beta 1 and gamma 1 decreased.", "output": "There is no related enetity." }, { "input": "The mRNA of laminin chains alpha 2 and alpha 4 also decreased.", "output": "There is no related enetity." }, { "input": "Matrix metalloproteinases 2 and 9 decreased, but the tissue inhibitors of metalloproteinases 1 and 2 did not change.", "output": "There is no related enetity." }, { "input": "Treating vitamin - A - deficient rats with retinoic acid reversed all alterations, but laminin chains alpha 2, alpha 4 and alpha 5 and matrix metalloproteinase 2 remained low.", "output": "vitamin - A, retinoic acid." }, { "input": "In conclusion, vitamin A deficiency alters the subunit composition of collagen IV and laminin and the lung ' s proteolytic potential, which are partly reverted by retinoic acid.", "output": "vitamin A, retinoic acid." }, { "input": "These alterations could contribute to impaired lung function and predispose to pulmonary disease.", "output": "There is no related enetity." }, { "input": "The alignment of barium ferrite nanoparticles from their suspensions in electric and magnetic fields.", "output": "barium ferrite." }, { "input": "The alignment of plate - like barium ferrite nanoparticles, with diameters of 10 - 350 nm and thicknesses of 3 - 10 nm, in electric and / or magnetic fields was studied.", "output": "barium ferrite." }, { "input": "Stable suspensions were prepared in 1 - butanol with dodecylbenzenesulphonic acid as a surfactant.", "output": "1 - butanol, dodecylbenzenesulphonic acid." }, { "input": "The deposits were produced from the suspensions with classic electrophoretic deposition, electrophoretic deposition in a magnetic field, and with drying in a magnetic field.", "output": "There is no related enetity." }, { "input": "The experiments, supported by theoretical calculations, show that the alignment of the nanoplates in the deposits was determined by the interplay between the hydrodynamic, electric, and magnetic forces.", "output": "There is no related enetity." }, { "input": "The preferential alignment of the nanoplates in plane with the substrate coincided with their magnetic orientation, and it increased with the shape anisotropy of the particles.", "output": "There is no related enetity." }, { "input": "The deposits were sintered at 1150 degrees C for 5 h to obtain ceramic films, which showed a magnetic orientation up to 90 %.", "output": "There is no related enetity." }, { "input": "Sclerostin antibody improves skeletal parameters in a Brtl / + mouse model of osteogenesis imperfecta.", "output": "There is no related enetity." }, { "input": "Osteogenesis imperfecta ( OI ) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture.", "output": "There is no related enetity." }, { "input": "Symptoms are most prominent during childhood.", "output": "There is no related enetity." }, { "input": "Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long - bone fracture rates.", "output": "There is no related enetity." }, { "input": "New treatments for OI are needed to increase bone mass throughout the skeleton.", "output": "There is no related enetity." }, { "input": "Sclerostin antibody ( Scl - Ab ) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI.", "output": "There is no related enetity." }, { "input": "In this study, Scl - Ab therapy was investigated in mice heterozygous for a typical OI - causing Gly --> Cys substitution in col1a1.", "output": "Gly, Cys." }, { "input": "Two weeks of Scl - Ab successfully stimulated osteoblast bone formation in a knock - in model for moderately severe OI ( Brtl / + ) and in WT mice, leading to improved bone mass and reduced long - bone fragility.", "output": "There is no related enetity." }, { "input": "Image - guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl - Ab.", "output": "There is no related enetity." }, { "input": "These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility.", "output": "There is no related enetity." }, { "input": "In conclusion, short - term Scl - Ab was successfully anabolic in osteoblasts harboring a typical OI - causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI.", "output": "There is no related enetity." }, { "input": "Hospitalized osteoporotic vertebral fracture increases the risk of stroke: a population - based cohort study.", "output": "There is no related enetity." }, { "input": "The association between osteoporosis and cardiovascular diseases has been demonstrated.", "output": "There is no related enetity." }, { "input": "Higher cardiovascular risk has also been correlated with vertebral fractures.", "output": "There is no related enetity." }, { "input": "However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain.", "output": "There is no related enetity." }, { "input": "This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture.", "output": "There is no related enetity." }, { "input": "Patients with osteoporotic vertebral fracture were identified ( n = 380 ) and 10 age - and sex - matched controls per case ( comparison group, n = 3795 ) were chosen from a nationwide representative cohort of 999, 997 people from 1998 to 2005.", "output": "There is no related enetity." }, { "input": "Both groups were followed - up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities ( ie, hypertension, diabetes, arrhythmia, or coronary heart diseases ) and exposure to medications ( ie, aspirin, lipid lowering drug, or nitrates ), and assessed by Kaplan - Meier and Cox regression analyses.", "output": "aspirin, nitrates." }, { "input": "The incidence rate of stroke in the osteoporotic vertebral fracture group ( 37. 5 per 1000 person - years; 95 % confidence interval [ CI ], 27. 5 - 51. 2 ) was significantly higher than in the comparison group ( 14. 0 per 1000 person - years; 95 % CI, 12. 0 - 16. 4, p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Stroke was more likely to occur in the osteoporotic vertebral fracture patients than in the normal controls ( crude hazard ratio [ HR ] 2. 68, 95 % CI 1. 89 - 3. 79, p < 0. 001; adjusted HR 2. 71, 95 % CI 1. 90 - 3. 86, p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "In conclusion, patients with osteoporotic vertebral fracture have a higher risk of stroke ( ie, both ischemic and hemorrhagic ) and require stroke prevention strategies.", "output": "There is no related enetity." }, { "input": "Three new diarylbutane lignans from the resin of Bursera fagaroides.", "output": "diarylbutane lignans." }, { "input": "Three new diarylbutane lignans, named 9 - acetyl - 9 ' - pentadecanoil - dihydroclusin ( 1 ), 2, 3 - demethoxy - secoisolintetralin monoacetate ( 4 ) and dihydroclusin monoacetate ( 5 ), have been isolated from the resin of Bursera fagaroides, together with two known ones, 2, 3 - demethoxy - secoisolintetralin diacetate ( 2 ) and dihydroclusin diacetate ( 3 ).", "output": "diarylbutane lignans, 9 - acetyl - 9 ' - pentadecanoil - dihydroclusin, 2 , 3 - demethoxy - secoisolintetralin monoacetate, dihydroclusin monoacetate, 2 , 3 - demethoxy - secoisolintetralin diacetate, dihydroclusin diacetate." }, { "input": "The complete structure assignments were obtained by means of ( 1 ) H and ( 13 ) C NMR spectra.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "Pelargonium graveolens L ' Her. and Artemisia arborescens L. essential oils: Chemical composition, antifungal activity against Rhizoctonia solani and insecticidal activity against Rhysopertha dominica.", "output": "There is no related enetity." }, { "input": "The chemical composition of the Pelargonium graveolens essential oil allowed the identification of 15 compounds ( 93. 86 % of the total essential oil ).", "output": "There is no related enetity." }, { "input": "The major fractions were citronellol ( 35 % ) and geraniol ( 28. 8 % ).", "output": "citronellol, geraniol." }, { "input": "The chemical composition of the Artemisia arborescens essential oil revealed twenty - one compounds representing 93. 57 % of the total essential oil.", "output": "There is no related enetity." }, { "input": "The main compounds were chamazulene ( 31. 9 % ) and camphor ( 25. 8 % ).", "output": "chamazulene, camphor." }, { "input": "The insecticidal effects were tested towards the insect Rhysopertha dominica.", "output": "There is no related enetity." }, { "input": "Results revealed that these two essential oils were highly effective against R. dominica at the dose of 50 micro L on Petri dish of 8. 5 cm of diameter.", "output": "There is no related enetity." }, { "input": "The antifungal activity was evaluated against Rhizoctonia solani and results showed that both of the essential oils were highly active at a dose of 12. 5 micro L / 20 mL of PDA.", "output": "There is no related enetity." }, { "input": "Moreover, the inhibitory effect of P. graveolens essential oil was evidenced as stronger than that of the A. arborescens oil for all the tested doses.", "output": "There is no related enetity." }, { "input": "A new cyclonerol derivative from a marine - derived fungus Ascotricha sp.", "output": "cyclonerol." }, { "input": "ZJ - M - 5.", "output": "There is no related enetity." }, { "input": "A new sesquiterpene, ascotrichic acid ( 1 ), was isolated from a marine - derived fungus Ascotricha sp., together with the other two known analogues, cyclonerodiol ( 2 ) and 10 ( Z ) - cyclonerotriol ( 3 ).", "output": "sesquiterpene, cyclonerodiol, 10 ( Z ) - cyclonerotriol." }, { "input": "Its structure was established by spectroscopic methods ( 1D and 2D NMR, HR - ESI - MS ).", "output": "There is no related enetity." }, { "input": "Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb / c mice.", "output": "Methylselenol, selenium." }, { "input": "It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo.", "output": "methylselenol, selenium." }, { "input": "In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells.", "output": "methylselenol." }, { "input": "The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis.", "output": "methylselenol." }, { "input": "Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c - Myc, E2F1 and Phos p38 MAP kinase.", "output": "methylselenol." }, { "input": "Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S - phase in mouse colon cancer MC26 cells.", "output": "methylselenol." }, { "input": "When the MC26 cells were transplanted to their immune - competent Balb / c mice, methylselenol - treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells.", "output": "methylselenol." }, { "input": "Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth.", "output": "methylselenol." }, { "input": "Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and beta - cell proportion.", "output": "biotin, glucose." }, { "input": "Besides its role as a carboxylase cofactor, biotin has a wide repertoire of effects on gene expression, development and metabolism.", "output": "biotin." }, { "input": "Pharmacological concentrations of biotin enhance insulin secretion and the expression of genes and signaling pathways that favor islet function in vitro.", "output": "biotin." }, { "input": "However, the in vivo effects of biotin supplementation on pancreatic islet function are largely unknown.", "output": "biotin." }, { "input": "In the present study, we investigated whether in vivo biotin supplementation in the diet has positive effects in rodent pancreatic islets.", "output": "biotin." }, { "input": "Male BALB / cAnN Hsd mice were fed a control or a biotin - supplemented diet over 8 weeks postweaning and tested for glucose homeostasis, insulin secretion, islet gene expression and pancreatic morphometry.", "output": "biotin, glucose." }, { "input": "Insulin secretion increased from the islets of biotin - supplemented mice, together with the messenger RNA ( mRNA ) expression of several transcription factors regulating insulin expression and secretion, including forkhead box A2, pancreatic and duodenal homeobox 1 and hepatocyte nuclear factor 4 alpha.", "output": "biotin." }, { "input": "The mRNA abundance of glucokinase, Cacna1d, acetyl - CoA carboxylase, and insulin also increased.", "output": "acetyl - CoA." }, { "input": "Consistent with these effects, glucose tolerance improved, and glucose - stimulated serum insulin levels increased in biotin - supplemented mice, without changes in fasting glucose levels or insulin tolerance.", "output": "glucose, glucose, biotin, glucose." }, { "input": "Biotin supplementation augmented the proportion of beta cells by enlarging islet size and, unexpectedly, also increased the percentage of islets with alpha cells at the islet core.", "output": "Biotin." }, { "input": "mRNA expression of neural cell adhesion molecule 1, an adhesion protein participating in the maintenance of islet architecture, decreased in biotin - supplemented islets.", "output": "biotin." }, { "input": "These findings provide, for the first time, insight into how biotin supplementation exerts its effects on function and proportion of beta cells, suggesting a role for biotin in the prevention and treatment of diabetes.", "output": "biotin, biotin." }, { "input": "Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle - aged rats.", "output": "caffeine." }, { "input": "Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown.", "output": "caffeine." }, { "input": "Because brain - derived neurotrophic factor ( BDNF ) is associated with memory formation and BDNF ' s actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine ( 1 mg / mL drinking solution for 30 days ) on short - and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young ( 3 month old ) and middle - aged ( 12 month old ) rats.", "output": "adenosine, caffeine, caffeine." }, { "input": "Caffeine treatment substantially reduced i ) age - related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii ) parallel increases in hippocampal BDNF levels.", "output": "Caffeine." }, { "input": "In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age.", "output": "caffeine." }, { "input": "These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro - cognitive effects of caffeine on age - associated losses in memory encoding.", "output": "caffeine." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Cognitive enhancement by omega - 3 fatty acids from child - hood to old age: findings from animal and clinical studies.", "output": "omega - 3 fatty acids." }, { "input": "Omega - ( n ) - 3 polyunsaturated fatty acids ( PUFAs ), including docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) are major components of neuronal membranes and have a wide range of functions, from modulating synaptic plasticity and neurochemistry, to neuroimmune - modulation and neuroprotection.", "output": "Omega - ( n ) - 3 polyunsaturated fatty acids, PUFAs, docosahexaenoic acid, DHA, eicosapentaenoic acid, EPA." }, { "input": "Thus, it is not surprising that n - 3 PUFA are widely acknowledged to have cognitive - enhancing effects.", "output": "PUFA." }, { "input": "Although clinical evidence is somewhat conflicting, probably in large part due to methodological issues, animal studies have consistently demonstrated that n - 3 PUFA are indispensable for proper brain development, may enhance cognitive function in healthy, adult individuals and attenuate cognitive impairment in aging and age - related disorders, such as dementia.", "output": "PUFA." }, { "input": "This review discusses and integrates up to date evidence from clinical and animal studies investigating the cognitive - enhancing effects of n - 3 PUFA during development, child - and adult - hood, as well as old - age with associated neurodegenerative diseases, such as Alzheimer ' s disease.", "output": "PUFA." }, { "input": "Furthermore, we cover the major underlying biochemical and neurophysiological mechanisms by which n - 3 PUFA mediate these effects on cognition.", "output": "PUFA." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Interaction of tumor cells with the immune system: implications for dendritic cell therapy and cancer progression.", "output": "There is no related enetity." }, { "input": "There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells.", "output": "There is no related enetity." }, { "input": "Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non - clinical proof of safety and efficacy of these immunotherapies is summarized.", "output": "There is no related enetity." }, { "input": "Immunoinformatic approaches look promising to unfold this potential, although still unstable and difficult to interpret.", "output": "There is no related enetity." }, { "input": "Animal models have progressed a great deal in recent years, finally narrowing the gap from bench to bedside.", "output": "There is no related enetity." }, { "input": "However, translation to the clinic should be done with precaution.", "output": "There is no related enetity." }, { "input": "The most significant results concerning clinical benefit might come from detailed immunologic investigations made during well designed clinical trials of dendritic - cell - based therapies, which in general prove safe.", "output": "There is no related enetity." }, { "input": "Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKM zeta in neurons.", "output": "ZIP." }, { "input": "PKM zeta is an autonomously active, atypical protein kinase C ( aPKC ) isoform that is both necessary and sufficient for maintaining long - term potentiation ( LTP ) and long - term memory.", "output": "There is no related enetity." }, { "input": "The myristoylated zeta - pseudosubstrate peptide, ZIP, potently inhibits PKM zeta biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses LTP maintenance and erases long - term memory storage.", "output": "myristoylated zeta - pseudosubstrate peptide, ZIP." }, { "input": "A recent study ( Wu - Zhang et al., 2012 ), however, suggested ZIP was not effective on a PKM zeta fusion protein overexpressed in cultured cells.", "output": "ZIP." }, { "input": "Chelerythrine, a redox - sensitive PKC inhibitor that inhibits PKM zeta and disrupts LTP maintenance and memory storage, was also reported by Wu - Zhang et al.", "output": "Chelerythrine." }, { "input": "( 2012 ) not to inhibit the expressed PKM zeta fusion protein.", "output": "There is no related enetity." }, { "input": "However, the efficacy of inhibitors on endogenous enzymes in cells may not be adequately assessed in expression systems in which levels of expression of exogenous enzymes greatly exceed those of endogenous enzymes.", "output": "There is no related enetity." }, { "input": "Thus, we show, biochemically, that when PKM zeta reaches a level beyond that necessary for substrate phosphorylation such that much of the enzyme is excess or ' spare ' kinase, ZIP and chelerythrine do not effectively block substrate phosphorylation.", "output": "ZIP, chelerythrine." }, { "input": "We also show that the cellular overexpression techniques used by Wu - Zhang et al.", "output": "There is no related enetity." }, { "input": "( 2012 ) increase kinase levels ~ 30 - 40 fold above normal levels in transfected cells.", "output": "There is no related enetity." }, { "input": "Using a mathematical model we show that at such level of overexpression, standard concentrations of inhibitor should have no noticeable effect.", "output": "There is no related enetity." }, { "input": "Furthermore, we demonstrate the standard concentrations of ZIP, but not scrambled ZIP, inhibit the ability of PKM zeta to potentiate AMPAR responses at postsynaptic sites, the physiological function of the kinase.", "output": "ZIP, ZIP." }, { "input": "Wu - Zhang et al.", "output": "There is no related enetity." }, { "input": "( 2012 ) had also claimed that staurosporine, a general kinase inhibitor that does not effectively inhibit PKM zeta biochemically in vitro, nonetheless indirectly blocked the PKM zeta fusion protein overexpressed in cultured cells by inhibiting phosphoinositide - dependent protein kinase - 1 ( PDK1 ).", "output": "staurosporine." }, { "input": "However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKM zeta in hippocampal slices.", "output": "staurosporine." }, { "input": "Thus, the biochemical in vitro effects of PKM zeta inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKM zeta in neurons.", "output": "ZIP, chelerythrine, ZIP, staurosporine." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "NT, NPY and PGP 9. 5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology.", "output": "There is no related enetity." }, { "input": "The uterine myoma pseudocapsule is a neurovascular bundle surrounding fibroid, containing neuropeptides, probably involved in uterine scar healing.", "output": "There is no related enetity." }, { "input": "We studied neurotensin ( NT ), neuropeptide tyrosine ( NPY ), and protein gene product 9. 5 ( PGP 9. 5 ) nerve fibres in the pseudocapsule neurovascular bundle of intramural uterine fibroids on 67 no pregnant women by intracapsular myomectomy sparing the neurovascular bundle, sampling full thickness specimens of the pseudocapsule of uterine fibroids ( PUF ) and normal myometrium ( NM ) obtained from the fundus uteri ( FU ) and the uterine body ( UB ).", "output": "neurotensin, tyrosine." }, { "input": "The samples were sent for histological and immunofluorescent analyses and compared by morphometrical quantification.", "output": "There is no related enetity." }, { "input": "The Conventional Unit ( C. U. ) difference of NT, NPY, and PGP 9. 5 nerve fibres was statistically analyzed.", "output": "There is no related enetity." }, { "input": "Our results showed that NT, NPY, and PGP 9. 5 neurofibers are almost equally present in PUF as in NM of a no pregnant uterus.", "output": "There is no related enetity." }, { "input": "As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing.", "output": "There is no related enetity." }, { "input": "A myomectomy respecting the pseudocapsule neurofibers should facilitate smooth muscle scarring and promote restoration of normal uterine peristalsis with a possible positive influence on fertility.", "output": "There is no related enetity." }, { "input": "Increased expression of transthyretin in leptin - deficient ob / ob mice is not causative for their major phenotypic abnormalities.", "output": "There is no related enetity." }, { "input": "The hormone leptin is a critical regulator of adipogenesis and energy metabolism.", "output": "There is no related enetity." }, { "input": "Similarly, leptin - deficient ob / ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass.", "output": "There is no related enetity." }, { "input": "By genome - wide expression analysis using hypothalamus RNA from wild - type and ob / ob mice, we observed the increased expression of the gene for transthyretin ( Ttr ) in the latter, as confirmed by quantitative real - time - polymerase chain reaction.", "output": "There is no related enetity." }, { "input": "Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob / ob mice, we investigated whether the additional absence of Ttr would influence the ob / ob phenotype.", "output": "There is no related enetity." }, { "input": "It was found that Ttr - deficient ob / ob mice were indistinguishable from ob / ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels.", "output": "glucose, cholesterol." }, { "input": "Although all of these parameters were identical to wild - type controls in Ttr - deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue.", "output": "There is no related enetity." }, { "input": "Interestingly, all these latter parameters were highest in Ttr - deficient ob / ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age.", "output": "There is no related enetity." }, { "input": "Taken together, our data demonstrate that the increased expression of Ttr in ob / ob mice does not cause ( but rather attenuates ) their phenotypic abnormalities.", "output": "There is no related enetity." }, { "input": "Effects of fenofibrate, a PPAR - alpha ligand, on the haemodynamics of glycerol - induced renal failure in rats.", "output": "fenofibrate, glycerol." }, { "input": "The modulating effect of peroxisome proliferator - activated receptor alpha ligand on haemodynamic effects of phenylepherine ( PE ), angiotensin II ( AII ), endothelin 1 ( ET1 ), acetylcholine ( Ach ), sodium nitroprusside ( SNP ) and isoproterenol ( ISO ) were evaluated in glycerol - induced acute kidney injury in rats.", "output": "phenylepherine, acetylcholine, Ach, sodium nitroprusside, SNP, isoproterenol, ISO, glycerol." }, { "input": "The effect of PE on fenofibrate - treated animals was a dose - dependent increase in mean arterial blood pressure ( MAP ).", "output": "fenofibrate." }, { "input": "For AII and ET1, MAP was also increased for the fenofibrate group but not in a dose - dependent fashion.", "output": "fenofibrate." }, { "input": "On the medullary blood flow ( MBF ), while the lower doses of PE and AII increased the perfusion unit on the fenofibrate - treated group, the higher doses decreased the perfusion unit.", "output": "fenofibrate." }, { "input": "The ET1 increased the perfusion unit on this group but not in dose - dependent fashion.", "output": "There is no related enetity." }, { "input": "The effects of PE and AII on the cortical blood flow ( CBF ) of fenofibrate - treated group is similar to that of MBF for the same group but not for ET1.", "output": "fenofibrate." }, { "input": "The effect of Ach, SNP and ISO in all the groups was the decrease in MAP.", "output": "Ach, SNP, ISO." }, { "input": "ISO caused dose - dependent increase in MBF of fenofibrate - treated group.", "output": "ISO, fenofibrate." }, { "input": "The effect of Ach, SNP and ISO on the CBF perfusion unit was that of the increase for the fenofibrate - treated group.", "output": "Ach, SNP, ISO, fenofibrate." }, { "input": "The study showed that fenofibrate did not attenuate increased blood pressure induced by PE, AII and ET1 but caused enhanced vasodilation by Ach, SNP and ISO.", "output": "fenofibrate, Ach, SNP, ISO." }, { "input": "Incretin and pancreatic hormone secretion in Caucasian non - diabetic carriers of the TCF7L2 rs7903146 risk T allele.", "output": "There is no related enetity." }, { "input": "We characterised 62 non - diabetic, middle - aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7 - like 2 ( TCF7L2 ) with regard to secretion of insulin, glucagon, glucose - dependent insulinotropic polypeptide ( GIP ), glucagon - like peptide - 1 ( GLP - 1 ) as well as insulin sensitivity and endogenous glucose production.", "output": "glucose, glucose." }, { "input": "All participants had a 3 - h oral glucose tolerance test ( OGTT ), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp.", "output": "glucose, glucose." }, { "input": "After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels ( p = 0. 030 ), reduced first - phase insulin response ( p = 0. 048 ), higher peripheral insulin sensitivity ( p = 0. 050 ) and lower fasting GIP concentrations ( p = 0. 003 ) than CC allele carriers.", "output": "There is no related enetity." }, { "input": "The latter was also reflected by lower total GIP secretion during the OGTT ( p = 0. 018 ).", "output": "There is no related enetity." }, { "input": "We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP - 1 between the groups.", "output": "glucose, glucose." }, { "input": "The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.", "output": "There is no related enetity." }, { "input": "Aurora A kinase ( AURKA ) in normal and pathological cell division.", "output": "There is no related enetity." }, { "input": "Temporally and spatially controlled activation of the Aurora A kinase ( AURKA ) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis.", "output": "There is no related enetity." }, { "input": "Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis.", "output": "There is no related enetity." }, { "input": "These properties have led Aurora A to be considered a high - value target for development of cancer therapeutics, with multiple agents currently in early - phase clinical trials.", "output": "There is no related enetity." }, { "input": "More recently, identification of additional, non - mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors.", "output": "There is no related enetity." }, { "input": "Here we review the mitotic and non - mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer.", "output": "There is no related enetity." }, { "input": "The R740S mutation in the V - ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis.", "output": "There is no related enetity." }, { "input": "Vacuolar H ( + ) - ATPase ( V - ATPase ), a multisubunit enzyme located at the ruffled border and in lysosomes of osteoclasts, is necessary for bone resorption.", "output": "H ( + )." }, { "input": "We previously showed that heterozygous mice with an R740S mutation in the a3 subunit of V - ATPase ( + / R740S ) have mild osteopetrosis resulting from an ~ 90 % reduction in proton translocation across osteoclast membranes.", "output": "There is no related enetity." }, { "input": "Here we show that lysosomal pH is also higher in + / R740S compared with wild - type ( + / + ) osteoclasts.", "output": "There is no related enetity." }, { "input": "Both osteoclast number and size were decreased in cultures of + / R740S compared with + / + bone marrow cells, with concomitant decreased expression of key osteoclast markers ( TRAP, cathepsin K, OSCAR, DC - STAMP, and NFATc1 ), suggesting that low lysosomal pH plays an important role in osteoclastogenesis.", "output": "There is no related enetity." }, { "input": "To elucidate the molecular mechanism of this inhibition, NFATc1 activation was assessed.", "output": "There is no related enetity." }, { "input": "NFATc1 nuclear translocation was significantly reduced in + / R740S compared with + / + cells; however, this was not because of impaired enzymatic activity of calcineurin, the phosphatase responsible for NFATc1 dephosphorylation.", "output": "There is no related enetity." }, { "input": "Protein and RNA expression levels of regulator of calcineurin 1 ( RCAN1 ), an endogenous inhibitor of NFATc1 activation and a protein degraded in lysosomes, were not significantly different between + / R740S and + / + osteoclasts, but the RCAN1 / NFATc1 ratio was significantly higher in + / R740S versus + / + cells.", "output": "There is no related enetity." }, { "input": "The lysosomal inhibitor chloroquine significantly increased RCAN1 accumulation in + / + cells, consistent with the hypothesis that higher lysosomal pH impairs RCAN1 degradation, leading to a higher RCAN1 / NFATc1 ratio and consequently NFATc1 inhibition.", "output": "chloroquine." }, { "input": "Our data indicate that increased lysosomal pH in osteoclasts leads to decreased NFATc1 signaling and nuclear translocation, resulting in a cell autonomous impairment of osteoclastogenesis in vitro.", "output": "There is no related enetity." }, { "input": "Metabolic profiling of TRPV1 antagonists of the benzothiazole amide series: implications for in vitro genotoxicity assessment.", "output": "benzothiazole amide." }, { "input": "In vitro metabolic profiling and in vitro genotoxicity assessment are important aspects of the drug discovery program as they eliminate harmful compounds from further development.", "output": "There is no related enetity." }, { "input": "In standard in vitro genotoxicity testing, induced rat liver S9 is used as an exogenous bio - activation system for detecting promutagens.", "output": "There is no related enetity." }, { "input": "In this study we show that rat liver S9 is an insufficient system regarding the conversion of TRPV1 antagonists of the benzothiazole amide series into relevant in vivo metabolites.", "output": "benzothiazole amide." }, { "input": "Human and rat hepatocyte experiments demonstrated generation of an aryl amine metabolite that was subsequently N - acetylated.", "output": "aryl amine, N." }, { "input": "The hydrolyzed metabolites as well as the parent compound were also metabolized into glutathione ( GSH ) conjugates.", "output": "glutathione, GSH." }, { "input": "Rat liver S9 exhibited a very low amide hydrolysis capacity and no formation of GSH conjugates when supplemented with NADPH and GSH.", "output": "amide, GSH, NADPH, GSH." }, { "input": "The discrepancy in metabolic capability between hepatocytes and rat liver S9 led to confounding results in in vitro genotoxicity assessment for this chemical class as judged by the results of Ames test, mouse lymphoma assay, SOS / umu test and Comet assay in rat hepatocytes.", "output": "There is no related enetity." }, { "input": "This study highlights the pivotal role that understanding the mechanism of metabolite formation has in interpreting as well as designing reliable and relevant in vitro genotoxicity experiments.", "output": "There is no related enetity." }, { "input": "The CDKL5 disorder is an independent clinical entity associated with early - onset encephalopathy.", "output": "There is no related enetity." }, { "input": "The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres.", "output": "There is no related enetity." }, { "input": "This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome ( RTT ).", "output": "There is no related enetity." }, { "input": "Information on individuals with cyclin - dependent kinase - like 5 ( CDKL5 ) mutations ( n = 86 ) and females with MECP2 mutations ( n = 920 ) was sourced from the InterRett database.", "output": "There is no related enetity." }, { "input": "Available photographs of CDKL5 patients were examined for dysmorphic features.", "output": "There is no related enetity." }, { "input": "The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined.", "output": "There is no related enetity." }, { "input": "Logistic regression and time - to - event analyses were used to compare the occurrence of Rett - like features in those with MECP2 and CDKL5 mutations.", "output": "There is no related enetity." }, { "input": "Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non - dysmorphic features.", "output": "There is no related enetity." }, { "input": "Less than one - quarter met the criteria for early - onset seizure variant RTT.", "output": "There is no related enetity." }, { "input": "Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common.", "output": "There is no related enetity." }, { "input": "The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early - onset encephalopathies.", "output": "There is no related enetity." }, { "input": "Although mutations in the CDKL5 gene have been described in association with the early - onset variant of RTT, in our study the majority did not meet these criteria.", "output": "There is no related enetity." }, { "input": "Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.", "output": "There is no related enetity." }, { "input": "The impact of FANCD2 deficiency on formaldehyde - induced toxicity in human lymphoblastoid cell lines.", "output": "formaldehyde." }, { "input": "Formaldehyde ( FA ), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen.", "output": "Formaldehyde." }, { "input": "The major mode of action of FA is thought to be the formation of DNA - protein cross - links ( DPCs ).", "output": "There is no related enetity." }, { "input": "Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway are limited, particularly in human hematopoietic cells.", "output": "There is no related enetity." }, { "input": "Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA - induced toxicity in human lymphoblast cell models of FANCD2 deficiency ( PD20 cells ) and FANCD2 sufficiency ( PD20 - D2 cells ).", "output": "There is no related enetity." }, { "input": "After treatment of the cells with 0 - 150 mu M FA for 24 h, DPCs were increased in a dose - dependent manner in both cell lines, with greater increases in FANCD2 - deficient PD20 cells.", "output": "There is no related enetity." }, { "input": "FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose - dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells.", "output": "There is no related enetity." }, { "input": "Increased levels of gamma - ATR and gamma - H2AX in both cell lines suggested the recognition of FA - induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2 - deficient PD20 cells, potentially reducing the capacity to repair DPCs.", "output": "There is no related enetity." }, { "input": "Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity.", "output": "There is no related enetity." }, { "input": "Future studies are needed to delineate the role of this pathway in mitigating FA - induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia.", "output": "There is no related enetity." }, { "input": "AKRs expression in peripheral blood lymphocytes from smokers: The role of body mass index.", "output": "There is no related enetity." }, { "input": "Aldo - keto reductases ( AKRs ) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons ( PAHs ), generating metabolites ( o - quinones ) and reactive oxygen species ( ROS ), which are capable of initiating and promoting carcinogenesis.", "output": "Aldo - keto, polycyclic aromatic hydrocarbons, PAHs, o - quinones, oxygen." }, { "input": "Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage.", "output": "PAHs." }, { "input": "Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals.", "output": "There is no related enetity." }, { "input": "Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes ( PBLs ).", "output": "PAHs, PAHs." }, { "input": "The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1 * 2 and AKR1C3 * 2 polymorphisms, on AKR1A1 and AKR1C1 - AKR1C3 messenger RNA ( mRNA ) levels in PBLs from smokers.", "output": "There is no related enetity." }, { "input": "In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index ( BMI ) less than 25.", "output": "cotinine." }, { "input": "However, AKR1A1 * 2 and AKR1C3 * 2 alleles did not influence AKR1A1 and AKR1C1 - AKR1C3 mRNA levels.", "output": "There is no related enetity." }, { "input": "These results suggest that AKRs induction by PAHs in smokers ' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs ' effects needs further investigation.", "output": "PAHs, PAHs." }, { "input": "Novel non - canonical TGF - beta signaling networks: emerging roles in airway smooth muscle phenotype and function.", "output": "There is no related enetity." }, { "input": "The airway smooth muscle ( ASM ) plays an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease ( COPD ).", "output": "There is no related enetity." }, { "input": "ASM cells express a wide range of receptors involved in contraction, growth, matrix protein production and the secretion of cytokines and chemokines.", "output": "There is no related enetity." }, { "input": "Transforming growth factor beta ( TGF - beta ) is one of the major players in determining the structural and functional abnormalities of the ASM in asthma and COPD.", "output": "There is no related enetity." }, { "input": "It is increasingly evident that TGF - beta functions as a master switch, controlling a network of intracellular and autocrine signaling loops that effect ASM phenotype and function.", "output": "There is no related enetity." }, { "input": "In this review, the various elements that participate in non - canonical TGF - beta signaling, including MAPK, PI3K, WNT / beta - catenin, and Ca ( 2 + ), are discussed, focusing on their effect on ASM phenotype and function.", "output": "Ca ( 2 + )." }, { "input": "In addition, new aspects of ASM biology and their possible association with non - canonical TGF - beta signaling will be discussed.", "output": "There is no related enetity." }, { "input": "Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs used as modulators of the nitroxidative stress.", "output": "Nitrogen, oxygen, sulfur." }, { "input": "Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti - inflammatory and anti - migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management.", "output": "nitrogen, oxygen." }, { "input": "Both classical analgesics ( nonsteroidal anti - inflammatory drugs, opioid drugs ) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and alpha - lipoic acid can modulate the balance between pro - oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug - related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate - induced hyperalgesia and tolerance.", "output": "desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin, carbamazepine, alpha - lipoic acid, indomethacin, meloxicam, tenoxicam, valdecoxib." }, { "input": "The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion ( ONOO - ), namely the peroxynitrite decomposition catalysts or as superoxide ( O2 * - ) - scavengers which are the functional mimetics of superoxide dismutase ( SOD ) enzymes ( SODm ), as well as the derivatives of 6 - nitro - 3, 4 - methylenedioxyphenyl - Nacylhydrazone ( LASSBio - 881 ) or gamma - butyrolactone ( LPP1, BM113, BM113A, BM138 and BM138A ) are also discussed as potent and promising future heterocyclic analgesics.", "output": "peroxynitrite, ONOO -, peroxynitrite, superoxide, O2 * -, superoxide, 6 - nitro - 3 , 4 - methylenedioxyphenyl - Nacylhydrazone, LASSBio - 881, gamma - butyrolactone." }, { "input": "Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update.", "output": "There is no related enetity." }, { "input": "Heat shock proteins ( HSP ) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress.", "output": "There is no related enetity." }, { "input": "HSP genes are activated at the transcriptional level by heat shock transcription factor 1 ( HSF1 ).", "output": "There is no related enetity." }, { "input": "During the progression of many types of cancer, this heat shock transcriptional regulon becomes co - opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell.", "output": "There is no related enetity." }, { "input": "Concerted activation of HSF1 and the accumulation of HSPs then participate in many of the traits that permit the malignant phenotype.", "output": "There is no related enetity." }, { "input": "Thus, cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic.", "output": "There is no related enetity." }, { "input": "We review here the extensive work that has been carried out and is still in progress aimed at ( 1 ) understanding the oncogenic mechanisms by which HSP genes are switched on, ( 2 ) determining the roles of HSF1 / HSP in malignant transformation and ( 3 ) discovering approaches to therapy based on disrupting the influence of the HSF1 - controlled transcriptome in cancer.", "output": "There is no related enetity." }, { "input": "Microfabricated nanotopological surfaces for study of adhesion - dependent cell mechanosensitivity.", "output": "There is no related enetity." }, { "input": "Cells exhibit high sensitivity and diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery.", "output": "There is no related enetity." }, { "input": "A simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces by using photolithography and reactive ion etching is reported.", "output": "There is no related enetity." }, { "input": "It is demonstrated that local nanoroughness as a biophysical cue could regulate a diverse array of NIH / 3T3 fibroblast behaviors, including cell morphology, adhesion, proliferation, migration, and cytoskeleton contractility.", "output": "There is no related enetity." }, { "input": "The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo for functional tissue engineering.", "output": "There is no related enetity." }, { "input": "The human Aurora kinase inhibitor danusertib is a lead compound for anti - trypanosomal drug discovery via target repurposing.", "output": "danusertib." }, { "input": "New drugs for neglected tropical diseases such as human African trypanosomiasis ( HAT ) are needed, yet drug discovery efforts are not often focused on this area due to cost.", "output": "There is no related enetity." }, { "input": "Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated.", "output": "There is no related enetity." }, { "input": "In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib ( 1 ), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 ( TbAUK1 ) and effective in parasite killing in vitro.", "output": "danusertib." }, { "input": "Informed by homology modeling and docking, a series of analogs of 1 were prepared that explored the scope of the chemotype and provided a nearly 25 - fold improvement in cellular selectivity for parasite cells over human cells.", "output": "There is no related enetity." }, { "input": "Chemoprevention of benzo ( a ) pyrene - induced colon polyps in ApcMin mice by resveratrol.", "output": "benzo ( a ) pyrene, resveratrol." }, { "input": "Human dietary exposure to benzo ( a ) pyrene ( BaP ) has generated interest with regard to the association of BaP with gastrointestinal carcinogenesis.", "output": "benzo ( a ) pyrene, BaP, BaP." }, { "input": "Since colon cancer ranks third among cancer - related mortalities, it is necessary to evaluate the effect of phytochemicals on colon cancer initiation and progression.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the preventive effects of resveratrol ( RVT ) on BaP - induced colon carcinogenesis in Apc ( Min ) mouse model.", "output": "resveratrol, RVT, BaP." }, { "input": "For the first group of mice, 100 mu g BaP / kg body weight was administered to mice in peanut oil via oral gavage over a 60 - day period.", "output": "BaP." }, { "input": "For the second group, RVT was coadministered with BaP at a dose of 45 mu g / kg.", "output": "RVT, BaP." }, { "input": "For the third group, RVT was administered for 1 week prior to BaP exposure for 60 days.", "output": "RVT, BaP." }, { "input": "Jejunum, colon and liver were collected at 60 days post BaP and RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology.", "output": "BaP, RVT." }, { "input": "RVT reduced the number of colon adenomas in BaP + RVT - treated mice significantly compared to that in mice that received BaP alone.", "output": "RVT, BaP, RVT, BaP." }, { "input": "While dysplasia of varying degrees was noted in colon of BaP - treated mice, the dysplasias were of limited occurrence in RVT - treated mice.", "output": "BaP, RVT." }, { "input": "To ascertain whether the tumor inhibition is a result of altered BaP - induced toxicity of tumor cells, growth, apoptosis and proliferation of adenocarcinoma cells were assessed posttreatment with RVT and BaP.", "output": "BaP, RVT, BaP." }, { "input": "Cotreatment with RVT increased apoptosis and decreased cell proliferation to a greater extent than with BaP alone.", "output": "RVT, BaP." }, { "input": "Overall, our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP and holds promise as a therapeutic agent.", "output": "RVT, BaP." }, { "input": "Microcrack density and nanomechanical properties in the subchondral region of the immature piglet femoral head following ischemic osteonecrosis.", "output": "There is no related enetity." }, { "input": "Development of a subchondral fracture is one of the earliest signs of structural failure of the immature femoral head following ischemic osteonecrosis, and this eventually leads to a flattening deformity of the femoral head.", "output": "There is no related enetity." }, { "input": "The mechanical and mineralization changes in the femoral head preceding subchondral fracture have not been elucidated.", "output": "There is no related enetity." }, { "input": "We hypothesized that ischemic osteonecrosis leads to early material and mechanical alterations in the bone of the subchondral region.", "output": "There is no related enetity." }, { "input": "The purpose of this investigation was to assess the bone of the subchondral region for changes in the histology of bone cells, microcrack density, mineral content, and nanoindentation properties at an early stage of ischemic osteonecrosis in a piglet model.", "output": "There is no related enetity." }, { "input": "This large animal model has been shown to develop a subchondral fracture and femoral head deformity resembling juvenile femoral head osteonecrosis.", "output": "There is no related enetity." }, { "input": "The unoperated, left femoral head of each piglet ( n = 8 ) was used as a normal control, while the right side had a surgical ischemia induced by disrupting the femoral neck vessels with a ligature.", "output": "There is no related enetity." }, { "input": "Hematoxylin and eosin ( H & E ) staining and TUNEL assay were performed on femoral heads from 3 piglets.", "output": "Hematoxylin, eosin." }, { "input": "Quantitative backscattered electron imaging, nanoindentation, and microcrack assessments were performed on the subchondral region of both control and ischemic femoral heads from 5 piglets.", "output": "There is no related enetity." }, { "input": "H & E staining and TUNEL assay showed extensive cell death and an absence of osteoblasts in the ischemic side compared to the normal control.", "output": "There is no related enetity." }, { "input": "Microcrack density in the ischemic side ( 3. 2 +/- 0. 79 cracks / mm ( 2 ) ) was significantly higher compared to the normal side ( 0. 27 +/- 0. 27 cracks / mm ( 2 ) ) in the subchondral region ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "The weighted mean of the weight percent distribution of calcium ( CaMean ) also was significantly higher in the ischemic subchondral region ( p < 0. 05 ).", "output": "calcium." }, { "input": "Furthermore, the nanoindentation modulus within localized areas of subchondral bone was significantly increased in the ischemic side ( 16. 8 +/- 2. 7GPa ) compared to the normal control ( 13. 3 +/- 3. 2GPa ) ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Taken together, these results support the hypothesis that the nanoindentation modulus of the subchondral trabecular bone is increased in the early stage of ischemic osteonecrosis of the immature femoral head and makes it more susceptible to microcrack formation.", "output": "There is no related enetity." }, { "input": "We postulate that continued loading of the hip joint when there is a lack of bone cells to repair the microcracks due to ischemic osteonecrosis leads to microcrack accumulation and subsequent subchondral fracture.", "output": "There is no related enetity." }, { "input": "The major indole alkaloid N, beta - D - glucopyranosyl vincosamide from leaves of Psychotria leiocarpa Cham.", "output": "indole alkaloid, N , beta - D - glucopyranosyl vincosamide." }, { "input": "& Schltdl.", "output": "There is no related enetity." }, { "input": "is not an antifeedant but shows broad antioxidant activity.", "output": "There is no related enetity." }, { "input": "N, beta - D - glucopyranosyl vincosamide ( GPV ), a major alkaloid of Psychotria leiocarpa, constitutes up to 2. 5 % of the dry weight in leaves.", "output": "N , beta - D - glucopyranosyl vincosamide, GPV." }, { "input": "Alkaloid content was not elicited by mechanical wounding or jasmonate.", "output": "There is no related enetity." }, { "input": "At concentrations found in natural conditions or 2. 5 fold higher, GPV did not inhibit herbivory in two unrelated generalist models ( Helix aspersa and Spodoptera frugiperda ) or in a specific interaction model ( Heliconius erato fed with Passiflora suberosa ).", "output": "GPV." }, { "input": "In situ staining assay showed quenching activity of hydrogen peroxide by GPV.", "output": "hydrogen peroxide, GPV." }, { "input": "Exposure of P. leiocarpa to acute UV - B stress did not change GPV or chlorophyll content, indicating high tolerance to this stress by the species.", "output": "GPV, chlorophyll." }, { "input": "In vitro antioxidant tests against singlet oxygen, superoxide anions and hydroxyl radicals showed efficient quenching activity of the alkaloid.", "output": "oxygen, superoxide, hydroxyl." }, { "input": "GPV was not effective as antifeedant, but it may act indirectly in P. leiocarpa protection against oxidative stress generated upon wounding, UV exposure and perhaps other environmental stresses.", "output": "GPV." }, { "input": "Assessment of developmental delay in the zebrafish embryo teratogenicity assay.", "output": "There is no related enetity." }, { "input": "In this study we analyzed some aspects of the assessment of developmental delay in the zebrafish embryotoxicity / teratogenicity test and explored the suitability of acetylcholinesterase ( AChE ) activity as a biochemical marker and as a higher throughput alternative to morphological endpoints such as head - trunk angle, tail length and morphological score.", "output": "There is no related enetity." }, { "input": "Embryos were exposed from 4 to 52 h post - fertilization ( hpf ) to a selection of known embryotoxic / teratogen compounds ( valproic acid, retinoic acid, caffeine, sodium salicylate, glucose, hydroxyurea, methoxyacetic acid, boric acid and paraoxon - methyl ) over a concentration range.", "output": "valproic acid, retinoic acid, caffeine, sodium salicylate, glucose, hydroxyurea, methoxyacetic acid, boric acid, paraoxon - methyl." }, { "input": "They were evaluated for AChE activity, head - trunk angle, tail length and several qualitative parameters integrated in a morphological score.", "output": "There is no related enetity." }, { "input": "In general, the different patterns of the concentration - response curves allowed distinguishing between chemicals that produced growth retardation ( valproic and methoxyacetic acid ) and chemicals that produced non - growth - delay related malformations.", "output": "valproic and methoxyacetic acid." }, { "input": "An acceptable correlation between the morphological score, AChE activity and head - trunk angle as markers of developmental delay was observed, being AChE activity particularly sensitive to detect delay in the absence of malformations.", "output": "There is no related enetity." }, { "input": "Human and cattle ergotism since 1900: Symptoms, outbreaks, and regulations.", "output": "There is no related enetity." }, { "input": "Ergotism in humans and cattle are caused by several species of Claviceps that infect rye and other cereal grains.", "output": "There is no related enetity." }, { "input": "Symptoms in humans vary greatly and are generally classified as convulsive, gangrenous, or gastrointestinal ( enteric ).", "output": "There is no related enetity." }, { "input": "Cattle are particularly susceptible to both gangrenous and hyperthermic ergotism ( also called summer syndrome ).", "output": "There is no related enetity." }, { "input": "The prevalence of ergotism has decreased as knowledge of the fungus has increased, mainly through implementation of regulations and advances in milling procedures.", "output": "There is no related enetity." }, { "input": "However, outbreaks in humans have recently occurred in lower socioeconomic populations of Ethiopia ( 1977 and 2001 ) and India ( 1975 ) with devastating results.", "output": "There is no related enetity." }, { "input": "Prominent outbreaks in cattle have occurred in Australia ( 1987 ), the United States ( 1996 ), South Africa ( 1996 - 1997 ), and Brazil ( 1999 ) and, as opposed to human cases, they do not appear to be bound by economic development.", "output": "There is no related enetity." }, { "input": "This review provides a detailed summary of all major ergot epidemics since 1900 in both humans and cattle.", "output": "There is no related enetity." }, { "input": "Special attention is devoted to the ergotism symptoms and to the regulations surrounding the control of ergot in the food supply.", "output": "There is no related enetity." }, { "input": "RETRACTED: Effects of nanometer - sized silver materials on survival response of Caspian roach ( Rutilus rutilus caspicus ).", "output": "silver." }, { "input": "RETRACTED.", "output": "There is no related enetity." }, { "input": "Extracellular and intracellular anti - mutagenic effects of bile pigments in the Salmonella typhimurium reverse mutation assay.", "output": "There is no related enetity." }, { "input": "In vitro anti - genotoxic properties of bile pigments have been explored and confirmed recently.", "output": "There is no related enetity." }, { "input": "Despite these reports mechanisms to explain DNA protection by endogenous bile pigments remain unclear.", "output": "There is no related enetity." }, { "input": "Surprisingly, the quantification of cellular pigment absorption which could represent a fundamental prerequisite for intracellular ( e. g., anti - mutagenic ) effects, has not been explored.", "output": "There is no related enetity." }, { "input": "Therefore, we aimed to measure the amounts of un - / conjugated bilirubin as well as biliverdin absorbed into colonies of Salmonella typhimurium, utilising HPLC analyses, and to observe whether intracellular compound concentrations could predict anti - genotoxic effects.", "output": "bilirubin, biliverdin." }, { "input": "HPLC analyses confirmed that bacterial bile pigment absorption was concentration - dependent.", "output": "There is no related enetity." }, { "input": "Plate bile pigment concentrations were inversely associated with genotoxicity of all tested mutagens, irrespective of strain and test conditions.", "output": "There is no related enetity." }, { "input": "However, protection against frame - shift mutation in strain TA98 most strongly depended on the bacterial absorption of bilirubin and biliverdin, which indicates that bile pigments can protect by intercepting mutations extracellularly and specifically inhibit frame - shift mutations intracellularly.", "output": "bilirubin, biliverdin." }, { "input": "Chemicals inducing acute irritant contact dermatitis mobilize intracellular calcium in human keratinocytes.", "output": "calcium." }, { "input": "Intracellular Ca ( 2 + ) increase is a common feature of multiple cellular pathways associated with receptor and channel activation, mediator secretion and gene regulation.", "output": "Ca ( 2 + )." }, { "input": "We investigated the possibility of using this Ca ( 2 + ) signal as a biomarker for a reaction to chemical irritants of normal human keratinocytes ( NHK ) in submerged primary cell culture.", "output": "Ca ( 2 + )." }, { "input": "We tested 14 referenced chemical compounds classified as strong ( seven ), weak ( four ) or non - ( three ) irritants in acute irritant contact dermatitis.", "output": "There is no related enetity." }, { "input": "We found that the strong irritant compounds tested at 20 - 40 mM induced an intracellular Ca ( 2 + ) increase measurable by spectrofluorimetry in an automated test.", "output": "Ca ( 2 + )." }, { "input": "Weak and non - irritant compounds however did not increase intracellular Ca ( 2 + ) concentration.", "output": "Ca ( 2 + )." }, { "input": "We further investigated the mechanisms by which the amine heptylamine, classified as a R34 corrosive compound, increases intracellular Ca ( 2 + ).", "output": "amine, heptylamine, Ca ( 2 + )." }, { "input": "Heptylamine ( 20mM ) induced an ATP release that persisted in the absence of intra - and extra - cellular Ca ( 2 + ).", "output": "Heptylamine, ATP, Ca ( 2 + )." }, { "input": "In addition, we found that this ATP activates NHK purinergic receptors that subsequently cause the increase in intracellular Ca ( 2 + ) from sarcoplasmic reticular stores.", "output": "ATP, Ca ( 2 + )." }, { "input": "We conclude that measuring the intracellular Ca ( 2 + ) concentration in NHK is a suitable and easy way of determining any potential reaction to soluble chemical compounds.", "output": "Ca ( 2 + )." }, { "input": "Comparison of two in vitro systems to assess cellular effects of nanoparticles - containing aerosols.", "output": "There is no related enetity." }, { "input": "Inhalation treatment with nanoparticle containing aerosols appears a promising new therapeutic option but new formulations have to be assessed for efficacy and toxicity.", "output": "There is no related enetity." }, { "input": "We evaluated the utility of a VITROCELL (R) 6 PT - CF + PARI LC SPRINT (R) Baby Nebulizer ( PARI BOY ) system compared with a conventional MicroSprayer.", "output": "There is no related enetity." }, { "input": "A549 cells were cultured in the air - liquid interface, exposed to nanoparticle aerosols and characterized by measurement of transepithelial electrical resistance and staining for tight junction proteins.", "output": "There is no related enetity." }, { "input": "Deposition and distribution rates of polystyrene particles and of carbon nanotubes on the cells were assessed.", "output": "polystyrene, carbon." }, { "input": "In addition, cytotoxicity of aerosols containing polystyrene particles was compared with cytotoxicity of polystyrene particles in suspension tested in submersed cultures.", "output": "polystyrene, polystyrene." }, { "input": "Exposure by itself in both exposure systems did not damage the cells.", "output": "There is no related enetity." }, { "input": "Deposition rates of aerosolized polystyrene particles were about 700 times and that of carbon nanotubes about 4 times higher in the MicroSprayer than in the VITROCELL (R) 6 PT - CF system.", "output": "polystyrene, carbon." }, { "input": "Cytotoxicity of amine - functionalized polystyrene nanoparticles was significantly higher when applied as an aerosol on cell cultured in air - liquid interface culture compared with nanoparticle suspensions tested in submersed culture.", "output": "amine, polystyrene." }, { "input": "The higher cytotoxicity of aerosolized nanoparticles underscores the importance of relevant exposure systems.", "output": "There is no related enetity." }, { "input": "The AChE membrane - binding tail PRiMA is down - regulated in muscle and nerve of mice with muscular dystrophy by merosin deficiency.", "output": "There is no related enetity." }, { "input": "Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin - glycoprotein complex ( DGC ).", "output": "There is no related enetity." }, { "input": "Through laminin - 2, the DGC bridges the muscle cytoskeleton and the extracellular matrix.", "output": "There is no related enetity." }, { "input": "Decreased levels of PRiMA - linked acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) have been observed in dystrophic muscle and nerve of dystrophin - deficient ( mdx ) and laminin - 2 deficient ( Lama2dy ) mice.", "output": "There is no related enetity." }, { "input": "To help explain these observations, the relative content of AChE, BuChE and PRiMA mRNAs were compared in normal and Lama2dy mouse muscle and sciatic nerve.", "output": "There is no related enetity." }, { "input": "The 17 - fold lower level of PRiMA mRNA in Lama2dy muscle explained the deficit in PRiMA - linked ChEs.", "output": "There is no related enetity." }, { "input": "This would increase acetylcholine availability and, eventually, the desensitization of nicotinic receptors.", "output": "There is no related enetity." }, { "input": "Abnormal development of the Schwann cells led to peripheral neuropathy in the Lama2dy mouse.", "output": "There is no related enetity." }, { "input": "Compared with normal nerve, dystrophic nerve displayed 4 - fold less AChE - T mRNA, 3 - fold more BuChE mRNA and 2. 5 - fold less PRiMA mRNA, which agreed with the lower AChE activity in dystrophic nerve, its increased BuChE activity and the specific drop in PRiMA - linked BuChE.", "output": "There is no related enetity." }, { "input": "The widely accepted role of glial cells as the source of BuChE, the observed dysmyelination of Lama2dy nerve and its increased BuChE activity support the idea that BuChE up - regulation is related with the aberrant differentiation of the Schwann cells.", "output": "There is no related enetity." }, { "input": "Superhydrophobic graphene foams.", "output": "graphene." }, { "input": "The static and dynamic wetting properties of a 3D graphene foam network are reported.", "output": "graphene." }, { "input": "The foam is synthesized using template - directed chemical vapor deposition and contains pores several hundred micrometers in dimension while the walls of the foam comprise few - layer graphene sheets that are coated with Teflon.", "output": "graphene, Teflon." }, { "input": "Water contact angle measurements reveal that the foam is superhydrophobic with an advancing contact angle of ~ 163 degrees while the receding contact angle is ~ 143 degrees.", "output": "There is no related enetity." }, { "input": "The extremely water repellent nature of the foam is also confirmed when impacting water droplets are able to completely rebound from the surface.", "output": "There is no related enetity." }, { "input": "Such superhydrophobic graphene foams show potential in a variety of applications ranging from anti - sticking and self - cleaning to anti - corrosion and low - friction coatings.", "output": "graphene." }, { "input": "Effects of mycophenolic acid alone and in combination with its metabolite mycophenolic acid glucuronide on rat embryos in vitro.", "output": "mycophenolic acid, mycophenolic acid glucuronide." }, { "input": "Mycophenolic acid ( MPA ) is an immunosuppressive agent that acts as a selective, non - reversible inhibitor of the enzyme inosine - 5 ' - monophosphate dehydrogenase ( IMPDH ).", "output": "Mycophenolic acid, MPA, inosine - 5 ' - monophosphate." }, { "input": "Malformations have been described in children after maternal exposure to mycophenolate.", "output": "mycophenolate." }, { "input": "However, the causal link is unclear in most cases because women had been treated with a combination of drugs and birth defects may have other causes.", "output": "There is no related enetity." }, { "input": "Therefore, it is important to study the action of this drug and its main metabolite on embryonic tissue.", "output": "There is no related enetity." }, { "input": "We studied the teratogenic potential of MPA and its major metabolite, the mycophenolic acid glucuronide ( MPAG ) in the rat whole - embryo culture.", "output": "MPA, mycophenolic acid glucuronide, MPAG." }, { "input": "A total of 147 day 9. 5 embryos were cultivated for 48 h in the standard medium containing 85 % serum.", "output": "There is no related enetity." }, { "input": "We tested MPA at concentrations of 0. 1; 0. 25; 0. 5; 0. 75 mg / l ( 0. 31; 0. 78; 1. 56; 2. 34 mu M ) and MPA glucuronide at concentrations of 3; 10; 30; 100 mg / l ( 6. 04; 20. 14; 60. 43; 201. 43 mu M ).", "output": "MPA, MPA glucuronide." }, { "input": "Both substances are highly protein bound, and MPA glucuronide might displace MPA from protein binding.", "output": "MPA glucuronide, MPA." }, { "input": "Therefore, we examined whether the effects of MPA can be enhanced when studied in combination with the glucuronide.", "output": "MPA." }, { "input": "Furthermore, the focus was on additional endpoints to the standard evaluation of cultivated embryos, such as development of cranial nerves [ trigeminal nerve ( V ), facial nerve ( VII ), glossopharyngeal nerve ( IX ), vagus nerve ( X ) ] after staining with an antibody against 2H3 neurofilament.", "output": "There is no related enetity." }, { "input": "Ultrastructural changes were evaluated by electron microscopy.", "output": "There is no related enetity." }, { "input": "At a concentration of 0. 75 mg MPA / l medium, all embryos showed dysmorphic changes.", "output": "MPA." }, { "input": "Embryos exposed to 0. 25 mg MPA / l medium showed impaired development of nerves, and at 0. 1 mg / l, no effects were detectable.", "output": "MPA." }, { "input": "Concentration - dependent ultrastructural changes, such as signs of apoptosis, were found by electron microscopy.", "output": "There is no related enetity." }, { "input": "The examination of the metabolite in this assay showed that at a concentration of 100 mg MPAG / l, the embryos exhibited distinct malformations.", "output": "MPAG." }, { "input": "This is probably caused by MPA, which was detectable at 0. 6 % in the material used for our experiments.", "output": "MPA." }, { "input": "The combination of the parent compound ( 0. 03; 0. 1; 0. 25 mg / l ) with its metabolite MPAG ( 3 mg / l ) did not cause enhanced toxicity under our experimental conditions.", "output": "MPAG." }, { "input": "IMPDH, the target enzyme of MPA, could be detected in rat embryos on day 9. 5 of embryonic development as well as at the end of the culture period 48 h later.", "output": "MPA." }, { "input": "In summary, MPA impairs embryonic development at low, therapeutically relevant concentrations, but the glucuronide does not exhibit such a potential.", "output": "MPA." }, { "input": "Activity of MPA is not enhanced by MPAG.", "output": "MPA, MPAG." }, { "input": "Catalytic activities of a cocaine hydrolase engineered from human butyrylcholinesterase against ( + ) - and ( - ) - cocaine.", "output": "cocaine, ( + ) - and ( - ) - cocaine." }, { "input": "It can be argued that an ideal anti - cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine - metabolizing pathway, i. e., hydrolysis catalyzed by butyrylcholinesterase ( BChE ) in plasma.", "output": "cocaine, cocaine, cocaine." }, { "input": "However, wild - type BChE has a low catalytic efficiency against naturally occurring ( - ) - cocaine.", "output": "( - ) - cocaine." }, { "input": "Interestingly, wild - type BChE has a much higher catalytic activity against unnatural ( + ) - cocaine.", "output": "( + ) - cocaine." }, { "input": "According to available positron emission tomography ( PET ) imaging analysis using [ ( 11 ) C ] ( - ) - cocaine and [ ( 11 ) C ] ( + ) - cocaine tracers in human subjects, only [ ( 11 ) C ] ( - ) - cocaine was observed in the brain, whereas no significant [ ( 11 ) C ] ( + ) - cocaine signal was observed in the brain.", "output": "[ ( 11 ) C ] ( - ) - cocaine, [ ( 11 ) C ] ( + ) - cocaine, [ ( 11 ) C ] ( - ) - cocaine, [ ( 11 ) C ] ( + ) - cocaine." }, { "input": "The available PET data imply that an effective therapeutic enzyme for treatment of cocaine abuse could be an exogenous cocaine - metabolizing enzyme with a catalytic activity against ( - ) - cocaine comparable to that of wild - type BChE against ( + ) - cocaine.", "output": "cocaine, cocaine, ( - ) - cocaine, ( + ) - cocaine." }, { "input": "Our recently designed A199S / F227A / S287G / A328 W / Y332G mutant of human BChE has a considerably improved catalytic efficiency against ( - ) - cocaine and has been proven active in vivo.", "output": "( - ) - cocaine." }, { "input": "In the present study, we have characterized the catalytic activities of wild - type BChE and the A199S / F227A / S287G / A328 W / Y332G mutant against both ( + ) - and ( - ) - cocaine at the same time under the same experimental conditions.", "output": "( + ) - and ( - ) - cocaine." }, { "input": "Based on the obtained kinetic data, the A199S / F227A / S287G / A328 W / Y332G mutant has a similarly high catalytic efficiency ( kcat / KM ) against ( + ) - and ( - ) - cocaine, and indeed has a catalytic efficiency ( kcat / KM = 1. 84 x 10 ( 9 ) M ( - 1 ) min ( - 1 ) ) against ( - ) - cocaine comparable to that ( kcat / KM = 1. 37 x 10 ( 9 ) M ( - 1 ) min ( - 1 ) ) of wild - type BChE against ( + ) - cocaine.", "output": "( + ) - and ( - ) - cocaine, ( - ) - cocaine, ( + ) - cocaine." }, { "input": "Thus, the mutant may be used to effectively prevent ( - ) - cocaine from entering brain and producing physiological effects in the enzyme - based treatment of cocaine abuse.", "output": "( - ) - cocaine." }, { "input": "An unusual cause of factitious arthritis.", "output": "There is no related enetity." }, { "input": "Septic arthritis and toxic synovitis are clinical conditions that can develop in association with various causes and involve symptoms such as pain, swelling, redness, sensitivity and restricted movement in the joint.", "output": "There is no related enetity." }, { "input": "A 42 - year - old male presented to the emergency department with severe joint pain and nausea after injecting a 1 - cc mixture of turpentine oil, eucalyptus oil, mint oil and thyme oil, which he purchased from an alternative medicine store, into his right knee with a syringe because of chronic knee pain.", "output": "There is no related enetity." }, { "input": "Ballottement and sensitivity were present at physical examination.", "output": "There is no related enetity." }, { "input": "Knee puncture yielded 60 cc of cloudy fluid.", "output": "There is no related enetity." }, { "input": "There was no growth in the material obtained.", "output": "There is no related enetity." }, { "input": "Improvement was observed following subsequent arthroscopic washing of the joint space and IV antibiotherapy, and the patient was discharged on day 21 of hospitalization with oral antibiotic and analgesic therapy.", "output": "There is no related enetity." }, { "input": "Intra - articular injection of foreign bodies into the knee joint space for therapeutic purposes, as in this case report, is a very rare occurrence, but may lead to potentially complicated arthritis.", "output": "There is no related enetity." }, { "input": "Repair efficiency and PUVA therapeutic response variation in patients with vitiligo.", "output": "There is no related enetity." }, { "input": "Vitiligo is an acquired depigmentation disorder affecting 0. 1 % to > 8. 8 % in Indian population.", "output": "There is no related enetity." }, { "input": "Psoralen and ultraviolet A radiation ( PUVA ) is a gold standard treatment for vitiligo, however, response is still empirical.", "output": "Psoralen." }, { "input": "In order to investigate whether drug response variation is influenced by the repair ability of PUVA treated vitiligo subjects, single cell gel electrophoresis ( SCGE ) for genotoxicity and serum malonaldehyde ( MDA ) for cytotoxicity were performed on 107 subjects ( 77 cases and 30 healthy controls ) in South Indian population.", "output": "malonaldehyde, MDA." }, { "input": "In vitro repair ability was assessed by considering the residual damage.", "output": "There is no related enetity." }, { "input": "A significant difference was observed between the patients and controls with regard to their mean values of DNA damage and MDA levels ( p < 0. 05 ).", "output": "MDA." }, { "input": "On categorization to fast and slow responders based on the time of response, patients exhibited a significant deviation in residual DNA damage, suggestive of variation with respect to DNA repair efficiency ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "This is the first study to our knowledge with respect to PUVA drug response variation in vitiligo in relation to DNA repair.", "output": "There is no related enetity." }, { "input": "Large systematic studies on DNA repair may help in a better understanding of the mechanisms involved in the PUVA drug response variation.", "output": "There is no related enetity." }, { "input": "Liver glycogen loading dampens glycogen synthesis seen in response to either hyperinsulinemia or intraportal glucose infusion.", "output": "glucose." }, { "input": "The purpose of this study was to determine the effect of liver glycogen loading on net hepatic glycogen synthesis during hyperinsulinemia or hepatic portal vein glucose infusion in vivo.", "output": "glucose." }, { "input": "Liver glycogen levels were supercompensated ( SCGly ) in two groups ( using intraportal fructose infusion ) but not in two others ( Gly ) during hyperglycemic - normoinsulinemia.", "output": "fructose." }, { "input": "Following a 2 - h control period during which fructose infusion was stopped, there was a 2 - h experimental period in which the response to hyperglycemia plus either 4 x basal insulin ( INS ) or portal vein glucose infusion ( PoG ) was measured.", "output": "fructose, glucose." }, { "input": "Increased hepatic glycogen reduced the percent of glucose taken up by the liver that was deposited in glycogen ( 74 +/- 3 vs. 53 +/- 5 % in Gly + INS and SCGly + INS, respectively, and 72 +/- 3 vs. 50 +/- 6 % in Gly + PoG and SCGly + PoG, respectively ).", "output": "glucose." }, { "input": "The reduction in liver glycogen synthesis in SCGly + INS was accompanied by a decrease in both insulin signaling and an increase in AMPK activation, whereas only the latter was observed in SCGly + PoG.", "output": "There is no related enetity." }, { "input": "These data indicate that liver glycogen loading impairs glycogen synthesis regardless of the signal used to stimulate it.", "output": "There is no related enetity." }, { "input": "A bioactive probe of the oxidative pentose phosphate cycle: novel strategy to reverse radioresistance in glucose deprived human colon cancer cells.", "output": "pentose phosphate, glucose." }, { "input": "The specific effects of glucose deprivation on oxidative pentose phosphate cycle ( OPPC ) function, thiol homeostasis, protein function and cell survival remain unclear due to lack of a glucose - sensitive chemical probe.", "output": "glucose, pentose phosphate, thiol, glucose." }, { "input": "Using p53 wild type and mutant human colon cells, we determined the effects of hydroxyethyl disulfide ( HEDS ) on NADPH, GSH, GSSG, total glutathione, total non - protein and protein thiol levels, the function of the DNA repair protein Ku, and the susceptibility to radiation - induced free radicals under normal glucose or glucose - deprived conditions.", "output": "hydroxyethyl disulfide, HEDS, NADPH, GSH, GSSG, glutathione, glucose, glucose." }, { "input": "HEDS is rapidly detoxified in normal glucose but triggered a p53 - independent metabolic stress in glucose depleted state that caused loss of NADPH, protein and non - protein thiol homeostasis and Ku function, and enhanced sensitivity of both p53 wild type and mutant cells to radiation induced oxidative stress.", "output": "HEDS, glucose, glucose, NADPH, thiol." }, { "input": "Additionally, high concentration of HEDS alone induced cell death in p53 wild type cells without significant effect on p53 mutant cells.", "output": "HEDS." }, { "input": "HEDS offers a useful tool to gain insights into how glucose metabolism affects OPPC dependent stress - induced cellular functions and injury, including in tumor cells, where our findings imply a novel therapeutic approach to target glucose deprived tumor.", "output": "HEDS, glucose, glucose." }, { "input": "Our work introduces a novel probe to address cancer metabolism and ischemic pathology.", "output": "There is no related enetity." }, { "input": "Genetic perspectives on the origin of clicks in Bantu languages from southwestern Zambia.", "output": "There is no related enetity." }, { "input": "Some Bantu languages spoken in southwestern Zambia and neighboring regions of Botswana, Namibia, and Angola are characterized by the presence of click consonants, whereas their closest linguistic relatives lack such clicks.", "output": "There is no related enetity." }, { "input": "As clicks are a typical feature not of the Bantu language family, but of Khoisan languages, it is highly probable that the Bantu languages in question borrowed the clicks from Khoisan languages.", "output": "There is no related enetity." }, { "input": "In this paper, we combine complete mitochondrial genome sequences from a representative sample of populations from the Western Province of Zambia speaking Bantu languages with and without clicks, with fine - scaled analyses of Y - chromosomal single nucleotide polymorphisms and short tandem repeats to investigate the prehistoric contact that led to this borrowing of click consonants.", "output": "There is no related enetity." }, { "input": "Our results reveal complex population - specific histories, with female - biased admixture from Khoisan - speaking groups associated with the incorporation of click sounds in one Bantu - speaking population, while concomitant levels of potential Khoisan admixture did not result in sound change in another.", "output": "There is no related enetity." }, { "input": "Furthermore, the lack of sequence sharing between the Bantu - speaking groups from southwestern Zambia investigated here and extant Khoisan populations provides an indication that there must have been genetic substructure in the Khoisan - speaking indigenous groups of southern Africa that did not survive until the present or has been substantially reduced.", "output": "There is no related enetity." }, { "input": "Clinical pharmacology of etoposide in children undergoing autologous stem cell transplantation for various solid tumours.", "output": "etoposide." }, { "input": "1. The population pharmacokinetics of high - dose etoposide was studied in a group of young children and adolescents.", "output": "There is no related enetity." }, { "input": "2. Twenty - six children and adolescent were administered high - dose etoposide as a continuous infusion over 24 h.", "output": "etoposide." }, { "input": "Etoposide plasma concentration - time data was modelled using NONMEM (R) 7.", "output": "Etoposide." }, { "input": "The effect of age, weight, serum creatinine ( SCr ), and gender on pharmacokinetic parameters ( CL and V ( d ) ) were determined by a nonlinear mixed effect model.", "output": "creatinine." }, { "input": "3. The pharmacokinetics of etoposide based on BSA dosing was best described with a 1 - compartment structural model which was parameterised in terms of clearance ( CL ) and volume of distribution ( V ( d ) ).", "output": "etoposide." }, { "input": "An exponential error model was used to explain intersubject variability and a proportional error model was used to describe residual or intrapatient variability.", "output": "There is no related enetity." }, { "input": "The final model parameter estimates for the typical ( normalised to 70 kg ) values of CL and V ( d ) were 2. 31 L / hr and 17. 5 L, respectively.", "output": "There is no related enetity." }, { "input": "The CL and V ( d ) allometrically increased with weight with the power of 3 / 4 and 1, respectively.", "output": "There is no related enetity." }, { "input": "After accounting for weight dependence using the allometric scaling, age, serum creatinine, and gender did not have any influence on model parameters.", "output": "creatinine." }, { "input": "4. The results of this children and adolescent population pharmacokinetic study indicates that etoposide pharmacokinetics were influenced by body weight on an allometric basis.", "output": "etoposide." }, { "input": "The pharmacokinetic parameters CL and V ( d ) increased with increasing weight similar to BSA.", "output": "There is no related enetity." }, { "input": "Elucidation of the mechanism of ribose conjugation in a pyrazole - containing compound in rodent liver.", "output": "ribose, pyrazole." }, { "input": "1.", "output": "There is no related enetity." }, { "input": "Here we report on the mechanism of ribose conjugation, through NADH as a cofactor, of a pyrazole - containing compound ( PT ).", "output": "ribose, NADH, pyrazole." }, { "input": "Incubation of PT in rat liver microsomes supplemented with NADP + / H, NAD + / H, and beta - nicotinamide mononucleotide ( NMN ) resulted in complete conjugation to the adenine dinucleotide phosphate conjugate ( ADP - C ), adenine dinucleotide conjugate ( AD - C ), and 5 - phosphoribose conjugate ( Rib - C1 ), respectively.", "output": "NADP, H, NAD, H, beta - nicotinamide mononucleotide, NMN, adenine dinucleotide phosphate, ADP, adenine, 5 - phosphoribose, Rib." }, { "input": "In hepatocytes, PT predominantly formed three ribose conjugates: Rib - C1, the ribose conjugate ( Rib - C2 ), and the carboxylic acid of Rib - C2 ( Rib - C3 ).", "output": "ribose, Rib, ribose, Rib, carboxylic acid, Rib, Rib." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "Phosphatase inhibitors were added to hepatocyte incubations.", "output": "There is no related enetity." }, { "input": "AD - C was detected in this reaction, which suggests that one of the major pathways for the formation of the ribose conjugates is through NAD + / H.", "output": "ribose, NAD, H." }, { "input": "When AD - C was incubated with phosphatase, Rib - C1 and Rib - C2 formed.", "output": "Rib, Rib." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "To understand the in vivo relevance of this metabolic pathway, rats were dosed with PT and Rib - C2 was found in the urine.", "output": "Rib." }, { "input": "4.", "output": "There is no related enetity." }, { "input": "Structure - activity relationship shows that replacement of the distal thiazole group in the PT to a phenyl group abolishes this conjugation.", "output": "thiazole, phenyl." }, { "input": "Three amino acid residues in the active site preferentially interact with the sulfur atom in the thiazole of PT.", "output": "amino acid, sulfur, thiazole." }, { "input": "5.", "output": "There is no related enetity." }, { "input": "In summary, PT forms direct AD - C in hepatocytes, which is further hydrolyzed by phosphatase to give ribose conjugates.", "output": "ribose." }, { "input": "In silico drug repositioning: what we need to know.", "output": "There is no related enetity." }, { "input": "Drug repositioning, exemplified by sildenafil and thalidomide, is a promising way to explore alternative indications for existing drugs.", "output": "sildenafil, thalidomide." }, { "input": "Recent research has shown that bioinformatics - based approaches have the potential to offer systematic insights into the complex relationships among drugs, targets and diseases necessary for successful repositioning.", "output": "There is no related enetity." }, { "input": "In this article, we propose the key bioinformatics steps essential for discovering valuable repositioning methods.", "output": "There is no related enetity." }, { "input": "The proposed steps ( repurposing with a purpose, repurposing with a strategy and repurposing with confidence ) are aimed at providing a repurposing pipeline, with particular focus on the proposed Drugs of New Indications ( DNI ) database, which can be used alongside currently available resources to improve in silico drug repositioning.", "output": "There is no related enetity." }, { "input": "Human beta - cell killing by autoreactive preproinsulin - specific CD8 T cells is predominantly granule - mediated with the potency dependent upon T - cell receptor avidity.", "output": "There is no related enetity." }, { "input": "The end - stage immunopathology of type 1 diabetes resulting in beta - cell destruction appears to be strongly dominated by cytotoxic CD8 T lymphocytes ( CD8 T cells ).", "output": "There is no related enetity." }, { "input": "However, the mechanism of cytotoxicity used by autoreactive CD8 T cells in the human setting remains unknown.", "output": "There is no related enetity." }, { "input": "Using type 1 diabetes patient - derived preproinsulin - specific CD8 T - cell clones recognizing either an HLA - A2 ( A * 0201 ) or HLA - A24 ( A * 2402 ) - restricted epitope ( peptide of preproinsulin [ PPI ] ( 15 - 24 ), ALWGPDPAAA; or PPI ( 3 - 11 ), LWMRLLPLL ), we assessed the use of conventional mediators of cytotoxicity in the destruction of human beta - cells in vitro compared with virus - specific cytotoxic CD8 T - cell clones.", "output": "There is no related enetity." }, { "input": "We show that PPI - specific CD8 T - cell clones are mainly reliant upon cytotoxic degranulation for inducing beta - cell death.", "output": "There is no related enetity." }, { "input": "Furthermore, we find that in comparison with virus - specific CD8 T cells, there are differences in the killing potency of PPI - specific CD8 T cells that are not due to cell - intrinsic differences, but rather are mediated by differences in strength of signaling by peptide - HLA ligands.", "output": "There is no related enetity." }, { "input": "The study highlights the regulation of beta - cell killing as a potential point for therapeutic control, including the possibility of blocking autoreactive CD8 T - cell function without impacting upon general immune competence.", "output": "There is no related enetity." }, { "input": "Osteocyte control of osteoclastogenesis.", "output": "There is no related enetity." }, { "input": "Multiple lines of evidence support the idea that osteocytes act as mechanosensors in bone and that they control bone formation, in part, by expressing the Wnt antagonist sclerostin.", "output": "There is no related enetity." }, { "input": "However, the role of osteocytes in the control of bone resorption has been less clear.", "output": "There is no related enetity." }, { "input": "Recent studies have demonstrated that osteocytes are the major source of the cytokine RANKL involved in osteoclast formation in cancellous bone.", "output": "There is no related enetity." }, { "input": "The goal of this review is to discuss these and other studies that reveal mechanisms whereby osteocytes control osteoclast formation and thus bone resorption.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled \" The Osteocyte \".", "output": "There is no related enetity." }, { "input": "Relation between dynamics, activity and thermal stability within the cholinesterase family.", "output": "There is no related enetity." }, { "input": "Incoherent neutron scattering is one of the most powerful tools for studying dynamics in biological matter.", "output": "There is no related enetity." }, { "input": "Using the cold neutron backscattering spectrometer IN16 at the Institut Laue Langevin ( ILL, Grenoble, France ), temperature dependence of cholinesterases ' dynamics ( human butyrylcholinesterase from plasma: hBChE; recombinant human acetylcholinesterase: hAChE and recombinant mouse acetylcholinesterase: mAChE ) was examined using elastic incoherent neutron scattering ( EINS ).", "output": "There is no related enetity." }, { "input": "The dynamics was characterized by the averaged atomic mean square displacement ( MSD ), associated with the sample flexibility at a given temperature.", "output": "There is no related enetity." }, { "input": "We found MSD values of hAChE above the dynamical transition temperature ( around 200K ) larger than for mAChE and hBChE, implying that hAChE is more flexible than the other ChEs.", "output": "There is no related enetity." }, { "input": "Activation energies for thermodynamical transition were extracted through the frequency window model ( FWM ) ( Becker et al. 2004 ) [ 1 ] and turned out to increase from hBChE to mAChE and finally to hAChE, inversely to the MSDs relations.", "output": "There is no related enetity." }, { "input": "Between 280 and 316K, catalytic studies of these enzymes were carried out using thiocholine esters: at the same temperature, the hAChE activity was systematically higher than the mAChE or hBChE ones.", "output": "thiocholine esters." }, { "input": "Our results thus suggest a strong correlation between dynamics and activity within the ChE family.", "output": "There is no related enetity." }, { "input": "We also studied and compared the ChEs thermal inactivation kinetics.", "output": "There is no related enetity." }, { "input": "Here, no direct correlation with the dynamics was observed, thus suggesting that relations between enzyme dynamics and catalytic stability are more complex.", "output": "There is no related enetity." }, { "input": "Finally, the possible relation between flexibility and protein ability to grow in crystals is discussed.", "output": "There is no related enetity." }, { "input": "Quantum chemical investigation of the intra - and intermolecular proton transfer reactions and hydrogen bonding interactions in 4 - amino - 5 - ( 2 - hydroxyphenyl ) - 2H - 1, 2, 4 - triazole - 3 ( 4H ) - thione.", "output": "hydrogen, 4 - amino - 5 - ( 2 - hydroxyphenyl ) - 2H - 1 , 2 , 4 - triazole - 3 ( 4H ) - thione." }, { "input": "The intramolecular thione - thiol tautomerism and intermolecular double proton transfer reaction of the hydrogen - bonded thione and thiol dimers in the title triazole compound were studied at the B3LYP level of theory using 6 - 311 + + G ( d, p ) basis function.", "output": "thione - thiol, hydrogen, thione and thiol dimers, triazole." }, { "input": "The influence of the solvent on the single and double proton transfer reactions was examined in three solvents ( chloroform, methanol and water ) using the polarizable continuum model ( PCM ) approximation.", "output": "chloroform, methanol." }, { "input": "The computational results show that the thione tautomer is the most stable isomer with a very high tautomeric energy barrier both in the gas phase and in solution phase, indicating a quite disfavored process.", "output": "thione." }, { "input": "The solvent effect is found to be sizable with increasing polarity.", "output": "There is no related enetity." }, { "input": "In the double proton transfer reaction, the thione dimer is found to be more stable than thiol dimer both in the gas phase and in solution phase.", "output": "thione dimer, thiol dimer." }, { "input": "The energetic and thermodynamic parameters of the double proton transfer process show that the double proton exchange from thione dimer to thiol dimer is thermodynamically unfavored.", "output": "thione dimer, thiol dimer." }, { "input": "However, the exchange from thiol dimer to thione dimer for the gas phase and water phase seems to be feasible with a low barrier height and with a negative value in enthalpy and free energy changes.", "output": "thiol dimer, thione dimer." }, { "input": "In addition, the hydrogen bonding interactions were analyzed in the gas phase regarding their geometries and energies.", "output": "hydrogen." }, { "input": "It is found that all complex formations are enthalpically favored, and the stability of the H - bonds comes in the order of S1 - H2... N2 > N2 - H2... S1 > N3 - H3B... O1.", "output": "H, S1, H2, N2, N2, H2, S1, N3, H3B, O1." }, { "input": "Finally, non - linear optical properties were carried out at the same calculation level in the gas phase.", "output": "There is no related enetity." }, { "input": "Type 2 diabetes and cardiovascular disease in women.", "output": "There is no related enetity." }, { "input": "Cardiovascular disease is the leading cause of death in both men and women.", "output": "There is no related enetity." }, { "input": "This is also true for patients with diabetes.", "output": "There is no related enetity." }, { "input": "In general, differences between the sexes are present in several areas, such as epidemiology, pathophysiology, diagnostics, treatment response and prognosis, as well as the way in which disease is experienced and expressed.", "output": "There is no related enetity." }, { "input": "Cardiovascular disease presents later in life in women, who are therefore more likely to suffer from comorbidities.", "output": "There is no related enetity." }, { "input": "However, this age - related difference is attenuated in women with diabetes, who suffer their first myocardial infarction at about the same age as men with diabetes.", "output": "There is no related enetity." }, { "input": "Diabetes mellitus increases the risk of cardiovascular disease by three to four times in women and two to three times in men, after adjusting for other risk factors.", "output": "There is no related enetity." }, { "input": "This paper describes the differences in cardiovascular disease in men and women and the special situation of women with type 2 diabetes when it comes to risk factors, symptoms and the setting of acute coronary syndromes.", "output": "There is no related enetity." }, { "input": "Furthermore, it highlights the importance of sex - specific analyses in clinical research to improve our knowledge of cardiovascular disease in women in general and in women with diabetes in particular.", "output": "There is no related enetity." }, { "input": "The importance of taking sex into account when treating women and men at risk of cardiovascular disease is discussed.", "output": "There is no related enetity." }, { "input": "Methylation levels of sodium - iodide symporter ( NIS ) promoter in benign and malignant thyroid tumors with reduced NIS expression.", "output": "sodium - iodide." }, { "input": "DNA methylation regulates gene expression.", "output": "There is no related enetity." }, { "input": "Aberrant methylation plays an important role in human tumorigenesis.", "output": "There is no related enetity." }, { "input": "We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non - tumor tissues.", "output": "There is no related enetity." }, { "input": "Thus, in this study we investigated whether the methylation of the CpG - island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors.", "output": "There is no related enetity." }, { "input": "Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors ( T ) along with matched non - tumor ( NT ) areas were determined by semiquantitative methylation specific - PCR.", "output": "There is no related enetity." }, { "input": "NIS methylation was detected in all samples.", "output": "There is no related enetity." }, { "input": "Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status.", "output": "There is no related enetity." }, { "input": "Highest methylation levels and frequencies were detected in the 5 ' region of the CpG - island decreasing toward the 3 ' end.", "output": "CpG." }, { "input": "Intraindividual analysis ( T versus NT ) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression.", "output": "There is no related enetity." }, { "input": "No quantitative correlation was detected between methylation levels and mRNA expression in any the groups.", "output": "There is no related enetity." }, { "input": "The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non - homogeneous methylation pattern along the CpG island.", "output": "CpG." }, { "input": "Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted.", "output": "There is no related enetity." }, { "input": "Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.", "output": "There is no related enetity." }, { "input": "The epidermis acts as a functional barrier against the external environment.", "output": "There is no related enetity." }, { "input": "Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis.", "output": "There is no related enetity." }, { "input": "Ceramides are a critical natural element of the protective epidermal barrier.", "output": "There is no related enetity." }, { "input": "The aim of this study was to evaluate whether the oral intake of beet ( Beta vulgaris ) extract, a natural product rich in glucosylceramide ( GlcCer ), may prevent disturbance in skin barrier function.", "output": "There is no related enetity." }, { "input": "When HR - 1 hairless mice were fed a special diet ( HR - AD ), transepidermal water loss ( TEWL ) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks.", "output": "There is no related enetity." }, { "input": "Mice fed with HR - AD had dry skin with erythema and showed increased scratching behaviour.", "output": "There is no related enetity." }, { "input": "Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks.", "output": "There is no related enetity." }, { "input": "Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0. 1 %, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks.", "output": "There is no related enetity." }, { "input": "These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2012 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen.", "output": "lysines." }, { "input": "Although biallelic mutations in non - collagen genes account for < 10 % of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes.", "output": "There is no related enetity." }, { "input": "We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis - trans isomerase, FKBP65, in 38 members of 21 families with OI.", "output": "prolyl." }, { "input": "These include 10 families from the Samoan Islands who share a founder mutation.", "output": "There is no related enetity." }, { "input": "Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability.", "output": "There is no related enetity." }, { "input": "In four families missense mutations result in loss of most of the protein.", "output": "There is no related enetity." }, { "input": "The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families.", "output": "There is no related enetity." }, { "input": "The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross - link formation in bone.", "output": "lysyl." }, { "input": "The phenotype overlaps with that seen with mutations in PLOD2 ( Bruck syndrome II ), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues.", "output": "hydroxylates, lysyl." }, { "input": "These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post - translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.", "output": "There is no related enetity." }, { "input": "In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking.", "output": "There is no related enetity." }, { "input": "Atherosclerotic cardiovascular disease is a prevalent human disorder and a significant cause of human morbidity and mortality.", "output": "There is no related enetity." }, { "input": "A number of risk factors may predispose an individual to developing atherosclerosis, and of these factors, cigarette smoking is strongly associated with the development of cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Current thinking suggests that exposure to toxicants found in cigarette smoke may be responsible for this elevated disease likelihood, and this gives rise to the idea that reductions in the levels of some smoke toxicants may reduce the harm associated with cigarette smoking.", "output": "There is no related enetity." }, { "input": "To assess the disease risk of individuals who smoke cigarettes with altered toxicant levels, a weight - of - evidence approach is required examining both exposure and disease - related endpoints.", "output": "There is no related enetity." }, { "input": "A key element of such an assessment framework are data derived from the use of in vitro models of cardiovascular disease, which when considered alongside other forms of data ( e. g. from clinical studies ) may support evidence of potential reduced risk.", "output": "There is no related enetity." }, { "input": "Importantly, such models may also be used to provide mechanistic insight into the effects of smoking and of smoke toxicant exposure in cardiovascular disease development.", "output": "There is no related enetity." }, { "input": "In this review the use of in vitro models of cardiovascular disease and one of the contributory factors, oxidative stress, is discussed in the context of assessing the risk potential of both conventional and modified cigarettes.", "output": "There is no related enetity." }, { "input": "Practical issues concerning the use of these models for cardiovascular disease understanding and risk assessment are highlighted and areas of development necessary to enhance the power and predictive capacity of in vitro disease models in risk assessment are discussed.", "output": "There is no related enetity." }, { "input": "Can first - trimester screening program detect women at high risk for gestational diabetes mellitus?", "output": "There is no related enetity." }, { "input": "This study was designed to compare first - trimester maternal serum biochemical markers of aneuploidy and fetal nuchal translucency in pregnancies complicated by gestational diabetes mellitus and those of a control group.", "output": "There is no related enetity." }, { "input": "The study included 60 gestational diabetic and 60 control women who attended the first - trimester combined screening program for Down syndrome between 11 and 14 gestational weeks with complete follow - up data and delivered in our institution.", "output": "There is no related enetity." }, { "input": "Maternal serum free beta - human chorionic gonadotropin, pregnancy - associated plasma protein - A and fetal nuchal translucency were investigated.", "output": "There is no related enetity." }, { "input": "The combined risks, double test risks and age risks were calculated by PRISCA software version 4. 0.", "output": "There is no related enetity." }, { "input": "Comparison of the results between the two groups yielded no significant differences in serum levels of free beta - human chorionic gonadotropin and fetal nuchal translucency.", "output": "There is no related enetity." }, { "input": "However, women who developed gestational diabetes mellitus had significantly lower pregnancy - associated plasma protein - A.", "output": "There is no related enetity." }, { "input": "And also, the combined risks and double test risks calculated by PRISCA software were statistically higher in gestational diabetic women than normal pregnant women.", "output": "There is no related enetity." }, { "input": "These results suggest that differences can be seen between diabetic and healthy pregnant women in first - trimester maternal serum biochemical markers of aneuploidy.", "output": "There is no related enetity." }, { "input": "Attenuated effect of tungsten carbide nanoparticles on voltage - gated sodium current of hippocampal CA1 pyramidal neurons.", "output": "tungsten carbide, sodium." }, { "input": "Nanomaterials and relevant products are now being widely used in the world, and their safety becomes a great concern for the general public.", "output": "There is no related enetity." }, { "input": "Tungsten carbide nanoparticles ( nano - WC ) are widely used in metallurgy, aeronautics and astronautics, however our knowledge regarding the influence of nano - WC on neurons is still lacking.", "output": "Tungsten carbide, WC, WC." }, { "input": "The aim of this study was to investigate the impact of nano - WC on tetrodotoxin ( TTX ) - sensitive voltage - activated sodium current ( I ( Na ) ) of hippocampal CA1 pyramidal neurons.", "output": "WC, tetrodotoxin, TTX, sodium, Na." }, { "input": "Results showed that acute exposure of nano - WC attenuated the peak amplitudes of I ( Na ) in a concentration - dependent manner.", "output": "WC, Na." }, { "input": "The minimal effective concentration was 10 ( - 5 ) g / ml.", "output": "There is no related enetity." }, { "input": "The exposure of nano - WC significantly decreased current amplitudes of the current - voltage curves of I ( Na ) from - 50 to + 50 mV, shifted the steady - state activation and inactivation curves of I ( Na ) negatively and delayed the recovery of I ( Na ) from inactivation state.", "output": "WC, Na, Na, Na." }, { "input": "After exposure to nano - WC, the peak amplitudes, overshoots and the V - thresholds of action potentials ( APs ) were markedly reduced.", "output": "WC." }, { "input": "These results suggested that exposure of nano - WC could influence some characteristics of APs evoked from the hippocampal CA1 neurons by modifying the kinetics of voltage - gated sodium channels ( VGSCs ).", "output": "WC, sodium." }, { "input": "IKK - beta mediates hydrogen peroxide induced cell death through p85 S6K1.", "output": "hydrogen peroxide." }, { "input": "The I kappa B kinase ( IKK ) / NF - kappa B pathway has been shown to be a major regulator in cell survival.", "output": "There is no related enetity." }, { "input": "However, the mechanisms through which IKK mediates cell death are not clear.", "output": "There is no related enetity." }, { "input": "In this study, we showed that IKK - beta contributed to hydrogen peroxide ( H ( 2 ) O ( 2 ) ) - induced cell death independent of the NF - kappa B pathway.", "output": "hydrogen peroxide, H ( 2 ) O ( 2 )." }, { "input": "Our results demonstrated that the pro - death function of IKK - beta under oxidative stress was mediated by p85 S6K1 ( S6 kinase 1 ), but not p70 S6K1 through a rapamycin - insensitive and mammalian target of rapamycin complex 1 kinase - independent mechanism.", "output": "rapamycin, rapamycin." }, { "input": "We found that IKK - beta associated with p85, but not p70 S6K1, which was required for H ( 2 ) O ( 2 ) - induced activation of p85 S6K1.", "output": "H ( 2 ) O ( 2 )." }, { "input": "IKK - beta and p85 S6K1 contributed to H ( 2 ) O ( 2 ) - induced phosphorylation of Mdm2 ( S166 ) and p53 accumulation.", "output": "H ( 2 ) O ( 2 )." }, { "input": "p85 S6K1 is critical for IKK - beta - mediated cell death.", "output": "There is no related enetity." }, { "input": "Thus, these findings established a novel oxidative stress - responsive pathway that involves IKK - beta, p85 S6K1 and Mdm2, which is response for H ( 2 ) O ( 2 ) - induced cell death.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Our results have important implications for IKK - beta and p85 S6K1 as potential targets for the prevention of diseases involved in oxidative stress - induced aberrant cell death.", "output": "There is no related enetity." }, { "input": "Differential mouse pulmonary dose and time course responses to titanium dioxide nanospheres and nanobelts.", "output": "titanium dioxide." }, { "input": "Three anatase titanium dioxide ( TiO ( 2 ) ) nanoparticles ( NPs ) were prepared; nanospheres ( NSs ), short nanobelts ( NB1 ), and long nanobelts ( NB2 ).", "output": "titanium dioxide, TiO ( 2 )." }, { "input": "These NPs were used to investigate the effect of NP shape and length on lung toxicity.", "output": "There is no related enetity." }, { "input": "Mice were exposed ( 0 - 30 micro g per mouse ) by pharyngeal aspiration and pulmonary toxicity was assessed over a 112 - day time course.", "output": "There is no related enetity." }, { "input": "Whole lung lavage data indicated that NB1 - and NB2 - exposed mice, but not NS - exposed mice, had significant dose - and time - dependent pulmonary inflammation and damage.", "output": "There is no related enetity." }, { "input": "Histopathological analyses at 112 days postexposure determined no interstitial fibrosis in any NS - exposed mice, an increased incidence in 30 micro g NB1 - exposed mice, and significant interstitial fibrosis in 30 micro g NB2 - exposed mice.", "output": "There is no related enetity." }, { "input": "At 112 days postexposure, lung burden of NS was decreased by 96. 4 % and NB2 by 80. 5 % from initial deposition levels.", "output": "There is no related enetity." }, { "input": "At 112 days postexposure, enhanced dark field microscopy determined that alveolar macro - phages were the dominant deposition site, but a fraction of NB1 and NB2 was observed in the alveolar interstitial spaces.", "output": "There is no related enetity." }, { "input": "For the 30 micro g exposure groups at 112 days postexposure, confocal micro - scopy and immunofluorescent staining demonstrated that retained NB2 but not NS were present in the interstitium subjacent to the terminal bronchiole near the normal location of the smallest lymphatic capillaries in the lung.", "output": "There is no related enetity." }, { "input": "These lymphatic capillaries play a critical role in particle clearance, and the accumulation of NB2, but not NS, suggests possible impaired lymphatic clearance by the high aspect ratio particles.", "output": "There is no related enetity." }, { "input": "In summary, our data indicate that TiO ( 2 ) NP shape alters pulmonary responses, with severity of responses being ranked as NS < NB1 < NB2.", "output": "TiO ( 2 )." }, { "input": "Effects of parabens on adipocyte differentiation.", "output": "parabens." }, { "input": "Parabens are a group of alkyl esters of p - hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben.", "output": "Parabens, alkyl esters, p - hydroxybenzoic acid, methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben." }, { "input": "Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals.", "output": "Paraben esters and their salts." }, { "input": "Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation.", "output": "parabens." }, { "input": "However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have not been systematically studied.", "output": "parabens, parabens." }, { "input": "Here, we report that ( 1 ) parabens promote adipogenesis ( or adipocyte differentiation ) in murine 3T3 - L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA expression of adipocyte - specific markers; ( 2 ) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl - < ethyl - < propyl - < butylparaben.", "output": "parabens, parabens, methyl, ethyl, propyl, butylparaben." }, { "input": "The extension of the linear alkyl chain with an aromatic ring in benzylparaben further augments the adipogenic ability, whereas 4 - hydroxybenzoic acid, the common metabolite of all parabens, and the structurally related benzoic acid ( without the OH group ) are inactive in promoting 3T3 - L1 adipocyte differentiation; ( 3 ) parabens activate glucocorticoid receptor and / or peroxisome proliferator - activated receptor gamma in 3T3 - L1 preadipocytes; however, no direct binding to, or modulation of, the ligand binding domain of the glucocorticoid receptor by parabens was detected by glucocorticoid receptor competitor assays; and lastly, ( 4 ) parabens, butyl - and benzylparaben in particular, also promote adipose conversion of human adipose - derived multipotent stromal cells.", "output": "benzylparaben, 4 - hydroxybenzoic acid, parabens, benzoic acid, OH, parabens, parabens, parabens, butyl - and benzylparaben." }, { "input": "Our results suggest that parabens may contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo needs to be examined further.", "output": "parabens, parabens." }, { "input": "PPTOX III: environmental stressors in the developmental origins of disease - - evidence and mechanisms.", "output": "There is no related enetity." }, { "input": "Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards.", "output": "There is no related enetity." }, { "input": "Subtle effects during development can lead to functional deficits and increased disease risk later in life.", "output": "There is no related enetity." }, { "input": "The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies.", "output": "There is no related enetity." }, { "input": "Similar observations have been made on the long - term impact of nutritional unbalance during early development.", "output": "There is no related enetity." }, { "input": "In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work.", "output": "There is no related enetity." }, { "input": "This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees.", "output": "There is no related enetity." }, { "input": "Recommendations for the application and improvement of current and future research efforts are also presented.", "output": "There is no related enetity." }, { "input": "Increased responses to the actions of fibroblast growth factor 21 on energy balance and body weight in a seasonal model of adiposity.", "output": "There is no related enetity." }, { "input": "The present study aimed to investigate the actions of fibroblast growth factor 21 ( FGF21 ) on energy balance in a natural model of relative fatness, the Siberian hamster.", "output": "There is no related enetity." }, { "input": "Hamsters were studied under long days ( LD ) to promote weight gain, or short days to induce weight loss, and treated with rhFGF21 ( 3 mg / kg / day ) via s. c. minipumps for 14 days.", "output": "There is no related enetity." }, { "input": "On days 7 - 9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made.", "output": "There is no related enetity." }, { "input": "FGF21 caused substantial ( P < 0. 0001 ) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21 - treated hamsters in LD lost 18 % of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD.", "output": "There is no related enetity." }, { "input": "Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19 % in FGF21 treated hamsters in LD, whereas no difference was found in SD.", "output": "There is no related enetity." }, { "input": "Body weight loss in LD was associated with a reduction in food intake ( P < 0. 001 ) and a decreased respiratory exchange ratio ( P < 0. 001 ), indicating increased fat oxidation.", "output": "There is no related enetity." }, { "input": "Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected.", "output": "oxygen, carbon dioxide." }, { "input": "These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype.", "output": "There is no related enetity." }, { "input": "The observed differences in FGF21 sensitivity may relate to day length - induced changes in adipose tissue mass.", "output": "There is no related enetity." }, { "input": "Differential cell - specific cytotoxic responses of oral cavity cells to tobacco preparations.", "output": "There is no related enetity." }, { "input": "To examine the effects of standardized ( reference ) tobacco preparations on human oral cavity cells, two oral squamous cell carcinoma cell lines ( 101A, 101B ) and normal human gingival epithelial cells ( HGEC ) were treated with cigarette smoke total particulate matter ( TPM ), smokeless tobacco extracted with complete artificial saliva ( ST / CAS ), or whole - smoke conditioned media ( WS - CM ).", "output": "There is no related enetity." }, { "input": "EC - 50 values, as determined by sulforhodamine B assays, varied among the cell types and agents.", "output": "sulforhodamine B." }, { "input": "When normalized to nicotine content, cytotoxicity for WS - CM and TPM was higher compared to that observed with ST / CAS.", "output": "nicotine." }, { "input": "Nicotine alone had no or only minimal cytotoxicity for all cell types in the applied range.", "output": "Nicotine." }, { "input": "Activation of pro - apoptotic caspase - 3 was examined in all cell types at their respective EC - 50 doses for the three agents.", "output": "There is no related enetity." }, { "input": "TPM, but not ST / CAS or WS - CM significantly activated caspase - 3 in all three cell types.", "output": "There is no related enetity." }, { "input": "Fluorescence - activated cell sorting ( FACS ) for expression of the early apoptosis marker Annexin V and for nuclear staining by 7 - aminoactinomycin ( 7 - AAD ) revealed different extents of apoptosis versus non - apoptotic cell death for the three agents.", "output": "7 - aminoactinomycin, 7 - AAD." }, { "input": "These data characterize differential responses of normal and malignant oral cells after exposure to TPM, ST / CAS, or WS - CM.", "output": "There is no related enetity." }, { "input": "They assist in understanding differential effects of combustible versus non - combustible tobacco products, and in identifying novel biomarkers for tobacco smoke exposure and effect in the oral cavity.", "output": "There is no related enetity." }, { "input": "Loss of TDAG51 results in mature - onset obesity, hepatic steatosis, and insulin resistance by regulating lipogenesis.", "output": "There is no related enetity." }, { "input": "Regulation of energy metabolism is critical for the prevention of obesity, diabetes, and hepatic steatosis.", "output": "There is no related enetity." }, { "input": "Here, we report an important role for the pleckstrin homology - related domain family member, T - cell death - associated gene 51 ( TDAG51 ), in the regulation of energy metabolism.", "output": "There is no related enetity." }, { "input": "TDAG51 expression was examined during adipocyte differentiation.", "output": "There is no related enetity." }, { "input": "Adipogenic potential of preadipocytes with knockdown or absence of TDAG51 was assessed.", "output": "There is no related enetity." }, { "input": "Weight gain, insulin sensitivity, metabolic rate, and liver lipid content were also compared between TDAG51 - deficient ( TDAG51 ( - / - ) ) and wild - type mice.", "output": "There is no related enetity." }, { "input": "In addition to its relatively high expression in liver, TDAG51 was also present in white adipose tissue ( WAT ).", "output": "There is no related enetity." }, { "input": "TDAG51 was downregulated during adipogenesis, and TDAG51 ( - / - ) preadipocytes exhibited greater lipogenic potential.", "output": "There is no related enetity." }, { "input": "TDAG51 ( - / - ) mice fed a chow diet exhibited greater body and WAT mass, had reduced energy expenditure, displayed mature - onset insulin resistance ( IR ), and were predisposed to hepatic steatosis.", "output": "There is no related enetity." }, { "input": "TDAG51 ( - / - ) mice had increased hepatic triglycerides and SREBP - 1 target gene expression.", "output": "triglycerides." }, { "input": "Furthermore, TDAG51 expression was inversely correlated with fatty liver in multiple mouse models of hepatic steatosis.", "output": "There is no related enetity." }, { "input": "Taken together, our findings suggest that TDAG51 is involved in energy homeostasis at least in part by regulating lipogenesis in liver and WAT, and hence, may constitute a novel therapeutic target for the treatment of obesity and IR.", "output": "There is no related enetity." }, { "input": "A convective replica - exchange method for sampling new energy basins.", "output": "There is no related enetity." }, { "input": "Replica - exchange is a powerful simulation method for sampling the basins of a rugged energy landscape.", "output": "There is no related enetity." }, { "input": "The replica - exchange method ' s sampling is efficient because it allows replicas to perform round trips in temperature space, thereby visiting both low and high temperatures in the same simulation.", "output": "There is no related enetity." }, { "input": "However, replicas have a diffusive walk in temperature space, and the round trip rate decreases significantly with the system size.", "output": "There is no related enetity." }, { "input": "These drawbacks make convergence of the simulation even more difficult than it already is when bigger systems are tackled.", "output": "There is no related enetity." }, { "input": "Here, we present a simple modification of the exchange method.", "output": "There is no related enetity." }, { "input": "In this method, one of the replicas steadily raises or lowers its temperature.", "output": "There is no related enetity." }, { "input": "We tested the convective replica - exchange method on three systems of varying complexity: the alanine dipeptide in implicit solvent, the GB1 beta - hairpin in explicit solvent and the A beta ( 25 - 35 ) homotrimer in a coarse grained representation.", "output": "alanine dipeptide." }, { "input": "For the highly frustrated A beta ( 25 - 35 ) homotrimer, the proposed \" convective \" replica - exchange method is twice as fast as the standard method.", "output": "There is no related enetity." }, { "input": "It discovered 24 out of 27 free - energy basins in less than 500 ns.", "output": "There is no related enetity." }, { "input": "It also prevented the formation of groups of replicas that usually form on either side of an exchange bottleneck, leading to a more efficient sampling of new energy basins than in the standard method.", "output": "There is no related enetity." }, { "input": "Oriented electrophoretic deposition of GdOCl nanoplatelets.", "output": "GdOCl." }, { "input": "Electrophoretic deposition has emerged as a versatile and precisely tunable approach for the rapid deposition of conformal thin films of colloidal nanocrystals.", "output": "There is no related enetity." }, { "input": "The electrophoretic deposition of phosphor particles has assumed special significance in recent years as a commercially viable means toward the fabrication of large - area, ultrathin high - resolution emissive display screens.", "output": "There is no related enetity." }, { "input": "Here, we demonstrate that the anisotropic shape of colloidal ligand - passivated GdOCl nanoplatelets enables their assembly with remarkable substrate alignment and a high packing density upon electrophoretic deposition.", "output": "GdOCl." }, { "input": "GdOCl nanocrystals are promising candidates for phosphor applications given their low maximum phonon cutoff energy, robust chemical stability over prolonged periods of operation, and ability to promote efficacious phonon energy transfer to dopant ions.", "output": "GdOCl." }, { "input": "Potentiostatic deposition of GdOCl nanoplatelets from cyclohexane dispersions allows the deposition of individual nanoplatelets with their basal planes parallel to the electrode surface.", "output": "GdOCl, cyclohexane." }, { "input": "Tuning the applied voltage and solution concentration allows control of film thickness, ranging up to several tens of micrometers.", "output": "There is no related enetity." }, { "input": "The high degree of particle alignment is attributed to anisotropic charge distribution and entrainment within electroosmotic flows established in the vicinity of the electrode surface.", "output": "There is no related enetity." }, { "input": "The oriented high - particle - density GdOCl nanoplatelet thin films are possible candidates for phosphor applications, which is illustrated by the green emission from a Tb - doped GdOCl thin film on indium tin oxide ( ITO ) - coated glass.", "output": "GdOCl, Tb - doped GdOCl, indium tin oxide, ITO." }, { "input": "Inhaled Muscarinic Acetylcholine Receptor Antagonists for Treatment of COPD.", "output": "There is no related enetity." }, { "input": "Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD.", "output": "There is no related enetity." }, { "input": "Inhaled long - acting beta - agonists ( LABA ) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD.", "output": "There is no related enetity." }, { "input": "Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta - agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies.", "output": "There is no related enetity." }, { "input": "Their therapeutic efficacy is based on the fact that vagally mediated bronchoconstriction is the major reversible component of airflow obstruction in patients with COPD.", "output": "There is no related enetity." }, { "input": "However, bronchodilators are effective only on the reversible component of airflow obstruction, which by definition is limited, as COPD is characterized by a fixed or poorly reversible airflow obstruction.", "output": "There is no related enetity." }, { "input": "Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD include ipratropium bromide, oxitropium bromide and tiotropium bromide.", "output": "ipratropium bromide, oxitropium bromide, tiotropium bromide." }, { "input": "Ipratropium bromide, the prototype of anticholinergic bronchodilators, is a short - acting agent.", "output": "Ipratropium bromide." }, { "input": "Oxitropium bromide is administered twice a day.", "output": "Oxitropium bromide." }, { "input": "Tiotropium bromide, the only long - acting antimuscarinic agent ( LAMA ) currently approved, is administered once a day.", "output": "Tiotropium bromide." }, { "input": "Newer LAMAs including aclidinium bromide and glycopyrrolate bromide are currently in phase III development for treatment of COPD.", "output": "aclidinium bromide, glycopyrrolate bromide." }, { "input": "Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action.", "output": "tiotropium." }, { "input": "New LAMAs and their combination with ultra - LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD.", "output": "There is no related enetity." }, { "input": "Dual - pharmacology muscarinic antagonist - beta2 agonist ( MABA ) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.", "output": "There is no related enetity." }, { "input": "Development of New Drugs for COPD.", "output": "There is no related enetity." }, { "input": "Chronic obstructive pulmonary disease ( COPD ) is an increasing global health problem and cause of death.", "output": "There is no related enetity." }, { "input": "COPD is a chronic inflammatory disease predominantly affecting small airways and lung parenchyma that leads to progressive airway obstruction.", "output": "There is no related enetity." }, { "input": "However, current therapies fail to prevent either disease progression or mortality.", "output": "There is no related enetity." }, { "input": "The mainstay of current drug therapy is long - acting bronchodilators.", "output": "There is no related enetity." }, { "input": "Several once daily inhaled beta 2 - agonists and muscarinic antagonists ( and combinations ) are now in development.", "output": "There is no related enetity." }, { "input": "No treatments effectively suppress chronic inflammation in COPD lungs.", "output": "There is no related enetity." }, { "input": "With better understanding of the inflammatory and destructive process in the pathophysiology of COPD, several new therapeutic targets have been identified.", "output": "There is no related enetity." }, { "input": "Several mediator antagonists or inhibitors tested in COPD have so far been disappointing, but CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment are more promising.", "output": "There is no related enetity." }, { "input": "Broad spectrum anti - inflammatory drugs may be more effective, and include inhibitors of the proinflammatory enzymes phosphodiesterase - 4, p38 mitogen - activated protein kinase, Janus kinases, NF - kappa B kinase and PI3 kinase - gamma and - delta, but side effects after oral administration are a major limitation so that in future inhaled delivery may be necessary.", "output": "There is no related enetity." }, { "input": "A new promising approach is reversal of corticosteroid resistance through increasing histone deacetylase - 2 ( HDAC2 ) activity.", "output": "corticosteroid." }, { "input": "This might be achieved by existing treatments such as theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase - delta inhibitors.", "output": "theophylline, nortriptyline, macrolides." }, { "input": "Thus although there have been major advances in the development of long - acting bronchodilators for COPD, it has proved difficult to find anti - inflammatory treatments that are safe and effective.", "output": "There is no related enetity." }, { "input": "A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging.", "output": "methionine." }, { "input": "It has been reported that most tumor cells show an increased uptake of variety of amino acids specially methionine when compared with normal cells and amino acid transport is generally increased in malignant transformation.", "output": "amino acids, methionine, amino acid." }, { "input": "Based on the evidences, two novel nanosized analogues of methionine ( Anionic Linear Globular Dendrimer G ( 2 ), a biodigredabale anionic linear globular - Methionin, and DTPA - Methionine ( 1 ) conjugates ) were synthesized and labeled with ( 99m ) Tc and used in tumor imaging / therapy in vitro and in vivo.", "output": "methionine, Methionin, DTPA, Methionine, ( 99m ) Tc." }, { "input": "The results showed marked tumor SPECT molecular imaging liabilities for both compounds but with a better performance by administration of ( 99m ) Tc - Dendrimer G ( 2 ) - Methionin.", "output": "( 99m ) Tc, Methionin." }, { "input": "The results also showed a good anticancer activity for 99mTc - DTPA - Methionine.", "output": "99mTc, DTPA, Methionine." }, { "input": "Based on the present study ( 99m ) Tc - Dendrimer G ( 2 ) - Methionin or 99mTc - DTPA - ( Methionine ) ( 1 ) have potentials to be used in tumor molecular imaging as well as cancer therapy in future.", "output": "( 99m ) Tc, Methionin, 99mTc, DTPA, Methionine." }, { "input": "Tub has a key role in insulin and leptin signaling and action in vivo in hypothalamic nuclei.", "output": "There is no related enetity." }, { "input": "Mutation of tub gene in mice induces obesity, suggesting that tub could be an important regulator of energy balance.", "output": "There is no related enetity." }, { "input": "In the current study, we investigated whether insulin, leptin, and obesity can modulate Tub in vivo in hypothalamic nuclei, and we investigated possible consequences on energy balance, neuropeptide expression, and hepatic glucose metabolism.", "output": "glucose." }, { "input": "Food intake, metabolic characteristics, signaling proteins, and neuropeptide expression were measured in response to fasting and refeeding, intracerebroventricular insulin and leptin, and Tub antisense oligonucleotide ( ASO ).", "output": "There is no related enetity." }, { "input": "Tub tyrosine phosphorylation ( Tub - p - tyr ) is modulated by nutritional status.", "output": "tyrosine, tyr." }, { "input": "Tub is a substrate of insulin receptor tyrosine kinase ( IRTK ) and leptin receptor ( LEPR ) - Janus kinase 2 ( JAK2 ) in hypothalamic nuclei.", "output": "tyrosine." }, { "input": "After leptin or insulin stimulation, Tub translocates to the nucleus.", "output": "There is no related enetity." }, { "input": "Inhibition of Tub expression in hypothalamus by ASO increased food intake, fasting blood glucose, and hepatic glucose output, decreased O ( 2 ) consumption, and blunted the effect of insulin or leptin on proopiomelanocortin, thyroid - releasing hormone, melanin - concentrating hormone, and orexin expression.", "output": "glucose, glucose, O ( 2 )." }, { "input": "In hypothalamus of mice administered a high - fat diet, there is a reduction in leptin and insulin - induced Tub - p - tyr and nuclear translocation, which is reversed by reducing protein tyrosine phosphatase 1B expression.", "output": "tyr, tyrosine." }, { "input": "These results indicate that Tub has a key role in the control of insulin and leptin effects on food intake, and the modulation of Tub may contribute to insulin and leptin resistance in DIO mice.", "output": "There is no related enetity." }, { "input": "Anti - obesity effects of glabridin - rich supercritical carbon dioxide extract of licorice in high - fat - fed obese mice.", "output": "glabridin, carbon dioxide." }, { "input": "Licorice ( Glycyrrhiza glabra Linne ) is a well - known medicinal plant and glabridin is an isoflavan isolated from licorice.", "output": "glabridin, isoflavan." }, { "input": "In this study, we investigated the anti - obesity effect of glabridin and glabridin - rich supercritical fluid extract of licorice ( LSC ).", "output": "glabridin, glabridin." }, { "input": "Glabridin effectively inhibited adipogenesis in 3T3 - L1 cells.", "output": "Glabridin." }, { "input": "Moreover, LSC showed inhibitory effect on adipogenesis in a dose - dependent manner.", "output": "There is no related enetity." }, { "input": "The inhibitory effect of LSC resulted from inhibiting the induction of the transcriptional factors CCAAT enhancer binding protein alpha and peroxisome proliferator - activated receptor gamma.", "output": "There is no related enetity." }, { "input": "Then we fed mice with high - fat diet containing none, 0. 1 % and 0. 25 % LSC for 8weeks to explore the anti - obesity effect of LSC in vivo.", "output": "There is no related enetity." }, { "input": "LSC significantly reduced weight gain by high - fat diet in a dose - dependent manner.", "output": "There is no related enetity." }, { "input": "The reductions of the hypertrophy of white adipose tissue and of fat cell size were also observed.", "output": "There is no related enetity." }, { "input": "In the liver, LSC supplementation effectively inhibited high - fat diet - induced hepatic steatosis through downregulation of gluconeogenesis related phosphoenolpyruvate carboxykinase and glucose 6 - phosphatase and upregulation of the beta - oxidation related carnitine palmitoyltransferase 1.", "output": "phosphoenolpyruvate, glucose, carnitine." }, { "input": "Taken together, our results suggest that glabridin and glabridin - rich licorice extract would be effective anti - obesity agents.", "output": "glabridin, glabridin." }, { "input": "Effects of metabotropic glutamate receptor ligands on male sexual behavior in rats.", "output": "glutamate." }, { "input": "Metabotropic glutamate receptors ( mGluRs ), particularly mGluR2 / 3, mGluR5 and mGluR7, have received much attention in medication development for the treatment of drug addiction and other neuropsychiatric diseases.", "output": "glutamate." }, { "input": "However, little is known as to whether mGluR ligands also alter natural sexual behavior, a possible unwanted effect when used in humans.", "output": "There is no related enetity." }, { "input": "In the present study, we used classical copulatory behaviors to evaluate the effects of LY379268 ( a selective mGluR2 / 3 agonist ), MPEP ( a selective mGluR5 antagonist ) and AMN082 ( a selective mGluR7 agonist ), on male sexual performance in rats.", "output": "LY379268, MPEP, AMN082." }, { "input": "We found that systemic administration of LY379268 ( 1, 3 mg / kg, i. p. ) had no effect, while MPEP ( 20 mg / kg, but not 10 mg / kg, i. p. ) and AMN082 ( 10, 20 mg / kg, but not 3 mg / kg ) produced a significant and dose - dependent reduction in both sex - seeking and sex - performance behaviors, manifested as an increase in mount or intromission latency and time required for ejaculation, and a reduction in mount or intromission frequency.", "output": "LY379268, MPEP, AMN082." }, { "input": "This inhibition lasted for about 30 - 60 min.", "output": "There is no related enetity." }, { "input": "These findings suggest that compounds that target mGluR5 or mGluR7, but not mGluR2 / 3, may have short - term inhibitory effects on male sexual performance.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Metabotropic Glutamate Receptors '.", "output": "There is no related enetity." }, { "input": "Public support and consent preference for biomedical research and biobanking in Jordan.", "output": "There is no related enetity." }, { "input": "The success of any biobank depends on a number of factors including public ' s view of research and the extent to which it is willing to participate in research.", "output": "There is no related enetity." }, { "input": "As a prototype of surrounding countries, public interest in research and biobanking in addition to the influence and type of informed consent for biobanking were investigated in Jordan.", "output": "There is no related enetity." }, { "input": "Data were collected as part of a national survey of 3196 individuals representing the Jordanian population.", "output": "There is no related enetity." }, { "input": "The majority of respondents ( 88. 6 % ) had a positive perception of the level of research in Jordan and they overwhelmingly ( 98. 2 % ) agreed to the concept of investing as a country in research.", "output": "There is no related enetity." }, { "input": "When respondents were asked if the presence of an informed consent would influence their decision to participate in biobanking, more individuals ( 19. 8 % ) considered having an informed consent mechanism as a positive factor than those who considered it to have negative connotations ( 13. 1 % ).", "output": "There is no related enetity." }, { "input": "However, a substantial portion ( 65 % ) did not feel it affected their decision.", "output": "There is no related enetity." }, { "input": "The majority of survey participants ( 64 % ) expressed willingness to participate in biobanking and over 90 % of them preferred an opt - in consent form whether general ( 75. 2 % ) or specific for disease or treatment ( 16. 9 % ).", "output": "There is no related enetity." }, { "input": "These results indicate a promising ground for research and biobanking in Jordan.", "output": "There is no related enetity." }, { "input": "Educational programs or mass awareness campaigns to promote participation in biobanking and increase awareness about informed consent and individual rights in research will benefit both the scientific community as well as the public.", "output": "There is no related enetity." }, { "input": "GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients.", "output": "cortisol." }, { "input": "It is well established that obese patients are hypo - responsive to classical GH - releasing stimuli, including aerobic exercise.", "output": "There is no related enetity." }, { "input": "Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH - releasing stimulus.", "output": "There is no related enetity." }, { "input": "Furthermore, we have shown the ability of a respiratory muscle endurance training ( RMET ) to stimulate GH and cortisol secretion in healthy subjects.", "output": "cortisol." }, { "input": "The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients.", "output": "cortisol." }, { "input": "Eight severely obese patients ( 4 M / 4 F, mean age +/- SEM: 22. 8 +/- 1. 6 years, body mass index, BMI: 39. 9 +/- 1. 1 kg / m2 ) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device ( Spiro Tiger (R) ).", "output": "There is no related enetity." }, { "input": "The 12th session of RMET ( 15 min duration: 1 min at a respiration rate of 28 acts / min, 5 min at 32 acts / min, 5 min at 34 acts / min, 4 min at 36 acts / min ) was associated with blood samplings for determination of GH, cortisol, and lactate ( LA ) levels.", "output": "cortisol, lactate." }, { "input": "An age - and sex - matched normal - weighted control group ( n = 7, 4 M / 3 F, age: 26. 1 +/- 3. 1 years, BMI: 22. 4 +/- 0. 6 kg / m2 ) was also recruited.", "output": "There is no related enetity." }, { "input": "In both normal - weighted subjects and obese patients, GH secretion significantly increased after a 15 - min RMET session.", "output": "There is no related enetity." }, { "input": "Although serum GH levels at 30 min were higher in normal - weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups.", "output": "There is no related enetity." }, { "input": "RMET significantly increased serum cortisol levels in normal - weighted subjects, but was associated to a progressive cortisol decline in obese patients.", "output": "cortisol, cortisol." }, { "input": "RMET stimulated LA production, with no significant differences in normal - weighted subjects and in obese patients.", "output": "There is no related enetity." }, { "input": "A 15 - min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normal - weighted subjects.", "output": "There is no related enetity." }, { "input": "A progressive decline in serum cortisol levels occurred in obese patients after RMET, while an opposite pattern ( i. e., a significant cortisol increase ) was found in normal - weighted subjects.", "output": "cortisol, cortisol." }, { "input": "Optimization of long - term RMET protocols could represent a valid strategy to ( physiologically ) stimulate GH / IGF - I system in those GH hyposecretory states such as obesity.", "output": "There is no related enetity." }, { "input": "Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling.", "output": "There is no related enetity." }, { "input": "The molecular mechanisms by which cellular energy status regulates global protein synthesis in mammary epithelial cells have not been characterized.", "output": "There is no related enetity." }, { "input": "The objective of this study was to examine the effect of AMP - activated protein kinase ( AMPK ) activation by 2 - deoxyglucose on protein synthesis and the mammalian target of rapamycin complex 1 ( mTORC1 ) signaling pathway in bovine mammary epithelial cells.", "output": "2 - deoxyglucose, rapamycin." }, { "input": "Phosphorylation of AMPK at Thr172 increased by 1. 4 - fold within 5 min, and remained elevated throughout a 30 - min time course, in response to 2 - deoxyglucose.", "output": "Thr172, 2 - deoxyglucose." }, { "input": "Global rates of protein synthesis declined by 78 % of control values.", "output": "There is no related enetity." }, { "input": "The decline in protein synthesis was associated with repression of mTORC1 signaling, as indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein - 1 ( 4E - BP1 ).", "output": "There is no related enetity." }, { "input": "Phosphorylation of ER - stress marker eIF2 alpha was also increased but only at 30 min of 2 - deoxyglucose exposure.", "output": "2 - deoxyglucose." }, { "input": "2 - Deoxyglucose increased phosphorylation of tuberous sclerosis complex 2 ( TSC2 ) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2.", "output": "2 - Deoxyglucose." }, { "input": "Activation of AMPK did not result in changes in the amount of raptor bound to mTOR.", "output": "There is no related enetity." }, { "input": "The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor.", "output": "Ser792." }, { "input": "Collectively, the results suggest that activation of AMPK represses global protein synthesis in mammary epithelial cells through inhibition of mTORC1 signaling.", "output": "There is no related enetity." }, { "input": "Factors associated with the glucose - lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes.", "output": "glucose, vildagliptin, glucose." }, { "input": "In order to investigate the factors contributing to the glucose - lowering effect of vildagliptin, we analyzed the results of the oral glucose tolerance test together with several clinical parameters in Japanese patients with type 2 diabetes before and after 24 weeks of treatment with vildagliptin.", "output": "glucose, vildagliptin, glucose, vildagliptin." }, { "input": "The data of the 13 patients who satisfactorily completed the follow - up examinations were included.", "output": "There is no related enetity." }, { "input": "After 24 weeks treatment with vildagliptin, the patients were classified into a responder group ( 69. 2 % ) and a non - responder group ( 30. 8 % ); the responders consisting of subjects whose HbA1c decreased following 24 weeks treatment with vildagliptin, and the non - responders consisting of subjects who did not show any significant decrease of HbA1c.", "output": "vildagliptin, vildagliptin." }, { "input": "There were no differences in baseline characteristics between the two groups before administration of vildagliptin.", "output": "vildagliptin." }, { "input": "After 24 weeks of treatment, HbA1c was significantly reduced from 7. 3 +/- 0. 5 % to 6. 7 +/- 0. 5 % in the responder group ( P = 0. 0077 ), while it tended to rather increased from 7. 1 +/- 0. 6 % to 7. 5 +/- 0. 7 % in the non - responder group ( P = 0. 0679 ).", "output": "There is no related enetity." }, { "input": "Also, parameters reflecting the glucose - stimulated insulin secretion, such as the insulinogenic index and oral disposition index, were significantly higher in the responder group than in the non - responder group, whereas insulin sensitivity was similar between the two groups.", "output": "glucose." }, { "input": "These results suggest that the difference in the degree of improvement of the glucose tolerance between the responder group and non - responder group in this study could be associated with the effect of vildagliptin on the glucose - stimulated insulin secretion, but not on the insulin sensitivity.", "output": "glucose, vildagliptin, glucose." }, { "input": "Luminescent neutral platinum complexes bearing an asymmetric N ( ^ ) N ( ^ ) N ligand for high - performance solution - processed OLEDs.", "output": "platinum." }, { "input": "The synthesis and full characterization of new platinum complexes bearing a bulky asymmetric dianionic tridentate ligand is reported.", "output": "platinum." }, { "input": "The hindrance of the ligand prevents detrimental intermolecular interactions yielding to highly emitting species in both crystalline state and thin - film.", "output": "There is no related enetity." }, { "input": "Such properties prompted their successful use in solution - processed OLEDs, showing remarkable external quantum efficiency up to 5. 6 %.", "output": "There is no related enetity." }, { "input": "Alpha - asarone from Acorus gramineus alleviates epilepsy by modulating A - type GABA receptors.", "output": "Alpha - asarone, GABA." }, { "input": "Alpha ( alpha ) - asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear.", "output": "( alpha ) - asarone." }, { "input": "In this study, we have characterized the action of alpha - asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo.", "output": "alpha - asarone, pentylenetetrazole, kainate." }, { "input": "Under cell - attached configuration, the firing rate of spontaneous spiking was inhibited by application of alpha - asarone, which was maintained in the Mg ( 2 + ) - free solution.", "output": "alpha - asarone, Mg ( 2 + )." }, { "input": "Under whole - cell configuration, alpha - asarone induced inward currents in a concentration - dependent manner with an EC ( 50 ) of 248 +/- 33 mu M, which was inhibited by a GABA ( A ) receptor blocker picotoxin and a competitive GABA ( A ) receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine.", "output": "GABA, picotoxin, GABA, bicuculline, glycine, strychnine." }, { "input": "Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that alpha - asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected.", "output": "GABA, alpha - asarone." }, { "input": "In both pentylenetetrazole and kainate seizure models, alpha - asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABA ( A ) receptors.", "output": "pentylenetetrazole, kainate, alpha - asarone, GABA." }, { "input": "In summary, our results suggest that alpha - asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition.", "output": "alpha - asarone." }, { "input": "Mechanism of interaction of novel uncharged, centrally active reactivators with OP - hAChE conjugates.", "output": "There is no related enetity." }, { "input": "A library of more than 200 novel uncharged oxime reactivators was used to select and refine lead reactivators of human acetylcholinesterase ( hAChE ) covalently conjugated with sarin, cyclosarin, VX, paraoxon and tabun.", "output": "oxime, sarin, cyclosarin, paraoxon, tabun." }, { "input": "N - substituted 2 - hydroxyiminoacetamido alkylamines were identified as best reactivators and reactivation kinetics of the lead oximes, RS41A and RS194B, were analyzed in detail.", "output": "N - substituted 2 - hydroxyiminoacetamido alkylamines, oximes, RS41A, RS194B." }, { "input": "Compared to reference pyridinium reactivators, 2PAM and MMB4, molecular recognition of RS41A reflected in its Kox constant was compromised by an order of magnitude on average for different OP - hAChE conjugates, without significant differences in the first order maximal phosphorylation rate constant k2.", "output": "pyridinium, 2PAM, MMB4, RS41A." }, { "input": "Systematic structural modifications of the RS41A lead resulted in several - fold improvement with reactivator, RS194B.", "output": "RS41A, RS194B." }, { "input": "Kinetic analysis indicated Kox reduction for RS194B as the main kinetic constant leading to efficient reactivation.", "output": "RS194B." }, { "input": "Subtle structural modifications of RS194B were used to identify essential determinants for efficient reactivation.", "output": "RS194B." }, { "input": "Computational molecular modeling of RS41A and RS194B interactions with VX inhibited hAChE, bound reversibly in Michaelis type complex and covalently in the pentacoordinate reaction intermediate suggests that the faster reactivation reaction is a consequence of a tighter RS194B interactions with hAChE peripheral site ( PAS ) residues, in particular with D74, resulting in lower interaction energies for formation of both the binding and reactivation states.", "output": "RS41A, RS194B, RS194B." }, { "input": "Desirable in vitro reactivation properties of RS194B, when coupled with its in vivo pharmacokinetics and disposition in the body, reveal the potential of this oxime design as promising centrally and peripherally active antidotes for OP toxicity.", "output": "RS194B, oxime." }, { "input": "Emerging opportunities for allosteric modulation of G - protein coupled receptors.", "output": "There is no related enetity." }, { "input": "Their ubiquitous nature, wide cellular distribution and versatile molecular recognition and signalling help make G - protein binding receptors ( GPCRs ) the most important class of membrane proteins in clinical medicine, accounting for ~ 40 % of all current therapeutics.", "output": "There is no related enetity." }, { "input": "A large percentage of current drugs target the endogenous ligand binding ( orthosteric ) site, which are structurally and evolutionarily conserved, particularly among members of the same GPCR subfamily.", "output": "There is no related enetity." }, { "input": "With the recent advances in GPCR X - ray crystallography, new opportunities for developing novel subtype selective drugs have emerged.", "output": "There is no related enetity." }, { "input": "Given the increasing recognition that the extracellular surface conformation changes in response to ligand binding, it is likely that all GPCRs possess an allosteric site ( s ) capable of regulating GPCR signalling.", "output": "There is no related enetity." }, { "input": "Allosteric sites are less structurally conserved than their corresponding orthosteric site and thus provide new opportunities for the development of more selective drugs.", "output": "There is no related enetity." }, { "input": "Constitutive oligomerisation ( dimerisation ) identified in many of the GPCRs investigated, adds another dimension to the structural and functional complexity of GPCRs.", "output": "There is no related enetity." }, { "input": "In this review, we compare 60 crystal structures of nine GPCR subtypes ( rhodopsin, beta 2 - AR, beta 1 - AR, A ( 2a ) - AR, CXCR4, D 3 R, H 1 R, M 2 R, M 3 R ) across four subfamilies of Class A GPCRs, and discuss mechanisms involved in receptor activation and potential allosteric binding sites across the highly variable extracellular surface of these GPCRs.", "output": "There is no related enetity." }, { "input": "This analysis has identified a new extracellular salt bridge ( ESB - 2 ) that might be exploited in the design of allosteric modulators.", "output": "There is no related enetity." }, { "input": "Loss of HtrA2 / Omi activity in non - neuronal tissues of adult mice causes premature aging.", "output": "There is no related enetity." }, { "input": "mnd2 mice die prematurely as a result of neurodegeneration 30 - 40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2 / Omi.", "output": "There is no related enetity." }, { "input": "Here, we show that transgenic expression of human HtrA2 / Omi in the central nervous system of mnd2 mice rescues them from neurodegeneration and prevents their premature death.", "output": "There is no related enetity." }, { "input": "Interestingly, adult transgenic mnd2 mice develop accelerated aging phenotypes, such as premature weight loss, hair loss, reduced fertility, curvature of the spine, heart enlargement, increased autophagy, and death by 12 - 17 months of age.", "output": "There is no related enetity." }, { "input": "These mice also have elevated levels of clonally expanded mitochondrial DNA ( mtDNA ) deletions in their tissues.", "output": "There is no related enetity." }, { "input": "Our results provide direct genetic evidence linking mitochondrial protein quality control to mtDNA deletions and aging in mammals.", "output": "There is no related enetity." }, { "input": "CTNNA3 ( alpha - catenin ) gene variants are associated with diisocyanate asthma: a replication study in a caucasian worker population.", "output": "diisocyanate." }, { "input": "Recently, a genome - wide association study ( GWAS ) conducted in Korean subjects identified four CTNNA3 ( alpha - T catenin ) single nucleotide polymorphisms ( SNPs ) ( rs10762058, rs7088181, rs1786929, and rs4378283 ) associated with diisocyanate - induced occupational asthma ( DA ).", "output": "diisocyanate." }, { "input": "The CTNNA3 gene codes for a cadherin involved in formation of stretch - resistant cell - cell adhesions.", "output": "There is no related enetity." }, { "input": "We conducted a candidate gene association study to replicate these findings in Caucasian workers.", "output": "There is no related enetity." }, { "input": "Genotyping was performed on DNA using a 5 ' nuclease PCR assay collected from 410 diisocyanate - exposed and predominantly Canadian workers including 132 workers with DA confirmed by a specific inhalation challenge ( DA + ); 131 symptomatic workers in whom DA was excluded by a negative challenge ( DA - ); and 147 hexamethylene diisocyanate - exposed asymptomatic workers ( AWs ).", "output": "diisocyanate, hexamethylene diisocyanate." }, { "input": "As in the Korean study, highly linked CTNNA3 rs7088181 and rs10762058 SNPs ( but not rs4378283 and rs1786929 ) were significantly associated with DA + when compared with AWs but not in comparison with DA - workers ( p <= 0. 05 ).", "output": "There is no related enetity." }, { "input": "After adjusting for potentially confounding variables of age, smoking status, and duration of exposure, minor allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA compared with AWs ( OR = 9. 05 [ 95 % CI: 1. 69, 48. 54 ] and OR = 6. 82 [ 95 % CI: 1. 65, 28. 24 ], respectively ).", "output": "There is no related enetity." }, { "input": "In conclusion, we replicated results from the only reported GWAS study of DA demonstrating an association between two closely linked CTNNA3 gene SNPs and DA.", "output": "There is no related enetity." }, { "input": "These findings lend further support to the clinical relevance of these genotypes in predicting susceptibility to DA and the potential importance of catenins in the disease process.", "output": "There is no related enetity." }, { "input": "Something ' s got to give: psychiatric disease on the rise and novel drug development on the decline.", "output": "There is no related enetity." }, { "input": "Research and development of drugs for psychiatric disease is currently in a state of decline.", "output": "There is no related enetity." }, { "input": "Despite the increasing prevalence and healthcare costs of psychiatric disease, the costly and unpredictable drug development process has led to decreased public and investor confidence in the abilities of companies to develop safe and efficacious drugs.", "output": "There is no related enetity." }, { "input": "Industrial research in this disease area is therefore being scaled back owing to various scientific, corporate, financial and legal factors.", "output": "There is no related enetity." }, { "input": "This review will consider how these factors contribute to the current status of psychiatric drug development and offer several avenues forward to spur reinvestment in this type of research.", "output": "There is no related enetity." }, { "input": "Such a shift is needed to reduce the burden psychiatric disease imposes on the healthcare system and its patient populations.", "output": "There is no related enetity." }, { "input": "Oral delivery of anticancer drugs III: formulation using drug delivery systems.", "output": "There is no related enetity." }, { "input": "In the past few years, the growth of nanometric size drug delivery systems ( DDS ) has burst into challenging innovations enabling real progresses to achieve oral delivery of anticancer drugs.", "output": "There is no related enetity." }, { "input": "DDS, such as polymeric nanoparticles, micelles, dendrimers and lipid - based formulations enable physico - chemical properties of cytotoxic agents to be improved and oral bioavailability to be enhanced.", "output": "There is no related enetity." }, { "input": "In this review we highlight current DDS used for the oral delivery of anticancer drugs.", "output": "There is no related enetity." }, { "input": "Orphan drugs: the regulatory environment.", "output": "There is no related enetity." }, { "input": "The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country.", "output": "There is no related enetity." }, { "input": "The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide.", "output": "There is no related enetity." }, { "input": "Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length.", "output": "There is no related enetity." }, { "input": "Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined.", "output": "There is no related enetity." }, { "input": "This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America ( US ), European Union ( EU ), Japan, Australia, Singapore, Taiwan and Canada.", "output": "There is no related enetity." }, { "input": "The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared.", "output": "There is no related enetity." }, { "input": "The legislations and policies are to some extent similar but not the same.", "output": "There is no related enetity." }, { "input": "It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases.", "output": "There is no related enetity." }, { "input": "Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis.", "output": "There is no related enetity." }, { "input": "Acetylcholinesterase ( AChE ) at the neuromuscular junction ( NMJ ) is anchored to the synaptic basal lamina via a triple helical collagen Q ( ColQ ) in the form of asymmetric AChE ( AChE / ColQ ).", "output": "There is no related enetity." }, { "input": "The C - terminal domain of ColQ binds to MuSK, the muscle - specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor ( AChR ) clustering at the NMJ.", "output": "C, tyrosine, acetylcholine." }, { "input": "ColQ also binds to heparan sulfate proteoglycans including perlecan.", "output": "There is no related enetity." }, { "input": "Congenital defects of ColQ cause endplate AChE deficiency.", "output": "There is no related enetity." }, { "input": "A single intravenous administration of adeno - associated virus serotype 8 ( AAV8 ) - COLQ to Colq - / - mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ.", "output": "There is no related enetity." }, { "input": "We also injected AAV1 - COLQ - IRES - EGFP to the left tibialis anterior and observed colocalization of AChE / ColQ at all the examined NMJs of the non - injected limbs.", "output": "There is no related enetity." }, { "input": "Additionally, injection of purified recombinant AChE / ColQ protein complex into gluteus maximus accumulated AChE in non - injected forelimbs.", "output": "There is no related enetity." }, { "input": "These observations suggest that the tissue - targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue.", "output": "There is no related enetity." }, { "input": "MuSK antibody - positive myasthenia gravis ( MG ) accounts for 5 - 15 % of autoimmune MG.", "output": "There is no related enetity." }, { "input": "As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient ' s MuSK - IgG interferes with binding of ColQ to MuSK.", "output": "There is no related enetity." }, { "input": "In vitro overlay of AChE / ColQ to muscle sections of Colq - / - mice revealed that MuSK - IgG blocks binding of ColQ to the NMJ.", "output": "There is no related enetity." }, { "input": "In vitro plate - binding of MuSK to ColQ disclosed that MuSK - IgG exerts a dose - dependent block of MuSK - ColQ interaction.", "output": "There is no related enetity." }, { "input": "In addition, passive transfer of MuSK - IgG to mice reduced the size and density of ColQ to ~ 10 % of controls and had a lesser effect on the sizes and densities of AChR and MuSK.", "output": "There is no related enetity." }, { "input": "Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq - / - mice and to reveal bases of anti - MuSK MG.", "output": "There is no related enetity." }, { "input": "Verrucarin A sensitizes TRAIL - induced apoptosis via the upregulation of DR5 in an eIF2 alpha / CHOP - dependent manner.", "output": "Verrucarin A." }, { "input": "Tumor necrosis factor - related apoptosis - inducing ligand ( TRAIL ) is one of the most promising candidates for new cancer therapeutics.", "output": "There is no related enetity." }, { "input": "However, resistance to TRAIL in some cancers remains a current problem in recent.", "output": "There is no related enetity." }, { "input": "The protein - folding compartment of the endoplasmic reticulum ( ER ) is particularly sensitive to disturbances, which, if severe, may trigger apoptosis.", "output": "There is no related enetity." }, { "input": "Therefore, we examined whether verrucarin A ( VA ) sensitize TRAIL - induced apoptosis in cancer cells by induction of ER stress.", "output": "verrucarin A." }, { "input": "We first found that VA induces a major molecule of ER stress, CCAAT / enhancer binding protein homologous protein ( CHOP ) - dependent DR5 induction and subsequently increases TRAIL - induced cleavage of caspases and PARP in TRAIL - resistant Hep3B cells.", "output": "There is no related enetity." }, { "input": "Importantly, the transient knockdown using siRNA for CHOP abrogated VA - induced DR5 expression and attenuated TRAIL - induced apoptosis.", "output": "There is no related enetity." }, { "input": "Treatment with VA also increased the levels of phosphorylation of eukaryotic translation initiation factor - 2 alpha ( eIF2 alpha ), which is a common cellular response of ER stress.", "output": "There is no related enetity." }, { "input": "Furthermore, salubrinal, a specific eIF2 alpha phosphorylation - inducing agent, increased CHOP and DR5 expression in the presence of VA.", "output": "salubrinal." }, { "input": "In contrast, transfection of mutant - eIF2 alpha significantly reversed VA - induced apoptosis with downregulation of CHOP - dependent DR5 expression.", "output": "There is no related enetity." }, { "input": "Therefore, VA - induced eIF2 alpha phosphorylation seemed to be important for CHOP and DR5 upregulation and TRAIL - induced apoptosis.", "output": "There is no related enetity." }, { "input": "In addition, generation of reactive oxygen species ( ROS ) is an effector molecular in sensitization of VA - induced ER stress.", "output": "oxygen." }, { "input": "We concluded that VA triggers TRAIL - induced apoptosis by eIF2 alpha / CHOP - dependent DR5 induction via ROS generation.", "output": "There is no related enetity." }, { "input": "A chemistry wiki to facilitate and enhance compound design in drug discovery.", "output": "There is no related enetity." }, { "input": "At AstraZeneca a focus on hypothesis - driven design and the formation of drug design teams has placed a greater emphasis on collaboration in the drug discovery process.", "output": "There is no related enetity." }, { "input": "We have created a novel software tool based on the principles of wikis and social networks to facilitate collaborative working, visual planning and incorporation of predictive science to improve design capability.", "output": "There is no related enetity." }, { "input": "Monitoring the design and make process via the tool enabled the identification of bottlenecks and delays.", "output": "There is no related enetity." }, { "input": "Solutions to these problems were implemented, reducing the time taken from the initial idea stage to the generation of the synthesised compound by more than 50 %.", "output": "There is no related enetity." }, { "input": "A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds.", "output": "oxime, organophosphorus." }, { "input": "Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus ( OP ) compounds, which is usually attributed to OP inhibition of acetylcholinesterase ( AChE ).", "output": "oxime, organophosphorus." }, { "input": "Rate constants for reactivation of OP - inhibited AChE by even the best oximes, such as HI - 6 and obidoxime, can vary > 100 - fold between OP - AChE conjugates that are easily reactivated and those that are difficult to reactivate.", "output": "HI - 6, obidoxime." }, { "input": "To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues.", "output": "oxime, oxime." }, { "input": "Our objective was to identify common mechanism ( s ) among OP - AChE conjugates of phosphates, phosphonates and phosphoramidates that result in resistance to oxime reactivation.", "output": "phosphates, phosphonates, phosphoramidates, oxime." }, { "input": "Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O - methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O - methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70 - fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin.", "output": "oxime, O - methyl isopropylphosphonofluoridate, cyclosarin, O - methyl cyclohexylphosphonofluoridate, sarin, cyclosarin." }, { "input": "In addition, AChE inhibited by an analogue of tabun ( i. e., O - ethyl isopropylphosphonofluoridate ) was nearly as resistant to reactivation as tabun - inhibited AChE.", "output": "tabun, O - ethyl isopropylphosphonofluoridate, tabun." }, { "input": "QSAR analysis of oxime reactivation of AChE inhibited by these OP compounds and others suggested that the presence of both a large substituent ( i. e., <= the size of dimethylamine ) and an alkoxy substituent in the structure of OP compounds is the common feature that results in resistance to oxime reactivation of OP - AChE conjugates whether the OP is a phosphate, phosphonate or phosphoramidate.", "output": "dimethylamine, alkoxy, oxime, phosphate, phosphonate, phosphoramidate." }, { "input": "The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons.", "output": "amphetamines." }, { "input": "3, 4 - Methylenedioxymethamphetamine ( MDMA or \" Ecstasy \" ) and 2, 5 - dimethoxy - 4 - iodoamphetamine hydrochloride ( DOI ) are hallucinogenic amphetamines with addictive properties.", "output": "3 , 4 - Methylenedioxymethamphetamine, MDMA, Ecstasy, 2 , 5 - dimethoxy - 4 - iodoamphetamine hydrochloride, DOI, amphetamines." }, { "input": "The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine ' s neurotoxicity.", "output": "amphetamine." }, { "input": "We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos ( E - 17 to E - 19 ).", "output": "DOI, MDMA." }, { "input": "Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA ( 100 - 800 mu M ) or DOI ( 10 - 100 mu M ).", "output": "MDMA, DOI." }, { "input": "Both the lactate dehydrogenase ( LDH ) release and the tetrazolium - based ( MTT ) assays revealed a concentration - and time - dependent neuronal death and mitochondrial dysfunction after exposure to both drugs.", "output": "lactate, tetrazolium, MTT." }, { "input": "Both drugs promoted a significant increase in caspase - 8 and caspase - 3 activities.", "output": "There is no related enetity." }, { "input": "At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA.", "output": "DOI, MDMA." }, { "input": "In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor ( AIF ) by Western blot.", "output": "DOI, MDMA." }, { "input": "Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons.", "output": "DOI." }, { "input": "Pre - treatment with an antibody raised against the 5 - HT ( 2A ) - receptor ( an irreversible antagonist ) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA.", "output": "5 - HT, DOI, MDMA." }, { "input": "In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators.", "output": "amphetamines." }, { "input": "Death was dependent, at least in part, on the stimulation of the 5 - HT ( 2A ) - receptors.", "output": "5 - HT." }, { "input": "A DFT study on the initial stage of thermal degradation of Poly ( methyl methacrylate ) / carbon nanotube system.", "output": "Poly ( methyl methacrylate ), carbon." }, { "input": "DFT calculations, with VWN exchange correlation functional and double numeric basis set, were used to evaluate the energies required for the scission reactions taking place in the initial stage of the thermal degradation of Poly ( methyl methacrylate ) ( PMMA ) in the presence of a carbon nanotube ( CNT ).", "output": "Poly ( methyl methacrylate ), PMMA, carbon." }, { "input": "Side group and main chain scissions were investigated.", "output": "There is no related enetity." }, { "input": "The results averaged from five configurations of pure PMMA ( DP = 5 ) were used as references and compared to the results obtained for the five same configurations of PMMA grafted on three carbon nanotubes of similar diameter ( 1. 49 nm ).", "output": "PMMA, PMMA, carbon." }, { "input": "The bond dissociation energies ( BDE ) of main chain scission evaluated for grafted PMMA was 4 % less endothermic than for pure PMMA.", "output": "PMMA, PMMA." }, { "input": "These results seemed independent of the tested chirality ( 11, 11 ); ( 12, 10 ) and ( 16, 5 ) of the carbon nanotubes.", "output": "carbon." }, { "input": "Comparisons with the BDE of the weakest bonds due to intrinsic defaults ( head to head and unsaturated end chain ) were performed.", "output": "There is no related enetity." }, { "input": "Ectopic acromegaly due to growth hormone releasing hormone.", "output": "There is no related enetity." }, { "input": "Acromegaly secondary to extra - pituitary tumors secreting growth hormone releasing hormone ( GHRH ) is rarely encountered.", "output": "There is no related enetity." }, { "input": "We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma.", "output": "There is no related enetity." }, { "input": "Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed.", "output": "There is no related enetity." }, { "input": "Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas.", "output": "There is no related enetity." }, { "input": "We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma.", "output": "There is no related enetity." }, { "input": "Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression.", "output": "There is no related enetity." }, { "input": "Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs.", "output": "There is no related enetity." }, { "input": "The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly.", "output": "There is no related enetity." }, { "input": "Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long - term morbidity and mortality with ectopic acromegaly.", "output": "There is no related enetity." }, { "input": "Comparative cytological responses of lung epithelial and pleural mesothelial cells following in vitro exposure to nanoscale SiO2.", "output": "SiO2." }, { "input": "Due to unique surface chemistries and the ability to easily functionalize their surface, amorphous silica nanoparticles are being assimilated into medicinal and consumer products at an increasing rate.", "output": "silica." }, { "input": "Subsequently, there is an emergent need to understand the interactions of these particulates with biological systems in an attempt to mitigate toxicity.", "output": "There is no related enetity." }, { "input": "The identification of susceptible or resistant cell types of the pulmonary system remains a critical step in the development of toxicity assessments for nanoparticle - based platforms.", "output": "There is no related enetity." }, { "input": "Specific to this study, the cellular responses of A549 lung epithelial and MeT - 5A pleural mesothelial cell lines as a means of detecting nanoparticle - induced oxidative stress were examined.", "output": "There is no related enetity." }, { "input": "Basal expression and cellular antioxidant activity, including SOD, CAT, and GSH, were examined prior to H ( 2 ) O ( 2 ) and ~ 30 nm SiO ( 2 ) ( 0. 01 - 100mg / L ) exposures.", "output": "GSH, H ( 2 ) O ( 2 ), SiO ( 2 )." }, { "input": "Dose - response observations were made regarding oxidant production, cytotoxicity, GSH depletion and NRF2 transcription factor activation.", "output": "GSH." }, { "input": "Results indicated that, while both cell types exhibited susceptibility to H ( 2 ) O ( 2 ) and SiO ( 2 ) - induced oxidative stress and damage, the A549 cell line was relatively more resilient.", "output": "H ( 2 ) O ( 2 ), SiO ( 2 )." }, { "input": "Ultrasonic treatment and synthesis of sugar alcohol modified Na + - montmorillonite clay.", "output": "sugar alcohol, Na +, montmorillonite." }, { "input": "Na ( + ) - montmorillonite clay ( generally referred to as MMT ) is very useful for reinforcing polymeric matrix at very low concentrations ( typically, 2 - 5 % wt ).", "output": "Na ( + ), montmorillonite, MMT." }, { "input": "These clay particles are typically exfoliated before they can demonstrate the significant gains in heat deflection temperature, modulus, and elongation properties.", "output": "There is no related enetity." }, { "input": "In the case of hydrophilic biopolymer based matrices, such as carbohydrates and chitosan, exfoliating these nanoclay particles needs greater attention because the exfoliation is typically carried out using hydrophobic oligomers through ion - exchange.", "output": "carbohydrates." }, { "input": "This study reports a new method of synthesizing completely hydrophilic MMT - assemblages using hydrophilic plasticizers for biopolymers.", "output": "MMT." }, { "input": "We used sugar alcohols ( glycerol, xylitol with 3 and 5 hydroxyl groups ) and polysaccharide maltodextrin to exfoliate the MMT.", "output": "sugar alcohols, glycerol, xylitol, hydroxyl, MMT." }, { "input": "Sonication was conducted for MMT nanoclay and plasticizers at different weight ratios.", "output": "MMT." }, { "input": "It was confirmed that all plasticizer / modifier led to expansion of MMT gallery spacing ( d - spacing ) and the change in d - spacing could be related to the molecular structure of the plasticizer.", "output": "MMT." }, { "input": "Meanwhile, the extent of exfoliation was maximum with maltodextrin ( fully exfoliation with 1: 10 and 1: 20 ratio of MMT: plasticizer ) across all test samples and interestingly, glycerol and xylitol samples quickly established within the MMT galleries and exhibited minimal influence with further increase in relative concentrations.", "output": "MMT, glycerol, xylitol, MMT." }, { "input": "Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini - pigs.", "output": "isoflavones." }, { "input": "Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified.", "output": "isoflavones." }, { "input": "The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini - pigs, as well as the expression of adipokines and myokines.", "output": "isoflavones." }, { "input": "A total of 36 male Huanjiang mini - pigs were fed basal diet ( control, Con ), low - dose soy isoflavones ( LSI ) and high - dose soy isoflavones ( HSI ).", "output": "isoflavones, isoflavones." }, { "input": "The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous ( DSA ), abdominal subcutaneous ( ASA ) and perirenal ( PRA ) adipose tissue depots, as well as longissimus dorsi muscle ( LDM ) and liver.", "output": "fatty acids." }, { "input": "LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini - pigs.", "output": "There is no related enetity." }, { "input": "In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months.", "output": "isoflavones, glucose." }, { "input": "Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities.", "output": "isoflavones." }, { "input": "Decreased serum chemerin levels in male Japanese patients with type 2 diabetes: sex dimorphism.", "output": "There is no related enetity." }, { "input": "Chemerin, a recently discovered adipocytokine plays an important role in obesity and obesity - associated metabolic complications.", "output": "There is no related enetity." }, { "input": "However, the role of chemerin in the pathogenesis of type 2 diabetes mellitus ( T2DM ) has not fully been elucidated.", "output": "There is no related enetity." }, { "input": "We compared the serum chemerin levels and metabolic parameters between 88 control subjects, 86 patients with metabolic syndrome ( MS ), and 147 patients with T2DM in a Japanese population and further analyzed their correlation.", "output": "There is no related enetity." }, { "input": "Enzyme - linked immunosorbent assay was used to measure the serum chemerin levels.", "output": "There is no related enetity." }, { "input": "The chemerin levels were significantly higher in male than in female control subjects ( p < 0. 005 ), with significant decreases in patients with T2DM compared with those with MS and control subjects ( 164. 9 +/- 6. 3 ng / mL vs. 209. 8 +/- 7. 7 and 218. 7 +/- 7. 3 ng / mL; p < 0. 0001 vs. p < 0. 0001, respectively ) but no significant differences in female subjects.", "output": "There is no related enetity." }, { "input": "The multiple regression analysis revealed that the chemerin levels negatively correlated with the fasting glucose and HbA1c levels in total and male subjects.", "output": "glucose." }, { "input": "In the patients with T2DM, the chemerin levels negatively correlated with fasting glucose and high - density lipoprotein cholesterol but positively correlated with body mass index ( BMI ), and total cholesterol and triglyceride levels.", "output": "glucose, cholesterol, cholesterol, triglyceride." }, { "input": "The negative correlation between the chemerin and fasting glucose levels remained significant after adjustment for age, sex, and BMI in the total and male subjects and those with T2DM.", "output": "glucose." }, { "input": "These results suggest the role of chemerin in sex dimorphism and a potential link between chemerin levels and T2DM pathogenesis in a Japanese population.", "output": "There is no related enetity." }, { "input": "Comparative antioxidant effects of lycopene, apo - 10 ' - lycopenoic acid and apo - 14 ' - lycopenoic acid in human macrophages exposed to H2O2 and cigarette smoke extract.", "output": "apo - 10 ' - lycopenoic acid, apo - 14 ' - lycopenoic acid, H2O2." }, { "input": "Much of the beneficial effects of tomato lycopene in the prevention of chronic diseases has been attributed to its antioxidant properties, which could be mediated by its metabolites and / or oxidation products.", "output": "lycopene." }, { "input": "However, the biological functions of these lycopene derivatives remain still unknown.", "output": "lycopene." }, { "input": "In the present study, we evaluated and compared the antioxidant efficacy of the lycopene eccentric cleavage products apo - 10 ' - lycopenoic acid and apo - 14 ' - lycopenoic acid in counteracting the oxidative effects of H ( 2 ) O ( 2 ) and cigarette smoke extract ( CSE ) in THP - 1 macrophages.", "output": "lycopene, apo - 10 ' - lycopenoic acid, apo - 14 ' - lycopenoic acid, H ( 2 ) O ( 2 )." }, { "input": "Both apo - 10 ' - lycopenoic acid and apo - 14 ' - lycopenoic acid were able to inhibit spontaneous and H ( 2 ) O ( 2 ) - induced ROS production in a dose - dependent manner.", "output": "apo - 10 ' - lycopenoic acid, apo - 14 ' - lycopenoic acid, H ( 2 ) O ( 2 )." }, { "input": "Such an effect was accompanied by an inhibition of MAPK phosphorylation, by NF - kappa B inactivation, and by inhibition of hsp - 70 and hsp - 90 expressions.", "output": "There is no related enetity." }, { "input": "Both apo - lycopenoic acids also decreased CSE - induced ROS production, 8 - OHdG formation and reduced the increase in NOX - 4 and COX - 2 expressions caused by CSE.", "output": "apo - lycopenoic acids, 8 - OHdG." }, { "input": "However, in both the models of oxidative stress, apo - 14 ' - lycopenoic acid was much more potent as an antioxidant than apo - 10 ' - lycopenoic acid, showing antioxidant properties similar to lycopene.", "output": "apo - 14 ' - lycopenoic acid, apo - 10 ' - lycopenoic acid, lycopene." }, { "input": "These data strongly suggest that apo - lycopenoic acids, and particularly apo - 14 ' - lycopenoic acid, may mediate some of the antioxidant functions of lycopene in cells.", "output": "apo - lycopenoic acids, apo - 14 ' - lycopenoic acid." }, { "input": "Efficacy of all - trans retinoid acid in preventing nickel induced cardiotoxicity in myocardial cells of rats.", "output": "all - trans retinoid acid, nickel." }, { "input": "Nickel, a metal commonly found in battery plants and welding factories, has potential cardiotoxicity, while all - trans retinoid acid ( atRA ) can promote cardiovascular repair and myocardial recovery.", "output": "Nickel, all - trans retinoid acid, atRA." }, { "input": "The purpose of this study was to investigate whether atRA could prevent cardiotoxicity induced by nickel both in vitro and in vivo.", "output": "atRA, nickel." }, { "input": "In the study, a rat myocardial cell line ( H9c2 ) exposed to different concentrations of nickel chloride ( NiCl ( 2 ) ) displayed apoptotic features accompanied by reactive oxygen species generation.", "output": "nickel chloride, NiCl ( 2 ), oxygen." }, { "input": "In addition, NiCl ( 2 ) also caused obvious apoptosis and systolic dysfunction in primary myocardial cells.", "output": "NiCl ( 2 )." }, { "input": "Treatment with atRA efficiently attenuated the cytotoxicities triggered by NiCl ( 2 ) as it significantly mitigated ROS generation and decreased MAP kinases activity in NiCl ( 2 ) - treated cardiomyocytes.", "output": "atRA, NiCl ( 2 ), NiCl ( 2 )." }, { "input": "Additionally, NiCl ( 2 ) exposure caused obvious arrhythmia in Sprague - Dawley rats with the maximum tolerance dose of NiCl ( 2 ) between 2 and 3mg / kg.", "output": "NiCl ( 2 ), NiCl ( 2 )." }, { "input": "A combinational intragastric administration of 40mg / kg atRA can partially reverse NiCl ( 2 ) - induced arrhythmia in rats.", "output": "atRA, NiCl ( 2 )." }, { "input": "Our results suggested that atRA might have therapeutic potential in alleviating the adverse effects of nickel on the cardiovascular system.", "output": "atRA, nickel." }, { "input": "Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.", "output": "Pioglitazone, cisplatin." }, { "input": "Cisplatin - induced nephrotoxicity is a serious problem that limits its use in cancer treatment.", "output": "Cisplatin." }, { "input": "The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin - induced nephrotoxicity.", "output": "pioglitazone, cisplatin." }, { "input": "The underlying suggested mechanism ( s ) and whether this nephroprotective effect ( if any ) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated.", "output": "cisplatin." }, { "input": "Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected ( Peroxisome proliferator - activated receptor gamma ( PPAR - gamma ) antagonist ), or their combination were administered to rats one hour before cisplatin injection.", "output": "Pioglitazone, Bisphenol A diglycidyl ether, BADGE, cisplatin." }, { "input": "Moreover, their effects on the cell viability of human renal adenocarcinoma cell models ( ACHN ) were studied.", "output": "There is no related enetity." }, { "input": "The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde ( MDA ), tumor necrosis factor alpha ( TNF - alpha ), nuclear factor kappa B ( NF - kappa B ) genes expression in cisplatin injected rats.", "output": "pioglitazone, malondialdehyde, MDA, cisplatin." }, { "input": "It increased both renal reduced glutathione ( GSH ) content and PPAR - gamma gene expression.", "output": "glutathione, GSH." }, { "input": "In contrast to the data obtained by prior administration of BADGE.", "output": "BADGE." }, { "input": "Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration.", "output": "Pioglitazone, cisplatin, BADGE." }, { "input": "In conclusion, these results suggested that pioglitazone protected against cisplatin - induced nephrotoxicity through its interaction with PPAR - gamma receptors and antioxidant effects.", "output": "pioglitazone, cisplatin." }, { "input": "Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.", "output": "pioglitazone, cisplatin." }, { "input": "Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.", "output": "There is no related enetity." }, { "input": "The primary role of apolipoprotein E ( apoE ) is to mediate the cellular uptake of lipoproteins.", "output": "There is no related enetity." }, { "input": "However, a new role for apoE as a regulator of bone metabolism in mice has recently been established.", "output": "There is no related enetity." }, { "input": "In contrast to mice, the human APOE gene is characterized by three common isoforms APOE epsilon 2, epsilon 3, and epsilon 4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans.", "output": "There is no related enetity." }, { "input": "To clarify this, we investigated bone phenotypes of apoE knock - in ( k. i. ) mice, which express one human isoform each ( apoE2 k. i., apoE3 k. i., apoE4 k. i. ) in place of the mouse apoE.", "output": "There is no related enetity." }, { "input": "Analysis of 12 - week - old female k. i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k. i. animals as compared to apoE3 k. i. and apoE4 k. i., with a reduced osteoprotegerin ( OPG ) / receptor activator of NF - kappa B ligand ( RANKL ) ratio in apoE2 k. i., indicating increased turnover with prevailing resorption in apoE2 k. i.", "output": "There is no related enetity." }, { "input": "Accordingly, histomorphometric and micro - computed tomography ( micro CT ) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k. i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance.", "output": "There is no related enetity." }, { "input": "Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms.", "output": "There is no related enetity." }, { "input": "To extend these observations to the human situation, plasma from middle - aged healthy men homozygous for epsilon 2 / epsilon 2, epsilon 3 / epsilon 3, and epsilon 4 / epsilon 4 ( n = 21, n = 80, n = 55, respectively ) was analyzed with regard to bone turnover markers.", "output": "There is no related enetity." }, { "input": "In analogy to apoE2 k. i. mice, a lower OPG / RANKL ratio was observed in the serum of epsilon 2 / epsilon 2 carriers as compared to epsilon 3 / epsilon 3 and epsilon 4 / epsilon 4 individuals ( p = 0. 02 for epsilon 2 / epsilon 2 versus epsilon 4 / epsilon 4 ).", "output": "There is no related enetity." }, { "input": "In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE epsilon 2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans.", "output": "There is no related enetity." }, { "input": "Acute effect of calcium citrate on serum calcium and cardiovascular function.", "output": "calcium citrate, calcium." }, { "input": "Calcium supplements have been associated with an increased risk of cardiovascular events.", "output": "Calcium." }, { "input": "However, the validity of these findings has been questioned.", "output": "There is no related enetity." }, { "input": "A major concern is that the mechanism underlying an increase in cardiovascular events has not been demonstrated.", "output": "There is no related enetity." }, { "input": "Calcium initiates cardiac and vascular contraction following influx of calcium into cardiac and smooth muscle from extracellular fluid.", "output": "Calcium, calcium." }, { "input": "We have investigated whether the acute rise in serum calcium following calcium supplement administration is associated with adverse changes in cardiovascular function.", "output": "calcium, calcium." }, { "input": "In an open interventional study, we recruited 25 volunteers ( 16 female, age 60. 3 +/- 6. 5 years, body mass index 25. 7 +/- 2. 7 kg / m2 ) from the community who were not taking calcium supplements.", "output": "calcium." }, { "input": "Participants were studied before and 3 hours after a single oral dose of 1000 mg calcium citrate.", "output": "calcium citrate." }, { "input": "We assessed well - validated markers of arterial stiffness ( pulse wave velocity [ PWV ] ), arterial wave reflection ( augmentation index [ AIx ] ), and myocardial perfusion ( subendocardial viability ratio [ SEVR ] ) by pulse wave analysis and endothelial function ( reactive hyperemia index [ RHI ] ) by peripheral arterial tonometry.", "output": "There is no related enetity." }, { "input": "Total and ionized serum calcium were acutely increased by 0. 10 +/- 0. 07 and 0. 06 +/- 0. 03 mmol / L, respectively, 3 hours after calcium citrate administration ( p < 0. 0001 for both comparisons ).", "output": "calcium, calcium citrate." }, { "input": "Following administration of calcium citrate there was a fall in AIx from a median of 29. 7 % ( 23. 8 % to 34. 0 % ) to 26. 4 % ( 22. 7 % to 34. 0 %, p = 0. 03 ) and an increase in SEVR from 163 % ( 148 % to 174 % ) to 170 % ( 149 % to 185 %, p = 0. 007 ).", "output": "calcium citrate." }, { "input": "PWV and RHI were not significantly altered.", "output": "There is no related enetity." }, { "input": "The change in total calcium was negatively correlated with the change in AIx ( r = - 0. 48, p = 0. 02 ).", "output": "calcium." }, { "input": "In summary, the acute increase in serum calcium following calcium supplement administration is associated with reduced arterial wave reflection and a marker of increased myocardial perfusion.", "output": "calcium, calcium." }, { "input": "If maintained long - term, these changes would be expected to reduce cardiovascular risk.", "output": "There is no related enetity." }, { "input": "Acute serum calcium - mediated changes in these parameters of cardiovascular function are unlikely to underlie an association between calcium supplementation and cardiovascular events.", "output": "calcium, calcium." }, { "input": "Can peripheral blood gamma delta T cells predict osteonecrosis of the jaw?", "output": "There is no related enetity." }, { "input": "An immunological perspective on the adverse drug effects of aminobisphosphonate therapy.", "output": "aminobisphosphonate." }, { "input": "Nitrogen - bisphosphonates ( n - BP ), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility.", "output": "Nitrogen - bisphosphonates, n - BP, aminobisphosphonates." }, { "input": "However, long - term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate - associated osteonecrosis of the jaw ( BAONJ ).", "output": "bisphosphonate." }, { "input": "n - BP use is known to unintentionally activate a subset of innate T cells called V gamma 9V delta 2 T cells, but the consequence of this chronic immune stimulation has remained unexplored.", "output": "n - BP." }, { "input": "The primary objectives of this study were to 1 ) determine the fate of V gamma 9V delta 2 T cells in osteoporotic patients on n - BP therapy as a function of time and type of therapy; 2 ) evaluate the proportion of V gamma 9V delta 2 T cells in patients who had recently experienced n - BP - associated ONJ.", "output": "n - BP, n - BP." }, { "input": "We found there is a notable loss of V gamma 9V delta 2 T cells over time in osteoporotic patients on n - BP therapy, particularly those on intravenous ( iv ) therapy ( Spearman r = - 0. 55, p < 0. 0001 iv; r = - 0. 3, p < 0. 03 oral ) ( n = 68 ); no difference was observed in total T cells, monocytes, or granulocytes.", "output": "n - BP." }, { "input": "Importantly, the observed negative effect on V gamma 9V delta 2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ.", "output": "There is no related enetity." }, { "input": "Patients ( n = 6 ) who had experienced BAONJ were all found to be significantly deficient in V gamma 9V delta 2 T cells ( median = 0. 07 % ) in comparison to age - and sex - matched treatment - na i ve controls ( N = 11; median = 2. 40 % ), U = 0, p = 0. 001; this was the only consistent difference in the leukocytes assessed.", "output": "There is no related enetity." }, { "input": "All BAONJ cases had an underlying condition that further contributed to impaired immunity.", "output": "There is no related enetity." }, { "input": "We propose V gamma 9V delta 2 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n - BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ.", "output": "n - BP." }, { "input": "The role of adipokines in beta - cell failure of type 2 diabetes.", "output": "There is no related enetity." }, { "input": "beta - Cell failure coupled with insulin resistance is a key factor in the development of type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Changes in circulating levels of adipokines, factors released from adipose tissue, form a significant link between excessive adiposity in obesity and both aforementioned factors.", "output": "There is no related enetity." }, { "input": "In this review, we consider the published evidence for the role of individual adipokines on the function, proliferation, death and failure of beta - cells, focusing on those reported to have the most significant effects ( leptin, adiponectin, tumour necrosis factor alpha, resistin, visfatin, dipeptidyl peptidase IV and apelin ).", "output": "There is no related enetity." }, { "input": "It is apparent that some adipokines have beneficial effects whereas others have detrimental properties; the overall contribution to beta - cell failure of changed concentrations of adipokines in the blood of obese pre - diabetic subjects will be highly dependent on the balance between these effects and the interactions between the adipokines, which act on the beta - cell via a number of intersecting intracellular signalling pathways.", "output": "There is no related enetity." }, { "input": "We emphasise the importance, and comparative dearth, of studies into the combined effects of adipokines on beta - cells.", "output": "There is no related enetity." }, { "input": "Genetic correlate of cognitive training response in schizophrenia.", "output": "There is no related enetity." }, { "input": "Intensive computerized auditory training results in improved cognition for schizophrenia patients, but participants show variation in their cognitive gains and the biological factors that affect the response to training are unknown.", "output": "There is no related enetity." }, { "input": "Single nucleotide polymorphisms ( SNPs ) in the catechol - O - methyltransferase ( COMT ) gene have been related to cognitive function.", "output": "catechol, O." }, { "input": "Here we asked if functional variation in this gene has an impact on the response of schizophrenia patients to cognitive training.", "output": "There is no related enetity." }, { "input": "We genotyped 48 schizophrenia patients who completed 50 h of computerized cognitive training and analyzed the association between DNA variants in the COMT gene and the improvement in global cognition.", "output": "There is no related enetity." }, { "input": "Although conventional analyses did not reveal any significant associations, a set - based analysis examining the aggregate effect of common variation in the COMT gene ( 42 SNPs ) suggested association with improvement in global cognition.", "output": "There is no related enetity." }, { "input": "Eight SNPs, mostly located in the 3 ' end of the COMT gene, were nominally associated with improvement in cognition.", "output": "There is no related enetity." }, { "input": "These data suggest that genotype influences the response to intensive cognitive training in schizophrenia, and may indicate that cognitive training regimens need to be personalized to the underlying biosignatures of each individual patient.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Cognitive Enhancers '.", "output": "There is no related enetity." }, { "input": "Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation.", "output": "glucose." }, { "input": "Adipose triglyceride lipase ( ATGL ) is the predominant triacylglycerol ( TAG ) hydrolase in mammals; however, the tissue - specific effects of ATGL outside of adipose tissue have not been well characterized.", "output": "triglyceride, triacylglycerol, TAG." }, { "input": "Hence, we tested the contribution of hepatic ATGL on mediating glucose tolerance and insulin action.", "output": "glucose." }, { "input": "Glucose or insulin tolerance tests and insulin signaling were performed in C57BL / 6 mice administered control ( nongene specific shRNA ) or Atgl shRNA adenoviruses.", "output": "Glucose." }, { "input": "Glucose and lipid metabolism assays were conducted in primary hepatocytes isolated from mice transduced with control or Atgl shRNA adenoviruses.", "output": "Glucose." }, { "input": "Knocking down hepatic ATGL completely abrogated the increase in serum insulin following either 1 or 12 wk of feeding a high - fat ( HF ) diet despite higher hepatic TAG content.", "output": "TAG." }, { "input": "Glucose tolerance tests demonstrated that ATGL knockdown normalized glucose tolerance in HF - diet - fed mice.", "output": "Glucose, glucose." }, { "input": "The observed improvements in glucose tolerance were present despite unaltered hepatic insulin signaling and increased liver TAG.", "output": "glucose, TAG." }, { "input": "Mice with suppressed hepatic ATGL had reduced hepatic glucose production in vivo, and hepatocytes isolated from Atgl shRNA - treated mice displayed a 26 % decrease in glucose production and a 38 % increase in glucose oxidation compared to control cells.", "output": "glucose, glucose, glucose." }, { "input": "Taken together, these data suggest that hepatic ATGL knockdown enhances glucose tolerance by increasing hepatic glucose utilization and uncouples impairments in insulin action from hepatic TAG accumulation.", "output": "glucose, glucose, TAG." }, { "input": "Inference on population histories by approximating infinite alleles diffusion.", "output": "There is no related enetity." }, { "input": "Reconstruction of the past is an important task of evolutionary biology.", "output": "There is no related enetity." }, { "input": "It takes place at different points in a hierarchy of molecular variation, including genes, individuals, populations, and species.", "output": "There is no related enetity." }, { "input": "Statistical inference about population histories has recently received considerable attention, following the development of computational tools to provide tractable approaches to this very challenging problem.", "output": "There is no related enetity." }, { "input": "Here, we introduce a likelihood - based approach which generalizes a recently developed model for random fluctuations in allele frequencies based on an approximation to the neutral Wright - Fisher diffusion.", "output": "There is no related enetity." }, { "input": "Our new framework approximates the infinite alleles Wright - Fisher model and uses an implementation with an adaptive Markov chain Monte Carlo algorithm.", "output": "There is no related enetity." }, { "input": "The method is especially well suited to data sets harboring large population samples and relatively few loci for which other likelihood - based models are currently computationally intractable.", "output": "There is no related enetity." }, { "input": "Using our model, we reconstruct the global population history of a major human pathogen, Streptococcus pneumoniae.", "output": "There is no related enetity." }, { "input": "The results illustrate the potential to reach important biological insights to an evolutionary process by a population genetics approach, which can appropriately accommodate very large population samples.", "output": "There is no related enetity." }, { "input": "Crosslinked linear polyethylenimine enhances delivery of DNA to the cytoplasm.", "output": "polyethylenimine." }, { "input": "Crosslinked polyethylenimines ( PEIs ) have been frequently examined over the past decade since they can maintain the transfection efficiency of commercially available, 25k branched PEI, but exhibit less cytotoxicity.", "output": "polyethylenimines, PEIs, PEI." }, { "input": "The argument is often made that the degradability of such polymers, generally synthesized with either disulfide or hydrolytically degradable crosslinkers, is critical to the high efficiency and low toxicity of the system.", "output": "disulfide." }, { "input": "In this work, we present a crosslinked linear PEI ( xLPEI ) system in which either disulfide - responsive or non - degradable linkages are incorporated.", "output": "PEI, disulfide." }, { "input": "As with previous systems, strong transfection efficiency in comparison with commercial standards was achieved with low cytotoxicity.", "output": "There is no related enetity." }, { "input": "However, these properties were shown to be present when either the degradable or non - degradable crosslinker was used.", "output": "There is no related enetity." }, { "input": "Uncomplexed polymer was demonstrated to be the critical factor determining transfection efficiency for these polymers, mediating efficient endosomal escape without signs of cell membrane damage.", "output": "There is no related enetity." }, { "input": "While several crosslinked PEI systems in the literature have demonstrated the effect of the disulfide moiety, this work demonstrates that disulfide - mediated unpackaging may not be as important as conventionally thought for some PEI systems.", "output": "PEI, disulfide, disulfide, PEI." }, { "input": "Molecular phylogeny of North American Branchiobdellida ( Annelida: Clitellata ).", "output": "There is no related enetity." }, { "input": "Branchiobdellidans, or crayfish worms, are ectosymbiotic clitellate annelids associated primarily with freshwater crayfishes.", "output": "There is no related enetity." }, { "input": "The main objectives of our study were to infer a molecular phylogeny for the North American Branchiobdellida, examine its congruence with morphology - based hypotheses of relationships at the subfamily and genus level, and use our dataset to assess consistency of GenBank - archived branchiobdellidan sequences.", "output": "There is no related enetity." }, { "input": "We used nucleotide sequence data from two mtDNA genes ( COI and 16S rDNA ) and three nuclear genes ( 28S rDNA, 18S rDNA, and ITS1 ) to estimate phylogenetic relationships among 47 described and one undescribed species of Branchiobdellida.", "output": "nucleotide." }, { "input": "We recovered a monophyletic branchiobdellidan clade with generally short branch lengths, suggesting that a large portion of the taxon has likely undergone a recent and rapid radiation in North America.", "output": "There is no related enetity." }, { "input": "Results from our phylogenetic analyses indicate that current taxonomic groupings are largely unsupported by the molecular data.", "output": "There is no related enetity." }, { "input": "All four subfamilies are either paraphyletic or polyphyletic, and only three of seven sampled non - monotypic genera were monophyletic.", "output": "There is no related enetity." }, { "input": "We found a high rate ( 49 % ) of inconsistency in GenBank - archived sequences, over 70 % of which can be attributed to field - or laboratory - based error.", "output": "There is no related enetity." }, { "input": "Evidence for substrate - dependent inhibition profiles for human liver aldehyde oxidase.", "output": "aldehyde." }, { "input": "The goal of this study was to provide a reasonable assessment of how probe substrate selection may impact the results of in vitro aldehyde oxidase ( AO ) inhibition experiments.", "output": "aldehyde." }, { "input": "Here, we used a previously studied set of seven known AO inhibitors to probe the inhibition profile of a pharmacologically relevant substrate N - [ ( 2 - dimethylamino ) ethyl ] acridine - 4 - carboxamide ( DACA ).", "output": "N - [ ( 2 - dimethylamino ) ethyl ] acridine - 4 - carboxamide, DACA." }, { "input": "DACA oxidation in human liver cytosol was characterized with a measured V ( max ) of 2. 3 +/- 0. 08 nmol product. min ( - 1 ). mg ( - 1 ) and a K ( m ) of 6. 3 +/- 0. 8 micro M.", "output": "DACA." }, { "input": "The K ( ii ) and K ( is ) values describing the inhibition of DACA oxidation by the panel of seven inhibitors were tabulated and compared with previous findings with phthalazine as the substrate.", "output": "DACA, phthalazine." }, { "input": "In every case, the inhibition profile shifted to a much less uncompetitive mode of inhibition for DACA relative to phthalazine.", "output": "DACA, phthalazine." }, { "input": "With the exception of one inhibitor, raloxifene, this change in inhibition profile seems to be a result of a decrease in the uncompetitive mode of inhibition ( an affected K ( ii ) value ), whereas the competitive mode ( K ( is ) ) seems to be relatively consistent between substrates.", "output": "raloxifene." }, { "input": "Raloxifene was found to inhibit competitively when using DACA as a probe, and a previous report showed that raloxifene inhibited uncompetitively with other substrates.", "output": "Raloxifene, DACA, raloxifene." }, { "input": "The relevance of these data to the mechanistic understanding of aldehyde oxidase inhibition and potential implications on drug - drug interactions is discussed.", "output": "aldehyde." }, { "input": "Overall, it appears that the choice in substrate may be critical when conducting mechanistic inhibition or in vitro drug - drug interactions prediction studies with AO.", "output": "There is no related enetity." }, { "input": "Dual imaging and photoactivated nanoprobe for controlled cell tracking.", "output": "There is no related enetity." }, { "input": "A photoactivated nanoprobe for cell labeling and tracking is demonstrated.", "output": "There is no related enetity." }, { "input": "The nanoprobe enables all targeted cells to be imaged ( at 680 nm ) as well as specific cells to be photoactivated using 405 nm light.", "output": "There is no related enetity." }, { "input": "Photoactivated cells can then be tracked ( at 525 nm ) spatiotemporally in a separate channel over prolonged periods.", "output": "There is no related enetity." }, { "input": "Comparison of emetic potencies of the 8 - ketotrichothecenes deoxynivalenol, 15 - acetyldeoxynivalenol, 3 - acetyldeoxynivalenol, fusarenon X, and nivalenol.", "output": "8 - ketotrichothecenes deoxynivalenol, 15 - acetyldeoxynivalenol, 3 - acetyldeoxynivalenol, fusarenon X, nivalenol." }, { "input": "Although the acute toxic effects of trichothecene mycotoxin deoxynivalenol ( DON or vomitoxin ), a known cause of human food poisoning, have been well characterized in several animal species, much less is known about closely related 8 - ketotrichothecenes that similarly occur in cereal grains colonized by toxigenic fusaria.", "output": "trichothecene, deoxynivalenol, DON, vomitoxin, 8 - ketotrichothecenes." }, { "input": "To address this, we compared potencies of DON, 15 - acetyldeoxynivalenol ( 15 - ADON ), 3 - acetyldeoxynivalenol ( 3 - ADON ), fusarenon X ( FX ), and nivalenol ( NIV ) in the mink emesis model following intraperitoneal ( ip ) and oral administration.", "output": "DON, 15 - acetyldeoxynivalenol, 15 - ADON, 3 - acetyldeoxynivalenol, 3 - ADON, fusarenon X, nivalenol, NIV." }, { "input": "All five congeners dose - dependently induced emesis by both administration methods.", "output": "There is no related enetity." }, { "input": "With increasing doses, there were marked decreases in latency to emesis with corresponding increases in emesis duration and number of emetic events.", "output": "There is no related enetity." }, { "input": "The effective doses resulting in emetic events in 50 % of the animals for ip exposure to DON, 15 - ADON, 3 - ADON, FX, and NIV were 80, 170, 180, 70, and 60 micro g / kg bw, respectively, and for oral exposure, they were 30, 40, 290, 30, and 250 micro g / kg bw, respectively.", "output": "DON, 15 - ADON, 3 - ADON, NIV." }, { "input": "The emetic potency of DON determined here was comparable to that reported in analogous studies conducted in pigs and dogs, suggesting that the mink is a suitable small animal model for investigating acute trichothecene toxicity.", "output": "DON, trichothecene." }, { "input": "The use of a mouse pica model, based on the consumption of kaolin, was also evaluated as a possible surrogate for studying emesis but was found unsuitable.", "output": "kaolin." }, { "input": "From a public health perspective, comparative emetic potency data derived from small animal models such as the mink should be useful for establishing toxic equivalency factors for DON and other trichothecenes.", "output": "DON, trichothecenes." }, { "input": "SiC - CNT composite prepared by electrophoretic codeposition and the polymer infiltration and pyrolysis process.", "output": "SiC." }, { "input": "The paper reports on the successful anodic codeposition of submicrometer SiC powder and multiwalled carbon nanotubes from aqueous suspensions to form SiC - CNT composites.", "output": "SiC, carbon, SiC." }, { "input": "On the basis of the comprehensive analysis of the aqueous suspensions with different pHs, solids contents, and CNT contents, optimal conditions for deposition were determined.", "output": "There is no related enetity." }, { "input": "Besides having the necessary high absolute value of the zeta - potential, the suspensions that resulted in firm deposits were characterized by limited conductivity ( < 1 mS / cm ).", "output": "There is no related enetity." }, { "input": "Lowering of suspension conductivity was achieved either by dilution of the suspension or by dialysis of the as - received CNT suspension with high intrinsic conductivity.", "output": "There is no related enetity." }, { "input": "Selected SiC - CNT deposits were further densified by use of the polymer infiltration and pyrolysis process.", "output": "SiC." }, { "input": "Three - finger toxins, a deadly weapon of elapid venom - - milestones of discovery.", "output": "There is no related enetity." }, { "input": "Three - finger toxins ( TFTs ) are the main venom components of snakes from Elapidae family.", "output": "There is no related enetity." }, { "input": "Amino acid sequences of more than five hundreds TFTs are determined; these toxins form one of the largest protein families present in snake venoms.", "output": "Amino acid." }, { "input": "The first TFT alpha - bungarotoxin was isolated almost half a century ago and so far it remains a valuable tool in the study of nicotinic acetylcholine receptors.", "output": "acetylcholine." }, { "input": "TFTs possess diverse biological activities; for example, alpha - neurotoxins bind specifically with high affinity to nicotinic acetylcholine receptors, while cytotoxins induce non - specific lysis in great variety of cells.", "output": "acetylcholine." }, { "input": "These toxins are widely used as instruments in different branches of life sciences.", "output": "There is no related enetity." }, { "input": "In this review the main landmarks in TFT study are considered.", "output": "There is no related enetity." }, { "input": "These are the discovery and isolation of TFTs, determination of their structure and mode of action as well as evolution and relationship within the family.", "output": "There is no related enetity." }, { "input": "Bioconversion of quercetin and rutin and the cytotoxicity activities of the transformed products.", "output": "quercetin, rutin." }, { "input": "Quercetin and rutin are well - know flavonoids.", "output": "Quercetin, rutin, flavonoids." }, { "input": "In spite of this, the comprehension of their metabolism is still incomplete.", "output": "There is no related enetity." }, { "input": "In this work, the cytotoxic activity of quercetin and rutin and its metabolites produced by metabolism of filamentous fungi was investigated.", "output": "quercetin, rutin." }, { "input": "Flavonoids metabolism was monitored by HPLC and LC - MS.", "output": "Flavonoids." }, { "input": "Both flavonoids were extensively metabolized.", "output": "flavonoids." }, { "input": "Quercetin was converted into metabolite methylquercetin ( 2 ) and quercetin glucuronide ( 3 ) and rutin into metabolite rutin sulphate ( 5 ), methylrutin ( 6 ) and rutin glucuronide ( 7 ).", "output": "Quercetin, methylquercetin, quercetin glucuronide, rutin, rutin sulphate, methylrutin, rutin glucuronide." }, { "input": "Cytotoxic effects of rutin, quercetin and its metabolites were measured by MTT tetrazolium reduction test and the trypan blue exclusion assay on HL - 60 leukemic cells.", "output": "rutin, quercetin, MTT, tetrazolium, trypan blue." }, { "input": "The results showed similar concentration - dependent cytotoxic effect for rutin and rutin sulphate ( 5 ), while no cytotoxic effect was detected with the metabolites 6 and 7.", "output": "rutin, rutin sulphate." }, { "input": "In relation to the quercetin and its metabolites the results showed that all compounds have a similar concentration - dependent inhibitory effect on HL - 60 cells.", "output": "quercetin." }, { "input": "These findings corroborate the literature, showing that bioconversion is a useful strategy for production of biological active metabolites.", "output": "There is no related enetity." }, { "input": "Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes.", "output": "mollugin." }, { "input": "Mollugin originally isolated from Rubia cordifolia is a pharmacological compound for its anti - inflammation, anti - cancer, and anti - viral activity.", "output": "Mollugin." }, { "input": "In the present study, a cocktail probe assay was performed for determination of the selective inhibitory effect of mollugin on cytochrome P450 ( CYP ) enzymes in human liver microsomes ( HLM ).", "output": "mollugin." }, { "input": "Incubation of isoform - specific substrate probes CYPs with mollugin ( 0 - 25 mu M ) in HLM resulted in strong inhibition of CYP1A2 - catalyzed phenacetin O - deethylation, showing IC ( 50 ) values of 1. 03 and 3. 55 mu M without and with pre - incubation, respectively.", "output": "mollugin, phenacetin, O." }, { "input": "Mollugin - caused inhibition of phenacetin O - deethylation was concentration - dependent in HLMs, but not time - dependent.", "output": "Mollugin, phenacetin, O." }, { "input": "In addition, the Lineweaver - Burk plot indicated a typical competitive inhibition.", "output": "There is no related enetity." }, { "input": "Inhibitory effects of mollugin on human recombinant cDNA - expressed CYP1A1 and 1A2 were comparable.", "output": "mollugin." }, { "input": "Taken together, the results suggested that mollugin might cause herb - drug interaction through selective inhibition of CYP1A2 in humans receiving herbal medications, including R. cordifolia.", "output": "mollugin." }, { "input": "A 90 - day feeding study of glyphosate - tolerant maize with the G2 - aroA gene in Sprague - Dawley rats.", "output": "glyphosate." }, { "input": "Maize is not only a staple food crop but also an important raw material for feed and industry; however, the threat of weeds leads to a serious decline in its output and quality.", "output": "There is no related enetity." }, { "input": "The G2 - aroA gene confers glyphosate herbicide tolerance to crops.", "output": "glyphosate." }, { "input": "In this study, the food safety of genetically modified ( GM ), glyphosate - tolerant maize with the G2 - aroA gene was evaluated in a 90 - day feeding study in Sprague - Dawley ( SD ) rats.", "output": "glyphosate." }, { "input": "Maize grain from GM or non - GM isogenic control lines were separately formulated into rodent diets at concentrations of 12. 5 % ( low level ), 25 % ( middle level ), and 50 % ( high level ).", "output": "There is no related enetity." }, { "input": "An additional group of rats were fed a commercialized diet as a control.", "output": "There is no related enetity." }, { "input": "The toxicological response variables, including body weights, food consumption, serum biochemistry, hematology, and absolute and relative organ weights, were compared between rats fed GM maize and those fed non - GM maize after consumption of test diets for 90days.", "output": "There is no related enetity." }, { "input": "In addition, gross and microscopic pathology were conducted among treatment groups.", "output": "There is no related enetity." }, { "input": "No adverse effects related to the consumption of GM maize were detected in the subchronic feeding study.", "output": "There is no related enetity." }, { "input": "These results indicated that the GM glyphosate - tolerant maize was as safe and nutritious as conventional maize.", "output": "glyphosate." }, { "input": "Characterization of acetylcholinesterase in Hong Kong oyster ( Crassostrea hongkongensis ) from South China Sea.", "output": "There is no related enetity." }, { "input": "Acetylcholinesterase ( AChE ) activity has been used to evaluate the exposure of mollusk bivalves to organophosphates, carbamate pesticides, and heavy metals.", "output": "organophosphates, carbamate." }, { "input": "Crassostrea hongkongensis is a Hong Kong endemic oyster, and has a high commercial value along the coastal area of South China.", "output": "There is no related enetity." }, { "input": "The use of this species as a bio - indicator of the marine environment, and the use of AChE activity measurements in tissues of C. hongkongensis require prior characterization of AChE in this species.", "output": "There is no related enetity." }, { "input": "Here, we report that gill tissue contains the highest AChE activity in C. hongkongensis, and that the molecular form of AChE is most likely to be a dimeric form.", "output": "There is no related enetity." }, { "input": "In addition, the effect of the pesticide acephate on AChE activity in the gill of C. hongkongensis was analyzed, and the mean inhibition concentration ( IC50 ) value was determined.", "output": "There is no related enetity." }, { "input": "This study suggests that AChE activity in the gill tissue of C. hongkongensis might be used as a biomarker in monitoring organophosphate contamination in the marine fauna of South China.", "output": "organophosphate." }, { "input": "- 116A and K BCHE gene variants associated with obesity and hypertriglyceridemia in adolescents from Southern Brazil.", "output": "There is no related enetity." }, { "input": "Butyrylcholinesterase ( BChE ) has been associated to body mass index ( BMI ), weight, cholesterol and triglyceride levels.", "output": "cholesterol, triglyceride." }, { "input": "- 116A ( rs1126680 ) and K ( A539T, 1615A, rs1803274 ) BCHE gene variants had previously been associated to BChE activity, weight and BMI variance in adults.", "output": "There is no related enetity." }, { "input": "The present study examined - 116A and K variants, BChE activity, anthropometric and biochemical variables associated with obesity in adolescents ( 120 obese and 150 non - obese from Curitiba, Brazil ).", "output": "There is no related enetity." }, { "input": "Both - 116A and K variants were found with significantly lower frequencies ( p < 0. 05 ) in obese adolescents when compared with non - obese adolescents and with the general population.", "output": "There is no related enetity." }, { "input": "Mean BChE activity ( KU / L ) was significantly higher in obese adolescents when compared with non - obese adolescents and with the general population.", "output": "There is no related enetity." }, { "input": "Analyzing only the obese adolescents, it was found that carriers of the - 116A variant showed lower BChE activity and higher triglyceride levels than homozygotes for the usual allele.", "output": "triglyceride." }, { "input": "Indeed, obese carriers of the - 116A variant had triglyceride levels considered high according to reference values for serum triglycerides in Brazilian adolescents.", "output": "triglyceride, triglycerides." }, { "input": "These results show: ( 1 ) a protective effect of - 116A and K variants on juvenile obesity risk, suggesting a role for the BCHE gene on juvenile onset obesity different from that observed on adult onset obesity and ( 2 ) an association of the - 116A variant with hypertriglyceridemia in obese adolescents probably because of its effect on lowering BChE activity and consequently diminishing the enzyme capability of maintaining homeostasis on lipid metabolism during the metabolic stress caused by obesity.", "output": "There is no related enetity." }, { "input": "Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity.", "output": "cocaine." }, { "input": "Cocaine addiction affects millions of people with disastrous personal and social consequences.", "output": "Cocaine." }, { "input": "Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80 % chance of relapse.", "output": "Cocaine." }, { "input": "Yet there is no FDA - approved treatment to decrease the likelihood of relapse in rehabilitated addicts.", "output": "There is no related enetity." }, { "input": "Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase ( BChE ), which is capable of breaking down naturally occurring ( - ) - cocaine before the drug can influence the reward centers of the brain or affect other areas of the body.", "output": "( - ) - cocaine." }, { "input": "This activity of wild - type ( WT ) BChE, however, is relatively low.", "output": "There is no related enetity." }, { "input": "This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against ( - ) - cocaine.", "output": "( - ) - cocaine." }, { "input": "Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources.", "output": "cocaine." }, { "input": "Here, in expressing cocaine - hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus - assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof - of - principle that plants can express engineered BChE proteins with desired properties.", "output": "cocaine." }, { "input": "Experimental tooth movement - induced osteoclast activation is regulated by sympathetic signaling.", "output": "There is no related enetity." }, { "input": "Experimental tooth movement ( ETM ) changes the distribution of sensory nerve fibers in periodontal ligament and the bone architecture through the stimulation of bone remodeling.", "output": "There is no related enetity." }, { "input": "As the sympathetic nervous system is involved in bone remodeling, we examined whether ETM is controlled by sympathetic signaling or not.", "output": "There is no related enetity." }, { "input": "In male mice, elastic rubber was inserted between upper left first molar ( M1 ) and second molar ( M2 ) for 3 or 5 days.", "output": "There is no related enetity." }, { "input": "Nerve fibers immunoreactive for not only sensory neuromarkers, such as calcitonin gene - related peptide ( CGRP ), but also sympathetic neuromarkers, such as tyrosine hydroxylase ( TH ) and neuropeptide Y ( NPY ) were increased in the periodontal ligament during ETM.", "output": "tyrosine." }, { "input": "To elucidate the effect of the sympathetic signal mediated by ETM, mice were intraperitoneally injected with a beta - antagonist, propranolol ( PRO: 20 mu g / g / day ), or a beta - agonist, isoproterenol ( ISO: 5 mu g / g / day ) from 7 days before ETM.", "output": "propranolol, PRO, isoproterenol, ISO." }, { "input": "PRO treatment suppressed the amount of tooth movement by 12. 9 % in 3 - day ETM and by 32. 2 % in 5 - day ETM compared with vehicle treatment.", "output": "PRO." }, { "input": "On the other hand, ISO treatment increased it.", "output": "ISO." }, { "input": "Furthermore, ETM remarkably increased the osteoclast number on the bone surface ( alveolar socket ) ( Oc. N / BS ) in all drug treatments.", "output": "There is no related enetity." }, { "input": "PRO treatment suppressed Oc. N / BS by 39. 4 % in 3 - day ETM, while ISO treatment increased it by 32. 1 % in 3 - day ETM compared with vehicle treatment.", "output": "PRO, ISO." }, { "input": "Chemical sympathectomy using 6 - hydroxydopamine ( 6 - OHDA: 250 mu g / g ) showed results similar to those for PRO treatment in terms of both the amount of tooth movement and osteoclast parameters.", "output": "6 - hydroxydopamine, 6 - OHDA, PRO." }, { "input": "Our data showed that blockade of sympathetic signaling inhibited the tooth movement and osteoclast increase induced by ETM, and stimulation of sympathetic signaling accelerated these responses.", "output": "There is no related enetity." }, { "input": "These data suggest that the mechano - adaptive response induced by ETM is controlled by sympathetic signaling through osteoclast activation.", "output": "There is no related enetity." }, { "input": "Chronic toxicity of tire and road wear particles to water - and sediment - dwelling organisms.", "output": "There is no related enetity." }, { "input": "Tire and road wear particles ( TRWP ) consist of a complex mixture of rubber, and pavement released from tires during use on road surfaces.", "output": "There is no related enetity." }, { "input": "Subsequent transport of the TRWP into freshwater sediments has raised some concern about the potential adverse effects on aquatic organisms.", "output": "There is no related enetity." }, { "input": "Previous studies have shown some potential for toxicity for tread particles, however, toxicity studies of TRWP collected from a road simulator system revealed no acute toxicity to green algae, daphnids, or fathead minnows at concentrations up to 10, 000 mg / kg under conditions representative of receiving water bodies.", "output": "There is no related enetity." }, { "input": "In this study, the chronic toxicity of TRWP was evaluated in four aquatic species.", "output": "There is no related enetity." }, { "input": "Test animals were exposed to whole sediment spiked with TRWP at concentrations up to 10, 000 mg / kg sediment or elutriates from spiked sediment.", "output": "There is no related enetity." }, { "input": "Exposure to TRWP spiked sediment caused mild growth inhibition in Chironomus dilutus but had no adverse effect on growth or reproduction in Hyalella azteca.", "output": "There is no related enetity." }, { "input": "Exposure to TRWP elutriates resulted in slightly diminished survival in larval Pimephales promelas but had no adverse effect on growth or reproduction in Ceriodaphnia dubia.", "output": "There is no related enetity." }, { "input": "No other endpoints in these species were affected.", "output": "There is no related enetity." }, { "input": "These results, together with previous studies demonstrating no acute toxicity of TRWP, indicate that under typical exposure conditions TRWP in sediments pose a low risk of toxicity to aquatic organisms.", "output": "There is no related enetity." }, { "input": "Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism.", "output": "Levothyroxine, vitamin E." }, { "input": "Hypothyroidism has a variety of adverse effects on cognitive function.", "output": "There is no related enetity." }, { "input": "The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients.", "output": "levothyroxine." }, { "input": "Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease.", "output": "vitamin E." }, { "input": "Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit.", "output": "levothyroxine, vitamin E." }, { "input": "Sprague - Dawley rats were randomly divided into five groups: control group, PTU group, PTU + Vit E group, PTU + L - T4 group, and PTU + L - T4 + Vit E group.", "output": "PTU, PTU, Vit E, PTU, L - T4, PTU, L - T4, Vit E." }, { "input": "Serum and hippocampus malondialdehyde ( MDA ) levels were determined using the thiobarbituric - acid reactive substances method.", "output": "malondialdehyde, MDA, thiobarbituric - acid." }, { "input": "Serum and hippocampus superoxide dismutase ( SOD ) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium.", "output": "superoxide, nitroblue tetrazolium." }, { "input": "Learning and memory was assessed by Morris water maze test.", "output": "There is no related enetity." }, { "input": "In the present study, we found that the rats of PTU + Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group.", "output": "PTU, Vit E, PTU." }, { "input": "Moreover, the rats of PTU + L - T4 + Vit E group spent less time to find the platform on days 4 and 5 than the PTU + L - T4 group.", "output": "PTU, L - T4, Vit E, PTU, L - T4." }, { "input": "The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups.", "output": "There is no related enetity." }, { "input": "Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat.", "output": "There is no related enetity." }, { "input": "SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU + Vit E and PTU + L - T4 + Vit E groups than the PTU and PTU + L - T4 groups.", "output": "MDA, PTU, Vit E, PTU, L - T4, Vit E, PTU, PTU, L - T4." }, { "input": "Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU - induced hypothyroidism through the decrease of oxidative stress status.", "output": "levothyroxine, vitamin E, PTU." }, { "input": "Gold nanoprisms as optoacoustic signal nanoamplifiers for in vivo bioimaging of gastrointestinal cancers.", "output": "There is no related enetity." }, { "input": "Early detection of cancer greatly increases the chances of a simpler and more effective treatment.", "output": "There is no related enetity." }, { "input": "Traditional imaging techniques are often limited by shallow penetration, low sensitivity, low specificity, poor spatial resolution or the use of ionizing radiation.", "output": "There is no related enetity." }, { "input": "Hybrid modalities, like optoacoustic imaging, an emerging molecular imaging modality, contribute to improving most of these limitations.", "output": "There is no related enetity." }, { "input": "However, this imaging method is hindered by relatively low signal contrast.", "output": "There is no related enetity." }, { "input": "Here, gold nanoprisms ( AuNPrs ) are used as signal amplifiers in multispectral optoacoustic tomography ( MSOT ) to visualize gastrointestinal cancer.", "output": "There is no related enetity." }, { "input": "PEGylated AuNPrs are successfully internalized by HT - 29 gastrointestinal cancer cells in vitro.", "output": "There is no related enetity." }, { "input": "Moreover, the particles show good biocompatibility and exhibit a surface plasmon band centered at 830 nm, a suitable wavelength for optoacoustic imaging purposes.", "output": "There is no related enetity." }, { "input": "These findings extend well to an in vivo setting, in which mice are injected with PEGylated AuNPrs in order to visualize tumor angiogenesis in gastrointestinal cancer cells.", "output": "There is no related enetity." }, { "input": "Overall, both our in vitro and in vivo results show that PEGylated AuNPrs have the capacity to penetrate tumors and provide a high - resolution signal amplifier for optoacoustic imaging.", "output": "There is no related enetity." }, { "input": "The combination of PEGylated AuNPrs and MSOT represents a significant advance for the in vivo imaging of cancers.", "output": "There is no related enetity." }, { "input": "Arterial stiffness is inversely related to plasma adiponectin levels in young normotensive patients with type 1 diabetes.", "output": "There is no related enetity." }, { "input": "OBJECTIVE This study investigated the association between arterial stiffness and plasma adiponectin in patients with type 1 diabetes.", "output": "There is no related enetity." }, { "input": "RESEARCH DESIGN AND METHODS Participants were normotensive patients with type 1 diabetes who were up to age 40 years.", "output": "There is no related enetity." }, { "input": "Subjects on statins with macrovascular disease or overt nephropathy were excluded.", "output": "statins." }, { "input": "Large artery stiffness was assessed by measurement of carotid - femoral pulse wave velocity ( PWV ), whereas plasma adiponectin was measured by radioimmunoassay.", "output": "There is no related enetity." }, { "input": "RESULTS Data from 80 patients ( age 27. 1 +/- 6. 1 years, BMI 24. 2 +/- 3. 1 kg / m ( 2 ), HbA ( 1c ) 7. 5 +/- 1. 6 %, 39 men, adiponectin 13. 9 +/- 6. 7 mu g / mL, and PWV 5. 6 +/- 0. 9 m / s ) were analyzed.", "output": "There is no related enetity." }, { "input": "Log adiponectin inversely correlated with age - adjusted PWV ( r = - 0. 291, P = 0. 009 ) and waist circumference ( r = - 0. 427, P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "In a fully adjusted model, age, expiration / inspiration index, and log adiponectin were independently associated with PWV, explaining 39. 6 % of its variance.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS Arterial stiffness is inversely related to adiponectin concentration in young patients with type 1 diabetes without major complications.", "output": "There is no related enetity." }, { "input": "Effect of ifenprodil on GluN1 / GluN2B N - methyl - D - aspartate receptor gating.", "output": "ifenprodil, N - methyl - D - aspartate." }, { "input": "Ifenprodil is an allosteric inhibitor of GluN1 / GluN2B N - methyl - D - aspartate receptors.", "output": "Ifenprodil, N - methyl - D - aspartate." }, { "input": "Despite its widespread use as a prototype for drug development and a subtype - selective tool for physiologic experiments, its precise effect on GluN1 / GluN2B gating is yet to be fully understood.", "output": "There is no related enetity." }, { "input": "Interestingly, recent crystallographic evidence identified that ifenprodil, unlike zinc, binds at the interface of the GluN1 / GluN2B amino terminal domain dimer by an induced - fit mechanism.", "output": "ifenprodil ,, zinc, amino." }, { "input": "To delineate the effect of this unique binding on GluN1 / GluN2B receptor gating, we recorded steady - state currents from cell - attached and outside - out patches.", "output": "There is no related enetity." }, { "input": "At pH 7. 9 in cell - attached patches, ifenprodil increased the occupancy of the long - lived shut conformations, thereby reducing the open probability of the receptor with no change in the mean open time.", "output": "ifenprodil." }, { "input": "In addition, ifenprodil selectively affected the area of shut time constants, but not the time constants themselves.", "output": "ifenprodil." }, { "input": "Kinetic analyses suggested that ifenprodil prevents the transition of the receptor to an open state and increases its dwell time in an intrinsically occurring closed conformation or desensitized state.", "output": "ifenprodil." }, { "input": "We found distinct differences in the action of ifenprodil at GluN1 / GluN2B in comparison with previous studies on the effect of zinc on GluN1 / GluN2A gating, which may arise due to their unique binding sites.", "output": "ifenprodil, zinc." }, { "input": "Our data also uncover the potential pH - dependent action of ifenprodil on gating.", "output": "ifenprodil." }, { "input": "At a low pH ( pH 7. 4 ), but not pH 7. 9, ifenprodil reduces the mean open time of GluN1 / GluN2B receptors, which may be responsible for its usefulness as a context - dependent inhibitor in conditions like ischemia and stroke, when the pH of the extracellular milieu becomes acidic.", "output": "ifenprodil." }, { "input": "Developmental immunotoxicity of ethanol in an extended one - generation reproductive toxicity study.", "output": "ethanol." }, { "input": "The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols.", "output": "There is no related enetity." }, { "input": "In this study, a wide range of immune endpoints was included in an extended one - generation reproduction toxicity study ( EOGRTS ) design to determine the relative sensitivity of immune and developmental parameters to ethanol ( EtOH ), a well - known developmental toxicant with immunomodulatory properties.", "output": "ethanol, EtOH." }, { "input": "Adult Wistar rats were exposed to EtOH via drinking water ( 0, 1. 5, 4, 6. 5, 9, 11. 5 and 14 % ( w / v EtOH ) ) during premating, mating, gestation and lactation and continuation of exposure of the F ( 1 ) from weaning until killed.", "output": "EtOH, EtOH." }, { "input": "Immune assessments were performed at postnatal days ( PNDs ) 21, 42 and 70.", "output": "There is no related enetity." }, { "input": "Keyhole limpet hemocyanin ( KLH ) - specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35.", "output": "There is no related enetity." }, { "input": "EtOH exposure affected innate as well as adaptive immune responses.", "output": "EtOH." }, { "input": "The most sensitive immune parameters included white blood cell subpopulations, ConA - stimulated splenocyte proliferation, LPS - induced NO and TNF - alpha production by adherent splenocytes and KLH - specific immune responses.", "output": "NO." }, { "input": "Most parameters showed recovery after cessation of EtOH exposure after weaning in the 14 % exposure group.", "output": "EtOH." }, { "input": "However, effects on LPS - induced NO and TNF - alpha production by adherent splenocytes and KLH - specific parameters persisted until PND 70.", "output": "NO." }, { "input": "The results demonstrate the relative sensitivity to EtOH of especially functional immune parameters and confirm the added value of immune parameters in the EOGRTS.", "output": "EtOH." }, { "input": "Furthermore, this study identified an expanded KLH - specific parameter set and LPS - induced NO and TNF - alpha production by adherent splenocytes as valuable parameters that can provide additional information on functional immune effects.", "output": "NO." }, { "input": "Lack of enantioselectivity in the SULT1A3 - catalyzed sulfoconjugation of normetanephrine enantiomers: an in vitro and computational study.", "output": "normetanephrine." }, { "input": "( 1R ) - Normetanephrine is the natural stereoisomeric substrate for sulfotransferase 1A3 ( SULT1A3 ) - catalyzed sulfonation.", "output": "( 1R ) - Normetanephrine." }, { "input": "Nothing appears known on the enantioselectivity of the reaction despite its potential significance in the metabolism of adrenergic amines and in clinical biochemistry.", "output": "adrenergic amines." }, { "input": "We confronted the kinetic parameters of the sulfoconjugation of synthetic ( 1R ) - normetanephrine and ( 1S ) - normetanephrine by recombinant human SULT1A3 to a docking model of each normetanephrine enantiomer with SULT1A3 and the 3 ' - phosphoadenosine - 5 ' - phosphosulfate cofactor on the basis of molecular modeling and molecular dynamics simulations of the stability of the complexes.", "output": "( 1R ) - normetanephrine, ( 1S ) - normetanephrine, normetanephrine, 3 ' - phosphoadenosine - 5 ' - phosphosulfate." }, { "input": "The K ( M ), V ( max ), and k ( cat ) values for the sulfonation of ( 1R ) - normetanephrine, ( 1S ) - normetanephrine, and racemic normetanephrine were similar.", "output": "( 1R ) - normetanephrine, ( 1S ) - normetanephrine, normetanephrine." }, { "input": "In silico models were consistent with these findings as they showed that the binding modes of the two enantiomers were almost identical.", "output": "There is no related enetity." }, { "input": "In conclusion, SULT1A3 is not substrate - enantioselective toward normetanephrine, an unexpected finding explainable by a mutual adaptability between the ligands and SULT1A3 through an \" induced - fit model \" in the catalytic pocket.", "output": "There is no related enetity." }, { "input": "Bonding and electronic transport properties of fullerene and fullerene derivatives in break - junction geometries.", "output": "fullerene, fullerene." }, { "input": "Fullerenes are considered anchoring groups for molecular electronics due to a large contact area and their affinity for noble metals.", "output": "Fullerenes." }, { "input": "The conductances of fullerene - terminated molecules, however, are found to be even lower than for thiol termination.", "output": "fullerene, thiol." }, { "input": "The effects of weak molecule - metal coupling and symmetry breaking are studied by transport measurements of C ( 60 ) and functionalized C ( 60 ).", "output": "C ( 60 ), C ( 60 )." }, { "input": "The results demonstrate highy efficient contacts between Au and C ( 60 ), despite of deposition from solution.", "output": "Au, C ( 60 )." }, { "input": "Ocular perfusion pressure and ocular blood flow in glaucoma.", "output": "There is no related enetity." }, { "input": "Glaucoma is a progressive optic neuropathy of unknown origin.", "output": "There is no related enetity." }, { "input": "It has been hypothesized that a vascular component is involved in glaucoma pathophysiology.", "output": "There is no related enetity." }, { "input": "This hypothesis has gained support from studies showing that reduced ocular perfusion pressure is a risk factor for the disease.", "output": "There is no related enetity." }, { "input": "The exact nature of the involvement is, however, still a matter of debate.", "output": "There is no related enetity." }, { "input": "Based on recent evidence we propose a model including primary and secondary insults in glaucoma.", "output": "There is no related enetity." }, { "input": "The primary insult appears to happen at the optic nerve head.", "output": "There is no related enetity." }, { "input": "Increased intraocular pressure and ischemia at the post - laminar optic nerve head affects retinal ganglion cell axons.", "output": "There is no related enetity." }, { "input": "Modulating factors are the biomechanical properties of the tissues and cerebrospinal fluid pressure.", "output": "There is no related enetity." }, { "input": "After this primary insult retinal ganglion cells function at a reduced energy level and are sensitive to secondary insults.", "output": "There is no related enetity." }, { "input": "These secondary insults may happen if ocular perfusion pressure falls below the lower limit of autoregulation or if neurovascular coupling fails.", "output": "There is no related enetity." }, { "input": "Evidence for both faulty autoregulation and reduced hyperemic response to neuronal stimulation has been provided in glaucoma patients.", "output": "There is no related enetity." }, { "input": "The mechanisms appear to involve vascular endothelial dysfunction and impaired astrocyte - vessel signaling.", "output": "There is no related enetity." }, { "input": "A more detailed understanding of these pathways is required to direct neuroprotective strategies via the neurovascular pathway.", "output": "There is no related enetity." }, { "input": "The long road of research on snake venom serine proteinases.", "output": "serine." }, { "input": "It has long been recognized that snake venom serine proteinases ( SVSPs ) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation.", "output": "serine." }, { "input": "Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions.", "output": "There is no related enetity." }, { "input": "The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century.", "output": "There is no related enetity." }, { "input": "It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field.", "output": "There is no related enetity." }, { "input": "A brief review of the scientific history of several lesser - known snake venom proteins: l - amino acid oxidases, hyaluronidases and phosphodiesterases.", "output": "l - amino acid." }, { "input": "When considering the proteins and toxins in snake venom one ' s thoughts generally migrate to the proteinases, neurotoxins and phospholipases since these families of proteins are comprised by many of the toxins found in venom.", "output": "There is no related enetity." }, { "input": "However as modern proteomic and transcriptomic venom research has abundantly shown snake venoms are complex and containing numerous families of protein beyond the \" big three \".", "output": "There is no related enetity." }, { "input": "In this brief review we will discuss three of the lesser discussed proteins typically found in snake venoms: l - amino acid oxidases ( LAAO ); hyaluronidases and phosphodiesterases.", "output": "l - amino acid." }, { "input": "These proteins have long been known to be part of many venoms ' proteomes with reports appearing in the literature as early as 1944 for LAAO, 1947 for hyaluronidase ( spreading factor ), and 1932 for venom phosphodiesterase.", "output": "There is no related enetity." }, { "input": "These are more or less contemporary with the first reports ( circa 1950 ) on snake venom proteases.", "output": "There is no related enetity." }, { "input": "Thus, the relatively modest literature on these snake venom proteins stems not from lack of early discovery but rather more likely to their ostensibly minor role in snake venom pathophysiology.", "output": "There is no related enetity." }, { "input": "In this review we will provide an overview of the experimental history of these venom proteins, their biochemical and structural features and their role in snake venom toxinology with the aim of bringing a fuller, more comprehensive, understanding of the history of laboratory research on snake venoms.", "output": "There is no related enetity." }, { "input": "In addition, there are some comments on these proteins from investigators who were actively engaged in their investigation.", "output": "There is no related enetity." }, { "input": "Functional and structural interaction of ( - ) - reboxetine with the human alpha 4 beta 2 nicotinic acetylcholine receptor.", "output": "( - ) - reboxetine, acetylcholine." }, { "input": "The interaction of the selective norepinephrine reuptake inhibitor ( - ) - reboxetine with the human alpha 4 beta 2 nicotinic acetylcholine receptor ( nAChR ) in different conformational states was studied by several functional and structural approaches.", "output": "norepinephrine, ( - ) - reboxetine, acetylcholine." }, { "input": "Patch - clamp and Ca ( 2 + ) - influx results indicate that ( - ) - reboxetine does not activate h alpha 4 beta 2 nAChRs via interaction with the orthosteric sites, but inhibits agonist - induced h alpha 4 beta 2 activation by a noncompetitive mechanism.", "output": "Ca ( 2 + ), ( - ) - reboxetine." }, { "input": "Consistently, the results from the electrophysiology - based functional approach suggest that ( - ) - reboxetine may act via open channel block; therefore, it is capable of producing a use - dependent type of inhibition of the h alpha 4 beta 2 nAChR function.", "output": "( - ) - reboxetine." }, { "input": "We tested whether ( - ) - reboxetine binds to the luminal [ ( 3 ) H ] imipramine site.", "output": "( - ) - reboxetine, [ ( 3 ) H ] imipramine." }, { "input": "The results indicate that, although ( - ) - reboxetine binds with low affinity to this site, it discriminates between the resting and desensitized h alpha 4 beta 2 nAChR ion channels.", "output": "( - ) - reboxetine." }, { "input": "Patch - clamp results also indicate that ( - ) - reboxetine progressively inhibits the h alpha 4 beta 2 nAChR with two - fold higher potency at the end of one - second application of agonist, compared with the peak current.", "output": "( - ) - reboxetine." }, { "input": "The molecular docking studies show that ( - ) - reboxetine blocks the ion channel at the level of the imipramine locus, between M2 rings 6 ' and 14 '.", "output": "( - ) - reboxetine, imipramine." }, { "input": "In addition, we found a ( - ) - reboxetine conformer that docks in the helix bundle of the alpha 4 subunit, near the middle region.", "output": "( - ) - reboxetine." }, { "input": "According to molecular dynamics simulations, ( - ) - reboxetine binding is stable for both sites, albeit less stable than imipramine.", "output": "( - ) - reboxetine, imipramine." }, { "input": "The interaction of these drugs with the helix bundle might alter allostericaly the functionality of the channel.", "output": "There is no related enetity." }, { "input": "In conclusion, the clinical action of ( - ) - reboxetine may be produced ( at least partially ) by its inhibitory action on h alpha 4 beta 2 nAChRs.", "output": "( - ) - reboxetine." }, { "input": "Proteins with an alpha / beta hydrolase fold: Relationships between subfamilies in an ever - growing superfamily.", "output": "There is no related enetity." }, { "input": "Alpha / beta hydrolases function as hydrolases, lyases, transferases, hormone precursors or transporters, chaperones or routers of other proteins.", "output": "There is no related enetity." }, { "input": "The amount of structural and functional available data related to this protein superfamily expands exponentially, as does the number of proteins classified as alpha / beta hydrolases despite poor sequence similarity and lack of experimental data.", "output": "There is no related enetity." }, { "input": "However the superfamily can be rationally divided according to sequence or structural homologies, leading to subfamilies of proteins with potentially similar functions.", "output": "There is no related enetity." }, { "input": "Since the discovery of proteins homologous to cholinesterases but devoid of enzymatic activity ( e. g., the neuroligins ), divergent functions have been ascribed to members of other subfamilies ( e. g., lipases, dipeptidylaminopeptidase IV, etc. ).", "output": "There is no related enetity." }, { "input": "To study the potentially moonlighting properties of alpha / beta hydrolases, the ESTHER database ( for ESTerase and alpha / beta Hydrolase Enzymes and Relatives; http: / / bioweb. ensam. inra. fr / esther ), which collects, organizes and disseminates structural and functional information related to alpha / beta hydrolases, has been updated with new tools and the web server interface has been upgraded.", "output": "There is no related enetity." }, { "input": "A new Overall Table along with a new Tree based on HMM models has been included to tentatively group subfamilies.", "output": "There is no related enetity." }, { "input": "These tools provide starting points for phylogenetic studies aimed at pinpointing the origin of duplications leading to paralogous genes ( e. g., acetylcholinesterase versus butyrylcholinesterase, or neuroligin versus carboxylesterase ).", "output": "There is no related enetity." }, { "input": "Another of our goals is to implement new tools to distinguish catalytically active enzymes from non - catalytic proteins in poorly studied or annotated subfamilies.", "output": "There is no related enetity." }, { "input": "Enantioselective apoptosis induction in histiocytic lymphoma cells and acute promyelocytic leukemia cells.", "output": "There is no related enetity." }, { "input": "The aim of this study was to identify valproic acid ( VPA ) analogs with a broad spectrum of anti - cancer activities and an increased apoptosis - inducing potential compared with the parent VPA, which is enrolled as histone deacetylase ( HDAC ) inhibitor in a large number of clinical trials.", "output": "valproic acid, VPA, VPA." }, { "input": "We identified a chiral VPA derivative, ( S ) - 2 - pentyl - 4 - pentynoic acid, previously characterized as HDAC inhibitor that induced massive programmed cell death in a strongly enantioselective manner in U937 histiocytic lymphoma cells and NB4 acute promyelocytic leukemia cells.", "output": "VPA, ( S ) - 2 - pentyl - 4 - pentynoic acid." }, { "input": "By performing fluorescence - activated cell sorting and Western blotting analyses, we established that enantiomer ( S ) - 2 - pentyl - 4 - pentynoic acid has higher apoptosis - inducing potential than VPA itself.", "output": "( S ) - 2 - pentyl - 4 - pentynoic acid, VPA." }, { "input": "The optic antipode ( R ) - 2 - pentyl - 4 - pentynoic acid and VPA caused under the same conditions only a weak growth inhibition without inducing cell differentiation and apoptosis.", "output": "( R ) - 2 - pentyl - 4 - pentynoic acid, VPA." }, { "input": "( S ) - 2 - pentyl - 4 - pentynoic acid is more apoptogenic than VPA and displays enantioselective anti - cancer properties that warrant further research regarding the mechanistic basis of its activity and its potential use in cancer therapy.", "output": "( S ) - 2 - pentyl - 4 - pentynoic acid, VPA." }, { "input": "Influence of pH, light cycle, and temperature on ecotoxicity of four sulfonylurea herbicides towards Lemna gibba.", "output": "sulfonylurea." }, { "input": "In chemical regulation, e. g. the EU Water Framework Directive, REACH, or the Pesticide Directive, standardized ecotoxicological tests are applied to evaluate and rank the hazard of compounds and for deriving environmental quality standards ( EQS ).", "output": "There is no related enetity." }, { "input": "Standardized test methods prescribe fixed testing conditions e. g. specific temperature, pH, light intensity etc.", "output": "There is no related enetity." }, { "input": "However, environmental conditions under which the organisms live are rarely identical to the standard conditions.", "output": "There is no related enetity." }, { "input": "Thus, the ecotoxicity of compounds found in standard test is not only a function of the compounds inherent physico - chemical properties but is also affected by test conditions.", "output": "There is no related enetity." }, { "input": "It is therefore important to study the effect of changes in test conditions in order to get reliable input ecotoxicity data for assessing the potential risk posed by a compound.", "output": "There is no related enetity." }, { "input": "The objective of this study was to investigate the implications of changing test conditions on the toxicity of four sulfonylurea herbicides ( SUs ).", "output": "sulfonylurea." }, { "input": "The toxicity of the four SUs towards Lemna gibba was investigated at three pH levels ( 6, 7. 5 and 9 ), at two temperatures ( 15 and 24 degrees C ) and two light regimes ( continuous and 12: 12 h light: dark cycle ) The EC50 increased twofold to tenfold for the four SUs when pH was increased from 6 to 9.", "output": "There is no related enetity." }, { "input": "Decreasing the temperature from 24 to 15 degrees C or introducing a dark: light cycle did not cause any trends in changes in toxicity.", "output": "There is no related enetity." }, { "input": "The results show that test conditions can have an effect on the toxicity and this should be considered when the standard test results are used for derivation of EQS.", "output": "There is no related enetity." }, { "input": "Nondestructive indices of mercury exposure in three species of turtles occupying different trophic niches downstream from a former chloralkali facility.", "output": "mercury." }, { "input": "Turtles are useful for studying bioaccumulative pollutants such as mercury ( Hg ) because they have long life spans and feed at trophic levels that result in high exposure to anthropogenic chemicals.", "output": "mercury, Hg." }, { "input": "We compared total Hg concentrations in blood and toenails of three species of turtles ( Chelydra serpentina, Sternotherus odoratus, and Graptemys geographica ) with different feeding ecologies from locations up - and downstream of a superfund site in Virginia, USA.", "output": "Hg." }, { "input": "Mercury concentrations in turtle tissues were low at the reference site ( average +/- 1SE: blood = 48 +/- 6 ng g ( - 1 ); nail = 2, 464 +/- 339 ng g ( - 1 ) FW ) but rose near the contamination source to concentrations among the highest ever reported in turtles [ up to 1, 800 ng g ( - 1 ) ( blood ) and 42, 250 ng g ( - 1 ) ( nail ) FW ].", "output": "Mercury." }, { "input": "Tissue concentrations remained elevated ~ 130 km downstream from the source compared to reference concentrations.", "output": "There is no related enetity." }, { "input": "Tissue Hg concentrations were higher for C. serpentina and S. odoratus than G. geographica, consistent with the feeding ecology and our stable isotope ( delta ( 13 ) C and delta ( 15 ) N ) analyses of these species.", "output": "Hg, ( 13 ) C, ( 15 ) N." }, { "input": "In addition, we suggest that toenails were a better indication of Hg exposure than blood, probably because this keratinized tissue represents integrated exposure over time.", "output": "Hg." }, { "input": "Our results demonstrate that downstream transport of Hg from point sources can persist over vast expanses of river thereby posing potential exposure risks to turtles, but relative exposure varies with trophic level.", "output": "Hg." }, { "input": "In addition, our study identifies turtle toenails as a simple, cost - efficient, and minimally invasive tissue for conservation - minded sampling of these long - lived vertebrates.", "output": "There is no related enetity." }, { "input": "Comparative analysis of the protective effects of caffeic acid phenethyl ester ( CAPE ) on pulmonary contusion lung oxidative stress and serum copper and zinc levels in experimental rat model.", "output": "caffeic acid phenethyl ester, CAPE, copper, zinc." }, { "input": "The aim of this study was to investigate the effects of caffeic acid phenethyl ester ( CAPE ) in the lungs by biochemical and histopathological analyses in an experimental isolated lung contusion model.", "output": "caffeic acid phenethyl ester, CAPE." }, { "input": "Eighty - one male Sprague - Dawley rats were used.", "output": "There is no related enetity." }, { "input": "The animals were divided randomly into four groups: group 1 ( n = 9 ) was defined as without contusion and without CAPE injection.", "output": "CAPE." }, { "input": "Group 2 ( n = 9 ) was defined as CAPE 10 mu mol / kg injection without lung contusion.", "output": "CAPE." }, { "input": "Group 3 ( n = 36 ) was defined as contusion without CAPE - administrated group which consisted of four subgroups that were created according to analysis between days 0, 1, 2, and 3.", "output": "CAPE." }, { "input": "Group 4 ( n = 27 ) was defined as CAPE 10 mu mol / kg administrated after contusion group divided into three subgroups according to analysis on days 1, 2, and 3.", "output": "CAPE." }, { "input": "CAPE 10 mu mol / kg was injected intraperitoneally 30 min after trauma and on days 1 and 2.", "output": "CAPE." }, { "input": "Blood samples were obtained to measure catalase ( CAT ) and superoxide dismutase ( SOD ) activities and level of malondialdehyde ( MDA ) and for blood gas analysis.", "output": "superoxide, malondialdehyde, MDA." }, { "input": "Trace elements such as zinc and copper were measured in serum.", "output": "zinc, copper." }, { "input": "The lung tissue was also removed for histopathological examination.", "output": "There is no related enetity." }, { "input": "Isolated lung contusion increased serum and tissue SOD and CAT activities and MDA levels ( p < 0. 05 ).", "output": "MDA." }, { "input": "Both serum and tissue SOD, MDA, and CAT levels on day 3 were lower in group 4 compared to group 3 ( p < 0. 05 ).", "output": "MDA." }, { "input": "Further, the levels of SOD, MDA, and CAT in group 4 were similar compared to group 1 ( p > 0. 05 ).", "output": "MDA." }, { "input": "CAPE also had a significant beneficial effect on blood gases ( p < 0. 05 ).", "output": "CAPE." }, { "input": "Both serum zinc and copper levels were ( p < 0. 05 ) influenced by the administration of CAPE.", "output": "zinc, copper, CAPE." }, { "input": "Histopathological examination revealed lower scores in group 4 compared to group 3 ( p < 0. 05 ) and no significant differences compared to group 1 ( p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "CAPE appears to be effective in protecting against severe oxidative stress and tissue damage caused by pulmonary contusion in an experimental setting.", "output": "CAPE." }, { "input": "Therefore, we conclude that administration of CAPE may be used for a variety of conditions associated with pulmonary contusion.", "output": "CAPE." }, { "input": "Clinical use of CAPE may have the advantage of prevention of pulmonary contusion.", "output": "CAPE." }, { "input": "Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse.", "output": "There is no related enetity." }, { "input": "Carboxylesterases ( CES ) are a well recognized, yet incompletely characterized family of proteins that catalyze neutral lipid hydrolysis.", "output": "There is no related enetity." }, { "input": "Some CES have well - defined roles in xenobiotic clearance, pharmacologic prodrug activation, and narcotic detoxification.", "output": "There is no related enetity." }, { "input": "In addition, emerging evidence suggests other CES may have roles in lipid metabolism.", "output": "There is no related enetity." }, { "input": "Humans have six CES genes, whereas mice have 20 Ces genes grouped into five isoenzyme classes.", "output": "There is no related enetity." }, { "input": "Perhaps due to the high sequence similarity shared by the mouse Ces genes, the tissue - specific distribution of expression for these enzymes has not been fully addressed.", "output": "There is no related enetity." }, { "input": "Therefore, we performed studies to provide a comprehensive tissue distribution analysis of mouse Ces mRNAs.", "output": "There is no related enetity." }, { "input": "These data demonstrated that while the mouse Ces family 1 is highly expressed in liver and family 2 in intestine, many Ces genes have a wide and unique tissue distribution defined by relative mRNA levels.", "output": "There is no related enetity." }, { "input": "Furthermore, evaluating Ces gene expression in response to pharmacologic activation of lipid - and xenobiotic - sensing nuclear hormone receptors showed differential regulation.", "output": "There is no related enetity." }, { "input": "Finally, specific shifts in Ces gene expression were seen in peritoneal macrophages following lipopolysaccharide treatment and in a steatotic liver model induced by high - fat feeding, two model systems relevant to disease.", "output": "There is no related enetity." }, { "input": "Overall these data show that each mouse Ces gene has its own distinctive tissue expression pattern and suggest that some CES may have tissue - specific roles in lipid metabolism and xenobiotic clearance.", "output": "There is no related enetity." }, { "input": "DCPIB, the proposed selective blocker of volume - regulated anion channels, inhibits several glutamate transport pathways in glial cells.", "output": "DCPIB, glutamate." }, { "input": "4 - ( 2 - Butyl - 6, 7 - dichloro - 2 - cyclopentyl - indan - 1 - on - 5 - yl ) oxobutyric acid ( DCPIB ) was identified as the selective blocker of volume - regulated anion channels ( VRAC ).", "output": "4 - ( 2 - Butyl - 6 , 7 - dichloro - 2 - cyclopentyl - indan - 1 - on - 5 - yl ) oxobutyric acid, DCPIB." }, { "input": "VRAC are permeable to small inorganic and organic anions, including the excitatory neurotransmitter glutamate.", "output": "There is no related enetity." }, { "input": "In recent years DCPIB has been increasingly used for probing the physiologic and pathologic roles of VRAC and was found to potently suppress pathologic glutamate release in cerebral ischemia.", "output": "DCPIB, glutamate." }, { "input": "Because ischemic glutamate release can be mediated by a plethora of mechanisms, in this study we explored the selectivity of DCPIB toward the majority of previously identified glutamate transporters and permeability pathways.", "output": "glutamate, DCPIB, glutamate." }, { "input": "l - [ ( 3 ) H ] glutamate, d - [ ( 3 ) H ] aspartate, and l - [ ( 14 ) C ] cystine were used to trace amino acid release and uptake.", "output": "l - [ ( 3 ) H ] glutamate, d - [ ( 3 ) H ] aspartate, l - [ ( 14 ) C ] cystine, amino acid." }, { "input": "We found that in addition to its well - characterized effect on VRAC, DCPIB potently inhibited glutamate release via connexin hemichannels and glutamate uptake via the glutamate transporter GLT - 1 in rat glial cells.", "output": "DCPIB, glutamate, glutamate, glutamate." }, { "input": "In contrast, DCPIB had no direct effect on vesicular glutamate release from rat brain synaptosomes or the cystine / glutamate exchange in astrocytes.", "output": "DCPIB, glutamate, cystine, glutamate." }, { "input": "The compound did not affect the astrocytic glutamate transporter GLAST, nor did it block glutamate release via the P2X ( 7 ) / pannexin permeability pathway.", "output": "glutamate, glutamate." }, { "input": "The ability of DCPIB to directly block connexin hemichannels was confirmed using a gene - specific siRNA knockdown approach.", "output": "DCPIB." }, { "input": "Overall, our data demonstrate that DCPIB influences several glutamate transport pathways and that its effects on VRAC in vivo should be verified using additional pharmacological controls.", "output": "DCPIB, glutamate." }, { "input": "Molecular mechanism aspect of ER stress in Alzheimer ' s disease: current approaches and future strategies.", "output": "There is no related enetity." }, { "input": "Alzheimer ' s disease ( AD ) is a progressive neurodegenerative disorder that is characterized by progressive loss of memory and cognitive impairment.", "output": "There is no related enetity." }, { "input": "Aggregation of amyloid - beta ( A beta ) peptides is the crucial factor in the onset of AD.", "output": "There is no related enetity." }, { "input": "The toxic A beta peptides A beta 40 and A beta 42 are produced from the A beta precursor protein ( APP ), a transmembrane protein which is folded and modified in endoplasmic reticulum ( ER ).", "output": "There is no related enetity." }, { "input": "ER is the main organelle for the synthesis and processing of nearly all proteins as well as the main cellular source of Ca2 +.", "output": "Ca2 +." }, { "input": "Under stress conditions, three main ER pathways including inositol - requiring enzyme 1, protein kinase RNA - like ER kinase, and activating transcription factor 6 become activated causing the accumulation of unfolded or misfolded proteins within ER lumen.", "output": "inositol." }, { "input": "These pathways manage the stress by regulating the expression of chaperones and enzymes involved in protein folding.", "output": "There is no related enetity." }, { "input": "Several studies have reported the dysfunction of these stress - sensing pathways in pathological conditions, including neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Recent studies have proposed that neuronal death in AD arises from dysfunction of the ER.", "output": "There is no related enetity." }, { "input": "Here, we will review recent research findings on the interaction between ER and mitochondria, and its effect on apoptotic pathways.", "output": "There is no related enetity." }, { "input": "We further provide insights into studies which suggest the role of ER in animal and / or cellular models of AD.", "output": "There is no related enetity." }, { "input": "Therapeutic strategies that modulate ER could represent a promising approach for prevention or treatment of AD.", "output": "There is no related enetity." }, { "input": "Phenolic profiles of cultivated, in vitro cultured and commercial samples of Melissa officinalis L. infusions.", "output": "There is no related enetity." }, { "input": "Melissa officinalis L.", "output": "There is no related enetity." }, { "input": "( lemon balm ) is normally consumed as an infusion and presents therapeutic properties, such as sedative, carminative and antispasmodic, also being included in some pharmaceutical preparations.", "output": "There is no related enetity." }, { "input": "The phenolic profiles of different samples of lemon balm, prepared as infusions, were evaluated by HPLC - DAD - ESI / MS.", "output": "There is no related enetity." }, { "input": "The profiles were compared in order to understand the differences between cultivated, in vitro cultured and commercial ( bags and granulated ) samples.", "output": "There is no related enetity." }, { "input": "All the samples showed a similar phenolic profile, presenting differences only in the quantities found of each compound.", "output": "There is no related enetity." }, { "input": "Rosmarinic acid was the most abundant compound, being higher in commercial samples, especially in tea bag sample ( 55. 68mg / g of infusion ) and lower in in vitro cultured sample ( 15. 46mg / g ).", "output": "Rosmarinic acid." }, { "input": "Moreover, dimers, trimers and tetramers of caffeic acid were identified and quantified for the first time in lemon balm.", "output": "caffeic acid." }, { "input": "Only one flavonoid, luteolin - 3 ' - O - glucuronide was found in all the samples, ranging from 8. 43mg / g in commercial granulate sample to 1. 22mg / g in in vitro cultured sample.", "output": "flavonoid, luteolin - 3 ' - O - glucuronide." }, { "input": "Overall, cultivated and in vitro cultured samples presented the lowest amounts of phenolic compounds ( 59. 59 and 30. 21mg / g, respectively ); otherwise, commercial samples showed the highest contents ( 109. 24mg / g for tea bag and 101. 03mg / g for granulate sample ).", "output": "There is no related enetity." }, { "input": "The present study shows that infusion of lemon balm can be a source of phenolic compounds, known for their bioactive effects.", "output": "There is no related enetity." }, { "input": "SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT / mTOR signalling pathway.", "output": "SB365, Pulsatilla saponin D." }, { "input": "Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer.", "output": "SB365, Pulsatilla saponin D." }, { "input": "We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis.", "output": "SB365." }, { "input": "Also, SB365 showed anti - angiogenic activity by decreasing the expression of HIF - 1 alpha and VEGF.", "output": "SB365." }, { "input": "These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5 - FU.", "output": "SB365, 5 - FU." }, { "input": "When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT / mTOR pathway both in vitro and in vivo.", "output": "SB365." }, { "input": "Taken together, our study demonstrated that SB365 inhibits the AKT / mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis.", "output": "SB365." }, { "input": "Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.", "output": "SB365." }, { "input": "Studies on the antioxidant potential of flavones of Allium vineale isolated from its water - soluble fraction.", "output": "flavones." }, { "input": "The aim of this work was to examine the chemical constituents and antioxidant potential of water - soluble fractions from the commonly consumed vegetable, Allium vineale.", "output": "There is no related enetity." }, { "input": "The water - soluble fraction, containing phenolic compounds, was extracted with ethyl acetate to obtain flavonoids which were separated and purified by repeated column chromatography over Sephadex LH - 20, RP C18 and silica gel.", "output": "ethyl acetate, flavonoids, silica gel." }, { "input": "The isolated compounds were identified according to their physicochemical properties and spectral data ( UV, HPLC - TOF / MS, ( 1 ) H NMR, ( 13 ) C NMR and 2D NMR ).", "output": "( 1 ) H, ( 13 ) C." }, { "input": "Three flavonoids were isolated and identified as chrysoeriol - 7 - O - [ 2 '' - O - E - feruloyl ] - beta - d - glucoside ( 1 ), chrysoeriol ( 2 ), and isorhamnetin - 3 - beta - d - glucoside ( 3 ).", "output": "chrysoeriol - 7 - O - [ 2 '' - O - E - feruloyl ] - beta - d - glucoside, chrysoeriol, isorhamnetin - 3 - beta - d - glucoside." }, { "input": "Antioxidant studies of the aqueous extract and three isolated compounds, 1, 2, 3, were undertaken and they were found to have significant antioxidant activity.", "output": "There is no related enetity." }, { "input": "Antioxidant activities were evaluated for total antioxidant activity by the ferric thiocyanate method, ferric ion ( Fe ( 3 + ) ) reducing antioxidant power assay ( FRAP ), ferrous ion ( Fe ( 2 + ) ) metal chelating activity, and DPPH free radical - scavenging activity.", "output": "ferric thiocyanate, ferric, Fe ( 3 + ), ferrous, Fe ( 2 + ), DPPH." }, { "input": "The water - soluble ethyl acetate and methanol extraction methods were also compared using HPLC - TOF / MS.", "output": "ethyl acetate, methanol." }, { "input": "Proteomic evaluation of myofibrillar carbonylation in chilled fish mince and its inhibition by catechin.", "output": "catechin." }, { "input": "The present study investigates the susceptibility of individual myofibrillar proteins from mackerel ( Scomber scombrus ) mince to undergo carbonylation reactions during chilled storage, and the antioxidant capacity of ( + ) - catechin to prevent oxidative processes of proteins.", "output": "( + ) - catechin." }, { "input": "The carbonylation of each particular protein was quantified by combining the labelling of protein carbonyls by fluorescein - 5 - thiosemicarbazide ( FTSC ) with 1 - D or 2 - D gel electrophoresis.", "output": "fluorescein - 5 - thiosemicarbazide, FTSC." }, { "input": "Alpha skeletal actin, glycogen phosphorylase, unnamed protein product ( UNP ) similar to enolase, pyruvate kinase, isoforms of creatine kinase, aldolase A and an isoform of glyceraldehyde 3 - phosphate dehydrogenase ( G3PDH ) showed elevated oxidation in chilled non - supplemented mince.", "output": "pyruvate, creatine, glyceraldehyde." }, { "input": "Myosin heavy chain ( MHC ) was not carbonylated in chilled muscle, but an extensive MHC degradation was observed in those samples.", "output": "There is no related enetity." }, { "input": "The supplementation of catechin reduced protein oxidation and lipid oxidation in a concentration - dependent manner: control > 25 > 100 =~ 200ppm.", "output": "catechin." }, { "input": "Therefore, the highest catechin concentrations ( 100 and 200ppm ) exhibited the strongest antioxidant activity.", "output": "catechin." }, { "input": "Catechin ( 200ppm ) reduced significantly carbonylation of protein spots identified as glycogen phosphorylase, pyruvate kinase muscle isozyme, isoforms of creatine kinase.", "output": "Catechin, pyruvate, creatine." }, { "input": "Conversely, catechin was ineffective to inhibit the oxidation of actin and UNP similar to enolase.", "output": "catechin." }, { "input": "These results draw attention to the inefficiency of catechin to prevent actin oxidation, in contrast to the extremely high efficiency of catechin in inhibiting oxidation of lipids and other proteins.", "output": "catechin, catechin." }, { "input": "Can the dietary element content of virgin argan oils really be used for adulteration detection?", "output": "There is no related enetity." }, { "input": "Levels of eight dietary elements were assessed by ICP - AES in virgin edible and beauty argan oil samples prepared from four remote locations of the argan forest, and over a three - year period.", "output": "There is no related enetity." }, { "input": "The data showed sufficiently little variability to assess that all argan oil samples present, in terms of dietary elements, a similar composition, independently from the tree location within the argan forest.", "output": "There is no related enetity." }, { "input": "Therefore, adulteration detection by trace element analysis in edible and beauty argan oil is a method that can be generalised.", "output": "There is no related enetity." }, { "input": "Genistein and dicarboximide fungicides in infant formulae from the EU market.", "output": "Genistein, dicarboximide." }, { "input": "A method based on ultrasonic extraction and purification by solid phase extraction followed by LC - MS / MS and GC - MS analysis was developed for the determination of genistein, genistin, iprodione, vinclozolin and procymidone in infant powdered formulas.", "output": "genistein, genistin, iprodione, vinclozolin, procymidone." }, { "input": "The method was tested for different formulations: milk, soy and hypoallergenic, and was applied to European pooled samples.", "output": "There is no related enetity." }, { "input": "Spike recoveries ranged from 53. 1 % to 91. 5 % and the relative standard deviation values for repeatability ranged from 9. 6 % to 17. 7 %, except for iprodione in milk formula ( 22. 3 % ).", "output": "iprodione." }, { "input": "None of the fungicides were found in the European pooled formulae, while genistein was found at 9. 7 mu g / g in soy formula and the concentration of genistin, its beta - glycosylated form, was respectively 31. 4ng / g and 476ng / g in milk and soy formula.", "output": "genistein, genistin , its beta - glycosylated." }, { "input": "Sugar metabolism in relation to chilling tolerance of loquat fruit.", "output": "Sugar." }, { "input": "The relationship between chilling injury and sugar metabolism was investigated in loquat fruit stored at 1 degrees C for 35days.", "output": "sugar." }, { "input": "No symptoms of chilling injury occurred in the fruit, of ' Ninghaibai ' cultivar, during the whole storage whereas, in ' Dahongpao ' fruit, severe chilling symptoms were observed after 20days of storage at 1 degrees C.", "output": "There is no related enetity." }, { "input": "' Ninghaibai ' fruit had higher levels of glucose and fructose and higher activities of sucrose hydrolyzing enzymes, such as sucrose synthase - cleavage and invertase, than had ' Dahongpao '.", "output": "glucose, fructose, sucrose, sucrose." }, { "input": "Furthermore, the chilling resistant ' Ninghaibai ' fruit also showed higher activities of hexokinase and fructokinase, involved in hexose phoshorylation and sugar signal generation.", "output": "hexose, sugar." }, { "input": "These results suggest that the higher content of hexoses and activities of hexose sensors were likely part of the mechanism for chilling tolerance of loquat fruit.", "output": "hexoses, hexose." }, { "input": "GABA shunt and polyamine degradation pathway on gamma - aminobutyric acid accumulation in germinating fava bean ( Vicia faba L. ) under hypoxia.", "output": "GABA, polyamine, gamma - aminobutyric acid." }, { "input": "GABA shunt and polyamine degradation pathway on gamma - aminobutyric acid ( GABA ) accumulation in germinating fava bean under hypoxia was investigated.", "output": "GABA, polyamine, gamma - aminobutyric acid, GABA." }, { "input": "GABA content, GAD and DAO activity were significantly increased under hypoxia treatment.", "output": "GABA." }, { "input": "Glu and polyamine contents enhanced largely and thus supplied as sufficient substrates for GABA formation.", "output": "Glu, polyamine, GABA." }, { "input": "In contrast, GABA content decreased, mainly in the embryo, after removing the hypoxia stress.", "output": "GABA." }, { "input": "DAO activity, Glu and polyamines contents decreased, while an increment of GAD activity was observed.", "output": "Glu, polyamines." }, { "input": "This indicated that GAD activity can be not only regulated by hypoxia, but by the rapid growth of embryo after the recovery from hypoxia stress.", "output": "There is no related enetity." }, { "input": "When treated with AG, DAO activity was almost inhibited completely, and the GABA content decreased by 32. 96 % and 32. 07 % after treated for 3 and 5 days, respectively.", "output": "GABA." }, { "input": "Hence, it can be inferred that about 30 % of GABA formed in germinating fava bean under hypoxia was supplied by polyamine degradation pathway.", "output": "GABA, polyamine." }, { "input": "Soymilk phenolic compounds, isoflavones and antioxidant activity as affected by in vitro gastrointestinal digestion.", "output": "phenolic, isoflavones." }, { "input": "The aim of this research was to evaluate changes in the phenolic compounds, isoflavones and antioxidant activity of soymilk following in vitro gastrointestinal digestion ( including dialysis ).", "output": "phenolic, isoflavones." }, { "input": "Gastric digestion significantly influenced the release of bioactive substances from the soymilk matrix, increasing the concentration of total phenolic components ( 35 % as the sum of individuals and 14 % by Folin - Ciocalteu [ F - C ] method ), total isoflavone content ( 22 % ) and total antioxidant activity ( 76 % ).", "output": "phenolic, isoflavone." }, { "input": "The concentration of all those compounds was reduced significantly in the duodenal fraction in comparison to gastric digestion and their lowest concentration was observed in the dialysed fraction, where phenolic acids were not detected.", "output": "phenolic acids." }, { "input": "The bioaccessibility of soymilk phenolic compounds was 15 % as the sum of individuals and 20 % by F - C assay; isoflavones 36 % and constituents with antioxidant activity 27 %.", "output": "phenolic, isoflavones." }, { "input": "Results suggest that most of these compounds were sufficiently available to be absorbed and could contribute health benefits.", "output": "There is no related enetity." }, { "input": "Pre - bottling use of dehydrated waste grape skins to improve colour, phenolic and aroma composition of red wines.", "output": "There is no related enetity." }, { "input": "Different dehydrated waste grape skins from the juice industry were added into aged and young red wines as an innovative way of compensating for colour loss before bottling.", "output": "There is no related enetity." }, { "input": "After addition of grape skins, colour intensity of wines increased a mean 11 % and a maximum of 31 % with predominance of the red component.", "output": "There is no related enetity." }, { "input": "Total polyphenols mean increase was 10 % with a maximum value of 20 %.", "output": "polyphenols." }, { "input": "Analysis of low molecular weight phenolic compounds by HPLC - DAD showed a significant ( p < 0. 05 ) content increase of the bioactive compounds gallic acid, ( + ) - catechin, ( - ) - epicatechin, and ( E ) - resveratrol.", "output": "gallic acid, ( + ) - catechin, ( - ) - epicatechin, ( E ) - resveratrol." }, { "input": "Anthocyanins content also increased at an average of 50mg / l.", "output": "Anthocyanins." }, { "input": "The volatile profile of wines analysed by SBSE - GC - MS was only moderately influenced by the treatments.", "output": "There is no related enetity." }, { "input": "Mixtures of dehydrated waste grape skins were useful to improve the colour and polyphenol profile of red wines, considering them a useful tool for correcting colour loss before bottling.", "output": "polyphenol." }, { "input": "Light exposure during storage preserving soluble sugar and l - ascorbic acid content of minimally processed romaine lettuce ( Lactuca sativa L. var. longifolia ).", "output": "sugar, l - ascorbic acid." }, { "input": "Minimally processed romaine lettuce ( MPRL ) leaves were stored in light condition ( 2500lux ) or darkness at 4 degrees C for 7d.", "output": "There is no related enetity." }, { "input": "Light exposure significantly delayed the degradation of chlorophyll and decrease of glucose, reducing sugar, and sucrose content, and thus preserved more total soluble solid ( TSS ) content at the end of storage in comparison with darkness.", "output": "glucose, sugar, sucrose." }, { "input": "While, it did not influenced starch content that progressively decreased over time.", "output": "There is no related enetity." }, { "input": "The l - ascorbic acid ( AA ) accumulated in light - stored leaves, but deteriorated in dark - stored leaves during storage.", "output": "l - ascorbic acid." }, { "input": "The dehydroascorbic acid ( DHA ) increased in all leaves stored in both light and dark condition, of which light condition resulted in less DHA than darkness.", "output": "dehydroascorbic acid, DHA, DHA." }, { "input": "In addition, the fresh weight loss and dry matter significantly increased and these increases were accelerated by light exposure.", "output": "There is no related enetity." }, { "input": "Conclusively, light exposure in applied intensity effectively alleviated MPRL quality deterioration by delaying the decreases of pigments, soluble sugar, TSS content and accumulating AA.", "output": "sugar." }, { "input": "The role of personalized medicine in identifying appropriate candidates for menopausal estrogen therapy.", "output": "estrogen." }, { "input": "Menopausal estrogen therapy has a complex balance of benefits and risks and is no longer routinely recommended for the majority of women during or after the transition to menopause.", "output": "estrogen." }, { "input": "Recent findings from the Women ' s Health Initiative ( WHI ) and other studies suggest that a woman ' s clinical and biological characteristics may modify her health outcomes on hormone therapy ( HT ) and that some women may be more appropriate candidates for therapy than others.", "output": "There is no related enetity." }, { "input": "An emerging body of evidence suggests that it may be possible to identify women who are more likely to have favorable outcomes and less likely to have adverse events on HT, as well as to tailor the optimal dose, formulation, and route of delivery of treatment, by the use of individual risk stratification and a personalized approach.", "output": "There is no related enetity." }, { "input": "Several clinical characteristics that have been proposed for this purpose include a woman ' s age, time since menopause, symptom severity, baseline vascular health, risk for breast cancer, biomarker levels, and genetic predisposition.", "output": "There is no related enetity." }, { "input": "The underlying rationale for personalized medicine, that each person has a unique biologic profile that can help to guide the choice of therapy, applies well to HT decision making and holds promise for improved treatment efficacy and safety.", "output": "There is no related enetity." }, { "input": "This report, which focuses on vascular health, reviews the evidence on the role of such markers in tailoring the use of hormone therapy to appropriate candidates, with the ultimate goal of developing a personalized risk: benefit prediction model that takes into account clinical and genetic factors, \" patient - centered \" outcomes including sense of well being and quality of life, and other variables.", "output": "There is no related enetity." }, { "input": "The proposed personalized approach to HT decision making has the potential to improve the quality of health care.", "output": "There is no related enetity." }, { "input": "Reversal of dopamine D2 agonist - induced inhibition of ventral tegmental area neurons by Gq - linked neurotransmitters is dependent on protein kinase C, G protein - coupled receptor kinase, and dynamin.", "output": "dopamine." }, { "input": "Dopaminergic neurons of the ventral tegmental area are important components of brain pathways related to addiction.", "output": "There is no related enetity." }, { "input": "Prolonged exposure of these neurons to moderate concentrations of dopamine ( DA ) decreases their sensitivity to inhibition by DA, a process called DA - inhibition reversal ( DIR ).", "output": "dopamine." }, { "input": "DIR is mediated by phospholipase C and conventional subtype of protein kinase C ( cPKC ) through concurrent stimulation of D2 and D1 - like DA receptors, or by D2 stimulation concurrent with activation of 5 - HT ( 2 ) or neurotensin receptors.", "output": "5 - HT, neurotensin." }, { "input": "In the present study, we further characterized this phenomenon by use of extracellular recordings in brain slices to examine whether DIR is linked to G protein - coupled receptor kinase - 2 ( GRK2 ) or dynamin by assessing DIR in the presence of antagonists of these enzymes.", "output": "There is no related enetity." }, { "input": "DIR was blocked by beta - ARK1 inhibitor, which inhibits GRK2, and by dynasore, which blocks dynamin.", "output": "There is no related enetity." }, { "input": "Reversal of inhibition by D2 agonist quinpirole was produced by serotonin ( 50 micro M ) and by neurotensin ( 5 - 10 nM ).", "output": "quinpirole, serotonin, neurotensin." }, { "input": "Serotonin - induced or neurotensin - induced reversal was blocked by beta - ARK1 inhibitor, dynasore, or cPKC antagonist 5, 6, 7, 13 - tetrahydro - 13 - methyl - 5 - oxo - 12H - indolo [ 2, 3 - a ] pyrrolo [ 3, 4c ] carbazole - 12 - propanenitrile ( G o 6976 ).", "output": "Serotonin, neurotensin, 5 , 6 , 7 , 13 - tetrahydro - 13 - methyl - 5 - oxo - 12H - indolo [ 2 , 3 - a ] pyrrolo [ 3 , 4c ] carbazole - 12 - propanenitrile, G o 6976." }, { "input": "This further characterization of DIR indicates that cPKC, GRK2, and dynamin play important roles in the desensitization of D2 receptors.", "output": "There is no related enetity." }, { "input": "As drugs of abuse produce persistent increases in DA concentration in the ventral tegmental area, reduction of D2 receptor sensitivity as a result of drug abuse may be a critical factor in the processes of addiction.", "output": "There is no related enetity." }, { "input": "A comparative analysis of computational approaches to relative protein quantification using peptide peak intensities in label - free LC - MS proteomics experiments.", "output": "There is no related enetity." }, { "input": "Liquid chromatography coupled with mass spectrometry ( LC - MS ) is widely used to identify and quantify peptides in complex biological samples.", "output": "There is no related enetity." }, { "input": "In particular, label - free shotgun proteomics is highly effective for the identification of peptides and subsequently obtaining a global protein profile of a sample.", "output": "There is no related enetity." }, { "input": "As a result, this approach is widely used for discovery studies.", "output": "There is no related enetity." }, { "input": "Typically, the objective of these discovery studies is to identify proteins that are affected by some condition of interest ( e. g. disease, exposure ).", "output": "There is no related enetity." }, { "input": "However, for complex biological samples, label - free LC - MS proteomics experiments measure peptides and do not directly yield protein quantities.", "output": "There is no related enetity." }, { "input": "Thus, protein quantification must be inferred from one or more measured peptides.", "output": "There is no related enetity." }, { "input": "In recent years, many computational approaches to relative protein quantification of label - free LC - MS data have been published.", "output": "There is no related enetity." }, { "input": "In this review, we examine the most commonly employed quantification approaches to relative protein abundance from peak intensity values, evaluate their individual merits, and discuss challenges in the use of the various computational approaches.", "output": "There is no related enetity." }, { "input": "Mithramycin A inhibits myeloid cell leukemia - 1 to induce apoptosis in oral squamous cell carcinomas and tumor xenograft through activation of Bax and oligomerization.", "output": "Mithramycin A." }, { "input": "In several human malignancies, overexpression of myeloid cell leukemia - 1 ( Mcl - 1 ) confers resistance to induction of apoptosis; however, Mcl - 1 - mediated inhibition of apoptosis in oral squamous cell carcinoma ( OSCC ) is not fully understood and has been investigated in this study.", "output": "There is no related enetity." }, { "input": "The Mcl - 1 promoter activators ( TPA ) and epidermal growth factor ( EGF ) enhanced neoplastic transformation of JB6 cells and this response was accompanied by enhanced expression of Mcl - 1, and knockdown of Mcl - 1 by RNA interference ( RNAi ) decreased JB6 cell transformation.", "output": "There is no related enetity." }, { "input": "In the same cell line, we also demonstrated that mithramycin A ( Mith ) decreased TPA - induced JB6 cell transformation and Mcl - 1 expression.", "output": "mithramycin A, Mith." }, { "input": "Mcl - 1 was overexpressed in human oral tumors compared with normal oral mucosa and also in several OSCC cell lines including HN22 and HSC - 4 cells.", "output": "There is no related enetity." }, { "input": "Treatment of these cells with Mith also decreased Mcl - 1 expression and neoplastic cell transformation, and this was accompanied by induction of several markers of apoptosis.", "output": "Mith." }, { "input": "Knockdown of Mcl - 1 by RNAi also induced apoptotic cell death.", "output": "There is no related enetity." }, { "input": "The downregulation of Mcl - 1 by Mith and RNAi increased pro - apoptotic protein Bax, resulting in the Bax translocation into mitochondria and its oligomerization.", "output": "Mith." }, { "input": "Mith also suppressed tumor growth in vivo and induced apoptosis in tumor by also regulating expression of Mcl - 1 and Bax proteins.", "output": "Mith." }, { "input": "These indicate a critical role for Mcl - 1 in the growth and survival of OSCC and demonstrate that Mith may be a potential anticancer drug candidate for clinical treatment of OSCC.", "output": "Mith." }, { "input": "Novel assays for detection of urinary KIM - 1 in mouse models of kidney injury.", "output": "There is no related enetity." }, { "input": "Kidney injury molecule - 1 ( KIM - 1 ) has been qualified by the Food and Drug Administration and European Medicines Agency as a urinary biomarker to monitor preclinical nephrotoxicity in rats and on a case - by - case basis for the translation of potentially nephrotoxic drugs into first - in human studies.", "output": "There is no related enetity." }, { "input": "Although mouse models are widely employed in preclinical studies, few urinary biomarker studies have been performed in mice due to limited urine availability and lack of sensitive assays.", "output": "There is no related enetity." }, { "input": "Here, we report the development and validation of two different assays for quantitative assessment of mouse urinary KIM - 1 ( uKIM - 1 ) and compare the sensitivity of KIM - 1 relative to other standard markers in ischemia reperfusion and aristolochic acid ( AA ) - induced kidney injury in mice.", "output": "aristolochic acid." }, { "input": "A sensitive, reproducible, and quantitative microbead - based KIM - 1 ELISA was established, which requires only 10 mu l urine for triplicate determination with an assay range of 12. 21 pg / ml to 50 ng / ml.", "output": "There is no related enetity." }, { "input": "The second assay is a laminar flow dipstick assay, which has an assay range of 195 pg / ml to 50 ng / ml and provides quantitative assessment of KIM - 1 in 15 min.", "output": "There is no related enetity." }, { "input": "uKIM - 1 levels increased with increasing time of ischemia or time after AA administration.", "output": "There is no related enetity." }, { "input": "After only 10 - min ischemia followed by 24 - h reperfusion, uKIM - 1 was significantly elevated by 13 - fold, whereas serum creatinine ( sCr ), blood urea nitrogen, N - acetyl - beta - glucosaminidase ( NAG ), and proteinuria levels did not change.", "output": "creatinine, urea, nitrogen, N - acetyl." }, { "input": "After AA administration, uKIM - 1 levels were significantly upregulated by greater than threefold within 12 h, whereas sCr and NAG levels were unchanged.", "output": "There is no related enetity." }, { "input": "Mouse KIM - 1 was stable for multiple freeze - thaw cycles, for up to 5 days at room temperature and up to at least an year when stored at - 80 degrees C.", "output": "There is no related enetity." }, { "input": "Performance of urinary and gene expression biomarkers in detecting the nephrotoxic effects of melamine and cyanuric acid following diverse scenarios of co - exposure.", "output": "melamine, cyanuric acid." }, { "input": "Although standard nephrotoxicity assessments primarily detect impaired renal function, KIM - 1, clusterin, NGAL, osteopontin and TIMP - 1 were recently identified biomarkers proposed to indicate earlier perturbations in renal integrity.", "output": "There is no related enetity." }, { "input": "The recent adulteration of infant and pet food with melamine ( MEL ) and structurally - related compounds revealed that co - ingestion of MEL and cyanuric acid ( CYA ) could form melamine - cyanurate crystals which obstruct renal tubules and induce acute renal failure.", "output": "melamine, MEL, MEL, cyanuric acid, CYA, melamine, cyanurate." }, { "input": "This study concurrently evaluated the ability of multiplexed urinary biomarker immunoassays and biomarker gene expression analysis to detect nephrotoxicity in F344 rats co - administered 60ppm each of MEL and CYA in feed or via gavage for 28days.", "output": "MEL, CYA." }, { "input": "The biomarkers were also evaluated for the ability to differentiate the effects of the compounds when co - administered using diverse dosing schedules ( i. e., consecutive vs. staggered gavage ) and dosing matrixes ( i. e., feed vs. gavage ).", "output": "There is no related enetity." }, { "input": "Our results illustrate the ability of both methods to detect and differentiate the severity of adverse effects in the staggered and consecutive gavage groups at much lower doses than previously observed in animals co - exposed to the compounds in feed.", "output": "There is no related enetity." }, { "input": "We also demonstrate that these urinary biomarkers outperform traditional diagnostic methods and represent a powerful, non - invasive indicator of chemical - induced nephrotoxicity prior to the onset of renal dysfunction.", "output": "There is no related enetity." }, { "input": "NMDA receptor blockade impairs the muscarinic conversion of sub - threshold transient depression into long - lasting LTD in the hippocampus - prefrontal cortex pathway in vivo: correlation with gamma oscillations.", "output": "NMDA." }, { "input": "Cholinergic fibers from the brainstem and basal forebrain innervate the medial prefrontal cortex ( mPFC ) modulating neuronal activity and synaptic plasticity responses to hippocampal inputs.", "output": "There is no related enetity." }, { "input": "Here, we investigated the muscarinic and glutamatergic modulation of long - term depression ( LTD ) in the intact projections from CA1 to mPFC in vivo.", "output": "There is no related enetity." }, { "input": "Cortical - evoked responses were recorded in urethane - anesthetized rats for 30 min during baseline and 4 h following LTD.", "output": "urethane." }, { "input": "In order to test the potentiating effects of pilocarpine ( PILO ), independent groups of rats received either a microinjection of PILO ( 40 nmol; i. c. v. ) or vehicle, immediately before or 20 min after a sub - threshold LTD protocol ( 600 pulses, 1 Hz; LFS600 ).", "output": "pilocarpine, PILO, PILO." }, { "input": "Other groups received either an infusion of the selective NMDA receptor antagonist ( AP7; 10 nmol; intra - mPFC ) or vehicle, 10 min prior to PILO preceding LFS600, or prior to a supra - threshold LTD protocol ( 900 pulses, 1 Hz; LFS900 ).", "output": "NMDA, AP7, PILO." }, { "input": "Our results show that PILO converts a transient cortical depression induced by LFS600 into a robust LTD, stable for at least 4 h.", "output": "PILO." }, { "input": "When applied after LFS600, PILO does not change either mPFC basal neurotransmission or late LTD.", "output": "PILO." }, { "input": "Our data also indicate that NMDA receptor pre - activation is essential to the muscarinic enhancement of mPFC synaptic depression, since AP7 microinjection into the mPFC blocked the conversion of transient depression into long - lasting LTD produced by PILO.", "output": "NMDA, AP7, PILO." }, { "input": "In addition, AP7 effectively blocked the long - lasting LTD induced by LFS900.", "output": "AP7." }, { "input": "Therefore, our findings suggest that the glutamatergic co - activation of prefrontal neurons is important for the effects of PILO on mPFC synaptic depression, which could play an important role in the control of executive and emotional functions.", "output": "PILO." }, { "input": "The effects of alpha - tocopherol on oxidative damage and serum levels of Clara cell protein 16 in aspiration pneumonitis induced by bile acids.", "output": "alpha - tocopherol." }, { "input": "Our aim in this study is to examine the effects of alpha - tocopherol ( AT ) on rats with aspiration pneumonitis induced with bile acids ( BAs ).", "output": "alpha - tocopherol, bile acids, BAs." }, { "input": "The animals were divided in to four groups, namely saline group ( n = 7 ), saline + AT group ( n = 7 ), BA group ( n = 7 ), and BA + AT group ( n = 7 ).", "output": "There is no related enetity." }, { "input": "Saline and BA groups aspirated intratracheally with 1 ml / kg saline and 1 ml / kg bile acids, respectively.", "output": "bile acids." }, { "input": "AT was given at 20 mg / kg / day dosage for 7 days to the groups.", "output": "There is no related enetity." }, { "input": "AT group was given 20 mg / kg / day AT for 7 days.", "output": "There is no related enetity." }, { "input": "Malondialdehyde ( MDA ), Clara cell protein 16 ( CC - 16 ), catalase ( CAT ), superoxide dismutase ( SOD ), as well as peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, and necrosis were evaluated.", "output": "Malondialdehyde, MDA, superoxide." }, { "input": "The CAT activity of the BA group was significantly lower than the saline group.", "output": "There is no related enetity." }, { "input": "In the BA + AT group, there was a significant increase in SOD and CAT activities when compared with that of the BA group.", "output": "There is no related enetity." }, { "input": "The CC - 16 and MDA contents in the BA group were significantly higher than in the saline group.", "output": "MDA." }, { "input": "The CC - 16 and MDA levels of the BA + AT group were significantly lower than BA group.", "output": "MDA." }, { "input": "Histopathologic changes were seen in BA group, and there was a significant decrease in the BA + AT group.", "output": "There is no related enetity." }, { "input": "In conclusion, AT might be beneficial in the treatment of aspiration pneumonitis induced by BAs because AT decreased oxidative damage and resulted in a decrease in CC - 16 levels.", "output": "BAs." }, { "input": "Resveratrol attenuates hepatotoxicity of rats exposed to arsenic trioxide.", "output": "Resveratrol, arsenic trioxide." }, { "input": "Arsenic trioxide ( As ( 2 ) O ( 3 ) ) is an environmental pollutant and potent toxicant to humans.", "output": "Arsenic trioxide, As ( 2 ) O ( 3 )." }, { "input": "However, it also shows substantial anti - cancer activity in individuals with acute promyelocytic leukemia ( APL ).", "output": "There is no related enetity." }, { "input": "Unfortunately, As ( 2 ) O ( 3 ) - treated leukemia patients suffer hepatotoxicity.", "output": "As ( 2 ) O ( 3 )." }, { "input": "Resveratrol has been demonstrated to have efficient antioxidant and antineoplastic activities.", "output": "Resveratrol." }, { "input": "The study that how As ( 2 ) O ( 3 ) in combination with resveratrol affects hepatotoxicity and arsenic accumulation in the liver is lacking, and the present study tackles this question.", "output": "As ( 2 ) O ( 3 ), resveratrol, arsenic." }, { "input": "Wistar rats were injected with 3mg / kg As ( 2 ) O ( 3 ) on alternate days; resveratrol ( 8mg / kg ) was administered 1h before As ( 2 ) O ( 3 ).", "output": "As ( 2 ) O ( 3 ), resveratrol, As ( 2 ) O ( 3 )." }, { "input": "Rats were killed on the 8th day to determine histological liver damage, the antioxidant enzymes in serum, the ratio of reduced glutathione ( GSH ) to oxidized glutathione ( GSSG ), and arsenic accumulation in the liver.", "output": "reduced glutathione, GSH, oxidized glutathione, GSSG, arsenic." }, { "input": "In the resveratrol + As ( 2 ) O ( 3 ) group, activities of superoxide dismutase, catalase in serum and GSH / GSSG were significantly increased, histopathological effects were reduced, and arsenic accumulation markedly decreased in the liver, compared with the As ( 2 ) O ( 3 ) - treated group.", "output": "resveratrol, As ( 2 ) O ( 3 ), superoxide, GSH, GSSG, arsenic, As ( 2 ) O ( 3 )." }, { "input": "Thus, resveratrol attenuated As ( 2 ) O ( 3 ) - induced hepatotoxicity by decreasing oxidative stress and arsenic accumulation in the liver.", "output": "resveratrol, As ( 2 ) O ( 3 ), arsenic." }, { "input": "These data suggest that use of resveratrol as post - remission therapy of APL and adjunctive therapy in patients with chronic exposure to arsenic may decrease arsenic hepatotoxicity.", "output": "resveratrol, arsenic, arsenic." }, { "input": "Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish.", "output": "There is no related enetity." }, { "input": "A mechanistic mass balance bioconcentration model is developed and parameterized for ionogenic organic chemicals ( IOCs ) in fish and evaluated against a compilation of empirical bioconcentration factors ( BCFs ).", "output": "There is no related enetity." }, { "input": "The model is subsequently applied to a set of perfluoroalkyl acids.", "output": "perfluoroalkyl acids." }, { "input": "Key aspects of model development include revised methods to estimate the chemical absorption efficiency of IOCs at the respiratory surface ( E ( W ) ) and the use of distribution ratios to characterize the overall sorption capacity of the organism.", "output": "There is no related enetity." }, { "input": "Membrane - water distribution ratios ( D ( MW ) ) are used to characterize sorption to phospholipids instead of only considering the octanol - water distribution ratio ( D ( OW ) ).", "output": "octanol." }, { "input": "Modeled BCFs are well correlated with the observations ( e. g., r ( 2 ) = 0. 68 and 0. 75 for organic acids and bases, respectively ) and accurate to within a factor of three on average.", "output": "There is no related enetity." }, { "input": "Model prediction errors appear to be largely the result of uncertainties in the biotransformation rate constant ( k ( M ) ) estimates and the generic approaches for estimating sorption capacity ( e. g., D ( MW ) ).", "output": "There is no related enetity." }, { "input": "Model performance for the set of perfluoroalkyl acids considered is highly dependent on the input parameters describing hydrophobicity ( i. e., log K ( OW ) of the neutral form ).", "output": "perfluoroalkyl acids." }, { "input": "The model applications broadly support the hypothesis that phospholipids contribute substantially to the sorption capacity of fish, particularly for compounds that exhibit a high degree of ionization at biologically relevant pH.", "output": "There is no related enetity." }, { "input": "Additional empirical data on biotransformation and sorption to phospholipids and subsequent incorporation into property estimation approaches ( e. g., k ( M ), D ( MW ) ) are priorities with respect to improving model performance.", "output": "There is no related enetity." }, { "input": "In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.", "output": "There is no related enetity." }, { "input": "Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans.", "output": "There is no related enetity." }, { "input": "A proposed solution is rapid testing of chemicals using in vitro high - throughput screening ( HTS ) assays for targets in pathways linked to disease processes to build models for priority setting and further testing.", "output": "There is no related enetity." }, { "input": "We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes.", "output": "There is no related enetity." }, { "input": "All data come from the EPA ToxCast project.", "output": "There is no related enetity." }, { "input": "The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database ( ToxRefDB ).", "output": "There is no related enetity." }, { "input": "Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression.", "output": "There is no related enetity." }, { "input": "Rodent liver cancer endpoints were linked to well - documented pathways such as peroxisome proliferator - activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR.", "output": "There is no related enetity." }, { "input": "Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease.", "output": "There is no related enetity." }, { "input": "A model was developed in which these genes / pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption.", "output": "There is no related enetity." }, { "input": "A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs.", "output": "There is no related enetity." }, { "input": "This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA ' s Office of Pesticide Programs and successfully ( p = 0. 024 ) differentiated between chemicals classified as \" possible \" / \" probable \" / \" likely \" carcinogens and those designated as \" not likely \" or with \" evidence of noncarcinogenicity. \" This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.", "output": "There is no related enetity." }, { "input": "Cassia tora ( Leguminosae ) seed extract alleviates high - fat diet - induced nonalcoholic fatty liver.", "output": "There is no related enetity." }, { "input": "The aim of this study was to examine the effects of Cassia tora seeds on high - fat diet ( HFD ) - induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects.", "output": "There is no related enetity." }, { "input": "After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract ( CSEE ) ( 100, 200, or 300mg / kg ) once daily for 8weeks.", "output": "ethanol." }, { "input": "CSEE induced dose - dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation.", "output": "There is no related enetity." }, { "input": "Furthermore, CSEE treatment improved HFD - induced hepatic histological lesions.", "output": "There is no related enetity." }, { "input": "CSEE enhanced the phosphorylation of AMP - activated protein kinase ( AMPK ) and its primary downstream targeting enzyme, acetyl - CoA carboxylase, up - regulated the gene expression of carnitine palmitoyl transferase 1, and down - regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the livers of HFD - fed rats.", "output": "AMP, acetyl - CoA, carnitine palmitoyl, sterol, fatty acid." }, { "input": "AMPK inhibition by compound C retarded CSEE - induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin.", "output": "triglyceride." }, { "input": "Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK - dependent signaling pathway.", "output": "There is no related enetity." }, { "input": "Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity - related non - alcoholic fatty liver disease.", "output": "There is no related enetity." }, { "input": "Light induced nanowire assembly: the electrostatic alignment of semiconductor nanowires into functional macroscopic yarns.", "output": "There is no related enetity." }, { "input": "The electrostatic alignment and directed assembly of semiconductor nanowires into macroscopic, centimeter - long yarns is demonstrated.", "output": "There is no related enetity." }, { "input": "Different morphologies can be produced, including longitudinally segmented / graded yarns or mixed composition fibers.", "output": "There is no related enetity." }, { "input": "Nanowire yarns display long range photoconductivities and open up exciting opportunities for potential use in future nanowire - based textiles or in solar photovoltaics.", "output": "There is no related enetity." }, { "input": "Mechanisms in endocrinology.", "output": "There is no related enetity." }, { "input": "Role of emotional stress in the pathophysiology of Graves ' disease.", "output": "There is no related enetity." }, { "input": "The role of stress in the pathophysiology of Graves ' disease is suggested by several clinical observations, by recent advances in immunology and by better understanding of autoimmune diseases which provides new insights into potential effects of stress hormones on T helper cell imbalance involved in the pathogenesis of autoimmune diseases.", "output": "There is no related enetity." }, { "input": "Stress management should therefore be an important part of the treatment of Graves ' disease, as stress reduction may improve the effect of therapy.", "output": "There is no related enetity." }, { "input": "However, this field still requires interventional data to support stress management in the treatment of Graves ' disease.", "output": "There is no related enetity." }, { "input": "Autoinhibition of CYP3A4 leads to important role of CYP2C8 in imatinib metabolism: variability in CYP2C8 activity may alter plasma concentrations and response.", "output": "imatinib." }, { "input": "Recent data suggest that the role of CYP3A4 in imatinib metabolism is smaller than presumed.", "output": "imatinib." }, { "input": "This study aimed to evaluate the quantitative importance of different cytochrome P450 ( P450 ) enzymes in imatinib pharmacokinetics.", "output": "imatinib." }, { "input": "First, the metabolism of imatinib was investigated using recombinant P450 enzymes and human liver microsomes with P450 isoform - selective inhibitors.", "output": "imatinib." }, { "input": "Thereafter, an in silico model for imatinib was constructed to perform pharmacokinetic simulations to assess the roles of P450 enzymes in imatinib elimination at clinically used imatinib doses.", "output": "imatinib, imatinib, imatinib." }, { "input": "In vitro, CYP2C8 inhibitors and CYP3A4 inhibitors inhibited the depletion of 0. 1 micro M imatinib by 45 and 80 %, respectively, and the formation of the main metabolite of imatinib, N - desmethylimatinib, by > 50 %.", "output": "imatinib, imatinib, N - desmethylimatinib." }, { "input": "Likewise, recombinant CYP2C8 and CYP3A4 metabolized imatinib extensively, whereas other isoforms had minor effect on imatinib concentrations.", "output": "imatinib, imatinib." }, { "input": "In the beginning of imatinib treatment, the fractions of its hepatic clearance mediated by CYP2C8 and CYP3A4 were predicted to approximate 40 and 60 %, respectively.", "output": "imatinib." }, { "input": "During long - term treatment with imatinib 400 mg once or twice daily, up to 65 or 75 % of its hepatic elimination was predicted to occur via CYP2C8, and only about 35 or 25 % by CYP3A4, due to dose - and time - dependent autoinactivation of CYP3A4 by imatinib.", "output": "imatinib, imatinib." }, { "input": "Thus, although CYP2C8 and CYP3A4 are the main enzymes in imatinib metabolism in vitro, in silico predictions indicate that imatinib inhibits its own CYP3A4 - mediated metabolism, assigning a key role for CYP2C8.", "output": "imatinib, imatinib." }, { "input": "During multiple dosing, pharmacogenetic polymorphisms and drug interactions affecting CYP2C8 activity may cause marked interindividual variation in the exposure and response to imatinib.", "output": "imatinib." }, { "input": "Direct measurement of coherency limits for strain relaxation in heteroepitaxial core / shell nanowires.", "output": "There is no related enetity." }, { "input": "The growth of heteroepitaxially strained semiconductors at the nanoscale enables tailoring of material properties for enhanced device performance.", "output": "There is no related enetity." }, { "input": "For core / shell nanowires ( NWs ), theoretical predictions of the coherency limits and the implications they carry remain uncertain without proper identification of the mechanisms by which strains relax.", "output": "There is no related enetity." }, { "input": "We present here for the Ge / Si core / shell NW system the first experimental measurement of critical shell thickness for strain relaxation in a semiconductor NW heterostructure and the identification of the relaxation mechanisms.", "output": "Ge, Si." }, { "input": "Axial and tangential strain relief is initiated by the formation of periodic a / 2 < 110 > perfect dislocations via nucleation and glide on { 111 } slip - planes.", "output": "There is no related enetity." }, { "input": "Glide of dislocation segments is directly confirmed by real - time in situ transmission electron microscope observations and by dislocation dynamics simulations.", "output": "There is no related enetity." }, { "input": "Further shell growth leads to roughening and grain formation which provides additional strain relief.", "output": "There is no related enetity." }, { "input": "As a consequence of core / shell strain sharing in NWs, a 16 nm radius Ge NW with a 3 nm Si shell is shown to accommodate 3 % coherent strain at equilibrium, a factor of 3 increase over the 1 nm equilibrium critical thickness for planar Si / Ge heteroepitaxial growth.", "output": "Ge, Si, Si, Ge." }, { "input": "In vitro metabolism of the 5 - hydroxytryptamine1B receptor antagonist elzasonan.", "output": "elzasonan." }, { "input": "The metabolism of elzasonan has been examined in vitro using hepatic microsomes from human and recombinant heterologously expressed P450 enzymes ( rCYP ).", "output": "elzasonan." }, { "input": "Metabolism occurs primarily via oxidative N - demethylation to form M4 and oxidation reactions to form elzasonan N - oxide ( M5 ) and 5 - hydroxyelzasonan metabolite ( M3 ).", "output": "N, elzasonan N - oxide, 5 - hydroxyelzasonan." }, { "input": "Additionally, elzasonan was shown to be metabolized to the novel cyclized indole metabolite ( M6 ) which undergoes subsequent oxidation to form the iminium ion metabolite ( M3a ).", "output": "elzasonan, indole, iminium." }, { "input": "The rCYP data was normalized relative to the levels of each CYP form in native human liver microsomes to better assess the contribution of each rCYP in the metabolism of elzasonan.", "output": "elzasonan." }, { "input": "Results demonstrated the involvement of CYP3A4 in the pathways leading to M3a, M3, M5 and M6 and CYP2C8 in the formation of M4.", "output": "There is no related enetity." }, { "input": "Kinetic constants for the formation of M3 were determined and correlation and inhibition studies suggested that CYP3A4 is primarily responsible for the formation of M3 and CYP2C19 plays a very minor role in its formation.", "output": "There is no related enetity." }, { "input": "Cytochrome b5 has shown to be an essential component in P450 3A4 catalyzed 5 - hydroxyelzasonan formation and provides insights on the disconnect between human liver microsomes data and that of rCYP.", "output": "5 - hydroxyelzasonan." }, { "input": "Furthermore, rCYP3A4 containing b5 are useful models for predicting the rates for liver microsomes P450 - dependent drug oxidations and should be utilized routinely.", "output": "There is no related enetity." }, { "input": "Use of precision - cut renal cortical slices in nephrotoxicity studies.", "output": "There is no related enetity." }, { "input": "1. Unlike cell lines and primary cells in culture, precision - cut tissue slices remain metabolically differentiated for at least 24 - 48 h and allow to study the effect of xenobiotics during short - term and long - term incubations.", "output": "There is no related enetity." }, { "input": "2. In this article, we illustrate the use of such an experimental model to study the nephrotoxic effects of ( i ) chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, ( ii ) of cobalt chloride, a potential leakage product of the cobalt - containing nanoparticles, and ( iii ) of valproate, a widely used antiepileptic drug.", "output": "chloroacetaldehyde, ifosfamide, cobalt chloride, cobalt, valproate." }, { "input": "3. Since all the latter test compounds, like many toxic compounds, negatively interact with cellular metabolic pathways, we also illustrate our biochemical toxicology approach in which we used not only enzymatic but also carbon 13 NMR measurements and mathematical modelling of metabolic pathways.", "output": "carbon 13." }, { "input": "4. This original approach, which can be applied to any tissue, allows to predict the nephrotoxic effects of milligram amounts of test compounds very early during the research and development processes of drugs and chemicals.", "output": "There is no related enetity." }, { "input": "This approach, combined with the use of cells that retain their in vivo metabolic properties and, therefore, are predictive, reduces the risk, the time and cost of such processes.", "output": "There is no related enetity." }, { "input": "Effective phagocytosis of low Her2 tumor cell lines with engineered, aglycosylated IgG displaying high Fc gamma RIIa affinity and selectivity.", "output": "There is no related enetity." }, { "input": "Glycans anchored to residue N297 of the antibody IgG Fc domain are critical in mediating binding toward Fc gamma Rs to direct both adaptive and innate immune responses.", "output": "There is no related enetity." }, { "input": "However, using a full length bacterial IgG display system, we have isolated aglycosylated Fc domains with mutations that confer up to a 160 - fold increase in the affinity toward the low affinity Fc gamma RIIa - R131 allele as well as high selectivity against binding to the remarkably homologous human inhibitory receptor, Fc gamma RIIb.", "output": "There is no related enetity." }, { "input": "The mutant Fc domain ( AglycoT - Fc1004 ) contained a total of 5 amino acid substitutions that conferred an activating to inhibitory ratio of 25 ( A / I ratio; FcyRIIa - R131: Fc gamma RIIb ).", "output": "amino acid." }, { "input": "Incorporation of this engineered Fc into trastuzumab, an anti - Her2 antibody, resulted in a 75 % increase in tumor cell phagocytosis by macrophages compared to that of the parental glycosylated trastuzumab with both medium and low Her2 - expressing cancer cells.", "output": "There is no related enetity." }, { "input": "A mathematical model has been developed to help explain how receptor affinity and the A / I ratio relate to improved antibody dependent cell - mediated phagocytosis.", "output": "There is no related enetity." }, { "input": "Our model provides guidelines for the future engineering of Fc domains with enhanced effector function.", "output": "There is no related enetity." }, { "input": "8 - Hydroxycalamenene isolated from the rhizomes of Reynoutria elliptica exerts neuroprotective effects both in vitro and in vivo.", "output": "8 - Hydroxycalamenene." }, { "input": "Retinal ganglion cells ( RGCs ) death caused by oxidative stress is a common risk factor for glaucoma.", "output": "There is no related enetity." }, { "input": "In the present study, 8 - hydroxycalamenene was isolated from the hexane fraction of Reynoutria elliptica.", "output": "8 - hydroxycalamenene, hexane." }, { "input": "We showed that 8 - hydroxycalamenene attenuated the cell death of transformed RGC - 5 cells.", "output": "8 - hydroxycalamenene." }, { "input": "This compound also produced a dose - dependent decrease in the expression of apoptotic proteins ( cleaved PARP and caspase - 3 ) induced by l - buthionine - ( S, R ) - sulfoximine ( BSO ) plus glutamate and stimulated glutathione and glutathione S - transferase activity.", "output": "l - buthionine - ( S , R ) - sulfoximine, BSO, glutamate, glutathione, glutathione, S." }, { "input": "Moreover, the addition of 8 - hydroxycalamenene to cell cultures restored the reduced mitochondrial membrane potential resulting from glutamate / BSO treatment.", "output": "8 - hydroxycalamenene, glutamate, BSO." }, { "input": "The presence of N - methyl - d - aspartate in the retina of rats affected the thickness of the inner plexiform layer ( IPL ) and increased the number of TUNEL - positive RGCs.", "output": "N - methyl - d - aspartate." }, { "input": "However, 8 - hydroxycalamenene protected against thinning of the IPL and reduced TUNEL - positive cells in the ganglion cell layer.", "output": "8 - hydroxycalamenene." }, { "input": "Thus, 8 - hydroxycalamenene isolated from R. elliptica exerts neuroprotective effects both in vitro and in vivo.", "output": "8 - hydroxycalamenene." }, { "input": "DNA methylation and histone modification profiles of mouse organic anion transporting polypeptides.", "output": "There is no related enetity." }, { "input": "Organic anion transporting polypeptides ( rodents, Oatps; human, OATPs ) are primarily involved in the transmembrane transportation of a wide range of endogenous and exogenous compounds.", "output": "There is no related enetity." }, { "input": "Multiple mouse Oatp1 isoforms are closely located on chromosome 6, where each isoform shows distinct tissue distribution; Oatp1b2, Oatp1a6, and Oatp1c1 are expressed exclusively in the liver, kidney, and cerebrum, respectively; Oatp1a1 in the liver and kidney; and Oatp1a4 in the liver and cerebrum.", "output": "There is no related enetity." }, { "input": "We have identified tissue - dependent differentially methylated region ( T - DMR ) around the transcriptional start site ( TSS ) of Oatp1b2, which correlates with its liver - specific expression.", "output": "There is no related enetity." }, { "input": "Bisulfite sequencing also demonstrated the presence of T - DMRs around the TSS in other Oatp1 genes: CpG dinucleotides at + 149 relative to the TSS for Oatp1c1; - 48, + 101, and + 356 for Oatp1a4; - 572 and - 550 for Oatp1a1; and - 122 and + 216 for Oatp1a6 were differentially methylated among the liver, kidney, and cerebrum.", "output": "Bisulfite." }, { "input": "These methylation profiles were largely consistent with the tissue distribution of Oatp1 mRNAs.", "output": "There is no related enetity." }, { "input": "Chromatin immunoprecipitation assay revealed that the mRNA expression of Oatp1 genes was accompanied by acetylated histone H3.", "output": "There is no related enetity." }, { "input": "Human OATP1B1 and OATP1B3 are located on chromosome 12p12 in the OATP1 cluster; both show predominant expression in the liver.", "output": "There is no related enetity." }, { "input": "These genes also contained T - DMRs that were hypomethylated in the liver, compared with kidney cortex: - 511, - 411, and + 92 relative to the TSS for OATP1B1 and - 331, + 70, and + 73 for OATP1B3.", "output": "There is no related enetity." }, { "input": "These results suggest that the difference in epigenetic profiles comprising DNA methylation and histone acetylation determines the distinct tissue distribution of Oatp / OATP mRNAs.", "output": "There is no related enetity." }, { "input": "Interplay between protein carbonylation and nitrosylation in plants.", "output": "There is no related enetity." }, { "input": "ROS and reactive nitrogen species ( RNS ) are key regulators of redox homeostasis in living organisms including plants.", "output": "nitrogen." }, { "input": "As control of redox homeostasis plays a central function in plant biology, redox proteomics could help in characterizing the potential roles played by ROS / RNS - induced posttranslational modification in plant cells.", "output": "There is no related enetity." }, { "input": "In this review, we focus on two posttranslational modifications: protein carbonylation ( a marker of protein oxidation ) and protein S - nitrosylation, both of which having recently emerged as important regulatory mechanisms during numerous fundamental biological processes.", "output": "S." }, { "input": "Here, we describe the recent progress in proteomic analysis of carbonylated and nitrosylated proteins and highlight the achievements made in understanding the physiological basis of these oxy / nitro modifications in plants.", "output": "oxy, nitro." }, { "input": "In addition, we document the existence of a relationship between ROS - based carbonylation and RNS - based nitrosylation thus supporting the finding that crosstalk between cellular signaling stress pathways induced by ROS and RNS could be mediated by specific protein modifications.", "output": "There is no related enetity." }, { "input": "In search of new targets for retinal neuroprotection: is there a role for autophagy?", "output": "There is no related enetity." }, { "input": "Autophagy is a highly conserved catabolic pathway in which proteins and organelles are engulfed by vacuoles that are targeted to lysosomes for degradation.", "output": "There is no related enetity." }, { "input": "Defects in the autophagic machinery have been described in several neurodegenerative diseases uncovering the tight dependency of neuronal survival on the efficiency of the autophagic process.", "output": "There is no related enetity." }, { "input": "Despite the large amount of literature investigating autophagy in a number of pathological conditions our knowledge of its role in glaucoma neurodegeneration is just beginning.", "output": "There is no related enetity." }, { "input": "However, recent experimental data revealing that autophagy modulation occurs in retinal ganglion cells ( RGCs ) under glaucoma - related stressing conditions support the hypothesis that dysfunctional autophagy might underlie the process leading to RGC death.", "output": "There is no related enetity." }, { "input": "Although our understanding of the role of autophagy in glaucoma is still developing, there is the possibility that neuroprotection may be achieved by modulating autophagy.", "output": "There is no related enetity." }, { "input": "This would be a promising approach as it could lead to the much - sought development of alternative therapeutic strategies to prevent visual loss in glaucoma.", "output": "There is no related enetity." }, { "input": "Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value.", "output": "There is no related enetity." }, { "input": "With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability.", "output": "There is no related enetity." }, { "input": "In vitro estrogenic potencies of three model compounds ( bisphenol A, genistein, and 4 - nonylphenol ) relative to ethinylestradiol ( EE2 ), determined with the estrogen receptor alpha ( ER alpha ) transcriptional activation assay using hER - HeLa - 9903 cells, were taken from literature and used to calculate the EE2 equivalent ( EE2EQ ) effect doses in the predominantly ER alpha - dependent rat uterotrophic assay.", "output": "bisphenol A, genistein, 4 - nonylphenol, ethinylestradiol, EE2, estrogen, EE2." }, { "input": "Compound - specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated.", "output": "EE2." }, { "input": "The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6 - 25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1. 6 - 2. 1 for especially genistein and bisphenol A.", "output": "genistein, bisphenol A." }, { "input": "Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance.", "output": "EE2." }, { "input": "For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites.", "output": "There is no related enetity." }, { "input": "Simple photosystem II water oxidation centre analogues in visible light oxygen and H + generation.", "output": "oxygen, H +." }, { "input": "Calcium manganese oxide nanoparticles for application in water oxidation are synthesized by combination with a carboxylated biopolymer stabilizing agent to form very simple but effective analogues of the photosynthetic PSII oxygen evolving complex.", "output": "Calcium manganese oxide, oxygen." }, { "input": "The relative efficiency of these materials for production of O ( 2 ) and protons under visible light - promoted reactions is evaluated and prolonged reaction lifetimes are observed.", "output": "O ( 2 )." }, { "input": "A calibrated human Y - chromosomal phylogeny based on resequencing.", "output": "There is no related enetity." }, { "input": "We have identified variants present in high - coverage complete sequences of 36 diverse human Y chromosomes from Africa, Europe, South Asia, East Asia, and the Americas, representing eight major haplogroups.", "output": "There is no related enetity." }, { "input": "After restricting our analysis to 8. 97 Mb of the unique male - specific Y sequence, we identified 6662 high - confidence variants, including single - nucleotide polymorphisms ( SNPs ), multi - nucleotide polymorphisms ( MNPs ), and indels.", "output": "There is no related enetity." }, { "input": "We constructed phylogenetic trees using these variants, or subsets of them, and recapitulated the known structure of the tree.", "output": "There is no related enetity." }, { "input": "Assuming a male mutation rate of 1 x 10 ( - 9 ) per base pair per year, the time depth of the tree ( haplogroups A3 - R ) was ~ 101, 000 - 115, 000 yr, and the lineages found outside Africa dated to 57, 000 - 74, 000 yr, both as expected.", "output": "There is no related enetity." }, { "input": "In addition, we dated a striking Paleolithic male lineage expansion to 41, 000 - 52, 000 yr ago and the node representing the major European Y lineage, R1b, to 4000 - 13, 000 yr ago, supporting a Neolithic origin for these modern European Y chromosomes.", "output": "There is no related enetity." }, { "input": "In all, we provide a nearly 10 - fold increase in the number of Y markers with phylogenetic information, and novel historical insights derived from placing them on a calibrated phylogenetic tree.", "output": "There is no related enetity." }, { "input": "Pim kinases in cancer: diagnostic, prognostic and treatment opportunities.", "output": "There is no related enetity." }, { "input": "PIM proteins belong to a family of ser / thr kinases composed of 3 members, PIM1, PIM2 and PIM3, with greatly overlapping functions.", "output": "ser, thr." }, { "input": "PIM kinases are mainly responsible for cell cycle regulation, antiapoptotic activity and the homing and migration of receptor tyrosine kinases mediated via the JAK / STAT pathway.", "output": "tyrosine." }, { "input": "PIM kinases have been found to be upregulated in many hematological malignancies and solid tumors.", "output": "There is no related enetity." }, { "input": "Although these kinases have been described as weak oncogenes, they are heavily targeted for anticancer drug discovery.", "output": "There is no related enetity." }, { "input": "The present review summarizes the discoveries made to date regarding PIM kinases as driving oncogenes in the process of tumorigenesis and their validation as drug targets.", "output": "There is no related enetity." }, { "input": "Process analytical tools for monitoring, understanding, and control of pharmaceutical fluidized bed granulation: A review.", "output": "There is no related enetity." }, { "input": "Fluidized bed granulation is a widely applied wet granulation technique in the pharmaceutical industry to produce solid dosage forms.", "output": "There is no related enetity." }, { "input": "The process involves the spraying of a binder liquid onto fluidizing powder particles.", "output": "There is no related enetity." }, { "input": "As a result, the ( wetted ) particles collide with each other and form larger permanent aggregates ( granules ).", "output": "There is no related enetity." }, { "input": "After spraying the required amount of granulation liquid, the wet granules are rapidly dried in the fluid bed granulator.", "output": "There is no related enetity." }, { "input": "Since the FDA launched its Process Analytical Technology initiative ( and even before ), a wide range of analytical process sensors has been used for real - time monitoring and control of fluid bed granulation processes.", "output": "There is no related enetity." }, { "input": "By applying various data analysis techniques to the multitude of data collected from the process analyzers implemented in fluid bed granulators, a deeper understanding of the process has been achieved.", "output": "There is no related enetity." }, { "input": "This review gives an overview of the process analytical technologies used during fluid bed granulation to monitor and control the process.", "output": "There is no related enetity." }, { "input": "The fundamentals of the mechanisms contributing to wet granule growth and the characteristics of fluid bed granulation processing are briefly discussed.", "output": "There is no related enetity." }, { "input": "This is followed by a detailed overview of the in - line applied process analyzers, contributing to improved fluid bed granulation understanding, modeling, control, and endpoint detection.", "output": "There is no related enetity." }, { "input": "Analysis and modeling tools enabling the extraction of the relevant information from the complex data collected during granulation and the control of the process are highlighted.", "output": "There is no related enetity." }, { "input": "Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate.", "output": "eldecalcitol, alendronate, alfacalcidol, alendronate." }, { "input": "Eldecalcitol ( ELD ), a 2 beta - hydroxypropyloxy derivative of 1 alpha, 25 ( OH ) 2D3, inhibits bone resorption more potently than alfacalcidol ( ALF ) while maintaining osteoblastic function in an ovariectomized ( OVX ) osteoporosis rat model.", "output": "Eldecalcitol, ELD, 2 beta - hydroxypropyloxy, 1 alpha , 25 ( OH ) 2D3, alfacalcidol, ALF." }, { "input": "Alendronate ( ALN ), which is the most common bisphosphonate used for the treatment of osteoporosis, increases the bone mineral density ( BMD ) by suppressing bone resorption.", "output": "Alendronate, ALN, bisphosphonate." }, { "input": "In this study, we investigated the effects of combination treatments with ELD and ALN or with ALF and ALN on bone mass and strength in OVX rats.", "output": "ELD, ALN, ALF, ALN." }, { "input": "Seventy female rats, 32 weeks old, were assigned to seven groups: ( 1 ) a sham - operated control group; ( 2 ) an OVX - control group; ( 3 ) an ELD group; ( 4 ) an ALF group; ( 5 ) an ALN group; ( 6 ) an ELD + ALN group; and ( 7 ) an ALF + ALN group.", "output": "ELD, ALF, ALN, ELD, ALN, ALF, ALN." }, { "input": "OVX rats were orally treated with ELD ( 0. 015 mu g / kg ), ALF ( 0. 0375 mu g / kg ), or ALN ( 0. 2mg / kg ) daily for 12 weeks.", "output": "ELD, ALF, ALN." }, { "input": "In both the lumbar spine and the femur, ELD and ALF monotherapy significantly increased the BMD, and ELD + ALN and ALF + ALN significantly increased the BMD, compared with ALN monotherapy, as an additive effect.", "output": "ELD, ALF, ELD, ALN, ALF, ALN, ALN." }, { "input": "In particular, ELD + ALN resulted in a significantly higher BMD than ALF + ALN in the femur.", "output": "ELD, ALN, ALF, ALN." }, { "input": "On mechanical testing of the lumbar spine, ELD and ALF monotherapy significantly increased the ultimate load, and ELD + ALN and ALF + ALN significantly increased the ultimate load compared with ALN monotherapy.", "output": "ELD, ALF, ELD, ALN, ALF, ALN, ALN." }, { "input": "In the femur, ELD, ELD + ALN, and ALF + ALN treatment significantly increased the ultimate load, compared with the OVX - control group, and ELD + ALN resulted in a significantly higher ultimate load than ALN monotherapy.", "output": "ELD, ELD, ALN, ALF, ALN, ELD, ALN, ALN." }, { "input": "A histomorphometric analysis showed that ELD monotherapy and ELD + ALN combination therapy had a potent inhibitory effect on bone resorption parameters ( osteoclast surface and eroded surface ), while maintaining bone formation parameters ( osteoblast surface and osteoid surface ).", "output": "ELD, ELD, ALN." }, { "input": "By contrast, ALF and ALF + ALN significantly lowered the histological parameters of both bone resorption and formation.", "output": "ALF, ALF, ALN." }, { "input": "These results suggested that ELD or ALF used in combination with ALN has therapeutic advantages over ALN monotherapy, with ELD + ALN combination treatment producing an especially beneficial anti - osteoporotic effect by inhibiting osteoclastic bone resorption and maintaining osteoblastic function, compared with ALF + ALN combination treatment.", "output": "ELD, ALF, ALN, ALN, ELD, ALN, ALF, ALN." }, { "input": "Ischemia - induced synaptic plasticity drives sustained expression of calcium - permeable AMPA receptors in the hippocampus.", "output": "calcium." }, { "input": "Long lasting enhancement of synaptic transmission can be triggered by brief bursts of afferent stimulation, underlying long - term potentiation ( LTP ), and also by brief ischemia in a process known as i - LTP.", "output": "There is no related enetity." }, { "input": "The extent to which LTP and i - LTP rely on comparable cellular mechanisms remains unclear.", "output": "There is no related enetity." }, { "input": "Under physiological conditions, LTP induction drives transient expression of calcium - permeable AMPARs ( CP - AMPARs ) at synapses, whose ability to undergo plasticity is primed by endogenous activation of adenosine A ( 2A ) receptors ( A ( 2A ) Rs ).", "output": "calcium, adenosine." }, { "input": "The present work thus addressed the contribution of CP - AMPARs and A ( 2A ) Rs to i - LTP, which was induced in rat hippocampal slices by brief ( 10 min ) oxygen / glucose deprivation ( OGD ).", "output": "oxygen, glucose." }, { "input": "The amplitude of afferent - evoked excitatory postsynaptic currents ( EPSCs ) recorded from CA1 pyramidal neurons was decreased during OGD but gradually recovered toward values significantly above ( 157 +/- 17 % ) the baseline ( 100 % ) 40 - 50 min after re - oxygenation.", "output": "There is no related enetity." }, { "input": "This i - LTP was precluded by CP - AMPAR blockade ( internal spermine ( 500 mu M ) or extracellular NASPM ( 20 mu M ) application ) as well as by A ( 2A ) R blockade with a selective antagonist ( SCH 58261, 100 nM ).", "output": "spermine, NASPM, SCH 58261." }, { "input": "OGD prompted sustained ( > 70 min ) facilitation of mEPSC amplitude and frequency, and decreased mEPSC decay time, all of which were prevented by SCH 58261 ( 100 nM ).", "output": "SCH 58261." }, { "input": "The ability of NASPM ( 20 mu M ) to acutely inhibit EPSCs 1 h after OGD, but not in control conditions nor in OGD - challenged slices when in the presence of SCH 58261 ( 100 nM ), further supports sustained CP - AMPAR recruitment by i - LTP in an A ( 2A ) R - dependent way.", "output": "NASPM, SCH 58261." }, { "input": "We propose that although i - LTP may initially mimic LTP, failure of auto - regulated CP - AMPAR removal from synapses could constitute an early divergent event between these forms of plasticity.", "output": "There is no related enetity." }, { "input": "Salt bridge switching from Arg290 / Glu167 to Arg290 / ATP promotes the closed - to - open transition of the P2X2 receptor.", "output": "Arg290, Glu167, Arg290, ATP." }, { "input": "P2X receptors are trimeric adenosine - 5 ' - triphosphate ( ATP ) - gated cation channels involved in fast signal transduction in many cell types.", "output": "adenosine - 5 ' - triphosphate, ATP." }, { "input": "In this study, we used homology modeling of the rat P2X2 receptor with the zebrafish P2X4 X - ray template to determine that the side chains of the Glu167 and Arg290 residues are in close spatial vicinity within the ATP - binding pocket when the rat P2X2 channel is closed.", "output": "Glu167, Arg290, ATP." }, { "input": "Through charge reversal mutation analysis and mutant cycle analysis, we obtained evidence that Glu167 and Arg290 form an electrostatic interaction.", "output": "Glu167, Arg290." }, { "input": "In addition, disulfide trapping indicated the close proximity of Glu167 and Arg290 when the channel is in the closed state, but not in the ATP - bound open state.", "output": "disulfide, Glu167, Arg290, ATP." }, { "input": "Consistent with a gating - induced movement that disrupts the Glu167 / Arg290 salt bridge, a comparison of the closed and open rat P2X2 receptor models revealed a significant rearrangement of the protein backbone and the side chains of the Glu167 and Arg290 residues during the closed - to - open transition.", "output": "Glu167, Arg290, Glu167, Arg290." }, { "input": "The associated release of the Glu167 / Arg290 salt bridge during channel opening allows a strong ionic interaction between Arg290 and a gamma - phosphate oxygen of ATP.", "output": "Glu167, Arg290, Arg290, gamma - phosphate oxygen, ATP." }, { "input": "We conclude from these results that the state - dependent salt bridge switching from Arg290 / Glu167 to Arg290 / ATP fulfills a dual role: to destabilize the closed state of the receptor and to promote the ionic coordination of ATP in the ATP - binding pocket.", "output": "Arg290, Glu167, Arg290, ATP, ATP, ATP." }, { "input": "Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.", "output": "organochlorine, dieldrin." }, { "input": "Organochlorine pesticides ( OCPs ) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates.", "output": "Organochlorine, dieldrin." }, { "input": "In this study, female and male largemouth bass ( Micropterus salmoides ) ( LMB ) were exposed to 3mg dieldrin / kg feed in a 2 month feeding exposure ( August - October ) to ( 1 ) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; ( 2 ) characterize cell signaling cascades underlying dieldrin neurotoxicity; and ( 3 ) determine whether or not co - feeding with 17 beta - estradiol ( E ( 2 ) ), a hormone with neuroprotective roles, mitigates responses in males to dieldrin.", "output": "dieldrin, dieldrin, dieldrin, 17 beta - estradiol, dieldrin." }, { "input": "Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints ( e. g. gonadosomatic index, vitellogenin, or plasma E ( 2 ) ).", "output": "estrogen, dieldrin." }, { "input": "Sub - network ( SNEA ) and gene set enrichment analysis ( GSEA ) revealed that neuro - hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure.", "output": "dieldrin." }, { "input": "Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin.", "output": "dieldrin." }, { "input": "These data suggest that ( 1 ) there are sexually dimorphic responses in the teleost hypothalamus; ( 2 ) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and ( 3 ) males co - fed dieldrin and E ( 2 ) had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E ( 2 ) may mitigate the effects of dieldrin in the central nervous system.", "output": "dieldrin, dieldrin, dieldrin." }, { "input": "Exposure to valproic acid inhibits chondrogenesis and osteogenesis in mid - organogenesis mouse limbs.", "output": "valproic acid." }, { "input": "In utero exposure to valproic acid ( VPA ), a histone deacetylase ( HDAC ) inhibitor, causes neural tube, heart, and limb defects.", "output": "valproic acid, VPA." }, { "input": "Valpromide ( VPD ), the amide derivative of VPA, does not inhibit HDAC activity and is a weak teratogen in vivo.", "output": "Valpromide, VPD, amide, VPA." }, { "input": "The detailed mechanism of action of VPA as a teratogen is not known.", "output": "VPA." }, { "input": "The goal of this study was to test the hypothesis that VPA disrupts regulation of the expression of genes that are critical in chondrogenesis and osteogenesis during limb development.", "output": "VPA." }, { "input": "Murine gestation day - 12 embryonic forelimbs were excised and exposed to VPA or VPD in a limb bud culture system.", "output": "VPA, VPD." }, { "input": "VPA caused a significant concentration - dependent increase in limb abnormalities, which was correlated with its HDAC inhibitory effect.", "output": "VPA." }, { "input": "The signaling of both Sox9 and Runx2, key regulators of chondrogenesis, was downregulated by VPA.", "output": "VPA." }, { "input": "In contrast, VPD had little effect on limb morphology and no significant effect on HDAC activity or the expression of marker genes.", "output": "VPD." }, { "input": "Thus, VPA exposure dysregulated the expression of target genes directly involved in chondrogenesis and osteogenesis in the developing limb.", "output": "VPA." }, { "input": "Disturbances in these signaling pathways are likely to be a consequence of HDAC inhibition because VPD did not affect their expressions.", "output": "VPD." }, { "input": "Tumor necrosis factor - alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.", "output": "amiodarone." }, { "input": "Amiodarone ( AMD ), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients.", "output": "Amiodarone, AMD." }, { "input": "We demonstrated previously that tumor necrosis factor - alpha ( TNF - alpha ) plays an important role in a rat model of AMD - induced hepatotoxicity under inflammatory stress.", "output": "AMD." }, { "input": "In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity.", "output": "AMD." }, { "input": "AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity.", "output": "AMD." }, { "input": "Activation of caspases 9 and 3 / 7 was observed in AMD / TNF - cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity.", "output": "AMD." }, { "input": "Intracellular reactive oxygen species ( ROS ) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment.", "output": "oxygen, AMD." }, { "input": "Adding water - soluble antioxidants ( trolox, N - acetylcysteine, glutathione, or ascorbate ) produced only minor attenuation of AMD / TNF - induced cytotoxicity and did not influence the effect of AMD alone.", "output": "trolox, N - acetylcysteine, glutathione, ascorbate, AMD, AMD." }, { "input": "On the other hand, alpha - tocopherol ( TOCO ), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD / TNF cotreatment.", "output": "alpha - tocopherol, TOCO, AMD, AMD." }, { "input": "alpha - TOCO plus a pancaspase inhibitor completely abolished AMD / TNF - induced cytotoxicity.", "output": "alpha - TOCO, AMD." }, { "input": "In summary, activation of caspases and oxidative stress were observed after AMD / TNF cotreatment, and caspase inhibitors and a lipid - soluble free - radical scavenger attenuated AMD / TNF - induced cytotoxicity.", "output": "AMD, AMD." }, { "input": "Cannabidiol inhibits THC - elicited paranoid symptoms and hippocampal - dependent memory impairment.", "output": "Cannabidiol, THC." }, { "input": "Community - based studies suggest that cannabis products that are high in Delta 9 - tetrahydrocannabinol ( THC ) but low in cannabidiol ( CBD ) are particularly hazardous for mental health.", "output": "Delta 9 - tetrahydrocannabinol, THC, cannabidiol, CBD." }, { "input": "Laboratory - based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions.", "output": "THC, CBD." }, { "input": "In a between - subjects design, we tested the hypothesis that pre - treatment with CBD inhibited THC - elicited psychosis and cognitive impairment.", "output": "CBD, THC." }, { "input": "Healthy participants were randomised to receive oral CBD 600 mg ( n = 22 ) or placebo ( n = 26 ), 210 min ahead of intravenous ( IV ) THC ( 1. 5 mg ).", "output": "CBD, THC." }, { "input": "Post - THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance.", "output": "THC, CBD." }, { "input": "However, clinically significant positive psychotic symptoms ( defined a priori as increases >= 3 points ) were less likely in the CBD group compared with the placebo group, odds ratio ( OR ) = 0. 22 ( chi (2) = 4. 74, p < 0. 05 ).", "output": "CBD." }, { "input": "In agreement, post - THC paranoia, as rated with the State Social Paranoia Scale ( SSPS ), was less in the CBD group compared with the placebo group ( t = 2. 28, p < 0. 05 ).", "output": "THC, CBD." }, { "input": "Episodic memory, indexed by scores on the Hopkins Verbal Learning Task - revised ( HVLT - R ), was poorer, relative to baseline, in the placebo pre - treated group ( - 10. 6 +/- 18. 9 % ) compared with the CBD group ( - 0. 4 % +/- 9. 7 % ) ( t = 2. 39, p < 0. 05 ).", "output": "CBD." }, { "input": "These findings support the idea that high - THC / low - CBD cannabis products are associated with increased risks for mental health.", "output": "THC, CBD." }, { "input": "Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter.", "output": "amino acids, cholesterol." }, { "input": "The bihelical apolipoprotein mimetic peptide 5A effluxes cholesterol from cells and reduces inflammation and atherosclerosis in animal models.", "output": "cholesterol." }, { "input": "We investigated how hydrophobic residues in the hinge region between the two helices are important in the structure and function of this peptide.", "output": "There is no related enetity." }, { "input": "By simulated annealing analysis and molecular dynamics modeling, two hydrophobic amino acids, F - 18 and W - 21, in the hinge region were predicted to be relatively surface - exposed and to interact with the aqueous solvent.", "output": "amino acids." }, { "input": "Using a series of 5A peptide analogs in which F - 18 or W - 21 was changed to either F, W, A, or E, only peptides with hydrophobic amino acids in these two positions were able to readily bind and solubilize phospholipid vesicles.", "output": "amino acids." }, { "input": "Compared with active peptides containing F or W, peptides containing E in either of these two positions were more than 10 - fold less effective in effluxing cholesterol by the ABCA1 transporter.", "output": "cholesterol." }, { "input": "Intravenous injection of 5A in C57BL / 6 mice increased plasma - free cholesterol ( 5A: 89. 9 +/- 13. 6 mg / dl; control: 38. 7 +/- 4. 3 mg / dl ( mean +/- S. D. ); P < 0. 05 ) and triglycerides ( 5A: 887. 0 +/- 172. 0 mg / dl; control: 108. 9 +/- 9. 9 mg / dl; P < 0. 05 ), whereas the EE peptide containing E in both positions had no effect.", "output": "cholesterol, triglycerides." }, { "input": "Finally, 5A increased cholesterol efflux approximately 2. 5 - fold in vivo from radiolabeled macrophages, whereas the EE peptide was inactive.", "output": "cholesterol." }, { "input": "These results provide a rationale for future design of therapeutic apolipoprotein mimetic peptides and provide new insights into the interaction of hydrophobic residues on apolipoproteins with phospholipids in the lipid microdomain created by the ABCA1 transporter during the cholesterol efflux process.", "output": "cholesterol." }, { "input": "Efficacy of the GluK1 / AMPA receptor antagonist LY293558 against seizures and neuropathology in a soman - exposure model without pretreatment and its pharmacokinetics after intramuscular administration.", "output": "AMPA, LY293558." }, { "input": "Control of brain seizures after exposure to nerve agents is imperative for the prevention of brain damage and death.", "output": "There is no related enetity." }, { "input": "Animal models of nerve agent exposure make use of pretreatments, or medication administered within 1 minute after exposure, in order to prevent rapid death from peripheral toxic effects and respiratory failure, which then allows the testing of anticonvulsant compounds.", "output": "There is no related enetity." }, { "input": "However, in a real - case scenario of an unexpected attack with nerve agents, pretreatment would not be possible, and medical assistance may not be available immediately.", "output": "There is no related enetity." }, { "input": "To determine if control of seizures and survival are still possible without pretreatment or immediate pharmacologic intervention, we studied the anticonvulsant efficacy of the GluK1 ( GluR5 ) / alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazolepropionic acid ( AMPA ) receptor antagonist ( 3S, 4aR, 6R, 8aR ) - 6 - [ 2 - ( 1 ( 2 ) H - tetrazole - 5 - yl ) ethyl ] decahydroisoquinoline - 3 - carboxylic acid ( LY293558 ) in rats that did not receive any treatment until 20 minutes after exposure to the nerve agent soman.", "output": "alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazolepropionic acid, AMPA, ( 3S , 4aR , 6R , 8aR ) - 6 - [ 2 - ( 1 ( 2 ) H - tetrazole - 5 - yl ) ethyl ] decahydroisoquinoline - 3 - carboxylic acid, LY293558." }, { "input": "We injected LY293558 intramuscularly, as this would be the most likely route of administration to humans.", "output": "LY293558." }, { "input": "LY293558 ( 15 mg / kg ), injected along with atropine and the oxime HI - 6 at 20 minutes after soman exposure, stopped seizures and increased survival rate from 64 % to 100 %.", "output": "LY293558, oxime, HI - 6." }, { "input": "LY293558 also prevented neuronal loss in the amygdala and hippocampus, and reduced neurodegeneration in a number of brain regions studied 7 days after soman exposure.", "output": "LY293558." }, { "input": "Analysis of the LY293558 pharmacokinetics after intramuscular administration showed that this compound readily crosses the blood - brain barrier.", "output": "LY293558." }, { "input": "There was good correspondence between the time course of seizure suppression by LY293558 and the brain levels of the compound.", "output": "LY293558." }, { "input": "Regulation of a viral proteinase by a peptide and DNA in one - dimensional space: II. adenovirus proteinase is activated in an unusual one - dimensional biochemical reaction.", "output": "There is no related enetity." }, { "input": "Late in an adenovirus infection, the viral proteinase ( AVP ) becomes activated to process virion precursor proteins used in virus assembly.", "output": "There is no related enetity." }, { "input": "AVP is activated by two cofactors, the viral DNA and pVIc, an 11 - amino acid peptide originating from the C terminus of the precursor protein pVI.", "output": "pVIc, amino acid, C." }, { "input": "There is a conundrum in the activation of AVP in that AVP and pVI are sequence - independent DNA - binding proteins with nm equilibrium dissociation constants such that in the virus particle, they are predicted to be essentially irreversibly bound to the viral DNA.", "output": "There is no related enetity." }, { "input": "Here, we resolve that conundrum by showing that activation of AVP takes place on the one - dimensional contour of DNA.", "output": "There is no related enetity." }, { "input": "In vitro, pVI, a substrate, slides on DNA via one - dimensional diffusion, D ( 1 ) = 1. 45 x 10 ( 6 ) bp ( 2 ) / s, until it binds to AVP also on the same DNA molecule.", "output": "There is no related enetity." }, { "input": "AVP, partially activated by being bound to DNA, excises pVIc, which binds to the AVP molecule that cut it out.", "output": "pVIc." }, { "input": "pVIc then forms a disulfide bond with AVP forming the fully active AVP - pVIc complex bound to DNA.", "output": "pVIc, disulfide, pVIc." }, { "input": "In vivo, in heat - disrupted immature virus, AVP was also activated by pVI in DNA - dependent reactions.", "output": "There is no related enetity." }, { "input": "This activation mechanism illustrates a new paradigm for virion maturation and a new way, by sliding on DNA, for bimolecular complexes to form among proteins not involved in DNA metabolism.", "output": "There is no related enetity." }, { "input": "Grafting efficiency of synthetic polymers onto biomaterials: a comparative study of grafting - from versus grafting - to.", "output": "There is no related enetity." }, { "input": "In the present study, the two grafting techniques grafting - from - by activators regenerated by electron transfer atom transfer radical polymerization ( ARGET ATRP ) - and grafting - to - by copper ( I ) - catalyzed azide - alkyne cycloaddition ( CuAAC ) - were systematically compared, employing cellulose as a substrate.", "output": "copper ( I ), azide - alkyne." }, { "input": "In order to obtain a meaningful comparison, it is crucial that the graft lengths of the polymers that are grafted from and to the substrates are essentially identical.", "output": "There is no related enetity." }, { "input": "Herein, this was achieved by utilizing the free polymer formed in parallel to the grafting - from reaction as the polymer for the grafting - to reaction.", "output": "There is no related enetity." }, { "input": "Four graft lengths were investigated, and the molar masses of the four free polymers ( 21 <= M ( n ) <= 100 kDa; 1. 07 <= D ( M ) <= 1. 26 ), i. e. the polymers subsequently employed in the grafting - to reaction, were shown to be in the same range as the molar masses of the polymers grafted from the surface ( 23 <= M ( n ) <= 87 kDa; 1. 08 <= D ( M ) <= 1. 31 ).", "output": "There is no related enetity." }, { "input": "The molecular weights of the chains grafted from the surface were established after cleavage from the cellulose substrates via size exclusion chromatography ( SEC ).", "output": "There is no related enetity." }, { "input": "High - resolution Fourier transform infrared microscopy ( FT - IRM ) was employed as an efficient tool to study the spatial distribution of the polymer content on the grafted substrates.", "output": "There is no related enetity." }, { "input": "In addition, the functionalized substrates were analyzed by X - ray photoelectron spectroscopy ( XPS ), contact angle ( CA ) measurements, and field - emission scanning electron microscopy ( FE - SEM ).", "output": "There is no related enetity." }, { "input": "For cellulose substrates modified via the grafting - from approach, the content of polymer on the surfaces increased with increasing graft length, confirming the possibility to tailor not only the length of the polymer grafts but also the polymeric content on the surface.", "output": "There is no related enetity." }, { "input": "In comparison, for the grafting - to reaction, the grafted content could not be controlled by varying the length of the preformed polymer: the polymer content was essentially the same for the four graft lengths.", "output": "There is no related enetity." }, { "input": "Consequently, the obtained results, when employing cellulose as a substrate and under these conditions, suggest that the grafting - from approach is superior to the grafting - to technique with respect to controlling the distribution of the polymeric content on the surface.", "output": "There is no related enetity." }, { "input": "A temporary decrease in mineral density in perinatal mouse long bones.", "output": "There is no related enetity." }, { "input": "Fetal and postnatal bone development in humans is traditionally viewed as a process characterized by progressively increasing mineral density.", "output": "There is no related enetity." }, { "input": "Yet, a temporary decrease in mineral density has been described in the long bones of infants in the immediate postnatal period.", "output": "There is no related enetity." }, { "input": "The mechanism that underlies this phenomenon, as well as its causes and consequences, remain unclear.", "output": "There is no related enetity." }, { "input": "Using daily mu CT scans of murine femora and tibiae during perinatal development, we show that a temporary decrease in tissue mineral density ( TMD ) is evident in mice.", "output": "There is no related enetity." }, { "input": "By monitoring spatial and temporal structural changes during normal growth and in a mouse strain in which osteoclasts are non - functional ( Src - null ), we show that endosteal bone resorption is the main cause for the perinatal decrease in TMD.", "output": "There is no related enetity." }, { "input": "Mechanical testing revealed that this temporary decrease is correlated with reduced stiffness of the bones.", "output": "There is no related enetity." }, { "input": "We also show, by administration of a progestational agent to pregnant mice, that the decrease in TMD is not the result of parturition itself.", "output": "There is no related enetity." }, { "input": "This study provides a comprehensive view of perinatal long bone development in mice, and describes the process as well as the consequences of density fluctuation during this period.", "output": "There is no related enetity." }, { "input": "The early mouse 3D osteocyte network in the presence and absence of mechanical loading.", "output": "There is no related enetity." }, { "input": "Osteocytes are considered to act as mechanosensory cells in bone.", "output": "There is no related enetity." }, { "input": "They form a functional synctia in which their processes become interconnected to constitute a three - dimensional ( 3D ) network.", "output": "There is no related enetity." }, { "input": "Previous studies reported that in mice, the two - dimensional osteocyte network becomes progressively more regular as they grow, although the key factors governing the arrangement of the osteocyte network during bone growth remain unknown.", "output": "There is no related enetity." }, { "input": "In this study, we characterized the 3D formation of the osteocyte network during bone growth.", "output": "There is no related enetity." }, { "input": "Morphological skeletal changes have been reported to occur in response to mechanical loading and unloading.", "output": "There is no related enetity." }, { "input": "In order to evaluate the effect of mechanical unloading on osteocyte network formation, we subjected newborn mice to sciatic neurectomy in order to immobilize their left hind limb as an unloading model.", "output": "There is no related enetity." }, { "input": "The osteocyte network was visualized by staining osteocyte cell bodies and processes with fluorescently labeled phalloidin.", "output": "phalloidin." }, { "input": "First, we compared the osteocyte network in the femora of embryonic and 6 - week - old mice in order to understand the morphological changes that occur with normal growth and mechanical loading.", "output": "There is no related enetity." }, { "input": "In embryonic mice, the osteocyte network in the femur cortical bone displayed a random cell body distribution, non - directional orientation of cell processes, and irregularly shaped cells.", "output": "There is no related enetity." }, { "input": "In 6 - week - old mice, the 3D network contained spindle - shaped osteocytes, which were arranged parallel to the longitudinal axis of the femur.", "output": "There is no related enetity." }, { "input": "In addition, more and longer cell processes radiated from each osteocyte.", "output": "There is no related enetity." }, { "input": "Second, we compared the cortical osteocyte networks of 6 - week - old mice that had or had not undergone sciatic neurectomy in order to evaluate the effect of unloading on osteocyte network formation.", "output": "There is no related enetity." }, { "input": "The osteocyte network formation in both cortical bone and cancellous bone was affected by mechanical loading.", "output": "There is no related enetity." }, { "input": "However, there were differences in the extent of network formation between cortical bone and cancellous bone in response to mechanical loading with regard to the orientation, nuclear shape and branch formation.", "output": "There is no related enetity." }, { "input": "Ketamine combinations for the field treatment of soman - induced self - sustaining status epilepticus.", "output": "Ketamine, soman." }, { "input": "Review of current data and perspectives.", "output": "There is no related enetity." }, { "input": "Organophosphorus nerve agents ( NA ), potent irreversible cholinesterase inhibitors, could induce severe seizures, status epilepticus ( SE ), seizure - related brain damage ( SRBD ) and lethality.", "output": "Organophosphorus." }, { "input": "Despite the lack of data in the case of NA, clinical evidences suggest that SE survivors could suffer from neurological / cognitive deficits and impairments such as spontaneous recurrent seizures ( epilepsy ) after a latent period of epileptogenesis.", "output": "There is no related enetity." }, { "input": "It is beyond doubt that an effective and quick management of the initial seizures and prevention of SRBD are critical to prevent these long - term consequences, explaining why most experimental data are focusing on the 5 - 40min post - exposure time frame.", "output": "There is no related enetity." }, { "input": "However, in field conditions, treatment may be delayed and with the exception of NMDA receptor antagonists, currently no drug provides protection ( against lethality, seizures, SRBD and neurological consequences ) when seizures are left unabated for one hour or more.", "output": "NMDA." }, { "input": "Ketamine ( KET ) is the only NMDA antagonist licensed as an injectable drug in different countries and remains an anesthetic of choice in some difficult field conditions.", "output": "Ketamine, KET, NMDA." }, { "input": "In this short review paper, after a presentation of some of the key points of the pathophysiology of NA - induced SE and a quick survey of the potential therapeutic avenues in the context of delayed treatment of NA - induced SE, we will review the recent data we obtained showing that KET, in combination with atropine sulfate ( AS ), with or without a benzodiazepine, considerably reduces soman - induced neuroinflammation, provides neuroprotection, histologically and functionally, and also positively modify soman - induced changes in brain metabolism.", "output": "KET, atropine sulfate, benzodiazepine, soman, soman." }, { "input": "Finally, we will also mention some results from safety studies including those bringing evidence that, at difference with MK - 801, KET does not impair thermoregulation and even seems to reduce AS - induced heat stress.", "output": "MK - 801, KET." }, { "input": "All in all, KET, in combination, appears a good candidate for the out - of - hospital treatment of severe NA - induced SE.", "output": "KET." }, { "input": "A cross - linked polymeric micellar delivery system for cisplatin ( IV ) complex.", "output": "cisplatin ( IV )." }, { "input": "A polymeric cisplatin ( IV ) prodrug in the form of cross - linked micelles ( M ( Pt ( IV ) ) was prepared by first constructing MPEG - b - PCL - b - PLL micelles and then attaching a cisplatin ( IV ) complex with two axial succinic moieties to the lysine residues of the carrier polymer in aqueous medium.", "output": "cisplatin ( IV ), Pt ( IV ), cisplatin ( IV )." }, { "input": "The micelles obtained were characterized by TEM, DLS, and zeta potential measurement.", "output": "There is no related enetity." }, { "input": "Their in vitro release experiments were carried out at pH 7. 4 and 5. 0 or in the presence of 5mM sodium ascorbate ( NaAsc ).", "output": "sodium ascorbate, NaAsc." }, { "input": "Results showed that the micelles were sensitive to both acidic hydrolysis and mild reducing agents; in the presence of 5mM NaAsc, cisplatin ( II ) was directly released and the released cisplatin ( II ) could chelate with nucleobases; the micelles displayed comparable cytotoxicities to cisplatin; and the micelles were much more efficiently internalized by the cells than cisplatin ( II ) and cisplatin ( IV ) counterparts.", "output": "cisplatin ( II ), cisplatin ( II ), nucleobases, cisplatin, cisplatin ( II ), cisplatin ( IV )." }, { "input": "Moreover, in vivo study showed accumulation of more Pt species in the tumor site and lower systematic toxicity compared to free cisplatin ( II ) and cisplatin ( IV ).", "output": "cisplatin ( II ), cisplatin ( IV )." }, { "input": "This polymeric prodrug of cisplatin is expected to be used more for future study and applications.", "output": "cisplatin." }, { "input": "Design, synthesis and biological evaluation of benzothiazepinones ( BTZs ) as novel non - ATP competitive inhibitors of glycogen synthase kinase - 3 beta ( GSK - 3 beta ).", "output": "benzothiazepinones, BTZs, ATP." }, { "input": "Glycogen synthase kinase - 3 beta ( GSK - 3 beta ) plays a key role in type II diabetes and Alzheimer ' s diseases, to which non - ATP competitive inhibitors represent an effectively therapeutical approach due to their good specificity.", "output": "ATP." }, { "input": "Herein, a series of small molecules benzothiazepinones ( BTZs ) as novel non - ATP competitive inhibitors of GSK - 3 beta have been designed and synthesized.", "output": "benzothiazepinones, BTZs, ATP." }, { "input": "The in vitro evaluation performed by luminescent assay showed most BTZ derivatives have inhibitory effects in micromolar scale.", "output": "BTZ." }, { "input": "Among them compounds 6l, 6t and 6v have the IC50 values of 25. 0 mu M, 27. 8 mu M and 23. 0 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Moreover 6v is devoid of any inhibitory activity in the assays to other thirteen protein kinases.", "output": "There is no related enetity." }, { "input": "Besides, SAR is analyzed and a hypothetical enzymatic binding mode is proposed by molecular docking study, which would be useful for new candidates design.", "output": "There is no related enetity." }, { "input": "The cholinergic and non - cholinergic effects of organophosphates and oximes in cultured human myoblasts.", "output": "organophosphates, oximes." }, { "input": "Organophosphorus compounds ( OPs ) and oximes may interfere with other molecules than AChE in the living systems, affecting in this way various cellular processes and underlying mechanisms.", "output": "Organophosphorus, oximes." }, { "input": "These non - cholinergic effects may contribute to the clinical status in OP poisoning and therefore deserve equal scientific attention.", "output": "There is no related enetity." }, { "input": "Here, we investigated the effects of tabun and oxime K048 on the processes known to be involved in muscle response to the environmental factors, like IL - 6 release and the regulation of the heat shock proteins ( HSPs ).", "output": "tabun, oxime, K048." }, { "input": "While IL - 6 stimulates muscle regeneration, which follows well known OP - induced myopathy, HSPs have cytoprotective effect against various stress factors including xenobiotics.", "output": "There is no related enetity." }, { "input": "All our experiments were carried out on cultured human myoblasts, as the precursors of muscle regeneration.", "output": "There is no related enetity." }, { "input": "We found unchanged AChE mRNA level after tabun / K048 treatment meaning that tabun and K048 did not interfere with the transcription or stability of this mRNA in the time period tested, even if AChE catalytic activity was significantly affected.", "output": "tabun, K048, tabun, K048." }, { "input": "On the other hand, after myoblast exposure to tabun, we observed significant changes in the protein levels of HSP 27 and in the secretion of IL - 6.", "output": "tabun." }, { "input": "Namely, secretion of IL - 6 decreased to 53 % and the level of HSP 27 increased by 34 % compared to the control level.", "output": "There is no related enetity." }, { "input": "Both effects were attenuated if myoblasts were pretreated with oxime K048, but not if they were treated with K048 after exposure to tabun.", "output": "oxime, K048, K048, tabun." }, { "input": "The molecular mechanism underlying these effects remains to be elucidated.", "output": "There is no related enetity." }, { "input": "However, it seems that these effects could be associated with OPs and oximes as a specific group of compounds rather than as a specific compound itself.", "output": "oximes." }, { "input": "Overall, the effects of OPs and oximes demonstrated here might play an important role in muscle regeneration which importantly determines the final outcome of OP myotoxicity.", "output": "oximes." }, { "input": "A versatile multicomponent assembly via beta - cyclodextrin host - guest chemistry on graphene for biomedical applications.", "output": "beta - cyclodextrin, graphene." }, { "input": "A multi - component nanosystem based on graphene and comprising individual cyclodextrins at its surface is assembled, creating hybrid structures enabling new and important functionalities: optical imaging, drug storage, and cell targeting for medical diagnosis and treatment.", "output": "graphene." }, { "input": "These nanohybrids are part of a universal system of interchangeable units, capable of mutilple functionalities.", "output": "There is no related enetity." }, { "input": "The surface components, made of individual beta - cyclodextrin molecules, are the \" hosts \" for functional units, which may be used as imaging agents, for anti - cancer drug delivery, and as tumor - specific ligands.", "output": "beta - cyclodextrin." }, { "input": "Specifically, individual beta - cyclodextrin ( beta - CD ), with a known capability to host various molecules, is considered a module unit that is assembled onto graphene nanosheet ( GNS ).", "output": "beta - cyclodextrin, beta - CD, graphene." }, { "input": "The cyclodextrin - functionalized graphene nanosheet ( GNS / beta - CD ) enables \" host - guest \" chemistry between the nanohybrid and functional \" payloads \".", "output": "graphene, beta - CD." }, { "input": "The structure, composition, and morphology of the graphene nanosheet hybrid have been investigated.", "output": "graphene." }, { "input": "The nanohybrid, GNS / beta - CD, is highly dispersive in various physiological solutions, reflecting the high biostability of cyclodextrin.", "output": "beta - CD." }, { "input": "Regarding the host capability, the nanohybrid is fully capable of selectively accommodating various biological and functional agents in a controlled fashion, including the antivirus drug amantadine, fluorescent dye [ 5 ( 6 ) - carboxyfluorescein ], and Arg - Gly - Asp ( RGD ) peptide - targeting ligands assisted by an adamantine linker.", "output": "amantadine, 5 ( 6 ) - carboxyfluorescein, Arg - Gly - Asp, adamantine." }, { "input": "The loading ratio of 5 ( 6 ) - carboxyfluorescein is as high as 110 % with a drug concentration of 0. 45 mg mL ( - 1 ).", "output": "5 ( 6 ) - carboxyfluorescein." }, { "input": "The cyclic RGD - functionalized nanohybrid exhibits remarkable targeting for HeLa cells.", "output": "cyclic RGD." }, { "input": "L - BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH - SY5Y cells at low nonexcitotoxic concentrations.", "output": "L - BMAA." }, { "input": "The cyanobacterial beta - N - methylamino - L - alanine ( L - BMAA ) is described as a low - potency excitotoxin, possibly a factor in the increased incidence of amyotrophic lateral sclerosis ( ALS ) and Parkinsonism - dementia complex ( PDC ) in Guam.", "output": "beta - N - methylamino - L - alanine, L - BMAA." }, { "input": "The latter association is intensively disputed, as L - BMAA concentrations required for toxic effects exceed those assumed to occur via food.", "output": "L - BMAA." }, { "input": "The question thus was raised whether L - BMAA leads to neurodegeneration at nonexcitotoxic conditions.", "output": "L - BMAA." }, { "input": "Using human SH - SY5Y neuroblastoma cells, L - BMAA - transport, incorporation into proteins, and subsequent impairment of cellular protein homeostasis were investigated.", "output": "L - BMAA." }, { "input": "Binding of L - BMAA to intracellular proteins, but no clear protein incorporation was detected in response to ( 14 ) C - L - BMAA exposures.", "output": "L - BMAA, ( 14 ) C, L - BMAA." }, { "input": "Nevertheless, low L - BMAA concentrations ( >= 0. 1mM, 48 h ) increased protein ubiquitination, 20S proteasomal and caspase 12 activity, expression of the endoplasmic reticulum ( ER ) stress marker CHOP, and enhanced phosphorylation of elf2 alpha in SH - SY5Y cells.", "output": "L - BMAA." }, { "input": "In contrast, high L - BMAA concentrations ( >= 1mM, 48 h ) increased reactive oxygen species and protein oxidization, which were partially ameliorated by coincubation with vitamin E.", "output": "L - BMAA, oxygen, vitamin E." }, { "input": "L - BMAA - mediated cytotoxicity was observable 48 h following >= 2mM L - BMAA treatment.", "output": "L - BMAA, L - BMAA." }, { "input": "Consequently, the data presented here suggest that low L - BMAA concentrations result in a dysregulation of the cellular protein homeostasis with ensuing ER stress that is independent from high - concentration effects such as excitotoxicity and oxidative stress.", "output": "L - BMAA." }, { "input": "Thus, the latter could be a contributing factor in the onset and slow progression of ALS / PDC in Guam.", "output": "There is no related enetity." }, { "input": "Ribavirin - induced intracellular GTP depletion activates transcription elongation in coagulation factor VII gene expression.", "output": "Ribavirin, GTP." }, { "input": "Coagulation FVII ( Factor VII ) is a vitamin K - dependent glycoprotein synthesized in hepatocytes.", "output": "vitamin K." }, { "input": "It was reported previously that FVII gene ( F7 ) expression was up - regulated by ribavirin treatment in hepatitis C virus - infected haemophilia patients; however, its precise mechanism is still unknown.", "output": "ribavirin." }, { "input": "In the present study, we investigated the molecular mechanism of ribavirin - induced up - regulation of F7 expression in HepG2 ( human hepatoma cell line ).", "output": "ribavirin." }, { "input": "We found that intracellular GTP depletion by ribavirin as well as other IMPDH ( inosine - 5 ' - monophosphate dehydrogenase ) inhibitors, such as mycophenolic acid and 6 - mercaptopurine, up - regulated F7 expression.", "output": "GTP, ribavirin, inosine - 5 ' - monophosphate, mycophenolic acid, 6 - mercaptopurine." }, { "input": "FVII mRNA transcription was mainly enhanced by accelerated transcription elongation, which was mediated by the P - TEFb ( positive - transcription elongation factor b ) complex, rather than by promoter activation.", "output": "There is no related enetity." }, { "input": "Ribavirin unregulated ELL ( eleven - nineteen lysine - rich leukaemia ) 3 mRNA expression before F7 up - regulation.", "output": "Ribavirin, lysine." }, { "input": "We observed that ribavirin enhanced ELL3 recruitment to F7, whereas knockdown of ELL3 diminished ribavirin - induced FVII mRNA up - regulation.", "output": "ribavirin, ribavirin." }, { "input": "Ribavirin also enhanced recruitment of CDK9 ( cyclin - dependent kinase 9 ) and AFF4 to F7.", "output": "Ribavirin." }, { "input": "These data suggest that ribavirin - induced intracellular GTP depletion recruits a super elongation complex containing P - TEFb, AFF4 and ELL3, to F7, and modulates FVII mRNA transcription elongation.", "output": "ribavirin, GTP." }, { "input": "Collectively, we have elucidated a basal mechanism for ribavirin - induced FVII mRNA up - regulation by acceleration of transcription elongation, which may be crucial in understanding its pleiotropic functions in vivo.", "output": "ribavirin." }, { "input": "Hard - metal ( WC - Co ) particles trigger a signaling cascade involving p38 MAPK, HIF - 1 alpha, HMOX1, and p53 activation in human PBMC.", "output": "WC, Co." }, { "input": "Hard - metals are made of tungsten carbide ( WC ) and metallic cobalt ( Co ) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties.", "output": "tungsten carbide, WC, cobalt, Co." }, { "input": "While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC - Co particle mixture was shown to increase the risk of lung cancer in exposed workers.", "output": "Co, WC, Co." }, { "input": "We have previously shown that WC - Co specifically induces a burst of reactive oxygen species ( ROS ) and in vitro mutagenic / apoptogenic effects in human peripheral blood mononucleated cells ( PBMC ) used as a validated experimental model.", "output": "WC, Co, oxygen." }, { "input": "In the present study, PBMCs were treated during a short period ( 15 min ) to focus on the very rapid ROS burst induced by WC - Co.", "output": "WC, Co." }, { "input": "We investigated by microarray the response to WC - Co versus Co ( 2 + ) ions ( CoCl ( 2 ) ) after 15 min exposure and found that the oxidative stress response HMOX1 gene was highly expressed in WC - Co - treated samples.", "output": "WC, Co, Co ( 2 + ), CoCl ( 2 ), WC, Co." }, { "input": "This result was confirmed by qRT - PCR, and western blotting was carried out to analyze translational and post - translational regulation of genes belonging to the HMOX1 pathway.", "output": "There is no related enetity." }, { "input": "We show here that WC - Co, and metallic Co particles although with slower kinetics, but not CoCl ( 2 ) or WC alone, induced a temporally ordered cascade of events.", "output": "WC, Co, Co, CoCl ( 2 ), WC." }, { "input": "This cascade implies p38 / MAP kinase activation, HIF - 1 alpha stabilization, HMOX1 transcriptional activation, and ATM - independent p53 stabilization.", "output": "There is no related enetity." }, { "input": "These events, and in particular HIF - 1 alpha stabilization, could contribute to the carcinogenic activity of WC - Co dusts.", "output": "WC, Co." }, { "input": "Neuropeptide Y Y1 receptor knockdown can modify glutathione peroxidase and c - AMP response element - binding protein in phenylpropanolamine - treated rats.", "output": "glutathione, c - AMP, phenylpropanolamine." }, { "input": "It has been reported that antioxidative enzymes, neuropeptide Y ( NPY ), and c - AMP response element - binding protein ( CREB ) are involved in regulating phenylpropanolamine ( PPA ) - mediated appetite suppression.", "output": "c - AMP, phenylpropanolamine, PPA." }, { "input": "Here, we investigated whether Y1 receptor ( Y1R ) might be involved in this regulation.", "output": "There is no related enetity." }, { "input": "Rats were daily treated with PPA for 4 days.", "output": "PPA." }, { "input": "Changes in the contents of NPY, Y1R, glutathione peroxidase ( GP ), and CREB were assessed and compared.", "output": "glutathione." }, { "input": "Results showed that Y1R, GP, and CREB increased, with a maximal increase about 100, 200, and 150 %, respectively, on Day 2.", "output": "There is no related enetity." }, { "input": "By contrast, NPY decreased with a biggest reduction about 48 % on Day 2 and the pattern of expression during PPA treatment was opposite to those of Y1R, GP, and CREB.", "output": "PPA." }, { "input": "Central knockdown ( using antisense ) or inhibition ( using antagonist ) of Y1R expression modulated the anorectic response of PPA and the reciprocal regulation between NPY and GP ( or CREB ), revealing an essential role of Y1R in regulating NPY, GP, and CREB.", "output": "PPA." }, { "input": "These results suggest that Y1R participates in the reciprocal regulation of NPY, GP, and CREB in the hypothalamus during PPA treatment in conscious rats.", "output": "PPA." }, { "input": "The present results may aid the therapeutic research of PPA and related antiobesity drugs.", "output": "PPA." }, { "input": "Enhanced light focusing in self - assembled optoplasmonic clusters with subwavelength dimensions.", "output": "There is no related enetity." }, { "input": "Compact metallo - dielectric hybrid clusters with subwavelength dimensions are fabricated by template guided self - assembly.", "output": "There is no related enetity." }, { "input": "Elastic and inelastic scattering spectroscopy and electromagnetic simulations reveal that hybrid clusters comprising TiO ( 2 ) nanoparticles on top of a cluster of strongly coupled gold nanoparticles harness synergistic electromagnetic interactions between the building blocks.", "output": "TiO ( 2 )." }, { "input": "This results in a boost of the peak electric field intensity and a redistribution of the field in the ambient medium.", "output": "There is no related enetity." }, { "input": "The complex phase landscape in the clusters features optical vortices that enhance the magnetic field.", "output": "There is no related enetity." }, { "input": "Alternative copolymerization of a conjugated segment and a flexible segment and fabrication of a fluorescent sensing film for HCl in the vapor phase.", "output": "HCl." }, { "input": "A novel fluorescently active co - oligomer ( P1 ) was designed and prepared by alternative co - polymerization of oligo ( p - phenyleneethynylene ) ( OPE ), possessing two cholesterol - containing side chains, and ethanediamine.", "output": "oligo ( p - phenyleneethynylene ), OPE, cholesterol, ethanediamine." }, { "input": "A control co - oligomer ( P2 ) possessing similar structure to P1 was also prepared, but in this case the OPE bears no side chains.", "output": "OPE." }, { "input": "P1 and P2 have been used for the fabrication of two fluorescent films, film 1 and film 2, respectively.", "output": "There is no related enetity." }, { "input": "Fluorescence studies demonstrated that the emission of film 1 is sensitive and selective to the presence of trace amounts of HCl in air.", "output": "HCl." }, { "input": "In contrast, film 2 shows no such response.", "output": "There is no related enetity." }, { "input": "The quenching has been attributed to the protonation of the imino groups within the oligomer chains, and the difference in the sensing behaviors of the two films was rationalized by supposing the existence of molecular channels in film 1.", "output": "imino." }, { "input": "The proposed mechanism is supported by the results from additional experiments and theoretical calculations.", "output": "There is no related enetity." }, { "input": "Furthermore, the film as fabricated is robust, and thereby it is believed that film 1 has the potential to be developed into a new generation of sensitive and selective HCl sensor.", "output": "HCl." }, { "input": "Evaluation of metabolically stabilized angiotensin IV analogs as procognitive / antidementia agents.", "output": "angiotensin IV." }, { "input": "Angiotensin IV ( AngIV: VYIHPF ) - related peptides have long been recognized as procognitive agents with potential as antidementia therapeutics.", "output": "Angiotensin IV, AngIV." }, { "input": "Their development as useful therapeutics, however, has been limited by physiochemical properties that make them susceptible to metabolic degradation and impermeable to gut and blood - brain barriers.", "output": "There is no related enetity." }, { "input": "A previous study demonstrated that the core structural information required to impart the procognitive activity of the AngIV analog, norleucine ( 1 ) - angiotensin IV, resides in its three N - terminal amino acids, Nle - Tyr - Ile.", "output": "AngIV, norleucine, angiotensin IV, N, amino acids, Nle - Tyr - Ile." }, { "input": "The goal of this project was to chemically modify this tripeptide in such a way to enhance its metabolic stability and barrier permeability to produce a drug candidate with potential clinical utility.", "output": "tripeptide." }, { "input": "Initial results demonstrated that several N - and C - terminal modifications lead to dramatically improved stability while maintaining the capability to reverse scopolamine - induced deficits in Morris water maze performance and augment hippocampal synaptogenesis.", "output": "N, C, scopolamine." }, { "input": "Subsequent chemical modifications, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood - barrier permeant, metabolically stabilized analog, N - hexanoic - Tyr - Ile - ( 6 ) aminohexanoic amide ( dihexa ), that exhibits excellent antidementia activity in the scopolamine and aged rat models and marked synaptogenic activity.", "output": "hydrogen, N - hexanoic - Tyr - Ile - ( 6 ) aminohexanoic amide, dihexa, scopolamine." }, { "input": "These data suggest that dihexa may have therapeutic potential as a treatment of disorders, such as Alzheimer ' s disease, where augmented synaptic connectivity may be beneficial.", "output": "dihexa." }, { "input": "A new approach to counteract bacteria resistance: a comparative study between moxifloxacin and a new moxifloxacin derivative in different model systems of bacterial membrane.", "output": "moxifloxacin, moxifloxacin." }, { "input": "New drug design has been one of the major challenges to combat bacterial resistance over the past decade.", "output": "There is no related enetity." }, { "input": "Conventional antibiotics act by destroying bacterial cell wall or by blocking biosynthetic pathways necessary for its survival.", "output": "There is no related enetity." }, { "input": "Unfortunately, there has been a fast increase in multiresistance, to several conventional antibiotics, in clinical bacterial strains.", "output": "There is no related enetity." }, { "input": "Previous studies have shown that metalloantibiotics, ternary complexes of antibiotic - metal - phenanthroline, present an increased potential as antimicrobial agents.", "output": "phenanthroline." }, { "input": "In this work moxifloxacin, a fourth - generation quinolone, with a broad spectrum of action, and its copper ternary complex ( metalloantibiotic ) have been study by fluorescence spectroscopy.", "output": "moxifloxacin, quinolone, copper." }, { "input": "Partition coefficients were determined and showed that while free moxifloxacin exhibits the same behaviour independently of the lipidic system tested, the metalloantibiotic presents higher partition to liposomes, in a lipid composition - dependent way.", "output": "moxifloxacin." }, { "input": "These significant differences in the interaction of the metalloantibiotic with model bacteria membranes point out for a putative change in its uptake mechanism with increased drug - lipid interaction potentiating metalloantibiotic influx.", "output": "There is no related enetity." }, { "input": "A comprehensive study to evaluate the effect of constant low voltage iontophoresis on transungual delivery.", "output": "There is no related enetity." }, { "input": "Treatment of nail diseases by topical drug delivery continues to draw much attention in the recent days.", "output": "There is no related enetity." }, { "input": "This study aims to systematically investigate the effect of constant voltage iontophoresis in the transungual drug delivery, using ciclopirox as a model drug.", "output": "ciclopirox." }, { "input": "Preliminary permeation studies were carried out by applying constant voltage ( 6 V for 24 h ) using a gel formulation across the human nail plate in a Franz diffusion cell.", "output": "There is no related enetity." }, { "input": "Different protocols have been studied to authenticate the potential of the proposed technique.", "output": "There is no related enetity." }, { "input": "Antifungal studies were carried out to assess the pharmacodynamic effect of drug depot formed in the nail plate.", "output": "There is no related enetity." }, { "input": "Initial studies revealed that application of constant voltage iontophoresis enhanced the permeation by an order of magnitude ( p = 0. 019 ) and delivered significant amount of drug into the deeper nail layers.", "output": "There is no related enetity." }, { "input": "Noticeably higher permeation was observed during the active phase in on - off studies.", "output": "There is no related enetity." }, { "input": "Excellent correlation was observed in permeation ( r ( 2 ) = 0. 98 ) and drug load ( r ( 2 ) = 0. 97 ) with the increase in applied voltage ( 3 - 12 V ), indicating that the current technique is predictable.", "output": "There is no related enetity." }, { "input": "The data observed suggest that any further increase in voltage could eventually lead to increase in the permeation and drug load, as the saturation level is very distant.", "output": "There is no related enetity." }, { "input": "Furthermore, the enhancement in permeation with the applied voltage ( 3 - 12 V ) was found to be 6 - 20 folds, compared to the passive process.", "output": "There is no related enetity." }, { "input": "Results of step up and step down studies substantiated the viability of the current technique.", "output": "There is no related enetity." }, { "input": "Zone of inhibition measured during the antifungal studies demonstrated that the drug molecules loaded into the nail plate by low voltage iontophoresis is active and releases over an extended period of time ( ~ 32 days ).", "output": "There is no related enetity." }, { "input": "Given the excellent results, the current technique could be used as an effective approach for the delivery of antimycotics, which would localize the drug at the infection site and potentially offer higher patient compliance.", "output": "There is no related enetity." }, { "input": "Non - enzymatic proteins from snake venoms: a gold mine of pharmacological tools and drug leads.", "output": "There is no related enetity." }, { "input": "Non - enzymatic proteins from snake venoms play important roles in the immobilization of prey, and include some large and well - recognized families of toxins.", "output": "There is no related enetity." }, { "input": "The study of such proteins has expanded not only our understanding of venom toxicity, but also the knowledge of normal and disease states in human physiology.", "output": "There is no related enetity." }, { "input": "In many cases their characterization has led to the development of powerful research tools, diagnostic techniques, and pharmaceutical drugs.", "output": "There is no related enetity." }, { "input": "They have further yielded basic understanding of protein structure - function relationships.", "output": "There is no related enetity." }, { "input": "Therefore a number of studies on these non - enzymatic proteins had major impact on several life science and medical fields.", "output": "There is no related enetity." }, { "input": "They have led to life - saving therapeutics, the Nobel prize, and development of molecular scalpels for elucidation of ion channel function, vasoconstriction, complement system activity, platelet aggregation, blood coagulation, signal transduction, and blood pressure regulation.", "output": "There is no related enetity." }, { "input": "Here, we identify research papers that have had significant impact on the life sciences.", "output": "There is no related enetity." }, { "input": "We discuss how these findings have changed the course of science, and have also included the personal recollections of the original authors of these studies.", "output": "There is no related enetity." }, { "input": "We expect that this review will provide impetus for even further exciting research on novel toxins yet to be discovered.", "output": "There is no related enetity." }, { "input": "The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice.", "output": "There is no related enetity." }, { "input": "Bone remodeling is affected by mechanical loading and inflammatory mediators, including chemokines.", "output": "There is no related enetity." }, { "input": "The chemokine ( C - C motif ) ligand 3 ( CCL3 ) is involved in bone remodeling by binding to C - C chemokine receptors 1 and 5 ( CCR1 and CCR5 ) expressed on osteoclasts and osteoblasts.", "output": "There is no related enetity." }, { "input": "Our group has previously demonstrated that CCR5 down - regulates mechanical loading - induced bone resorption.", "output": "There is no related enetity." }, { "input": "Thus, the present study aimed to investigate the role of CCR1 and CCL3 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice.", "output": "There is no related enetity." }, { "input": "Our results showed that bone remodeling was significantly decreased in CCL3 ( - / - ) and CCR1 ( - / - ) mice and in animals treated with Met - RANTES ( an antagonist of CCR5 and CCR1 ).", "output": "Met." }, { "input": "mRNA levels of receptor activator of nuclear factor kappa - B ( RANK ), its ligand RANKL, tumor necrosis factor alpha ( TNF - alpha ) and RANKL / osteoprotegerin ( OPG ) ratio were diminished in the periodontium of CCL3 ( - / - ) mice and in the group treated with Met - RANTES.", "output": "Met." }, { "input": "Met - RANTES treatment also reduced the levels of cathepsin K and metalloproteinase 13 ( MMP13 ).", "output": "Met." }, { "input": "The expression of the osteoblast markers runt - related transcription factor 2 ( RUNX2 ) and periostin was decreased, while osteocalcin ( OCN ) was augmented in CCL3 ( - / - ) and Met - RANTES - treated mice.", "output": "Met." }, { "input": "Altogether, these findings show that CCR1 is pivotal for bone remodeling induced by mechanical loading during orthodontic tooth movement and these actions depend, at least in part, on CCL3.", "output": "There is no related enetity." }, { "input": "A sensitive H2O2 assay based on dumbbell - like PtPd - Fe3O4 nanoparticles.", "output": "H2O2, PtPd - Fe3O4." }, { "input": "Dumbbell - like Pt ( 48 ) Pd ( 52 ) - Fe ( 3 ) O ( 4 ) nanoparticles are synthesized and functionalized with oleylamine - polyethyleneglycol to serve as an efficient catalyst for H ( 2 ) O ( 2 ) reduction and tetramethylbenzidine ( TMB ) oxidation in biological solutions.", "output": "Pt ( 48 ) Pd ( 52 ) - Fe ( 3 ) O ( 4 ), oleylamine, polyethyleneglycol, H ( 2 ) O ( 2 ), tetramethylbenzidine, TMB." }, { "input": "The Pt ( 48 ) Pd ( 52 ) - Fe ( 3 ) O ( 4 ) / TMB kit is even more active than the natural enzyme for H ( 2 ) O ( 2 ) detection with a detection limit reaching 2 mu M, and is successfully used to quantitatively monitor the extracellular H ( 2 ) O ( 2 ) generated by neutrophils.", "output": "Pt ( 48 ) Pd ( 52 ) - Fe ( 3 ) O ( 4 ), TMB, H ( 2 ) O ( 2 ), H ( 2 ) O ( 2 )." }, { "input": "Organosilicon molecules with medicinal applications.", "output": "Organosilicon." }, { "input": "The incorporation of silicon and synthesis of organosilicon small molecules provide unique opportunities for medicinal applications.", "output": "silicon, organosilicon." }, { "input": "The biological investigation of organosilicon small molecules is particularly interesting because of differences in their chemical properties that can contribute to enhanced potency and improved pharmacological attributes.", "output": "organosilicon." }, { "input": "Applications such as inhibitor design, imaging, drug release technology, and mapping inhibitor binding are discussed.", "output": "There is no related enetity." }, { "input": "Menthol - - pharmacology of an important naturally medicinal \" cool \".", "output": "Menthol." }, { "input": "Menthol, a natural product of the peppermint plant Mentha x piperita ( Lamiaceae ), is a monoterpene which is widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other compounds.", "output": "Menthol, monoterpene." }, { "input": "Various extracts from peppermint contain menthol as a major active constituent and have been used for centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome as well as an insect repellent.", "output": "menthol." }, { "input": "Menthol ' s characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential ( TRP ) channels, in particular transient receptor potential melastatin family member 8 ( TRPM8 ) and transient receptor potential subfamily A, member 1 ( TRPA1 ).", "output": "Menthol." }, { "input": "Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site.", "output": "calcium, calcium." }, { "input": "Aside from its cold - inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia.", "output": "menthol, GABA, sodium." }, { "input": "Notwithstanding its plethora of benefits, menthol ' s coldsensitivity response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in mentholated cigarette brands thus potentially leading to toxic effects.", "output": "menthol, nicotine." }, { "input": "Menthol may prove a valuable lead structure for the synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.", "output": "Menthol." }, { "input": "Biomarkers in marine mussels, Mytilus galloprovincialis, exposed to environmentally relevant levels of the pesticides, chlorpyrifos and penoxsulam.", "output": "chlorpyrifos, penoxsulam." }, { "input": "The present study examines the influence of environmentally relevant concentrations of two pesticides, chlorpyrifos and penoxsulam on mussel physiological status.", "output": "chlorpyrifos, penoxsulam." }, { "input": "For this reason, lysosomal membrane stability ( LMS ), reactive oxygen species ( ROS ), DNA damage, protein carbonylation ( PCC ) and antioxidant capacity ( TAC ) in hemaolymph and hemocytes of the mussels was measured.", "output": "oxygen." }, { "input": "Mussels were exposed to a range of concentrations of the pesticides chlorpyrifos and penoxsulam and the response of animals to the destabilization of lysosomal membrane in hemocytes ( LMS ) was studied.", "output": "chlorpyrifos, penoxsulam." }, { "input": "Subsequently, the half maximal effective concentration ( EC50 ) for both pesticides was calculated.", "output": "There is no related enetity." }, { "input": "The animals were subsequently exposed for 0, 1, 3, 5, 7, 15 and 30 days to 10 times less concentration than EC50 of each pesticide ( 0. 05 mu g / l ) and changes in LMS, ROS, DNA damage, protein carbonylation and antioxidant capacity of mussels was evaluated.", "output": "There is no related enetity." }, { "input": "Our results showed a significant change in the response of mussels for all parameters tested after 30 days exposure, in relation to the controls.", "output": "There is no related enetity." }, { "input": "The pesticides at the environmental concentrations used induced changes to the animal physiology through causing oxidative stress and lysosomal abnormalities and their usage in the agriculture demands great care.", "output": "There is no related enetity." }, { "input": "In addition, the results show that ROS, DNA damage, protein carbonylation and antioxidant capacity could constitute, after further investigation, reliable biomarkers for the evaluation of pollution or other environmental stressors.", "output": "There is no related enetity." }, { "input": "Two stressors and a community: effects of hydrological disturbance and a toxicant on freshwater zooplankton.", "output": "There is no related enetity." }, { "input": "Climate change models predict an increase in the frequency and intensity of extreme fluctuations in water level in aquatic habitats.", "output": "There is no related enetity." }, { "input": "Therefore, it is necessary to understand the combined effects of hydrological fluctuations and toxicants on aquatic biological communities.", "output": "There is no related enetity." }, { "input": "We investigated the individual and combined effects of the insecticide esfenvalerate and recurring fluctuations in water level on zooplankton communities in a system of 55 outdoor pond microcosms.", "output": "esfenvalerate." }, { "input": "The communities were exposed to esfenvalerate contamination as a single pulse ( at 0. 03, 0. 3, or 3 mu g / L ) and gradual removal of water and its subsequent replacement over three cycles and monitored until 84 days after contamination.", "output": "esfenvalerate." }, { "input": "The results showed that the sensitivities of the community and its constituent populations to the toxicant were increased by the hydrological stress.", "output": "There is no related enetity." }, { "input": "Specifically, for both the community structure and abundance of Daphnia spp. the lowest - observed - effect concentrations ( LOEC ) were 0. 03 and 0. 3 mu g / L for the series with fluctuating and constant water levels, respectively.", "output": "There is no related enetity." }, { "input": "Despite these differences in sensitivity, the interactive effects of the two stressors were found to be additive for both the community structure and the abundance of the most affected species.", "output": "There is no related enetity." }, { "input": "Presumably, it was not possible to detect synergism due to the strong individual effects of the water level fluctuations.", "output": "There is no related enetity." }, { "input": "Recovery times in the series exposed to the highest pesticide concentration were 64 and 55 days under fluctuating and constant water level regimes, respectively.", "output": "There is no related enetity." }, { "input": "Competition and water quality are suggested to be the major factors that underlie the observed effects of fluctuations in the water level.", "output": "There is no related enetity." }, { "input": "For the ecological risk assessment of toxicants, the present results suggest that ( i ) community sensitivity may vary substantially, depending on the environmental context, and ( ii ) this variability can be assessed experimentally to derive safety factors ( coefficients used to avoid unexpected effects and define safe concentrations of toxicants ) based on empirical findings.", "output": "There is no related enetity." }, { "input": "This contrasts with the current approach where such factors are usually defined arbitrarily.", "output": "There is no related enetity." }, { "input": "Parental exposure to natural mixtures of POPs reduced embryo production and altered gene transcription in zebrafish embryos.", "output": "There is no related enetity." }, { "input": "Determination of toxicity of complex mixtures has been proposed to be one of the most important challenges for modern toxicology.", "output": "There is no related enetity." }, { "input": "In this study we performed genome wide transcriptome profiling to assess potential toxicant induced changes in gene regulation in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants ( POPs ).", "output": "There is no related enetity." }, { "input": "The mixtures used were extracted from burbot ( Lota lota ) liver originating from two lakes ( Lake Mj o sa and Lake Losna ) belonging to the same freshwater system in Norway.", "output": "There is no related enetity." }, { "input": "The dominating groups of contaminants were polybrominated diphenyl ethers ( PBDEs ), polychlorinated biphenyls ( PCBs ) and dichlorodiphenyltrichloroethane metabolites ( DDTs ).", "output": "polybrominated diphenyl ethers, PBDEs, polychlorinated biphenyls, PCBs, dichlorodiphenyltrichloroethane." }, { "input": "Because both mixtures used in the present study induced similar effects, it is likely that the same toxicants are involved.", "output": "There is no related enetity." }, { "input": "The Mj o sa mixture contains high levels of PBDEs while this group of pollutants is low in the Losna mixture.", "output": "PBDEs." }, { "input": "However, both mixtures contain substantial concentrations of PCB and DDT suggesting these contaminants as the predominant contributors to the toxicity observed.", "output": "PCB, DDT." }, { "input": "The observed effects included phenotypic traits, like embryo production and survival, and gene transcription changes corresponding with disease and biological functions such as cancer, reproductive system disease, cardiovascular disease, lipid and protein metabolism, small molecule biochemistry and cell cycle.", "output": "There is no related enetity." }, { "input": "The changes in gene transcription included genes regulated by HNF4A, insulin, LH, FSH and NF - kappa B which are known to be central regulators of endocrine signaling, metabolism, metabolic homeostasis, immune functions, cancer development and reproduction.", "output": "There is no related enetity." }, { "input": "The results suggest that relative low concentrations of the natural mixtures of POPs used in the present study might pose a threat to wild freshwater fish living in the lakes from which the POPs mixtures originated.", "output": "There is no related enetity." }, { "input": "Characterisation of the roles of ABCB1, ABCC1, ABCC2 and ABCG2 in the transport and pharmacokinetics of actinomycin D in vitro and in vivo.", "output": "actinomycin D." }, { "input": "Actinomycin D plays a key role in the successful treatment of Wilms tumour.", "output": "Actinomycin D." }, { "input": "However, associated liver toxicities remain a drawback to potentially curative treatment.", "output": "There is no related enetity." }, { "input": "We have used MDCKII cells over - expressing ABCB1, ABCC1, ABCC2 and ABCG2, alongside knockout mouse models to characterise actinomycin D transport and its impact on pharmacokinetics.", "output": "actinomycin D." }, { "input": "Growth inhibition, intracellular accumulation and cellular efflux assays were utilised.", "output": "There is no related enetity." }, { "input": "A 59 - fold difference in GI ( 50 ) was observed between MDCKII - WT and MDCKII - ABCB1 cells ( 12. 7 nM vs. 745 nM, p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Reduced sensitivity was also seen in MDCKII - ABCC1 and ABCC2 cells ( GI ( 50 ) 25. 7 and 40. 4 nM respectively, p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Lower intracellular accumulation of actinomycin D was observed in MDCKII - ABCB1 cells as compared to MDCKII - WT ( 0. 98 nM vs. 0. 1 nM, p < 0. 0001 ), which was reversed upon ABCB1 inhibition.", "output": "actinomycin D." }, { "input": "Lower accumulation was also seen in MDCKII - ABCC1 and ABCC2 cells.", "output": "There is no related enetity." }, { "input": "Actinomycin D efflux over 2 h was most pronounced in MDCKII - ABCB1 cells, with 5. 5 - fold lower intracellular levels compared to WT.", "output": "Actinomycin D." }, { "input": "In vivo studies showed that actinomycin D plasma concentrations were significantly higher in Abcb1a / 1b ( - / - ) as compared to WT mice following administration of 0. 5 mg / kg actinomycin D ( AUC ( 0 - 6 h ) 242 vs. 152 mu g / Lh respectively ).", "output": "actinomycin D, actinomycin D." }, { "input": "While comparable actinomycin D concentrations were observed in the kidneys and livers of Abcb1a / 1b ( - / - ) and Abcc2 ( - / - ) mice, concentrations in the brain were significantly higher at 6h following drug administration in Abcb1a / 1b ( - / - ) mice compared to WT.", "output": "actinomycin D." }, { "input": "Results confirm actinomycin D as a substrate for ABCB1, ABCC1 and ABCC2, and indicate that Abcb1a / 1b and Abcc2 can influence the in vivo disposition of actinomycin D.", "output": "actinomycin D, actinomycin D." }, { "input": "These data have implications for ongoing clinical pharmacology trials involving children treated with actinomycin D.", "output": "actinomycin D." }, { "input": "Artemisinic acid inhibits melanogenesis through downregulation of C / EBP alpha - dependent expression of HMG - CoA reductase gene.", "output": "Artemisinic acid, HMG - CoA." }, { "input": "Cholesterol is associated with the regulation of melanogenesis which is the major physiological defense against solar irradiation.", "output": "Cholesterol." }, { "input": "The present study was designed to determine the effects of artemisinic acid on melanogenesis and its mechanisms of action in human epidermal melanocytes.", "output": "artemisinic acid." }, { "input": "In this study, we found that artemisinic acid inhibited melanin content.", "output": "artemisinic acid." }, { "input": "The mRNA levels of microphthalmia - associated transcription factor ( MITF ) and its downstream genes tyrosinase, tyrosinase - related protein ( TRP ) - 1, and TRP - 2 were reduced by artemisinic acid treatment.", "output": "artemisinic acid." }, { "input": "Additionally, the mRNA levels of melanogenesis - related genes ( c - KIT, stem cell factor ( SCF ), and macrophage migration inhibitory factor ( MIF ) ) were down - regulated by artemisinic acid.", "output": "artemisinic acid." }, { "input": "Furthermore, cAMP production and protein kinase A ( PKA ) activity were suppressed by artemisinic acid.", "output": "cAMP, artemisinic acid." }, { "input": "Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid - mediated effects revealed that artemisinic acid regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA ( HMG CoA ) reductase gene, which was mediated through reduced expression of the CCAAT / enhancer - binding protein ( C / EBP ) alpha gene.", "output": "artemisinic acid, artemisinic acid, cholesterol, hydroxymethylglutaryl CoA, HMG CoA." }, { "input": "Taken together, these findings indicate that the inhibition of melanogenesis by artemisinic acid occurs through reduced expression of the HMG CoA reductase gene, which is mediated by C / EBP alpha inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor.", "output": "artemisinic acid, HMG CoA, artemisinic acid." }, { "input": "Herbacetin induces apoptosis in HepG2 cells: Involvements of ROS and PI3K / Akt pathway.", "output": "Herbacetin." }, { "input": "Herbacetin ( HER ) is a natural flavonoid compound that can be extracted from Ramose Scouring Rush Herb, and its biological and pharmacological activities lack of corresponding attention.", "output": "Herbacetin, HER, flavonoid." }, { "input": "In this study, the apoptotic effect of HER against the human hepatoma cell line ( HepG2 ) was investigated.", "output": "HER." }, { "input": "The results showed that HepG2 cells apoptosis occurred in a dose - dependent manner within 48h incubated with HER, which was confirmed by DNA fragmentation, nuclear shrinkage, and poly ( ADP - ribose ) polymerase ( PARP ) cleavage.", "output": "HER, poly ( ADP - ribose )." }, { "input": "HER at 25 - 100 mu M induced a mitochondria - dependent apoptotic pathway associated with Bcl - 2 / Bax ratio decrease, mitochondrial membrane potential ( Delta Psi ) collapse, cytochrome c release, and caspase - 3 activation.", "output": "HER." }, { "input": "Increasing expression of peroxisome proliferator - activated receptor - gamma coactivator 1 alpha ( PGC - 1 alpha ) was also observed in HER - treated cells.", "output": "HER." }, { "input": "Furthermore, the addition of a ROS inhibitor ( N - Acetyl - l - cysteine, NAC ) significantly attenuated the apoptosis induced by HER and also blocked the expression of PGC - 1 alpha protein.", "output": "N - Acetyl - l - cysteine, NAC, HER." }, { "input": "Additionally, HER effectively inhibited the phosphorylation of Akt and the phosphatidylinositol - 3 kinase ( PI3K ) inhibitor LY294002 increased the inhibition effect of HER on Akt phosphorylation.", "output": "HER, phosphatidylinositol, LY294002, HER." }, { "input": "These findings provide evidences that HER induces HepG2 apoptosis in a ROS - mediated mitochondria - dependent manner that correlate with the inactivation of the PI3K / Akt pathway.", "output": "HER." }, { "input": "Evolutionary dynamism of the primate LRRC37 gene family.", "output": "There is no related enetity." }, { "input": "Core duplicons in the human genome represent ancestral duplication modules shared by the majority of intrachromosomal duplication blocks within a given chromosome.", "output": "There is no related enetity." }, { "input": "These cores are associated with the emergence of novel gene families in the hominoid lineage, but their genomic organization and gene characterization among other primates are largely unknown.", "output": "There is no related enetity." }, { "input": "Here, we investigate the genomic organization and expression of the core duplicon on chromosome 17 that led to the expansion of LRRC37 during primate evolution.", "output": "There is no related enetity." }, { "input": "A comparison of the LRRC37 gene family organization in human, orangutan, macaque, marmoset, and lemur genomes shows the presence of both orthologous and species - specific gene copies in all primate lineages.", "output": "There is no related enetity." }, { "input": "Expression profiling in mouse, macaque, and human tissues reveals that the ancestral expression of LRRC37 was restricted to the testis.", "output": "There is no related enetity." }, { "input": "In the hominid lineage, the pattern of LRRC37 became increasingly ubiquitous, with significantly higher levels of expression in the cerebellum and thymus, and showed a remarkable diversity of alternative splice forms.", "output": "There is no related enetity." }, { "input": "Transfection studies in HeLa cells indicate that the human FLAG - tagged recombinant LRRC37 protein is secreted after cleavage of a transmembrane precursor and its overexpression can induce filipodia formation.", "output": "There is no related enetity." }, { "input": "Rapid estimation of nuclear magnetic resonance experiment time in low - concentration environmental samples.", "output": "There is no related enetity." }, { "input": "Nuclear magnetic resonance ( NMR ) spectroscopy is an essential tool for studying environmental samples but is often hindered by low sensitivity, especially for the direct detection of nuclei such as ( 13 ) C.", "output": "( 13 ) C." }, { "input": "In very heterogeneous samples with NMR nuclei at low abundance, such as soils, sediments, and air particulates, it can take days to acquire a conventional ( 13 ) C spectrum.", "output": "( 13 ) C." }, { "input": "The present study describes a prescreening method that permits the rapid prediction of experimental run time in natural samples.", "output": "There is no related enetity." }, { "input": "The approach focuses the NMR chemical shift dispersion into a single spike, and, even in samples with extremely low carbon content, the spike can be observed in two to three minutes, or less.", "output": "carbon." }, { "input": "The intensity of the spike is directly proportional to the total concentration of nuclei of interest in the sample.", "output": "There is no related enetity." }, { "input": "Consequently, the spike intensity can be used as a powerful prescreening method that answers two key questions: ( 1 ) Will this sample produce a conventional NMR spectrum?", "output": "There is no related enetity." }, { "input": "( 2 ) How much instrument time is required to record a spectrum with a specific signal - to - noise ( S / N ) ratio?", "output": "There is no related enetity." }, { "input": "The approach identifies samples to avoid ( or pretreat ) and permits additional NMR experiments to be performed on samples producing high - quality NMR data.", "output": "There is no related enetity." }, { "input": "Applications in solid - and liquid - state ( 13 ) C NMR are demonstrated, and it is shown that the technique is applicable to a range of nuclei.", "output": "( 13 ) C." }, { "input": "A novel EPAC - specific inhibitor suppresses pancreatic cancer cell migration and invasion.", "output": "There is no related enetity." }, { "input": "Exchange protein directly activated by cAMP ( EPAC ) and cAMP - dependent protein kinase ( PKA ) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP.", "output": "cAMP, cAMP, cAMP." }, { "input": "Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the research field.", "output": "There is no related enetity." }, { "input": "Herein, we report the identification and characterization of 3 - ( 5 - tert - butyl - isoxazol - 3 - yl ) - 2 - [ ( 3 - chloro - phenyl ) - hydrazono ] - 3 - oxo - propionitrile ( ESI - 09 ), a novel noncyclic nucleotide EPAC antagonist that is capable of specifically blocking intracellular EPAC - mediated Rap1 activation and Akt phosphorylation, as well as EPAC - mediated insulin secretion in pancreatic beta cells.", "output": "3 - ( 5 - tert - butyl - isoxazol - 3 - yl ) - 2 - [ ( 3 - chloro - phenyl ) - hydrazono ] - 3 - oxo - propionitrile, ESI - 09, nucleotide." }, { "input": "Using this novel EPAC - specific inhibitor, we have probed the functional roles of overexpression of EPAC1 in pancreatic cancer cells.", "output": "There is no related enetity." }, { "input": "Our studies show that EPAC1 plays an important role in pancreatic cancer cell migration and invasion, and thus represents a potential target for developing novel therapeutic strategies for pancreatic cancer.", "output": "There is no related enetity." }, { "input": "Two new alkaloids from marine sponge Callyspongia sp.", "output": "There is no related enetity." }, { "input": "Two new alkaloids, callylactam A ( 1 ) and callyimine A ( 4 ), along with three known ones ( 2, 3 and 5 ), were isolated from the marine sponge Callyspongia sp.", "output": "callylactam A, callyimine A." }, { "input": "The structures were determined on the basis of NMR and MS analysis.", "output": "There is no related enetity." }, { "input": "Back to the future: can physical models of passive membrane permeability help reduce drug candidate attrition and move us beyond QSPR?", "output": "There is no related enetity." }, { "input": "It is widely recognized that adsorption, distribution, metabolism, excretion, and toxicology liabilities kill the majority of drug candidates that progress to clinical trials.", "output": "There is no related enetity." }, { "input": "The development of computational models to predict small molecule membrane permeability is therefore of considerable scientific and public health interest.", "output": "There is no related enetity." }, { "input": "Empirical qualitative structure permeability relationship models of permeability have been a mainstay in industrial applications, but lack a deep understanding of the underlying biologic physics.", "output": "There is no related enetity." }, { "input": "Others and we have shown that implicit solvent models to predict passive permeability for small molecules exhibit mediocre predictive performance when validated across experimental test sets.", "output": "There is no related enetity." }, { "input": "Given the vast increase in computer power, more efficient parallelization schemes, and extension of current atomistic simulation codes to general use graphical processing units, the development and application of physical models based on all - atom simulations may now be feasible.", "output": "There is no related enetity." }, { "input": "Preliminary results from rigorous free energy calculations using all - atom simulations indicate that performance relative to implicit solvent models may be improved, but many outstanding questions remain.", "output": "There is no related enetity." }, { "input": "Here, we review the current state - of - the - art physical models for passive membrane permeability prediction and present a prospective look at promising new directions for all - atom approaches.", "output": "There is no related enetity." }, { "input": "Protein - ligand interaction study of CpOGA in complex with GlcNAcstatin.", "output": "GlcNAcstatin." }, { "input": "The GlcNAcstatin is a potent inhibitor of O - glycoprotein 2 - acetamino - 2 - deoxy - beta - D - glucopyranosidase, which has been related with type II diabetes and neurodegenerative disorders.", "output": "GlcNAcstatin, 2 - acetamino." }, { "input": "Herein, hybrid quantum mechanics / molecular mechanics, molecular dynamics simulations, and potential of mean force were employed to study the interactions established between GlcNAcstatin and a bacterial O - GlcNAcase enzyme from Clostridium perfringens.", "output": "GlcNAcstatin." }, { "input": "The results reveal that the imidazole nitrogen atom of GlcNAcstatin has shown a better interaction with the active site of Clostridium perfringens in its protonated form, which is compatible with a substrate - assisted reaction mechanism involving two conserved aspartate residues ( 297 and 298 ).", "output": "imidazole, nitrogen, GlcNAcstatin, aspartate." }, { "input": "Furthermore, the quantum mechanics / molecular mechanics - molecular dynamics simulations appointed a strong interaction between Asp401, Asp298, and Asp297 residues and the GlcNAcstatin inhibitor, which is in accordance with experimental data.", "output": "Asp401, Asp298, Asp297, GlcNAcstatin." }, { "input": "Lastly, these results may contribute to understand the molecular mechanism of inhibition of Clostridium perfringens by GlcNAcstatin inhibitor and, consequently, this study might be useful to design new molecules with more interesting inhibitory activity.", "output": "GlcNAcstatin." }, { "input": "Methylparaben protects 6 - hydroxydopamine - induced neurotoxicity in SH - SY5Y cells and improved behavioral impairments in mouse model of Parkinson ' s disease.", "output": "Methylparaben, 6 - hydroxydopamine." }, { "input": "Parkinson ' s disease ( PD ) is a progressive neurodegenerative disorder of unknown etiology.", "output": "There is no related enetity." }, { "input": "Considerable evidence suggests that free radical formation and oxidative stress might play an important role in the pathogenesis of PD.", "output": "There is no related enetity." }, { "input": "In the present investigation we evaluated the therapeutic potential of methylparaben ( MP ) a well known pharmaceutical preservative against 6 - hydroxydopamine ( 6 - OHDA ) neurotoxicity in SH - SY5Y cells and in a mouse model of PD.", "output": "methylparaben, 6 - hydroxydopamine, 6 - OHDA." }, { "input": "At nanomolar concentrations MP ( 0. 01, 0. 1 and 1 nM ) significantly attenuated the 6 - OHDA - and hydrogen peroxide - induced cytotoxicity in SH - SY5Y cells.", "output": "6 - OHDA, hydrogen peroxide." }, { "input": "The reactive oxygen species generated by 6 - OHDA in SH - SY5Y cells was also inhibited by MP in a concentration dependent fashion.", "output": "oxygen, 6 - OHDA." }, { "input": "Further, intranigral damage induced by stereotaxically injecting 6 - OHDA in mouse brain was significantly attenuated by MP treatment.", "output": "6 - OHDA." }, { "input": "MP ( 1, 10 or 50 mu g / kg, i. p. ) prevented apomorphine - induced rotational behavior and significantly improved motor deficits in 6 - OHDA - lesioned mice.", "output": "apomorphine, 6 - OHDA." }, { "input": "The cognitive impairments as evaluated by passive avoidance and Y - maze task in mice were also attenuated by MP concentration dependently.", "output": "There is no related enetity." }, { "input": "Immunohistochemical analysis of substantia nigra in MP treated mice showed significantly higher number of surviving tyrosine hydroxylase positive cells.", "output": "tyrosine." }, { "input": "Furthermore, MP also suppressed the lipid peroxidation products in 6 - OHDA - lesioned mouse brain tissues.", "output": "6 - OHDA." }, { "input": "Considering the results obtained, the marked neuroprotection exhibited by MP might be attributed to its potent antioxidant property.", "output": "There is no related enetity." }, { "input": "In conclusion, this study reports the neuroprotective properties of MP in experimental models of PD for the first time and can be developed as a potential therapeutic agent.", "output": "There is no related enetity." }, { "input": "A case study of real - time monitoring of solid - state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy.", "output": "There is no related enetity." }, { "input": "The objective of this study was to monitor the amorphous - to - crystalline solid - state phase transformation kinetics of the model drug ibuprofen with spectroscopic methods during acoustic levitation.", "output": "ibuprofen." }, { "input": "Chemical and physical information was obtained by real - time near infrared ( NIRS ) and Raman spectroscopy measurements.", "output": "There is no related enetity." }, { "input": "The recrystallisation kinetic parameters ( overall recrystallisation rate constant beta and the time needed to reach 50 % of the equilibrated level t ( 50 ) ), were determined using a multivariate curve resolution approach.", "output": "There is no related enetity." }, { "input": "The acoustic levitation device coupled with non - invasive spectroscopy enabled monitoring of the recrystallisation process of the difficult - to - handle ( adhesive ) amorphous sample.", "output": "There is no related enetity." }, { "input": "The application of multivariate curve resolution enabled isolation of the underlying pure spectra, which corresponded well with the reference spectra of amorphous and crystalline ibuprofen.", "output": "ibuprofen." }, { "input": "The recrystallisation kinetic parameters were estimated from the recrystallisation profiles.", "output": "There is no related enetity." }, { "input": "While the empirical recrystallisation rate constant determined by NIR and Raman spectroscopy were comparable, the lag time for recrystallisation was significantly lower with Raman spectroscopy as compared to NIRS.", "output": "There is no related enetity." }, { "input": "This observation was explained by the high energy density of the Raman laser beam, which might have led to local heating effects of the sample and thus reduced the recrystallisation onset time.", "output": "There is no related enetity." }, { "input": "It was concluded that acoustic levitation with NIR and Raman spectroscopy combined with multivariate curve resolution allowed direct determination of the recrystallisation kinetics of amorphous drugs and thus is a promising technique for monitoring solid - state phase transformations of adhesive small - sized samples during the early phase of drug development.", "output": "There is no related enetity." }, { "input": "Cathepsin K knockout mitigates high - fat diet - induced cardiac hypertrophy and contractile dysfunction.", "output": "There is no related enetity." }, { "input": "The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease.", "output": "There is no related enetity." }, { "input": "We hypothesized that ablation of cathepsin K protects against obesity - associated cardiac dysfunction.", "output": "There is no related enetity." }, { "input": "Wild - type mice fed a high - fat diet exhibited elevated heart weight, enlarged cardiomyocytes, increased left ventricular wall thickness, and decreased fractional shortening.", "output": "There is no related enetity." }, { "input": "All these changes were reconciled in cathepsin K knockout mice.", "output": "There is no related enetity." }, { "input": "Cathepsin K knockout partly reversed the impaired cardiomyocyte contractility and dysregulated calcium handling associated with high - fat diet.", "output": "calcium." }, { "input": "Additionally, cathepsin K knockout alleviated whole - body glucose intolerance and improved insulin - stimulated Akt phosphorylation in high - fat diet - fed mice.", "output": "glucose." }, { "input": "High - fat feeding increased the expression of cardiac hypertrophic proteins and apoptotic markers, which were inhibited by cathepsin K knockout.", "output": "There is no related enetity." }, { "input": "Furthermore, high - fat feeding resulted in cathepsin K release from lysosomes into the cytoplasm.", "output": "There is no related enetity." }, { "input": "In H9c2 myoblasts, silencing of cathepsin K inhibited palmitic acid - induced release of cytochrome c from mitochondria and expression of proapoptotic signaling molecules.", "output": "palmitic acid." }, { "input": "Collectively, our data indicate that cathepsin K contributes to the development of obesity - associated cardiac hypertrophy and may represent a potential target for the treatment to obesity - associated cardiac anomalies.", "output": "There is no related enetity." }, { "input": "Electric control of the giant Rashba effect in bulk GeTe.", "output": "GeTe." }, { "input": "Relativistic effects, including the Rashba effect, are increasingly seen as key ingredients in spintronics.", "output": "There is no related enetity." }, { "input": "A link between Rashba physics and the field of ferroelectrics is established by predicting giant Rashba spin - splitting in bulk GeTe ( see the Figure showing the band - structure as well as in - plane and out - of - plane spin polarization for a constant energy cut ).", "output": "GeTe." }, { "input": "Potentiation of sulfonylurea action by an EPAC - selective cAMP analog in INS - 1 cells: comparison of tolbutamide and gliclazide and a potential role for EPAC activation of a 2 - APB - sensitive Ca2 + influx.", "output": "sulfonylurea, cAMP, tolbutamide, gliclazide." }, { "input": "Tolbutamide and gliclazide block the K ( ATP ) channel K ( ir ) 6. 2 / Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells.", "output": "Tolbutamide." }, { "input": "We examined the ability of the EPAC - selective cAMP analog 8 - pCPT - 2 ' - O - Me - cAMP - AM to potentiate the action of these drugs and the mechanism that might account for it.", "output": "cAMP, 8 - pCPT - 2 ' - O - Me - cAMP - AM." }, { "input": "Insulin secretion stimulated by both 200 mu M tolbutamide and 20 mu M gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin ( 1 mu M ) or the L - type Ca ( 2 + ) channel blocker nicardipine ( 2 mu M ) and was potentiated by 8 - pCPT - 2 ' - O - Me - cAMP - AM at concentrations >= 2 mu M in INS - 1 cells.", "output": "tolbutamide, gliclazide, thapsigargin, Ca ( 2 + ), nicardipine, 8 - pCPT - 2 ' - O - Me - cAMP - AM." }, { "input": "Ca ( 2 + ) transients stimulated by either tolbutamide or gliclazide were inhibited by thapsigargin or nicardipine and were significantly potentiated by 8 - pCPT - 2 ' - O - Me - cAMP - AM at 5 mu M but not 1 mu M.", "output": "Ca ( 2 + ), tolbutamide, gliclazide, thapsigargin, nicardipine." }, { "input": "Both tolbutamide and gliclazide stimulated phospholipase C activity; however, only gliclazide did so independently of its activity at K ( ATP ) channels, and this activity was partially inhibited by pertussis toxin.", "output": "tolbutamide, gliclazide, gliclazide, K, ATP." }, { "input": "8 - pCPT - 2 ' - O - Me - cAMP - AM alone ( 5 mu M ) did not stimulate insulin secretion, but did increase intracellular Ca ( 2 + ) concentration significantly, and this activity was inhibited by 25 mu M 2 - aminoethoxydiphenylborate ( 2 - APB ) or the removal of extracellular Ca ( 2 + ).", "output": "8 - pCPT - 2 ' - O - Me - cAMP - AM, Ca ( 2 + ), 2 - aminoethoxydiphenylborate, 2 - APB, Ca ( 2 + )." }, { "input": "8 - pCPT - 2 ' - O - Me - cAMP - AM potentiation of insulin secretion stimulated by tolbutamide was markedly inhibited by 2 - APB ( 25 mu M ) and enhanced by the PKC inhibitor bisindolylmaleimide I ( 1 mu M ).", "output": "8 - pCPT - 2 ' - O - Me - cAMP - AM, tolbutamide, 2 - APB, bisindolylmaleimide I." }, { "input": "Our data demonstrate that the actions of both tolbutamide and gliclazide are strongly potentiated by 8 - pCPT - 2 ' - O - Me - cAMP - AM, that gliclazide can stimulate phospholipase C activity via a partially pertussis toxin - sensitive mechanism, and that 8 - pCPT - 2 ' - O - Me - cAMP - AM potentiation of tolbutamide action may involve activation of a 2 - APB - sensitive Ca ( 2 + ) influx.", "output": "tolbutamide, gliclazide, 8 - pCPT - 2 ' - O - Me - cAMP - AM, gliclazide, 8 - pCPT - 2 ' - O - Me - cAMP - AM, 2 - APB, Ca ( 2 + )." }, { "input": "ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice.", "output": "There is no related enetity." }, { "input": "The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression.", "output": "There is no related enetity." }, { "input": "Using adipose tissue transplantation from wild - type ( WT ) to apoE knockout ( EKO ) mice, we show that adipose tissue also contributes to circulating apoE.", "output": "There is no related enetity." }, { "input": "Different from circulating apoE produced by bone marrow transplantation ( BMT ), however, adipose tissue - derived apoE does not correct hyperlipidemia or suppress atherosclerosis.", "output": "There is no related enetity." }, { "input": "ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes.", "output": "There is no related enetity." }, { "input": "The incremental binding can be entirely accounted for by binding to the LDL receptor.", "output": "There is no related enetity." }, { "input": "After BMT into EKO hosts, plasma cholesterol and macrophage - derived apoE are largely within IDL / LDL - and HDL - sized particles.", "output": "cholesterol." }, { "input": "After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL.", "output": "cholesterol." }, { "input": "After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation.", "output": "There is no related enetity." }, { "input": "In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis.", "output": "There is no related enetity." }, { "input": "A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors.", "output": "There is no related enetity." }, { "input": "In vitro and in vivo approaches to study osteocyte biology.", "output": "There is no related enetity." }, { "input": "Osteocytes, the most abundant cell population of the bone lineage, have been a major focus in the bone research field in recent years.", "output": "There is no related enetity." }, { "input": "This population of cells that resides within mineralized matrix is now thought to be the mechanosensory cell in bone and plays major roles in the regulation of bone formation and resorption.", "output": "There is no related enetity." }, { "input": "Studies of osteocytes had been impaired by their location, resulting in numerous attempts to isolate primary osteocytes and to generate cell lines representative of the osteocytic phenotype.", "output": "There is no related enetity." }, { "input": "Progress has been achieved in recent years by utilizing in vivo genetic technology and generation of osteocyte directed transgenic and gene deficiency mouse models.", "output": "There is no related enetity." }, { "input": "We will provide an overview of the current in vitro and in vivo models utilized to study osteocyte biology.", "output": "There is no related enetity." }, { "input": "We discuss generation of osteocyte - like cell lines and isolation of primary osteocytes and summarize studies that have utilized these cellular models to understand the functional role of osteocytes.", "output": "There is no related enetity." }, { "input": "Approaches that attempt to selectively identify and isolate osteocytes using fluorescent protein reporters driven by regulatory elements of genes that are highly expressed in osteocytes will be discussed.", "output": "There is no related enetity." }, { "input": "In addition, recent in vivo studies utilizing overexpression or conditional deletion of various genes using dentin matrix protein ( Dmp1 ) directed Cre recombinase are outlined.", "output": "There is no related enetity." }, { "input": "In conclusion, evaluation of the benefits and deficiencies of currently used cell lines / genetic models in understanding osteocyte biology underlines the current progress in this field.", "output": "There is no related enetity." }, { "input": "The future efforts will be directed towards developing novel in vitro and in vivo models that would additionally facilitate in understanding the multiple roles of osteocytes.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled \" The Osteocyte \".", "output": "There is no related enetity." }, { "input": "Effects of conjugated linoleic acid supplementation and exercise on post - heparin lipoprotein lipase, butyrylcholinesterase, blood lipid profile and glucose metabolism in young men.", "output": "linoleic acid, glucose." }, { "input": "This study was designed to investigate the effects of conjugated linoleic acid ( CLA ) supplementation and endurance exercise training - induced changes on post - heparin lipoprotein lipase ( PH - LPL ) and butyrylcholinesterase ( BChE ) activities along with leptin, insulin and lipid levels in plasma by a randomized double blind experiment.", "output": "linoleic acid, CLA." }, { "input": "Eighteen sedentary male volunteers were randomly divided into CLA and Placebo ( PLC ) supplementation groups.", "output": "CLA." }, { "input": "Both groups underwent daily supplementation of either 3g CLA or 3g placebo for 30days, respectively, and performed exercise on a bicycle ergometer 3 times per week for 30 - 40min at 50 % VO2 peak workload.", "output": "CLA." }, { "input": "For plasma glucose, insulin and leptin levels and BChE activity fasting blood was used.", "output": "glucose." }, { "input": "For PH - LPL measurements, blood was collected 15min after 50IU / kg iv heparin injection.", "output": "There is no related enetity." }, { "input": "In all groups, there is a statistically significant decrease in BChE ( p = 0. 03, p = 0. 02 ) and leptin ( p = 0. 002 ), insulin and HOMA - IR levels ( p = 0. 02 ).", "output": "There is no related enetity." }, { "input": "Exercise with or without CLA supplementation decreased insulin levels and increased insulin sensitivity.", "output": "CLA." }, { "input": "PH - LPL activity was increased significantly in both groups, displaying increased fatty acid mobilization.", "output": "There is no related enetity." }, { "input": "We conclude that though CLA supplementation and exercise can affect these parameters, CLA is not more effective than exercise alone.", "output": "CLA, CLA." }, { "input": "Hence, a prolonged supplementation regime may be more effective.", "output": "There is no related enetity." }, { "input": "Taken together in our small study group, our findings display that BChE is a potential marker for synthetic function of liver, fat metabolism, an obesity marker, a function long overlooked.", "output": "There is no related enetity." }, { "input": "In vivo genotoxicity of methyleugenol in gpt delta transgenic rats following medium - term exposure.", "output": "methyleugenol." }, { "input": "Methyleugenol ( MEG ), which is commonly used as a fragrance and flavoring agent, has been shown to induce hepatocellular tumors in rodents.", "output": "Methyleugenol, MEG." }, { "input": "However, the role of genotoxicity as a possible mechanism of action is not fully understood even though the DNA - reactive metabolite of MEG has been identified.", "output": "MEG." }, { "input": "In this study, a gpt delta transgenic rat model was used to clarify whether genotoxic mechanisms are involved in MEG - induced hepatocarcinogenesis following medium - term exposure.", "output": "MEG." }, { "input": "F344 gpt delta rats were subjected to repeated oral administration of MEG at dosages of 0, 10, 30, or 100mg / kg ( a carcinogenic dose ) for 13 weeks.", "output": "MEG." }, { "input": "The relative weight of the liver of the male and female rats that were administered 100mg / kg MEG and the absolute weight of the liver of the male rats that were administered 100mg / kg MEG were significantly increased.", "output": "MEG, MEG." }, { "input": "In addition, the number and area of glutathione S - transferase placental form ( GST - P ) positive foci and proliferating cell nuclear antigen ( PCNA ) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg / kg MEG compared with the control animals.", "output": "glutathione, S, MEG." }, { "input": "In the in vivo mutation assays, a significant increase in the gpt and Spi ( - ) mutant frequencies was observed in both sexes at the carcinogenic dose.", "output": "There is no related enetity." }, { "input": "These results suggest the possible participation of genotoxic mechanisms in MEG - induced hepatocarcinogenesis.", "output": "MEG." }, { "input": "Temperature controlled water / oil wettability of a surface fabricated by a block copolymer: application as a dual water / oil on - off switch.", "output": "There is no related enetity." }, { "input": "A temperature controlled dual water / oil on - off switch is achieved by using a PMMA - b - PNIPAAm block - copolymer coated mesh, determined by the conformational change of the PNIPAAm chain around the lower critical solution temperature ( LCST ) and also the cooperation between PNIPAAm and PMMA.", "output": "PMMA - b - PNIPAAm, PNIPAAm, PNIPAAm, PMMA." }, { "input": "Water can permeate through the BCP - coated mesh, and oil cannot below the LCST, whereas oil can and water cannot above the LCST.", "output": "There is no related enetity." }, { "input": "Resolving sub - molecular binding and electrical switching mechanisms of single proteins at electroactive conducting polymers.", "output": "There is no related enetity." }, { "input": "Polymer - based electrodes for interfacing biological tissues are becoming increasingly sophisticated.", "output": "There is no related enetity." }, { "input": "Their many functions place them at the cross - roads of electromaterials, biomaterials, and drug - delivery systems.", "output": "There is no related enetity." }, { "input": "For conducting polymers, the mechanism of conductivity requires doping with anionic molecules such as extracellular matrix molecules, a process that distinguishes them as biomaterials and provides a means to control interactions at the cellular - electrode interface.", "output": "There is no related enetity." }, { "input": "However, due to their complex structure, directly observing the selective binding of target molecules or proteins has so far eluded researchers.", "output": "There is no related enetity." }, { "input": "This situation is compounded by the polymer ' s ability to adopt different electronic states that alter the polymer - dopant interactions.", "output": "There is no related enetity." }, { "input": "Here, the ability to resolve sub - molecular binding specificity between sulfate and carboxyl groups of dopants and heparin binding domains of human plasma fibronectin is demonstrated.", "output": "carboxyl." }, { "input": "The interaction exploits a form of biological ' charge complementarity ' to enable specificity.", "output": "There is no related enetity." }, { "input": "When an electrical signal is applied to the polymer, the specific interaction is switched to a non - specific, high - affinity binding state that can be reversibly controlled using electrochemical processes.", "output": "There is no related enetity." }, { "input": "Both the specific and non - specific interactions are integral for controlling protein conformation and dynamics.", "output": "There is no related enetity." }, { "input": "These details, which represent the first direct measurement of biomolecular recognition between a single protein and any type of organic conductor, give new molecular insight into controlling cellular interactions on these polymer surfaces.", "output": "There is no related enetity." }, { "input": "The iron chelator, deferasirox, as a novel strategy for cancer treatment: oral activity against human lung tumor xenografts and molecular mechanism of action.", "output": "iron, deferasirox." }, { "input": "Deferasirox is an orally effective iron ( Fe ) chelator currently used for the treatment of iron - overload disease and has been implemented as an alternative to the gold standard chelator, desferrioxamine ( DFO ).", "output": "Deferasirox, iron, Fe, iron, desferrioxamine, DFO." }, { "input": "Earlier studies demonstrated that DFO exhibits anticancer activity due to its ability to deplete cancer cells of iron.", "output": "DFO, iron." }, { "input": "In this investigation, we examined the in vitro and in vivo activity of deferasirox against cells from human solid tumors.", "output": "There is no related enetity." }, { "input": "To date, there have been no studies to investigate the effect of deferasirox on these types of tumors in vivo.", "output": "deferasirox." }, { "input": "Deferasirox demonstrated similar activity at inhibiting proliferation of DMS - 53 lung carcinoma and SK - N - MC neuroepithelioma cell lines compared with DFO.", "output": "Deferasirox, DFO." }, { "input": "Furthermore, deferasirox was generally similar or slightly more effective than DFO at mobilizing cellular ( 59 ) Fe and inhibiting iron uptake from human transferrin depending on the cell type.", "output": "deferasirox, DFO, ( 59 ) Fe." }, { "input": "However, deferasirox potently inhibited DMS - 53 xenograft growth in nude mice when given by oral gavage, with no marked alterations in normal tissue histology.", "output": "deferasirox." }, { "input": "To understand the antitumor activity of deferasirox, we investigated its effect on the expression of molecules that play key roles in metastasis, cell cycle control, and apoptosis.", "output": "deferasirox." }, { "input": "We demonstrated that deferasirox increased expression of the metastasis suppressor protein N - myc downstream - regulated gene 1 and upregulated the cyclin - dependent kinase inhibitor p21 ( CIP1 / WAF1 ) while decreasing cyclin D1 levels.", "output": "deferasirox." }, { "input": "Moreover, this agent increased the expression of apoptosis markers, including cleaved caspase - 3 and cleaved poly ( ADP - ribose ) polymerase 1.", "output": "poly ( ADP - ribose )." }, { "input": "Collectively, we demonstrate that deferasirox is an orally effective antitumor agent against solid tumors.", "output": "deferasirox." }, { "input": "Nature of halogen bonding.", "output": "halogen." }, { "input": "A study based on the topological analysis of the Laplacian of the electron charge density and an energy decomposition analysis.", "output": "There is no related enetity." }, { "input": "In this work we investigate the nature of the Cl... N interactions in complexes formed between substituted ammonium [ NHn ( X3 - n ) ( with n = 0, 1, 2, 3 and X = - CH3, - F ] as Lewis bases and F - Cl molecule as Lewis acid.", "output": "Cl, N, NHn ( X3 - n ), CH3, F, Lewis bases, F, Cl, Lewis acid." }, { "input": "They have been chosen as a study case due to the wide range of variation of their binding energies, BEs.", "output": "There is no related enetity." }, { "input": "M o ller - Plesset [ MP2 / 6 - 311 + + G ( 2d, 2p ) ] calculations show that the BEs for this set of complexes lie in the range from 1. 27 kcal / mol ( in F - Cl... NF3 ) to 27. 62 kcal / mol [ in F - Cl... N ( CH3 ) 3 ].", "output": "F, Cl, NF3, F, Cl, N ( CH3 ) 3." }, { "input": "The intermolecular distribution of the electronic charge density and their L ( r ) = - (1/4) nabla ( 2 ) rho ( r ) function have been investigated within the framework of the atoms in molecules ( AIM ) theory.", "output": "There is no related enetity." }, { "input": "The intermolecular interaction energy decomposition has also been analyzed using the reduced variational space ( RVS ) method.", "output": "There is no related enetity." }, { "input": "The topological analysis of the L ( r ) function reveals that the local topological properties measured at the ( 3, + 1 ) critical point [ in L ( r ) topology ] are good descriptors of the strength of the halogen bonding interactions.", "output": "halogen." }, { "input": "The results obtained from energy decomposition analysis indicate that electrostatic interactions play a key role in these halogen bonding interactions.", "output": "halogen." }, { "input": "These results allow us to establish that, when the halogen atom is bonded to a group with high electron - withdrawing capacity, the electrostatic interaction between the electron cloud of the Lewis base and the halogen atom unprotected nucleus of the Lewis acid produces the formation and determines the geometry of the halogen bonded complexes.", "output": "halogen, Lewis base, halogen, Lewis acid, halogen." }, { "input": "In addition, a good linear relationship has been established between: the natural logarithm of the BEs and the electrostatic interaction energy between electron charge distribution of N atom and nucleus of Cl atom, denoted as V e - n ( N, Cl ) within the AIM theory.", "output": "N, Cl, N, Cl." }, { "input": "Contamination, parasitism and condition of Anguilla anguilla in three Italian stocks.", "output": "There is no related enetity." }, { "input": "In conjunction with habitat loss and overfishing, pollution and parasitism are believed to be relevant causes of collapse of Anguilla, as these can affect eel swimming ability and the development of gonads and embryos.", "output": "There is no related enetity." }, { "input": "The present study investigated Persistent Organic Pollutant ( POP ) concentrations, infection levels of Anguillicoloides crassus, lipid content and gonad abnormalities in eels sampled in 2007 - 2008 in three Italian water bodies ( Caprolace Lake, Lesina Lagoon and Tevere River ) that vary in salinity, trophic condition, contamination level and fishing pressure.", "output": "There is no related enetity." }, { "input": "Our analysis revealed that low - to - moderate levels of contamination and parasitism were not associated with gonad abnormalities in Caprolace Lake and Lesina Lagoon.", "output": "There is no related enetity." }, { "input": "On the contrary, POP concentrations and abundances of swim bladder nematodes were remarkably high in eels from the heavily urbanized Tevere River and were associated with significant gonad and swim bladder alterations.", "output": "There is no related enetity." }, { "input": "Contamination and infestation levels were so high to potentially impair spawner successful migration and reproduction.", "output": "There is no related enetity." }, { "input": "POP concentrations in Tevere eels also exceeded levels considered safe for food consumption.", "output": "There is no related enetity." }, { "input": "Though marginally contaminated, eels from the oligotrophic Caprolace Lake were in critical health condition: their lipid reserve was so low as to be considered insufficient to sustain the energetic costs of the transoceanic migration.", "output": "There is no related enetity." }, { "input": "Lesina eel stock was the only one displaying relatively good quality but here spawner abundance is likely limited by overfishing.", "output": "There is no related enetity." }, { "input": "Our results suggest that multiple stressors may potentially affect eel reproductive success.", "output": "There is no related enetity." }, { "input": "More definitive studies are needed to assess whether health effects caused by these multiple stressors are additive, compensatory or synergistic.", "output": "There is no related enetity." }, { "input": "Induction of hepatic multidrug resistance - associated protein 3 by ethynylestradiol is independent of cholestasis and mediated by estrogen receptor.", "output": "ethynylestradiol, estrogen." }, { "input": "Multidrug resistance - associated protein 3 ( Mrp3; Abcc3 ) expression and activity are up - regulated in rat liver after in vivo repeated administration of ethynylestradiol ( EE ), a cholestatic synthetic estrogen, whereas multidrug resistance - associated protein 2 ( Mrp2 ) is down - regulated.", "output": "ethynylestradiol, estrogen." }, { "input": "This study was undertaken to determine whether Mrp3 induction results from a direct effect of EE, independent of accumulation of any endogenous common Mrp2 / Mrp3 substrates resulting from cholestasis and the potential mediation of estrogen receptor ( ER ).", "output": "estrogen." }, { "input": "In in vivo studies, male rats were given a single, noncholestatic dose of EE ( 5 mg / kg s. c. ), and basal bile flow and the biliary excretion rate of bile salts and glutathione were measured 5 hours later.", "output": "bile salts, glutathione." }, { "input": "This treatment increased Mrp3 mRNA by 4 - fold, detected by real - time polymerase chain reaction, despite the absence of cholestasis.", "output": "There is no related enetity." }, { "input": "Primary culture of rat hepatocytes incubated with EE ( 1 - 10 micro M ) for 5 hours exhibited a 3 - fold increase in Mrp3 mRNA ( 10 micro M ), consistent with in vivo findings.", "output": "There is no related enetity." }, { "input": "The increase in Mrp3 mRNA by EE was prevented by actinomycin D, indicating transcriptional regulation.", "output": "actinomycin D." }, { "input": "When hepatocytes were incubated with an ER antagonist [ 7 alpha, 17 beta - [ 9 - [ ( 4, 4, 5, 5, 5 - Pentafluoropentyl ) sulfinyl ] nonyl ] estra - 1, 3, 5 ( 10 ) - triene - 3, 17 - diol ( ICI182 / 780 ), 1 micro M ], in addition to EE, induction of Mrp3 mRNA was abolished, implicating ER as a key mediator.", "output": "7 alpha , 17 beta - [ 9 - [ ( 4 , 4 , 5 , 5 , 5 - Pentafluoropentyl ) sulfinyl ] nonyl ] estra - 1 , 3 , 5 ( 10 ) - triene - 3 , 17 - diol, ICI182 / 780." }, { "input": "EE induced an increase in ER - alpha phosphorylation at 30 minutes and expression of c - Jun, a well - known ER target gene, at 60 minutes, as detected by Western blotting of nuclear extracts.", "output": "There is no related enetity." }, { "input": "These increases were prevented by ICI182 / 780.", "output": "ICI182 / 780." }, { "input": "In summary, EE increased the expression of hepatic Mrp3 transcriptionally and independently of any cholestatic manifestation and required participation of an ER, most likely ER - alpha, through its phosphorylation.", "output": "There is no related enetity." }, { "input": "Cell loss and autophagy in the extra - adrenal chromaffin organ of Zuckerkandl are regulated by glucocorticoid signalling.", "output": "There is no related enetity." }, { "input": "Neuroendocrine chromaffin cells exist in both intra - and extra - adrenal locations; the organ of Zuckerkandl ( OZ ) constitutes the largest accumulation of extra - adrenal chromaffin tissue in mammals.", "output": "There is no related enetity." }, { "input": "The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids ( GC ).", "output": "There is no related enetity." }, { "input": "Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified.", "output": "There is no related enetity." }, { "input": "Using mice with a conditional deletion of the GC - receptor ( GR ) gene restricted to cells expressing the dopamine beta - hydroxylase ( DBH ) gene [ GR ( fl / fl ); DBHCre abbreviated ( GR ( DBHCre ) ) ], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GR ( DBHCre ) mice are doubled compared to wild - type littermates.", "output": "dopamine." }, { "input": "We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy.", "output": "There is no related enetity." }, { "input": "Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells.", "output": "There is no related enetity." }, { "input": "Autophagy in OZ extra - adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene ( Atg5 ( DBHCre ) mice ).", "output": "There is no related enetity." }, { "input": "Cathepsin - D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8.", "output": "There is no related enetity." }, { "input": "Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GR ( DBHCre ) mice than in wild - type littermates.", "output": "There is no related enetity." }, { "input": "In summary, our results indicate that extra - adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling.", "output": "There is no related enetity." }, { "input": "Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin.", "output": "sirolimus, curcumin." }, { "input": "The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not - human cell lines.", "output": "sirolimus, curcumin." }, { "input": "Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic.", "output": "sirolimus, curcumin." }, { "input": "To answer this question we investigated the interaction of both these substances on OKT3 - induced human peripheral blood mononuclear cell ( PBMC ) proliferation.", "output": "There is no related enetity." }, { "input": "OKT3 - induced human PBMC proliferation was determined by measuring ( 3 ) H - thymidine incorporation.", "output": "( 3 ) H - thymidine." }, { "input": "Influence of curcumin on interleukin - 2 ( IL - 2 ) release and I kappa B - phosphorylation in PBMC was determined by ELISA and western blot, respectively.", "output": "curcumin." }, { "input": "Curcumin - induced apoptosis and necrosis was analyzed by FACS analysis.", "output": "Curcumin." }, { "input": "Whereas curcumin completely inhibited OKT3 - induced PBMC proliferation in a dose - dependent manner with an IC ( 50 ) of 2. 8 mu M, sirolimus could reduce PBMC proliferation dose - dependently only to a minimum of 28 % at a concentration of 5 ng / ml ( IC ( 50 ) 1. 1 ng / ml ).", "output": "curcumin, sirolimus." }, { "input": "When curcumin was combined at concentrations of 1. 25 - 2. 5 mu M with sirolimus at concentrations from 0. 63 to 1. 25 ng / ml the effects were synergistic.", "output": "curcumin, sirolimus." }, { "input": "Combination of curcumin ( 1. 25 - 2. 5 mu M ) with sirolimus ( 5 ng / ml ) showed additive effects.", "output": "curcumin, sirolimus." }, { "input": "The effects after combination of curcumin at 5 mu M with each sirolimus concentration and sirolimus at 10 ng / ml with each curcumin concentration were presumably antagonistic.", "output": "curcumin, sirolimus, sirolimus, curcumin." }, { "input": "We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3 - activated PBMC.", "output": "curcumin, sirolimus." }, { "input": "Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models.", "output": "curcumin, sirolimus." }, { "input": "Patterned assembly of quantum dots onto surfaces modified with click microcontact printing.", "output": "There is no related enetity." }, { "input": "The self - assembly of CdSe quantum dots ( QDs ) onto a patterned silica surface generated from surface microcontact click printing is presented.", "output": "There is no related enetity." }, { "input": "The mechanically robust self - assembly process produces patterns of QDs which remain steadfast, even as subsequent reactions are performed on the substrate, demonstrating the utility and ease of this self - assembly process.", "output": "There is no related enetity." }, { "input": "Pluripotent stem cells escape from senescence - associated DNA methylation changes.", "output": "There is no related enetity." }, { "input": "Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions, and this is accompanied by specific senescence - associated DNA methylation ( SA - DNAm ) changes.", "output": "There is no related enetity." }, { "input": "Here, we investigate SA - DNAm changes in mesenchymal stromal cells ( MSC ) upon long - term culture, irradiation - induced senescence, immortalization, and reprogramming into induced pluripotent stem cells ( iPSC ) using high - density HumanMethylation450 BeadChips.", "output": "There is no related enetity." }, { "input": "SA - DNAm changes are highly reproducible and they are enriched in intergenic and nonpromoter regions of developmental genes.", "output": "There is no related enetity." }, { "input": "Furthermore, SA - hypomethylation in particular appears to be associated with H3K9me3, H3K27me3, and Polycomb - group 2 target genes.", "output": "There is no related enetity." }, { "input": "We demonstrate that ionizing irradiation, although associated with a senescence phenotype, does not affect SA - DNAm.", "output": "There is no related enetity." }, { "input": "Furthermore, overexpression of the catalytic subunit of the human telomerase ( TERT ) or conditional immortalization with a doxycycline - inducible system ( TERT and SV40 - TAg ) result in telomere extension, but do not prevent SA - DNAm.", "output": "doxycycline." }, { "input": "In contrast, we demonstrate that reprogramming into iPSC prevents almost the entire set of SA - DNAm changes.", "output": "There is no related enetity." }, { "input": "Our results indicate that long - term culture is associated with an epigenetically controlled process that stalls cells in a particular functional state, whereas irradiation - induced senescence and immortalization are not causally related to this process.", "output": "There is no related enetity." }, { "input": "Absence of SA - DNAm in pluripotent cells may play a central role for their escape from cellular senescence.", "output": "There is no related enetity." }, { "input": "Fungicide prochloraz and environmental pollutant dioxin induce the ABCG2 transporter in bovine mammary epithelial cells by the arylhydrocarbon receptor signaling pathway.", "output": "prochloraz, dioxin, arylhydrocarbon." }, { "input": "The molecular mechanisms by which environmental pollutants including 2, 3, 7, 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) or widely used imidazole fungicide prochloraz display their toxic effects in vertebrates are still not well understood.", "output": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin, TCDD, imidazole, prochloraz." }, { "input": "Using computer analysis, we recently identified nuclear aryl hydrocarbon receptor ( AhR ) binding sites termed \" dioxin response elements \" ( DREs ) in the 5 ' - untranslated region ( 5 ' - UTR ) of efflux transporter ABCG2 ( Accession No. EU570105 ) from the bovine mammary gland.", "output": "aryl hydrocarbon, dioxin." }, { "input": "As these regulatory motifs mediate regulation of target genes by AhR agonists including TCDD and prochloraz, we have systematically investigated the effect of both contaminants on functional ABCG2 transport activity in primary bovine mammary epithelial cells.", "output": "TCDD, prochloraz." }, { "input": "TCDD or prochloraz doubled ABCG2 - mediated Hoechst H33342 secretion.", "output": "TCDD, prochloraz, Hoechst H33342." }, { "input": "This effect was almost completely reversed by specific ABCG2 inhibitor Ko143.", "output": "Ko143." }, { "input": "In further mechanistic studies, we showed that this induction was due to binding of activated AhR to DRE sequences in the ABCG2 5 ' - UTR.", "output": "There is no related enetity." }, { "input": "Receptor binding was significantly reduced by specific AhR antagonist salicyl amide.", "output": "salicyl amide." }, { "input": "Induction of AhR by TCDD and prochloraz resulted in a time - and dose - dependent increase of ABCG2 gene expression and transporter protein levels.", "output": "TCDD, prochloraz." }, { "input": "As ABCG2 represents the main mammary transporter for xenobiotics including drugs and toxins, exposure to prevalent AhR agonists may enhance transporter - mediated secretion of potential harmful compounds into milk.", "output": "There is no related enetity." }, { "input": "Through identification of mammary ABCG2 as a novel target gene of pesticide prochloraz and dioxin, our results may therefore help to improve the protection of breast - feeding infants and the consumer of dairy products.", "output": "prochloraz, dioxin." }, { "input": "Chlorine - enhanced surface mobility of Au ( 100 ).", "output": "Chlorine, Au." }, { "input": "Motivated by experimental studies of two - dimensional Ostwald ripening on Au ( 100 ) electrodes in chlorine - containing electrolytes, we have studied diffusion processes using density functional theory.", "output": "Au, chlorine." }, { "input": "We find that chlorine has a propensity to temporary form AuCl complexes, which diffuse significantly faster than gold adatoms.", "output": "chlorine, AuCl." }, { "input": "With and without chlorine, the lowest activation energy is found for the exchange mechanism.", "output": "chlorine." }, { "input": "Chlorine furthermore reduces the activation energy for the detachment from kink sites.", "output": "Chlorine." }, { "input": "Kinetic Monte Carlo simulations were performed on the basis of extensive density functional theory calculations.", "output": "There is no related enetity." }, { "input": "The island - decay rate obtained from these Monte Carlo simulations, as well as the decay rate obtained from the theoretical activation energies and frequency factors when inserted into analytical solutions for Ostwald ripening, are in agreement with experimental island - decay rates in chlorine - containing electrolytes.", "output": "chlorine." }, { "input": "Histone deacetylase 3 is required for maintenance of bone mass during aging.", "output": "There is no related enetity." }, { "input": "Histone deacetylase 3 ( Hdac3 ) is a nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression.", "output": "acetyl, lysine." }, { "input": "Hdac3 interacts with bone - related transcription factors and co - factors such as Runx2 and Zfp521, and thus is poised to play a key role in the skeletal system.", "output": "There is no related enetity." }, { "input": "To understand the role of Hdac3 in osteoblasts and osteocytes, Hdac3 conditional knockout ( CKO ) mice were created with the osteocalcin ( OCN ) promoter driving Cre expression.", "output": "There is no related enetity." }, { "input": "Hdac3 CKO ( OCN ) mice were of normal size and weight, but progressively lost trabecular and cortical bone mass with age.", "output": "There is no related enetity." }, { "input": "The Hdac3 CKO ( OCN ) mice exhibited reduced cortical bone mineralization and material properties and suffered frequent fractures.", "output": "There is no related enetity." }, { "input": "Bone resorption was lower, not higher, in the Hdac3 CKO ( OCN ) mice, suggesting that primary defects in osteoblasts caused the reduced bone mass.", "output": "There is no related enetity." }, { "input": "Indeed, reductions in bone formation were observed.", "output": "There is no related enetity." }, { "input": "Osteoblasts and osteocytes from Hdac3 CKO ( OCN ) mice showed increased DNA damage and reduced functional activity in vivo and in vitro.", "output": "There is no related enetity." }, { "input": "Thus, Hdac3 expression in osteoblasts and osteocytes is essential for bone maintenance during aging.", "output": "There is no related enetity." }, { "input": "Zymosan induces NADPH oxidase activation in human neutrophils by inducing the phosphorylation of p47phox and the activation of Rac2: involvement of protein tyrosine kinases, PI3Kinase, PKC, ERK1 / 2 and p38MAPkinase.", "output": "NADPH, tyrosine." }, { "input": "Reactive oxygen species ( ROS ) production by the neutrophil NADPH oxidase plays a key role in host defense against pathogens, such as bacteria and fungi.", "output": "oxygen, NADPH." }, { "input": "Zymosan a cell - wall preparation from Saccharomyces cerevisiae is largely used to activate neutrophils in its opsonized form.", "output": "There is no related enetity." }, { "input": "In this study, we show that non - opsonized zymosan alone induced ROS production by human neutrophils.", "output": "There is no related enetity." }, { "input": "Zymosan - induced ROS production is higher than the formyl - methionyl - leucyl - phenylalanine ( fMLF ) - or the phorbol myristate acetate ( PMA ) - induced ROS production but is lower than the one induced by opsonized zymosan.", "output": "formyl - methionyl - leucyl - phenylalanine, fMLF, phorbol myristate acetate, PMA." }, { "input": "Most of the zymosan - induced ROS production is intracellular.", "output": "There is no related enetity." }, { "input": "Interestingly, zymosan induced the phosphorylation of the NADPH oxidase cytosolic component p47phox on several sites which are Ser315, Ser328 and Ser345.", "output": "NADPH, Ser315, Ser328, Ser345." }, { "input": "Zymosan induced also the activation of the small G - protein Rac2.", "output": "There is no related enetity." }, { "input": "Phosphorylation of the p47phox as well as Rac2 activation were inhibited by genistein a broad range protein tyrosine kinase inhibitor and by wortmannin a PI3Kinase inhibitor.", "output": "genistein, tyrosine, wortmannin." }, { "input": "GF109203X a PKC inhibitor inhibited phosphorylation of p47phox on Ser315 and Ser328.", "output": "GF109203X, Ser315, Ser328." }, { "input": "SB203580 and UO126, inhibitors of p38MAPK and ERK1 / 2 - pathway, respectively, inhibited phosphorylation of p47phox on Ser345.", "output": "SB203580, UO126, Ser345." }, { "input": "Zymosan - induced ROS production was completely inhibited by genistein and wortmannin and partially inhibited by SB203580, UO126 and GF109203X.", "output": "genistein, wortmannin, SB203580, UO126, GF109203X." }, { "input": "These results show that zymosan alone is able to activate NADPH oxidase in human neutrophils via the phosphorylation of p47phox and Rac2 activation and that a protein tyrosine kinase, PI3Kinase, p38MAPK, ERK1 / 2 and PKC are involved in this process.", "output": "NADPH, tyrosine." }, { "input": "These pathways could be potential pharmacological targets to treat zymosan - and S. cerevisiae - induced inflammation.", "output": "There is no related enetity." }, { "input": "Solid dispersions for preparation of phototoxic supersaturated solutions for antimicrobial photodynamic therapy ( aPDT ): Studies on curcumin and curcuminoides L.", "output": "curcumin." }, { "input": "Curcumin is under investigation as a potential photosensitizer ( PS ) in antimicrobial photodynamic therapy ( aPDT ).", "output": "Curcumin." }, { "input": "The therapeutic potential of curcumin as a PS is limited by its low aqueous solubility, susceptibility to hydrolytic and photolytic degradation, and limited phototoxicity toward Gram negative ( G - ) bacteria.", "output": "curcumin." }, { "input": "Supersaturated solutions of curcumin have demonstrated high phototoxicity toward several species of Gram positive ( G + ) bacteria as well as the G - Escherichia ( E ) coli.", "output": "curcumin." }, { "input": "Thus, solid dispersions that can form supersaturated solutions of curcumin upon hydration may be beneficial in aPDT.", "output": "curcumin." }, { "input": "In the present study, solid dispersions of curcumin have been prepared through lyophilization of concentrated solutions obtained from dissolution of hydroxypropyl - beta - cyclodextrin ( HP beta CD ) - curcumin co - precipitates.", "output": "curcumin, hydroxypropyl - beta - cyclodextrin, HP beta CD, curcumin." }, { "input": "Hydroxypropyl methylcellulose ( HPMC ) was added to curcumin solutions prior to lyophilization.", "output": "Hydroxypropyl, curcumin." }, { "input": "The resulting lyophilizates were porous, amorphous and hydrated and dissolved rapidly in contact with a model physiological salt solution.", "output": "There is no related enetity." }, { "input": "The detected drug load of the lyophilizates was in the range 0. 5 - 1. 0 % ( w / w ) and was dependent on the selected ratio between HP beta CD and curcumin in the co - precipitate.", "output": "HP beta CD, curcumin." }, { "input": "The lyophilizate with the highest drug load could easily be dissolved in aqueous medium to form curcumin solutions of relevant concentrations for aPDT ( i. e., 10 mu M ).", "output": "curcumin." }, { "input": "Selected solutions of the curcumin solid dispersions showed a pronounced decrease in curcumin concentration up to 90 % after storage for 168h, which indicated that supersaturated curcumin solutions were initially formed upon dissolution of the lyophilizates.", "output": "curcumin, curcumin, curcumin." }, { "input": "Both freshly prepared and 2days old solutions of one selected curcumin lyophilizate induced significant inactivation of E. coli ( ~ 1 % bacterial survival ) after exposure to a light dose of only 5J / cm ( 2 ).", "output": "curcumin." }, { "input": "In vivo - in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems.", "output": "There is no related enetity." }, { "input": "The usefulness of in vitro systems to predict acute inhalation toxicity was investigated.", "output": "There is no related enetity." }, { "input": "Nineteen substances were tested in three - dimensional human airway epithelial models, EpiAirway (TM) and MucilAir (TM), and in A549 and 3T3 monolayer cell cultures.", "output": "There is no related enetity." }, { "input": "IC ( 50 ) values were compared to rat four - hour LC ( 50 ) values classified according to EPA and GHS hazard categories.", "output": "There is no related enetity." }, { "input": "Best results were achieved with a prediction model distinguishing toxic from non - toxic substances, with satisfactory specificities and sensitivities.", "output": "There is no related enetity." }, { "input": "Using a self - made four - level prediction model to classify substances into four in vitro hazard categories, in vivo - in vitro concordance was mediocre, but could be improved by excluding substances causing pulmonary edema and emphysema in vivo.", "output": "There is no related enetity." }, { "input": "None of the test systems was outstanding, and there was no evidence that tissue or monolayer systems using respiratory tract cells provide an added value.", "output": "There is no related enetity." }, { "input": "However, the test systems only reflected bronchiole epithelia and alveolar cells and investigated cytotoxicity.", "output": "There is no related enetity." }, { "input": "Effects occurring in other cells by other mechanisms could not be recognised.", "output": "There is no related enetity." }, { "input": "Further work should optimise test protocols and expand the set of substances tested to define applicability domains.", "output": "There is no related enetity." }, { "input": "In vivo respiratory toxicity data for in vitro comparisons should distinguish different modes of action, and their relevance for human health effects should be ensured.", "output": "There is no related enetity." }, { "input": "Nitrogen - containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and Bim - mediated activation of the intrinsic apoptotic pathway.", "output": "Nitrogen, bisphosphonates." }, { "input": "Nitrogen - containing bisphosphonates ( N - BPs ) induce apoptosis in tumor cells by inhibiting the prenylation of small G - proteins.", "output": "Nitrogen, bisphosphonates, N, BPs." }, { "input": "However, the details of the apoptosis - inducing mechanism remain obscure.", "output": "There is no related enetity." }, { "input": "The present study showed that the induction of apoptosis by N - BPs in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of geranylgeranyl pyrophosphate ( GGPP ) biosynthesis.", "output": "N, BPs, geranylgeranyl pyrophosphate, GGPP." }, { "input": "Furthermore, N - BPs decreased the levels of phosphorylated extracellular signal - regulated kinase ( ERK ) and mTOR via suppression of Ras prenylation and enhanced Bim expression.", "output": "N, BPs." }, { "input": "The present results indicated that N - BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase - 9 and caspase - 3, and enhancing Bim expression through inhibition of the Ras / MEK / ERK and Ras / mTOR pathways.", "output": "N, BPs." }, { "input": "The accumulation of N - BPs in bones suggests that they may act more effectively on tumors that have spread to bones or on Ras - variable tumors.", "output": "N, BPs." }, { "input": "This is the first study to show that the specific molecular pathways of N - BP - induced apoptosis.", "output": "N." }, { "input": "Changes in women ' s feelings about their romantic relationships across the ovulatory cycle.", "output": "There is no related enetity." }, { "input": "According to the dual mating hypothesis, women possess two overlapping suites of mate - choice mechanisms: one leading to preferences for sexually desirable men who have high - fitness genes and one leading to preferences for men who are able to invest in a woman and her children.", "output": "There is no related enetity." }, { "input": "Evidence increasingly demonstrates that women ' s preference for sexual desirability ( but not investment attractiveness ) increases when women are most fertile within the ovulatory cycle.", "output": "There is no related enetity." }, { "input": "Little is known, however, about the implications of these preference shifts for women ' s relationships with their long - term partners.", "output": "There is no related enetity." }, { "input": "Using luteinizing hormone tests to verify ovulation, across two studies ( Samples 1 and 2 ), we found that women whose partners were relatively low in sexual desirability felt less close to their partner ( Samples 1 and 2 ) and were more critical of their partner ' s faults ( Sample 2 ) on high - fertility days of the cycle just prior to ovulation compared with low - fertility days of the cycle.", "output": "There is no related enetity." }, { "input": "Women whose partners were relatively high in sexual desirability felt closer to their partner ( Sample 1 ) and more satisfied with their relationship ( Sample 2 ) on high - than low - fertility days of the cycle.", "output": "There is no related enetity." }, { "input": "There were no such shifts in women ' s commitment to their relationship.", "output": "There is no related enetity." }, { "input": "Therefore, partner sexual desirability predicts women ' s high - fertility assessments of relationship quality but not their intentions to stay in their relationship, consistent with the dual mating hypothesis.", "output": "There is no related enetity." }, { "input": "These findings suggest that variations across the ovulation cycle in women ' s reproductive hormones play an important role in relationship dynamics.", "output": "There is no related enetity." }, { "input": "Aryl hydrocarbon receptor - mediated disruption of contact inhibition is associated with connexin43 downregulation and inhibition of gap junctional intercellular communication.", "output": "Aryl hydrocarbon." }, { "input": "The aryl hydrocarbon receptor ( AhR ) contributes to the control of cell - to - cell communication, cell adhesion, migration or proliferation.", "output": "aryl hydrocarbon." }, { "input": "In the present study, we investigated the regulation of connexin43 ( Cx43 ) and Cx43 - mediated gap junctional intercellular communication ( GJIC ) during the AhR - dependent disruption of contact inhibition in non - tumorigenic liver epithelial cells.", "output": "There is no related enetity." }, { "input": "The contact inhibition of cell proliferation is a process restricting the cell division of confluent non - transformed cells, which is frequently abolished in cancer cells; however, the mechanisms contributing to its disruption are still only partially understood.", "output": "There is no related enetity." }, { "input": "Disruption of contact inhibition, which was induced by toxic AhR ligands 2, 3, 7, 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) or polycyclic aromatic hydrocarbons in epithelial WB - F344 cells, reduced Cx43 protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR - dependent manner.", "output": "2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin, TCDD, polycyclic aromatic hydrocarbons." }, { "input": "Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by TCDD, siRNA - mediated Cx43 knock - down was not sufficient to stimulate proliferation in contact - inhibited cells.", "output": "TCDD." }, { "input": "Our data suggest that downregulation of Cx43 / GJIC in non - transformed epithelial cells is an inherent part of disruption of contact inhibition, which occurs at the post - transcriptional level.", "output": "There is no related enetity." }, { "input": "This process runs in parallel with alterations of other forms of cell - to - cell communication, thus suggesting that toxic AhR agonists may simultaneously abrogate contact inhibition and reduce GJIC, two essential mechanisms linked to deregulation of cell - to - cell communication during tumor promotion and progression.", "output": "There is no related enetity." }, { "input": "Actinin - 4 in keratinocytes regulates motility via an effect on lamellipodia stability and matrix adhesions.", "output": "There is no related enetity." }, { "input": "During wound repair, epidermal cells at the edge of an injury establish front - rear polarity through orchestrated changes in their cytoskeleton and adhesion structures.", "output": "There is no related enetity." }, { "input": "The polarity and directed migration of such cells is determined by the assembly, extension, and stabilization of a lamellipodium.", "output": "There is no related enetity." }, { "input": "Actinin - 4 associates with lamellipodia and has been implicated in regulating lamellipodial structure, function and assembly.", "output": "There is no related enetity." }, { "input": "To study the functions of actinin - 4 in human keratinocytes, we used shRNA to generate knockdown cells and compared their motility behavior and matrix adhesion assembly to scrambled shRNA treated control keratinocytes.", "output": "There is no related enetity." }, { "input": "Actinin - 4 knockdown keratinocytes lack polarity, assemble multiple lamellipodia with a 2 x increased area over controls, display reduced activity of the actin remodeling protein cofilin, and fail to migrate in a directional manner.", "output": "There is no related enetity." }, { "input": "This motility defect is rescued by plating knockdown cells on preformed laminin - 332 matrix.", "output": "There is no related enetity." }, { "input": "In actinin - 4 - knockdown keratinocytes, focal contact area is increased by 25 %, and hemidesmosome proteins are mislocalized.", "output": "There is no related enetity." }, { "input": "Specifically, alpha 6 beta 4 integrin localizes to large lamellipodial extensions, displays reduced dynamics, and fails to recruit its bullous pemphigoid antigen binding partners.", "output": "There is no related enetity." }, { "input": "Together, our data indicate a role for actinin - 4 in regulating the steering mechanism of keratinocytes via profound effects on their matrix adhesion sites.", "output": "There is no related enetity." }, { "input": "PGC - 1 alpha improves glucose homeostasis in skeletal muscle in an activity - dependent manner.", "output": "glucose." }, { "input": "Metabolic disorders are a major burden for public health systems globally.", "output": "There is no related enetity." }, { "input": "Regular exercise improves metabolic health.", "output": "There is no related enetity." }, { "input": "Pharmacological targeting of exercise mediators might facilitate physical activity or amplify the effects of exercise.", "output": "There is no related enetity." }, { "input": "The peroxisome proliferator - activated receptor gamma coactivator 1 alpha ( PGC - 1 alpha ) largely mediates musculoskeletal adaptations to exercise, including lipid refueling, and thus constitutes such a putative target.", "output": "There is no related enetity." }, { "input": "Paradoxically, forced expression of PGC - 1 alpha in muscle promotes diet - induced insulin resistance in sedentary animals.", "output": "There is no related enetity." }, { "input": "We show that elevated PGC - 1 alpha in combination with exercise preferentially improves glucose homeostasis, increases Krebs cycle activity, and reduces the levels of acylcarnitines and sphingosine.", "output": "glucose, acylcarnitines, sphingosine." }, { "input": "Moreover, patterns of lipid partitioning are altered in favor of enhanced insulin sensitivity in response to combined PGC - 1 alpha and exercise.", "output": "There is no related enetity." }, { "input": "Our findings reveal how physical activity improves glucose homeostasis.", "output": "There is no related enetity." }, { "input": "Furthermore, our data suggest that the combination of elevated muscle PGC - 1 alpha and exercise constitutes a promising approach for the treatment of metabolic disorders.", "output": "There is no related enetity." }, { "input": "PAQR3 modulates insulin signaling by shunting phosphoinositide 3 - kinase p110 alpha to the Golgi apparatus.", "output": "There is no related enetity." }, { "input": "Phosphoinositide 3 - kinase ( PI3K ) mediates insulin actions by relaying signals from insulin receptors ( IRs ) to downstream targets.", "output": "There is no related enetity." }, { "input": "The p110 alpha catalytic subunit of class IA PI3K is the primary insulin - responsive PI3K implicated in insulin signaling.", "output": "There is no related enetity." }, { "input": "We demonstrate here a new mode of spatial regulation for the p110 alpha subunit of PI3K by PAQR3 that is exclusively localized in the Golgi apparatus.", "output": "There is no related enetity." }, { "input": "PAQR3 interacts with p110 alpha, and the intracellular targeting of p110 alpha to the Golgi apparatus is reduced by PAQR3 downregulation and increased by PAQR3 overexpression.", "output": "There is no related enetity." }, { "input": "Insulin - stimulated PI3K activity and phosphoinositide ( 3, 4, 5 ) - triphosphate production are enhanced by Paqr3 deletion and reduced by PAQR3 overexpression in hepatocytes.", "output": "phosphoinositide ( 3 , 4 , 5 ) - triphosphate." }, { "input": "Deletion of Paqr3 enhances insulin - stimulated phosphorylation of AKT and glycogen synthase kinase 3 beta, but not phosphorylation of IR and IR substrate - 1 ( IRS - 1 ), in hepatocytes, mouse liver, and skeletal muscle.", "output": "There is no related enetity." }, { "input": "Insulin - stimulated GLUT4 translocation to the plasma membrane and glucose uptake are enhanced by Paqr3 ablation.", "output": "glucose." }, { "input": "Furthermore, PAQR3 interacts with the domain of p110 alpha involved in its binding with p85, the regulatory subunit of PI3K.", "output": "There is no related enetity." }, { "input": "Overexpression of PAQR3 dose - dependently reduces the interaction of p85 alpha with p110 alpha.", "output": "There is no related enetity." }, { "input": "Thus, PAQR3 negatively regulates insulin signaling by shunting cytosolic p110 alpha to the Golgi apparatus while competing with p85 subunit in forming a PI3K complex with p110 alpha.", "output": "There is no related enetity." }, { "input": "NADPH - cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.", "output": "NADPH." }, { "input": "This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012.", "output": "There is no related enetity." }, { "input": "The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH - cytochrome P450 oxidoreductase ( POR ), a flavoprotein involved in electron transfer to microsomal cytochromes P450 ( P450 ), cytochrome b ( 5 ), squalene mono - oxygenase, and heme oxygenase.", "output": "NADPH, squalene, heme." }, { "input": "Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues.", "output": "There is no related enetity." }, { "input": "Additional mouse models with global or conditional hepatic deletion of cytochrome b ( 5 ) are helping to clarify the P450 isoform - and substrate - specific influences of cytochrome b ( 5 ) on P450 electron transfer and catalytic function.", "output": "There is no related enetity." }, { "input": "This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell - culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver.", "output": "There is no related enetity." }, { "input": "The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism.", "output": "steroid." }, { "input": "Importance of UDP - glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism.", "output": "UDP." }, { "input": "UDP - glucuronosyltransferase A1 ( UGT2A1 ) is expressed in the lung and exhibits activity against polycyclic aromatic hydrocarbons ( PAHs ), suggesting UGT2A1 involvement in the local metabolism of PAH tobacco carcinogens.", "output": "UDP, polycyclic aromatic hydrocarbons, PAHs, PAH." }, { "input": "The goal of the present study was to investigate the importance of two additional UGT2A enzymes, UGT2A2 and UGT2A3, in tobacco carcinogen metabolism.", "output": "There is no related enetity." }, { "input": "Real - time polymerase chain reaction suggested that wild - type UGT2A2 had the highest expression in the breast, followed by trachea > larynx > kidney.", "output": "There is no related enetity." }, { "input": "A novel splice variant of UGT2A2 lacking exon 3 ( termed UGT2A2 Delta exon3 ) was investigated, with UGT2A2 Delta exon3 expression determined to be 25 - 50 % that of wild - type UGT2A2 in all tissues examined.", "output": "There is no related enetity." }, { "input": "UGT2A3 was determined to be well expressed in the liver and colon, followed by pancreas > kidney > lung > tonsil > trachea > larynx.", "output": "There is no related enetity." }, { "input": "Cell homogenates prepared from human embryonic kidney ( HEK ) 293 cells overexpressing wild - type UGT2A2 ( termed UGT2A2 _ i1 ) exhibited glucuronidation activity, as observed by reverse - phase ultra - pressure liquid chromatography, against 1 - hydroxy - ( OH ) - pyrene, 1 - naphthol, and hydroxylated benzo ( a ) pyrene metabolites, whereas homogenates prepared from HEK293 cells overexpressing UGT2A3 only showed activity against simple PAHs like 1 - OH - pyrene and 1 - naphthol.", "output": "1 - hydroxy - ( OH ) - pyrene, 1 - naphthol, hydroxylated benzo ( a ) pyrene, PAHs, 1 - OH - pyrene, 1 - naphthol." }, { "input": "Activity assays showed the UGT2A2 Delta exon3 protein ( termed UGT2A2 _ i2 ) exhibited no detectable glucuronidation activity against all substrates examined; however, coexpression studies suggested that UGT2A2 _ i2 negatively modulates UGT2A2 _ i1 activity.", "output": "There is no related enetity." }, { "input": "Both UGT2A2 and UGT2A3 exhibited no detectable activity against complex PAH proximate carcinogens, tobacco - specific nitrosamines, or heterocyclic amines.", "output": "PAH, nitrosamines, heterocyclic amines." }, { "input": "These data suggest that, although UGT2A1 is the only UGT2A enzyme active against PAH proximate carcinogens ( including PAH diols ), both UGTs 2A1 and 2A2 play an important role in the local detoxification of procarcinogenic monohydroxylated PAH metabolites.", "output": "PAH, PAH, diols, monohydroxylated PAH." }, { "input": "Low - molecular - weight CXCR4 ligands with variable spacers.", "output": "There is no related enetity." }, { "input": "Low - molecular - weight CXCR4 ligands based on known lead compounds including the 14 - mer peptide T140, the cyclic pentapeptide FC131, peptide mimetics, and dipicolylamine - containing compounds were designed and synthesized.", "output": "cyclic pentapeptide, FC131, dipicolylamine." }, { "input": "Three types of aromatic spacers, 1, 4 - phenylenedimethanamine, naphthalene - 2, 6 - diyldimethanamine, and [ 1, 1 ' - biphenyl ] - 4, 4 ' - diyldimethanamine, were used to build four pharmacophore groups.", "output": "1 , 4 - phenylenedimethanamine, naphthalene - 2 , 6 - diyldimethanamine, [ 1 , 1 ' - biphenyl ] - 4 , 4 ' - diyldimethanamine." }, { "input": "As pharmacophore groups, 2 - pyridylmethyl and 1 - naphthylmethyl are present in all of the compounds, and several aromatic groups and a cationic group from 1 - propylguanidine and 1, 1, 3, 3 - tetramethyl - 2 - propylguanidine were also used.", "output": "2 - pyridylmethyl, 1 - naphthylmethyl, 1 - propylguanidine, 1 , 1 , 3 , 3 - tetramethyl - 2 - propylguanidine." }, { "input": "Several compounds showed significant CXCR4 binding affinity, and zinc ( II ) complexation of bis ( pyridin - 2 - ylmethyl ) amine moieties resulted in a remarkable increase in CXCR4 binding affinity.", "output": "zinc ( II ), bis ( pyridin - 2 - ylmethyl ) amine." }, { "input": "Lysine 48 - linked polyubiquitination of organic anion transporter - 1 is essential for its protein kinase C - regulated endocytosis.", "output": "Lysine." }, { "input": "Organic anion transporter - 1 ( OAT1 ) mediates the body ' s disposition of a diverse array of environmental toxins and clinically important drugs.", "output": "There is no related enetity." }, { "input": "Therefore, understanding the regulation of this transporter has profound clinical significance.", "output": "There is no related enetity." }, { "input": "We had previously established that OAT1 undergoes constitutive internalization from and recycling back to the cell surface and that acute activation of protein kinase C ( PKC ) inhibits OAT1 activity by reducing OAT1 cell - surface expression through accelerating its internalization from cell surface to intracellular compartments.", "output": "There is no related enetity." }, { "input": "However, the underlying mechanisms are poorly understood.", "output": "There is no related enetity." }, { "input": "In the current study, we provide novel evidence that acute activation of PKC significantly enhances OAT1 ubiquitination both in vitro and ex vivo.", "output": "There is no related enetity." }, { "input": "We further show that ubiquitination of cell - surface OAT1 increases in cells transfected with dominant negative mutant of dynamin - 2, a maneuver blocking OAT1 internalization, which suggests that OAT1 ubiquitination proceeds before OAT1 internalization.", "output": "There is no related enetity." }, { "input": "Mass spectroscopy has revealed that ubiquitination of OAT1 consists of polyubiquitin chains, primarily through lysine 48 linkage.", "output": "lysine." }, { "input": "Transfection of cells with the dominant negative mutant of ubiquitin Ub - K48R, which prevents the formation of Lys48 - linked polyubiquitin chains, abolishes PKC - stimulated OAT1 ubiquitination and internalization.", "output": "Lys48." }, { "input": "Together, our findings demonstrate for the first time that Lys48 - linked polyubiquitination is essential for PKC - regulated OAT1 trafficking.", "output": "Lys48." }, { "input": "ATP binding cassette transporters in two distinct compartments of the skin contribute to transdermal absorption of a typical substrate.", "output": "ATP." }, { "input": "The role of two ATP binding cassette transporters, P - glycoprotein ( P - gp ) and breast cancer resistance protein ( BCRP ), in transdermal absorption of a typical common substrate was examined in vivo.", "output": "ATP." }, { "input": "Skin and plasma concentrations of rhodamine123 ( Rho123 ) after dermal application were reduced in P - gp knockout ( mdr1a / 1b - / - ) mice and were below the detection limit in P - gp and BCRP triple - knockout ( mdr1a / 1b / bcrp - / - ) mice.", "output": "rhodamine123, Rho123." }, { "input": "Lower epidermal - to - hypodermal permeation of Rho123 in mdr1a / 1b / bcrp - / - mouse skin compared to the wild - type mouse skin was confirmed in an Ussing - type chamber experiment.", "output": "There is no related enetity." }, { "input": "The reduction in skin concentration after dermal application in mdr1a / 1b / bcrp - / - mice was greater in the dermis than in the epidermis, suggesting functional expressions of these transporters in two distinct skin compartments.", "output": "There is no related enetity." }, { "input": "Coadministration of the inhibitor itraconazole reduced the skin and plasma concentrations of Rho123 in the wild - type mice, but not in mdr1a / 1b / bcrp - / - mice, and a marked decrease of Rho123 concentration was seen in the dermis, demonstrating that the functional activities of these transporters can be modulated in vivo.", "output": "itraconazole, Rho123, Rho123." }, { "input": "On the other hand, the distribution of Rho123 after intravenous infusion was higher in mdr1a / 1b / bcrp - / - mice than in the wild - type mice.", "output": "Rho123." }, { "input": "This supports the occurrence of vectorial transport from the skin into systemic circulation, and is consistent with the immunohistochemical localization of P - gp and BCRP in mouse dermal endothelial cells.", "output": "There is no related enetity." }, { "input": "BCRP was immunohistochemically identified in human epidermis and dermal endothelial cells.", "output": "There is no related enetity." }, { "input": "Thus, our findings show that ABC transporters in different compartments of the skin contribute to transdermal absorption of a typical substrate in vivo and can be modulated by a specific inhibitor.", "output": "There is no related enetity." }, { "input": "These findings have implications for transdermal drug delivery.", "output": "There is no related enetity." }, { "input": "A - kinase - anchoring protein - Lbc anchors I kappa B kinase beta to support interleukin - 6 - mediated cardiomyocyte hypertrophy.", "output": "There is no related enetity." }, { "input": "In response to stress, the heart undergoes a pathological remodeling process associated with hypertrophy and the reexpression of a fetal gene program that ultimately causes cardiac dysfunction and heart failure.", "output": "There is no related enetity." }, { "input": "In this study, we show that A - kinase - anchoring protein ( AKAP ) - Lbc and the inhibitor of NF - kappa B kinase subunit beta ( IKK beta ) form a transduction complex in cardiomyocytes that controls the production of proinflammatory cytokines mediating cardiomyocyte hypertrophy.", "output": "There is no related enetity." }, { "input": "In particular, we can show that activation of IKK beta within the AKAP - Lbc complex promotes NF - kappa B - dependent production of interleukin - 6 ( IL - 6 ), which in turn enhances fetal gene expression and cardiomyocyte growth.", "output": "There is no related enetity." }, { "input": "These findings provide a new mechanistic hypothesis explaining how hypertrophic signals are coordinated and conveyed to interleukin - mediated transcriptional reprogramming events in cardiomyocytes.", "output": "There is no related enetity." }, { "input": "Identification of Dlk1 - Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion.", "output": "There is no related enetity." }, { "input": "The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long - lasting perturbations of gene expression.", "output": "There is no related enetity." }, { "input": "Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital ( PB ) mediated liver tumor promotion in vivo.", "output": "phenobarbital." }, { "input": "Molecular profiling ( mRNA, microRNA [ miRNA ], DNA methylation, and proteins ) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1 - Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans.", "output": "There is no related enetity." }, { "input": "PB induction of the Dlk1 - Dio3 cluster noncoding RNA ( ncRNA ) Meg3 was localized to glutamine synthetase - positive hypertrophic perivenous hepatocytes, suggesting a role for beta - catenin signaling in the dysregulation of Dlk1 - Dio3 ncRNAs.", "output": "glutamine." }, { "input": "The carcinogenic relevance of Dlk1 - Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and beta - catenin pathways.", "output": "androstane." }, { "input": "Our data identify Dlk1 - Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.", "output": "There is no related enetity." }, { "input": "Pharmacokinetic mechanism involved in the prolonged high retention of laninamivir in mouse respiratory tissues after intranasal administration of its prodrug laninamivir octanoate.", "output": "laninamivir, laninamivir octanoate." }, { "input": "Laninamivir octanoate ( LO ) ( Inavir; Daiichi Sankyo, Japan ) is an ester prodrug of the neuraminidase inhibitor laninamivir.", "output": "Laninamivir octanoate, Inavir, ester, laninamivir." }, { "input": "We previously reported that a prolonged high retention of laninamivir in mouse respiratory tissues was achieved by intranasal administration of LO.", "output": "laninamivir." }, { "input": "In this study, we evaluated intrapulmonary pharmacokinetics both in vivo and in vitro to investigate the potential mechanism involved in such a preferable retention.", "output": "There is no related enetity." }, { "input": "After intranasal administration of LO to mice ( 0. 5 mu mol / kg ), the drug was distributed from the airway space into the lungs, and laninamivir remained in the lung at 24 hours postdose ( 2680 pmol / g ), with a higher concentration than that in the epithelial lining fluid.", "output": "laninamivir." }, { "input": "The laninamivir was localized mainly on the epithelial cells of airway tracts, determined by microautoradiography using ( 14 ) C - labeled LO.", "output": "laninamivir, ( 14 ) C." }, { "input": "In mouse airway epithelial cells, the cellular uptake and hydrolysis of LO were observed over incubation time without any apparent saturation at the highest concentration tested ( 1000 mu M ).", "output": "There is no related enetity." }, { "input": "Furthermore, after additional incubation in drug - free medium, the intracellular laninamivir was released very slowly into the medium with an estimate rate constant of 0. 0707 h ( - 1 ), which was regarded as a rate - limiting step in the cellular retention.", "output": "laninamivir." }, { "input": "These results demonstrated that the prolonged high retention of laninamivir in the respiratory tissues was attributed to a consecutive series of three steps: uptake of LO into the airway epithelial cells, hydrolysis of LO into laninamivir by intracellular esterase ( s ), and limited efflux of the generated laninamivir due to its poor membrane permeability.", "output": "laninamivir, laninamivir, laninamivir." }, { "input": "This prodrug approach could be useful for lung - targeting drug delivery.", "output": "There is no related enetity." }, { "input": "A metabolomic study reveals novel plasma lyso - Gb3 analogs as Fabry disease biomarkers.", "output": "There is no related enetity." }, { "input": "Fabry disease is an X - linked, multisystemic lysosomal storage disorder due to alpha - galactosidase A deficiency.", "output": "There is no related enetity." }, { "input": "It is characterized by the accumulation of glycosphingolipids, mainly globotriaosylceramide ( Gb ( 3 ) ), in biological fluids, vascular endothelium, heart, and kidneys.", "output": "There is no related enetity." }, { "input": "Treatment by enzyme replacement therapy has been shown to be beneficial in both males and females affected with the disease.", "output": "There is no related enetity." }, { "input": "In addition to Gb ( 3 ), increased concentrations of globotriaosylsphingosine ( lyso - Gb ( 3 ) ) have recently been reported in urine and plasma of Fabry patients.", "output": "There is no related enetity." }, { "input": "The overall objective of this metabolomic study was to identify and characterize new potential plasma biomarkers in treated and untreated males and females affected with Fabry disease which might better reflect disease severity and progression.", "output": "There is no related enetity." }, { "input": "We employed a time - of - flight mass spectrometry metabolomic approach using plasma samples of Fabry patients compared to age - matched controls.", "output": "There is no related enetity." }, { "input": "We found three new lyso - Gb ( 3 ) analogs in Fabry patients presenting m / z ratios at 802, 804, and 820.", "output": "There is no related enetity." }, { "input": "As previously detected by our group, we also found a m / z ratio of 784 corresponding to the lyso - Gb ( 3 ) molecule minus two hydrogen atoms.", "output": "hydrogen." }, { "input": "Using exact mass measurements and tandem mass spectrometry, we confirmed that these analogs result from modifications of the lyso - Gb ( 3 ) sphingosine moiety.", "output": "There is no related enetity." }, { "input": "We evaluated the relative plasma concentration by measuring area counts for each lyso - Gb ( 3 ) analog.", "output": "There is no related enetity." }, { "input": "None of these analogs was detected in the majority of healthy controls.", "output": "There is no related enetity." }, { "input": "The relative concentration of each analog was higher in males compared to female Fabry patients.", "output": "There is no related enetity." }, { "input": "We demonstrated that mass spectrometry combined to a metabolomic approach is a powerful tool to detect and identify new potential biomarkers.", "output": "There is no related enetity." }, { "input": "Pump - Probe Microscopy: Spatially Resolved Carrier Dynamics in ZnO Rods and the Influence of Optical Cavity Resonator Modes.", "output": "ZnO." }, { "input": "Femtosecond pump - probe microscopy is used to investigate the charge recombination dynamics at different points within a single needle - shaped ZnO rod.", "output": "ZnO." }, { "input": "Recombination in the tips of the rod occurs through an excitonic or electron - hole plasma state, taking place on a picosecond time scale.", "output": "There is no related enetity." }, { "input": "Photoexcitation in the larger diameter sections of the interior exhibit dramatically slower recombination that occurs primarily through defects sites, i. e., trap mediated recombination.", "output": "There is no related enetity." }, { "input": "Transient absorption imaging shows that the spatial variation in the dynamics is also influenced by the cavity resonances supported within the hexagonal cross section of the rod.", "output": "There is no related enetity." }, { "input": "Finite element simulations suggest that these optical resonator modes produce qualitatively different intensity patterns in the two different locations.", "output": "There is no related enetity." }, { "input": "Near the end of the rod, the intensity pattern has significant standing - wave character, which leads to the creation of photoexcited carriers in the core of the structure.", "output": "There is no related enetity." }, { "input": "The larger diameter regions, on the other hand, exhibit intensity distributions in which the whispering gallery ( WG ) mode character dominates.", "output": "There is no related enetity." }, { "input": "At these locations, the photoexcited carriers are produced in subsurface depletion zone, where the internal fields separate the electrons and holes and lead to a greater degree of trap recombination on longer time scales.", "output": "There is no related enetity." }, { "input": "Chemical profile and biological activities of Deguelia duckeana A. M. G.", "output": "There is no related enetity." }, { "input": "Azevedo ( Fabaceae ).", "output": "There is no related enetity." }, { "input": "Deguelia duckeana is popularly known as timb o and used by indigenous people as ictiotoxic.", "output": "There is no related enetity." }, { "input": "On account of there being no literature pertaining to the chemical profile or biological activity of this plant, the hexane, methanol and aqueous crude extracts from leaves, stems and roots were assayed that presented very high cytotoxic potential against Artemia salina, achieving 100 % mortality in up to 5. 0 micro g mL ( - 1 ) concentration, but lower antioxidant potential on 2, 2 - diphenyl - 1 - picryl - hydrazyl and Fe ( 3 + ) / Phenanthroline assays.", "output": "hexane, methanol, 2 , 2 - diphenyl - 1 - picryl - hydrazyl, Fe ( 3 + ), Phenanthroline." }, { "input": "The phytochemical analysis of crude extracts showed the presence of flavonoids and related compounds as major constituents as well as steroids in all of them, and tannins in polar extracts.", "output": "flavonoids, steroids, tannins." }, { "input": "All the extracts were assayed for antibacterial activity but only the hexane extract of stems showed moderate activity on Staphylococcus aureus, which was fractionated and yielded a mixture of 3, 5, 4 ' - trimethoxy - 4 - prenylstilbene, lonchocarpine, 4 - hydroxylonchocarpine and derricidine, reported for the first time in D. duckeana and other fraction with beta - sitosterol and stigmasterol mixture.", "output": "hexane, 3 , 5 , 4 ' - trimethoxy - 4 - prenylstilbene, lonchocarpine, 4 - hydroxylonchocarpine, derricidine, beta - sitosterol, stigmasterol." }, { "input": "Lipophilic stinging nettle extracts possess potent anti - inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.", "output": "There is no related enetity." }, { "input": "Extracts of four plant portions ( roots, stems, leaves and flowers ) of Urtica dioica ( the stinging nettle ) were prepared using accelerated solvent extraction ( ASE ) involving water, hexanes, methanol and dichloromethane.", "output": "hexanes, methanol, dichloromethane." }, { "input": "The extracts were evaluated for their anti - inflammatory and cytotoxic activities in an NF - kappa B luciferase and MTT assay using macrophage immune ( RAW264. 7 ) cells.", "output": "MTT." }, { "input": "A standardized commercial ethanol extract of nettle leaves was also evaluated.", "output": "ethanol." }, { "input": "The methanolic extract of the flowering portions displayed significant anti - inflammatory activity on par with a standard compound celastrol ( 1 ) but were moderately cytotoxic.", "output": "celastrol." }, { "input": "Alternatively, the polar extracts ( water, methanol, ethanol ) of the roots, stems and leaves displayed moderate to weak anti - inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity.", "output": "methanol, ethanol, methanol." }, { "input": "In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti - inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264. 7 cells.", "output": "dichloromethane." }, { "input": "Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures ( water, methanol, ethanol ) in clinical evaluations for the treatment of inflammatory disorders especially arthritis.", "output": "methanol, ethanol." }, { "input": "A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound ( s ) responsible for their observed anti - inflammatory activity is further warranted.", "output": "There is no related enetity." }, { "input": "GH improves spatial memory and reverses certain anabolic androgenic steroid - induced effects in intact rats.", "output": "There is no related enetity." }, { "input": "GH has previously been shown to promote cognitive functions in GH - deficient rodents.", "output": "There is no related enetity." }, { "input": "In this study we report the effects of GH on learning and memory in intact rats pretreated with the anabolic androgenic steroid nandrolone.", "output": "steroid, nandrolone." }, { "input": "Male Wistar rats received nandrolone decanoate ( 15 mg / kg ) or peanut oil every third day for 3 weeks and were subsequently treated with recombinant human GH ( 1. 0 IU / kg ) or saline for 10 consecutive days.", "output": "nandrolone decanoate." }, { "input": "During the GH / saline treatment spatial learning and memory were tested in the Morris water maze ( MWM ).", "output": "There is no related enetity." }, { "input": "Also, plasma levels of IGF1 were assessed and the gene expression of the GH receptors ( Ghr ), Igf1 and Igf2, in hippocampus and frontal cortex was analyzed.", "output": "There is no related enetity." }, { "input": "The results demonstrated a significant positive effect of GH on memory functions and increased gene expression of Igf1 in the hippocampus was found in the animals treated with GH.", "output": "There is no related enetity." }, { "input": "In addition, GH was demonstrated to increase the body weight gain and was able to attenuate the reduced body weight seen in nandrolone - treated animals.", "output": "nandrolone." }, { "input": "In general, the rats treated with nandrolone alone did not exhibit any pronounced alteration in memory compared with controls in the MWM, and in many cases GH did not induce any alteration.", "output": "nandrolone." }, { "input": "Regarding target zone crossings, considered to be associated with spatial memory, the difference between GH - and steroid - treated animals was significant and administration of GH improved this parameter in the latter group.", "output": "There is no related enetity." }, { "input": "In conclusion, GH improves spatial memory in intact rats and can reverse certain effects induced by anabolic androgenic steroid.", "output": "steroid." }, { "input": "PET and SPECT tracers for glutamate receptors.", "output": "glutamate." }, { "input": "Radioligands for PET imaging of glutamate receptors will have the potential for studying neurological and neuropsychiatric disorders and their diagnosis and therapeutic intervention.", "output": "glutamate." }, { "input": "Glutamate is the major excitatory neurotransmitter in the brain and is implicated in the pathophysiology of many neurodegenerative and neuropsychiatric disorders.", "output": "Glutamate." }, { "input": "Glutamate and its receptors are potential targets in the treatment of these disorders.", "output": "Glutamate." }, { "input": "Glutamate signaling is mediated through ionotropic and metabotropic receptors.", "output": "Glutamate." }, { "input": "The abundant concentration of these receptors can facilitate their in vivo quantification using positron emission tomography ( PET ).", "output": "There is no related enetity." }, { "input": "Glutamate receptors are a potentially important set of targets for monitoring disease progression, for evaluating the effect of therapy and for new treatment development based on the quantification of receptor occupancy.", "output": "Glutamate." }, { "input": "Here, we review the PET and single - photon emission computed tomography ( SPECT ) radioligands that have been developed for imaging glutamate receptors in living brain.", "output": "glutamate." }, { "input": "The Online Protein Processing Resource ( TOPPR ): a database and analysis platform for protein processing events.", "output": "There is no related enetity." }, { "input": "We here present The Online Protein Processing Resource ( TOPPR; http: / / iomics. ugent. be / toppr / ), an online database that contains thousands of published proteolytically processed sites in human and mouse proteins.", "output": "There is no related enetity." }, { "input": "These cleavage events were identified with COmbinded FRActional DIagonal Chromatography proteomics technologies, and the resulting database is provided with full data provenance.", "output": "There is no related enetity." }, { "input": "Indeed, TOPPR provides an interactive visual display of the actual fragmentation mass spectrum that led to each identification of a reported processed site, complete with fragment ion annotations and search engine scores.", "output": "There is no related enetity." }, { "input": "Apart from warehousing and disseminating these data in an intuitive manner, TOPPR also provides an online analysis platform, including methods to analyze protease specificity and substrate - centric analyses.", "output": "There is no related enetity." }, { "input": "Concretely, TOPPR supports three ways to retrieve data: ( i ) the retrieval of all substrates for one or more cellular stimuli or assays; ( ii ) a substrate search by UniProtKB / Swiss - Prot accession number, entry name or description; and ( iii ) a motif search that retrieves substrates matching a user - defined protease specificity profile.", "output": "There is no related enetity." }, { "input": "The analysis of the substrates is supported through the presence of a variety of annotations, including predicted secondary structure, known domains and experimentally obtained 3D structure where available.", "output": "There is no related enetity." }, { "input": "Across substrates, substrate orthologs and conserved sequence stretches can also be shown, with iceLogo visualization provided for the latter.", "output": "There is no related enetity." }, { "input": "Silicon surface functionalization targeting Si - N linkages.", "output": "Silicon, Si - N." }, { "input": "Silicon substrates have been a fascinating topic of fundamental and applied research for well over 50 years.", "output": "Silicon." }, { "input": "They have attracted even more attention over the last couple of decades with advances in chemical functionalization that made oxide - free silicon surfaces a reality.", "output": "silicon." }, { "input": "Fundamentally new electronic properties and chemical reactivity became available, and the focus of chemical research turned more toward targeting specific chemical bonds and functionalities on silicon.", "output": "silicon." }, { "input": "Although thermodynamics clearly drives most processes under ambient conditions toward the formation of an oxide layer, kinetic control of the oxidation processes and thermodynamic tricks based on gaining stability of surface monolayers with high - density assembly have allowed for the formation of stable Si - C bonds and Si - O - C linkages on oxide - free silicon crystals.", "output": "Si - C, Si - O - C, silicon." }, { "input": "This feature article targets recent advances in making Si - N linkages on the same oxide - free single crystals.", "output": "Si - N." }, { "input": "It covers the range of chemical approaches to achieving this goal and offers possible chemistry that can take advantage of the systems produced.", "output": "There is no related enetity." }, { "input": "The present status of the field and the future directions of its development will be considered.", "output": "There is no related enetity." }, { "input": "Tanshinone derivatives: a patent review ( January 2006 - September 2012 ).", "output": "Tanshinone." }, { "input": "INTRODUCTION: Tanshinone IIA ( TSIIA ), cryptotanshinone and tanshinone I are major bioactive constituents of Danshen, a Chinese herbal medicine.", "output": "Tanshinone IIA, TSIIA, cryptotanshinone, tanshinone I." }, { "input": "Sodium tanshinone IIA sulfonate ( STS ) is a water - soluble derivative of TSIIA and it is currently used for treating cardiovascular diseases in China.", "output": "Sodium tanshinone IIA sulfonate, STS, TSIIA." }, { "input": "AREAS COVERED: The article presents a review of the anti - atherosclerosis, cardioprotective effects, neuroprotection and anti - tumor activities of TSIIA and a review of patents on tanshinone derivatives from January 2006 to September 2012.", "output": "TSIIA, tanshinone." }, { "input": "EXPERT OPINION: Mechanistic studies have discovered that TSIIA modulates ion channels, kinases, hormone receptors, apoptosis proteins, growth factors, cytokines, microRNA, tumor suppressor and many other targets, revealing an intricate biological network modulated by TSIIA.", "output": "TSIIA, TSIIA." }, { "input": "Many patents have attempted to overcome the low water solubility of TSIIA and tanshinone I by attaching a polar substituent or by a prodrug strategy.", "output": "TSIIA, tanshinone I." }, { "input": "However, biological activities of these tanshinone derivatives need to be further evaluated.", "output": "tanshinone." }, { "input": "Given the extensive in vitro and in vivo biological activities of TSIIA, this compound is a promising candidate to be further developed as a novel therapeutics for treating atherosclerosis, cardiovascular diseases, neurodegenerative diseases and cancer.", "output": "TSIIA." }, { "input": "Kainate receptor signaling in pain pathways.", "output": "Kainate." }, { "input": "Receptors and channels that underlie nociceptive signaling constitute potential sites of intervention for treatment of chronic pain states.", "output": "There is no related enetity." }, { "input": "The kainate receptor family of glutamate - gated ion channels represents one such candidate set of molecules.", "output": "kainate, glutamate." }, { "input": "They have a prominent role in modulation of excitatory signaling between sensory and spinal cord neurons.", "output": "There is no related enetity." }, { "input": "Kainate receptors are also expressed throughout central pain neuraxis, where their functional contributions to neural integration are less clearly defined.", "output": "Kainate." }, { "input": "Pharmacological inhibition or genetic ablation of kainate receptor activity reduces pain behaviors in a number of animal models of chronic pain, and small clinical trials have been conducted using several orthosteric antagonists.", "output": "kainate." }, { "input": "This review will cover kainate receptor function and participation in pain signaling as well as the pharmacological studies supporting further consideration as potential targets for therapeutic development.", "output": "kainate." }, { "input": "Subacute effects of ecstasy on mood: an exploration of associated risk factors.", "output": "ecstasy." }, { "input": "Ecstasy use may result in lowered mood, anxiety or aggression in the days following use.", "output": "Ecstasy." }, { "input": "Yet, few studies have investigated what factors increase the risk of experiencing such symptoms.", "output": "There is no related enetity." }, { "input": "Ecstasy users ( at least once in the last 12 months ) who subsequently took ecstasy ( n = 35 ) over the period of one week, were compared on measures of mood, sleep, stress and drug use, with those who abstained from ecstasy ( n = 21 ) that week.", "output": "Ecstasy, ecstasy, ecstasy." }, { "input": "Measures were administered the week prior to ecstasy use and one and three days following use, or the equivalent day for abstainers.", "output": "ecstasy." }, { "input": "Mood symptoms were assessed using the Kessler - 10 self - report psychological distress scale, a subjective mood rating ( 1 - 10 ), and using the depression, anxiety and hostility items from the clinician - rated Brief Psychiatric Rating Scale.", "output": "There is no related enetity." }, { "input": "Timeline Followback methods were used to collect information on drug use and life stress in the past month.", "output": "There is no related enetity." }, { "input": "Self - reported sleep quality was also assessed.", "output": "There is no related enetity." }, { "input": "Ecstasy use was not associated with subacute depressive, anxiety or aggressive symptoms.", "output": "Ecstasy." }, { "input": "Rather, lowered mood and increased psychological distress were associated with self - reported hours and quality of sleep obtained during the three - day follow - up.", "output": "There is no related enetity." }, { "input": "These findings highlight the importance of considering sleep disruption in understanding the short - term mood effects of ecstasy use.", "output": "ecstasy." }, { "input": "Simulated microgravity exposure modulates the phenotype of cultured vascular smooth muscle cells.", "output": "There is no related enetity." }, { "input": "Evidence from ground - based animal studies using tail - suspended hindlimb unloaded rats model has clearly demonstrated that simulated microgravity - induced smooth muscle cell phenotype conversion, a characteristic vascular structural and functional remodeling, may be one of the key contributors to postspaceflight orthostatic intolerance.", "output": "There is no related enetity." }, { "input": "However, the rats model involves multiple collective effects of microgravity including cephalic fluid shift and postural muscle unloading on smooth muscle cells ( SMCs ).", "output": "There is no related enetity." }, { "input": "It cannot isolate a single factor from the collective ones and therefore is not ideal to study the effects of gravitational vector alteration alone on SMCs.", "output": "There is no related enetity." }, { "input": "To test the hypothesis that gravitational vector alteration per se might affect smooth muscle cell phenotype, a roller culture apparatus was employed to expose cultured rat aortic smooth muscle cells ( RASMCs ) to simulated microgravity.", "output": "There is no related enetity." }, { "input": "Cell proliferation, cell cycle distribution, apoptosis, migration, and nitric oxide production rates were measured and compared between the control and the simulated microgravity groups.", "output": "nitric oxide." }, { "input": "Cell cytoskeleton reorganization induced by simulated microgravity was observed by confocal microscopy.", "output": "There is no related enetity." }, { "input": "Specific contractile and synthetic Gene expression at the mRNA level was quantified by reverse transcriptional polymerase chain reaction.", "output": "There is no related enetity." }, { "input": "It was observed that simulated microgravity suppressed RASMC proliferation and migration, enhanced cell apoptosis, stimulated NO release, and destroyed the original well - organized cytoskeleton.", "output": "NO." }, { "input": "Moreover, at the mRNA level, long - time exposure ( >= 72 h ) to simulated microgravity induced a contractile phenotype tendency by up - regulating smMHC expression.", "output": "There is no related enetity." }, { "input": "All these findings suggest that the phenotype modulation of vascular smooth muscle cells may be gravity dependent.", "output": "There is no related enetity." }, { "input": "Antiulcerogenic activities of the extracts and isolated flavonoids of Euphorbia cuneata Vahl.", "output": "flavonoids." }, { "input": "The total alcohol extracts of Euphorbia cuneata Vahl. ( Euphorbiaceae ) were screened for antiulcerogenic activity using an ethanol - induced ulcer model at doses of 125, 250 and 500 mg / kg.", "output": "alcohol, ethanol." }, { "input": "The extracts possessed antiulcerogenic activity in a dose - dependent manner.", "output": "There is no related enetity." }, { "input": "Four flavonoidal compounds were isolated and identified as naringenin, aromadendrin, apigenin and 4 ' - O - methoxy - luteolin - 7 - O - rhamnoglucoside, each demonstrating antiulcerogenic activity with curative ratios ranging from 75. 78 % to 88. 23 %.", "output": "flavonoidal, naringenin, aromadendrin, apigenin, 4 ' - O - methoxy - luteolin - 7 - O - rhamnoglucoside." }, { "input": "In addition, the alcohol extracts and isolated compounds were shown to scavenge the 1, 1 - diphenyl, 2 - picrylhydrazyl radical by different ratio, with the most effective being 4 ' - O - methoxy - luteolin - 7 - O - rhamnoglucoside ( 91. 14 % ).", "output": "alcohol, 1 , 1 - diphenyl , 2 - picrylhydrazyl, 4 ' - O - methoxy - luteolin - 7 - O - rhamnoglucoside." }, { "input": "The antioxidant activity of the alcohol extracts and the isolated compounds may explain the antiulcerogenic properties.", "output": "alcohol." }, { "input": "No side effects were observed on either liver or kidney functions.", "output": "There is no related enetity." }, { "input": "Effects of menstrual cycle phase on cocaine self - administration in rhesus macaques.", "output": "cocaine." }, { "input": "Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates.", "output": "cocaine, cocaine." }, { "input": "Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine ' s reinforcing effects than males, with estrous cycle stage as a key determinant of this effect.", "output": "cocaine." }, { "input": "The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans.", "output": "There is no related enetity." }, { "input": "Dose - dependent intravenous cocaine self - administration ( 0. 0125, 0. 0250, and 0. 0500 mg / kg / infusion ) using a progressive - ratio schedule of reinforcement was determined across the menstrual cycle.", "output": "cocaine." }, { "input": "The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone.", "output": "estradiol, progesterone." }, { "input": "Dependent variables including number of infusions self - administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase.", "output": "cocaine, cocaine." }, { "input": "Analysis of plasma hormone levels verified phase - dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase.", "output": "estradiol, progesterone, estrogen, progesterone." }, { "input": "Progressive ratio breakpoint, infusions self - administered, and cocaine intake did not consistently vary based on menstrual cycle phase.", "output": "cocaine." }, { "input": "These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques.", "output": "cocaine." }, { "input": "The catalytic competence of cytochrome P450 in the synthesis of serotonin from 5 - methoxytryptamine in the brain: an in vitro study.", "output": "serotonin, 5 - methoxytryptamine." }, { "input": "Brain serotonin has been implicated in the pathophysiology of a wide spectrum of psychiatric disorders, as well as in the mechanism of action of psychotropic drugs.", "output": "serotonin." }, { "input": "The aim of present study was to identify rat cytochrome P450 ( CYP ) isoforms which can catalyze the O - demethylation of 5 - methoxytryptamine to serotonin, and to find out whether that alternative pathway of serotonin synthesis may take place in the brain.", "output": "O, 5 - methoxytryptamine, serotonin, serotonin." }, { "input": "The study was conducted on cDNA - expressed CYPs ( rat CYP1A1 / 2, 2A1 / 2, 2B1, 2C6 / 11 / 13, 2D1 / 2 / 4 / 18, 2E1, 3A2 and human CYP2D6 ), on rat brain and liver microsomes and on human liver microsomes ( the wild - type CYP2D6 or the allelic variant 2D6 * 4 * 4 ).", "output": "There is no related enetity." }, { "input": "Of the rat CYP isoforms studied, CYP2D isoforms were the most efficient in catalyzing the O - demethylation of 5 - methoxytryptamine to serotonin, but they were less effective than the human isoform CYP2D6.", "output": "O, 5 - methoxytryptamine, serotonin." }, { "input": "Microsomes from different brain regions were capable of metabolizing 5 - methoxytryptamine to serotonin.", "output": "5 - methoxytryptamine, serotonin." }, { "input": "The reaction was inhibited by the specific CYP2D inhibitors quinine and fluoxetine.", "output": "quinine, fluoxetine." }, { "input": "Human liver microsomes of the wild - type CYP2D6 metabolized 5 - methoxytryptamine to serotonin more effectively than did the defective CYP2D6 * 4 * 4 ones.", "output": "5 - methoxytryptamine, serotonin." }, { "input": "The obtained results indicate that rat brain CYP2D isoforms catalyze the formation of serotonin from 5 - methoxytryptamine, and that the deficit or genetic defect of CYP2D may affect serotonin metabolism in the brain.", "output": "serotonin, 5 - methoxytryptamine, serotonin." }, { "input": "The results are discussed in the context of their possible physiological and pharmacological significance in vivo.", "output": "There is no related enetity." }, { "input": "A novel furanoeremophilane with an unusual oxygen bridge from Senecio nemorensis.", "output": "furanoeremophilane, oxygen." }, { "input": "Two new furanoeremophilanes, 1 alpha, 6 alpha - epoxy - 9 - oxo - 10 beta - hydroxyl - furanoeremophilane ( 1 ), and 9 - oxo - 1 alpha, 6 beta, 10 beta - trihydroxy - furanoeremophilane ( 2 ) were isolated from Senecio nemorensis.", "output": "furanoeremophilanes, 1 alpha , 6 alpha - epoxy - 9 - oxo - 10 beta - hydroxyl - furanoeremophilane, 9 - oxo - 1 alpha , 6 beta , 10 beta - trihydroxy - furanoeremophilane." }, { "input": "Their structures were elucidated by spectroscopic methods and X - ray crystallography.", "output": "There is no related enetity." }, { "input": "This is the first report of the isolation of the C1 - C6 oxygen bridge of furanoeremophilane.", "output": "C1 - C6, oxygen, furanoeremophilane." }, { "input": "Their cytotoxic effects on BEL7402 and NF - KB cell lines were tested.", "output": "There is no related enetity." }, { "input": "The role of transient receptor potential A 1 ( TRPA1 ) in the development and maintenance of carrageenan - induced hyperalgesia.", "output": "There is no related enetity." }, { "input": "Transient receptor potential ankyrin 1 ( TRPA1 ) is a nonselective cation channel important in setting nociceptive threshold.", "output": "There is no related enetity." }, { "input": "It is expressed in nociceptive C - fibers and in non - neuronal cells involved in pro - inflammatory mediators ' release.", "output": "There is no related enetity." }, { "input": "We asked whether TRPA1 contributes to carrageenan - induced hyperalgesia in rats, and if so, whether this contribution is mediated by mechanisms involved in inflammation such as cytokine release and neutrophil migration and / or by a direct sensitization of the primary afferent nociceptors.", "output": "There is no related enetity." }, { "input": "Pharmacological blockade of local TRPA1 by its selective antagonist HC 030031 prevented and reversed carrageenan - induced hyperalgesia, which was detected either by a mechanical or chemical ( low dose of capsaicin ) stimulus.", "output": "HC 030031, capsaicin." }, { "input": "However, it did not affect either carrageenan - induced cytokines expression or neutrophil migration.", "output": "There is no related enetity." }, { "input": "The neuronal TRPA1 gene silencing induced by intrathecal pre - treatment with antisense oligodoexynucleotide completely prevented carrageenan - induced hyperalgesia over 24 h and significantly reduced TRPA1 expression in the dorsal root ganglia cells ( L5 - 6 ), which was not affected by carrageenan treatment.", "output": "There is no related enetity." }, { "input": "We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan - induced inflammatory hyperalgesia by directly contributing to nociceptor excitability.", "output": "There is no related enetity." }, { "input": "Caffeine reduces cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis.", "output": "Caffeine, cadmium." }, { "input": "The aim of this study was to investigate the effects of caffeine ( 20 mg / L ) intake on cadmium ( 15 mg / L ) accumulation in the rat blood, testes, epididymis and prostate as well as cadmium - induced changes to the antioxidant defense system of the epididymis.", "output": "caffeine, cadmium, cadmium." }, { "input": "Caffeine reduced the cadmium concentration in all tissues analyzed.", "output": "Caffeine, cadmium." }, { "input": "Meanwhile, cadmium reduced catalase activity and increased superoxide dismutase ( SOD ) activity in the epididymis.", "output": "cadmium, superoxide." }, { "input": "Caffeine increased SOD activity, catalase and glutathione tissue expression and sustains the cadmium ' s effect on catalase and GSP - Px activity.", "output": "Caffeine, glutathione, cadmium." }, { "input": "No differences in the expression of metallothionein and lipid peroxidation were observed among the different treatments in the epididymis.", "output": "There is no related enetity." }, { "input": "In conclusion, low doses of cadmium alter the antioxidant enzymatic profile of the epididymis, but not induced oxidative lipid damage.", "output": "cadmium." }, { "input": "Caffeine intake reduces overall cadmium accumulation in the organism and enhances the levels of antioxidant protein expression in the epididymis, thus exerting a protective effect against this metal.", "output": "Caffeine, cadmium." }, { "input": "Teratogenic effects of diabetic conditions in chick heart in ovo and in micromass culture may be prevented by addition of vitamin C and folic acid.", "output": "vitamin C, folic acid." }, { "input": "Maternal diseases like diabetes mellitus may cause developmental defects.", "output": "There is no related enetity." }, { "input": "Supplementation with folic acid and vitamin C during the periconceptional period has been shown to prevent some neural tube and congenital heart defects.", "output": "folic acid, vitamin C." }, { "input": "Hearts were dissected from 5 days - old White Leghorn chick embryos, the cells isolated and cultured in micromass under diabetic conditions, with and without folic acid and vitamin C.", "output": "folic acid, vitamin C." }, { "input": "Contractile activity, cell viability ( resazurin reduction ) and protein assays were performed.", "output": "resazurin." }, { "input": "Results indicated diabetic conditions reduced contractile activity and cell viability, whilst vitamin C ( 100 mu M ) and folic acid ( 1 mM ) administered concurrently significantly improved them to values comparable with the control.", "output": "vitamin C, folic acid." }, { "input": "Day 3 chick embryos in ovo were injected with glucose + hydroxybutyrate or a combination of these and vitamins.", "output": "glucose, hydroxybutyrate." }, { "input": "Diabetic conditions caused gross and histological malformations, but these effects were abrogated by vitamin supplement.", "output": "There is no related enetity." }, { "input": "Teratogenic effects on heart development could possibly be prevented by vitamin supplementation during pregnancy.", "output": "There is no related enetity." }, { "input": "Association of NDRG1 Gene Promoter Methylation with Reduced NDRG1 Expression in Gastric Cancer Cells and Tissue Specimens.", "output": "There is no related enetity." }, { "input": "NDRG1 ( N - myc downstream - regulated gene 1 ) plays a role in cell differentiation and suppression of tumor metastasis.", "output": "There is no related enetity." }, { "input": "This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression.", "output": "There is no related enetity." }, { "input": "Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real - time PCR and Western blot.", "output": "There is no related enetity." }, { "input": "High - resolution melting analysis ( HRM ) and methylation - specific PCR ( MSP ) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples.", "output": "There is no related enetity." }, { "input": "Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues.", "output": "There is no related enetity." }, { "input": "Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein.", "output": "There is no related enetity." }, { "input": "HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples.", "output": "There is no related enetity." }, { "input": "Moreover, treatment with the DNA methyltransferase inhibitor 5 - Aza - 2 ' - deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A - treated HGC27 cells.", "output": "5 - Aza - 2 ' - deoxycytidine, trichostatin A." }, { "input": "In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter.", "output": "There is no related enetity." }, { "input": "Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.", "output": "There is no related enetity." }, { "input": "Influence of dietary carbon on mercury bioaccumulation in streams of the Adirondack Mountains of New York and the Coastal Plain of South Carolina, USA.", "output": "carbon, mercury." }, { "input": "We studied lower food webs in streams of two mercury - sensitive regions to determine whether variations in consumer foraging strategy and resultant dietary carbon signatures accounted for observed within - site and among - site variations in consumer mercury concentration.", "output": "mercury, carbon, mercury." }, { "input": "We collected macroinvertebrates ( primary consumers and predators ) and selected forage fishes from three sites in the Adirondack Mountains of New York, and three sites in the Coastal Plain of South Carolina, for analysis of mercury ( Hg ) and stable isotopes of carbon ( delta ( 13 ) C ) and nitrogen ( delta ( 15 ) N ).", "output": "mercury, Hg, carbon, ( 13 ) C, nitrogen, ( 15 ) N." }, { "input": "Among primary consumers, scrapers and filterers had higher MeHg and more depleted delta ( 13 ) C than shredders from the same site.", "output": "MeHg, ( 13 ) C." }, { "input": "Variation in delta ( 13 ) C accounted for up to 34 % of within - site variation in MeHg among primary consumers, beyond that explained by delta ( 15 ) N, an indicator of trophic position.", "output": "( 13 ) C, MeHg, ( 15 ) N." }, { "input": "Consumer delta ( 13 ) C accounted for 10 % of the variation in Hg among predatory macroinvertebrates and forage fishes across these six sites, after accounting for environmental aqueous methylmercury ( MeHg, 5 % of variation ) and base - N adjusted consumer trophic position ( Delta delta ( 15 ) N, 22 % of variation ).", "output": "( 13 ) C, Hg, methylmercury, MeHg, N, ( 15 ) N." }, { "input": "The delta ( 13 ) C spatial pattern within consumer taxa groups corresponded to differences in benthic habitat shading among sites.", "output": "( 13 ) C." }, { "input": "Consumers from relatively more - shaded sites had more enriched delta ( 13 ) C that was more similar to typical detrital delta ( 13 ) C, while those from the relatively more - open sites had more depleted delta ( 13 ) C.", "output": "( 13 ) C, ( 13 ) C, ( 13 ) C." }, { "input": "Although we could not clearly attribute these differences strictly to differences in assimilation of carbon from terrestrial or in - channel sources, greater potential for benthic primary production at more open sites might play a role.", "output": "carbon." }, { "input": "We found significant variation among consumers within and among sites in carbon source; this may be related to within - site differences in diet and foraging habitat, and to among - site differences in environmental conditions that influence primary production.", "output": "carbon." }, { "input": "These observations suggest that different foraging strategies and habitats influence MeHg bioaccumulation in streams, even at relatively small spatial scales.", "output": "MeHg." }, { "input": "Such influence must be considered when selecting lower trophic level consumers as sentinels of MeHg bioaccumulation for comparison within and among sites.", "output": "MeHg." }, { "input": "Enzyme kinetic and molecular docking studies for the inhibitions of miltirone on major human cytochrome P450 isozymes.", "output": "miltirone." }, { "input": "Previous studies have shown that major tanshinones isolated from Danshen ( Salvia miltiorrhiza ) inhibited human and rat CYP450 enzymes - mediated metabolism of model probe substrates, with potential in causing herb - drug interactions.", "output": "tanshinones." }, { "input": "Miltirone, another abietane type - diterpene quinone isolated from Danshen, has been reported for its anti - oxidative, anxiolytic and anti - cancer effects.", "output": "Miltirone, abietane, diterpene quinone." }, { "input": "The aim of this study was to study the effect of miltirone on the metabolism of model probe substrates of CYP1A2, 2C9, 2D6 and 3A4 in pooled human liver microsomes.", "output": "miltirone." }, { "input": "Miltirone showed moderate inhibition on CYP1A2 ( IC ( 50 ) = 1. 73 mu M ) and CYP2C9 ( IC ( 50 ) = 8. 61 mu M ), and weak inhibition on CYP2D6 ( IC ( 50 ) = 30. 20 mu M ) and CYP3A4 ( IC ( 50 ) = 33. 88 mu M ).", "output": "Miltirone." }, { "input": "Enzyme kinetic studies showed that miltirone competitively inhibited CYP2C9 ( K ( i ) = 1. 48 mu M ), and displayed mixed type inhibitions on CYP1A2, CYP2D6 and CYP3A4 with K ( i ) values of 3. 17 mu M, 24. 25 mu M and 35. 09 mu M, respectively.", "output": "miltirone." }, { "input": "Molecular docking study further confirmed the ligand - binding conformations of miltirone in the active sites of these human CYP450 isoforms, and provided some information on structure - activity relationships for the CYPs inhibition by tanshinones.", "output": "miltirone, tanshinones." }, { "input": "Taken together, CYPs inhibitions of miltirone were weaker than dihydrotanshinone, but stronger than cryptotanshinone, tanshinone I and tanshinone IIA.", "output": "miltirone, dihydrotanshinone, cryptotanshinone, tanshinone I, tanshinone IIA." }, { "input": "Social networks, web - based tools and diseases: implications for biomedical research.", "output": "There is no related enetity." }, { "input": "Advances in information technology have improved our ability to gather, collect and analyze information from individuals online.", "output": "There is no related enetity." }, { "input": "Social networks can be seen as a nonlinear superposition of a multitude of complex connections between people where the nodes represent individuals and the links between them capture a variety of different social interactions.", "output": "There is no related enetity." }, { "input": "The emergence of different types of social networks has fostered connections between individuals, thus facilitating data exchange in a variety of fields.", "output": "There is no related enetity." }, { "input": "Therefore, the question posed now is \" can these same tools be applied to life sciences in order to improve scientific and medical research? \" In this article, I will review how social networks and other web - based tools are changing the way we approach and track diseases in biomedical research.", "output": "There is no related enetity." }, { "input": "( - ) - Carvone: antispasmodic effect and mode of action.", "output": "( - ) - Carvone." }, { "input": "( - ) - Carvone is a monoterpene ketone found in spearmint ( Mentha spicata var. crispa ) essential oil that is widely used as an odor and flavor additive.", "output": "( - ) - Carvone, monoterpene ketone." }, { "input": "An intestinal antispasmodic effect was recently reported for ( - ) - carvone, and it has been shown to be more potent than its ( + ) - antipode.", "output": "( - ) - carvone." }, { "input": "The mechanism of ( - ) - carvone action in the intestines has not been investigated.", "output": "( - ) - carvone." }, { "input": "To gain a better understanding of the ( - ) - carvone antispasmodic effect, we investigated its pharmacological effects in the guinea pig ileum.", "output": "( - ) - carvone." }, { "input": "Terminal portions of the ileum were mounted for isotonic contraction recordings.", "output": "There is no related enetity." }, { "input": "The effect of ( - ) - carvone was compared with that of the classical calcium channel blocker ( CCB ) verapamil.", "output": "( - ) - carvone, calcium, verapamil." }, { "input": "In isolated ileal smooth muscle, ( - ) - carvone did not produce direct contractile or relaxation responses and did not modify electrically elicited contractions or low K ( + ) - evoked contractions.", "output": "( - ) - carvone, K ( + )." }, { "input": "The submaximal contractions induced by histamine ( p < 0. 001 ), BaCl2 ( p < 0. 05 ), and carbachol ( p < 0. 01 ) were significantly reduced by ( - ) - carvone.", "output": "histamine, BaCl2, carbachol, ( - ) - carvone." }, { "input": "The contractile response elicited by high concentrations of carbachol was reduced but not abolished by ( - ) - carvone.", "output": "carbachol, ( - ) - carvone." }, { "input": "No additive action was detected with co - incubation of ( - ) - carvone and verapamil on carbachol - induced contraction.", "output": "( - ) - carvone, verapamil, carbachol." }, { "input": "( - ) - Carvone reduced the contraction induced by high K ( + ) and was almost 100 times more potent than verapamil.", "output": "( - ) - Carvone, K ( + ), verapamil." }, { "input": "Thus, ( - ) - carvone showed a typical and potent CCB - like action.", "output": "( - ) - carvone." }, { "input": "Many effects described for both ( - ) - carvone and spearmint oil can be explained as a CCB - like mode of action.", "output": "( - ) - carvone." }, { "input": "Mitochondrial electron transfer chain complexes inhibition by different organochalcogens.", "output": "organochalcogens." }, { "input": "Mitochondrial dysfunction plays a pivotal role in the cell toxicology and death decision.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to investigate the effect of three organocompounds ( ebselen [ Ebs ], diphenyl diselenide [ ( PhSe ) ( 2 ) ] and diphenyl ditelluride [ ( PhTe ) ( 2 ) ] ) on mitochondrial complexes ( I, II, I - III, II - III and IV ) activity from rat liver and kidney to determine their potential role as molecular targets of organochalcogens.", "output": "diphenyl diselenide, ( PhSe ) ( 2 ), diphenyl ditelluride, ( PhTe ) ( 2 ), organochalcogens." }, { "input": "All studied organochalcogens caused a statistically significant inhibition of the mitochondrial complex I activity.", "output": "organochalcogens." }, { "input": "Ebs and ( PhTe ) ( 2 ) caused a statistically significant inhibition of the mitochondrial complex II activity in both hepatic and renal membranes.", "output": "( PhTe ) ( 2 )." }, { "input": "Hepatic mitochondrial complex II activity was practically unchanged by ( PhSe ) ( 2 ), whereas it significantly inhibited renal complex II activity.", "output": "( PhSe ) ( 2 )." }, { "input": "Mitochondrial complex IV activity was practically unchanged by the organochalcogens.", "output": "organochalcogens." }, { "input": "Furthermore, organochalcogens inhibited the mitochondrial respiration supported by complex I or complex II substrates.", "output": "organochalcogens." }, { "input": "The inhibitory effect of Ebs, ( PhSe ) ( 2 ) and ( PhTe ) ( 2 ) on mitochondrial complex I was prevented by NADH, but it was not prevented by catalase ( CAT ) and / or superoxide dismutase ( SOD ).", "output": "( PhSe ) ( 2 ), ( PhTe ) ( 2 ), NADH, superoxide." }, { "input": "Additionally, the organochalcogens - induced inhibition of complex I and II was completely reversed by reduced glutathione ( GSH ).", "output": "organochalcogens, reduced glutathione, GSH." }, { "input": "In conclusion, Ebs, ( PhSe ) ( 2 ) and ( PhTe ) ( 2 ) were more effective inhibitors of renal and hepatic mitochondrial complex I than complex II, whereas complexes III and IV were little modified by these compounds.", "output": "( PhSe ) ( 2 ), ( PhTe ) ( 2 )." }, { "input": "Taking into account the presented results, we suggest that organochalcogen - induced mitochondrial complexes I and II inhibition can be mediated by their thiol oxidation activity, i. e., Ebs, ( PhSe ) ( 2 ) and ( PhTe ) ( 2 ) can oxidize critical thiol groups from mitochondrial complexes I and II.", "output": "organochalcogen, thiol, ( PhSe ) ( 2 ), ( PhTe ) ( 2 )." }, { "input": "So, mitochondrial dysfunction can be considered an important factor in the toxicity of Ebs, ( PhSe ) ( 2 ) and ( PhTe ) ( 2 ).", "output": "( PhSe ) ( 2 ), ( PhTe ) ( 2 )." }, { "input": "Estrogen receptor signaling as a target for novel breast cancer therapeutics.", "output": "Estrogen." }, { "input": "In breast cancer ( BC ) epithelial cells, the mitogenic action of estradiol is transduced through binding to two receptors, ER alpha and ER beta, which act as transcription factors.", "output": "estradiol." }, { "input": "Anti - estrogens ( AEs ) and aromatase inhibitors ( AIs ) are used clinically to arrest the estrogen - dependent growth of BC.", "output": "estrogens, estrogen." }, { "input": "In the case of AE or AI resistance, Herceptin or lapatinib may be used to inhibit growth factors.", "output": "lapatinib." }, { "input": "Estrogen effects are mediated not only through nuclear ERs but also through cytoplasmic / membrane ERs and G - protein - coupled ERs.", "output": "Estrogen." }, { "input": "These estrogen - binding systems associate with various proteins that direct cell cycle signaling, proliferation and survival.", "output": "estrogen." }, { "input": "The partners of nuclear ER include SRC1 - 3, HDACs and ER beta itself as well as newly identified proteins, such as E6 - AP, LKB1, PELP1, PAX - 2 and FOXA1.", "output": "There is no related enetity." }, { "input": "The partners of extra - nuclear ER alpha include PI3K and the tyrosine kinase Src.", "output": "tyrosine." }, { "input": "These various factors are all potential targets for therapeutic intervention.", "output": "There is no related enetity." }, { "input": "In addition, BC proliferation is enhanced by insulin and EGF, which stimulate signaling through the MAPK and PI3K / AKT pathways by activation of the IGF - 1R and EGFR axes, respectively.", "output": "There is no related enetity." }, { "input": "These pathways are tightly interconnected with ER - activated signaling, and membrane ER alpha forms complexes with Src and PI3K.", "output": "There is no related enetity." }, { "input": "Chemokine - mediated signaling also modulates the estrogen response.", "output": "estrogen." }, { "input": "Inhibiting these pathways with specific inhibitors or activating some of the pathways by gene manipulation may be therapeutically valuable for arresting BC cell cycle progression and for inducing apoptosis to antagonize hormone - resistance.", "output": "There is no related enetity." }, { "input": "Here, we review some newly identified putatively targetable ER partners and highlight the need to develop tumor - targeting drug carrier systems affecting both the tumor cells and the tumor environment.", "output": "There is no related enetity." }, { "input": "Cytochrome P450 - mediated herb - drug interaction potential of Galgeun - tang.", "output": "There is no related enetity." }, { "input": "We evaluated the herb - drug interaction potential of Galgeun - tang ( GGT ) extracts, mediated by cytochrome P450 ( CYP ) inhibition / induction.", "output": "There is no related enetity." }, { "input": "Further, the effects of fermentation on the CYP - mediated herb - drug interaction potential of GGT extracts were determined.", "output": "There is no related enetity." }, { "input": "As measured by LC - ESI / MS / MS, GGT extracts ( 0 - 300 mu g / mL ) showed no inhibitory activity toward eight CYP isoforms ( 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 ) in pooled human liver microsomes, suggesting that GGT may have low potential for herb - drug interactions mediated by CYP inhibition.", "output": "There is no related enetity." }, { "input": "Hepatic CYP expression and activity in rats treated with GGT extracts twice per day for 1week was examined.", "output": "There is no related enetity." }, { "input": "Among the tested CYP isoforms ( 1A1, 1A2, 1B1, 2B1, 2C11, 2E1, 3A1, 3A2, and 4A1 ), CYP1B1 and 4A1 were increased by GGT extracts.", "output": "There is no related enetity." }, { "input": "Hepatic activities of 7 - ethoxyresorufin - O - deethylase, 7 - pentoxyresorufin - O - depentylase, and chlorzoxazone 6 - hydroxylase, but not midazolam hydroxylase were also elevated.", "output": "7 - ethoxyresorufin, O, 7 - pentoxyresorufin, O, chlorzoxazone, midazolam." }, { "input": "These results raise the possibility that GGT extracts may increase the toxicity of environmental toxicants through the elevating CYP - dependent metabolic activation.", "output": "There is no related enetity." }, { "input": "Interestingly, the increases in CYP1B1 and CYP4A1 levels, and 7 - ethoxyresorufin - O - deethylase, 7 - pentoxyresorufin - O - depentylase, and chlorzoxazone 6 - hydroxylase activities were attenuated by fermentation of GGT extract using Lactobacillus plantarum KFRI 402, but not 144.", "output": "7 - ethoxyresorufin, 7 - pentoxyresorufin, chlorzoxazone." }, { "input": "Further studies are needed to identify the CYP regulatory component ( s ) from GGT and determination its metabolism.", "output": "There is no related enetity." }, { "input": "Comparative study of equimolar doses of gamma - hydroxybutyrate ( GHB ), 1, 4 - butanediol ( 1, 4 - BD ) and gamma - butyrolactone ( GBL ) on catalepsy after acute and chronic administration.", "output": "gamma - hydroxybutyrate, GHB, 1 , 4 - butanediol, 1 , 4 - BD, gamma - butyrolactone, GBL." }, { "input": "Gamma - hydroxybutyrate ( GHB ), and its precursors 1, 4 - butanediol ( 1, 4 - BD ) and gamma - butyrolactone ( GBL ) are known drugs of abuse.", "output": "Gamma - hydroxybutyrate, GHB, 1 , 4 - butanediol, 1 , 4 - BD, GBL." }, { "input": "The ability of acute and chronic administration of equimolar doses of GHB ( 200mg / kg ), 1, 4 - BD ( 174mg / kg ) and GBL ( 166mg / kg ) to produce catalepsy in male Swiss Webster mice was examined.", "output": "GHB, 1 , 4 - BD, GBL." }, { "input": "GHB, 1, 4 - BD, GBL produced catalepsy when injected acutely.", "output": "GHB, 1 , 4 - BD, GBL." }, { "input": "Drug treatment was then continued for 14days.", "output": "There is no related enetity." }, { "input": "Tolerance development was determined on days 6, 14, and challenged with a higher dose on day 15 in those chronically pretreated mice, and compared with na i ve mice.", "output": "There is no related enetity." }, { "input": "Chronic GHB produced tolerance to catalepsy, as evidenced from area under the curve ( AUC ) of catalepsy versus time ( min - sec ) on days 6 ( 678 +/- 254 ), 14 ( 272 +/- 247 ), which were less than those on day 1 ( 1923 +/- 269 ).", "output": "GHB." }, { "input": "However, less tolerance was seen from GBL or 1, 4 - BD, as AUCs on days 6 and 14 were not significantly lower than that of day 1.", "output": "GBL, 1 , 4 - BD." }, { "input": "In conclusion, although equimolar doses were used, expecting similar levels of GHB in the body, 1, 4 - BD and GBL shared only some of the in vivo effects of GHB.", "output": "GHB, 1 , 4 - BD, GBL, GHB." }, { "input": "The rate of metabolic conversion of 1, 4 - BD and GBL into GHB might be responsible for the differences in the tolerance development to these drugs.", "output": "1 , 4 - BD, GBL, GHB." }, { "input": "Transient gestational and neonatal hypothyroidism - induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.", "output": "androgen." }, { "input": "The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational / neonatal - onset hypothyroidism.", "output": "androgen." }, { "input": "Pregnant and lactating rats were made hypothyroid by exposing to 0. 05 % methimazole in drinking water; gestational exposure was from embryonic day 9 - 14 ( group II ) or 21 ( group III ), lactational exposure was from postnatal day 1 - 14 ( group IV ) or 29 ( group V ).", "output": "methimazole." }, { "input": "Serum was collected for hormone assay.", "output": "There is no related enetity." }, { "input": "Androgen receptor status, Glu - 4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles.", "output": "Androgen." }, { "input": "Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control.", "output": "testosterone, estradiol, testosterone, estradiol." }, { "input": "Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism ( group II - V ).", "output": "Androgen." }, { "input": "Glut - 4 expression remained normal in skeletal and cardiac muscle of experimental rats.", "output": "There is no related enetity." }, { "input": "Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone.", "output": "lactate, creatine." }, { "input": "It is concluded that transient gestational / lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood.", "output": "methimazole." }, { "input": "Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood.", "output": "There is no related enetity." }, { "input": "Lung inflammatory effects, tumorigenesis, and emphysema development in a long - term inhalation study with cigarette mainstream smoke in mice.", "output": "There is no related enetity." }, { "input": "Cigarette smoking is the leading cause of lung cancer and chronic obstructive pulmonary disease, yet there is little mechanistic information available in the literature.", "output": "There is no related enetity." }, { "input": "To improve this, laboratory models for cigarette mainstream smoke ( MS ) inhalation - induced chronic disease development are needed.", "output": "There is no related enetity." }, { "input": "The current study investigated the effects of exposing male A / J mice to MS ( 6h / day, 5 days / week at 150 and 300 mg total particulate matter per cubic meter ) for 2. 5, 5, 10, and 18 months in selected combinations with postinhalation periods of 0, 4, 8, and 13 months.", "output": "There is no related enetity." }, { "input": "Histopathological examination of step - serial sections of the lungs revealed nodular hyperplasia of the alveolar epithelium and bronchioloalveolar adenoma and adenocarcinoma.", "output": "There is no related enetity." }, { "input": "At 18 months, lung tumors were found to be enhanced concentration dependently ( up to threefold beyond sham exposure ), irrespective of whether MS inhalation had been performed for the complete study duration or was interrupted after 5 or 10 months and followed by postinhalation periods.", "output": "There is no related enetity." }, { "input": "Morphometric analysis revealed an increase in the extent of emphysematous changes after 5 months of MS inhalation, which did not significantly change over the following 13 months of study duration, irrespective of whether MS exposure was continued or not.", "output": "There is no related enetity." }, { "input": "These changes were found to be accompanied by a complex pattern of transient and sustained pulmonary inflammatory changes that may contribute to the observed pathogeneses.", "output": "There is no related enetity." }, { "input": "Data from this study suggest that the A / J mouse model holds considerable promise as a relevant model for investigating smoking - related emphysema and adenocarcinoma development.", "output": "There is no related enetity." }, { "input": "Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens.", "output": "There is no related enetity." }, { "input": "Fibroblast activation protein ( FAP ) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases.", "output": "serine." }, { "input": "As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies.", "output": "There is no related enetity." }, { "input": "Using a competitive inhibition strategy, we used phage display techniques to identify 53 single - chain variable fragments ( scFvs ) after three rounds of panning against FAP.", "output": "There is no related enetity." }, { "input": "These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry.", "output": "There is no related enetity." }, { "input": "Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35 % of FAP cleavage of the fluorescent substrate Ala - Pro - 7 - amido - 4 - trifluoromethylcoumarin compared with nonfunctional scFv control.", "output": "Ala - Pro - 7 - amido - 4 - trifluoromethylcoumarin." }, { "input": "Furthermore, a mutant E3 scFv was identified by yeast affinity maturation.", "output": "There is no related enetity." }, { "input": "It had higher affinity ( 4 - fold ) and enhanced inhibitory effect on FAP enzyme activity ( 3 - fold ) than E3.", "output": "There is no related enetity." }, { "input": "The application of both inhibitory anti - FAP scFvs significantly affected the formation of 3 - dimensional FAP - positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41. 18 % ( negative antibody control ) to 34. 06 % ( E3 ) and 36. 15 % ( mutant E3 ), respectively.", "output": "There is no related enetity." }, { "input": "Thus, we have identified and affinity - maturated the first scFv antibody capable of inhibiting FAP function.", "output": "There is no related enetity." }, { "input": "This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.", "output": "There is no related enetity." }, { "input": "The velvet complex governs mycotoxin production and virulence of Fusarium oxysporum on plant and mammalian hosts.", "output": "There is no related enetity." }, { "input": "Fungal pathogens provoke devastating losses in agricultural production, contaminate food with mycotoxins and give rise to life - threatening infections in humans.", "output": "There is no related enetity." }, { "input": "The soil - borne ascomycete Fusarium oxysporum attacks over 100 different crops and can cause systemic fusariosis in immunocompromised individuals.", "output": "There is no related enetity." }, { "input": "Here we functionally characterized VeA, VelB, VelC and LaeA, four components of the velvet protein complex which regulates fungal development and secondary metabolism.", "output": "There is no related enetity." }, { "input": "Deletion of veA, velB and to a minor extent velC caused a derepression of conidiation as well as alterations in the shape and size of microconidia.", "output": "There is no related enetity." }, { "input": "VeA and LaeA were required for full virulence of F. oxysporum on tomato plants and on immunodepressed mice.", "output": "There is no related enetity." }, { "input": "A critical contribution of velvet consists in promoting chromatin accessibility and expression of the biosynthetic gene cluster for beauvericin, a depsipeptide mycotoxin that functions as a virulence determinant.", "output": "beauvericin, depsipeptide." }, { "input": "These results reveal a conserved role of the velvet complex during fungal infection on plants and mammals.", "output": "There is no related enetity." }, { "input": "Chemical constituents of Arisaema franchetianum tubers.", "output": "There is no related enetity." }, { "input": "A novel pyrrolidine alkaloid, ( 2R *, 3S *, 5S * ) - N, 2 - dimethyl - 3 - hydroxy - 5 - ( 10 - phenyldecyl ) pyrrolidine ( 1 ), and 17 known compounds were isolated from Arisaema franchetianum Engl.", "output": "pyrrolidine alkaloid, ( 2R * , 3S * , 5S * ) - N , 2 - dimethyl - 3 - hydroxy - 5 - ( 10 - phenyldecyl ) pyrrolidine." }, { "input": "( Araceae ) tubers.", "output": "There is no related enetity." }, { "input": "The 17 compounds were bergenin ( 2 ), emodin ( 3 ), caffeic acid ( 4 ), nobiletin ( 5 ), 3 - O - beta - d - galactopyranosyl - hederagenin 28 - O - beta - d - xylopyranosyl ( 1 --> 6 ) - beta - d - galactopyranosyl ester ( 6 ), coniferin ( 7 ), qingyangshengenin ( 8 ), methylconiferin ( 9 ), syringaresinol 4 ' - O - beta - d - glucopyranoside ( 10 ), gagaminine ( 11 ), perlolyrine ( 12 ), ( S ) - 1 - ( 1 ' - hydroxyethyl ) - beta - carboline ( 13 ), 1 - ( beta - carboline - 1 - yl ) - 3, 4, 5 - trihydroxy - 1 - pentanone ( 14 ), 1 - methoxycarbonyl - beta - carboline ( 15 ), indolo [ 2, 3 - alpha ] carbazole ( 16 ), 4 - hydroxycinnamic acid methyl ester ( 17 ), and methyl 4 - [ 2 - hydroxy - 2 - ( 4 - hydroxy - 3 - methoxyphenyl ) - 1 - ( hydroxymethyl ) ethyl ] ferulate ( 18 ).", "output": "bergenin, emodin, caffeic acid, nobiletin, 3 - O - beta - d - galactopyranosyl - hederagenin 28 - O - beta - d - xylopyranosyl ( 1 --> 6 ) - beta - d - galactopyranosyl ester, coniferin, qingyangshengenin, methylconiferin, syringaresinol 4 ' - O - beta - d - glucopyranoside, gagaminine, perlolyrine, ( S ) - 1 - ( 1 ' - hydroxyethyl ) - beta - carboline, 1 - ( beta - carboline - 1 - yl ) - 3 , 4 , 5 - trihydroxy - 1 - pentanone, 1 - methoxycarbonyl - beta - carboline, indolo [ 2 , 3 - alpha ] carbazole, 4 - hydroxycinnamic acid methyl ester, methyl 4 - [ 2 - hydroxy - 2 - ( 4 - hydroxy - 3 - methoxyphenyl ) - 1 - ( hydroxymethyl ) ethyl ] ferulate." }, { "input": "The inhibitory activities of compound 1 and its N - methyl derivative ( 1a ) against porcine respiratory and reproductive syndrome virus ( PRRSV ), human leukemic K562 cells, and human breast cancer MCF - 7 cells were evaluated.", "output": "N - methyl." }, { "input": "Compounds 1 [ 50 % inhibited concentration ( IC ( 50 ) ) = 12. 5 +/- 0. 6 mu M ] and 1a ( IC ( 50 ) = 15. 7 +/- 0. 9 mu M ) were cytotoxic against K562 cells.", "output": "There is no related enetity." }, { "input": "Compound 1a also had a weak effect on PRRSV with an IC ( 50 ) value of 31. 9 +/- 6. 0 mu M [ selectivity index ( SI ) = 18. 7 ].", "output": "There is no related enetity." }, { "input": "Ameliorative effect of Drynaria quercifolia ( L. ) J.", "output": "There is no related enetity." }, { "input": "Sm., an ethnomedicinal plant, in arthritic animals.", "output": "There is no related enetity." }, { "input": "Drynaria quercifolia ( L. ) J.", "output": "There is no related enetity." }, { "input": "Sm., is an ethnomedicinal plant used widely in Tamil Nadu to treat arthritis.", "output": "There is no related enetity." }, { "input": "The present study was aimed to evaluate the traditional claim of D. quercifolia rhizome water extract in adjuvant induced arthritic animals.", "output": "There is no related enetity." }, { "input": "Anti - arthritic effect was studied by assessing the levels of lysosomal enzymes, protein bound carbohydrates, urinary degradative collagen and serum cytokines on control and adjuvant induced arthritis.", "output": "carbohydrates." }, { "input": "The paw swelling and body weight were also analyzed.", "output": "There is no related enetity." }, { "input": "The levels of ROS and lysosomal enzymes in neutrophils of control and adjuvant induced animals were also estimated.", "output": "There is no related enetity." }, { "input": "D. quercifolia rhizome water extract at doses of 100 and 200mg / kg reduced the paw thickness and elevated the mean body weight of arthritic rats.", "output": "There is no related enetity." }, { "input": "The treatment with extract showed a significant reduction in the levels of plasma and liver lysosomal enzymes as well as protein bound carbohydrates and urinary degradative collagen levels.", "output": "There is no related enetity." }, { "input": "The treatment reduced the levels of ROS and lysosomal enzymes in neutrophils significantly.", "output": "There is no related enetity." }, { "input": "The significant reduction in the levels of serum pro - inflammatory cytokines ( TNF - alpha and IL - 1 beta ) and the increment in the levels of anti - inflammatory cytokine ( IL - 10 ) were also observed by the treatment.", "output": "There is no related enetity." }, { "input": "The present study supports the traditional claim of using D. quercifolia to treat rheumatism.", "output": "There is no related enetity." }, { "input": "On the origin of chirality in nanoplasmonic gyroid metamaterials.", "output": "There is no related enetity." }, { "input": "Metallic single gyroids, a new class of self - assembled nanoplasmonic metamaterials, are analyzed on the basis of a tri - helical metamaterial model.", "output": "There is no related enetity." }, { "input": "The physical mechanisms underlying the chiral optical behavior of the nanoplasmonic single gyroid are identified and it is shown that the optical chirality in this metallic structure is primarily determined by structural chirality and the connectivity of helices along the main cubic axes.", "output": "There is no related enetity." }, { "input": "Proximal femoral density distribution and structure in relation to age and hip fracture risk in women.", "output": "There is no related enetity." }, { "input": "Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture - related alterations in hip structure differ from those of aging.", "output": "There is no related enetity." }, { "input": "We employed computed tomography ( CT ) imaging to visualize the three - dimensional ( 3D ) spatial distribution of bone mineral density ( BMD ) in the hip in relation to age and incident hip fracture.", "output": "There is no related enetity." }, { "input": "We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years ( n = 349 ) and a group of women with ( n = 74 ) and without ( n = 148 ) incident hip fracture 4 to 7 years after their imaging session.", "output": "There is no related enetity." }, { "input": "Voxel - based morphometry was used to generate Student ' s t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture.", "output": "There is no related enetity." }, { "input": "Scaling factors derived from intersubject image registration were employed as measures of bone size.", "output": "There is no related enetity." }, { "input": "BMD comparisons of young, middle - aged, and older American women showed preservation of load - bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions.", "output": "There is no related enetity." }, { "input": "In contrast, comparisons of older Icelandic fracture women with age - matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load - bearing inferior cortex.", "output": "There is no related enetity." }, { "input": "Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls.", "output": "There is no related enetity." }, { "input": "The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age - related loss.", "output": "There is no related enetity." }, { "input": "The fracture - related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual - energy X - ray absorptiometry ( DXA ) and other clinical images.", "output": "There is no related enetity." }, { "input": "Microfluidic investigation of BDNF - enhanced neural stem cell chemotaxis in CXCL12 gradients.", "output": "There is no related enetity." }, { "input": "In vivo studies have suggested that gradients of CXCL12 ( aka stromal cell - derived factor 1 alpha ) may be critical for neural stem cell ( NSC ) migration during brain development and neural tissue regeneration.", "output": "There is no related enetity." }, { "input": "However, traditional in vitro chemotaxis tools are limited by unstable concentration gradients and the inability to decouple cell migration directionality and speed.", "output": "There is no related enetity." }, { "input": "These limitations have restricted the reproducible and quantitative analysis of neuronal migration, which is required for mechanism - based studies.", "output": "There is no related enetity." }, { "input": "Using a microfluidic gradient generator, nestin and Sox - 2 positive human embryonic NSC chemotaxis is quantified within a linear and stable CXCL12 gradient.", "output": "There is no related enetity." }, { "input": "While untreated NSCs are not able to chemotax within CXCL12 gradients, pre - treatment of the cells with brain - derived neurotrophic factor ( BDNF ) results in significant chemotactic, directional migration.", "output": "There is no related enetity." }, { "input": "BDNF pre - treatment has no effect on cell migration speed, which averages about 1 mu m min ( - 1 ).", "output": "There is no related enetity." }, { "input": "Quantitative analysis determines that CXCL12 concentrations above 9. 0 nM are above the minimum activation threshold, while concentrations below 14. 7 nM are below the saturation threshold.", "output": "There is no related enetity." }, { "input": "Interestingly, although inhibitor studies with AMD 3100 revealed that CXCL12 chemotaxis requires receptor CXCR4 activation, BDNF pre - treatment is found to have no profound effects on the mRNA levels or surface presentation of CXCR4 or the putative CXCR7 scavenger receptor.", "output": "There is no related enetity." }, { "input": "The microfluidic study of NSC migration within stable chemokine concentration profiles provides quantitative analysis as well as new insight into the migratory mechanism underlying BDNF - induced chemotaxis towards CXCL12.", "output": "There is no related enetity." }, { "input": "Modeling toxicity of binary metal mixtures ( Cu ( 2 + ) - Ag ( + ), Cu ( 2 + ) - Zn ( 2 + ) ) to lettuce, Lactuca sativa, with the biotic ligand model.", "output": "Cu ( 2 + ) - Ag ( + ), Cu ( 2 + ) - Zn ( 2 + )." }, { "input": "The biotic ligand model ( BLM ) was applied to predict metal toxicity to lettuce, Lactuca sativa.", "output": "There is no related enetity." }, { "input": "Cu ( 2 + ) had the lowest median effective activity ( EA50 ( M ) ), compared with Ag ( + ) and Zn ( 2 + ) ( EA50 ( Cu ) = 2. 60 x 10 ( - 8 ) M, EA50 ( Ag ) = 1. 34 x 10 ( - 7 ) M, EA50 ( Zn ) = 1. 06 x 10 ( - 4 ) M ).", "output": "Cu ( 2 + ), Ag ( + ), Zn ( 2 + ), Cu, Ag, Zn." }, { "input": "At the 50 % response level, the fraction of the total number of biotic ligands occupied by ions ( f50 ( M ) ) was lowest for Ag ( + ) among the metals ( f50 ( Ag ) = 0. 22, f50 ( Cu ) = 0. 36, f50 ( Zn ) = 0. 42 ).", "output": "Ag ( + ), Ag, Cu, Zn." }, { "input": "Cu ( 2 + ) had the highest affinity for biotic ligands compared with Ag ( + ) and Zn ( 2 + ), as shown by stability constants of the cation - biotic ligand binding, expressed as log K ( MBL ) ( log K ( CuBL ) = 7. 40, log K ( AgBL ) = 6. 39, log K ( ZnBL ) = 4. 00 ).", "output": "Cu ( 2 + ), Ag ( + ), Zn ( 2 + ), CuBL, AgBL, ZnBL." }, { "input": "Furthermore, the BLM was combined with the toxic equivalency factor approach in predicting toxicity of mixtures of Cu ( 2 + ) - Zn ( 2 + ) and Cu ( 2 + ) - Ag ( + ).", "output": "Cu ( 2 + ) - Zn ( 2 + ), Cu ( 2 + ) - Ag ( + )." }, { "input": "The fraction of biotic ligands occupied by ions was used to determine the relative toxic potency of metals and the toxic equivalency quotient ( TEQ ) of mixtures.", "output": "There is no related enetity." }, { "input": "This approach allowed for including interactions in estimating mixture toxicity and showed good predictive power ( r ( 2 ) = 0. 64 - 0. 84 ).", "output": "There is no related enetity." }, { "input": "The TEQ at the 50 % response level ( TEQ50, Cu ( 2 + ) equivalents ) for Cu ( 2 + ) - Zn ( 2 + ) mixtures was significantly lower than the value for Cu ( 2 + ) - Ag ( + ) mixtures.", "output": "Cu ( 2 + ), Cu ( 2 + ) - Zn ( 2 + ), Cu ( 2 + ) - Ag ( + )." }, { "input": "Joint toxicity depended on both TEQ and specific composition of the mixture.", "output": "There is no related enetity." }, { "input": "The present study supports the use of the accumulation of metal ions at the biotic ligands as a predictor of toxicity of single metals and mixtures.", "output": "There is no related enetity." }, { "input": "Enantioselective toxicity and bioaccumulation of fipronil in fathead minnows ( Pimephales promelas ) following water and sediment exposures.", "output": "fipronil." }, { "input": "Fipronil is a widely used, broad - spectrum pesticide that is applied as an equal mixture of two enantiomers.", "output": "Fipronil." }, { "input": "As regulations on older pesticides become more stringent, production and application of fipronil is expected to grow, leading to increased inputs into aquatic environments and complex exposures to biota.", "output": "fipronil." }, { "input": "To better understand the potential exposures introduced by fipronil contamination, we conducted subchronic toxicity tests with larval fathead minnows ( Pimephales promelas ) and waterborne fipronil and its enantiomers and exposed juvenile fathead minnows to fipronil - spiked sediment.", "output": "fipronil, fipronil, fipronil." }, { "input": "Enantioselective toxicity was observed in fish after the 7 - d subchronic exposure, with increased toxicity of the racemate and ( + ) enantiomer observed compared with the ( - ) enantiomer.", "output": "There is no related enetity." }, { "input": "Curiously, toxicities of the racemate and ( + ) enantiomer were not significantly different, even though the racemate contains 50 % of the ( + ) enantiomer and 50 % of the less toxic ( - ) enantiomer.", "output": "There is no related enetity." }, { "input": "During the sediment exposure, racemic fipronil in sediment was transformed primarily to fipronil sulfide, while exposed fish rapidly accumulated fipronil and / or fipronil sulfide and transformed the majority to fipronil sulfone.", "output": "fipronil, fipronil sulfide, fipronil, fipronil sulfide, fipronil sulfone." }, { "input": "Using the results of the sediment - exposure experiment, the authors explored a mechanism that may contribute to the interesting trends in enantioselective toxicity observed during the waterborne exposures.", "output": "There is no related enetity." }, { "input": "In tandem, the aquatic toxicity experiment and the spiked sediment exposure demonstrate the potentially complex behavior of fipronil in sediment and fish.", "output": "fipronil." }, { "input": "Large - scale production of edge - selectively functionalized graphene nanoplatelets via ball milling and their use as metal - free electrocatalysts for oxygen reduction reaction.", "output": "graphene, oxygen." }, { "input": "Edge - selectively functionalized graphene nanoplatelets ( EFGnPs ) with different functional groups were efficiently prepared simply by dry ball milling graphite in the presence of hydrogen, carbon dioxide, sulfur trioxide, or carbon dioxide / sulfur trioxide mixture.", "output": "graphene, graphite, hydrogen, carbon dioxide, sulfur trioxide, carbon dioxide, sulfur trioxide." }, { "input": "Upon exposure to air moisture, the resultant hydrogen - ( HGnP ), carboxylic acid - ( CGnP ), sulfonic acid - ( SGnP ), and carboxylic acid / sulfonic acid - ( CSGnP ) functionalized GnPs readily dispersed into various polar solvents, including neutral water.", "output": "hydrogen, carboxylic acid, sulfonic acid, carboxylic acid, sulfonic acid." }, { "input": "The resultant EFGnPs were then used as electrocatalysts for oxygen reduction reaction ( ORR ) in an alkaline electrolyte.", "output": "oxygen." }, { "input": "It was found that the edge polar nature of the newly prepared EFGnPs without heteroatom doping into their basal plane played an important role in regulating the ORR efficiency with the electrocatalytic activity in the order of SGnP > CSGnP > CGnP > HGnP > pristine graphite.", "output": "graphite." }, { "input": "More importantly, the sulfur - containing SGnP and CSGnP were found to have a superior ORR performance to commercially available platinum - based electrocatalyst.", "output": "sulfur, platinum." }, { "input": "The conjoint influence of home enriched environment and lead exposure on children ' s cognition and behaviour in a Mexican lead smelter community.", "output": "There is no related enetity." }, { "input": "A range of studies has been conducted on the detrimental effects of lead in mining and smelting communities.", "output": "There is no related enetity." }, { "input": "The neurocognitive and behavioural health effects of lead on children are well known.", "output": "There is no related enetity." }, { "input": "This research characterized the conjoint influence of lead exposure and home enriched environment on neurocognitive function and behaviour for first - grade children living in a Mexican lead smelter community.", "output": "There is no related enetity." }, { "input": "Structural equation models were used for this analysis with latent outcome variables, Cognition and Behaviour, constructed based on a battery of assessments administered to the first - grade children, their parents, and teachers.", "output": "There is no related enetity." }, { "input": "Structural equation modelling was used to describe complex relationships of exposure and health outcomes in a manner that permitted partition of both direct and indirect effects of the factors being measured.", "output": "There is no related enetity." }, { "input": "Home Environment ( a latent variable constructed from information on mother ' s education and support of school work and extracurricular activities ), and child blood lead concentration each had a main significant effect on cognition and behaviour.", "output": "There is no related enetity." }, { "input": "However, there were no statistically significant moderation relationships between lead and Home Environment on these latent outcomes.", "output": "There is no related enetity." }, { "input": "Home Environment had a significant indirect mediation effect between lead and both Cognition and Behaviour ( p - value < 0. 001 ).", "output": "There is no related enetity." }, { "input": "The mediation model had a good fit with Root Mean Square Error of Approximation < 0. 0001 and a Weighted Root Mean Square Residual of 0. 895.", "output": "There is no related enetity." }, { "input": "These results were highly significant and suggest that Home Environment has a moderate mediation effect with respect to lead effects on Behaviour ( beta = 0. 305 ) and a lower mediation effect on Cognition ( beta = 0. 184 ).", "output": "There is no related enetity." }, { "input": "The extent of home enrichment in this study was most highly related to the mother ' s support of schoolwork and slightly less by the mother ' s support of extracurricular activities or mother ' s education.", "output": "There is no related enetity." }, { "input": "Further research may be able to develop approaches to support families to make changes within their home and child rearing practices, or advocate for different approaches to support their child ' s behaviour to reduce the impact of lead exposure on children ' s cognitive and behavioural outcomes.", "output": "There is no related enetity." }, { "input": "Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision - cut liver slices.", "output": "There is no related enetity." }, { "input": "The exact mechanism of chilling injury ( by a decrease of temperature to sub - physiological values ), especially in the intact organ, is yet unknown.", "output": "There is no related enetity." }, { "input": "Precision - cut liver slices ( PCLS ), which closely resemble the organ from which they are derived, are an ideal in vitro model to study the mechanism of chilling injury in the intact organ.", "output": "There is no related enetity." }, { "input": "In the present study we were able to separate chilling injury from other damaging events such as cryoprotectant toxicity and ice - crystal injury and performed micro - array analysis of regulated genes.", "output": "There is no related enetity." }, { "input": "Pathway analysis revealed that different stress responses, lipid / fatty acid and cholesterol biosynthesis and metabolism were affected by chilling.", "output": "fatty acid, cholesterol." }, { "input": "This indicates that the cell - membrane might be the primary site and sensor for chilling, which may initiate and amplify downstream intracellular signaling events.", "output": "There is no related enetity." }, { "input": "Most importantly, we were able to identify gene expression responses from stellate cells and Kupffer cells suggesting the involvement of all liver cell types in the injury.", "output": "There is no related enetity." }, { "input": "In conclusion, a broad spectrum of previously unknown gene expression changes induced by chilling was identified in the tissue.", "output": "There is no related enetity." }, { "input": "This is the first report of a systematic investigation on the mechanism of chilling injury in integrated tissue by micro - array analysis under conditions in which other sources of injury are minimal.", "output": "There is no related enetity." }, { "input": "Syntheses and in vitro evaluations of uncharged reactivators for human acetylcholinesterase inhibited by organophosphorus nerve agents.", "output": "organophosphorus." }, { "input": "Organophosphorus nerve agents ( OPNAs ) are highly toxic compounds that represent a threat to both military and civilian populations.", "output": "Organophosphorus." }, { "input": "They cause an irreversible inhibition of acetylcholinesterase ( AChE ), by the formation of a covalent P - O bond with the catalytic serine.", "output": "P - O, serine." }, { "input": "Among the present treatment of nerve agents poisoning, pyridinium and bis - pyridinium aldoximes are used to reactivate this inhibited enzyme but these compounds do not readily cross the blood brain barrier ( BBB ) due to their permanent cationic charge and thus cannot efficiently reactivate cholinesterases in the central nervous system ( CNS ).", "output": "pyridinium and bis - pyridinium aldoximes." }, { "input": "In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun - inhibited human acetylcholinesterase ( hAChE ) has been evaluated.", "output": "oximes, tabun." }, { "input": "The dissociation constant KD of inhibited enzyme - oxime complex, the reactivity rate constant kr and the second order reactivation rate constant kr2 have been determined and have been compared to reference oximes HI - 6, Obidoxime and 2 - Pralidoxime ( 2 - PAM ).", "output": "oxime, oximes, HI - 6, Obidoxime, 2 - Pralidoxime, 2 - PAM." }, { "input": "Regarding the reactivation of VX - inhibited hAChE, all compounds show a better reactivation potency than those of 2 - PAM, nevertheless they are less efficient than obidoxime and HI - 6.", "output": "2 - PAM, obidoxime, HI - 6." }, { "input": "Moreover, one of seven described compounds presents an ability to reactivate tabun - inhibited hAChE equivalent to those of 2 - PAM.", "output": "2 - PAM." }, { "input": "Theoretical investigation of a novel high density cage compound 4, 8, 11, 14, 15 - pentanitro - 2, 6, 9, 13 - tetraoxa - 4, 8, 11, 14, 15 - pentaazaheptacyclo [ 5. 5. 1. 1 ( 3, 11 ). 1 ( 5, 9 ) ] pentadecane.", "output": "4 , 8 , 11 , 14 , 15 - pentanitro - 2 , 6 , 9 , 13 - tetraoxa - 4 , 8 , 11 , 14 , 15 - pentaazaheptacyclo [ 5 . 5 . 1 . 1 ( 3 , 11 ) . 1 ( 5 , 9 ) ] pentadecane." }, { "input": "A novel polynitro cage compound 4, 8, 11, 14, 15 - pentanitro - 2, 6, 9, 13 - tetraoxa - 4, 8, 11, 14, 15 - pentaazaheptacyclo [ 5. 5. 1. 1 ( 3, 11 ). 1 ( 5, 9 ) ] pentadecane ( PNTOPAHP ) has been designed and investigated at the DFT - B3LYP / 6 - 31 ( d ) level.", "output": "4 , 8 , 11 , 14 , 15 - pentanitro - 2 , 6 , 9 , 13 - tetraoxa - 4 , 8 , 11 , 14 , 15 - pentaazaheptacyclo [ 5 . 5 . 1 . 1 ( 3 , 11 ) . 1 ( 5 , 9 ) ] pentadecane, PNTOPAHP." }, { "input": "Properties, such as electronic structure, IR spectrum, heat of formation, thermodynamic properties and crystal structure have been predicted.", "output": "There is no related enetity." }, { "input": "This compound is most likely to crystallize in C2 / c space group, and the corresponding cell parameters are Z = 8, a = 29. 78 A, b = 6. 42 A, c = 32. 69 A, alpha = 90. 00 degrees, beta = 151. 05 degrees, gamma = 90. 00 degrees and rho = 1. 94 g / cm ( 3 ).", "output": "There is no related enetity." }, { "input": "In addition, the detonation velocity and pressure have also been calculated by the empirical Kamlet - Jacobs equation.", "output": "There is no related enetity." }, { "input": "As a result, the detonation velocity and pressure of this compound are 9. 82 km / s, 44. 67 GPa, respectively, a little higher than those of 4, 10 - dinitro - 2, 6, 8, 12 - tetraoxa - 4, 10 - diazaisowurtzitane ( TEX, 9. 28 km / s, 40. 72 GPa ).", "output": "4 , 10 - dinitro - 2 , 6 , 8 , 12 - tetraoxa - 4 , 10 - diazaisowurtzitane, TEX." }, { "input": "This compound has a comparable chemical stability to TEX, based on the N - NO ( 2 ) trigger bond length analysis.", "output": "TEX, N - NO ( 2 )." }, { "input": "The bond dissociation energy ranges from 153. 09 kJ mol ( - 1 ) to 186. 04 kJ mol ( - 1 ), which indicates that this compound meets the thermal stability requirement as an exploitable HEDM.", "output": "There is no related enetity." }, { "input": "Benchmarks for 0 - 0 transitions of aromatic organic molecules: DFT / B3LYP, ADC ( 2 ), CC2, SOS - CC2 and SCS - CC2 compared to high - resolution gas - phase data.", "output": "There is no related enetity." }, { "input": "In the present study a benchmark set of medium - sized and large aromatic organic molecules with 10 - 78 atoms is presented.", "output": "There is no related enetity." }, { "input": "For this test set 0 - 0 transition energies measured in supersonic jets are compared to those calculated with DFT and the B3LYP functional, ADC ( 2 ), CC2 and the spin - scaled CC2 variants SOS - CC2 and SCS - CC2.", "output": "There is no related enetity." }, { "input": "Geometries of the ground and excited states have been optimized with these methods in polarized triple zeta basis sets.", "output": "There is no related enetity." }, { "input": "Zero - point vibrational corrections have been calculated with the same methods and basis sets.", "output": "There is no related enetity." }, { "input": "In addition the energies have been corrected by single point calculations with a triple zeta basis augmented with diffuse functions, aug - cc - pVTZ.", "output": "There is no related enetity." }, { "input": "The deviations of the theoretical results from experimental electronic origins, which have all been measured in the gas phase with high - resolution techniques, were evaluated.", "output": "There is no related enetity." }, { "input": "The accuracy of SOS - CC2 is comparable to that of unscaled CC2, whereas ADC ( 2 ) has slightly larger errors.", "output": "There is no related enetity." }, { "input": "The lowest errors were found for SCS - CC2.", "output": "There is no related enetity." }, { "input": "All correlated wave function methods provide significantly better results than DFT with the B3LYP functional.", "output": "There is no related enetity." }, { "input": "The effects of the energy corrections from the augmented basis set and the method - consistent calculation of the zero - point vibrational corrections are small.", "output": "There is no related enetity." }, { "input": "With this benchmark set reliable reference data for 0 - 0 transition energies for larger organic chromophores are available that can be used to benchmark the accuracy of other quantum chemical methods such as new DFT functionals or semi - empirical methods for excitation energies and structures and thereby augments available benchmark sets augments present benchmark sets which include mainly smaller molecules.", "output": "There is no related enetity." }, { "input": "Emergency do not consume / do not use concentrations for ferric chloride in drinking water.", "output": "ferric chloride." }, { "input": "The U. S.", "output": "There is no related enetity." }, { "input": "Congress [ PL 107 - 188 ] amended the Safe Drinking Water Act and required each community water system serving more than 3, 000 people to conduct vulnerability assessments.", "output": "There is no related enetity." }, { "input": "These assessments address potential circumstances that could compromise the safety and reliability of municipal water.", "output": "There is no related enetity." }, { "input": "Ferric chloride is used in coagulation and flocculation, and it is used to treat raw water with high viral loads, elevated dissolved solids or high bromide.", "output": "Ferric chloride, bromide." }, { "input": "Iron is an essential nutrient, but elevated concentrations of FeCl3 are corrosive as a result of hydrolysis to HCl.", "output": "Iron, FeCl3, HCl." }, { "input": "Based on a no - observed - adverse effect level ( NOAEL ) of 0. 5 % FeCl3 * 6H2O administered in drinking water to male and female F344 rats for up to 2 years, a do not consume concentration of 200 mg FeCl3 / L can be derived.", "output": "FeCl3 * 6H2O, FeCl3." }, { "input": "Since instillation of 0. 3 M ( 48. 7 g / L ) FeCl3 in saline to rodent vagina failed to elicit damage, a topical do not use concentration of 2000 mg FeCl3 / L ( 600 mg Fe / L ) can be assigned.", "output": "FeCl3, FeCl3, Fe." }, { "input": "The only FeCl3 data available to quantify ocular toxicity involved a pH 1 solution in rabbit eyes, but HCl instillation ( pH 2. 5 ) to rabbit eyes found permanent corneal ulceration after 10 min.", "output": "FeCl3, HCl." }, { "input": "The pH of FeCl3 in water at the do not use limit ( 2. 4 - 2. 6 ) is near the pH ( 2. 0 ) considered corrosive by regulatory agencies.", "output": "FeCl3." }, { "input": "As direct eye contact with water at pH 4. 5 or below increases complaints of ocular discomfort, emergency response plans that address FeCl3 in drinking water must account for Fe levels and the pH of the affected water.", "output": "FeCl3, Fe." }, { "input": "Toxicity of cadmium and protective effect of bee honey, vitamins C and B complex.", "output": "cadmium, vitamins C and B." }, { "input": "The present work aimed to study the toxic effect of cadmium ( Cd ) on rabbits ' blood indices, as well as the therapeutic effect of the antioxidant agents, vitamins C and B complex and bee honey on Cd intoxicated rabbits.", "output": "cadmium, Cd, vitamins C and B, Cd." }, { "input": "Cadmium chloride ( CdCl2 ) was injected subcutaneously at a dose of 3 mg / kg of body weight.", "output": "Cadmium chloride, CdCl2." }, { "input": "The results showed a significant increase in serum glucose, triglycerides, cholesterol, total protein, albumin, globulin, urea and creatinine, compared to the control group.", "output": "glucose, triglycerides, cholesterol, urea, creatinine." }, { "input": "In addition, CdCl2 intoxication increased the levels of uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin.", "output": "CdCl2, uric acid, aspartate, alanine, bilirubin." }, { "input": "Concerning haematological parameters, the more obvious changes were an increase in mean corpuscular volume and a decrease in white blood cells count, platelets, lymphocytes, heamatocrit, haemoglobin and red blood cells count.", "output": "There is no related enetity." }, { "input": "Treatment of CdCl2 - intoxicated animals with vitamins C and B complex and bee honey showed a decrease in the harmful effects of Cd by restoring haematological and biochemical changes.", "output": "CdCl2, vitamins C and B, Cd." }, { "input": "Bee honey treatment was the most effective in providing recoveries in the altered blood parameters.", "output": "There is no related enetity." }, { "input": "Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds: genetic aspects of addiction with the selected drugs, amphetamine, tetrahydrocannabinol and opiates.", "output": "amphetamine, tetrahydrocannabinol." }, { "input": "The etiology of drug addiction, a central nervous system ( CNS ) disease, is not fully known.", "output": "There is no related enetity." }, { "input": "This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors.", "output": "There is no related enetity." }, { "input": "The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission.", "output": "There is no related enetity." }, { "input": "Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances.", "output": "ethanol." }, { "input": "Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction.", "output": "There is no related enetity." }, { "input": "A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene - coding DRD2 dopamine receptor.", "output": "There is no related enetity." }, { "input": "The latest results indicate the importance of brain - derived neurotrophic factor ( BDNF ) in the regulation of dopaminergic route.", "output": "There is no related enetity." }, { "input": "The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent.", "output": "There is no related enetity." }, { "input": "The examinations were performed with the Local Research Ethics Committee approval and patient ' s consent.", "output": "There is no related enetity." }, { "input": "The study group consisted of 100 patients ( 88 men and 12 women ) aged 18 - 52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision ( ICD - 10 ) requirements, medical examination and detailed questionnaire.", "output": "There is no related enetity." }, { "input": "Low cytotoxic elastic niosomes loaded with salmon calcitonin on human skin fibroblasts.", "output": "There is no related enetity." }, { "input": "A low cytotoxic elastic niosomal formulation loaded with salmon calcitonin was developed.", "output": "There is no related enetity." }, { "input": "The elastic niosomes were prepared from Tween 61 mixed with cholesterol at various concentrations of the edge activators ( sodium cholate ( NaC ) and sodium deoxycholate ( NaDC ); 0. 25, 0. 5, 2. 5, 5 and 10 % mole ) or ethanol ( 10 - 30 % v / v ).", "output": "Tween 61, cholesterol, sodium cholate, NaC, sodium deoxycholate, NaDC, ethanol." }, { "input": "The effects of the niosomal concentrations ( 5, 10 and 20 mM ) and phosphate buffer at pH 7. 0 ( 5, 10, 20 and 30 mM ) on the physical characteristics of niosomes were investigated.", "output": "phosphate." }, { "input": "The 5 mM elastic niosomes in 5 mM phosphate buffer containing calcitonin 0. 22 mg / mL gave the highest elasticity ( deformability index ( DI ) ) at 6. 79 +/- 2. 03 determined by the extrusion method.", "output": "phosphate." }, { "input": "The blank elastic niosomes comprised 2. 5 % mole NaDC, 5 % mole NaC or 20 % v / v ethanol showed the highest elasticity.", "output": "NaDC, NaC, ethanol." }, { "input": "The 5 % mole NaC elastic niosomes loaded with calcitonin gave the highest DI ( 21. 59 +/- 0. 91 ) and percentages of calcitonin entrapment efficiency ( 60. 11 +/- 4. 98 ).", "output": "NaC." }, { "input": "This study has demonstrated that this NaC elastic niosome did not only reduce the cytotoxicity of the loaded calcitonin but also gave superior cell viability to the ethanolic elastic niosome as well.", "output": "NaC." }, { "input": "Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature.", "output": "dexmedetomidine." }, { "input": "Prolonged infusion of dexmedetomidine, an alpha ( 2 ) - adrenoreceptor agonist anesthetic used in the intensive care unit, produces a withdrawal syndrome of sympathetic over - activity, characterized by tachycardia, hypertension and agitation, but there is no recommended standard treatment for this syndrome.", "output": "dexmedetomidine." }, { "input": "We describe two patients with a clinical diagnosis of acute dexmedetomidine withdrawal and its management with oral clonidine.", "output": "dexmedetomidine, clonidine." }, { "input": "We utilized the principle of managing acute drug withdrawal with longer acting medications.", "output": "There is no related enetity." }, { "input": "These two cases demonstrated the benefit of using oral, longer acting clonidine to manage acute withdrawal from shorter - acting, intravenous dexmedetomidine.", "output": "clonidine, dexmedetomidine." }, { "input": "Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and propofol in intensive care unit patients.", "output": "morphine, midazolam, fentanyl, propofol." }, { "input": "Therapeutic hypothermia ( TH ) may induce pharmacokinetic changes that may affect the level of sedation.", "output": "There is no related enetity." }, { "input": "We have compared the disposition of morphine, midazolam, fentanyl, and propofol in TH with normothermia in man.", "output": "morphine, midazolam, fentanyl, propofol." }, { "input": "Fourteen patients treated with TH following cardiac arrest ( 33 - 34 degrees C ) were compared with eight matched critically ill patients ( 36 - 38 degrees C ).", "output": "There is no related enetity." }, { "input": "Continuous infusions of morphine and midazolam were stopped and replaced with infusions of fentanyl and propofol to describe elimination and start of infusion pharmacokinetics, respectively.", "output": "morphine, midazolam, fentanyl, propofol." }, { "input": "Serial serum and urine samples were collected for 6 - 8 hours for validated quantification and subsequent pharmacokinetic analysis.", "output": "There is no related enetity." }, { "input": "During TH, morphine elimination half - life ( t ( 1 / 2 ) ) was significantly higher, while total clearance ( CL ( tot ) ) was significantly lower ( median [ semi - interquartile range ( s - iqr ) ] ): t ( 1 / 2 ), 266 ( 43 ) versus 168 ( 11 ) minutes, P < 0. 01; CL ( tot ), 1201 ( 283 ) versus 1687 ( 200 ) ml / min, P < 0. 01.", "output": "morphine." }, { "input": "No significant differences were seen for midazolam.", "output": "midazolam." }, { "input": "CL ( tot ) of fentanyl and propofol was significantly lower in hypothermic patients [ median ( s - iqr ) ]: fentanyl, 726 ( 230 ) versus 1331 ( 678 ) ml / min, P < 0. 05; propofol, 2046 ( 305 ) versus 2665 ( 223 ) ml / min, P < 0. 05.", "output": "fentanyl, propofol, fentanyl, propofol." }, { "input": "Compared with the matched, normothermic intensive care unit patients, t ( 1 / 2 ) of morphine was significantly higher during TH.", "output": "morphine." }, { "input": "CL ( tot ) was lower during TH for morphine, fentanyl, and propofol but not for midazolam.", "output": "morphine, fentanyl, propofol, midazolam." }, { "input": "Reducing the infusion rates of morphine, fentanyl, and propofol during TH is encouraged.", "output": "morphine, fentanyl, propofol." }, { "input": "STAAR: statistical analysis of aromatic rings.", "output": "There is no related enetity." }, { "input": "The statistical analysis of aromatic rings program allows for an automated search for anion - pi interactions between phenylalanine residues and carboxylic acid moieties of neighboring aspartic acid or glutamic acid residues in protein data bank ( PDB ) structures.", "output": "phenylalanine, carboxylic acid, aspartic acid, glutamic acid." }, { "input": "The program is written in C + + and is available both as a standalone code and through a web implementation that allows users to upload and analyze biomolecular structures in PDB format.", "output": "There is no related enetity." }, { "input": "The program outputs lists of Phe / Glu or Phe / Asp pairs involved in potential anion - pi interactions, together with geometrical ( distance and angle between the Phe ' s center of mass and Glu or Asp ' s center of charge ) and energetic ( quantum mechanical Kitaura - Morokuma interaction energy between the residues ) descriptions of each anion - pi interaction.", "output": "Phe, Glu, Phe, Asp, Phe, Glu, Asp." }, { "input": "Application of the program on the latest content of the PDB shows that anion - pi interactions are present in thousands of protein structures and can possess strong energies, as low as - 8. 72 kcal / mol.", "output": "There is no related enetity." }, { "input": "BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin - induced pulmonary fibrosis.", "output": "bleomycin." }, { "input": "Epigenetic alterations, such as histone acetylation, regulate the signaling outcomes and phenotypic responses of fibroblasts after growth factor stimulation.", "output": "There is no related enetity." }, { "input": "The bromodomain and extra - terminal domain - containing proteins ( Brd ) bind to acetylated histone residues, resulting in recruitment of components of the transcriptional machinery and subsequent gene transcription.", "output": "There is no related enetity." }, { "input": "Given the central importance of fibroblasts in tissue fibrosis, this study sought to determine the role of Brd proteins in human lung fibroblasts ( LFs ) after growth factor stimulation and in the murine bleomycin model of lung fibrosis.", "output": "bleomycin." }, { "input": "Using small interfering RNA against human Brd2 and Brd4 and pharmacologic Brd inhibitors, this study found that Brd2 and Brd4 are essential in mediating the phenotypic responses of LFs downstream of multiple growth factor pathways.", "output": "There is no related enetity." }, { "input": "Growth factor stimulation of LFs causes increased histone acetylation, association of Brd4 with growth factor - responsive genes, and enhanced transcription of these genes that could be attenuated with pharmacologic Brd inhibitors.", "output": "There is no related enetity." }, { "input": "Of note, lung fibrosis induced after intratracheal bleomycin challenge in mice could be prevented by pretreatment of animals with pharmacologic inhibitors of Brd proteins.", "output": "bleomycin." }, { "input": "This study is the first demonstration of a role for Brd2 and Brd4 proteins in mediating the responses of LFs after growth factor stimulation and in driving the induction of lung fibrosis in mice in response to bleomycin challenge.", "output": "bleomycin." }, { "input": "Hydrogen sulfide as an allosteric modulator of ATP - sensitive potassium channels in colonic inflammation.", "output": "Hydrogen sulfide, ATP, potassium." }, { "input": "The ATP - sensitive potassium channel ( K ( ATP ) ) in mouse colonic smooth muscle cell is a complex containing a pore - forming subunit ( Kir6. 1 ) and a sulfonylurea receptor subunit ( SUR2B ).", "output": "ATP, potassium, K, ATP, sulfonylurea." }, { "input": "These channels contribute to the cellular excitability of smooth muscle cells and hence regulate the motility patterns in the colon.", "output": "There is no related enetity." }, { "input": "Whole - cell voltage - clamp techniques were used to study the alterations in K ( ATP ) channels in smooth muscle cells in experimental colitis.", "output": "K, ATP." }, { "input": "Colonic inflammation was induced in BALB / C mice after intracolonic administration of trinitrobenzene sulfonic acid.", "output": "trinitrobenzene sulfonic acid." }, { "input": "K ( ATP ) currents were measured at a holding potential of - 60 mV in high K ( + ) external solution.", "output": "K, ATP, K ( + )." }, { "input": "The concentration response to levcromakalim ( LEVC ), a K ( ATP ) channel opener, was significantly shifted to the left in the inflamed smooth - muscle cells.", "output": "levcromakalim, LEVC, K, ATP." }, { "input": "Both the potency and maximal currents induced by LEVC were enhanced in inflammation.", "output": "LEVC." }, { "input": "The EC ( 50 ) values in control were 6259 nM ( n = 10 ) and 422 nM ( n = 8 ) in inflamed colon, and the maximal currents were 9. 9 +/- 0. 71 pA / pF ( 60 mu M ) in control and 39. 7 +/- 8. 8 pA / pF ( 3 mu M ) after inflammation.", "output": "There is no related enetity." }, { "input": "As was seen with LEVC, the potency and efficacy of sodium hydrogen sulfide ( NaHS ) ( 10 - 1000 mu M ) on K ( ATP ) currents were significantly greater in inflamed colon compared with controls.", "output": "LEVC, sodium hydrogen sulfide, NaHS, K, ATP." }, { "input": "In control cells, pretreatment with 100 micro M NaHS shifted the EC ( 50 ) for LEV - induced currents from 2838 ( n = 6 ) to 154 ( n = 8 ) nM.", "output": "NaHS." }, { "input": "Sulfhydration of sulfonylurea receptor 2B ( SUR2B ) was induced by NaHS and colonic inflammation.", "output": "sulfonylurea, NaHS." }, { "input": "These data suggest that sulfhydration of SUR2B induces allosteric modulation of K ( ATP ) currents in colonic inflammation.", "output": "K, ATP." }, { "input": "Stem cell lineage commitment by electrical fields and the potential application in drug discovery.", "output": "There is no related enetity." }, { "input": "Stem cells may be applied to improve the efficiency of drug discovery, but more effective protocols are first required to control the differentiation.", "output": "There is no related enetity." }, { "input": "Recent researches have revealed that physical stimulation is an important avenue for stem cell lineage commitment, such as electrical field stimulation.", "output": "There is no related enetity." }, { "input": "Here, we review literatures about stem cell differentiation by electrical field stimulation.", "output": "There is no related enetity." }, { "input": "Various forms of electrical fields with soluble induction factors have shown to produce a synergistic effect in order to enhance the osteogenic commitment.", "output": "There is no related enetity." }, { "input": "Moreover, electrical field stimulation alone shows marked effects of pre - commitment to cardiomyocyte and neuron.", "output": "There is no related enetity." }, { "input": "However, the related precise molecular regulatory mechanism is unclear.", "output": "There is no related enetity." }, { "input": "As cardiomyocyte and neuron are crucial factors in drug development process, electrical field stimulation may be proposed as an effect important for stem cell differentiation, exhibiting a potential application in drug discovery.", "output": "There is no related enetity." }, { "input": "In vivo DNA electrotransfer for immunotherapy of cancer and neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Electroporation is the process commonly referred to the transient increase in the permeability of cell membranes on submission to electric field pulses.", "output": "There is no related enetity." }, { "input": "Electroporation has become an increasingly extensive method to enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of DNA vaccines, mostly against cancer.", "output": "There is no related enetity." }, { "input": "In vivo gene electrotransfer is of special interest since it is the most efficient non - viral strategy for gene delivery and it is worthy of low manufacturing costs, ease of realization and favorable safety profile.", "output": "There is no related enetity." }, { "input": "No adverse findings observed in toxicology and biodistribution / integration studies have been warranted for the evaluation of this approach in humans.", "output": "There is no related enetity." }, { "input": "Therefore, gene delivery followed by electroporation is currently being investigated in several clinical trials.", "output": "There is no related enetity." }, { "input": "The positive outcomes of early studies suggest that the efficacy of gene delivery and immunogenicity has greatly improved by electroporation.", "output": "There is no related enetity." }, { "input": "This review briefly summarizes salient features and recent findings that have contributed to the rapid progress of electroimmunotherapy as well as an overview of advanced clinical studies in oncology.", "output": "There is no related enetity." }, { "input": "Translation of in vivo DNA electrovaccination for neurodegenerative diseases as well as future expectations are also discussed.", "output": "There is no related enetity." }, { "input": "Multivalent agents: a novel concept and preliminary practice in Anti - HIV drug discovery.", "output": "There is no related enetity." }, { "input": "The term multivalency ( polyvalency ) in the biological science is defined as the simultaneous binding of multiple ligands to one receptor ( or multiple receptors to one ligand ).", "output": "There is no related enetity." }, { "input": "The possibility of gaining potency and selectivity was significantly increased through the use of multivalent ligand as a homo - or hetero - dimer, thus multivalent ligands provided a more attractive strategy to design novel anti - HIV agents with therapeutic applications.", "output": "There is no related enetity." }, { "input": "Moreover, similar to phenomenon of multivalency, an alternative strategy is called the \" mixed sites inhibitor \", viz.", "output": "There is no related enetity." }, { "input": "a single molecule that possesses enough chemical space to maximize interactions with its complementary binding pocket, or to bind simultaneously in more than one regions in a target.", "output": "There is no related enetity." }, { "input": "Actually, the addition of a third heterocyclic nucleus to the parent compound resulted in \" mixed sites \" anti - HIV agents with broad spectrum of activities against the mutant HIV - 1 strains.", "output": "There is no related enetity." }, { "input": "Based on current representative examples, the present article provided a brief review on the rationale for the design of different classes of multivalency anti - HIV agents and also discussed the advantages over their monomeric counterparts, providing a novel paradigm to facilitate the development of anti - HIV / AIDS therapeutic agents in treatment of HIV infected community.", "output": "There is no related enetity." }, { "input": "Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride - intoxicated mice.", "output": "Rosmarinic acid, carbon tetrachloride." }, { "input": "The aim of this study was to investigate the therapeutic potential of rosmarinic acid ( RA ), a natural phenolic, in the treatment of acute liver toxicity.", "output": "rosmarinic acid." }, { "input": "RA at 10, 25 and 50mg / kg was administered by gavage once daily for 2 consecutive days, 6h after CCl ( 4 ) intoxication.", "output": "CCl ( 4 )." }, { "input": "CCl ( 4 ) intoxication caused hepatic necrosis and increased serum ALT activity.", "output": "CCl ( 4 )." }, { "input": "In the livers, oxidative / nitrosative stress was evidenced by increased 3 - nitrotyrosine ( 3 - NT ) and thiobarbituric acid reactive substances ( TBARS ) formation and a significant decrease in Cu / Zn superoxide dismutase ( SOD ) activity.", "output": "3 - nitrotyrosine, 3 - NT, thiobarbituric acid, Cu, Zn, superoxide." }, { "input": "CCl ( 4 ) administration triggered inflammatory response in mice livers by activating nuclear factor - kappaB ( NF - kappa B ), which coincided with the induction of tumor necrosis factor - alpha ( TNF - alpha ) and cyclooxygenase - 2 ( COX - 2 ).", "output": "CCl ( 4 )." }, { "input": "RA improved histological and serum markers of liver damage and significantly ameliorated oxidative / nitrosative stress and inflammatory response in liver tissue.", "output": "There is no related enetity." }, { "input": "Additionally, RA prevented transforming growth factor - beta1 ( TGF - beta 1 ) and alpha - smooth muscle actin ( alpha - SMA ) expression, suggesting suppression of profibrotic response.", "output": "There is no related enetity." }, { "input": "Furthermore, RA significantly inhibited the CCl ( 4 ) - induced apoptosis, which was evident from decreased cleavage of caspase - 3.", "output": "CCl ( 4 )." }, { "input": "The hepatoprotective activity of RA coincided with enhanced NF - E2 - related factor 2 ( Nrf2 ) and heme oxygenase - 1 ( HO - 1 ) expression.", "output": "There is no related enetity." }, { "input": "The results of this study indicates that RA possesses antioxidant, anti - inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.", "output": "There is no related enetity." }, { "input": "The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug - induced agranulocytosis.", "output": "There is no related enetity." }, { "input": "This study is aimed to explore the relationship between bone marrow characteristics and clinical prognosis of antithyroid drug ( ATD ) induced agranulocytosis.", "output": "There is no related enetity." }, { "input": "A retrospective study was conducted in the first affiliated hospital of the University of South China.", "output": "There is no related enetity." }, { "input": "A total of 33 hospitalized patients diagnosed with ATD - induced agranulocytosis were analyzed.", "output": "There is no related enetity." }, { "input": "The bone marrow characteristics were classified into two types.", "output": "There is no related enetity." }, { "input": "Type I was characterized by reduction or absence of granulocytic precursors and type II was recognized as hypercellular bone marrow with dysmaturity of granulocytic cells.", "output": "There is no related enetity." }, { "input": "Bone marrow of 20 cases ( 61 % ) were characterized with type I whereas 13 cases ( 39 % ) with type II.", "output": "There is no related enetity." }, { "input": "The median duration of neutrophil recovery and high - grade fever were 4. 7 +/- 1. 0 days and 3. 6 +/- 2. 5 days respectively for type II, compared to 8. 0 +/- 2. 8 days and 8. 6 +/- 3. 1 days for type I ( p < 0. 01 in both compared groups ).", "output": "There is no related enetity." }, { "input": "However, there was no significant difference between the two types in terms of age, median duration of drug administration before the diagnosis of agranulocytosis, the amount of neutrophil count on admission and the total administration dose of granulocyte - colony stimulating factor ( G - CSF ) before bone marrow examination.", "output": "There is no related enetity." }, { "input": "Two cases of type I died of complications from infection.", "output": "There is no related enetity." }, { "input": "This study showed that the bone marrow characteristics of ATD - induced agranulocytosis could be classifed into two types.", "output": "There is no related enetity." }, { "input": "Also, the clinical prognosis was closely related to the bone marrow features.", "output": "There is no related enetity." }, { "input": "Type I is the dominant type which is usually associated with worse clinical prognosis compared to type II.", "output": "There is no related enetity." }, { "input": "Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices.", "output": "There is no related enetity." }, { "input": "Charcot neuroarthropathy ( CN ), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus ( DM ) and peripheral neuropathy ( PN ).", "output": "There is no related enetity." }, { "input": "Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture.", "output": "There is no related enetity." }, { "input": "We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density ( BMD ) and geometric strength indices using volumetric quantitative computed tomography.", "output": "There is no related enetity." }, { "input": "Twenty individuals with DM + PN were compared to twenty age -, sex -, and race - matched individuals with DM + PN and acute CN.", "output": "There is no related enetity." }, { "input": "We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals.", "output": "There is no related enetity." }, { "input": "Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM + PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet.", "output": "There is no related enetity." }, { "input": "There was a non - significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM + PN and CN subjects despite the CN group ' s significantly lower BMD.", "output": "There is no related enetity." }, { "input": "Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively.", "output": "There is no related enetity." }, { "input": "In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i. e., a hypertrophic response to injury rather than increased fracture resistance.", "output": "There is no related enetity." }, { "input": "Future research using these techniques will aid further understanding of the inflammation - mediated bony changes associated with development and progression of CN and other diseases.", "output": "There is no related enetity." }, { "input": "Orexin - A suppresses postischemic glucose intolerance and neuronal damage through hypothalamic brain - derived neurotrophic factor.", "output": "glucose." }, { "input": "Orexin - A ( a glucose - sensing neuropeptide in the hypothalamus ) and brain - derived neurotrophic factor ( BDNF; a member of the neurotrophin family ) play roles in many physiologic functions, including regulation of glucose metabolism.", "output": "glucose, glucose." }, { "input": "We previously showed that the development of postischemic glucose intolerance is one of the triggers of ischemic neuronal damage.", "output": "glucose." }, { "input": "The aim of this study was to determine whether there was an interaction between orexin - A and BDNF functions in the hypothalamus after cerebral ischemic stress.", "output": "There is no related enetity." }, { "input": "Male ddY mice were subjected to 2 hours of middle cerebral artery occlusion ( MCAO ).", "output": "There is no related enetity." }, { "input": "Neuronal damage was estimated by histologic and behavioral analyses.", "output": "There is no related enetity." }, { "input": "Expression of protein levels was analyzed by Western blot.", "output": "There is no related enetity." }, { "input": "Small interfering RNA directed BDNF, orexin - A, and SB334867 [ N - ( 2 - methyl - 6 - benzoxazolyl ) - N ' - 1, 5 - naphthyridin - 4 - yl urea; a specific orexin - 1 receptor antagonist ] were administered directly into the hypothalamus.", "output": "SB334867, N - ( 2 - methyl - 6 - benzoxazolyl ) - N ' - 1 , 5 - naphthyridin - 4 - yl urea." }, { "input": "The level of hypothalamic orexin - A, detected by immunohistochemistry, was decreased on day 1 after MCAO.", "output": "There is no related enetity." }, { "input": "Intrahypothalamic administration of orexin - A ( 1 or 5 pmol / mouse ) significantly and dose - dependently suppressed the development of postischemic glucose intolerance on day 1 and development of neuronal damage on day 3.", "output": "glucose." }, { "input": "The MCAO - induced decrease in insulin receptor levels in the liver and skeletal muscle on day 1 was recovered to control levels by orexin - A, and this effect of orexin - A was reversed by the administration of SB334867 as well as by hypothalamic BDNF knockdown.", "output": "SB334867." }, { "input": "These results suggest that suppression of postischemic glucose intolerance by orexin - A assists in the prevention of cerebral ischemic neuronal damage.", "output": "glucose." }, { "input": "In addition, hypothalamic BDNF may play an important role in this effect of orexin - A.", "output": "There is no related enetity." }, { "input": "Role of 5 - hydroxytryptamine 1B ( 5 - HT1B ) receptors in the regulation of ethanol intake in rodents.", "output": "5 - hydroxytryptamine, ethanol." }, { "input": "Evidence indicates that the serotonergic system is important in mediating dependence on and craving for alcohol.", "output": "alcohol." }, { "input": "Among serotonin receptors, 5 - hydroxytryptamine 1B ( 5 - HT1B ) receptors have been associated with drug abuse including alcohol.", "output": "serotonin, 5 - hydroxytryptamine, alcohol." }, { "input": "In this review, the neurocircuitry involving 5 - HT1B receptors in central reward brain regions related to alcohol intake are discussed in detail.", "output": "alcohol." }, { "input": "Emphasis has been placed on the pharmacological manipulations of 5 - HT1B receptor - mediated alcohol intake.", "output": "alcohol." }, { "input": "Furthermore, 5 - HT1B auto - and hetero - receptors regulate alcohol intake through the regulatory mechanism involving release of 5 - HT, gamma - aminobutyric acid ( GABA ), dopamine, and glutamate is evaluated.", "output": "alcohol, 5 - HT, gamma - aminobutyric acid, GABA, dopamine, glutamate." }, { "input": "Thus, interactions between 5 - HT1B receptors and these neurotransmitter systems are suggested to modulate alcohol - drinking behavior.", "output": "alcohol." }, { "input": "This review on the role of 5 - HT1B receptors in neurotransmitter release and consequent alcohol intake provides important information about the potential therapeutic role of 5 - HT1B receptors for the treatment of alcohol dependence.", "output": "alcohol, alcohol." }, { "input": "In vivo and in vitro characterization of naltrindole - derived ligands at the kappa - opioid receptor.", "output": "naltrindole." }, { "input": "Accumulating evidence supports a role for kappa - opioid receptor antagonists in the treatment of mood disorders.", "output": "There is no related enetity." }, { "input": "Standard kappa - antagonists have an unusual pharmacodynamic action, with a single injection blocking receptor signaling for several weeks.", "output": "There is no related enetity." }, { "input": "Here, we have characterized the kappa - selective properties of two ligands, 5 ' - ( 2 - aminomethyl ) naltrindole ( 5 ' - AMN ) and N - ( ( Naltrindol - 5 - yl ) methyl ) pentanimidamide ( 5 ' - MABN ), to identify whether modifications of the naltrindole side chain produces short - acting kappa - antagonists.", "output": "5 ' - ( 2 - aminomethyl ) naltrindole, 5 ' - AMN, N - ( ( Naltrindol - 5 - yl ) methyl ) pentanimidamide, 5 ' - MABN, naltrindole." }, { "input": "Opioid receptor binding affinity and activity were assessed using [ ( 3 ) H ] - diprenorphine binding, guanosine - 5 ' - O - ( 3 - [ 35S ] - thio ) triphosphate ( [ ( 35 ) S ] - GTP gamma S ) binding and isolated guinea - pig ileum.", "output": "[ ( 3 ) H ] - diprenorphine, guanosine - 5 ' - O - ( 3 - [ 35S ] - thio ) triphosphate, [ ( 35 ) S ] - GTP gamma S." }, { "input": "Pharmacodynamic profiles of 5 ' - AMN and 5 ' - MABN ( 1 - 10 mg / kg ) were investigated using the tail - withdrawal assay and diuresis.", "output": "5 ' - AMN, 5 ' - MABN." }, { "input": "Efficacy was also determined in depression - and anxiety - related behavioral paradigms in CD - 1 mice.", "output": "There is no related enetity." }, { "input": "Both 5 ' - AMN and 5 ' - MABN had high affinity for kappa - receptors ( K ( i ) 1. 36 +/- 0. 98 and 0. 27 +/- 0. 08, respectively ) and were revealed as potent kappa - antagonists ( pA ( 2 ) 7. 43 and 8. 18, respectively ) and mu - receptor antagonists ( pA ( 2 ) 7. 62 and 7. 85, respectively ) in the ileum.", "output": "5 ' - AMN, 5 ' - MABN." }, { "input": "Contrary to our hypothesis, in vivo, 5 ' - AMN and 5 ' - MABN displayed long - lasting antagonist effects in mice, reducing the antinociceptive actions of U50, 488 ( 10 mg / kg ) at 28 and 21 days post - injection, respectively.", "output": "5 ' - AMN, 5 ' - MABN, U50 , 488." }, { "input": "Interestingly, while 5 ' - AMN and 5 ' - MABN were not kappa - selective, both compounds did show significant antidepressant - and anxiolytic - like effects at 7 - 14 days post - injection in mice.", "output": "5 ' - AMN, 5 ' - MABN." }, { "input": "EGR1 is critical for gastrin - dependent upregulation of anion exchanger 2 in gastric cancer cells.", "output": "There is no related enetity." }, { "input": "The essential anion exchanger ( AE ) involved in bicarbonate secretion is AE2 / SLC4A2, a membrane protein recognized to be relevant for the regulation of the intracellular pH in several cell types.", "output": "bicarbonate." }, { "input": "Here we report that gastrin, a major gastrointestinal hormone, upregulates the expression of AE2 mRNA and protein in a cholecystokinin B receptor dependent manner in gastric cancer cells.", "output": "There is no related enetity." }, { "input": "The upregulated species of AE2 mRNA originates from the classical upstream promoter of the AE2 gene ( here referred to as AE2a1 ) which provides the binding site for transcription factors early growth response 1 ( EGR1 ) and SP1.", "output": "There is no related enetity." }, { "input": "EGR1 upregulated the AE2 expression that can be competitively inhibited by SP1 in co - transfection experiments.", "output": "There is no related enetity." }, { "input": "This competitive inhibition was avoided in cells because the SP1 expression was time - staggered to EGR1 in response to gastrin.", "output": "There is no related enetity." }, { "input": "Overexpression or knockdown of EGR1 consistently increased or decreased the expression of AE2.", "output": "There is no related enetity." }, { "input": "Our data linked a novel signal pathway involved in gastrin - stimulated AE2 expression.", "output": "There is no related enetity." }, { "input": "Synthesis and evaluation of a series of 3, 4, 5 - trimethoxycinnamic acid derivatives as potential antinarcotic agents.", "output": "3 , 4 , 5 - trimethoxycinnamic acid." }, { "input": "A series of 3, 4, 5 - trimethoxycinnamic acid derivatives was prepared and evaluated for antinarcotic effects on morphine dependence in mice and binding affinities on serotonergic receptors.", "output": "3 , 4 , 5 - trimethoxycinnamic acid, morphine." }, { "input": "The key synthetic strategies involve generation of ketones 6 - 7, esters 9 - 12 through condensation reaction, and amides 13 - 19 via coupling reaction using 1 - hydroxybenzotriazole / ethyl ( dimethylaminopropryl ) carbodiimide system in high yield.", "output": "ketones, esters, amides, 1 - hydroxybenzotriazole, ethyl ( dimethylaminopropryl ) carbodiimide." }, { "input": "We found that the naloxone - induced morphine withdrawal syndrome was significantly suppressed by new synthetic 3, 4, 5 - trimethoxycinnamic acid derivatives ( 20 mg / kg / day ).", "output": "naloxone, morphine, 3 , 4 , 5 - trimethoxycinnamic acid." }, { "input": "Most of 3, 4, 5 - trimethoxycinnamic acid derivatives were found to have high affinity to 5 - HT ( 1A ) receptor.", "output": "3 , 4 , 5 - trimethoxycinnamic acid." }, { "input": "The naloxone - induced morphine withdrawal syndrome was attenuated by ( + ) 8 - OH - DPAT ( 0. 1 mg / kg / day, i. p. ), a 5 - HT ( 1A ) receptor agonist.", "output": "naloxone, morphine, ( + ) 8 - OH - DPAT." }, { "input": "In cortical neuronal cells, ( + ) 8 - OH - DPAT ( 1 mu M ) produced an elevation of the pERK 1 / 2 expression, and the elevated pERK levels were inhibited by WAY 100635, a 5 - HT ( 1A ) receptor - specific antagonist.", "output": "( + ) 8 - OH - DPAT, WAY 100635." }, { "input": "Interestingly, the pERK levels were increased by the 3, 4, 5 - trimethoxycinnamic acid derivatives and the derivatives - mediated changes in pERK levels were blocked by the WAY 100635.", "output": "3 , 4 , 5 - trimethoxycinnamic acid, WAY 100635." }, { "input": "These results suggested that new synthetic 3, 4, 5 - trimethoxycinnamic acid derivatives have a potential antinarcotic effect through acting as a 5 - HT ( 1A ) receptor agonist in mice.", "output": "3 , 4 , 5 - trimethoxycinnamic acid." }, { "input": "A novel mechanism for the promotion of quercetin glycoside absorption by megalo alpha - 1, 6 - glucosaccharide in the rat small intestine.", "output": "quercetin glycoside." }, { "input": "The presence of an alpha - 1, 6 - glucosaccharide enhances absorption of water - soluble quercetin glycosides, a mixture of quercetin - 3 - O - beta - d - glucoside ( Q3G, 31. 8 % ), mono ( 23. 3 % ), di ( 20. 3 % ) and more d - glucose adducts with alpha - 1, 4 - linkage to a d - glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats.", "output": "quercetin glycosides, quercetin - 3 - O - beta - d - glucoside, Q3G, d - glucose, d - glucose, Q3G." }, { "input": "We prepared alpha - 1, 6 - glucosaccharides with different degrees of polymerization ( DP ) enzymatically and separated them into a megalo - isomaltosaccharide - containing fraction ( M - IM, average DP = 11. 0 ) and an oligo - isomaltosaccharide - containing fraction ( O - IM, average DP = 3. 6 ).", "output": "There is no related enetity." }, { "input": "Luminal injection of either saccharide fraction promoted the absorption of total quercetin - derivatives from the small intestinal segment and this effect was greater for M - IM than O - IM addition.", "output": "saccharide, quercetin." }, { "input": "M - IM also increased Q3G, but not the quercetin aglycone, concentration in the water - phase of the luminal contents more strongly than O - IM.", "output": "Q3G, quercetin." }, { "input": "The enhancement of Q3G solubilization in the luminal contents may be responsible for the increases in the quercetin glucoside absorption promoted by alpha - 1, 6 - glucosaccharides, especially that by M - IM.", "output": "Q3G, quercetin glucoside." }, { "input": "These results suggest that the ingestion of alpha - 1, 6 - glucosaccharides promotes Q3G bioavailability.", "output": "Q3G." }, { "input": "alpha - Glucosidase inhibitor from Buthus martensi Karsch.", "output": "There is no related enetity." }, { "input": "A bioassay - guided fractionation of an ethanol extract of Buthus martensi Karsch led to the isolation of a potent alpha - glucosidase inhibitor ( compound S ).", "output": "ethanol." }, { "input": "The structure was elucidated as a novel beta - carboline glucoalkaloid, harmanyl beta - d - glucopyranoside, on the basis of spectral data, including ( 1 ) H NMR, ( 13 ) C NMR, ( 1 ) H - ( 1 ) H COSY, NOESY, and HMBC.", "output": "beta - carboline, glucoalkaloid, harmanyl beta - d - glucopyranoside, ( 1 ) H, ( 13 ) C, ( 1 ) H, ( 1 ) H." }, { "input": "Compound S showed potent inhibitory activity against alpha - glucosidase, with an IC ( 50 ) value of 24 mu M.", "output": "There is no related enetity." }, { "input": "A Lineweaver - Burk plot indicated that its inhibition of alpha - glucosidase was uncompetitive, with a Ki value of 16. 1 mu M.", "output": "There is no related enetity." }, { "input": "Thermal stability of yeast hydrolysate as a novel anti - obesity material.", "output": "There is no related enetity." }, { "input": "We examined the thermal stability of yeast hydrolysates before and after ultrafiltration ( UF ) in vitro, and the anti - obesity activity of yeast hydrolysates before and after heat treatment in vivo.", "output": "There is no related enetity." }, { "input": "Yeast hydrolysate after UF showed significantly higher thermal stability than before UF.", "output": "There is no related enetity." }, { "input": "Yeast hydrolysates before and after UF showed 3 and 4 thermal transition peaks in their thermograms, respectively, and the total thermal denaturation enthalpies of yeast hydrolysates before and after UF were 69. 5 and 36. 5 J / g, respectively.", "output": "There is no related enetity." }, { "input": "For the anti - obesity activity study, yeast hydrolysates before and after heating were administered ad libitum with water to 7 - week - old male SD rats.", "output": "There is no related enetity." }, { "input": "The administration of yeast hydrolysate ( YH - control; no heat treatment, YH - 1; heat treatment at 140 degrees C, and YH - 2; heat treatment at 160 degrees C ) significantly increased mRNA expression of cocaine - and amphetamine - regulated transcript ( CART ) compared with control rats ( saline administration ).", "output": "cocaine, amphetamine." }, { "input": "However, there was no significant difference between the heat - treated groups and YH - control and there was no significant difference in neuropeptide Y expression between the heat - treated groups and YH - control.", "output": "There is no related enetity." }, { "input": "These results suggest that yeast hydrolysate can be use an anti - obesity material after heat treatment.", "output": "There is no related enetity." }, { "input": "Lipid components prepared from a freshwater Clam ( Corbicula fluminea ) extract ameliorate hypercholesterolaemia in rats fed high - cholesterol diet.", "output": "There is no related enetity." }, { "input": "To explore the hypocholesterolaemic components in the fat fraction of freshwater clam extract ( FCE ), we further fractionated the fat fraction by silica gel column chromatography into nine fat subfractions.", "output": "silica gel." }, { "input": "In the present study, we used exogenous hypercholesterolaemic rats induced by feeding a high - cholesterol diet; the doses of the added fat subfractions were equivalent to those in 30 % FCE.", "output": "cholesterol." }, { "input": "Two ( FF1, FF2 ) out of the nine fat subfractions strongly reduced serum cholesterol levels in the rats fed a high - cholesterol diet.", "output": "cholesterol, cholesterol." }, { "input": "Both FF1 and FF2 up - regulated the hepatic gene expression of cholesterol 7 alpha - hydroxylase, a rate - limiting enzyme of bile acid biosynthesis.", "output": "cholesterol, bile acid." }, { "input": "Thin - layer chromatography showed that FF1 primarily contained sphingolipids, while FF2 mainly contained triacylglycerols and sterol esters.", "output": "sphingolipids, triacylglycerols, sterol esters." }, { "input": "These results indicate that fractions containing sphingolipids, triacylglycerols, and sterol esters are possibly responsible for the hypocholesterolaemic action in a novel manner through the up - regulation of the hepatic biosynthesis of bile acids.", "output": "sphingolipids, triacylglycerols, sterol esters." }, { "input": "Separation and purification of sulforaphene from radish seeds using macroporous resin and preparative high - performance liquid chromatography.", "output": "sulforaphene." }, { "input": "This present study described a rapid and cost - effective method for the separation and purification of natural sulforaphene from radish seeds by SP - 700 macroporous resin and preparative high - performance liquid chromatography ( HPLC ).", "output": "sulforaphene." }, { "input": "Sulforaphene with high purity and recovery was obtained by preparative HPLC with a C18 column and 30 % methanol in ultra - pure water as the mobile phase.", "output": "Sulforaphene, methanol." }, { "input": "12. 5 kg of radish seeds, which contained 87. 5 g of sulforaphene, produced 117. 5 g of sulforaphene - rich extract of 65. 8 % sulforaphene after primary separation by SP - 700 macroporous resin.", "output": "sulforaphene, sulforaphene, sulforaphene." }, { "input": "5. 9 g of 96. 5 % sulforaphene was obtained from 9. 5 g of the sulforaphene - rich extract after purification by preparative HPLC.", "output": "sulforaphene, sulforaphene." }, { "input": "The purified compound was assessed by analytical HPLC and characterised by ESI / MS, ( 1 ) H NMR and ( 13 ) C NMR.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "Standard curve was developed using the purified sulforaphene to allow quantification of sulforaphene in the extracts of radish seeds by analytical HPLC.", "output": "sulforaphene, sulforaphene." }, { "input": "Bacillus cereus AR156 induces resistance against Rhizopus rot through priming of defense responses in peach fruit.", "output": "There is no related enetity." }, { "input": "The biocontrol effects of Bacillus cereus AR156 on Rhizopus rot caused by Rhizopus stolonifer in postharvest peach fruit and the possible mechanisms were investigated.", "output": "There is no related enetity." }, { "input": "The results showed that fruit treated with B. cereus AR156 had significantly lower disease incidence and smaller lesion diameter than the control fruit did.", "output": "There is no related enetity." }, { "input": "B. cereus AR156 treatment remarkably enhanced activities of chitinase and beta - 1, 3 - glucanase, promoted accumulation of H ( 2 ) O ( 2 ), and improved total phenolic content and 2, 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ) radical - scavenging activity.", "output": "H ( 2 ) O ( 2 ), 2 , 2 - diphenyl - 1 - picrylhydrazyl, DPPH." }, { "input": "Transcripts of four defense related genes were only significantly enhanced in fruit both treated with B. cereus AR156 and inoculated with R. stolonifer compared with those that were only treated with B. cereus AR156 or inoculated with R. stolonifer.", "output": "There is no related enetity." }, { "input": "These results suggest that B. cereus AR156 can effectively inhibit Rhizopus rot caused by R. stolonifer and enhance antioxidant activity in peach fruit through the priming of defense responses.", "output": "There is no related enetity." }, { "input": "Discrimination against diacylglycerol ethers in lipase - catalysed ethanolysis of shark liver oil.", "output": "diacylglycerol ethers." }, { "input": "Lipase - catalysed ethanolysis of squalene - free shark liver oil was investigated.", "output": "squalene." }, { "input": "The mentioned shark liver oil was comprised mainly of diacylglycerol ether and triacylglycerols.", "output": "diacylglycerol ether, triacylglycerols." }, { "input": "In order to test discrimination against diacylglycerol ether, up to 10 different lipases were compared.", "output": "diacylglycerol ether." }, { "input": "The ratio of oil to ethanol and lipase stability were also evaluated.", "output": "ethanol." }, { "input": "Surprisingly, lipase from Pseudomonas stutzeri was the fastest biocatalyst among all assayed, although poor discrimination against diacylglycerol ether was observed.", "output": "diacylglycerol ether." }, { "input": "The best results in terms of selectivity and stability were obtained with immobilised lipase from Candida antarctica ( Novozym 435 ).", "output": "There is no related enetity." }, { "input": "Ethanolysis reaction after 24h in the presence of Novozym 435 produced total disappearance of triacylglycerol and a final reaction mixture comprised mainly of diacylglycerol ethers ( 10. 6 % ), monoacylglycerol ethers ( 32. 9 % ) and fatty acid ethyl esters ( 46. 0 % ).", "output": "triacylglycerol, diacylglycerol ethers, monoacylglycerol ethers, fatty acid ethyl esters." }, { "input": "In addition, when an excess of ethanol was used, diacylglycerol ethers completely disappeared after 15 h, giving a final product mainly composed of monoacylglycerol ethers ( 36. 6 % ) and fatty acid ethyl esters ( 46. 4 % ).", "output": "ethanol, diacylglycerol ethers, monoacylglycerol ethers, fatty acid ethyl esters." }, { "input": "Sustainable production of pectin from lime peel by high hydrostatic pressure treatment.", "output": "There is no related enetity." }, { "input": "The application of high hydrostatic pressure technology for enzymatic extraction of pectin was evaluated.", "output": "There is no related enetity." }, { "input": "Cellulase and xylanase under five different combinations ( cellulase / xylanase: 50 / 0, 50 / 25, 50 / 50, 25 / 50, and 0 / 50 U / g lime peel ) at ambient pressure, 100 and 200 MPa were used to extract pectin from dried lime peel.", "output": "There is no related enetity." }, { "input": "Extraction yield, galacturonic acid ( GalA ) content, average molecular weight ( M ( w, ave ) ), intrinsic viscosity [ eta ] ( w ), and degree of esterification ( DE ) were compared to those parameters obtained for pectins extracted using acid and aqueous processes.", "output": "galacturonic acid, GalA." }, { "input": "Pressure level, type and concentration of enzyme significantly ( p < 0. 05 ) influenced yield and DE of pectin.", "output": "There is no related enetity." }, { "input": "Enzyme and high pressure extraction resulted in yields which were significantly ( p < 0. 05 ) higher than those using acid and aqueous extraction.", "output": "There is no related enetity." }, { "input": "Although pressure - induced enzymatic treatment improves pectin yield, it does not have any significant effect on M ( w, ave ) and [ eta ] ( w ) of pectin extracts indicating the potential of high pressure treatment for enzymatic pectin production as a novel and sustainable process.", "output": "There is no related enetity." }, { "input": "Introduction and nutritional evaluation of germinated soy germ.", "output": "There is no related enetity." }, { "input": "Germinated soy germ ( GSG ) were developed and evaluated for their nutritional value.", "output": "There is no related enetity." }, { "input": "Separated soy germ was germinated at room temperature for 24h under running water.", "output": "There is no related enetity." }, { "input": "As germination progressed, the protein and fibre content of GSG increased slightly, while the lipid and carbon to nitrogen ( C / N ) ratio decreased; free amino acids including GABA increased considerably while free sugars decreased.", "output": "carbon, nitrogen, C, N, amino acids, GABA, sugars." }, { "input": "Linoleic and linolenic acid were the most abundant unsaturated fatty acids in soy germ, and slight changes were observed in GSG.", "output": "Linoleic and linolenic acid, unsaturated fatty acids." }, { "input": "The tocopherol and isoflavone contents showed a rapid increase of 32. 4 % and 27. 9 %, respectively, during germination.", "output": "tocopherol, isoflavone." }, { "input": "The abundance of GABA, isoflavones and tocopherols demonstrates the high nutritional value of GSG and suggests that GSG can be utilised as a reasonable and effective source of healthy foods.", "output": "GABA, isoflavones, tocopherols." }, { "input": "Chemical and sensory effects of the freezing process on the aroma profile of black truffles ( Tuber melanosporum ).", "output": "There is no related enetity." }, { "input": "The aim of this work was to evaluate the effect of freezing black truffles ( Tuber melanosporum ) on their aroma both in sensory and chemical terms.", "output": "There is no related enetity." }, { "input": "The truffles were frozen at temperatures of - 20 to - 80 degrees C.", "output": "There is no related enetity." }, { "input": "Descriptive and discriminative sensory and chemical analyses, based on headspace solid phase microextraction followed by gas chromatography - mass spectrometry analysis ( HS - SPME - GC - MS ), were carried out after 1, 20, 40 and 60 days.", "output": "There is no related enetity." }, { "input": "Fifteen compounds with high aromatic potential in truffles were determined.", "output": "There is no related enetity." }, { "input": "Their selective ion peak areas were calculated, summed and expressed as percentage of active odour compound, in order to monitor changes in odour profile.", "output": "There is no related enetity." }, { "input": "The aroma of frozen truffles differed significantly from the aroma of fresh truffles.", "output": "There is no related enetity." }, { "input": "Volatile composition data revealed that T. melanosporum aromatic profile is deeply modified as a consequence of a freezing process.", "output": "There is no related enetity." }, { "input": "These aromatic changes could explain the loss of freshness observed in all frozen truffles.", "output": "There is no related enetity." }, { "input": "Methional and some phenols were suggested as markers of freezing time.", "output": "Methional, phenols." }, { "input": "Interestingly, 1 - octen - 3 - one appeared as a general marker of freezing process.", "output": "1 - octen - 3 - one." }, { "input": "GC / MS analysis of volatiles obtained by headspace solid - phase microextraction and simultaneous - distillation extraction from Rabdosia serra ( MAXIM. ) HARA leaf and stem.", "output": "There is no related enetity." }, { "input": "Volatiles in Rabdosia serra were investigated by headspace solid phase microextraction ( HS - SPME ) and simultaneous - distillation extraction ( SDE ).", "output": "There is no related enetity." }, { "input": "The HS - SPME technique was previously evaluated to optimise sampling conditions.", "output": "There is no related enetity." }, { "input": "A total of 56 and 48 compounds including alcohols, aldehydes, hydrocarbons, ketones, carboxylic acid, ester, and aromatics were identified in leaf and stem by optimised HS - SPME method ( CAR / PDMS fibre; incubation time, 10 min; extraction temperature, 50 degrees C; extraction time, 40 min ), respectively.", "output": "alcohols, aldehydes, hydrocarbons, ketones, carboxylic acid, ester." }, { "input": "1 - Octen - 3 - ol and ( 2E ) - hexenal had significant contribution to R. serra aroma.", "output": "1 - Octen - 3 - ol, ( 2E ) - hexenal." }, { "input": "Cluster analysis indicated that leaf and stem exhibited different volatile diversity.", "output": "There is no related enetity." }, { "input": "Air drying was favourable for the retention of the volatiles, while freeze - and sun - drying led to the loss of volatiles.", "output": "There is no related enetity." }, { "input": "SDE method preferred to the analysis of compounds with low volatility including fatty acids and esters.", "output": "fatty acids, esters." }, { "input": "HS - SPME was a useful technique for the analysis of readily volatile components for the characteristics of R. serra aroma.", "output": "There is no related enetity." }, { "input": "Novel angiotensin I - converting enzyme inhibitory peptides derived from soya milk.", "output": "There is no related enetity." }, { "input": "Inhibitors of angiotensin I - converting enzyme ( ACE ) are useful in treating hypertension, and many have been derived from food products, including soybeans.", "output": "There is no related enetity." }, { "input": "Using the industrial protease PROTIN SD - NY10, we developed a processed soya milk ( PSM ) with enhanced ACE inhibitory activity.", "output": "There is no related enetity." }, { "input": "The ACE inhibitory activity of PSM ( IC ( 50 ) = 0. 26 mu g / ml ) was greater than that of regular soya milk ( IC ( 50 ) = 8. 75 mu g / ml ).", "output": "There is no related enetity." }, { "input": "Eight novel ACE inhibitory peptides were purified from PSM by reversed - phase chromatography: FFYY ( IC ( 50 ), 1. 9 mu M ), WHP ( 4. 8 mu M ), FVP ( 10. 1 mu M ), LHPGDAQR ( 10. 3 mu M ), IAV ( 27. 0 mu M ), VNP ( 32. 5 mu M ), LEPP ( 100. 1 mu M ), and WNPR ( 880. 0 mu M ).", "output": "There is no related enetity." }, { "input": "The IC ( 50 ) values of these peptides are comparable to those reported for other ACE inhibitory peptides derived from wheat, chicken, bonito, wine, etc.", "output": "There is no related enetity." }, { "input": "Due to the relatively low IC ( 50 ) values of several peptides identified in this study, they may serve as ideal base components of food supplements for patients with hypertension.", "output": "There is no related enetity." }, { "input": "Non - target screening of Allura Red AC photodegradation products in a beverage through ultra high performance liquid chromatography coupled with hybrid triple quadrupole / linear ion trap mass spectrometry.", "output": "Allura Red AC." }, { "input": "The study deals with the identification of the degradation products formed by simulated sunlight photoirradiation in a commercial beverage that contains Allura Red AC dye.", "output": "Allura Red AC." }, { "input": "An UHPLC - MS / MS method, that makes use of hybrid triple quadrupole / linear ion trap, was developed.", "output": "There is no related enetity." }, { "input": "In the identification step the software tool information dependent acquisition ( IDA ) was used to automatically obtain information about the species present and to build a multiple reaction monitoring ( MRM ) method with the MS / MS fragmentation pattern of the species considered.", "output": "There is no related enetity." }, { "input": "The results indicate that the identified degradation products are formed from side - reactions and / or interactions among the dye and other ingredients present in the beverage ( ascorbic acid, citric acid, sucrose, aromas, strawberry juice, and extract of chamomile flowers ).", "output": "ascorbic acid, citric acid, sucrose." }, { "input": "The presence of aromatic amine or amide functionalities in the chemical structures proposed for the degradation products might suggest potential hazards to consumer health.", "output": "aromatic amine or amide." }, { "input": "Maple polyphenols, ginnalins A - C, induce S - and G2 / M - cell cycle arrest in colon and breast cancer cells mediated by decreasing cyclins A and D1 levels.", "output": "polyphenols, ginnalins A - C." }, { "input": "Polyphenols are bioactive compounds found in plant foods.", "output": "Polyphenols." }, { "input": "Ginnalins A - C are polyphenols present in the sap and other parts of the sugar and red maple species which are used to produce maple syrup.", "output": "Ginnalins A - C, polyphenols, sugar." }, { "input": "Here we evaluated the antiproliferative effects of ginnalins A - C on colon ( HCT - 116 ) and breast ( MCF - 7 ) tumourigenic and non - tumourigenic colon ( CCD - 18Co ) cells and investigated whether these effects were mediated through cell cycle arrest and / or apoptosis.", "output": "ginnalins A - C." }, { "input": "Ginnalins A - C were twofold more effective against the tumourigenic than non - tumourigenic cells.", "output": "Ginnalins A - C." }, { "input": "Among the polyphenols, ginnalin A ( 84 %, HCT - 116; 49 %, MCF - 7 ) was more effective than ginnalins B and C ( 50 %, HCT - 116; 30 %, MCF - 7 ) at 50 mu M concentrations.", "output": "polyphenols, ginnalin A, ginnalins B and C." }, { "input": "Ginnalin A did not induce apoptosis of the cancer cells but arrested cell cycle ( in the S - and G ( 2 ) / M - phases ) and decreased cyclins A and D1 protein levels.", "output": "Ginnalin A." }, { "input": "These results suggest that maple polyphenols may have potential cancer chemopreventive effects mediated through cell cycle arrest.", "output": "polyphenols." }, { "input": "Hair mercury levels and food consumption in residents from the Pearl River Delta: South China.", "output": "mercury." }, { "input": "The Pearl River Delta ( PRD ) is located in the Southern part of China and is the main region for fish culture in Guangdong Province.", "output": "There is no related enetity." }, { "input": "In order to assess the potential health risks associated with dietary consumption of mercury, hair samples from 91 urban, town and fishing village residents, 37 species of fish, cereal, vegetables, and meat samples were collected.", "output": "mercury." }, { "input": "The average total mercury ( THg ) and methylmercury ( MeHg ) concentrations in hair were 1. 08 +/- 0. 94 and 0. 58 +/- 0. 59 mu g / g, respectively.", "output": "mercury, methylmercury, MeHg." }, { "input": "Daily Hg intake via fish consumption is significantly correlated with THg and MeHg accumulated in human hair ( r = 0. 48, p < 0. 01; r = 0. 43, p < 0. 01 ).", "output": "Hg, MeHg." }, { "input": "The estimated daily intake of Hg via different food types showed that both fish and cereal consumption were the two main routes of Hg exposure for residents in the sampling areas.", "output": "Hg, Hg." }, { "input": "Besides food intake, smoking was also an important source for daily THg intake in the smoke group, contributing 11 - 18 % to EDI of THg.", "output": "There is no related enetity." }, { "input": "Quantitative analysis of fungicide azoxystrobin in agricultural samples with rapid, simple and reliable monoclonal immunoassay.", "output": "azoxystrobin." }, { "input": "This work presents analytical performance of a kit - based direct competitive enzyme - linked immunosorbent assay ( dc - ELISA ) for azoxystrobin detection in agricultural products.", "output": "azoxystrobin." }, { "input": "The dc - ELISA was sufficiently sensitive for analysis of residue levels close to the maximum residue limits.", "output": "There is no related enetity." }, { "input": "The dc - ELISA did not show cross - reactivity to other strobilurin analogues.", "output": "strobilurin." }, { "input": "Absorbance decreased with the increase of methanol concentration in sample solution from 2 % to 40 %, while the standard curve became most linear when the sample solution contained 10 % methanol.", "output": "methanol, methanol." }, { "input": "Agricultural samples were extracted with methanol, and the extracts were diluted with water to 10 % methanol adequate.", "output": "methanol, methanol." }, { "input": "No significant matrix interference was observed.", "output": "There is no related enetity." }, { "input": "Satisfying recovery was found for all of spiked samples and the results were well agreed with the analysis with liquid chromatography.", "output": "There is no related enetity." }, { "input": "These results clearly indicate that the kit - based dc - ELISA is suitable for the rapid, simple, quantitative and reliable determination of the fungicide.", "output": "There is no related enetity." }, { "input": "CODEX - compliant eleven organophosphorus pesticides screening in multiple commodities using headspace - solid phase microextraction - gas chromatography - mass spectrometry.", "output": "organophosphorus." }, { "input": "A headspace - solid phase microextraction - gas chromatography - mass spectrometric ( HS - SPME - GC - MS, hereafter abbreviated as \" SPME \" ) method was developed for dedicated organophosphorus ( OP ) pesticides assessment in multiple vegetable and fruit commodities.", "output": "organophosphorus." }, { "input": "Specific extraction variables were optimised to achieve harmonised extraction performance of eleven OPs in a great span of seven characteristic commodities cataloged in Codex Alimentarius Commission.", "output": "There is no related enetity." }, { "input": "Comprehensive validation study confirmed analytical robustness of the SPME treatment in turnip, green cabbage, French beans, eggplant, apple, nectarine and grapes.", "output": "There is no related enetity." }, { "input": "Based on range - specific evaluation, extraction of individual OPs was characterised by sub - ppb level sensitivity and a wide 0. 01 - 2. 5 mg L ( - 1 ) dynamic range.", "output": "There is no related enetity." }, { "input": "Effective sample clean - up afforded precise quantification ( 0. 5 - 10. 9 % R. S. D. ) within a 70 - 120 % recovery range at the MRL levels specified for individual commodities.", "output": "There is no related enetity." }, { "input": "Compared to conventional methods currently used, the SPME treatment developed here is quick, accurate, and relatively environmental friendly; it represents an attractive, practical way to deliver international standards in OP screening routines.", "output": "There is no related enetity." }, { "input": "Differential sensitivity of D - galactose - binding lectins from fruits of dwarf elder ( Sambucus ebulus L. ) to a simulated gastric fluid.", "output": "D - galactose." }, { "input": "Some lectins from Sambucus spp. share amino acid sequences with the pollen Sam n1 allergen.", "output": "amino acid." }, { "input": "The lectins ebulin f and SELfd from the early stages of growth were isolated and subjected to analysis by MALDI - TOF mass spectrometry, tryptic peptide fingerprinting, molecular characterization and pepsin digestibility.", "output": "There is no related enetity." }, { "input": "The molecular mass ( 33. 214 ) and other structural features of the Sam n1 allergen fit best with a monomeric lectin like SELlm ( Mr 34. 2 kDa ) found in shoots of dwarf elder.", "output": "There is no related enetity." }, { "input": "Ebulin f toxicity to mice was higher intraperitoneally than orally at the same dose ( 5mg / kg body weight ).", "output": "There is no related enetity." }, { "input": "In contrast SELfd at the same dose lacks of apparent toxicity.", "output": "There is no related enetity." }, { "input": "Ebulin f, but not SELfd, undergoes extensive pepsin proteolysis, which could explain the differences in toxicity.", "output": "There is no related enetity." }, { "input": "The present study supports our hypothesis that the Sam n1 allergen could be a sequence - related monomeric lectin like SELlm present in shoots of Sambucus ebulus rather than ebulin.", "output": "There is no related enetity." }, { "input": "Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity - containing fraction from the seeds of Korean perilla ( Perilla frutescens ) cultivars.", "output": "There is no related enetity." }, { "input": "The present research was the first to investigate phenolic compound profiles and antioxidant properties in the seeds of various perilla ( Perilla frutescens ) cultivars.", "output": "There is no related enetity." }, { "input": "The 80 % methanol extract ( 50 mu g / ml ) of this species showed potent antioxidant activities against 2, 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ) and 2, 2 ' - azino - bis ( 3 - ethylbenzthiazoline - 6 - sulphonic acid ) ( ABTS ) radicals.", "output": "methanol, 2 , 2 - diphenyl - 1 - picrylhydrazyl, DPPH, 2 , 2 ' - azino - bis ( 3 - ethylbenzthiazoline - 6 - sulphonic acid ), ABTS." }, { "input": "Phenolic compounds were characterised by nuclear magnetic resonance ( NMR ) spectroscopy, and ultra performance liquid chromatography with photodiode array detector and electrospray ionisation / mass ( UPLC - PDA - ESI / MS ) analysis.", "output": "There is no related enetity." }, { "input": "Nine compounds were elucidated as caffeic acid - 3 - O - glucoside ( 1 ), caffeic acid ( 2 ), luteolin - 7 - O - glucoside ( 3 ), apigenin - 7 - O - glucoside ( 4 ), rosmarinic acid - 3 - O - glucoside ( 5 ), rosmarinic acid ( 6 ), luteolin ( 7 ), apigenin ( 8 ), and chrysoeriol ( 9 ).", "output": "caffeic acid - 3 - O - glucoside, caffeic acid, luteolin - 7 - O - glucoside, apigenin - 7 - O - glucoside, rosmarinic acid - 3 - O - glucoside, rosmarinic acid, luteolin, apigenin, chrysoeriol." }, { "input": "The individual and total phenolic contents were remarkably different, especially rosmarinic acid - 3 - O - glucoside ( 5 ) and rosmarinic acid ( 6 ) which were the predominant compounds ( > 95 % ) in all perilla cultivars.", "output": "rosmarinic acid - 3 - O - glucoside, rosmarinic acid." }, { "input": "Additionally, Yeupsil cultivar exhibited the highest phenolic content ( 5029. 0 mu g / g ) and antioxidant activity, whereas the lowest was shown by Dasil ( 2138. 7 mu g / g ).", "output": "There is no related enetity." }, { "input": "Therefore, these results suggest that antioxidant effects of perilla seeds are correlated with phenolic contents.", "output": "There is no related enetity." }, { "input": "Degradation kinetics of anthocyanins in acerola pulp: comparison between ohmic and conventional heat treatment.", "output": "anthocyanins." }, { "input": "Degradation kinetics of monomeric anthocyanins in acerola pulp during thermal treatment by ohmic and conventional heating was evaluated at different temperatures ( 75 - 90 degrees C ).", "output": "anthocyanins." }, { "input": "Anthocyanin degradation fitted a first - order reaction model and the rate constants ranged from 5. 9 to 19. 7 x 10 ( - 3 ) min ( - 1 ).", "output": "There is no related enetity." }, { "input": "There were no significant differences between the rate constants of the ohmic and the conventional heating processes at all evaluated temperatures.", "output": "There is no related enetity." }, { "input": "D - Values ranged from 116. 7 to 374. 5 for ohmic heating and from 134. 9 to 390. 4 for conventional heating.", "output": "There is no related enetity." }, { "input": "Values of the free energy of inactivation were within the range of 100. 19 and 101. 35 kJ mol ( - 1 ).", "output": "There is no related enetity." }, { "input": "The enthalpy of activation presented values between 71. 79 and 71. 94 kJ mol ( - 1 ) and the entropy of activation ranged from - 80. 15 to - 82. 63 J mol ( - 1 ) K ( - 1 ).", "output": "There is no related enetity." }, { "input": "Both heating technologies showed activation energy of 74. 8 kJ mol ( - 1 ) and close values for all thermodynamic parameters, indicating similar mechanisms of degradation.", "output": "There is no related enetity." }, { "input": "Hypotriglyceridemic and hypoglycemic effects of vescalagin from Pink wax apple [ Syzygium samarangense ( Blume ) Merrill and Perry cv. Pink ] in high - fructose diet - induced diabetic rats.", "output": "vescalagin, fructose." }, { "input": "Vescalagin, an active component from Pink wax apple [ Syzygium samarangense ( Blume ) Merrill and Perry cv. Pink ] fruit, with glucose uptake enhancing ability in insulin - resistant FL83B mouse hepatocytes, as shown in our previous study, was further evaluated for its hypotriglyceridemic and hypoglycemic effects in high - fructose diet ( HFD ) - induced diabetic rats.", "output": "Vescalagin, glucose, fructose." }, { "input": "Wistar rats were fed HFD for 16 weeks and orally administered with vescalagin from Pink wax apple daily during the last 4 weeks.", "output": "vescalagin." }, { "input": "The results of biochemical parameters showed that fasting blood glucose, C - peptide, fructosamine, triglyceride and free fatty acid contents decreased by 44. 7 %, 46. 2 %, 4. 0 %, 42. 5 %, and 10. 8 %, respectively, in the HFD - induced diabetic rats administered with vescalagin at 30 mg / kg body weight in comparison with those of control HFD - induced diabetic rats.", "output": "glucose, fructosamine, triglyceride, fatty acid, vescalagin." }, { "input": "However, high - density - lipoprotein - cholesterol content increased by 14. 4 % in the HFD rats treated with vescalagin.", "output": "cholesterol, vescalagin." }, { "input": "The present study reveals that vescalagin could have therapeutic value against diabetic progression via its anti - hypertriglyceridemic and anti - hyperglycemic effects.", "output": "vescalagin." }, { "input": "Carotenoid compositions of coloured tomato cultivars and contribution to antioxidant activities and protection against H ( 2 ) O ( 2 ) - induced cell death in H9c2.", "output": "H ( 2 ) O ( 2 )." }, { "input": "The carotenoid compositions, antioxidant activities and the potential cardio - protective role of 13 tomato cultivars with distinct colour were studied.", "output": "There is no related enetity." }, { "input": "Colour coordinates were evaluated by colorimeter and the carotenoid compositions were analysed by UPLC.", "output": "There is no related enetity." }, { "input": "Red tomatoes had the highest total carotenoid contents ( TCC ) and antioxidant activities, followed by purple, orange, pink and yellow ones.", "output": "There is no related enetity." }, { "input": "The TCC were 120. 5 - 278. 0 mu g / gDW, and the antioxidant activities were 21. 32 - 40. 07 mu molTE / gDW ( PCL ), 64. 42 - 89. 98 % ( DPPH ) and 10. 47 - 13. 76 mu molTE / g DW ( ORAC ), respectively.", "output": "DPPH." }, { "input": "The lipophilic extracts were also found to prevent cell death in a cell - based model system using cardiac H9c2 cells and H ( 2 ) O ( 2 ), via attenuation of the caspase - 3 and matrix metalloproteinase - 2 activities.", "output": "H ( 2 ) O ( 2 )." }, { "input": "The extracts of different tomatoes showed strong but different antioxidant activities.", "output": "There is no related enetity." }, { "input": "Roles of total and individual carotenoids in the antioxidant activities were studied and lycopene showed the highest correlation.", "output": "There is no related enetity." }, { "input": "Results of this study can be used to guide the development of new tomato cultivars and functional foods, and benefit the consumers.", "output": "There is no related enetity." }, { "input": "Medium chain and behenic acid incorporated structured lipids from sal, mango and kokum fats by lipase acidolysis.", "output": "behenic acid." }, { "input": "Medium chain ( MC ) and behenic fatty acids were incorporated into kokum, sal and mango fats using 1, 3 - specific lipase catalysed acidolysis.", "output": "fatty acids." }, { "input": "The incorporation of fatty acids increased with increase in concentration of fatty acids and duration of reaction.", "output": "fatty acids, fatty acids." }, { "input": "The order of incorporation of fatty acids was C22: 0 > C10: 0 > C8: 0, to the extent of 53 %, 42. 5 %, 35. 8 %, respectively, after 16 h, using kokum as substrate.", "output": "fatty acids." }, { "input": "The same trend was observed with sal or mango fats as substrates though the percentages incorporated were different.", "output": "There is no related enetity." }, { "input": "The modified products with higher contents of MC were liquids with no solid fats, even at 0 degrees C, and which showed low cloud point due to an increase in triacylglycerols containing lower chain fatty acids.", "output": "triacylglycerols, fatty acids." }, { "input": "The modified products after incorporating both MC and C22: 0 showed long melting ranges and were suitable for use in bakery, confectionery, etc. as vanaspati substitutes.", "output": "There is no related enetity." }, { "input": "Comparison of the affinity and selectivity of insoluble fibres and commercial proteins for wine proanthocyanidins.", "output": "proanthocyanidins." }, { "input": "The fining action of commercial proteins and insoluble fibres for wine proanthocyanidin ( PA ) were compared.", "output": "proanthocyanidin." }, { "input": "Fibres were prepared from fresh apple and grape sources, and their corresponding pomaces.", "output": "There is no related enetity." }, { "input": "PA removal by fibre was via adsorption, and required a higher dose to achieve a fining effect comparable with proteins.", "output": "There is no related enetity." }, { "input": "A principal component analysis data model revealed that PA molecular mass was significant in defining the fining response, and reflected changes in the proportion of the dominant terminal PA subunits catechin and epicatechin, but not epicatechin - 3 - O - gallate.", "output": "catechin, epicatechin, epicatechin - 3 - O - gallate." }, { "input": "For PA extension subunits, changes in epigallocatechin were inversely correlated with epicatechin and epicatechin - 3 - O - gallate.", "output": "epigallocatechin, epicatechin, epicatechin - 3 - O - gallate." }, { "input": "Generally, the application of proteins and fibres reduced PA molecular mass.", "output": "There is no related enetity." }, { "input": "Selectivity for PAs by subunit composition was variable between treatments, but differences were minor.", "output": "There is no related enetity." }, { "input": "This work demonstrates the potential use of fibres as an alternative to proteins in winemaking.", "output": "There is no related enetity." }, { "input": "Benefits, and possible limitations of such an approach are discussed.", "output": "There is no related enetity." }, { "input": "The influence of the malaxation temperature on the activity of polyphenoloxidase and peroxidase and on the phenolic composition of virgin olive oil.", "output": "There is no related enetity." }, { "input": "The effect of the malaxation temperature under sealed conditions on the qualitative and quantitative composition of the phenolic compounds in virgin olive oils produced from four Italian cultivars was assessed for two atmospheric conditions.", "output": "There is no related enetity." }, { "input": "In both cases, the results show a positive relationship between temperature and the concentration of the derivatives of the secoiridoid aglycones; the effect of the temperature on the oxidoreductases that promote oxidation ( polyphenoloxidase and peroxidase ) was investigated to determine their optimal temperatures and thermal stability.", "output": "secoiridoid aglycones." }, { "input": "While olive peroxidase ( POD ) showed the highest activity at 37 degrees C and high stability in the temperature range tested, polyphenoloxidase ( PPO ) exhibited the optimum activity at approximately 50 degrees C, but showed low stability at 40 degrees C, with a large variation in stability according to the olive cultivar.", "output": "There is no related enetity." }, { "input": "These results may contribute to an understanding of the increase in the phenol concentration found in virgin olive oils obtained following higher temperatures of malaxation.", "output": "phenol." }, { "input": "Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins.", "output": "There is no related enetity." }, { "input": "Two plant enzyme extracts from kiwifruit and asparagus were evaluated for their ability to hydrolyse commercially available substrates and proteins present in both beef connective tissue and topside myofibrillar extracts.", "output": "There is no related enetity." }, { "input": "The results show significant differences in protease activity depending on the assay used.", "output": "There is no related enetity." }, { "input": "Protease assays with connective tissue and meat myofibrillar extracts provide a more realistic evaluation of the potential of the enzymes for application in meat tenderization.", "output": "There is no related enetity." }, { "input": "Overall, the kiwifruit protease extract was found to be more effective at hydrolysing myofibrillar and collagen proteins than the asparagus protease extract.", "output": "There is no related enetity." }, { "input": "The two protease extracts appeared to target meat myofibrillar and collagen proteins differently, suggesting the potential of a synergistic effect of these proteases in improving the tenderness of specific cuts of meat, based on their intrinsic protein composition.", "output": "There is no related enetity." }, { "input": "Antidepressant - like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.", "output": "carnosol, betulinic acid." }, { "input": "The aim of this study was to investigate the antidepressant - like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 ( AcOEt1 and 2 ), hexane ( HEX ), ethanolic ( ET ), and essential oil - free ( EOF ) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity.", "output": "ethyl acetate, AcOEt1, hexane, HEX, carnosol, betulinic acid." }, { "input": "Swiss mice were acutely administered by oral route ( p. o. ) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open - field test.", "output": "There is no related enetity." }, { "input": "All of them produced a significant antidepressant - like effect: AcOEt1, ET, EOF fractions and essential oil ( 0. 1 - 100mg / kg, p. o ); HEX ( 0. 1 - 10mg / kg, p. o ) and AcOEt2 fraction ( 0. 1 - 1mg / kg, p. o ), carnosol ( 0. 01 - 0. 1mg / kg, p. o. ) isolated from the HEX fraction and betulinic acid ( 10mg / kg, p. o. ), isolated from the AcOEt1 and AcOEt2 fractions.", "output": "AcOEt1, HEX, AcOEt2, carnosol, HEX, betulinic acid, AcOEt1, AcOEt2." }, { "input": "No psychostimulant effect was shown in the open - field test, indicating that the effects in the tail suspension test are specific.", "output": "There is no related enetity." }, { "input": "This study suggests that carnosol and betulinic acid could be responsible for the anti - immobility effect of extracts from R. officinalis.", "output": "carnosol, betulinic acid." }, { "input": "Feasibility and application of an HPLC / UVD to determine dinotefuran and its shorter wavelength metabolites residues in melon with tandem mass confirmation.", "output": "dinotefuran." }, { "input": "A new analytical method was developed for dinotefuran and its metabolites, MNG, UF, and DN, in melon using high - performance liquid chromatography ( HPLC ) coupled with an ultraviolet detector ( UVD ).", "output": "dinotefuran, MNG." }, { "input": "Due to shorter wavelength, lower sensitivity to UV detection, and high water miscibility of some metabolites, QuEChERs acetate - buffered version was modified for extraction and purification.", "output": "There is no related enetity." }, { "input": "Mobile phases with different ion pairing or ionisation agents were tested in different reverse phase columns, and ammonium bicarbonate buffer was found as the best choice to increase the sensitivity of target analytes to the UV detector.", "output": "ammonium bicarbonate." }, { "input": "After failure of dispersive SPE clean - up with primary secondary amine, different solid phase extraction cartridges ( SPE ) were used to check the protecting capability of analytes against matrix interference.", "output": "primary secondary amine." }, { "input": "Finally, samples were extracted with a simple and rapid method using acetonitrile and salts, and purified through C ( 18 ) SPE.", "output": "acetonitrile and salts." }, { "input": "The method was validated at two spiking levels ( three replicates for each ) in the matrix.", "output": "There is no related enetity." }, { "input": "Good recoveries were observed for all of the analytes and ranged between 70. 6 % and 93. 5 %, with relative standard deviations of less than 10 %.", "output": "There is no related enetity." }, { "input": "Calibration curves were linear over the calibration ranges for all the analytes with r ( 2 ) >= 0. 998.", "output": "There is no related enetity." }, { "input": "Limits of detection ranged from 0. 02 to 0. 05 mg kg ( - 1 ), whereas limits of quantitation ranged from 0. 06 to 0. 16 mg kg ( - 1 ) for dinotefuran and its metabolites.", "output": "dinotefuran." }, { "input": "The method was successfully applied to real samples, where dinotefuran and UF residues were found in the field - incurred melon samples.", "output": "dinotefuran." }, { "input": "Residues were confirmed via LC - tandem mass spectrometry ( LC - MS / MS ) in positive - ion electrospray ionisation ( ESI ( + ) ) mode.", "output": "There is no related enetity." }, { "input": "Occurrence and sensory perception of Z - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid in rooibos ( Aspalathus linearis ).", "output": "Z - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid." }, { "input": "Z - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid ( PPAG ), a compound postulated to contribute to the taste and mouthfeel of fermented rooibos tea ( Aspalathus linearis ), was isolated from unfermented rooibos plant material.", "output": "Z - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid, PPAG." }, { "input": "Its structure was unequivocally confirmed by LC - MS, - MS ( 2 ), FT - IR and NMR of the underivatised natural product, and optical rotation measurements of the hydrolysed sugar moiety.", "output": "sugar." }, { "input": "A similar compound, postulated to be E - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid, was also detected.", "output": "E - 2 - ( beta - d - glucopyranosyloxy ) - 3 - phenylpropenoic acid." }, { "input": "Analysis of the leaves of a large number of rooibos plants ( n = 54 ), sampled at commercial plantations, showed that PPAG is not ubiquitously present in detectable quantities in the leaves of different plants.", "output": "PPAG." }, { "input": "This leads to large variation in the fermented plant material, infusions and food - grade extracts.", "output": "There is no related enetity." }, { "input": "PPAG was shown to have a slightly bitter to astringent taste and a detection threshold of 0. 4 mg / l in water.", "output": "PPAG." }, { "input": "Schisarisanlactones A and B: a new class of nortriterpenoids from the fruits of Schisandra arisanensis.", "output": "Schisarisanlactones A and B, nortriterpenoids." }, { "input": "Two novel highly oxygenated nortriterpenoids, schisarisanlactones A ( 1 ) and B ( 2 ), have been isolated from the fruits of Schisandra arisanensis, an endemic plant of Taiwan.", "output": "nortriterpenoids, schisarisanlactones A ( 1 ) and B." }, { "input": "Compounds 1 and 2 possess an unprecedented 5 / 5 / 7 / 5 / 5 - fused pentacyclic ring system.", "output": "There is no related enetity." }, { "input": "The structures of both compounds were determined on the basis of spectroscopic analyses, especially 2D NMR and MS.", "output": "There is no related enetity." }, { "input": "A plausible biogenetic pathway of 1 was proposed.", "output": "There is no related enetity." }, { "input": "Schisarisanlactone A ( 1 ) showed significant anti - HIV activity.", "output": "Schisarisanlactone A." }, { "input": "Optimisation of resistant starch II and III levels in durum wheat pasta to reduce in vitro digestibility while maintaining processing and sensory characteristics.", "output": "There is no related enetity." }, { "input": "Foods with elevated levels of resistant starch ( RS ) may have beneficial effects on human health.", "output": "There is no related enetity." }, { "input": "Pasta was enriched with commercial resistant starches ( RSII, Hi Maize (TM) 1043; RSIII, Novelose 330 (TM) ) at 10 %, 20 % and 50 % substitution of semolina for RSII and 10 % and 20 % for RSIII and compared with pasta made from 100 % durum wheat semolina to investigate technological, sensory, in vitro starch digestibility and structural properties.", "output": "There is no related enetity." }, { "input": "The resultant RS content of pasta increased from 1. 9 % to ~ 21 % and was not reduced on cooking.", "output": "There is no related enetity." }, { "input": "Significantly, the results indicate that 10 % and 20 % RSII and RSIII substitution of semolina had no significant effects on pasta cooking loss, texture and sensory properties, with only a minimal reduction in pasta yellowness.", "output": "There is no related enetity." }, { "input": "Both RS types lowered the extent of in vitro starch hydrolysis compared to that of control pasta.", "output": "There is no related enetity." }, { "input": "X - ray diffraction and small - angle scattering verified the incorporation of RS and, compared to the control sample, identified enhanced crystallinity and a changed molecular arrangement following digestion.", "output": "There is no related enetity." }, { "input": "These results can be contrasted with the negative impact on pasta resulting from substitution with equivalent amounts of more traditional dietary fibre such as bran.", "output": "There is no related enetity." }, { "input": "The study suggests that these RS - containing formulations may be ideal sources for the preparation of pasta with reduced starch digestibility.", "output": "There is no related enetity." }, { "input": "Abietane diterpenoids from Isodon lophanthoides var. graciliflorus and their cytotoxicity.", "output": "Abietane, diterpenoids." }, { "input": "Seven new ( 1 - 7 ) and three known ( 8 - 10 ) abietane diterpenoids were isolated from the methanolic extract of the aerial parts of Isodon lophanthoides var. graciliflorus ( Lamiaceae ), a folk Chinese medicine and an herb for functional beverages.", "output": "abietane, diterpenoids." }, { "input": "They were identified as 16 - acetoxylsugiol ( 1 ), graciliflorin E ( 2 ), graciliflorin F ( 3 ), 15 - O - methylgraciliflorin F ( 4 ), 15 - hydroxy - 20 - deoxocarnosol ( 5 ), 3 beta - hydroxysempervirol ( 6 ), 15 - hydroxy - 1 - oxosalvibretol ( 7 ), abieta - 8, 11, 13 - triene - 14, 19 - diol ( 8 ), 6, 12, 15 - trihydroxy - 5, 8, 11, 13 - abietatetraen - 7 - one ( 9 ), and 3 alpha - hinokiol ( 10 ) based on the spectroscopic data including COSY ( correlated spectroscopy ), HMBC ( heteronuclear multiple bond correlation ), and HR - ESI - MS ( high - resolution electrospray ionization mass spectrometry ).", "output": "16 - acetoxylsugiol, graciliflorin E, graciliflorin F, 15 - O - methylgraciliflorin F, 15 - hydroxy - 20 - deoxocarnosol, 3 beta - hydroxysempervirol, 15 - hydroxy - 1 - oxosalvibretol, abieta - 8 , 11 , 13 - triene - 14 , 19 - diol, 6 , 12 , 15 - trihydroxy - 5 , 8 , 11 , 13 - abietatetraen - 7 - one, 3 alpha - hinokiol." }, { "input": "All the compounds except 10 were obtained from I. lophanthoides for the first time.", "output": "There is no related enetity." }, { "input": "Compounds 1, 2, 5, 6, 8, and 9 exhibited in vitro cytotoxicity against A549 ( human lung adenocarcinoma ), MCF - 7 ( human breast adenocarcinoma ), and HeLa ( human cervical carcinoma ) cell lines with the IC ( 50 ) values of 1. 79 - 52. 67 mu M.", "output": "There is no related enetity." }, { "input": "Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone - hydrogel contact lenses.", "output": "timolol." }, { "input": "Glaucoma is the second major cause of blindness in the world after cataract.", "output": "There is no related enetity." }, { "input": "Glaucoma management through eye drops that reduce the intraocular pressure ( IOP ) has major deficiencies including low patient compliance and low bioavailability.", "output": "There is no related enetity." }, { "input": "Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability.", "output": "There is no related enetity." }, { "input": "To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT ( propoxylated glyceryl triacylate ) that contain a glaucoma drug timolol.", "output": "PGT, propoxylated glyceryl triacylate, timolol." }, { "input": "The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol.", "output": "ethanol." }, { "input": "The particle loaded gels can release timolol in phosphate buffered saline ( PBS ) for about a month at room temperature.", "output": "timolol, phosphate." }, { "input": "The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug - polymer chain cleavage, time - dependent drug permeability within the polymeric matrix, etc. may also be important.", "output": "timolol, PGT." }, { "input": "Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading.", "output": "oxygen." }, { "input": "A gel with 5 % particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties.", "output": "timolol." }, { "input": "Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP.", "output": "There is no related enetity." }, { "input": "Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.", "output": "There is no related enetity." }, { "input": "Carboxylesterases ( CEs ) are ubiquitously expressed proteins that are responsible for the detoxification of xenobiotics.", "output": "There is no related enetity." }, { "input": "They tend to be expressed in tissues likely to be exposed to such agents ( e. g., lung and gut epithelia, liver ) and can hydrolyze numerous agents, including many clinically used drugs.", "output": "There is no related enetity." }, { "input": "Due to the considerable structural similarity between cholinesterases ( ChE ) and CEs, we have assessed the ability of a series of ChE inhibitors to modulate the activity of the human liver ( hCE1 ) and the human intestinal CE ( hiCE ) isoforms.", "output": "There is no related enetity." }, { "input": "We observed inhibition of hCE1 and hiCE by carbamate - containing small molecules, including those used for the treatment of Alzheimer ' s disease.", "output": "carbamate." }, { "input": "For example, rivastigmine resulted in greater than 95 % inhibition of hiCE that was irreversible under the conditions used.", "output": "rivastigmine." }, { "input": "Hence, the administration of esterified drugs, in combination with these carbamates, may inadvertently result in decreased hydrolysis of the former, thereby limiting their efficacy.", "output": "carbamates." }, { "input": "Therefore drug: drug interactions should be carefully evaluated in individuals receiving ChE inhibitors.", "output": "There is no related enetity." }, { "input": "Assessing protection against OP pesticides and nerve agents provided by wild - type HuPON1 purified from Trichoplusia ni larvae or induced via adenoviral infection.", "output": "There is no related enetity." }, { "input": "Human paraoxonase - 1 ( HuPON1 ) has been proposed as a catalytic bioscavenger of organophosphorus ( OP ) pesticides and nerve agents.", "output": "organophosphorus." }, { "input": "We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms.", "output": "There is no related enetity." }, { "input": "First, recombinant HuPON1 purified from cabbage loopers ( iPON1; Trichoplusia ni ) was administered to guinea pigs, followed by exposure to at least 2times the median lethal dose ( LD50 ) of the OP nerve agents tabun ( GA ), sarin ( GB ), soman ( GD ), and cyclosarin ( GF ), or chlorpyrifos oxon, the toxic metabolite of the OP pesticide chlorpyrifos.", "output": "tabun, sarin, soman, cyclosarin, chlorpyrifos oxon, chlorpyrifos." }, { "input": "In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then exposed to sequential doses of GD, VX, or ( as reported previously ) diazoxon, the toxic metabolite of the OP pesticide diazinon.", "output": "diazoxon, diazinon." }, { "input": "In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents.", "output": "There is no related enetity." }, { "input": "Together, the results support prior modeling and in vitro activity data which suggest that wild - type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents.", "output": "There is no related enetity." }, { "input": "Seventy - two - hour release formulation of the poorly soluble drug silybin based on porous silica nanoparticles: in vitro release kinetics and in vitro / in vivo correlations in beagle dogs.", "output": "silybin, silica." }, { "input": "The objective of this study was to prepare a 72 h - release formulation of silybin ( 72 h - SLB ) using a combination of solid dispersion, gel matrix and porous silica nanoparticles ( PSNs ) and to investigate the in vitro / in vivo correlations ( IVIVCs ).", "output": "silybin, SLB, silica." }, { "input": "The results of scanning electron microscopy and N ( 2 ) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area ( 385. 89 +/- 1. 12 m ( 2 ) / g ) and a small pore size ( 2. 74 nm on average ).", "output": "There is no related enetity." }, { "input": "The in vitro dissolution profiles of both 72 h - SLB and silybin - loaded PSNs in different concentrations ( 0. 01, 0. 06 and 0. 08M ) of Na ( 2 ) CO ( 3 ) solutions revealed that 0. 06 M Na ( 2 ) CO ( 3 ) solution was the optimal medium in which silybin could be released from 72 h - SLB with first - order release kinetics and from PSNs with Higuchi kinetics.", "output": "SLB, silybin, Na ( 2 ) CO ( 3 ), Na ( 2 ) CO ( 3 ), silybin, SLB." }, { "input": "Furthermore, the IVIVCs of 72 h - SLB and silybin - loaded PSNs in beagle dogs were also established.", "output": "SLB, silybin." }, { "input": "Using 0. 06 M Na ( 2 ) CO ( 3 ) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h - SLB and silybin - loaded PSNs.", "output": "Na ( 2 ) CO ( 3 ), SLB, silybin." }, { "input": "The findings support the fact that the 72 h - SLB ( consisting of solid dispersion, regular gel matrix and PSNs ) together with Na ( 2 ) CO ( 3 ) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.", "output": "SLB, Na ( 2 ) CO ( 3 )." }, { "input": "Zymomonas mobilis culture protects against sepsis by modulating the inflammatory response, alleviating bacterial burden and suppressing splenocyte apoptosis.", "output": "There is no related enetity." }, { "input": "Microorganisms with immunomodulating effects beneficially affect the host organism by improving the microbial equilibrium and balancing the immune system.", "output": "There is no related enetity." }, { "input": "Zymomonas mobilis is reported to have antagonistic properties against yeast and other pathogenic microorganisms in humans and animals.", "output": "There is no related enetity." }, { "input": "This study assessed the effects of Z. mobilis UFPEDA 202 ( 10 ( 9 ) CFU / mL ) cultures on polymicrobial sepsis induced by cecal ligation and puncture ( CLP ).", "output": "There is no related enetity." }, { "input": "The survival of animals subjected to lethal sepsis was evaluated after pre - treatment, post - treatment or a combination of both.", "output": "There is no related enetity." }, { "input": "6h after the induction of sepsis, neutrophil migration, the number of bacteria, myeloperoxidase, TNF - alpha, MCP - 1, and IL - 10 were performed in the peritoneal lavage of animals.", "output": "There is no related enetity." }, { "input": "Histopathological changes in the spleen of animals were evaluated by light microscopy, and apoptosis of splenocytes was analyzed by transmission electron microscopy.", "output": "There is no related enetity." }, { "input": "The results showed that the combination of prophylactic and therapeutic treatment with Z. mobilis increased the survival of animals by 50 % at 96 h after the induction of sepsis.", "output": "There is no related enetity." }, { "input": "There was a reduction in the levels of TNF - alpha and myeloperoxidase ( MPO ) in lung tissue.", "output": "There is no related enetity." }, { "input": "There was also a reduction in the number of viable bacteria in peritoneal fluid.", "output": "There is no related enetity." }, { "input": "However, increases in neutrophil migration and IL - 10 levels were observed.", "output": "There is no related enetity." }, { "input": "The observed levels of MCP - 1 remained similar to the control.", "output": "There is no related enetity." }, { "input": "Histopathology analysis showed a decrease in acute lung injury.", "output": "There is no related enetity." }, { "input": "The group pre - treated with the Z. mobilis culture demonstrated a marked decrease in the number of apoptotic cells in the spleen ( 24 % ).", "output": "There is no related enetity." }, { "input": "This study demonstrates that Z. mobilis cultures increased the survival of animals with severe sepsis.", "output": "There is no related enetity." }, { "input": "This survival was mediated by improvement of neutrophil migration, enhanced activity against pathogenic enteric bacteria and reduced lung injury.", "output": "There is no related enetity." }, { "input": "Involvement of the ANGPTs / Tie - 2 system in ovarian hyperstimulation syndrome ( OHSS ).", "output": "There is no related enetity." }, { "input": "Ovarian hyperstimulation syndrome ( OHSS ) is a disorder associated with ovarian stimulation.", "output": "There is no related enetity." }, { "input": "OHSS features are ovarian enlargement with fluid shifting to the third space.", "output": "There is no related enetity." }, { "input": "Disturbances in the vasculature are considered the main changes that lead to OHSS.", "output": "There is no related enetity." }, { "input": "Our aim was to analyze the levels of angiopoietins 1 and 2 ( ANGPT1 and 2 ) and their soluble and membrane receptors ( s / mTie - 2 ) in follicular fluid ( FF ) and in granulosa - lutein cells culture ( GLCs ) from women at risk of developing OHSS.", "output": "lutein." }, { "input": "We also evaluated the effect of ANGPT1 on endothelial cell migration.", "output": "There is no related enetity." }, { "input": "In ovaries from an OHSS rat model, we analyzed the protein concentration of ANGPTs, their mTie - 2 receptor, and platelet - derived growth factor PDGF - B, - D and PDGFR - beta.", "output": "There is no related enetity." }, { "input": "ANGPT1 levels were increased in both FF and GLCs from women at risk of OHSS.", "output": "There is no related enetity." }, { "input": "Incubation of these FF with an ANGPT1 neutralizing antibody decreased endothelial cell migration.", "output": "There is no related enetity." }, { "input": "In the ovaries of OHSS rat model, mTie - 2 protein levels increased and PDGF - B and - D decreased.", "output": "There is no related enetity." }, { "input": "In summary, these results suggest that ANGPT1 could be another mediator in the development of OHSS.", "output": "There is no related enetity." }, { "input": "Estrogen receptor ESR1 regulates the phospholipase C - inositol phosphate signaling in the hippocampus from rats in proestrous and estrous phases.", "output": "Estrogen, inositol phosphate." }, { "input": "The aim of the present study was to investigate the involvement of estrogen receptors in the activation of phospholipase C ( PLC ) - phosphoinositide hydrolysis in the hippocampus from rats in estrous and proestrous phases.", "output": "estrogen." }, { "input": "17 beta - Estradiol ( E2 ) and ESR1 - selective agonist PPT, but not ESR2 - selective agonist DPN, induced a rapid increase on total [ (3) H ] - inositol phosphate accumulation in the hippocampus from both rats.", "output": "17 beta - Estradiol, PPT, DPN, [ (3) H ] - inositol phosphate." }, { "input": "These effects are mediated by PLC activation, since the inhibition of this protein decreased the total [ (3) H ] - inositol phosphate accumulation.", "output": "[ (3) H ] - inositol phosphate." }, { "input": "The pretreatment with ESR1 and ESR2 antagonist ICI 182, 780, but not with GPER antagonist G - 15, blocked the total [ (3) H ] - inositol phosphate accumulation induced by E2 and PPT, confirming that ESR1 is upstream component regulating this rapid effect.", "output": "ICI 182 , 780, G - 15, [ (3) H ] - inositol phosphate, PPT." }, { "input": "SRC family of protein tyrosine kinases inhibitor PP2 blocked the total [ (3) H ] - inositol phosphate accumulation induced by E2 and PPT in hippocampus, suggesting that ESR1 undergoes translocation from the nuclei to the plasma membrane region via SRC to activate rapid signaling pathways.", "output": "tyrosine, PP2, [ (3) H ] - inositol phosphate, PPT." }, { "input": "Furthermore, the magnitude of the response to E2 and PPT was higher in hippocampus from rats in proestrous than in estrous.", "output": "PPT." }, { "input": "On the other hand, the expression of the ESR1 is higher in hippocampus from rats in estrous than in proestrous, indicating that the regulation of this receptor by estrous cycle does not play a role in the magnitude of the response to E2 and PPT in hippocampus.", "output": "PPT." }, { "input": "In conclusion, our results indicate that E2 activates SRC - mediated translocation of ESR1 to the plasma membrane, which results in the activation of PLC - inositol phosphate signaling pathway in rat hippocampus.", "output": "inositol phosphate." }, { "input": "Thus, these rapid estrogen actions in hippocampus might be a key step mediating cellular events important for learning and memory.", "output": "estrogen." }, { "input": "Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat.", "output": "atrazine." }, { "input": "Atrazine ( ATR ) is used as a pre - and post - emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world.", "output": "Atrazine, ATR." }, { "input": "A recent study in rats has shown that chronic, daily exposure to 10 mg ATR / kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain.", "output": "ATR, dopamine." }, { "input": "In order to evaluate the short - term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague - Dawley rats received six IP injections of 100 mg ATR / kg BW or vehicle over two weeks.", "output": "ATR, monoamine, ATR." }, { "input": "After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn - SOD, Trx - 1, DAR - D ( 1 ), or DAR - D ( 2 ).", "output": "ATR, DOPAC, HVA, Mn." }, { "input": "In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down - regulation of Trx - 1 expression was detected shortly after the ATR treatment.", "output": "monoamine, ATR." }, { "input": "Moreover, in the ventral midbrain, we found that ATR induced a down - regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression.", "output": "ATR." }, { "input": "Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge ( 1 mg / kg ) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems.", "output": "monoamine, ATR, amphetamine, ATR, ATR." }, { "input": "These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed.", "output": "ATR." }, { "input": "Cadmium chelation by frustulins: a novel metal tolerance mechanism in Nitzschia palea ( K u tzing ) W.", "output": "Cadmium." }, { "input": "Smith.", "output": "There is no related enetity." }, { "input": "The ubiquity of diatom distribution, species richness, short generation time, and specific sensitivity to several environmental stressors such as metals, make diatoms particularly useful for scientific studies.", "output": "There is no related enetity." }, { "input": "Anthropogenic activities have increased the concentration of metals in air, soil and water.", "output": "There is no related enetity." }, { "input": "Due to their toxicity and persistent character, the effects of metals on organisms have been extensively studied.", "output": "There is no related enetity." }, { "input": "In this work, the association of cadmium to different extracellular molecules of Nitzschia palea cells was investigated.", "output": "cadmium." }, { "input": "Cells were grown in the absence and presence ( 0. 2 mg l ( - 1 ) ) of cadmium in Chu no. 10 medium.", "output": "cadmium." }, { "input": "Extracellular polysaccharides were extracted, and subsamples were used for polysaccharide and Cd determination.", "output": "Cd." }, { "input": "The frustules were broken mechanically under liquid nitrogen and the intracellular and frustule fractions separated.", "output": "nitrogen." }, { "input": "Frustulins, a protein family found on the outmost frustule layer, constituting a protection coating to environmental stress, were extracted.", "output": "There is no related enetity." }, { "input": "In each fraction proteins were quantified by the BCA method and separated by gel electrophoresis ( SDS - PAGE ).", "output": "There is no related enetity." }, { "input": "Cadmium associated to each fraction was quantified by Inductively Coupled Plasma Mass Spectrometry ( ICP - MS ) analysis.", "output": "Cadmium." }, { "input": "Exposure of Nitzschia palea to cadmium decreased extracellular polysaccharides by 52. 8 % and increased 6 times the amount of frustulins.", "output": "cadmium." }, { "input": "Cadmium was mostly retained extracellularly: 85. 4 % was bound to the frustulin fraction, and 11. 1 % to polysaccharides.", "output": "Cadmium." }, { "input": "The ability of Nitzschia palea to increase the production of frustulins due to the presence of Cd, the extracellular location of this frustulin coating and the ability of these proteins to bind Cd, suggests a new cellular defense mechanism to metals unknown until now.", "output": "Cd, Cd." }, { "input": "Kinetic properties of a novel Fusarium solani ( phospho ) lipase: a monolayer study.", "output": "There is no related enetity." }, { "input": "Using the monomolecular film technique, we studied interfacial properties of Fusarium solani lipase ( FSL ).", "output": "There is no related enetity." }, { "input": "This lipolytic enzyme was found to be unique among the fungal lipases possessing not only a lipase activity but also a high phospholipase one. The FSL was able to hydrolyze dicaprin films at various surface pressures.", "output": "dicaprin." }, { "input": "The surface pressure dependency, the stereospecificity, and the regioselectivity of FSL were performed using optically pure stereoisomers of diglyceride ( 1, 2 - sn - dicaprin and 2, 3 - sn - dicaprin ) and a prochiral isomer ( 1, 3 - sn - dicaprin ) spread as monomolecular films at the air - water interface.", "output": "diglyceride, 1 , 2 - sn - dicaprin, 2 , 3 - sn - dicaprin, 1 , 3 - sn - dicaprin." }, { "input": "The FSL prefers adjacent ester groups of the diglyceride isomers ( 1, 2 - sn - dicaprin and 2, 3 - sn - dicaprin ) at low and high surface pressures.", "output": "ester, diglyceride, 1 , 2 - sn - dicaprin, 2 , 3 - sn - dicaprin." }, { "input": "Furthermore, FSL was found to be markedly stereospecific for the sn - 1 position of the 1, 2 - sn - enantiomer of dicaprin at both low and high surface pressures. Moreover, FSL shows high activities on phospholipids monolayers.", "output": "dicaprin." }, { "input": "However, this enzyme displays high preference to zwitterionic phospholipids compared to the negatively charged ones.", "output": "There is no related enetity." }, { "input": "Transparent nanowire network electrode for textured semiconductors.", "output": "There is no related enetity." }, { "input": "This work presents an inexpensive and easily manufacturable, highly conductive and transparent nanowire network electrode for textured semiconductors.", "output": "There is no related enetity." }, { "input": "It is based on lines of silver nanoparticles transformed into a nanowire network by microwave or furnace sintering.", "output": "silver." }, { "input": "The nanonetwork electrode on crystalline silicon is demonstrated experimentally, with the nanoparticles self - assembling in the valleys between the pyramids of the textured surface.", "output": "silicon." }, { "input": "Optical experiments show that this conductive nanowire network electrode can be essentially ' invisible ' when covered with the conventional anti - reflection coating ( ARC ), and thus could be employed in photovoltaic applications.", "output": "There is no related enetity." }, { "input": "Free energy simulation of helical transitions.", "output": "There is no related enetity." }, { "input": "An umbrella sampling method for the calculation of free energies for helical transitions is presented.", "output": "There is no related enetity." }, { "input": "The method biases structures toward helices of a desired radius and pitch.", "output": "There is no related enetity." }, { "input": "Although computationally complex, the method has negligible overhead in actual applications.", "output": "There is no related enetity." }, { "input": "To illustrate the method, calculations of the helical free energy landscape of several peptides are presented for both the CHARMM and the AMBER force fields.", "output": "There is no related enetity." }, { "input": "Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes.", "output": "testosterone." }, { "input": "Testosterone is a final product of androgenic hormone biosynthesis, and Leydig cells are known to be the primary source of androgens.", "output": "Testosterone." }, { "input": "In the mammalian testis, two distinct populations of Leydig cells, the fetal and the adult Leydig cells, develop sequentially, and these two cell types differ both morphologically and functionally.", "output": "There is no related enetity." }, { "input": "It is well known that the adult Leydig cells maintain male reproductive function by producing testosterone.", "output": "testosterone." }, { "input": "However, it has been controversial whether fetal Leydig cells can produce testosterone, and the synthetic pathway of testosterone in the fetal testis is not fully understood.", "output": "testosterone, testosterone." }, { "input": "In the present study, we generated transgenic mice in which enhanced green fluorescence protein was expressed under the control of a fetal Leydig cell - specific enhancer of the Ad4BP / SF - 1 ( Nr5a1 ) gene.", "output": "There is no related enetity." }, { "input": "The transgene construct was prepared by mutating the LIM homeodomain transcription factor ( LHX9 ) - binding sequence in the promoter, which abolished promoter activity in the undifferentiated testicular cells.", "output": "There is no related enetity." }, { "input": "These transgenic mice were used to collect highly pure fetal Leydig cells.", "output": "There is no related enetity." }, { "input": "Gene expression and steroidogenic enzyme activities in the fetal Leydig cells as well as in the fetal Sertoli cells and adult Leydig cells were analyzed.", "output": "There is no related enetity." }, { "input": "Our results revealed that the fetal Leydig cells synthesize only androstenedione because they lack expression of Hsd17b3, and fetal Sertoli cells convert androstenedione to testosterone, whereas adult Leydig cells synthesize testosterone by themselves.", "output": "androstenedione, androstenedione, testosterone, testosterone." }, { "input": "The current study demonstrated that both Leydig and Sertoli cells are required for testosterone synthesis in the mouse fetal testis.", "output": "testosterone." }, { "input": "Absorption of triphenylmethane dyes Brilliant Blue and Patent Blue through intact skin, shaven skin and lingual mucosa from daily life products.", "output": "triphenylmethane, Brilliant Blue, Patent Blue." }, { "input": "Currently, there is evidence of health risks of triphenylmethane dyes after systemic absorption.", "output": "triphenylmethane." }, { "input": "This paper investigates the fate of Brilliant Blue ( BB ) and Patent Blue ( PB ) after 24 - h in vitro diffusion, firstly through intact and secondly through shaven pig - ear skin ( stored by freezing ) from four leave - on cosmetics under in - use conditions.", "output": "Brilliant Blue, Patent Blue." }, { "input": "Both dyes showed no measurable permeation through intact skin but significant permeation was found through shaven skin.", "output": "There is no related enetity." }, { "input": "From 250 ng / cm ( 2 ) of dye in one applied dose there were found 52 ng / cm ( 2 ) of BB and 91 ng / cm ( 2 ) of PB from ethanol - based after - shave, 39 ng / cm ( 2 ) of BB and 86 ng / cm ( 2 ) of PB from ethanol - free facial - cleanser, 35 ng / cm ( 2 ) of BB and 43 ng / cm ( 2 ) of PB from O / W emulsion, and no amount from W / O emulsion, as available to become systemically absorbed.", "output": "ethanol, ethanol." }, { "input": "Thirdly, the paper focuses on lingual mucosa after licking lollipops.", "output": "There is no related enetity." }, { "input": "Ex vivo porcine tongue dorsum was exposed to human saliva with 15, 000 ng / cm ( 2 ) of dye for 20 min.", "output": "There is no related enetity." }, { "input": "24 - h diffusion resulted in 34 ng / cm ( 2 ) of BB and 86 ng / cm ( 2 ) of PB which can be directly absorbed into the blood system.", "output": "There is no related enetity." }, { "input": "Findings are troubling, particularly with regard to the frequent use of after - shave products by the male population and repeated lollipops licking by children.", "output": "There is no related enetity." }, { "input": "Alleviative effects of resveratrol on nonalcoholic fatty liver disease are associated with up regulation of hepatic low density lipoprotein receptor and scavenger receptor class B type I gene expressions in rats.", "output": "resveratrol." }, { "input": "Lipid metabolic disorders are widely considered to be one of the most critical and basic link in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ).", "output": "There is no related enetity." }, { "input": "The aim of this study was to illustrate the alleviation function of resveratrol ( Res ) on NAFLD and the roles of hepatic fatty acid synthase ( FAS ), low density lipoprotein receptor ( LDLr ), scavenger receptor class B type I ( SR - BI ), and thyroid hormone receptor beta 1 ( TR beta 1 ), which are the key molecules involved in lipid metabolism.", "output": "resveratrol, Res, fatty acid." }, { "input": "Adult male Wistar rats were fed a normal diet or high fat / sucrose diet ( HFS ) with or without resveratrol for 13 weeks.", "output": "sucrose, resveratrol." }, { "input": "HFS induced NAFLD formation and increased the lipids concentrations in serum and livers of rats, while noticeable improvement has been reached by Res intervention.", "output": "Res." }, { "input": "Moreover, Res protected against HFS - induced decrease in hepatic LDLr and SR - BI mRNA and protein expressions, whereas TR beta 1 expressions were impervious with / without Res.", "output": "Res, Res." }, { "input": "Unexpectedly, hepatic FAS gene expressions were markedly diminished in NAFLD rats and were gradually increased by treatment with Res.", "output": "Res." }, { "input": "These data indicate that the alleviative effects of Res on NAFLD are associated with up regulation of hepatic LDLr and SR - BI gene expressions, which provide new insights into the pharmacological targets of Res in the prevention of NAFLD.", "output": "Res, Res." }, { "input": "Consumption of tomato products is associated with lower blood mercury levels in Inuit preschool children.", "output": "mercury." }, { "input": "Some evidence suggests that various diet components and nutrients, including vegetables, fruit and food - derived antioxidants, could mitigate contaminant exposure and / or adverse health effects of contaminants.", "output": "There is no related enetity." }, { "input": "To examine the effect of the consumption of tomato products on blood mercury levels in Inuit preschool children, 155 Inuit children ( 25. 0 +/- 9. 1months ) were recruited from 2006 - 2008 in Nunavik childcare centers ( northern Qu e bec, Canada ).", "output": "mercury." }, { "input": "Food frequency questionnaires were completed at home and at the childcare center, and total blood mercury concentration was measured by inductively coupled plasma - mass spectrometry.", "output": "mercury." }, { "input": "Multivariate regression analysis was performed after multiple imputation.", "output": "There is no related enetity." }, { "input": "The median blood concentration of mercury was 9. 5nmol / L.", "output": "mercury." }, { "input": "Age, duration of breastfeeding, annual consumption frequency of seal meat, and monthly consumption frequency of tomato products were significant predictors of blood mercury levels, whereas annual consumption frequencies of beluga muktuk, walrus, Arctic char, and caribou meat were not.", "output": "mercury." }, { "input": "Each time a participant consumed tomato products during the month before the interview was associated with a 4. 6 % lower blood mercury level ( p = 0. 0005 ).", "output": "mercury." }, { "input": "All other significant predictors in the model were positively associated with blood mercury levels.", "output": "mercury." }, { "input": "Further studies should explore interactions between consumption of healthy store - bought foods available in Arctic regions and contaminant exposure.", "output": "There is no related enetity." }, { "input": "Conjunctival modifications induced by medical and surgical therapies in patients with glaucoma.", "output": "There is no related enetity." }, { "input": "Lowering intra - ocular pressure, either medically or surgically, is the proven strategy to control glaucoma, though profound changes to the ocular surface and conjunctiva are caused.", "output": "There is no related enetity." }, { "input": "Toxicity and allergy initiated by medical therapy induce modifications, which progressively worsen with the length of treatment and number of drugs.", "output": "There is no related enetity." }, { "input": "Conjunctival changes lead to symptoms of ocular surface disease, reduced quality of life, reduced therapeutic compliance and increased risk of surgical failure.", "output": "There is no related enetity." }, { "input": "Surgery modifies conjunctiva by inducing bleb formation in fistulizing techniques, and by activating secondary aqueous humour outflow pathways, such as trans - scleral routes, in both filtration and bleb - less approaches.", "output": "There is no related enetity." }, { "input": "The use of unpreserved medications, limitation of intra - operative conjunctival damage and development of bleb - less surgery are advisable.", "output": "There is no related enetity." }, { "input": "Structure - based design of flavone derivatives as c - myc oncogene down - regulators.", "output": "flavone." }, { "input": "Based on molecular docking analysis of complexes between flavone and the c - myc G - quadruplex, we designed and screened 30 flavone derivatives containing various side chains that could potentially form interactions with the G - quadruplex grooves.", "output": "flavone, flavone." }, { "input": "As a proof - of - concept, the highest - scoring flavone derivatives containing cationic pyridinium side chains were synthesized and their interactions with the c - myc G - quadruplex were examined using a PCR - stop assay.", "output": "flavone, pyridinium." }, { "input": "The stabilizing effects of the flavone derivatives were found to be selective towards the c - myc G - quadruplex over other biologically relevant G - quadruplex structures, such as the human telomeric sequence ( HTS ).", "output": "flavone." }, { "input": "The interaction between the most potent compound of the series and the c - myc G - quadruplex was examined in depth using UV - Vis titration, molecular modeling and CD spectroscopy.", "output": "There is no related enetity." }, { "input": "Our results suggest that in addition to stabilizing the c - myc G - quadruplex, the flavone derivatives were capable of inducing the formation of the G - quadruplex structure even in the absence of monovalent cations.", "output": "flavone." }, { "input": "The flavone derivatives were found to be potent inhibitors of c - myc promoters within the cellular environment and displayed promising cytotoxic behavior against human cancer cell lines.", "output": "flavone." }, { "input": "Epidemiology and clinical effects of hump - nosed pit viper ( Genus: Hypnale ) envenoming in Sri Lanka.", "output": "There is no related enetity." }, { "input": "Hump - nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in Sri Lanka.", "output": "There is no related enetity." }, { "input": "Although there are many reports of local effects, coagulopathy and acute kidney injury, it remains unclear how frequent these clinical effects are and therefore the medical importance of this snake genus.", "output": "There is no related enetity." }, { "input": "The genus has been recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of Southern India, and the two endemic species to Sri Lanka, Hypnale zara and Hypnale nepa.", "output": "There is no related enetity." }, { "input": "This was a prospective hospital - based clinical study of definite Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals.", "output": "There is no related enetity." }, { "input": "There were 114 patients included and all snakes were correctly identified by hospital staff as Hypnale spp.", "output": "There is no related enetity." }, { "input": "Of these, 93 snakes were identified as H. hypnale by an expert, 16 as H. zara and five as H. nepa.", "output": "There is no related enetity." }, { "input": "Most bites occurred on the lower limbs in the daytime.", "output": "There is no related enetity." }, { "input": "There was no difference in the clinical effects between the three species.", "output": "There is no related enetity." }, { "input": "Pain and fang marks were present in all patients, 101 had local swelling and only 16 ( 14 % ) developed extensive local swelling that spread proximally and involved more than half of the bitten limb.", "output": "There is no related enetity." }, { "input": "Systemic symptoms occurred in 18 patients; four patients had an abnormal 20 min whole blood clotting test and one patient developed an acute kidney injury that required haemodialysis.", "output": "There is no related enetity." }, { "input": "All patients were discharged alive with a median length of stay of 2 days.", "output": "There is no related enetity." }, { "input": "This study confirms that hump - nosed viper bites cause only minor effects in most cases.", "output": "There is no related enetity." }, { "input": "Future studies need to undertake formal coagulation studies and identify important early indicators of renal impairment.", "output": "There is no related enetity." }, { "input": "Induction of nuclear anomalies in exfoliated buccal cells of coca chewers: results of a field study.", "output": "There is no related enetity." }, { "input": "The leaves of coca ( Erythroxylum coca var. coca ), a South American shrub which contains cocaine, other alkaloids and phenolics are widely used by indigenous populations of the Andes.", "output": "cocaine." }, { "input": "It is currently not known if coca consumption causes genotoxic effects in humans.", "output": "There is no related enetity." }, { "input": "This information is important to predict potential long - term toxic effects such as cancer induction.", "output": "There is no related enetity." }, { "input": "Therefore, the buccal cytome assay was used to analyze oral cells from 45 uni - and bilateral chewers and 23 controls living in the Altiplano of the Peruvian Andes.", "output": "There is no related enetity." }, { "input": "In total, 123, 471 cells were evaluated from chewers and 57, 916 from controls.", "output": "There is no related enetity." }, { "input": "Information concerning the consumption levels and habits and also use of lime were collected with questionnaires.", "output": "There is no related enetity." }, { "input": "Chewing of the leaves did not induce nuclear anomalies reflecting genetic damage such as micronuclei ( MNi ) and nuclear buds; in the highest exposure group ( but not in the overall group ) even a significant decrease in the frequencies of cells with MNi ( by 64 % ) was observed.", "output": "There is no related enetity." }, { "input": "However, we found significantly elevated levels of other nuclear anomalies ( karyorrhexis and karyolysis ) which reflect cytotoxic effects in the coca users.", "output": "There is no related enetity." }, { "input": "The frequencies of these anomalies increased with the daily consumption and when lime was used to improve the release of the alkaloids.", "output": "There is no related enetity." }, { "input": "In contrast to other chewing habits ( betel, tobacco and khat ), consumption of coca leaves does not induce genetic instability in cells from the oral cavity and our findings indicate that no adverse health effects take place in chewers which are associated with DNA damage.", "output": "There is no related enetity." }, { "input": "However, the significant increase in certain anomalies shows that acute toxic effects are caused by coca consumption.", "output": "There is no related enetity." }, { "input": "Characterization of substituted phenylpropylamides as highly selective agonists at the melatonin MT2 receptor.", "output": "phenylpropylamides, melatonin." }, { "input": "Melatonin is a widely distributed hormone that regulates several major physiological processes, including the circadian rhythm and seasonal adaptation.", "output": "Melatonin." }, { "input": "The two subtypes of mammalian G protein - coupled melatonin receptors are primarily responsible for mediating the actions of melatonin.", "output": "melatonin." }, { "input": "Because synthetic melatonin agonists have considerable therapeutic potentials in modulating insomnia and circadian - related sleep disorders, it is highly desirable to develop subtype - selective melatoninergic compounds.", "output": "melatonin." }, { "input": "The pharmacological potencies of a series of substituted N - [ 3 - ( 3 - methoxyphenyl ) propyl ] amides towards human melatonin MT ( 1 ) and MT ( 2 ) receptors were evaluated by the FLIPR high - throughput screening assay, whilst their subtype - selectivity was subsequently verified with ERK phosphorylation and cAMP assays.", "output": "N - [ 3 - ( 3 - methoxyphenyl ) propyl ] amides, melatonin, cAMP." }, { "input": "Structure - activity relationship analysis of highly potent subtype - selective ligands ( MT ( 2 ) EC ( 50 ) 10 - 90 pM ) revealed that a benzyloxyl substituent incorporated at C6 position of the 3 - methoxyphenyl ring dramatically enhanced the MT ( 2 ) potency and at the same time decreased MT ( 1 ) potency.", "output": "benzyloxyl, 3 - methoxyphenyl." }, { "input": "Incorporation of structural moieties conferring the subtype selectivity produced several extremely potent MT ( 2 ) - selective ligands.", "output": "There is no related enetity." }, { "input": "The most potent subtype - selective ligand, 2q had a substantially higher potency for MT ( 2 ) receptor than melatonin for elevation of [ Ca ( 2 + ) ] i and inhibition of forskolin - elevated cAMP.", "output": "melatonin, Ca ( 2 + )." }, { "input": "Representative MT ( 2 ) - selective ligands also induced ERK phosphorylation in both recombinant and native cell lines, and no cross - reactivity to 17 other GPCRs could be detected.", "output": "There is no related enetity." }, { "input": "These ligands represent invaluable tools for delineating the functional roles of distinct melatonin receptor subtypes and are viable candidates for drug development.", "output": "melatonin." }, { "input": "Is poor research the cause of the declining productivity of the pharmaceutical industry?", "output": "There is no related enetity." }, { "input": "An industry in need of a paradigm shift.", "output": "There is no related enetity." }, { "input": "For the past 20 years target - based drug discovery has been the main research paradigm used by the pharmaceutical industry and billions of dollars have been invested into this approach.", "output": "There is no related enetity." }, { "input": "However, recent industry data strongly indicate that the target - based approach is not an effective drug discovery paradigm and is likely to be the cause of the productivity crisis the industry is experiencing.", "output": "There is no related enetity." }, { "input": "However, from a theoretical and scientific perspective the target - based approach appears sound, so why is it not more successful?", "output": "There is no related enetity." }, { "input": "The purpose of this paper is first to analyse the real - life implementation of the target - based approach to identify possible reasons for the high failure rate and second to suggest changes to the drug discovery approach, which can improve productivity.", "output": "There is no related enetity." }, { "input": "Large, chemically diverse dataset of logP measurements for benchmarking studies.", "output": "There is no related enetity." }, { "input": "Lipophilicity is a crucial parameter in drug development since it impacts both ADME properties and target affinity of drug candidates.", "output": "There is no related enetity." }, { "input": "In early drug discovery stage, accurate tools for logP prediction are highly desired.", "output": "There is no related enetity." }, { "input": "Many calculation methods were developed to aid pharmaceutical scientists in drug research; however almost all suffer from insufficient accuracy and variation of performance in several regions of the chemical space associated with new chemical entities.", "output": "There is no related enetity." }, { "input": "The low predictive power of existing software packages can be explained by limited availability and / or variable quality of experimental logP values associated with training set used, which stem from various protocols and poorly cover chemical space.", "output": "There is no related enetity." }, { "input": "In this study, a dataset of 1000 diverse test compounds out of 4. 5 million was generated; logP values of 759 purchasable compounds ( 46 % non - ionizable, 30 % basic, 17 % acidic, 0. 5 % zwitterionic and 6. 5 % ampholytes ) from this selected set were experimentally determined by UHPLC followed by UV detection or MS detection when necessary.", "output": "There is no related enetity." }, { "input": "Finally, a data collection of 707 validated logP values ranging from 0. 30 to 7. 50 is now available for benchmarking of existing and development of new approaches to predict octanol / water partition coefficients of chemical compounds.", "output": "octanol." }, { "input": "Discovery of novel cannabinoid receptor ligands by a virtual screening approach: further development of 2, 4, 6 - trisubstituted 1, 3, 5 - triazines as CB2 agonists.", "output": "2 , 4 , 6 - trisubstituted 1 , 3 , 5 - triazines." }, { "input": "3D ligand - based virtual screening was employed to identify novel scaffolds for cannabinoid receptor ligand development.", "output": "There is no related enetity." }, { "input": "A total of 112 compounds with diverse structures were purchased from commercial vendors.", "output": "There is no related enetity." }, { "input": "12 CB1 receptor antagonists / inverse agonists and 10 CB2 receptor agonists were identified in vitro.", "output": "There is no related enetity." }, { "input": "One of the CB2 agonists, N - cyclopentyl - 4 - ethoxy - 6 - ( 4 - methylpiperidin - 1 - yl ) - 1, 3, 5 - triazin - 2 - amine ( 19, - logEC ( 50 ) = 7. 5, E ( max ) = 255 % ) was selected for further development.", "output": "N - cyclopentyl - 4 - ethoxy - 6 - ( 4 - methylpiperidin - 1 - yl ) - 1 , 3 , 5 - triazin - 2 - amine." }, { "input": "As far as we are aware, the compound ' s 1, 3, 5 - triazine scaffold represents a new core structure for CB2 agonists.", "output": "1 , 3 , 5 - triazine." }, { "input": "A library of fifty - seven 2, 4, 6 - trisubstituted - 1, 3, 5 - triazines was created to clarify the structure - activity relationship study of the analogs.", "output": "2 , 4 , 6 - trisubstituted - 1 , 3 , 5 - triazines." }, { "input": "In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor.", "output": "dolutegravir." }, { "input": "Dolutegravir ( DTG; S / GSK1349572 ) is a potent HIV - 1 integrase inhibitor with a distinct resistance profile and a once - daily dose regimen that does not require pharmacokinetic boosting.", "output": "Dolutegravir, DTG, S / GSK1349572." }, { "input": "This work investigated the in vitro drug transport and metabolism of DTG and assessed the potential for clinical drug - drug interactions.", "output": "DTG." }, { "input": "DTG is a substrate for the efflux transporters P - glycoprotein ( Pgp ) and human breast cancer resistance protein ( BCRP ).", "output": "DTG." }, { "input": "Its high intrinsic membrane permeability limits the impact these transporters have on DTG ' s intestinal absorption.", "output": "DTG." }, { "input": "UDP - glucuronosyltransferase ( UGT ) 1A1 is the main enzyme responsible for the metabolism of DTG in vivo, with cytochrome P450 ( P450 ) 3A4 being a notable pathway and UGT1A3 and UGT1A9 being only minor pathways.", "output": "UDP, DTG." }, { "input": "DTG demonstrated little or no inhibition ( IC ( 50 ) values > 30 mu M ) in vitro of the transporters Pgp, BCRP, multidrug resistance protein 2, organic anion transporting polypeptide 1B1 / 3, organic cation transporter ( OCT ) 1, or the drug metabolizing enzymes CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, or 2B7.", "output": "DTG." }, { "input": "Further, DTG did not induce CYP1A2, 2B6, or 3A4 mRNA in vitro using human hepatocytes.", "output": "DTG." }, { "input": "DTG does inhibit the renal OCT2 ( IC ( 50 ) = 1. 9 mu M ) transporter, which provides a mechanistic basis for the mild increases in serum creatinine observed in clinical studies.", "output": "DTG, creatinine." }, { "input": "These in vitro studies demonstrate a low propensity for DTG to be a perpetrator of clinical drug interactions and provide a basis for predicting when other drugs could result in a drug interaction with DTG.", "output": "DTG, DTG." }, { "input": "Ligand - dependent actions of the vitamin D receptor are required for activation of TGF - beta signaling during the inflammatory response to cutaneous injury.", "output": "vitamin D." }, { "input": "The vitamin D receptor ( VDR ) has both 1, 25 - dihydroxyvitamin D - dependent and - independent actions in the epidermis.", "output": "vitamin D, 1 , 25 - dihydroxyvitamin D." }, { "input": "Ligand - dependent actions of the VDR have been shown to promote keratinocyte differentiation and to regulate formation of the epidermal barrier.", "output": "There is no related enetity." }, { "input": "In contrast, the actions of the VDR that regulate postmorphogenic hair cycling do not require 1, 25 - dihydroxyvitamin D.", "output": "1 , 25 - dihydroxyvitamin D." }, { "input": "The VDR also has immunomodulatory actions that are dependent on its ligand, 1, 25 - dihydroxyvitamin D.", "output": "1 , 25 - dihydroxyvitamin D." }, { "input": "To determine whether the ligand - dependent or - independent actions of the VDR regulate the inflammatory response to cutaneous injury, studies were performed in control, VDR knockout, and vitamin D - deficient mice.", "output": "vitamin D." }, { "input": "These investigations demonstrate that absence of receptor or ligand impairs the dermal response to cutaneous injury.", "output": "There is no related enetity." }, { "input": "Although neutrophil recruitment is not affected, the absence of VDR signaling leads to defects in macrophage recruitment and granulation tissue formation.", "output": "There is no related enetity." }, { "input": "Studies performed to identify the molecular basis for this phenotype demonstrate that absence of the VDR, or its ligand, impairs TGF - beta signaling in the dermis, characterized by decreased expression of monocyte chemotactic protein - 1 and reduced phosphorylation of phosphorylated Smad - 3 as well as attenuated phosphorylated Smad - 3 phosphorylation in response to TGF - beta in primary dermal fibroblasts lacking the VDR.", "output": "There is no related enetity." }, { "input": "Thus, these data demonstrate that the liganded VDR interacts with the TGF - beta signaling pathway to promote the normal inflammatory response to cutaneous injury.", "output": "There is no related enetity." }, { "input": "Mechanical activation of CaO - based adsorbents for CO ( 2 ) capture.", "output": "CaO, CO ( 2 )." }, { "input": "The reversible cycling of CaO adsorbents to CaCO ( 3 ) for high - temperature CO ( 2 ) capture is substantially improved by mechanical treatment.", "output": "CaO, CaCO ( 3 ), CO ( 2 )." }, { "input": "The mechanical milling intensity and conditions of grinding ( e. g., wet vs. dry, planetary vs. vibratory milling ) were determined to be the main factors that control the effectiveness of the mechanochemical synthesis to enhance the recycling stability of the sorbents prepared.", "output": "There is no related enetity." }, { "input": "In addition, MgO was used as an example of an inert binder to help mitigate CaCO ( 3 ) sintering.", "output": "MgO, CaCO ( 3 )." }, { "input": "Wet planetary milling of MgO into CaCO ( 3 ) allowed efficient particle size reduction and the effective dispersion of MgO throughout the particles.", "output": "MgO, CaCO ( 3 ), MgO." }, { "input": "Wet planetary milling yielded the most stable sorbents during 50 cycles of carbonation - calcination.", "output": "There is no related enetity." }, { "input": "Synthesis and evaluation of 3, 4 - dihydropyrimidin - 2 ( 1H ) - ones as sodium iodide symporter inhibitors.", "output": "3 , 4 - dihydropyrimidin - 2 ( 1H ) - ones, sodium iodide." }, { "input": "The sodium iodide symporter ( NIS ) is responsible for the accumulation of iodide in the thyroid gland.", "output": "sodium iodide, iodide." }, { "input": "This transport process is involved in numerous thyroid dysfunctions and is the basis for human contamination in the case of exposure to radioactive iodine species.", "output": "iodine." }, { "input": "4 - Aryl - 3, 4 - dihydropyrimidin - 2 ( 1H ) - ones were recently discovered by high - throughput screening as the first NIS inhibitors.", "output": "4 - Aryl - 3 , 4 - dihydropyrimidin - 2 ( 1H ) - ones." }, { "input": "Described herein are the synthesis and evaluation of 115 derivatives with structural modifications at five key positions on the pyrimidone core.", "output": "pyrimidone." }, { "input": "This study provides extensive structure - activity relationships for this new class of inhibitors that will serve as a basis for further development of compounds with in vivo efficacy and adequate pharmacokinetic properties.", "output": "There is no related enetity." }, { "input": "In addition, the SAR investigation provided a more potent compound, which exhibits an IC ( 50 ) value of 3. 2 nM in a rat thyroid cell line ( FRTL5 ).", "output": "There is no related enetity." }, { "input": "Silk fibroin / hyaluronic acid 3D matrices for cartilage tissue engineering.", "output": "There is no related enetity." }, { "input": "In spite of commercially available products, the complete and sustained repair of damaged articular cartilage still presents various challenges.", "output": "There is no related enetity." }, { "input": "Among biomaterials proposed for cartilage repair, silk fibroin ( SF ) has been recently proposed as a material template for porous scaffolds cultured with chondrocytes and investigated in static and dynamic conditions.", "output": "There is no related enetity." }, { "input": "In addition to fibroin - based constructs, literature has reported that the combination of hyaluronic acid ( HA ) with other scaffold materials can protect the chondral phenotype and the cells in vitro response to the scaffold.", "output": "There is no related enetity." }, { "input": "In this study, the effect of the addition of HA on the physical properties of SF sponges, with and without cross - linking with genipin, was investigated.", "output": "There is no related enetity." }, { "input": "Salt - leached scaffolds were characterized in terms of morphology and structural and physical properties, as well as mechanical performance.", "output": "There is no related enetity." }, { "input": "Un - cross - linked sponges resulted in the physical separation of highly hydrophilic HA from the SF, while cross - linking prevented this phenomenon, resulting in a homogeneous blend.", "output": "There is no related enetity." }, { "input": "The presence of HA also influenced fibroin crystallinity and tended to decrease the cross - linking degree of the scaffolds when compared to the pure SF material.", "output": "There is no related enetity." }, { "input": "Mechanisms of hepatocellular toxicity associated with dronedarone - - a comparison to amiodarone.", "output": "dronedarone, amiodarone." }, { "input": "Dronedarone is a new antiarrhythmic drug with an amiodarone - like benzofuran structure.", "output": "Dronedarone, amiodarone, benzofuran." }, { "input": "Shortly after its introduction, dronedarone became implicated in causing severe liver injury.", "output": "dronedarone." }, { "input": "Amiodarone is a well - known mitochondrial toxicant.", "output": "Amiodarone." }, { "input": "The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone.", "output": "dronedarone, amiodarone." }, { "input": "We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h.", "output": "There is no related enetity." }, { "input": "After exposure of primary hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused cytotoxicity and apoptosis starting at 20 and 50 micro M, respectively.", "output": "dronedarone, amiodarone." }, { "input": "The cellular ATP content started to decrease at 20 micro M for both drugs, suggesting mitochondrial toxicity.", "output": "ATP." }, { "input": "Inhibition of the respiratory chain required concentrations of ~ 10 micro M and was caused by an impairment of complexes I and II for both drugs.", "output": "There is no related enetity." }, { "input": "In parallel, mitochondrial accumulation of reactive oxygen species ( ROS ) was observed.", "output": "oxygen." }, { "input": "In isolated rat liver mitochondria, acute treatment with dronedarone decreased the mitochondrial membrane potential, inhibited complex I, and uncoupled the respiratory chain.", "output": "dronedarone." }, { "input": "Furthermore, in acutely treated rat liver mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit mitochondrial beta - oxidation at 10 micro M and amiodarone at 20 micro M.", "output": "dronedarone, amiodarone." }, { "input": "Similar to amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial respiratory chain and of beta - oxidation both acutely and after exposure for 24h.", "output": "amiodarone, dronedarone." }, { "input": "Inhibition of mitochondrial function leads to accumulation of ROS and fatty acids, eventually leading to apoptosis and / or necrosis of hepatocytes.", "output": "fatty acids." }, { "input": "Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in vivo.", "output": "There is no related enetity." }, { "input": "Dioxin inhibits zebrafish epicardium and proepicardium development.", "output": "Dioxin." }, { "input": "Embryonic exposure to the environmental contaminant and aryl hydrocarbon receptor agonist, 2, 3, 7, 8 - tetrachlorodibenzo - p - dioxin ( TCDD, dioxin ), disrupts cardiac development and function in fish, birds, and mammals.", "output": "aryl hydrocarbon, 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin, TCDD, dioxin." }, { "input": "In zebrafish, the temporal window of sensitivity to the cardiotoxic effects of TCDD coincides with epicardium formation.", "output": "TCDD." }, { "input": "We hypothesized that this TCDD - induced heart failure results from disruption of epicardial development.", "output": "TCDD." }, { "input": "To determine whether embryonic TCDD exposure inhibits epicardium and proepicardium ( PE ) development in zebrafish, we used histology and fluorescence immunocytochemistry to examine the epicardium formation in fish exposed to TCDD.", "output": "TCDD, TCDD." }, { "input": "TCDD exposure prevented epicardium formation.", "output": "TCDD." }, { "input": "Using live imaging and in situ hybridization, we found that TCDD exposure blocked the formation of the PE cluster.", "output": "TCDD." }, { "input": "In situ hybridization experiments showed that TCDD exposure also prevented the expression of the PE marker tcf21 at the site where the PE normally forms.", "output": "TCDD." }, { "input": "TCDD also inhibited expansion of the epicardial layer across the developing heart: Exposure after PE formation was completed prevented further expansion of the epicardium.", "output": "TCDD." }, { "input": "However, TCDD exposure did not affect epicardial cells already present.", "output": "TCDD." }, { "input": "Because TCDD blocks epicardium formation, but is not directly toxic to the epicardium once complete, we propose that inhibition of epicardium formation can account for the window of sensitivity to TCDD cardiotoxicity in developing zebrafish.", "output": "TCDD, TCDD." }, { "input": "Epicardium development is crucial to heart development.", "output": "There is no related enetity." }, { "input": "Loss of this layer during development may account for most if not all of the TCDD - induced cardiotoxicity in zebrafish.", "output": "TCDD." }, { "input": "Protein - size molecularly imprinted polymer nanogels as synthetic antibodies, by localized polymerization with multi - initiators.", "output": "There is no related enetity." }, { "input": "A new approach is proposed for the synthesis of molecularly imprinted polymers ( MIPs ) ( synthetic antibodies ) as soluble nanogels with sizes close to the size of real antibodies.", "output": "There is no related enetity." }, { "input": "To imprint a molecular memory in particles consisting of only a few polymer chains, an initiator carrying multiple iniferter moieties is used.", "output": "There is no related enetity." }, { "input": "This allows for the simultaneous initiation of several polymer chains, and yields molecularly imprinted nanogels ( 17 nm, molecular weight ( MW ) = 97 kDa ) with good affinity and selectivity for the target.", "output": "There is no related enetity." }, { "input": "A novel matrix for the short - term storage of cells: utility in drug metabolism and drug transporter studies with rat, dog and human hepatocytes.", "output": "There is no related enetity." }, { "input": "1. The SureTran (TM) matrix is a novel method facilitating short - term maintenance of fresh primary hepatocyte cellular function and offers the potential use of primary cells \" as fresh \" for several days post isolation.", "output": "There is no related enetity." }, { "input": "In the study presented, the maintenance of several key phase I and II drug metabolizing enzyme and drug transporter activities is demonstrated with rat and dog hepatocytes preserved for up to 7 days after cell isolation.", "output": "There is no related enetity." }, { "input": "2. Intrinsic clearance values were determined for 60 new chemical entities using rat hepatocytes freshly isolated at AstraZeneca and rat hepatocytes prepared at the facilities of Abcellute Ltd ( SureTran (TM) purveyors ), stored and incubated 24 hours after isolation.", "output": "There is no related enetity." }, { "input": "A very good correspondence in the intrinsic clearance values underlines the utility of the cell maintenance matrix.", "output": "There is no related enetity." }, { "input": "3. For human hepatocytes many of the enzyme activities assayed were well maintained for 7 days of storage but some declined to below 50 % of initial values between day 4 and 7 of storage.", "output": "There is no related enetity." }, { "input": "Human OATP1B1 activity was only determined with one batch and declined to 51 % of the initial test value by day 4 and further down to 35 % by day 7.", "output": "There is no related enetity." }, { "input": "Influence of resveratrol on rheumatoid fibroblast - like synoviocytes analysed with gene chip transcription.", "output": "resveratrol." }, { "input": "Rheumatoid arthritis ( RA ) is a chronic, systemic autoimmune disease that primarily attacks joints and is therefore a common cause of chronic disability and articular destruction.", "output": "There is no related enetity." }, { "input": "The hyperplastic growth of RA - fibroblast - like synoviocytes ( FLSs ) and their resistance against apoptosis are considered pathological hallmarks of RA.", "output": "There is no related enetity." }, { "input": "The natural antioxidant resveratrol is known for its antiproliferative and pro - apoptotic properties.", "output": "resveratrol." }, { "input": "This study investigated the effect of resveratrol on RA - FLS.", "output": "resveratrol." }, { "input": "RA - FLS were isolated from the synovium of 10 RA patients undergoing synovectomy or joint replacement surgery.", "output": "There is no related enetity." }, { "input": "RA - FLS were first stressed by pre - incubation with interleukin 1beta ( IL - 1 beta ) and then treated with 100 mu M resveratrol for 24h.", "output": "resveratrol." }, { "input": "In order to evaluate the influence of resveratrol on the transcription of genes, a Gene Chip Human Gene 1. 0 ST Array was applied.", "output": "resveratrol." }, { "input": "In addition, the effect of dexamethasone on proliferation and apoptosis of RA - FLS was compared with that of resveratrol.", "output": "dexamethasone, resveratrol." }, { "input": "Gene array analysis showed highly significant effects of resveratrol on the expression of genes involved in mitosis, cell cycle, chromosome segregation and apoptosis.", "output": "resveratrol." }, { "input": "qRT - PCR, caspase - 3 / 7 and proliferation assays confirmed the results of gene array analysis.", "output": "There is no related enetity." }, { "input": "In comparison, dexamethasone showed little to no effect on reducing cell proliferation and apoptosis.", "output": "dexamethasone." }, { "input": "Our in vitro findings point towards resveratrol as a promising new therapeutic approach for local intra - articular application against RA, and further clinical studies will be necessary.", "output": "resveratrol." }, { "input": "Dietary exposure to mycotoxins and health risk assessment in the second French total diet study.", "output": "There is no related enetity." }, { "input": "Mycotoxins are produced in plants by micro - fungi species, and naturally contaminated the food chain.", "output": "There is no related enetity." }, { "input": "In the second French total diet study ( TDS ), mycotoxins were analyzed in 577 food samples collected in mainland France to be representative of the population diet and prepared ( ( as consumed ) ).", "output": "There is no related enetity." }, { "input": "Highest mean concentrations were found in wheat and cereal - based products ( bread, breakfast cereals, pasta, pastries, pizzas and savoury pastries ... ).", "output": "There is no related enetity." }, { "input": "Exposure of adult and child populations was assessed by combining national consumption data with analytical results, using lowerbound ( LB ) and upperbound ( UB ) assumptions for left - censorship management.", "output": "There is no related enetity." }, { "input": "Individual exposures were compared with available health - based guidance values ( HBGV ).", "output": "There is no related enetity." }, { "input": "Only the exposure to deoxynivalenol ( DON ) and its acetylated derivatives was found to significantly exceed the HBGV in LB in adults ( 0. 5 % [ 0. 1; 0. 8 ] ) and children ( 5 % [ 4; 6 ] ).", "output": "deoxynivalenol, DON." }, { "input": "HBGV was exceeded in UB only for T - 2 and HT - 2 toxins by, respectively, 0. 2 % [ 0. 02; 0. 05 ] and 4 % [ 3; 5 ] of adults, and 11 % [ 9; 12 ] and 35 % [ 32; 37 ] of children.", "output": "There is no related enetity." }, { "input": "Although the exposures assessed were generally lower than the previous French TDS, the results indicated a health concern for trichothecenes and a need to reduce dietary exposure as well as analytical limits.", "output": "trichothecenes." }, { "input": "The effect of copper on different phototrophic microorganisms determined in vivo and at cellular level by confocal laser microscopy.", "output": "copper." }, { "input": "Microbial mats are coastal ecosystems that consist mainly of cyanobacteria, primary producers in these habitats that play an important role in stabilising delta sediments.", "output": "There is no related enetity." }, { "input": "However, these ecosystems are subject to various kinds of pollution, including metal contamination, placing their survival at risk.", "output": "There is no related enetity." }, { "input": "Among heavy metals, copper is an essential metal at low doses and toxic at high doses.", "output": "copper." }, { "input": "This metal is present in different pesticides used in rice production, a thriving agro - industry in the Ebro Delta ( Spain ).", "output": "There is no related enetity." }, { "input": "For several years, our group has been studying the Ebro Delta microbial mats and has developed a method for determining the effect that metals cause on cyanobacteria populations.", "output": "There is no related enetity." }, { "input": "This method is based on confocal laser microscopy coupled to a spectrofluorometer, which rapidly provides simultaneous three - dimensional information on photosynthetic microorganisms and their fluorescence spectra profiles.", "output": "There is no related enetity." }, { "input": "The current study determines the copper effect on different photosynthetic microorganisms from culture collection ( Chroococcus sp. PCC 9106 and Spirulina sp. PCC 6313 ) and isolated from the environment ( Microcoleus - like and the microalga DE2009 ).", "output": "copper." }, { "input": "Comparing all results obtained it can be observed that the minimum dose of Cu that is capable of significantly altering chlorophyll a ( chl a ) fluorescence intensity were 1 x 10 ( - 7 ) M in Chroococcus sp.", "output": "Cu, chlorophyll a, chl a." }, { "input": "PCC 9106; 1 x 10 ( - 7 ) M in Spirulina sp.", "output": "There is no related enetity." }, { "input": "PCC 6313; 3 x 10 ( - 7 ) M in Microcoleus and 5 x 10 ( - 6 ) M in the microalga DE2009.", "output": "There is no related enetity." }, { "input": "Moreover, the sensitivity of the technique used was 1 x 10 ( - 7 ) M.", "output": "There is no related enetity." }, { "input": "New results on formaldehyde: the 2nd International Formaldehyde Science Conference ( Madrid, 19 - 20 April 2012 ).", "output": "formaldehyde, Formaldehyde." }, { "input": "The toxicology and epidemiology of formaldehyde were discussed on the 2nd International Formaldehyde Science Conference in Madrid, 19 - 20 April 2012.", "output": "formaldehyde, Formaldehyde." }, { "input": "It was noted that a substantial amount of new scientific data has appeared within the last years since the 1st conference in 2007.", "output": "There is no related enetity." }, { "input": "Progress has been made in characterisation of genotoxicity, toxicokinetics, formation of exogenous and endogenous DNA adducts, controlled human studies and epidemiology.", "output": "There is no related enetity." }, { "input": "Thus, new research results are now at hand to be incorporated into existing evaluations on formaldehyde by official bodies.", "output": "formaldehyde." }, { "input": "Homogeneous palladium - catalyzed asymmetric hydrogenation.", "output": "palladium." }, { "input": "The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds.", "output": "There is no related enetity." }, { "input": "Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts.", "output": "Pd, Ru, Rh, Ir." }, { "input": "Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes.", "output": "imines, enamines, olefins, ketones, heteroarenes." }, { "input": "It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds.", "output": "palladium." }, { "input": "This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area.", "output": "palladium." }, { "input": "The utility of modeling and simulation approaches to evaluate immunogenicity effect on the therapeutic protein pharmacokinetics.", "output": "There is no related enetity." }, { "input": "While therapeutic proteins ( TP ), particularly recombinant human proteins and fully human monoclonal antibodies, are designed to have a low immunogenic potential in humans, a clinical immune response does sometimes occur and cannot be predicted from preclinical studies.", "output": "There is no related enetity." }, { "input": "Changes in TP pharmacokinetics may be perceived as an early indication of antibody formation and serve as a surrogate for later changes in efficacy and safety in individual subjects.", "output": "There is no related enetity." }, { "input": "Given the substantial increase in number of biological products, including biosimilars, there is an urgent need to quantitatively predict and quantify the immune response and any consequential changes in TP pharmacokinetics.", "output": "There is no related enetity." }, { "input": "The purpose of this communication is to review the utility of population - based modeling and simulation approaches developed to date for investigating the development of an immune response and assessing its impact on TP pharmacokinetics.", "output": "There is no related enetity." }, { "input": "Two examples of empirical modeling approaches for pharmacokinetic assessment are presented.", "output": "There is no related enetity." }, { "input": "The first example presents methods to analyze pharmacokinetic data in the presence of anti - drug antibody ( ADA ) and confirm the effect of immunogenicity on TP pharmacokinetics in early phases of drug development.", "output": "There is no related enetity." }, { "input": "The second example provides a framework to analyze pharmacokinetic data in the absence or with very low incidence of ADA and confirm with enough power the lack of an immunogenicity effect on TP pharmacokinetics in late phases of drug development.", "output": "There is no related enetity." }, { "input": "Finally, a theoretical mechanism - based modeling framework is presented to mathematically relate the complex interaction among TP, their targets, and ADA.", "output": "There is no related enetity." }, { "input": "Determination of the dominant arachidonic acid cytochrome p450 monooxygenases in rat heart, lung, kidney, and liver: protein expression and metabolite kinetics.", "output": "arachidonic acid." }, { "input": "Cytochrome P450 ( P450 ) - derived arachidonic acid ( AA ) metabolites serve pivotal physiological roles.", "output": "arachidonic acid." }, { "input": "Therefore, it is important to determine the dominant P450 AA monooxygenases in different organs.", "output": "There is no related enetity." }, { "input": "We investigated the P450 AA monooxygenases protein expression as well as regioselectivity, immunoinhibition, and kinetic profile of AA epoxygenation and hydroxylation in rat heart, lung, kidney, and liver.", "output": "There is no related enetity." }, { "input": "Thereafter, the predominant P450 epoxygenases and P450 hydroxylases in these organs were characterized.", "output": "There is no related enetity." }, { "input": "Microsomes from heart, lung, kidney, and liver were incubated with AA.", "output": "There is no related enetity." }, { "input": "The protein expression of CYP2B1 / 2, CYP2C11, CYP2C23, CYP2J3, CYP4A1 / 2 / 3, and CYP4Fs in the heart, lung, kidney, and liver were determined by Western blot analysis.", "output": "There is no related enetity." }, { "input": "The levels of AA metabolites were determined by liquid chromatography - electrospray ionization mass spectroscopy.", "output": "There is no related enetity." }, { "input": "This was followed by determination of regioselectivity, immunoinhibition effect, and the kinetic profile of AA metabolism.", "output": "There is no related enetity." }, { "input": "AA was metabolized to epoxyeicosatrienoic acids and 19 - and 20 - hydroxyeicosatetraenoic acid in the heart, lung, kidney, and liver but with varying metabolic activities and regioselectivity.", "output": "epoxyeicosatrienoic acids, 19 - and 20 - hydroxyeicosatetraenoic acid." }, { "input": "Anti - P450 antibodies were found to differentially inhibit AA epoxygenation and hydroxylation in these organs.", "output": "There is no related enetity." }, { "input": "Our data suggest that the predominant epoxygenases are CYP2C11, CYP2B1, CYP2C23, and CYP2C11 / CYP2C23 for the heart, lung, kidney, and liver, respectively.", "output": "There is no related enetity." }, { "input": "On the other hand, CYP4A1 is the major omega - hydroxylase in the heart and kidney; whereas CYP4A2 and / or CYP4F1 / 4 are probably the major hydroxlases in the lung and liver.", "output": "There is no related enetity." }, { "input": "These results provide important insights into the activities of P450 epoxygenases and P450 hydroxylases - mediated AA metabolism in different organs and their associated P450 protein levels.", "output": "There is no related enetity." }, { "input": "The neuropathic diabetic foot ulcer microbiome is associated with clinical factors.", "output": "There is no related enetity." }, { "input": "Nonhealing diabetic foot ulcers ( DFUs ) are a common and costly complication of diabetes.", "output": "There is no related enetity." }, { "input": "Microbial burden, or \" bioburden, \" is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and / or pathogenicity.", "output": "There is no related enetity." }, { "input": "We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high - throughput sequencing of the bacterial 16S ribosomal RNA gene.", "output": "There is no related enetity." }, { "input": "Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens.", "output": "There is no related enetity." }, { "input": "DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity.", "output": "There is no related enetity." }, { "input": "Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus.", "output": "There is no related enetity." }, { "input": "Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus.", "output": "There is no related enetity." }, { "input": "Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus - rich and Streptococcus - rich ulcer clusters.", "output": "There is no related enetity." }, { "input": "Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.", "output": "There is no related enetity." }, { "input": "Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes.", "output": "gemfibrozil, itraconazole." }, { "input": "The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil.", "output": "repaglinide, itraconazole, gemfibrozil." }, { "input": "The present study analyzed this interaction based on a physiologically based pharmacokinetic ( PBPK ) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition.", "output": "There is no related enetity." }, { "input": "Firstly, the plasma concentration profiles of inhibitors ( itraconazole, gemfibrozil, and gemfibrozil glucuronide ) were reproduced by a PBPK model to obtain their pharmacokinetic parameters.", "output": "itraconazole, gemfibrozil, gemfibrozil glucuronide." }, { "input": "The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism - based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide ( OATP ) 1B1 by gemfibrozil and its glucuronide.", "output": "repaglinide, itraconazole, gemfibrozil glucuronide, gemfibrozil and its glucuronide." }, { "input": "The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants ( 0. 0676 nM for itraconazole against CYP3A4; 14. 2 mu M for gemfibrozil against OATP1B1; and 5. 48 mu M for gemfibrozil glucuronide against OATP1B1 ) and the fraction of repaglinide metabolized by CYP2C8 ( 0. 801 ) were consistent with the reported values.", "output": "repaglinide, itraconazole, gemfibrozil, gemfibrozil glucuronide, repaglinide." }, { "input": "The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings / doses.", "output": "repaglinide, gemfibrozil." }, { "input": "The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.", "output": "repaglinide, repaglinide." }, { "input": "Long range effect of mutations on specific conformational changes in the extracellular loop 2 of angiotensin II type 1 receptor.", "output": "There is no related enetity." }, { "input": "The topology of the second extracellular loop ( ECL2 ) and its interaction with ligands is unique in each G protein - coupled receptor.", "output": "There is no related enetity." }, { "input": "When the orthosteric ligand pocket located in the transmembrane ( TM ) domain is occupied, ligand - specific conformational changes occur in the ECL2.", "output": "There is no related enetity." }, { "input": "In more than 90 % of G protein - coupled receptors, ECL2 is tethered to the third TM helix via a disulfide bond.", "output": "There is no related enetity." }, { "input": "Therefore, understanding the extent to which the TM domain and ECL2 conformations are coupled is useful.", "output": "There is no related enetity." }, { "input": "To investigate this, we examined conformational changes in ECL2 of the angiotensin II type 1 receptor ( AT1R ) by introducing mutations in distant sites that alter the activation state equilibrium of the AT1R.", "output": "There is no related enetity." }, { "input": "Differential accessibility of reporter cysteines introduced at four conformation - sensitive sites in ECL2 of these mutants was measured.", "output": "cysteines." }, { "input": "Binding of the agonist angiotensin II ( AngII ) and inverse agonist losartan in wild - type AT1R changed the accessibility of reporter cysteines, and the pattern was consistent with ligand - specific \" lid \" conformations of ECL2.", "output": "losartan, cysteines." }, { "input": "Without agonist stimulation, the ECL2 in the gain of function mutant N111G assumed a lid conformation similar to AngII - bound wild - type AT1R.", "output": "There is no related enetity." }, { "input": "In the presence of inverse agonists, the conformation of ECL2 in the N111G mutant was similar to the inactive state of wild - type AT1R.", "output": "There is no related enetity." }, { "input": "In contrast, AngII did not induce a lid conformation in ECL2 in the loss of function D281A mutant, which is consistent with the reduced AngII binding affinity in this mutant.", "output": "There is no related enetity." }, { "input": "However, a lid conformation was induced by [ Sar ( 1 ), Gln ( 2 ), Ile ( 8 ) ] AngII, a specific analog that binds to the D281A mutant with better affinity than AngII.", "output": "Sar, Gln, Ile." }, { "input": "These results provide evidence for the emerging paradigm of domain coupling facilitated by long range interactions at distant sites on the same receptor.", "output": "There is no related enetity." }, { "input": "The effects of green tea consumption and resistance training on body composition and resting metabolic rate in overweight or obese women.", "output": "There is no related enetity." }, { "input": "Green tea has been shown to have thermogenic and antiobesity properties.", "output": "There is no related enetity." }, { "input": "Therefore, it is important to investigate its effect on weight loss in humans, especially in women.", "output": "There is no related enetity." }, { "input": "We investigated the effects of green tea consumption combined with resistance training on the body composition and the resting metabolic rate ( RMR ) in women who were overweight or obese ( grade I ).", "output": "There is no related enetity." }, { "input": "After 4 weeks on an adaptive diet, 36 women were divided into four groups ( group 1 green tea; group 2 placebo; group 3 green tea plus resistance training; group 4 placebo plus resistance training ).", "output": "There is no related enetity." }, { "input": "The study was double - blinded and placebo - controlled.", "output": "There is no related enetity." }, { "input": "The RMR and body composition were ascertained for each volunteer, blood tests were performed, and subjects in groups 3 and 4 were tested for their one repetition maximum.", "output": "There is no related enetity." }, { "input": "Each subject followed the protocol and continued the diet for eight additional weeks, and periodic evaluations were administered.", "output": "There is no related enetity." }, { "input": "The mean RMR of group 1 decreased significantly and was accompanied by weight loss, maintenance of lean body mass, and decreases in both waist circumference and body mass index.", "output": "There is no related enetity." }, { "input": "Group 2 showed no variations in anthropometric or blood variables and significantly decreased their mean RMR.", "output": "There is no related enetity." }, { "input": "Group 3 showed significant increases in RMR, lean body mass, and muscle strength, and significant decreases in body fat, triglycerides, and waist circumference as compared to group 4.", "output": "triglycerides." }, { "input": "Green tea combined with resistance training its potential is increased with decreasing body fat, waist circumference, and triacylglyceride levels and by increasing lean body mass and muscle strength.", "output": "triacylglyceride." }, { "input": "EGCG inhibits CTGF expression via blocking NF - kappa B activation in cardiac fibroblast.", "output": "EGCG." }, { "input": "Connective tissue growth factor ( CTGF ) has been reported to play an important role in tissue fibrosis and presents a promising therapeutic target for fibrotic diseases.", "output": "There is no related enetity." }, { "input": "In heart, inappropriate increase in level of CTGF promotes fibroblast proliferation and extracellular matrix ( ECM ) accumulation, thereby exacerbating cardiac hypertrophy and subsequent failure.", "output": "There is no related enetity." }, { "input": "Epigallocatechin - 3 - gallate ( EGCG ), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac fibrosis.", "output": "Epigallocatechin - 3 - gallate, EGCG, polyphenol." }, { "input": "However, the molecular mechanism by which EGCG exerts its anti - fibrotic effects has not been well investigated.", "output": "EGCG." }, { "input": "In this study, we found that EGCG could significantly reduce collagen synthesis, fibronectin ( FN ) expression and cell proliferation in rat cardiac fibroblasts stimulated with angiotensinII ( AngII ).", "output": "EGCG." }, { "input": "It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction ( AAC ).", "output": "There is no related enetity." }, { "input": "Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or AngII, and reduced the nuclear translocation of NF - kappa B p65 subunit and degradation of I kappa B - alpha.", "output": "EGCG." }, { "input": "Subsequently, we demonstrated that in cardiac fibroblasts NF - kappa B inhibition could suppress AngII - induced CTGF expression.", "output": "There is no related enetity." }, { "input": "Taken together, these findings provide the first evidence that the effect of EGCG against cardiac fibrosis may be attributed to its inhibition on NF - kappa B activation and subsequent CTGF overexpression, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.", "output": "EGCG, EGCG." }, { "input": "A soluble guanylate cyclase stimulator, BAY 41 - 8543, preserves right ventricular function in experimental pulmonary embolism.", "output": "BAY 41 - 8543." }, { "input": "Pulmonary embolism ( PE ) increases pulmonary vascular resistance, causing right ventricular ( RV ) dysfunction, and poor clinical outcome.", "output": "There is no related enetity." }, { "input": "Present studies test if the soluble guanylate cyclase stimulator BAY 41 - 8543 reduces pulmonary vascular resistance and protects RV function.", "output": "BAY 41 - 8543." }, { "input": "Experimental PE was induced in anesthetized, male Sprague - Dawley rats by infusing 25 mu m polystyrene microspheres ( 1. 95 million / 100 g body wt, right jugular vein ) producing moderate PE.", "output": "polystyrene." }, { "input": "Pulmonary artery vascular resistance, estimated as RVPSP / CO, increased 3 - fold after 5 h of PE.", "output": "There is no related enetity." }, { "input": "Treatment with BAY 41 - 8543 ( 50 mu g / kg, I. V.; given at the time of PE induction ) normalized this index by reducing RVPSP and markedly increasing CO, via preservation of heart rate and stroke volume.", "output": "BAY 41 - 8543." }, { "input": "Ex vivo RV heart function showed minimal changes at 5 h of PE, but decreased significantly after 18 h of PE, including peak systolic pressure ( PSP, Control 39 +/- 1 mmHg vs. 19 +/- 3 PE ), + dP / dt ( 1192 +/- 93 mmHg / s vs. 444 +/- 64 ) and - dP / dt ( - 576 +/- 60 mmHg / s vs. - 278 +/- 40 ).", "output": "There is no related enetity." }, { "input": "BAY 41 - 8543 significantly improved all three indices of RV heart function ( PSP 35 +/- 3. 5, + dP / dt 1129 +/- 100, - dP / dt - 568 +/- 87 ).", "output": "BAY 41 - 8543." }, { "input": "Experimental PE produced increased PVR and RV dysfunction, which were ameliorated by treatment with BAY 41 - 8543.", "output": "BAY 41 - 8543." }, { "input": "Thus, there is vasodilator reserve in this model of experimental PE that can be exploited to reduce the stress upon the heart and preserve RV contractile function.", "output": "There is no related enetity." }, { "input": "Microbiota of male genital tract: impact on the health of man and his partner.", "output": "There is no related enetity." }, { "input": "This manuscript describes the male genital tract microbiota and the significance of it on the host ' s and his partner ' s health.", "output": "There is no related enetity." }, { "input": "Microbiota exists in male lower genital tract, mostly in urethra and coronal sulcus while high inter - subject variability exists.", "output": "There is no related enetity." }, { "input": "Differences appear between sexually transmitted disease positive and negative men as well as circumcised and uncircumcised men.", "output": "There is no related enetity." }, { "input": "Upper genital tract is generally germ - free, except in case of infections.", "output": "There is no related enetity." }, { "input": "Prostatitis patients have frequently abundant polymicrobial communities in their semen, expressed prostatic secretion and / or post - massage urine.", "output": "There is no related enetity." }, { "input": "Coryneform bacteria have ambivalent role in male urogenital tract being frequently commensals but sometimes associated with prostatitis and urethritis.", "output": "There is no related enetity." }, { "input": "Interactions between male and female genital tract microbiota are highly likely yet there are very scarce studies on the couples ' genital tract microbiota.", "output": "There is no related enetity." }, { "input": "Increase of bacterial vaginosis - type microbiota and coliforms are the most typical findings in men while the adverse effect of male genital tract bacteria on in vitro fertilization and pregnancy outcome has also been indicated.", "output": "There is no related enetity." }, { "input": "Effect of developmental dioxin exposure on methylation and expression of specific imprinted genes in mice.", "output": "dioxin." }, { "input": "2, 3, 7, 8 - Tetrachlorodibenzo - p - dioxin ( TCDD ) is an endocrine disruptor affecting the reproductive system in humans.", "output": "2 , 3 , 7 , 8 - Tetrachlorodibenzo - p - dioxin, TCDD." }, { "input": "The aim of this study was to evaluate the effects of TCDD administered to pregnant mice at two different doses ( 2 - 10 ng / kg / day ), on imprinted genes in the male offspring.", "output": "TCDD." }, { "input": "The degree of methylation and the mRNA expression of Snrpn, Peg3 and Igf2r were analyzed in the sperm, skeletal muscle and liver.", "output": "There is no related enetity." }, { "input": "TCDD administration ( 10 ng / kg / day ) decreased the sperm count in the male offspring.", "output": "TCDD." }, { "input": "It did not affect methylation but increased mRNA expression of Snrpn, Peg3, Igf2r and Air ncRNA.", "output": "There is no related enetity." }, { "input": "In muscle and liver, TCDD ( 10 ng / kg / day ) induced increases in methylation and decreases in mRNA expression of Igf2r.", "output": "TCDD." }, { "input": "These results show that the robust effects of TCDD on the mRNA expression of Snrpn, Peg3 and Igf2r genes in the sperm and of Igf2r in the muscle and liver are unrelated to changes in methylation in their respective genes.", "output": "TCDD." }, { "input": "The 17 - beta - oestradiol inhibits osteoclast activity by increasing the cannabinoid CB2 receptor expression.", "output": "17 - beta - oestradiol." }, { "input": "Bone is a highly metabolically active tissue and its formation and resorption is at the base of bone remodelling.", "output": "There is no related enetity." }, { "input": "The critical importance of a balanced bone remodelling is demonstrated by human diseases, i. e. osteoporosis, in which a net increase in bone resorption is responsible of skeleton weakening and fracture risk.", "output": "There is no related enetity." }, { "input": "Oestrogens display anti - resorptive properties on bone metabolism.", "output": "Oestrogens." }, { "input": "Indeed, the so - called post - menopausal osteoporosis occurs after interruption of gonad function and benefits from hormonal replacement treatment.", "output": "There is no related enetity." }, { "input": "Recently, an important role for the endocannabinoid system in the regulation of skeletal remodelling in human has also been shown.", "output": "There is no related enetity." }, { "input": "In particular, we showed that CB2 stimulation is able to reduce the number of human OCs in vitro.", "output": "There is no related enetity." }, { "input": "Here, we provide unprecedented evidence that 17 - beta - oestradiol administration inhibits activity and formation of human OCs in vitro, demonstrating that oestrogens are able to induce an increase of CB2 expression probably through the recruitment of a putative oestrogens responsive element in the CB2 encoding for gene.", "output": "17 - beta - oestradiol, oestrogens, oestrogens." }, { "input": "Proto - oncogene PIM - 1 is a novel estrogen receptor target associating with high grade breast tumors.", "output": "estrogen." }, { "input": "We searched ER alpha cistromes of MCF - 7 breast cancer cells for previously unrecognized ER alpha targets and identified proto - oncogene PIM - 1 as a novel potential target gene.", "output": "There is no related enetity." }, { "input": "We show that the expression of PIM - 1 is induced in response to estradiol in MCF - 7 cells and that the induction is mediated by ER alpha - regulated enhancers located distally upstream from the gene.", "output": "estradiol." }, { "input": "In keeping with the growth - promoting role of the PIM - 1, depletion of the PIM - 1 attenuated the proliferation of the MCF - 7 cells, which was paralleled with up - regulation of cyclin - dependent protein kinase inhibitor CDKN1A and CDKN2B expression.", "output": "There is no related enetity." }, { "input": "Analysis of PIM - 1 expression between invasive breast tumors and benign breast tissue samples showed that elevated PIM - 1 expression is associated with malignancy and a higher tumor grade.", "output": "There is no related enetity." }, { "input": "In sum, identification of PIM - 1 as an ER alpha target gene adds a novel potential mechanism by which estrogens can contribute to breast cancer cell proliferation and carcinogenesis.", "output": "estrogens." }, { "input": "Dichlorodiphenyltrichloroethane ( DDT ), DDT metabolites and pregnancy outcomes.", "output": "Dichlorodiphenyltrichloroethane, DDT, DDT." }, { "input": "Organochlorine pesticides ( OCPs ) are persistent endocrine disruptors.", "output": "Organochlorine." }, { "input": "OCPs cross the placenta; this prenatal exposure has been associated with adverse pregnancy outcomes.", "output": "There is no related enetity." }, { "input": "We investigated associations between prenatal exposure to OCPs and gestational age and birth weight in 600 infants born between 1960 and 1963.", "output": "There is no related enetity." }, { "input": "The primary OCP was 1, 1, 1 - trichloro - 2, 2 - bis ( p - chlorophenyl ) ethane ( p, p ' - DDT ), its primary metabolite, 1, 1 ' - dichloro - 2, 2 ' - bis ( p - chlorophenyl ) ethylene ( p, p ' - DDE ) and the contaminant, 1, 1, 1 - trichloro - 2 - ( p - chlorophenyl ) - 2 - ( o - chlorophenyl ) - ethane ( o, p ' - DDT ).", "output": "1 , 1 , 1 - trichloro - 2 , 2 - bis ( p - chlorophenyl ) ethane, p , p ' - DDT, 1 , 1 ' - dichloro - 2 , 2 ' - bis ( p - chlorophenyl ) ethylene, p , p ' - DDE, 1 , 1 , 1 - trichloro - 2 - ( p - chlorophenyl ) - 2 - ( o - chlorophenyl ) - ethane, o , p ' - DDT." }, { "input": "Regression analysis indicated that for each natural log unit increase in p, p ' - DDT, birth weight increased by 274 g ( 95 % CI: 122, 425 ) when controlling for p, p ' - DDE and o, p ' - DDT.", "output": "p , p ' - DDT, p , p ' - DDE, o , p ' - DDT." }, { "input": "At a given level of p, p ' - DDT exposure, o, p ' - DDT and p, p ' - DDE were associated with decreased birth weight.", "output": "p , p ' - DDT, o , p ' - DDT, p , p ' - DDE." }, { "input": "p, p ' - DDE was negatively associated with length of gestation, controlling for p, p ' - DDT and o, p ' - DDT.", "output": "p , p ' - DDE, p , p ' - DDT, o , p ' - DDT." }, { "input": "These findings suggest opposing associations between exposure to p, p ' - DDT and p, p ' - DDE and birth weight.", "output": "p , p ' - DDT, p , p ' - DDE." }, { "input": "We did not find evidence to support mediation by maternal thyroid hormone status nor that the association differed by sex.", "output": "There is no related enetity." }, { "input": "Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography.", "output": "There is no related enetity." }, { "input": "Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated.", "output": "There is no related enetity." }, { "input": "With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography ( FMT ).", "output": "There is no related enetity." }, { "input": "In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro - computed tomography on a set of control mice, and mice in which load - adaptation was induced in the sixth caudal vertebra.", "output": "There is no related enetity." }, { "input": "The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16 %, indicating acceptable reproducibility.", "output": "There is no related enetity." }, { "input": "A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro - computed tomography only over the first 14days ( R = 0. 81, p < 0. 01 ), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro - CT.", "output": "There is no related enetity." }, { "input": "Bone formation measured by FMT was 89 - 109 % greater ( p < 0. 05 ) for mice subjected to mechanical loading than control mice.", "output": "There is no related enetity." }, { "input": "Bone resorption was 5 - 8 % lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT.", "output": "There is no related enetity." }, { "input": "In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice.", "output": "There is no related enetity." }, { "input": "Cadmium ( Cd ) - induced oxidative stress down - regulates the gene expression of DNA mismatch recognition proteins MutS homolog 2 ( MSH2 ) and MSH6 in zebrafish ( Danio rerio ) embryos.", "output": "Cadmium, Cd." }, { "input": "DNA mismatch repair ( MMR ) of simple base mismatches and small insertion - deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 ( MSH2 ) - MSH6 heterodimer to mismatched DNA.", "output": "There is no related enetity." }, { "input": "Cadmium ( Cd ) is a genotoxic heavy metal that has been recognized as a human carcinogen.", "output": "Cadmium, Cd." }, { "input": "Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity.", "output": "Cd." }, { "input": "Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish ( Danio rerio ) embryos.", "output": "Cd." }, { "input": "This study was undertaken to explore if Cd - induced oxidative stress down - regulated MSH gene activities.", "output": "Cd." }, { "input": "Following the exposure of zebrafish embryos at 1 h post fertilization ( hpf ) to sublethal concentrations of Cd at 3 - 5 mu M for 4 or 9 h, a parallel down - regulation of MSH2, MSH6 and Cu / Zn superoxide dismutase ( Cu / Zn - SOD ) gene expression was detected by real - time RT - PCR and the expression levels were 40 - 50 % of control after a 9 - h exposure.", "output": "Cd, Cu, Zn, superoxide, Cu, Zn." }, { "input": "Cd exposure also induced oxidative stress, yet no inhibition of catalase gene activity was observed.", "output": "Cd." }, { "input": "Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene ( BHT ), d - mannitol or N - acetylcysteine ( NAC ) at 1 - 10 mu M restored Cd - suppressed msh6 expression.", "output": "butylhydroxytoluene, BHT, d - mannitol, N - acetylcysteine, NAC, Cd." }, { "input": "QPCR confirmed the protective effects of antioxidants on Cd - suppressed msh2 / msh6 mRNA production.", "output": "Cd." }, { "input": "Down - regulated MSH gene activities reaching about 50 % of control were also induced in embryos exposed to paraquat, a reactive oxygen species ( ROS ) - generating herbicide, or hydrogen peroxide at 200 mu M.", "output": "paraquat, oxygen, hydrogen peroxide." }, { "input": "Hence, Cd at sublethal levels down - regulates msh2 / msh6 expression primarily via ROS as signaling molecules.", "output": "Cd." }, { "input": "The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 ( Sp1 ).", "output": "There is no related enetity." }, { "input": "Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay, therefore excluding the involvement of Sp1 inactivation in Cd - induced MSH gene inhibition in zebrafish embryos.", "output": "Cd, Cd." }, { "input": "Temperature dependence of long - term cadmium toxicity in the zebrafish is not explained by liver oxidative stress: evidence from transcript expression to physiology.", "output": "cadmium." }, { "input": "Standard ecotoxicity tests are performed at species ' specific standard temperatures, but temperature is known to affect chemical toxicity.", "output": "There is no related enetity." }, { "input": "A temperature increase has been shown to increase cadmium toxicity in several aquatic species but information in fish is scarce.", "output": "cadmium." }, { "input": "Based on literature we hypothesize that with increasing temperature, cadmium accumulation and oxidative stress increase, resulting in increased toxicity.", "output": "cadmium." }, { "input": "In this study zebrafish acclimated to 12, 18, 26 ( standard temperature ) or 34 degrees C for one month, were exposed to 5 mu M cadmium for 4 or 28 days at the respective acclimation temperature.", "output": "cadmium." }, { "input": "Cadmium toxicity ( mortality ) increased with increasing temperature.", "output": "Cadmium." }, { "input": "PCA showed that the high mortality at 34 degrees C was closely correlated to an increasing tissue cadmium accumulation with increasing temperature, but not to liver oxidative damage under the form of protein carbonyl content or lipid peroxidation ( measured as malondialdehyde levels ) or liver antioxidative potential.", "output": "cadmium, carbonyl, malondialdehyde." }, { "input": "Instead, acclimation to 12 degrees C induced the highest oxidative damage to liver proteins and lipids, and transcript levels of glucose - 6P - dehydrogenase, 6P - gluconate - dehydrogenase and glutathione peroxidase were particularly good markers of cold - induced oxidative stress.", "output": "glucose, gluconate, glutathione." }, { "input": "At this low temperature there was no interaction with cadmium exposure and there was no sign of cadmium sensitivity.", "output": "cadmium, cadmium." }, { "input": "Contrastingly, the combined effect of high temperature and cadmium exposure on mortality proved synergistic.", "output": "cadmium." }, { "input": "Therefore we conclude that interactions between temperature and cadmium toxicity increased with increasing temperature and that this probably played part in increasing cadmium sensitivity.", "output": "cadmium, cadmium." }, { "input": "Increased cadmium compartmentalization and protein carbonyl content in liver of zebrafish acclimated to the standard temperature of 26 degrees C probably played part in increased sensitivity towards the same cadmium body burden compared to lower temperatures.", "output": "cadmium, carbonyl, cadmium." }, { "input": "On the one hand we recognize and this study even confirms the importance of applying standard temperatures in standard ecotoxicity tests to ensure inter - study comparability.", "output": "There is no related enetity." }, { "input": "On the other hand temperatures in the field may deviate from standard temperatures and accounting for deviating temperatures, which can alter chemical sensitivity, in regulation can improve environmental protection.", "output": "There is no related enetity." }, { "input": "Induction of skin sensitization is augmented in Nrf2 - deficient mice.", "output": "There is no related enetity." }, { "input": "Several in vitro DNA microarray studies have shown the importance of nuclear factor ( erythroid - derived 2 ) - like 2 ( Nrf2 ) in skin sensitization.", "output": "There is no related enetity." }, { "input": "Nevertheless, the exact in vivo role of the Nrf2 - Keap1 pathway during the induction of skin sensitization remains unknown.", "output": "There is no related enetity." }, { "input": "To study the function of Nrf2, a local lymph node assay was performed in wild - type and Nrf2 - deficient mice using 2, 4 - dinitrochlorobenzene.", "output": "2 , 4 - dinitrochlorobenzene." }, { "input": "The Nrf2 - deficient mice show a more pronounced response, indicating that Nrf2 is involved in dampening the induction of skin sensitization.", "output": "There is no related enetity." }, { "input": "Survivin in adrenocortical tumors - pathophysiological implications and therapeutic potential.", "output": "There is no related enetity." }, { "input": "Treatment options for adrenocortical carcinoma ( ACC ) are very limited.", "output": "There is no related enetity." }, { "input": "In other solid tumors, small vaccination trials targeting the anti - apoptotic molecule survivin suggested immunological and clinical benefit in selected patients.", "output": "There is no related enetity." }, { "input": "Therefore, we investigated whether survivin might be a suitable target for immunotherapy in ACC.", "output": "There is no related enetity." }, { "input": "Survivin mRNA and protein expression was assessed in adrenal tissue specimens [ by real - time - PCR in 29 ACC, 24 adrenocortical adenomas ( ACA ) and 12 normal adrenal glands; by immunohistochemistry in 167 ACCs, 15 ACA, and 5 normal adrenal glands ].", "output": "There is no related enetity." }, { "input": "Expression was correlated with clinical outcome using Kaplan - Meier and Cox regression analyses.", "output": "There is no related enetity." }, { "input": "The anti - apoptotic role of survivin was investigated in the SW13 ACC cell line using survivin siRNA.", "output": "There is no related enetity." }, { "input": "The presence of spontaneous survivin specific T - cells in peripheral blood was assessed by FACS dextramere staining in 29 ACC patients in comparison to healthy controls.", "output": "There is no related enetity." }, { "input": "Survivin mRNA in ACC was significantly overexpressed when compared with ACA or normal adrenal glands.", "output": "There is no related enetity." }, { "input": "Immunohistochemistry confirmed survivin protein expression in 97 % of the ACCs.", "output": "There is no related enetity." }, { "input": "In 83 % of samples, staining was moderate or high and clinical outcome in this subgroup showed a trend towards poorer prognosis [ hazard ratio for death 2. 28 ( 95 % CI 0. 99 - 5. 28 ); p = 0. 053 ].", "output": "There is no related enetity." }, { "input": "Survivin knockdown in SW - 13 cell significantly increased the rate of apoptosis.", "output": "There is no related enetity." }, { "input": "Finally, spontaneous survivin - reactive T cells were detectable in 3 of 29 ACC patients.", "output": "There is no related enetity." }, { "input": "In conclusion, our data suggest that survivin could play an important role in the anti - apoptotic mechanisms in ACC and provide first hints that targeting survivin might be an interesting new therapeutic approach in this rare disease.", "output": "There is no related enetity." }, { "input": "Using chimeric mice with humanized livers to predict human drug metabolism and a drug - drug interaction.", "output": "There is no related enetity." }, { "input": "Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data to predict the drug metabolites or potential drug - drug interactions ( DDIs ) that will occur in humans.", "output": "There is no related enetity." }, { "input": "Although chimeric mice with humanized livers can produce known human metabolites for test substrates, we do not know whether chimeric mice can be used to prospectively predict human drug metabolism or a possible DDI.", "output": "There is no related enetity." }, { "input": "Therefore, we investigated whether they could provide a more predictive assessment for clemizole, a drug in clinical development for the treatment of hepatitis C virus ( HCV ) infection.", "output": "clemizole." }, { "input": "Our results demonstrate, for the first time, that analyses performed in chimeric mice can correctly identify the predominant human drug metabolite before human testing.", "output": "There is no related enetity." }, { "input": "The differences in the rodent and human pathways for clemizole metabolism were of importance, because the predominant human metabolite was found to have synergistic anti - HCV activity.", "output": "clemizole." }, { "input": "Moreover, studies in chimeric mice also correctly predicted that a DDI would occur in humans when clemizole was coadministered with a CYP3A4 inhibitor.", "output": "clemizole." }, { "input": "These results demonstrate that using chimeric mice can improve the quality of preclinical drug assessment.", "output": "There is no related enetity." }, { "input": "High - sensitivity real - time analysis of nanoparticle toxicity in green fluorescent protein - expressing zebrafish.", "output": "There is no related enetity." }, { "input": "Gold nanoparticles ( AuNP ) show great potential for diagnostic and therapeutic application in humans.", "output": "There is no related enetity." }, { "input": "A great number of studies have tested the cytotoxicity of AuNP using cell culture.", "output": "There is no related enetity." }, { "input": "There is, however, an urgent need to test AuNP in vertebrate animal models that interrogate biodistribution and complex biological traits like organ development, whole body metabolism, and cognitive function.", "output": "There is no related enetity." }, { "input": "The sheer number of different compounds precludes the use of small rodent model for initial screening.", "output": "There is no related enetity." }, { "input": "The extended fish embryo test ( FET ) is used here to bridge the gap between cell culture and small animal models.", "output": "There is no related enetity." }, { "input": "A study on the toxicity of ultrasmall AuNP in wild type and transgenic zebrafish is presented.", "output": "There is no related enetity." }, { "input": "FET faithfully reproduce all important findings of a previous study in HeLa cells and add new important information on teratogenicity and hepatotoxicity that could not be gained from studying cultured cells.", "output": "There is no related enetity." }, { "input": "Real - time fluorescence turn - on detection of alkaline phosphatase activity with a novel perylene probe.", "output": "perylene." }, { "input": "A tetracationic perylene probe ( probe 1 ) was designed and synthesized.", "output": "perylene." }, { "input": "Probe 1 was used for the real - time fluorescence turn - on assay of alkaline phosphatase ( ALP ) activity and inhibitor screening.", "output": "There is no related enetity." }, { "input": "Probe 1 monomer fluorescence could be very efficiently quenched by ATP through the formation of an ATP / probe 1 complex.", "output": "There is no related enetity." }, { "input": "ALP triggered the degradation of ATP, the breakdown of the ATP / probe 1 complex, and the recovery of the probe 1 monomer fluorescence.", "output": "There is no related enetity." }, { "input": "In the presence of an ALP inhibitor, a decrease in fluorescence recovery was observed.", "output": "There is no related enetity." }, { "input": "Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action.", "output": "phorbol ester, bryostatin 1, bryostatin." }, { "input": "Bryostatin 1, like the phorbol esters, binds to and activates protein kinase C ( PKC ) but paradoxically antagonizes many but not all phorbol ester responses.", "output": "Bryostatin 1, phorbol esters, phorbol ester." }, { "input": "Previously, we have compared patterns of biological response to bryostatin 1, phorbol ester, and the bryostatin 1 derivative Merle 23 in two human cancer cell lines, LNCaP and U937.", "output": "bryostatin 1, phorbol ester, bryostatin 1, Merle 23." }, { "input": "Bryostatin 1 fails to induce a typical phorbol ester biological response in either cell line, whereas Merle 23 resembles phorbol ester in the U937 cells and bryostatin 1 in the LNCaP cells.", "output": "Bryostatin 1, phorbol ester, Merle 23, phorbol ester, bryostatin 1." }, { "input": "Here, we have compared the pattern of their transcriptional response in both cell lines.", "output": "There is no related enetity." }, { "input": "We examined by qPCR the transcriptional response as a function of dose and time for a series of genes regulated by PKCs.", "output": "There is no related enetity." }, { "input": "In both cell lines bryostatin 1 differed primarily from phorbol ester in having a shorter duration of transcriptional modulation.", "output": "bryostatin 1, phorbol ester." }, { "input": "This was not due to bryostatin 1 instability, since bryostatin 1 suppressed the phorbol ester response.", "output": "bryostatin 1, bryostatin 1, phorbol ester." }, { "input": "In both cell lines Merle 23 induced a pattern of transcription largely like that of phorbol ester although with a modest reduction at later times in the LNCaP cells, suggesting that the difference in biological response of the two cell lines to Merle 23 lies downstream of this transcriptional regulation.", "output": "Merle 23, phorbol ester, Merle 23." }, { "input": "For a series of bryostatins and analogs which ranged from bryostatin 1 - like to phorbol ester - like in activity on the U937 cells, the duration of transcriptional response correlated with the pattern of biological activity, suggesting that this may provide a robust platform for structure activity analysis.", "output": "bryostatins, bryostatin 1, phorbol ester." }, { "input": "Synergistic anti - cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO - 211H cells.", "output": "resveratrol, clofarabine." }, { "input": "Dietary phytochemicals as adjuvants have been suggested to play important roles in enhancing chemotherapeutic potential owing to multitargeted chemopreventive properties and lack of substantial toxicity.", "output": "There is no related enetity." }, { "input": "Here, we investigated the efficacy of the combined treatment of various phytochemicals with the anticancer drug clofarabine in malignant mesothelioma MSTO - 211H cells and normal mesothelial MeT - 5A cells.", "output": "clofarabine." }, { "input": "The combined treatment of resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO - 211H cells, but not in MeT - 5A cells.", "output": "resveratrol, clofarabine." }, { "input": "In MSTO - 211H cells, the nuclear accumulation of Sp1 and the levels of p - Akt, Sp1, c - Met, cyclin D1, and p21 were effectively decreased by the combined treatment of them.", "output": "There is no related enetity." }, { "input": "In combination with clofarabine, the ability of resveratrol to reduce the contents of Sp1 and its target gene products was also evident in a time - and dose - dependent experiment.", "output": "clofarabine, resveratrol." }, { "input": "The inhibition of phosphoinositide 3 - kinase using Ly294002 augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1.", "output": "phosphoinositide, Ly294002." }, { "input": "Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.", "output": "resveratrol, clofarabine." }, { "input": "Purification and determination of two novel antioxidant peptides from flounder fish ( Paralichthys olivaceus ) using digestive proteases.", "output": "There is no related enetity." }, { "input": "We investigated the effects of bioactive - peptides from hydrolysates of flounder fish muscle ( FFM ) on antioxidant activity.", "output": "There is no related enetity." }, { "input": "The hydrolysates were prepared by enzymatic reactions of FFM using eight commercial proteases such as papain, pepsin, trypsin, neutrase, alcalase, kojizyme, protamex, and alpha - chymotrypsin.", "output": "There is no related enetity." }, { "input": "The alpha - chymotrypsin hydrolysate showed the strongest antioxidant activity among the eight enzymatic hydrolysates.", "output": "There is no related enetity." }, { "input": "Further separation of the alpha - chymotrypsin hydrolysate was performed by ultrafiltration, gel filtration, and reverse - phase high performance liquid chromatography.", "output": "There is no related enetity." }, { "input": "Consequently, two novel peptides with high antioxidant activity were purified, and their amino acid sequences were determined ( Val - Cys - Ser - Val [ VCSV ] and Cys - Ala - Ala - Pro [ CAAP ], respectively ).", "output": "amino acid, Val - Cys - Ser - Val, VCSV, Cys - Ala - Ala - Pro, CAAP." }, { "input": "The two peptides showed good scavenging activity against the 1, 1 - diphenyl - 2 - picrylhydrazyl ( DPPH ) free radical ( IC ( 50 ) values, 111. 32 and 26. 89 mu M, respectively ) and high cytoprotective activities against 2, 2 - azobis - ( 2 - amidino - propane ) dihydrochloride ( AAPH ) without cytotoxicity and scavenged total reactive oxygen species in Vero cells.", "output": "1 , 1 - diphenyl - 2 - picrylhydrazyl, DPPH, 2 , 2 - azobis - ( 2 - amidino - propane ) dihydrochloride, AAPH, oxygen." }, { "input": "In particular, apoptotic bodies produced by AAPH dose - dependently decreased following treatment with the CAAP peptide.", "output": "AAPH, CAAP." }, { "input": "These results revealed firstly the two peptides with strong antioxidative effects from FFM.", "output": "There is no related enetity." }, { "input": "Bisphenol A inhibits proliferation and induces apoptosis in micromass cultures of rat embryonic midbrain cells through the JNK, CREB and p53 signaling pathways.", "output": "Bisphenol A." }, { "input": "Bisphenol A ( BPA ) has been widely used in the manufacture of polycarbonate plastic, water bottles and food containers.", "output": "Bisphenol A, BPA, polycarbonate." }, { "input": "Previous studies have established that BPA could cause developmental toxicity by inhibiting the proliferation and differentiation of rat embryonic midbrain ( MB ) cells in vitro.", "output": "BPA." }, { "input": "However, the underlying mechanisms have not been well studied yet.", "output": "There is no related enetity." }, { "input": "In the current study, we examined the proliferation and differentiation of MB cells treated with 10 ( - 12 ) - 10 ( - 4 ) M BPA and found that only 10 ( - 4 ) M BPA inhibited proliferation and differentiation.", "output": "BPA, BPA." }, { "input": "Then, we investigated the cell cycle progression and apoptosis of MB cells; 10 ( - 4 ) M BPA caused an explicit S phase and G2 / M phase arrest in the cell cycle and increased the percentage of apoptotic cells.", "output": "BPA." }, { "input": "Moreover, the phosphorylation of mitogen - activated protein kinase ( MAPK ) and cyclic - AMP response binding protein ( CREB ) and the expression of some apoptotic regulatory genes were investigated.", "output": "There is no related enetity." }, { "input": "BPA ( 10 ( - 4 ) M ) reduced the phosphorylation of C - Jun N - terminal kinase ( JNK ) and CREB, and increased the mRNA expression level of Bax and p53.", "output": "BPA, N." }, { "input": "Our findings demonstrated that BPA could cause developmental toxicity through anti - proliferation and pro - apoptosis in MB cells.", "output": "BPA." }, { "input": "Multiple signaling pathways, such as the JNK, CREB and p53 - mitochondrial apoptosis pathways, participate in these effects.", "output": "There is no related enetity." }, { "input": "1H NMR - based metabonomics approach in a rat model of acute liver injury and regeneration induced by CCl4 administration.", "output": "1H." }, { "input": "The administration of carbon tetrachloride ( CCl ( 4 ) ) has been established as a model of toxin - induced acute and chronic liver injury.", "output": "carbon tetrachloride, CCl ( 4 )." }, { "input": "In the present study, we investigate the progression of the biochemical response to acute CCl ( 4 ) - induced liver injury, capturing metabolic variations during both toxic insult and regeneration using NMR - based metabonomic analysis of liver tissue and plasma.", "output": "CCl ( 4 )." }, { "input": "A single dose of CCl ( 4 ) ( 1 mL / kg BW ) was intraperitoneally administered to male Wister rats sacrificed every 12h up to 72 h post treatment, while healthy animals served as controls.", "output": "CCl ( 4 )." }, { "input": "Acquired ( 1 ) H NMR spectra of liver tissue extracts and plasma samples were explored with multivariate analysis and the resulted models were correlated with conventional biochemical and histopathological indices of toxicity for monitoring the progression of experimental injury.", "output": "( 1 ) H." }, { "input": "The metabonomic analysis resulted in discrimination between the subjects under toxic insult ( up to 36 h ) and those at the regenerative phase ( peaked at 48 h ).", "output": "There is no related enetity." }, { "input": "At 72 h normalization of liver ' s pathology similar to the controls group was apparent.", "output": "There is no related enetity." }, { "input": "Principal component analysis ( PCA ) trajectories highlighted the time points of the greater degree of toxic insult and the regenerative state.", "output": "There is no related enetity." }, { "input": "A number of metabolites such as glucose, lactate, choline, formate exhibited variations suggesting CCl ( 4 ) induced impairment in essential biochemical pathways as energy metabolism, lipid biosynthesis and transmethylation reactions.", "output": "glucose, lactate, choline, formate, CCl ( 4 )." }, { "input": "The latter provides new evidence of B12 and folate pathways deficiency, indicative of new mechanistic implications possibly by direct inhibition of B12 dependent enzymes by the chlorinated radicals of CCl ( 4 ) metabolism.", "output": "B12, folate, B12, CCl ( 4 )." }, { "input": "Physiologically based toxicokinetics of serum aflatoxin B1 - lysine adduct in F344 rats.", "output": "aflatoxin B1, lysine." }, { "input": "Aflatoxin B ( 1 ) - lysine adduct ( AFB - Lys ) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported.", "output": "Aflatoxin B ( 1 ), lysine, AFB, Lys, aflatoxin." }, { "input": "In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB ( 1 ) and the toxicokinetics of serum AFB - Lys that followed treatments were investigated.", "output": "AFB ( 1 ), AFB, Lys." }, { "input": "A single - dose of AFB ( 1 ) increased serum AFB - Lys levels rapidly peaking at 4h, followed by first - order elimination, through which the half - life was estimated to be 2. 31 days.", "output": "AFB ( 1 ), AFB, Lys." }, { "input": "A physiologically based pharmacokinetic model showed that approximately 3. 00 - 3. 90 % and 1. 12 - 1. 98 % of the administered AFB ( 1 ) doses were converted to serum AFB - Lys adducts at 2h and 24h post treatment, respectively.", "output": "AFB ( 1 ), AFB, Lys." }, { "input": "Repeated AFB ( 1 ) exposure at 5 - 25 mu g / kg body weight linearly increased serum AFB - Lys levels for 5 weeks in animals, resulting in a 1 - 1. 5 times higher AFB - Lys level overall.", "output": "AFB ( 1 ), AFB, Lys, AFB, Lys." }, { "input": "This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure.", "output": "There is no related enetity." }, { "input": "Higher dose exposure at 75 mu g / kg increased the level of AFB - Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks.", "output": "AFB, Lys." }, { "input": "In conclusion, this study systematically evaluated the toxicokinetics of serum AFB - Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker.", "output": "AFB, Lys." }, { "input": "Influence of ovarian and non - ovarian estrogens on weight gain in response to disruption of sweet taste - - calorie relations in female rats.", "output": "estrogens." }, { "input": "Regulation of energy balance in female rats is known to differ along a number of dimensions compared to male rats.", "output": "There is no related enetity." }, { "input": "Previous work from our lab has demonstrated that in female rats fed dietary supplements containing high - intensity sweeteners that may disrupt a predictive relation between sweet tastes and calories, excess weight gain is demonstrated only when females are also fed a diet high in fat and sugar, and is evidenced primarily in animals already prone to gain excess weight.", "output": "sugar." }, { "input": "In contrast, male rats show excess weight gain when fed saccharin - sweetened yogurt supplements when fed both standard chow diets and diets high in fat and sugar, and regardless of their proneness to excess weight gain.", "output": "saccharin, sugar." }, { "input": "The goal of the present experiments was to determine whether ovarian, or other sources of estrogens, contributes to the resistance to excess weight gain in female rats fed standard chow diets along with dietary supplements sweetened with yogurt.", "output": "estrogens." }, { "input": "Results of the first experiment indicated that when the ovaries were removed surgically in adult female rats, patterns of weight gain were similar in animals fed saccharin - sweetened compared to glucose - sweetened yogurt supplements.", "output": "saccharin, glucose." }, { "input": "In the second experiment, when the ovaries were surgically removed in adult female rats, and local production of estrogens was suppressed with the aromatase inhibitor anastrozole, females fed the saccharin - sweetened yogurt consumed more energy and gained more weight than females fed the glucose - sweetened yogurt.", "output": "estrogens, anastrozole, saccharin, glucose." }, { "input": "However, when the ovaries were surgically removed prior to the onset of puberty ( at 24 - 25 days of age ), females given saccharin - sweetened yogurt along with vehicle gained excess weight.", "output": "saccharin." }, { "input": "In contrast, weight gain was similar in those given saccharin - sweetened and glucose - sweetened yogurt along with anastrozole.", "output": "saccharin, glucose, anastrozole." }, { "input": "The results suggest that behavioral differences between males and females in response to disruption of sweet --> calorie relations may result from differences in patterns of local estrogen production.", "output": "estrogen." }, { "input": "These differences may be established developmentally during the pubertal period in females.", "output": "There is no related enetity." }, { "input": "Manganese transport via the transferrin mechanism.", "output": "Manganese." }, { "input": "Excessive manganese ( Mn ) uptake by brain cells, particularly in regions like the basal ganglia, can lead to toxicity.", "output": "manganese, Mn." }, { "input": "Mn ( 2 + ) is transported into cells via a number of mechanisms, while Mn ( 3 + ) is believed to be transported similarly to iron ( Fe ) via the transferrin ( Tf ) mechanism.", "output": "Mn ( 2 + ), Mn ( 3 + ), iron, Fe." }, { "input": "Cellular Mn uptake is therefore determined by the activity of the mechanisms transporting Mn into each type of cell and by the amounts of Mn ( 2 + ), Mn ( 3 + ) and their complexes to which these cells are exposed; this complicates understanding the contributions of each transporter to Mn toxicity.", "output": "Mn, Mn, Mn ( 2 + ), Mn ( 3 + ), Mn." }, { "input": "While uptake of Fe ( 3 + ) via the Tf mechanism is well understood, uptake of Mn ( 3 + ) via this mechanism has not been systematically studied.", "output": "Fe ( 3 + ), Mn ( 3 + )." }, { "input": "The stability of the Mn ( 3 + ) Tf complex allowed us to form and purify this complex and label it with a fluorescent ( Alexa green ) tag.", "output": "Mn ( 3 + ), Alexa green." }, { "input": "Using purified and labeled Mn ( 3 + ) Tf and biophysical tools, we have developed a novel approach to study Mn ( 3 + ) Tf transport independently of other Mn transport mechanisms.", "output": "Mn ( 3 + ), Mn ( 3 + ), Mn." }, { "input": "This approach was used to compare the uptake of Mn ( 3 + ) Tf into neuronal cell lines with published descriptions of Fe ( 3 + ) uptake via the Tf mechanism, and to obtain quantitative information on Mn uptake via the Tf mechanism.", "output": "Mn ( 3 + ), Fe ( 3 + ), Mn." }, { "input": "Results confirm that in these cell lines significant Mn ( 3 + ) is transported by the Tf mechanism similarly to Fe ( 3 + ) Tf transport; although Mn ( 3 + ) Tf transport is markedly slower than other Mn transport mechanisms.", "output": "Mn ( 3 + ), Fe ( 3 + ), Mn ( 3 + ), Mn." }, { "input": "This novel approach may prove useful for studying Mn toxicity in other systems and cell types.", "output": "Mn." }, { "input": "Organization of the BcgI restriction - modification protein for the cleavage of eight phosphodiester bonds in DNA.", "output": "phosphodiester." }, { "input": "Type IIB restriction - modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities.", "output": "There is no related enetity." }, { "input": "Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites.", "output": "There is no related enetity." }, { "input": "BcgI cuts all eight target phosphodiester bonds before dissociation.", "output": "phosphodiester." }, { "input": "The BcgI protein contains A and B polypeptides in a 2: 1 ratio: A has one catalytic centre for each activity; B recognizes the DNA.", "output": "There is no related enetity." }, { "input": "We show here that BcgI is organized as A ( 2 ) B protomers, with B at its centre, but that these protomers self - associate to assemblies containing several A ( 2 ) B units.", "output": "There is no related enetity." }, { "input": "Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA.", "output": "There is no related enetity." }, { "input": "DNA - bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain.", "output": "There is no related enetity." }, { "input": "Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI.", "output": "There is no related enetity." }, { "input": "Its nuclease reaction may thus involve two A ( 2 ) B units, each bound to a recognition site, with two more A ( 2 ) B units bridging the complexes by protein - protein interactions between the nuclease domains.", "output": "There is no related enetity." }, { "input": "Understanding the role of gut microbes and probiotics in obesity: how far are we?", "output": "There is no related enetity." }, { "input": "Obesity has been associated with structural alterations in the gut microbiota, suggesting potential causality between specific microbial taxa and this disorder.", "output": "There is no related enetity." }, { "input": "Studies in animal models have also provided evidence for plausible gut microbiota mechanisms of action underlying body weight regulation.", "output": "There is no related enetity." }, { "input": "Yet evidence identifying which specific microbes contribute to or predict obesity is not completely consistent across studies.", "output": "There is no related enetity." }, { "input": "More recently, diet has also been shown to be primarily involved in regulating the microbiota structure initially related to obesity, suggesting that the role of microbes in energy balance is under the influence of diet.", "output": "There is no related enetity." }, { "input": "Controversy over the role of components of the gut microbiota in obesity has extended to bacteria, which although weakly related to body weight in observational and human intervention studies, are of interest due to their use as probiotics.", "output": "There is no related enetity." }, { "input": "This review focuses exclusively on human observational studies and probiotic intervention trials, excluding animal studies and studies in infants at early developmental stages, since such results cannot be extrapolated to human obesity at later stages in life.", "output": "There is no related enetity." }, { "input": "In this context, evidence for relationships between the gut microbiota composition and obesity and the possible role of probiotics is reviewed, discussing the strengths and weaknesses of the studies conducted to date.", "output": "There is no related enetity." }, { "input": "Influence of experimental type 1 diabetes on the pulmonary effects of diesel exhaust particles in mice.", "output": "There is no related enetity." }, { "input": "Epidemiologically, exposure to particulate air pollution is associated with increases in morbidity and mortality, and diabetics are especially vulnerable to effects of particles.", "output": "There is no related enetity." }, { "input": "This study was carried out to determine the respiratory effect of diesel exhaust particles ( DEP; 0. 4mg / kg ) on mice rendered diabetic by the injection of streptozotocin or vehicle ( control ).", "output": "streptozotocin." }, { "input": "Four weeks following induction of diabetes, the animals were intratracheally instilled ( i. t. ) with DEP ( 0. 4mg / kg ) or saline.", "output": "There is no related enetity." }, { "input": "24h later, the measurement of airway reactivity to methacholine in vivo by a forced oscillation technique showed a significant and dose - dependent increase in airway resistance in non - diabetic mice exposed to DEP versus non - diabetic mice exposed to saline.", "output": "methacholine." }, { "input": "Similarly, the airway resistance was significantly increased in diabetic mice exposed to DEP versus diabetic mice exposed to saline.", "output": "There is no related enetity." }, { "input": "Nevertheless, there was no difference in the airway resistance between diabetic and non - diabetic mice after i. t. administration of DEP.", "output": "There is no related enetity." }, { "input": "Following DEP administration there were neutrophil polymorphs infiltration of pulmonary interalveolar septae and the alveolar spaces with many macrophages containing DEP in both diabetic and non - diabetic mice.", "output": "There is no related enetity." }, { "input": "Interestingly, apoptotic cells were only found in the examined lung sections from diabetic mice exposed to DEP.", "output": "There is no related enetity." }, { "input": "Total proteins and albumin concentrations in bronchoalveolar lavage ( BAL ) fluid, markers for increase of epithelial permeability, were significantly increased in diabetic mice exposed to DEP compared to saline - treated diabetic and DEP - treated non diabetic mice.", "output": "There is no related enetity." }, { "input": "Superoxide dismutase activity and reduced glutathione concentration in BAL were significantly decreased in diabetic mice exposed to DEP compared to saline - treated diabetic and DEP - treated non diabetic mice.", "output": "Superoxide." }, { "input": "Moreover, tumor necrosis factor alpha ( TNF alpha ) concentrations were significantly increased in diabetic mice exposed to DEP compared to saline - treated diabetic and DEP - treated non diabetic mice.", "output": "There is no related enetity." }, { "input": "We conclude that, at the dose and time point investigated, DEP equally increased airway resistance and caused infiltration of inflammatory cells in the lung of both diabetic and non - diabetic mice.", "output": "There is no related enetity." }, { "input": "However, the occurrence of oxidative stress, the presence lung apoptotic cells and the increase of total proteins, albumin and TNF alpha in BAL fluid were only seen in DEP - exposed diabetic mice suggesting an increased respiratory susceptibility to particulate air pollution.", "output": "There is no related enetity." }, { "input": "Iron oxide particles modulate the ovalbumin - induced Th2 immune response in mice.", "output": "Iron oxide." }, { "input": "This study was designed to investigate the modulatory effects of submicron and nanosized iron oxide ( Fe ( 2 ) O ( 3 ) ) particles on the ovalbumin ( OVA ) - induced immune Th2 response in BALB / c mice.", "output": "iron oxide, Fe ( 2 ) O ( 3 )." }, { "input": "Particles were intratracheally administered four times to mice before and during the OVA sensitization period.", "output": "There is no related enetity." }, { "input": "For each particle type, three different doses, namely 4 x 100, 4 x 250 or 4 x 500 mu g / mouse, were used and for each dose, four groups of mice, i. e. group saline solution ( 1 ), OVA ( 2 ), particles ( 3 ), and OVA plus particles ( 4 ), were constituted.", "output": "There is no related enetity." }, { "input": "Mice exposed to OVA alone exhibited an allergic Th2 - dominated response with a consistent increase in inflammatory scores, eosinophil numbers, specific IgE levels and IL - 4 production.", "output": "There is no related enetity." }, { "input": "When the mice were exposed to OVA and to high and intermediate doses of iron oxide submicron - or nanoparticles, the OVA - induced allergic response was significantly inhibited, as evidenced by the decrease in eosinophil cell influx and specific IgE levels.", "output": "iron oxide." }, { "input": "However, the low dose ( 4 x 100 mu g ) of submicron particles had no significant effect on the OVA allergic response while the same dose of nanoparticles had an adjuvant effect on the Th2 response to OVA.", "output": "There is no related enetity." }, { "input": "In conclusion, these data demonstrate that the pulmonary immune response to OVA is a sensitive target for intratracheally instilled particles.", "output": "There is no related enetity." }, { "input": "Depending on the particle dose and size, the allergic response was suppressed or enhanced.", "output": "There is no related enetity." }, { "input": "Mice heterozygous for AChE are more sensitive to AChE inhibitors but do not respond to BuChE inhibition.", "output": "There is no related enetity." }, { "input": "An impaired central cholinergic system is at least partly involved in Alzheimer ' s disease ( AD ) pathogenesis, with cholinergic markers such as acetylcholinesterase ( AChE ) activity and protein levels decreasing as cognitive decline progresses.", "output": "There is no related enetity." }, { "input": "AD patients receive AChE inhibitor drugs to enhance cholinergic responses in the brain.", "output": "There is no related enetity." }, { "input": "The present study characterises the cholinergic system of mice heterozygous for AChE ( HZ ) as a suitable in vivo model for permanently reduced AChE activity.", "output": "There is no related enetity." }, { "input": "In comparison to homozygous, wild type ( WT ) mice, HZ mice show a 40 % reduction of AChE activity in the brain, while their hippocampal ACh levels are increased by 56 % as measured by microdialysis; choline acetyltransferase levels remain unaltered, and choline uptake increases 2 - fold.", "output": "choline, choline." }, { "input": "We demonstrate that HZ mice are significantly more sensitive to local AChE inhibition ( BW284c51 ), but remain insensitive to butyrylcholinesterase ( BuChE ) inhibition ( bambuterol ).", "output": "BW284c51, bambuterol." }, { "input": "HZ mice are also more sensitive to the peripheral application of the selective AChE inhibitor donepezil or the mixed inhibitor physostigmine; extracellular ACh levels rise significantly after administration of both drugs; also glucose levels are moderately increased indicating potentially non - cholinergic effects of donepezil.", "output": "donepezil, physostigmine, glucose, donepezil." }, { "input": "Behavioural tests show comparable cognitive function in both mouse strains.", "output": "There is no related enetity." }, { "input": "Our results are discussed in relation to the use of AChE / BuChE inhibitors in AD patients.", "output": "There is no related enetity." }, { "input": "Decreased pain responses of C - C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli.", "output": "There is no related enetity." }, { "input": "Chemokines are small chemotactic cytokines that elicit many physiological and pathological effects through binding to their corresponding receptors.", "output": "There is no related enetity." }, { "input": "Recent studies have suggested that C - C chemokine receptor ( CCR ) 5 interacts with mu - opioid receptor and modifies a nociceptive reaction.", "output": "There is no related enetity." }, { "input": "We examined effects of CCR5 deficiency on pain responses by employing CCR5 knockout ( KO ) mice.", "output": "There is no related enetity." }, { "input": "We found that pain responses of CCR5 KO mice to chemical or inflammation stimuli were milder than those of CCR5 wild type ( WT ) mice.", "output": "There is no related enetity." }, { "input": "However, there was no remarkable change in thermal nociception.", "output": "There is no related enetity." }, { "input": "To prove the involvement of CCR5 deletion in lowered nociception, we examined pain reactions with CCR5 WT mice following treatment of a CCR5 antagonist ( D - Ala ( 1 ) - peptide T - NH ( 2, ) DAPTA ).", "output": "D - Ala ( 1 ) - peptide T - NH ( 2 , ), DAPTA." }, { "input": "Chemical or inflammatory pain behavior was significantly relieved by intracerebroventricular infusion of the inhibitor.", "output": "There is no related enetity." }, { "input": "When we assessed expression level of mu - opioid receptor ( MOR ) in the periaqueductal gray where the receptors are critical for analgesic effects, immunoreactivity of MOR was significantly higher in CCR5 KO mice than WT mice without change in phosphorylation level of the receptor.", "output": "There is no related enetity." }, { "input": "Reduced nociceptive responses in CCR5 KO mice were moderated by administration of naloxone and d - Phe - Cys - Tyr - d - Trp - Arg - Thr - Pen - Thr - NH2 ( CTAP ), MOR antagonists.", "output": "naloxone, d - Phe - Cys - Tyr - d - Trp - Arg - Thr - Pen - Thr - NH2, CTAP." }, { "input": "Our data indicate that CCR5 deficiency is related to up - regulation of MOR without an increase in the receptor desensitization which might result in increased analgesic effects against chemical or inflammatory stimuli.", "output": "There is no related enetity." }, { "input": "Alternatively, higher amount of opioid ligands in CCR5 mice might be linked to these results.", "output": "There is no related enetity." }, { "input": "Therefore, CCR5 appears to be a therapeutic target for treatment of pain related diseases such as inflammatory hyperalgesia.", "output": "There is no related enetity." }, { "input": "First - principles simulation of the absorption bands of fluorenone in zeolite L.", "output": "fluorenone, zeolite L." }, { "input": "The absorption spectrum of fluorenone in zeolite L is calculated from first - principles simulations.", "output": "fluorenone, zeolite L." }, { "input": "The broadening of each band is obtained from the explicit treatment of the interactions between the chromophore and its environment in the statistical ensemble.", "output": "There is no related enetity." }, { "input": "The comparison between the simulated and measured spectra reveals the main factors affecting the spectrum of the chromophore in hydrated zeolite L.", "output": "zeolite L." }, { "input": "Whereas each distinguishable band is found to originate from a single electronic transition, the bandwidth is determined by the statistical nature of the environment of the fluorenone molecule.", "output": "fluorenone." }, { "input": "The K ( + )... O = C motif is retained in all conformations.", "output": "K ( + ), O = C." }, { "input": "Although the interactions between K ( + ) and the fluorenone carbonyl group result in an average lengthening of the C [ double bond, length as m - dash ] O bond and in a redshift of the lowest energy absorption band compared to gas phase or non - polar solvents, the magnitude of this shift is noticeably smaller than the total shift.", "output": "K ( + ), fluorenone carbonyl, C, O." }, { "input": "An important factor affecting the shape of the band is fluorenone ' s orientation, which is strongly affected by the presence of water.", "output": "fluorenone." }, { "input": "The effect of direct interactions between fluorenone and water is, however, negligible.", "output": "fluorenone." }, { "input": "Uptake and toxicity of polycyclic aromatic hydrocarbons in terrestrial springtails - - studying bioconcentration kinetics and linking toxicity to chemical activity.", "output": "polycyclic aromatic hydrocarbons." }, { "input": "Passive dosing applies a polymer loaded with test compound ( s ) to establish and maintain constant exposure in laboratory experiments.", "output": "There is no related enetity." }, { "input": "Passive dosing with the silicone poly ( dimethylsiloxane ) was used to control exposure of the terrestrial springtail Folsomia candida to six polycyclic aromatic hydrocarbons ( PAHs ) in bioconcentration and toxicity experiments.", "output": "poly ( dimethylsiloxane ), polycyclic aromatic hydrocarbons, PAHs." }, { "input": "Folsomia candida could move freely on the PAH - loaded silicone, resulting in exposure via air and direct contact.", "output": "PAH, silicone." }, { "input": "The bioconcentration kinetics indicated efficient uptake of naphthalene, anthracene, and pyrene through air and ( near ) equilibrium partitioning of these PAHs to lipids and possibly the waxy layer of the springtail cuticle.", "output": "naphthalene, anthracene, pyrene." }, { "input": "Toxicities of naphthalene, phenanthrene, and pyrene were related to chemical activity, which quantifies the energetic level and drives spontaneous processes including diffusive biouptake.", "output": "naphthalene, phenanthrene, pyrene." }, { "input": "Chemical activity - response relationships yielded effective lethal chemical activities ( La50s ) well within the expected range for baseline toxicity ( 0. 01 - 0. 1 ).", "output": "There is no related enetity." }, { "input": "Effective lethal body burdens for naphthalene and pyrene exceeded the expected range of 2 to 8 mmol kg ( - 1 ) fresh weight, which again indicated the waxy layer to be a sorbing phase.", "output": "naphthalene, pyrene." }, { "input": "Finally, chemical activities were converted into equilibrium partitioning concentrations in lipids yielding effective lethal concentrations for naphthalene and phenanthrene in good correspondence with the lethal membrane burden for baseline toxicity ( 40 - 160 mmol kg ( - 1 ) lipid ).", "output": "naphthalene, phenanthrene." }, { "input": "Passive dosing was a practical approach for tightly controlling PAH exposure, which in turn provided new experimental possibilities and findings.", "output": "There is no related enetity." }, { "input": "Gamma - radiation induced formation of chromium oxide nanoparticles from dissolved dichromate.", "output": "chromium oxide, dichromate." }, { "input": "The formation of chromium oxide nanoparticles by gamma radiolysis of Cr ( VI ) ( CrO ( 4 ) ( 2 - ) or Cr ( 2 ) O ( 7 ) ( 2 - ) ) solutions was investigated as a function of pH and initial Cr ( VI ) concentration by measuring [ Cr ( VI ) ], the particle concentration ( [ Cr ( III ) ( col ) ] ) and [ H ( 2 ) ], and by characterizing the particles using TEM, Raman, FTIR and XPS.", "output": "chromium oxide, Cr ( VI ), CrO ( 4 ) ( 2 - ), Cr ( 2 ) O ( 7 ) ( 2 - ), Cr ( VI ), Cr ( VI ), Cr ( III ), H ( 2 )." }, { "input": "The results show that Cr ( VI ) is easily reduced to Cr ( III ) by a homogeneous aqueous reaction with. e ( aq ) ( - ), but, due to the stability of Cr ( III ) colloids, the growth of the Cr ( OH ) ( 3 ) particles is very slow.", "output": "Cr ( VI ), Cr ( III ), Cr ( III ), Cr ( OH ) ( 3 )." }, { "input": "As the particles grow the interior of the particle dehydrates to form Cr ( 2 ) O ( 3 ) while the outer layer remains hydrated.", "output": "Cr ( 2 ) O ( 3." }, { "input": "When most of the Cr ( VI ) that is initially present in the solution is converted to Cr ( OH ) ( 3 ) further redox reactions of chromium species occur on the particle surfaces.", "output": "Cr ( VI ), Cr ( OH ) ( 3 ), chromium." }, { "input": "The redox system reaches a pseudo - equilibrium state due to cyclic reactions of Cr ( III ) with. OH and H ( 2 ) O ( 2 ), and reactions of Cr ( VI ) with. e ( aq ) ( - ) and H ( 2 ) O ( 2 ).", "output": "Cr ( III ), OH, H ( 2 ) O ( 2 ), Cr ( VI ), H ( 2 ) O ( 2 )." }, { "input": "The size distribution of the particles that are formed is controlled by these solution - solid interface reactions.", "output": "There is no related enetity." }, { "input": "Assessing causation of the extirpation of stream macroinvertebrates by a mixture of ions.", "output": "There is no related enetity." }, { "input": "Increased ionic concentrations are associated with the impairment of benthic invertebrate assemblages.", "output": "There is no related enetity." }, { "input": "However, the causal nature of that relationship must be demonstrated so that it can be used to derive a benchmark for conductivity.", "output": "There is no related enetity." }, { "input": "The available evidence is organized in terms of six characteristics of causation: co - occurrence, preceding causation, interaction, alteration, sufficiency, and time order.", "output": "There is no related enetity." }, { "input": "The inferential approach is to weight the lines of evidence using a consistent scoring system, weigh the evidence for each causal characteristic, and then assess the body of evidence.", "output": "There is no related enetity." }, { "input": "Through this assessment, the authors found that a mixture containing the ions Ca ( + ), Mg ( + ), HCO 3 ( - ), and SO 4 ( - ), as measured by conductivity, is a common cause of extirpation of aquatic macroinvertebrates in Appalachia where surface coal mining is prevalent.", "output": "Ca ( + ), Mg ( + ), HCO 3 ( - ), SO 4 ( - ), coal." }, { "input": "The mixture of ions is implicated as the cause rather than any individual constituent of the mixture.", "output": "There is no related enetity." }, { "input": "The authors also expect that ionic concentrations sufficient to cause extirpations would occur with a similar salt mixture containing predominately HCO 3 ( - ), SO 4 ( 2 - ), Ca ( 2 + ), and Mg ( 2 + ) in other regions with naturally low conductivity.", "output": "HCO 3 ( - ), SO 4 ( 2 - ), Ca ( 2 + ), Mg ( 2 + )." }, { "input": "This case demonstrates the utility of the method for determining whether relationships identified in the field are causal.", "output": "There is no related enetity." }, { "input": "Experimental exposure of eggs to polybrominated diphenyl ethers BDE - 47 and BDE - 99 in red - eared sliders ( Trachemys scripta elegans ) and snapping turtles ( Chelydra serpentina ) and possible species - specific differences in debromination.", "output": "polybrominated diphenyl ethers, BDE - 47, BDE - 99." }, { "input": "Polybrominated diphenyl ethers ( PBDEs ) are a bioaccumulative, persistent, and toxic class of flame retardants that can potentially impact turtles in natural habitats via exposure through maternal transfer.", "output": "Polybrominated diphenyl ethers, PBDEs." }, { "input": "To simulate maternal transfer in the present study, PBDE congeners BDE - 47 and BDE - 99 were topically applied to the eggshell and were allowed to diffuse into the egg contents of the red - eared slider ( Trachemys scripta elegans ) and snapping turtle ( Chelydra serpentina ).", "output": "PBDE, BDE - 47, BDE - 99." }, { "input": "Eggs were topically dosed over 8 d to achieve a target concentration of 40 ng / g in the egg contents.", "output": "There is no related enetity." }, { "input": "Transfer efficiency was higher for BDE - 47 than for BDE - 99 in the red - eared sliders ( 25. 8 +/- 1. 9 % vs 9. 9 +/- 1. 1 % ) and snapping turtles ( 31. 3 +/- 1. 6 % vs 12. 5 +/- 1. 4 % ), resulting in greater BDE - 47 and lower BDE - 99 egg content concentrations relative to the 40 ng / g target.", "output": "BDE - 47, BDE - 99, BDE - 47, BDE - 99." }, { "input": "However, only 25. 8 and 31. 3 % of the total BDE - 47 and 9. 9 and 12. 5 % of the total BDE - 99 dose applied could be accounted for in the red - eared slider and snapping turtle egg contents, respectively.", "output": "BDE - 47, BDE - 99." }, { "input": "Additionally, increased BDE - 47 in red - eared slider egg contents dosed with only BDE - 99 indicate that BDE - 99 might have been debrominated to BDE - 47.", "output": "BDE - 47, BDE - 99, BDE - 99, BDE - 47." }, { "input": "The efficacy of topical dosing for administering desired embryonic exposures is clearly affected by the chemical properties of the applied compounds and was more successful for BDE - 47 in both species.", "output": "BDE - 47." }, { "input": "Gs - coupled adenosine receptors differentially limit antigen - induced mast cell activation.", "output": "adenosine." }, { "input": "Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes.", "output": "There is no related enetity." }, { "input": "Allergen - induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases.", "output": "There is no related enetity." }, { "input": "Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators.", "output": "There is no related enetity." }, { "input": "Many of these mediators, such as histamine, are released by mast cells.", "output": "histamine." }, { "input": "Targeting pathways that limit antigen - induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell.", "output": "There is no related enetity." }, { "input": "In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A ( 2B ) receptors, suggest that adenosine receptors, specifically the G ( s ) - coupled A ( 2A ) and A ( 2B ) receptors, might provide such a target.", "output": "adenosine." }, { "input": "Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo.", "output": "adenosine, adenosine." }, { "input": "We identify A ( 2B ) as the primary receptor limiting mast cell degranulation, whereas the combined activity of A ( 2A ) and A ( 2B ) is required for the inhibition of cytokine synthesis.", "output": "There is no related enetity." }, { "input": "QT dispersion in patients with acromegaly.", "output": "There is no related enetity." }, { "input": "Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone.", "output": "There is no related enetity." }, { "input": "The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta - analyses.", "output": "There is no related enetity." }, { "input": "Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known.", "output": "There is no related enetity." }, { "input": "QT dispersion ( dQT ) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death.", "output": "There is no related enetity." }, { "input": "This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients.", "output": "There is no related enetity." }, { "input": "This cross - sectional case - control study enrolled 20 patients ( 10 female and 10 male ) with acromegaly and 20 healthy controls ( 11 female and 9 male ) after exclusion criteria were applied.", "output": "There is no related enetity." }, { "input": "Each participant underwent 12 - lead electrocardiography, including >= 3 QRS complexes, at a speed of 25 mm / s after a 15 - min rest.", "output": "There is no related enetity." }, { "input": "In each participant, the QT interval ( beginning of the Q wave to the end of the T wave ) was corrected ( QTc ) for heart rate using Bazett ' s formula [ Formula: see text ] QTc dispersion ( dQTc ) ( QTc max - QTc min ) was also calculated.", "output": "There is no related enetity." }, { "input": "There was no significant difference in median dQTc between the acromegalic patients ( 0. 79 s ) and the controls ( 0. 45 s ) ( p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "Active acromegalic patients ( n = 14 ) were estimated to have a median dQTc of 0. 82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels < 0. 4 ng / mL, GH < 1 ng / mL based on oral glucose tolerance test, and normal IGF - I for age and gender.", "output": "glucose." }, { "input": "A significant difference was noted in median dQTc between the active acromegalic patients and the controls ( p = 0. 015 ).", "output": "There is no related enetity." }, { "input": "The dQT in active acromegalic patients was longer than that in the control group, which indicates that patients with active acromegaly might have an elevated risk for ventricular arrhythmia.", "output": "There is no related enetity." }, { "input": "We think that a non - invasive, simple and inexpensive marker - measurement of dQT - as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.", "output": "There is no related enetity." }, { "input": "Longitudinal cystic fibrosis care.", "output": "There is no related enetity." }, { "input": "Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges.", "output": "There is no related enetity." }, { "input": "Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities.", "output": "There is no related enetity." }, { "input": "From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy.", "output": "There is no related enetity." }, { "input": "With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator ( CFTR ) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation - specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport.", "output": "There is no related enetity." }, { "input": "Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease - transforming management options for individuals with cystic fibrosis.", "output": "There is no related enetity." }, { "input": "Maternal and fetal exposure to bisphenol a is associated with alterations of thyroid function in pregnant ewes and their newborn lambs.", "output": "bisphenol a." }, { "input": "The putative thyroid - disrupting properties of bisphenol A ( BPA ) highlight the need for an evaluation of fetal exposure and its consequence on the mother / newborn thyroid functions in models relevant to human.", "output": "bisphenol A, BPA." }, { "input": "The goals of this study were to characterize in sheep a relevant model for human pregnancy and thyroid physiology, the internal exposures of the fetuses and their mothers to BPA and its main metabolite BPA - glucuronide ( Gluc ), and to determine to what extent it might be associated with thyroid disruption.", "output": "BPA, BPA - glucuronide." }, { "input": "Ewes were treated with BPA [ 5 mg / ( kg. d ) sc ] or vehicle from d 28 until the end of pregnancy.", "output": "BPA." }, { "input": "Unconjugated BPA did not appear to accumulate in pregnant ewes, and its concentration was similar in the newborns and their mothers ( 0. 13 +/- 0. 02 and 0. 18 +/- 0. 03 nmol / ml in cord and maternal blood, respectively ).", "output": "BPA." }, { "input": "In amniotic fluid and cord blood, BPA - Gluc concentrations were about 1300 - fold higher than those of BPA.", "output": "BPA - Gluc, BPA." }, { "input": "Total T ( 4 ) concentrations were decreased in BPA - treated pregnant ewes and in the cord and the jugular blood of their newborns ( 30 % decrease ).", "output": "BPA." }, { "input": "A similar difference was observed for free T ( 4 ) plasma concentrations in the jugular blood of the newborns.", "output": "There is no related enetity." }, { "input": "Our results show in a long - gestation species with a similar regulatory scheme of thyroid function as humans that BPA in utero exposure can be associated with hypothyroidism in the newborns.", "output": "BPA." }, { "input": "If such an effect were to be confirmed for a more relevant exposure scheme to BPA, this would constitute a major issue for BPA risk assessment.", "output": "BPA." }, { "input": "Molecular modeling and simulation of membrane lipid - mediated effects on GPCRs.", "output": "There is no related enetity." }, { "input": "Functioning of G protein - coupled receptors ( GPCRs ) is tightly linked to the membrane environment, but a molecular level understanding of the modulation of GPCR by membrane lipids is not available.", "output": "There is no related enetity." }, { "input": "However, specific receptor - lipid interactions as well as unspecific effects mediated by the bulk properties of the membrane ( thickness, curvature, etc. ) have been proposed to be key regulators of GPCR modulation.", "output": "There is no related enetity." }, { "input": "In this review, we examine computational efforts made towards modeling and simulation of ( i ) the complex behavior of membrane lipids, ( ii ) membrane lipid - GPCR interactions as well as membrane lipid - mediated effects on GPCRs and ( iii ) GPCR oligomerization in a native - like membrane environment.", "output": "There is no related enetity." }, { "input": "We propose that, from the perspective of computational modeling, all three of these components need to be addressed in order to achieve a deeper understanding of GPCR functioning.", "output": "There is no related enetity." }, { "input": "Presently, we are able to simulate numerous lipid properties applying advanced computational techniques, although some barriers, such as the time - length of these simulations, need to be overcome.", "output": "There is no related enetity." }, { "input": "Implementing three - dimensional structures of GPCRs in such validated membrane systems can give novel insights in membrane - dependent receptor modulation and formation of higher order receptor complexes.", "output": "There is no related enetity." }, { "input": "Finally, more realistic GPCR - membrane models would provide a very useful tool in studying receptor behavior and its modulation by small drug - like ligands, a relevant issue for drug discovery.", "output": "There is no related enetity." }, { "input": "Metabotropic purinergic receptors in lipid membrane microdomains.", "output": "There is no related enetity." }, { "input": "There is broad evidence that association of transmembrane receptors and signalling molecules with lipid rafts / caveolae provides an enriched environment for protein - protein interactions necessary for signal transduction, and a mechanism for the modulation of neurotransmitter and / or growth factor receptor function.", "output": "There is no related enetity." }, { "input": "Several receptors translocate into submembrane compartments after ligand binding, while others move in the opposite direction.", "output": "There is no related enetity." }, { "input": "The role of such a dynamic localization and functional facilitation is signalling modulation and receptor desensitization or internalization.", "output": "There is no related enetity." }, { "input": "Purine and pyrimidine nucleotides have been viewed as primordial precursors in the evolution of all forms of intercellular communication, and they are now regarded as fundamental extracellular signalling molecules.", "output": "Purine, pyrimidine, nucleotides." }, { "input": "They propagate the purinergic signalling by binding to ionotropic and metabotropic receptors expressed on the plasma membrane of almost all cell types, tissues and organs.", "output": "There is no related enetity." }, { "input": "Here, we have illustrated the localization in lipid rafts / caveolae of G protein - coupled P1 receptors for adenosine and P2Y receptors for nucleoside tri - and di - phosphates.", "output": "adenosine, nucleoside tri - and di - phosphates." }, { "input": "We have highlighted that microdomain partitioning of these purinergic GPCRs is cell - specific, as is the overall expression levels of these same receptors.", "output": "There is no related enetity." }, { "input": "Moreover, we have described that disruption of submembrane compartments can shift the purinergic receptors from raft / caveolar to non - raft / non - caveolar fractions, and then abolish their ability to activate lipid signalling pathways and to integrate with additional lipid - controlled signalling events.", "output": "There is no related enetity." }, { "input": "This modulates the biological response to purinergic ligands and most of all indicates that the topology of the various purinergic components at the cell surface not only organizes the signal transduction machinery, but also controls the final cellular response.", "output": "There is no related enetity." }, { "input": "Stabilizing the pro - apoptotic BimBH3 helix ( BimSAHB ) does not necessarily enhance affinity or biological activity.", "output": "There is no related enetity." }, { "input": "An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their alpha - helical conformation, for example, stabilized BimBH3 peptides ( BimSAHB ) designed to induce apoptosis.", "output": "There is no related enetity." }, { "input": "Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the pro - survival Bcl - 2 proteins.", "output": "There is no related enetity." }, { "input": "We attribute this loss in affinity to disruption of a network of stabilizing intramolecular interactions present in the bound state of the native peptide.", "output": "There is no related enetity." }, { "input": "Altering this network may compromise binding affinity, as in the case of the BimBH3 stapled peptide studied here.", "output": "There is no related enetity." }, { "input": "Moreover, cells exposed to these peptides do not readily undergo apoptosis, strongly indicating that BimSAHB is not inherently cell permeable.", "output": "There is no related enetity." }, { "input": "Effect of Australian elapid venoms on blood coagulation: Australian Snakebite Project ( ASP - 17 ).", "output": "There is no related enetity." }, { "input": "Snake venoms contain toxins that activate the coagulation network and cause venom - induced consumption coagulopathy.", "output": "There is no related enetity." }, { "input": "A previously developed mathematical model of the coagulation network was refined and used to describe and predict the time course of changes in the coagulation factors following envenomation by Brown snake ( Pseudonaja spp. ), Tiger snake ( Notechis scutatus ), Rough - scaled snake ( Tropidechis carinatus ) and Hoplocephalus spp.", "output": "There is no related enetity." }, { "input": "( Stephens banded, Pale headed and Broad headed ).", "output": "There is no related enetity." }, { "input": "Simulations of the time course of the change in coagulation factors were compared to data obtained from a large prospective study of Australian snake bites - the Australian Snakebite Project.", "output": "There is no related enetity." }, { "input": "The model predictions were also compared against data for partial and complete VICC obtained from the same study.", "output": "There is no related enetity." }, { "input": "The model simulations were used to understand the differences in consumption and recovery of clotting factors in partial versus complete VICC as well as among bites from different snake types.", "output": "There is no related enetity." }, { "input": "The model suggested that the venoms were absorbed almost instantaneously and provided a reasonable prediction of the observed concentration of clotting factors over time in patients bitten by Australian elapid snakes.", "output": "There is no related enetity." }, { "input": "The model predictions suggested a higher consumption of factors ( fibrinogen, II and IX in particular ) in patients with complete VICC compared to those with partial VICC.", "output": "There is no related enetity." }, { "input": "The model also predicted that snakes with \" Xa - like \" venoms may produce a less severe VICC than snakes with \" Xa: Va - like \" venoms.", "output": "There is no related enetity." }, { "input": "One hundred years of helicene chemistry.", "output": "helicene." }, { "input": "Part 2: stereoselective syntheses and chiral separations of carbohelicenes.", "output": "carbohelicenes." }, { "input": "Carbohelicenes generally incorporate a helical, distorted, conjugated, polyaromatic system with ortho - fused benzenoid rings, which is a fundamental molecular characteristic of this class of compounds.", "output": "Carbohelicenes, benzenoid." }, { "input": "They have been described as \" molecules in distress \" due to their distortion.", "output": "There is no related enetity." }, { "input": "The generation of a chiral helicity in helicenes was observed because of a severe intramolecular steric strain.", "output": "helicenes." }, { "input": "Helicity is a molecular necessity in the higher series of carbohelicenes, when at some point, a helical pitch occurs when a second coil is formed.", "output": "carbohelicenes." }, { "input": "The most interesting properties resulting from such molecular distortion are the very high chiroptical and circular dichroism values.", "output": "There is no related enetity." }, { "input": "For instance, the resolution of some helicene racemates by \" hand picking \" of a few homochiral single enantiomeric crystals allowed for a measurement of their optical rotation.", "output": "helicene." }, { "input": "Due to that intrinsic chirality spanned over a large polyaromatic template, preliminary results clearly established the efficiency of carbohelicenes to induce asymmetry and chirality in organic synthesis and in supramolecular chemistry.", "output": "carbohelicenes." }, { "input": "Additionally, they have some potential uses in several fields: materials science, nanoscience, chemical biology and supramolecular chemistry.", "output": "There is no related enetity." }, { "input": "It has encouraged many attempts to develop new asymmetric syntheses of carbohelicenes, as well as some chiral separations of enantiomers and diastereoisomers.", "output": "carbohelicenes." }, { "input": "This review is thus dedicated to carbohelicene chirality.", "output": "carbohelicene." }, { "input": "It gathered a substantial collection of data, and a comprehensive review on the preparations of enantioenriched helicenes, either from an asymmetric synthesis or from a chiral separation.", "output": "helicenes." }, { "input": "Utilizations of non - racemic helicenes and their applications will be treated in the following review ( Part 3 ), and will not be the subject of this manuscript.", "output": "helicenes." }, { "input": "Antidepressant - like effect of oleanolic acid in mice exposed to the repeated forced swimming test.", "output": "oleanolic acid." }, { "input": "The study aimed to explore the antidepressant - like effect of oleanolic acid and its possible mechanism related to the monoaminergic system and neurotrophin in mice exposed to the repeated forced swimming test ( FST ).", "output": "oleanolic acid." }, { "input": "Both the duration and the latency of immobility affected by oleanolic acid ( 10, 20 and 40 mg / kg ) were evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by neurochemical and brain - derived neurotrophic factor ( BDNF ) analyses in the mouse brain regions of frontal cortex and whole hippocampus.", "output": "oleanolic acid." }, { "input": "A repeated analysis of variance ( ANOVA ) indicated that over retesting the immobility time increased, whereas latency to immobility tended to decrease.", "output": "There is no related enetity." }, { "input": "Minute - by - minute analysis showed that immobility time also increased during the 4 - min course of the test.", "output": "There is no related enetity." }, { "input": "In addition, post - hoc Dunnett ' s test demonstrated that sub - chronic and chronic, but not acute, oleanolic acid treatment reduced the immobility time ( sub - chronic: 20 mg / kg, 43. 5 %; chronic: 10 mg / kg, 19. 3 %; 20 mg / kg, 31. 8 % ) and increased the latency to immobility ( sub - chronic: 10 mg / kg, 60. 6 %; 20 mg / kg, 80. 1 %; chronic: 10 mg / kg, 121. 8 %; 20 mg / kg, 140. 8 %; 40 mg / kg, 80. 0 % ).", "output": "oleanolic acid." }, { "input": "Furthermore, chronic administration of oleanolic acid significantly increased serotonin ( 5 - HT ) levels ( frontal cortex: 44. 5 %, 41. 9 %, 27. 5 % for 10, 20, 40 mg / kg; hippocampus: 57. 2 %, 80. 9 % for 10, 20 mg / kg ), decreased 5 - hydroxyindoleacetic acid ( 5 - HIAA ) / 5 - HT ratio ( frontal cortex: 31. 6 %, 30. 1 %, 23. 5 %; hippocampus: 40. 6 %, 47. 7 %, 29. 2 % for 10, 20, 40 mg / kg ) and elevated norepinephrine ( NE ) levels ( hippocampus: 20 mg / kg, 45. 4 % ) but did not alter dopamine ( DA ) levels.", "output": "oleanolic acid, serotonin, 5 - HT, 5 - hydroxyindoleacetic acid, 5 - HIAA, 5 - HT, norepinephrine, dopamine." }, { "input": "Moreover, BDNF levels in the two brain regions were also elevated by chronic oleanolic acid treatment ( frontal cortex: 20 mg / kg, 67. 2 %; hippocampus: 10 mg / kg, 36. 4 %; 20 mg / kg, 55. 1 % ).", "output": "oleanolic acid." }, { "input": "Taken together, these findings imply that functions of 5 - HT, NE and BDNF may be involved in the antidepressant - like effect of oleanolic acid.", "output": "5 - HT, oleanolic acid." }, { "input": "A review of anti - inflammatory agents for symptoms of schizophrenia.", "output": "There is no related enetity." }, { "input": "Schizophrenia is a chronic debilitating mental disorder that affects about 1 % of the US population.", "output": "There is no related enetity." }, { "input": "The pathophysiology and etiology remain unknown, thus new treatment targets have been challenging and few novel treatments with new mechanisms of action have come to market in the past few decades.", "output": "There is no related enetity." }, { "input": "Increasing attention has been paid to the role of inflammation in schizophrenia and new data suggests that decreasing inflammation and inflammatory biomarkers may play some role in schizophrenia treatment.", "output": "There is no related enetity." }, { "input": "This review summarizes the clinical trial literature regarding medications that possess anti - inflammatory properties that have been tested for schizophrenia symptoms and covers such medications as non - steroidal anti - inflammatory agents, such as the cyclo - oxygenase - 2 ( COX - 2 ) inhibitors and aspirin, omega - 3 fatty acids, neurosteroids and minocycline.", "output": "steroidal, aspirin, omega - 3 fatty acids, neurosteroids, minocycline." }, { "input": "Overall, there is accumulating evidence, albeit mostly adjunctive treatments, that agents working on inflammatory pathways have some benefits in people with schizophrenia.", "output": "There is no related enetity." }, { "input": "In the next few years the field will begin to see data on many treatments with anti - inflammatory properties that are currently under study.", "output": "There is no related enetity." }, { "input": "Hopefully advancements in understanding inflammation and effective treatments having anti - inflammatory properties may help revolutionize our understanding and provide new targets for prevention and treatment in schizophrenia.", "output": "There is no related enetity." }, { "input": "Arsenic activates endothelin - 1 Gi protein - coupled receptor signaling to inhibit stem cell differentiation in adipogenesis.", "output": "Arsenic." }, { "input": "Dysfunctional lipid and glucose metabolism contribute to metabolic syndrome - a major public health concern that enhances cardiovascular disease risk.", "output": "glucose." }, { "input": "Arsenic ( As ( III ) ) exposure may increase metabolic syndrome and cardiovascular disease risk by impairing adipose tissue differentiation, function, and insulin sensitivity through pathogenic mechanisms that remain unclear.", "output": "Arsenic, As ( III )." }, { "input": "We hypothesized that As ( III ) signals through the Pertussis toxin ( Ptx ) sensitive, Gi protein - coupled receptor ( GPCR ) to impair adipogenesis, as previously demonstrated for its stimulation of vascular oxidant generation, angiogenesis, and remodeling.", "output": "As ( III )." }, { "input": "Because both As ( III ) and GPCR ligands inhibit progenitor cell differentiation into adipocytes, we investigated the hypothesis in a model of low - passage human mesenchymal stem cells ( hMSC ).", "output": "As ( III )." }, { "input": "As ( III ) ( 0. 1 - 1. 0 micro M ) suppressed dexamethasone / insulin - induced hMSC adipogenesis, as indicated by decreased transcriptional promoters of differentiation, decreased fat droplet formation, and decreased expression of differentiated adipocyte markers, such as adiponectin and perilipin.", "output": "As ( III ), dexamethasone." }, { "input": "Preincubating hMSC with Ptx prevented 90 % of the suppressive effect of As ( III ).", "output": "As ( III )." }, { "input": "Selective competitive antagonists of Gi - coupled endothelin - 1 type A and B receptors were ~ 60 % effective in blocking As ( III ) inhibition and combination of antagonists to both receptors were 85 % effective.", "output": "As ( III )." }, { "input": "In contrast, antagonists to the sphingosine - 1 - phosphate type 1 receptor ( previously shown to mediate As ( III ) vascular effects ) or the angiotensin II type 1 receptor were ineffective in blocking As ( III ) effects.", "output": "sphingosine - 1 - phosphate, As ( III ), As ( III )." }, { "input": "These studies suggest a majority of arsenic - inhibited adipocyte differentiation, and metabolism requires endothelin - 1 GPCRs and that As ( III ) effects on GPCR signaling are tissue and context specific.", "output": "arsenic, As ( III )." }, { "input": "This may represent a significant mechanism for the contribution of arsenic exposure to increased metabolic and cardiovascular diseases.", "output": "arsenic." }, { "input": "The progesterone positive feedback effect in women after ovariectomy.", "output": "progesterone." }, { "input": "Various ovarian substances regulate the secretion of gonadotrophins during the menstrual cycle, but there are still several unclarified issues.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate the positive feedback effect of progesterone during the immediate period following ovariectomy.", "output": "progesterone." }, { "input": "Experiments were performed in 12 normally cycling women ( aged 39 - 49 years ).", "output": "There is no related enetity." }, { "input": "Following abdominal hysterectomy plus bilateral ovariectomy performed on cycle day 3 ( day 0 ), the women received either estradiol via skin patches ( days 0 - 7, n = 6, group 1 ) or estradiol as above plus vaginal progesterone ( days 1 - 7, n = 6, group 2 ).", "output": "estradiol, estradiol." }, { "input": "Serum estradiol values increased similarly in the two groups.", "output": "estradiol." }, { "input": "After the operation, serum progesterone levels decreased significantly in group 1, while in group 2 they remained stable becoming higher than in group 1 ( p < 0. 05 ).", "output": "progesterone." }, { "input": "An LH and an FSH surge occurred in group 2 with the values after the peak returning to the pre - surge baseline.", "output": "There is no related enetity." }, { "input": "In contrast, in group 1 LH and FSH levels following an initial decrease, increased gradually until the end of the experiment.", "output": "There is no related enetity." }, { "input": "These results demonstrate that, despite a variable response to estrogens, the positive feedback effect of progesterone remained intact immediately after ovariectomy in women.", "output": "estrogens, progesterone." }, { "input": "It is suggested that it is the combining action of estradiol and progesterone that can ensure the expression of a positive feedback mechanism in women.", "output": "estradiol, progesterone." }, { "input": "A new approach to predicting human hepatic clearance of CYP3A4 substrates using monkey pharmacokinetic data.", "output": "There is no related enetity." }, { "input": "1.", "output": "There is no related enetity." }, { "input": "Focusing on the genetic similarity of CYP3A subfamily enzymes ( CYP3A4 and CYP3A5 ) between monkeys and humans, we have attempted to provide a single - species approach to predicting human hepatic clearance ( CLh ) of CYP3A4 substrates using pharmacokinetic parameters in cynomolgus monkeys following intravenous administrations.", "output": "There is no related enetity." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "Hepatic intrinsic clearance ( CLint, h ) of six CYP3A4 substrates ( alprazolam, clonazepam, diltiazem, midazolam, nifedipine, and quinidine ), covering a wide range of clearance, in monkeys correlated well with that cited in literature for humans ( R = 0. 90 ) with a simple equation of Y = 0. 165X ( Y: human CLint, h, X: monkey CLint, h, represented in mL / min / kg ).", "output": "alprazolam, clonazepam, diltiazem, midazolam, nifedipine, quinidine." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "To verify the predictability of human CLint, h, monkey CLint, h of a test set of CYP3A4 substrates cited in literature ( dexamethasone, nifedipine, midazolam, quinidine, tacrolimus, and verapamil ) was applied to the equation and human CLint, h was calculated.", "output": "dexamethasone, nifedipine, midazolam, quinidine, tacrolimus, verapamil." }, { "input": "The human CLint, h of all the substrates was predicted within 3 - fold error ( fold error: 0. 35 - 2. 77 ).", "output": "There is no related enetity." }, { "input": "4.", "output": "There is no related enetity." }, { "input": "The predictability of human CLh by our method was superior to common in vivo prediction methods ( allometry and liver blood flow method ).", "output": "There is no related enetity." }, { "input": "These results suggest that human hepatic clearance of CYP3A4 substrates can be predicted by applying cynomolgus monkey CLint, h obtained following intravenous administrations in each laboratory to the simple equation.", "output": "There is no related enetity." }, { "input": "Assessment of cytochrome P450 ( 1A2, 2B6, 2C9 and 3A4 ) induction in cryopreserved human hepatocytes cultured in 48 - well plates using the cocktail strategy.", "output": "There is no related enetity." }, { "input": "1. A fast, straightforward and cost - effective assay was validated for the assessment of CYP induction in cryopreserved human hepatocytes cultured in 48 - well plates.", "output": "There is no related enetity." }, { "input": "The cocktail strategy ( in situ incubation ) was used to assess the induction of CYP1A2, CYP2B6, CYP2C9 and CYP3A4 by using the recommended probe substrate, i. e. phenacetin, bupropion, diclofenac and midazolam, respectively.", "output": "phenacetin, bupropion, diclofenac, midazolam." }, { "input": "2. Cryopreserved human hepatocytes were treated for 72 h with prototypical reference inducers, beta - naphthoflavone ( 25 micro M ), phenobarbital ( 500 micro M ) and rifampicin ( 10 micro M ) as positive controls for CYP induction.", "output": "beta - naphthoflavone, phenobarbital, rifampicin." }, { "input": "The use of a cocktail strategy has been validated and compared to the classical approach ( single incubation ).", "output": "There is no related enetity." }, { "input": "The need of using phase II inhibitor ( salicylamide ) in CYP induction assay was also investigated.", "output": "salicylamide." }, { "input": "3. By using three different batches of cryopreserved human hepatocytes and our conditions of incubations, we showed that there was no relevant drug - drug interaction using the cocktail strategy.", "output": "There is no related enetity." }, { "input": "The same conclusions were observed when a broad range of enzyme activity has to be assessed ( wide range of reference inducers, i. e. EC50 - Emax experiment ).", "output": "There is no related enetity." }, { "input": "In addition, the interassay reproducibility assessment showed that the day - to - day variability was minimal.", "output": "There is no related enetity." }, { "input": "4. In summary, the study showed that the conditions used ( probe substrates, concentration of probe substrate and time of incubation ) for the cocktail approach were appropriate for investigations of CYP induction potential of new chemical entities.", "output": "There is no related enetity." }, { "input": "In addition, it was also clear that the use of salicylamide in the incubation media was not mandatory and could generate drug - drug interactions.", "output": "salicylamide." }, { "input": "For this reason, we recommend to not use salicylamide in CYP induction assay.", "output": "salicylamide." }, { "input": "Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre - and postablation scintigraphies and their relation to xerostomia symptoms.", "output": "radioactive iodine." }, { "input": "Background: Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine ( RAI ) therapy for thyroid cancer.", "output": "radioactive iodine, RAI." }, { "input": "To evaluate the long - term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies ( SGSs ) taken before and at 5 years after an RAI ablation.", "output": "RAI, RAI." }, { "input": "Methods: SGS was performed just before RAI ablation ( pre - SGS ) and ~ 5 years after RAI ablation ( F / U SGS ) in 213 subjects who underwent thyroidectomy for thyroid cancer.", "output": "RAI, RAI." }, { "input": "The uptake score ( U score ) was graded, and the ejection fraction ( EF ) was quantified for the parotid and submandibular glands at pre - SGS and F / U SGS.", "output": "There is no related enetity." }, { "input": "Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs.", "output": "There is no related enetity." }, { "input": "Xerostomia was assessed and compared with the SGS findings.", "output": "There is no related enetity." }, { "input": "Results: Worsening of the U score was observed in 182 of 852 salivary glands ( total: 21. 3 %; mild: 4. 2 %, moderate: 7. 4 %, severe: 9. 7 % ), and 47. 4 % of the patients had a worsening U score for at least one of four salivary glands.", "output": "There is no related enetity." }, { "input": "A decrease in EF was observed in 173 of 852 salivary glands ( total: 20. 3 %; mild: 5. 4 %, moderate: 6. 8 %, severe: 8. 1 % ), and 43. 7 % of the patients experienced a decrease in the EF of at least one of the four salivary glands.", "output": "There is no related enetity." }, { "input": "Bilateral parotid gland dysfunction was the most commonly observed condition.", "output": "There is no related enetity." }, { "input": "Thirty - five ( 16. 4 % ) patients complained of xerostomia at 5 years after RAI ablation.", "output": "RAI." }, { "input": "Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5. 55 GBq, compared with 3. 7 GBq.", "output": "There is no related enetity." }, { "input": "Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction ( 68. 8 % vs. 33. 3 %, p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "The number of dysfunctional salivary glands was correlated with xerostomia ( p < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Conclusion: About 20 % of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who received higher doses of RAI.", "output": "RAI, RAI." }, { "input": "While parotid glands are more susceptible to ( 131 ) I - related damage, xerostomia was more associated with submandibular gland dysfunction and the prevalence of dysfunctional salivary glands.", "output": "There is no related enetity." }, { "input": "IFN alpha converts IL - 22 into a cytokine efficiently activating STAT1 and its downstream targets.", "output": "There is no related enetity." }, { "input": "Besides their antiviral activity, type I Interferons ( IFN ) display context - specific immunomodulation.", "output": "There is no related enetity." }, { "input": "In contrast to long - known IFN alpha / beta, Interleukin ( IL ) - 22 is an anti - bacterial, largely tissue protective cytokine that recently gained attention.", "output": "There is no related enetity." }, { "input": "Herein, cellular IFN alpha / IL - 22 interactions are investigated.", "output": "There is no related enetity." }, { "input": "We report that pre - conditioning of epithelial cells with IFN alpha initiated dramatic changes in IL - 22 signaling normally dominated by signal transducer and activator of transcription ( STAT ) - 3.", "output": "There is no related enetity." }, { "input": "Specifically, by using human DLD1 colon epithelial / carcinoma cells we demonstrate that, upon IFN alpha, IL - 22 converts into a cytokine robustly activating STAT1 and its downstream pro - inflammatory targets CXCL9, CXCL10, and inducible nitric oxide synthase ( iNOS ).", "output": "nitric oxide." }, { "input": "Accordingly, only after IFN alpha pre - incubation was IL - 22 - induced STAT1 binding to the CXCL10 promoter detectable.", "output": "There is no related enetity." }, { "input": "Using the viral mimic polyinosinic: polycytidylic acid and the IFN alpha / beta antagonist B18R we furthermore demonstrate the capability of endogenous IFN to promote IL - 22 - induced STAT1 activation and expression of CXCL10.", "output": "polyinosinic : polycytidylic acid." }, { "input": "IL - 22 - induced STAT1 activation subsequent to IFN alpha priming became likewise apparent in human Caco2 colon epithelial / carcinoma cells, HepG2 hepatoma cells, and primary keratinocytes.", "output": "There is no related enetity." }, { "input": "Current observations may relate to characteristics of IFN alpha / beta in clinical therapy and expose margins of tissue protection by IL - 22 application.", "output": "There is no related enetity." }, { "input": "Proposed model for in vitro interaction between fenitrothion and DNA, by using competitive fluorescence, ( 31 ) P NMR, ( 1 ) H NMR, FT - IR, CD and molecular modeling.", "output": "fenitrothion, ( 31 ) P, ( 1 ) H." }, { "input": "In this work we proposed a model for in vitro interaction of fenitrothion ( FEN ) with calf thymus - DNA by combination of multispectroscopic and two dimensional molecular modeling ( ONIOM ) methods.", "output": "fenitrothion, FEN." }, { "input": "The circular dichroism results showed that FEN changes the conformation of B - DNA and caused some changes to C - DNA form.", "output": "FEN." }, { "input": "The FT - IR results confirmed a partial intercalation between FEN and edges of all base pairs.", "output": "FEN." }, { "input": "The competitive fluorescence, using methylene blue as fluorescence probe, in the presence of increasing amounts of FEN, revealed that FEN is able to release the non - intercalated methylene blue from the DNA.", "output": "methylene blue, FEN, FEN, methylene blue." }, { "input": "The weak chemical shift and peak broadening of ( 1 ) H NMR spectrum of FEN in the presence of DNA confirmed a non - intercalation mode.", "output": "( 1 ) H, FEN." }, { "input": "The ( 31 ) P NMR showed that FEN interacts more with DNA via its - NO2 moiety.", "output": "( 31 ) P, FEN, NO2." }, { "input": "The ONIOM, based on the hybridization of QM / MM ( DFT, 6. 31 + + G ( d, p ) / UFF ) methodology, was also performed by Gaussian 2003 package.", "output": "There is no related enetity." }, { "input": "The results revealed that the interaction is base sequence dependent, and FEN interacts more with AT base sequences.", "output": "FEN." }, { "input": "Three - dimensional imaging of collagen fibril organization in rat circumferential lamellar bone using a dual beam electron microscope reveals ordered and disordered sub - lamellar structures.", "output": "There is no related enetity." }, { "input": "Lamellar bone is a major component of most mammalian skeletons.", "output": "There is no related enetity." }, { "input": "A prominent component of individual lamellae are parallel arrays of mineralized type I collagen fibrils, organized in a plywood like motif.", "output": "There is no related enetity." }, { "input": "Here we use a dual beam microscope and the serial surface view ( SSV ) method to investigate the three dimensional collagen organization of circumferential lamellar bone from rat tibiae after demineralization and osmium staining.", "output": "There is no related enetity." }, { "input": "Fast Fourier transform analysis is used to quantitatively identify the mean collagen array orientations and local collagen fibril dispersion.", "output": "There is no related enetity." }, { "input": "Based on collagen fibril array orientations and variations in fibril dispersion, we identify 3 distinct sub - lamellar structural motifs: a plywood - like fanning sub - lamella, a unidirectional sub - lamella and a disordered sub - lamella.", "output": "There is no related enetity." }, { "input": "We also show that the disordered sub - lamella is less mineralized than the other sub - lamellae.", "output": "There is no related enetity." }, { "input": "The hubs and junctions of the canalicular network, which connect radially oriented canaliculi, are intimately associated with the disordered sub - lamella.", "output": "There is no related enetity." }, { "input": "We also note considerable variations in the proportions of these 3 sub - lamellar structural elements among different lamellae.", "output": "There is no related enetity." }, { "input": "This new application of Serial Surface View opens the way to quantitatively compare lamellar bone from different sources, and to clarify the 3 - dimensional structures of other bone types, as well as other biological structural materials.", "output": "There is no related enetity." }, { "input": "Modulation of the cellular redox status by the Alternaria toxins alternariol and alternariol monomethyl ether.", "output": "alternariol, alternariol monomethyl ether." }, { "input": "The mycotoxin alternariol ( AOH ) has been reported to possess genotoxic properties, inducing enhanced levels of DNA damage after only 1 h of incubation.", "output": "alternariol, AOH." }, { "input": "In the present study we addressed the question whether the induction of oxidative stress might contribute to the genotoxic effects of AOH or its naturally occurring monomethylether ( AME ).", "output": "AOH, monomethylether, AME." }, { "input": "In the dichlorofluorescein ( DCF ) assay, treatment of HT29 cells for 1 h enhanced the formation of dichlorofluorescein, indicative for ROS formation.", "output": "dichlorofluorescein, DCF, dichlorofluorescein." }, { "input": "The total glutathione ( tGSH ) was transiently decreased.", "output": "glutathione." }, { "input": "In accordance with the results of the DCF assay, AOH and AME enhanced the proportion of the transcription factor Nrf2 in the nucleus.", "output": "DCF, AOH, AME." }, { "input": "Concomitantly, the Nrf2 / ARE - dependent genes gamma - glutamylcysteine ligase ( gamma - GCL ) and glutathione - S - transferase ( GSTA1 / 2 ) showed enhanced transcript levels.", "output": "gamma - glutamylcysteine, glutathione, S." }, { "input": "After 24 h of incubation this effect was also reflected on the protein level by an increase of GST activity.", "output": "There is no related enetity." }, { "input": "However, in spite of the positive DCF assay and the activation of the redox - sensitive Nrf2 / ARE - pathway, the level of oxidative DNA damage, measured in the comet assay by the addition of formamidopyrimidine - DNA - glycosylase ( fpg ) remained unaffected.", "output": "DCF, formamidopyrimidine." }, { "input": "Of note, after 3 h of incubation no significant DNA damaging potential of AOH and AME was detectable, indicating either inactivation of the compounds or enhanced DNA repair.", "output": "AOH, AME." }, { "input": "In summary, the mycotoxins AOH and AME were found to modulate the redox balance of HT29 cells but without apparent negative effect on DNA integrity.", "output": "AOH, AME." }, { "input": "Sensory gating, Cannabinoids and Schizophrenia.", "output": "There is no related enetity." }, { "input": "Sensory gating, a mandatory process in early information processing, has been found to be defective in neuropsychiatric diseases such as schizophrenia.", "output": "There is no related enetity." }, { "input": "Understanding the neurobiology of sensory gating may provide insight into unravelling the neurobiology of information processing and to yet unanswered queries on the pathophysiology of disabling neuropsychiatric diseases.", "output": "There is no related enetity." }, { "input": "The endocannabinoid system has been linked to the pathophysiology of schizophrenia.", "output": "There is no related enetity." }, { "input": "Furthermore, cannabinoids disrupt sensory gating in animals and humans which supports the hypothesis that the disruption of sensory gating by alterations in the endocannabinoid system is a significant factor in the etiology of schizophrenia.", "output": "There is no related enetity." }, { "input": "Based on the above hypothesis this article reviews the sensory gating process in relation to the auditory conditioning - test paradigm with an emphasis on its association with the endocannabinoid system and schizophrenia.", "output": "There is no related enetity." }, { "input": "Synthesis of novel indole hydrazone derivatives and evaluation of their antiplatelet aggregation activity.", "output": "indole hydrazone." }, { "input": "Based on the existing reports regarding the antiplatelet aggregation activity of hydrazone derivatives, a series of indole hydrazone derivatives were considered as potential antiplatelet agents and synthesized.", "output": "hydrazone, indole hydrazone." }, { "input": "The structures of the synthesized compounds were confirmed by spectral data and elemental analysis.", "output": "There is no related enetity." }, { "input": "The new indole hydrazone derivatives were evaluated for their ability to inhibit platelet aggregation induced by adenosine diphosphate ( ADP ) and arachidonic acid ( AA ).", "output": "indole hydrazone, adenosine diphosphate, ADP, arachidonic acid." }, { "input": "Compounds 1h and 3h exhibited remarkable activity against arachidonic acid induced platelet aggregation with IC ( 50 ) values comparable to that of indomethacin and compound 1i efficiently inhibited platelet aggregation induced by both ADP and AA.", "output": "arachidonic acid, indomethacin, ADP." }, { "input": "Applications of asymmetric organocatalysis in medicinal chemistry.", "output": "There is no related enetity." }, { "input": "In the last decade, organocatalysis, the use of small chiral organic molecules as catalysts, has proven to be a valuable and attractive tool for the synthesis of enantiomerically enriched molecules.", "output": "There is no related enetity." }, { "input": "A number of organocatalysts and processes, such as one - pot, tandem, cascade or multicomponent reactions, have been reported to date.", "output": "There is no related enetity." }, { "input": "Furthermore, the many advantages of organocatalysis - robust, non - toxic, affordable, inert atmosphere, easy reaction manipulation, etc.", "output": "There is no related enetity." }, { "input": "- allow the preparation of bioactive compounds using simple and metal - free procedures, thus avoiding false positives in the biological evaluation.", "output": "There is no related enetity." }, { "input": "This mini - review focuses on medicinal chemistry programs that have synthesized biologically active compounds using one or more organocatalytic steps.", "output": "There is no related enetity." }, { "input": "In this respect, the potential of organocatalytic methods for enabling the chemical synthesis of important medicinal targets will be highlighted.", "output": "There is no related enetity." }, { "input": "Enhanced heterodimerization of Bax by Bcl - 2 mutants improves irradiated cell survival.", "output": "There is no related enetity." }, { "input": "B Cell Lymphoma - 2 ( Bcl - 2 ) protein suppresses ionizing radiation - induced apoptosis in hemato - lymphoid system.", "output": "There is no related enetity." }, { "input": "To enhance the survival of irradiated cells, we have compared the effects and mechanism of Bcl - 2 and its functional variants, D34A ( caspase - 3 resistant ) and S70E ( mimics phosphorylation on S70 ).", "output": "There is no related enetity." }, { "input": "Bcl - 2 and its mutants were transfected into hematopoietic cell line and assessed for cell survival, clonogenicity and cell cycle perturbations upon exposure to ionizing radiation.", "output": "There is no related enetity." }, { "input": "The electrostatic potential of BH3 cleft of Bcl - 2 / mutants and their heterodimerization with Bcl - 2 associated X protein ( Bax ) were computationally evaluated.", "output": "BH3." }, { "input": "Correspondingly, these results were verified by co - immunoprecipitation and western blotting.", "output": "There is no related enetity." }, { "input": "The mutants afford higher radioprotective effect than Bcl - 2 in apoptotic and clonogenic assays at D ( 0 ) ( radiation dose at which 37 % cell survival was observed ).", "output": "There is no related enetity." }, { "input": "The computational and functional analysis indicates that mutants have higher propensity to neutralize Bax protein by heterodimerization and have increased caspase - 9 suppression capability, which is responsible for enhanced survival.", "output": "There is no related enetity." }, { "input": "This study implies potential of Bcl - 2 mutants or their chemical / peptide mimics to elicit radioprotective effect in cells exposed to radiation.", "output": "There is no related enetity." }, { "input": "Inferring population histories using genome - wide allele frequency data.", "output": "There is no related enetity." }, { "input": "The recent development of high - throughput genotyping technologies has revolutionized the collection of data in a wide range of both model and nonmodel species.", "output": "There is no related enetity." }, { "input": "These data generally contain huge amounts of information about the demographic history of populations.", "output": "There is no related enetity." }, { "input": "In this study, we introduce a new method to estimate divergence times on a diffusion time scale from large single - nucleotide polymorphism ( SNP ) data sets, conditionally on a population history that is represented as a tree.", "output": "There is no related enetity." }, { "input": "We further assume that all the observed polymorphisms originate from the most ancestral ( root ) population; that is, we neglect mutations that occur after the split of the most ancestral population.", "output": "There is no related enetity." }, { "input": "This method relies on a hierarchical Bayesian model, based on Kimura ' s time - dependent diffusion approximation of genetic drift.", "output": "There is no related enetity." }, { "input": "We implemented a Metropolis - Hastings within Gibbs sampler to estimate the posterior distribution of the parameters of interest in this model, which we refer to as the Kimura model.", "output": "There is no related enetity." }, { "input": "Evaluating the Kimura model on simulated population histories, we found that it provides accurate estimates of divergence time.", "output": "There is no related enetity." }, { "input": "Assessing model fit using the deviance information criterion ( DIC ) proved efficient for retrieving the correct tree topology among a set of competing histories.", "output": "There is no related enetity." }, { "input": "We show that this procedure is robust to low - to - moderate gene flow, as well as to ascertainment bias, providing that the most distantly related populations are represented in the discovery panel.", "output": "There is no related enetity." }, { "input": "As an illustrative example, we finally analyzed published human data consisting in genotypes for 452, 198 SNPs from individuals belonging to four populations worldwide.", "output": "There is no related enetity." }, { "input": "Our results suggest that the Kimura model may be helpful to characterize the demographic history of differentiated populations, using genome - wide allele frequency data.", "output": "There is no related enetity." }, { "input": "Matrix metalloproteinase - 1 - mediated up - regulation of vascular endothelial growth factor - 2 in endothelial cells.", "output": "There is no related enetity." }, { "input": "Matrix metalloproteinase - 1 ( MMP - 1 ) is a collagenase that is highly active in extracellular matrix and vascular remodeling, angiogenesis, and tumor progression.", "output": "There is no related enetity." }, { "input": "Vascular endothelial growth factor receptor - 2 ( VEGFR2 ), the main receptor for VEGF - A, is expressed on endothelial cells and promotes cell survival, proliferation, and other functions.", "output": "There is no related enetity." }, { "input": "Although MMP - 1 and VEGFR2 co - exist in many normal and pathophysiological conditions, the effect of MMP - 1 on cellular VEGFR2 that can promote the above processes is unknown.", "output": "There is no related enetity." }, { "input": "In this study we test the hypothesis that stimulation of endothelial cells with MMP - 1 increases their levels of VEGFR2.", "output": "There is no related enetity." }, { "input": "The increased VEGFR2 is then available to bind VEGF - A, resulting in increased response.", "output": "There is no related enetity." }, { "input": "Indeed we found that endothelial cells incubated with active MMP - 1 had higher mRNA and protein levels of VEGFR2.", "output": "There is no related enetity." }, { "input": "Furthermore, VEGF - A - dependent phosphorylation of intracellular signaling molecules and endothelial proliferation were elevated after MMP - 1 treatment.", "output": "There is no related enetity." }, { "input": "MMP - 1 caused activation of the nuclear factor - kappa B ( NF - kappa B ) pathway ( p65 / RelA ) in endothelial cells, and this response was dependent upon activation of protease activated receptor - 1 ( PAR - 1 ).", "output": "There is no related enetity." }, { "input": "Chromatin immunoprecipitation was used to confirm NF - kappa B - mediated active transcription of the VEGFR2 ( KDR ) gene.", "output": "There is no related enetity." }, { "input": "Elevation in VEGFR2 after MMP - 1 stimulation was inhibited by PAR - 1 knockdown and NF - kappa B specific inhibition.", "output": "There is no related enetity." }, { "input": "We conclude that MMP - 1 promotes VEGFR2 expression and proliferation of endothelial cells through stimulation of PAR - 1 and activation of NF - kappa B.", "output": "There is no related enetity." }, { "input": "These results suggest a mechanism by which MMP - 1 may prime or sensitize endothelial cell functions.", "output": "There is no related enetity." }, { "input": "The scintigraphic evaluation and genetic correlation of joint involvements in pediatric patients with familial Mediterranean fever.", "output": "There is no related enetity." }, { "input": "Purpose: We aimed to evaluate the articular involvements in pediatric patients with familial Mediterranean fever ( FMF ) with joint symptoms by bone scintigraphy and to correlate the involved joints with the gene mutations.", "output": "There is no related enetity." }, { "input": "Materials and methods: A total of 41 newly diagnosed patients in pediatric age group ( 28 girls and 13 boys; mean age 9. 14 +/- 2. 91 years ) with joint involvement symptoms were included in this study.", "output": "There is no related enetity." }, { "input": "Scintigraphic images were obtained at 5th min ( blood pool or early phase ) and starting at 3 h ( late phase ) after ( after tracer injection ) intravenous administration of technetium - 99m ( 99mTc ) - methylendiphosphonate ( MDP ).", "output": "technetium - 99m, 99mTc, methylendiphosphonate, MDP." }, { "input": "Genomic DNA was isolated from leukocytes using standard salting out procedure.", "output": "There is no related enetity." }, { "input": "The sequencing data were analyzed.", "output": "There is no related enetity." }, { "input": "Results: Of the 41 patients, arthritis was found in 21 ( 51. 2 % ) patients.", "output": "There is no related enetity." }, { "input": "Of the 21 patients, there was single joint involvement in 15 ( 71. 4 % ) patients and multiple joint involvement in six ( 28. 6 % ) patients.", "output": "There is no related enetity." }, { "input": "The mean age of patients with joint involvement ( 8 +/- 2. 3 years ) were considerably lower than the patients without joint involvement ( 10. 35 +/- 3. 04 years ), and this was statistically significant ( p = 0. 008 ).", "output": "There is no related enetity." }, { "input": "The most commonly involved joints were ankles and knees.", "output": "There is no related enetity." }, { "input": "Multiple joint involvements were most frequently observed in the M694V and M694I gene mutations ( 16. 7 % ).", "output": "There is no related enetity." }, { "input": "Conclusions: We use and recommend the bone scintigraphy in patients with FMF to determine the presence and distribution of arthritis, since bone scintigraphy is inexpensive, noninvasive, easy - to - use, and also is more sensitive in the diagnosis and distribution of arthritis than conventional radiological methods and clinical examination.", "output": "There is no related enetity." }, { "input": "Micro / nanostructured hyaluronic acid matrices with tuned swelling and drug release properties.", "output": "There is no related enetity." }, { "input": "Hyaluronic acid ( HA ) hydrogels were structured in the form of porous monoliths by means of the ice - segregation - induced self - assembly ( ISISA ) method coupled with freeze - drying.", "output": "There is no related enetity." }, { "input": "Physical and chemical parameters were explored in order to fine - tune the microstructure and the incidence on both swelling and dissolution behavior in aqueous media.", "output": "There is no related enetity." }, { "input": "Gentamicin - loaded HA matrices with tuned drug release properties were also prepared; their inherent properties and behavior in solution are discussed in the framework of thermal analysis and scanning electron microscopy inspection.", "output": "Gentamicin." }, { "input": "Antipsychotic drug effects in schizophrenia: a review of longitudinal FMRI investigations and neural interpretations.", "output": "There is no related enetity." }, { "input": "The evidence that antipsychotics improve brain function and reduce symptoms in schizophrenia is unmistakable, but how antipsychotics change brain function is poorly understood, especially within neuronal systems.", "output": "There is no related enetity." }, { "input": "In this review, we investigated the hypothesized normalization of the functional magnetic resonance imaging ( fMRI ) blood oxygen level dependent signal in the context of antipsychotic treatment.", "output": "oxygen." }, { "input": "First, we conducted a systematic PubMed search to identify eight fMRI investigations that met the following inclusion criteria: case - control, longitudinal design; pre - and post - treatment contrasts with a healthy comparison group; and antipsychotic - free or antipsychotic - naive patients with schizophrenia at the start of the investigation.", "output": "There is no related enetity." }, { "input": "We hypothesized that aberrant activation patterns or connectivity between patients with schizophrenia and healthy comparisons at the first imaging assessment would no longer be apparent or \" normalize \" at the second imaging assessment.", "output": "There is no related enetity." }, { "input": "The included studies differed by analysis method and fMRI task but demonstrated normalization of fMRI activation or connectivity during the treatment interval.", "output": "There is no related enetity." }, { "input": "Second, we reviewed putative mechanisms from animal studies that support normalization of the BOLD signal in schizophrenia.", "output": "There is no related enetity." }, { "input": "We provided several neuronal - based interpretations of these changes of the BOLD signal that may be attributable to long - term antipsychotic administration.", "output": "There is no related enetity." }, { "input": "Systematic review of the influence of antipsychotics on the blood oxygenation level - dependent signal of functional magnetic resonance imaging.", "output": "There is no related enetity." }, { "input": "Functional Magnetic Resonance Imaging ( FMRI ) is a non - invasive technique for brain mapping and mostly performed using changes of the blood - oxygen - level - dependent ( BOLD ) - signal.", "output": "oxygen." }, { "input": "It has been widely used to investigate patients with schizophrenia.", "output": "There is no related enetity." }, { "input": "Most of the studies examine patients treated with antipsychotic drugs, although little is known about the effects of these drugs on the BOLDsignal.", "output": "There is no related enetity." }, { "input": "Here we examined studies of patients with schizophrenia treated with different antipsychotics to address the question whether and to what extent antipsychotic drugs in themselves produce BOLD - signal changes.", "output": "There is no related enetity." }, { "input": "We performed a PubMed - search for the period from 1999 until January 2012 with the search items \" schizophrenia \" and \" Magnetic Resonance Imaging \" and \" Antipsychotic Agents; or \" Magnetic Resonance Imaging \" and \" Antipsychotic Agents \"; or \" schizophrenia \" and \" Antipsychotic Agents \" and \" FMRI \".", "output": "There is no related enetity." }, { "input": "We extracted articles that examined at least two patient groups with different treatments, or patients examined on different medications at different times and that provided information about drug effects.", "output": "There is no related enetity." }, { "input": "No common effect of antipsychotics on BOLD - signal was found.", "output": "There is no related enetity." }, { "input": "However, based on the results for different antipsychotics ( haloperidol, olanzapine, quetiapine and risperidone ) we found evidence that the affinity to the dopamine ( DA ) D ( 2 ) - receptor may influence BOLD - signal.", "output": "haloperidol, olanzapine, quetiapine, risperidone, dopamine." }, { "input": "Prostate cancer, miRNAs, metallothioneins and resistance to cytostatic drugs.", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs ) translationally repressing their target messenger RNAs due to their gene - regulatory functions play an important but not unexpected role in a tumour development.", "output": "There is no related enetity." }, { "input": "More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metastases.", "output": "There is no related enetity." }, { "input": "Moreover, these small regulatory molecules play a role in the resistance of cancer cells to commonly used anti - cancer drugs, such as cisplatin, anthracyclines, and taxanes.", "output": "cisplatin, anthracyclines, taxanes." }, { "input": "In that respect, miRNAs become very attractive target for potential therapeutic interventions.", "output": "There is no related enetity." }, { "input": "Improvements in the sensitivity of miRNAs detection techniques led to discovery of circulating miRNAs which became very attractive non - invasive biomarker of cancer with a substantial predictive value.", "output": "There is no related enetity." }, { "input": "In this review, the authors focus on i ) oncogenic and anti - tumour acting miRNAs, ii ) function of miRNAs in tumour progression, iii ) possible role of miRNAs in resistance to anticancer drugs, and iv ) diagnostic potential of miRNAs for identification of cancer from circulating miRNAs with special emphasis on prostate cancer.", "output": "There is no related enetity." }, { "input": "Moreover, relationship between miRNAs and expression of metallothionein is discussed as a possible explanation of resistance against platinum based drugs.", "output": "platinum." }, { "input": "Ethanol modulates the neurovascular coupling.", "output": "Ethanol." }, { "input": "Despite some evidence of the underlying molecular mechanisms the neuronal basis of ethanol - induced effects on the neurovascular coupling that forms the BOLD ( blood oxygenation level dependent ) signal is poorly understood.", "output": "ethanol." }, { "input": "In a recent fMRI ( functional magnetic resonance imaging ) study monitoring ethanol - induced changes of the BOLD signal a reduction of the amplitude and a prolongation of the BOLD signal were observed.", "output": "ethanol." }, { "input": "However, the BOLD signal is assumed to consist of a complex superposition of different underlying signals.", "output": "There is no related enetity." }, { "input": "To gain insight how ethanol influences stimulus efficacy, oxygen extraction, transit time and vessel - related parameters the fMRI time series from the sensori - motor and the visual cortex were analyzed using the balloon model.", "output": "ethanol, oxygen." }, { "input": "The results show a region - dependent decrease of the stimulus efficacy to trigger a post - stimulus neurovascular response as well as a prolongation of the transit time through the venous compartment.", "output": "There is no related enetity." }, { "input": "Oxygen extraction, feedback mechanisms and other vessel - related parameters were not affected.", "output": "Oxygen." }, { "input": "The results may be interpreted as follows: the overall mechanisms of the neurovascular coupling are still acting well at the moderate ethanol level of about 0. 8 /1000 ( in particular the vessel - related parts ), but the potency to evoke a neurovascular response is already compromised most obviously in the supplementary motor area responsible for complex synchronizing and planning processes.", "output": "ethanol." }, { "input": "Perseverative behavior in rats with methamphetamine - induced neurotoxicity.", "output": "methamphetamine." }, { "input": "Methamphetamine induces monoamine depletions thought to contribute to cognitive and behavioral dysfunctions.", "output": "Methamphetamine." }, { "input": "Previously, we reported that methamphetamine - induced neurotoxicity is associated with impaired formation of stimulus - response associations.", "output": "methamphetamine." }, { "input": "Additionally, subjective observations suggested that behavioral flexibility might be affected.", "output": "There is no related enetity." }, { "input": "Thus, the present study examined whether methamphetamine neurotoxicity induces perseverative behavior.", "output": "methamphetamine." }, { "input": "Rats were pretreated with ( +/- ) - methamphetamine ( 4 x 10 mg / kg, 2 - hr intervals ) or saline.", "output": "( +/- ) - methamphetamine." }, { "input": "Three weeks later, rats were trained to press a lever on one side of an operant chamber and then retrieve the reinforcer from a magazine on the opposite side until they reached criterion ( > 50 reinforcers / 30 - min ).", "output": "There is no related enetity." }, { "input": "After four consecutive sessions performing the task at criterion, rats were sacrificed and brains removed for monoamine determinations.", "output": "There is no related enetity." }, { "input": "Methamphetamine - pretreated rats had ~ 50 % loss of striatal dopamine and prefrontal serotonin.", "output": "Methamphetamine, dopamine, serotonin." }, { "input": "Methamphetamine - and saline - pretreated rats were not different in the number of sessions required to reach criterion or in the total numbers of lever presses and / or head entries made across the four consecutive sessions at criterion - level performance.", "output": "Methamphetamine." }, { "input": "However, methamphetamine - pretreated rats earned fewer reinforcers, because they made extra lever - presses and head entries when they should have been retrieving the reinforcer or returning to the lever.", "output": "methamphetamine." }, { "input": "Latencies for methamphetamine - pretreated rats to switch between the two behaviors also were significantly slower than latencies for controls.", "output": "methamphetamine." }, { "input": "Interestingly, the degree of additional lever - presses negatively correlated with serotonin - transporter binding in the prefrontal cortex, even in saline - pretreated controls.", "output": "serotonin." }, { "input": "These data suggest that methamphetamine - induced partial monoamine toxicity is associated with perseveration and that the degree of perseveration may depend on serotonin innervation of the frontal cortex.", "output": "methamphetamine, serotonin." }, { "input": "Challenges and recommendations for obtaining chemical structures of industry - provided repurposing candidates.", "output": "There is no related enetity." }, { "input": "There is an expanding amount of interest directed at the repurposing and repositioning of drugs, as well as how in silico methods can assist these endeavors.", "output": "There is no related enetity." }, { "input": "Recent repurposing project tendering calls by the National Center for Advancing Translational Sciences ( USA ) and the Medical Research Council ( UK ) have included compound information and pharmacological data.", "output": "There is no related enetity." }, { "input": "However, none of the internal company development code names were assigned to chemical structures in the official documentation.", "output": "There is no related enetity." }, { "input": "This not only abrogates in silico analysis to support repurposing but consequently necessitates data gathering and curation to assign structures.", "output": "There is no related enetity." }, { "input": "Here, we describe the approaches, results and major challenges associated with this.", "output": "There is no related enetity." }, { "input": "High resolution fluorescence microscopy evidence on the transport of immunoglobulins.", "output": "There is no related enetity." }, { "input": "Differences between mammalian IgG, F ( ab ' ) 2 and avian IgY.", "output": "There is no related enetity." }, { "input": "We describe the subcellular localization of horse F ( ab ' ) ( 2 ) and IgG, and ostrich IgY labeled with fluorescein isothiocyanate ( FITC ) administered IV to mice.", "output": "fluorescein isothiocyanate, FITC." }, { "input": "We used wide field high sensitivity fluorescence microscopy deblurred by 3 - dimensional blind deconvolution of kidney, liver, lungs and brain sections.", "output": "There is no related enetity." }, { "input": "Sections were obtained from mice sacrificed 15 min, 1 or 5 h after receiving FITC - immunoproteins, counter - stained with DAPI ( 4 ', 6 ' - diamidino - 2 - phenylindole ) and Evans blue.", "output": "FITC, DAPI, 4 ' , 6 ' - diamidino - 2 - phenylindole, Evans blue." }, { "input": "FITC - IgG and its fractions are rapidly taken up and extravasated by vascular endothelium.", "output": "FITC." }, { "input": "FITC - IgG and FITC - F ( ab ' ) ( 2 ) appear to be quickly secreted by glomeruli endothelium and to be reabsorbed along all nephron segments.", "output": "FITC, FITC." }, { "input": "FITC - IgG and FITC - F ( ab ' ) ( 2 ) appeared 15 min after IV injection within bronchial, alveolar and bile duct epithelium.", "output": "FITC, FITC." }, { "input": "Hepatocytes were loaded with fluorescence after 15 min of administration.", "output": "There is no related enetity." }, { "input": "Fluorescence was absent from brain slices, except for the endothelium of some vessels in brain ventricles which appeared intensely fluorescent.", "output": "There is no related enetity." }, { "input": "Fluorescence appeared in intracellular vesicles which conferred the tissues a glowing foamy aspect for up to 5 h after inoculation.", "output": "There is no related enetity." }, { "input": "Arterial elastic layers were intensely green after horse FITC - Ig inoculation.", "output": "FITC." }, { "input": "Ostrich FITC - IgY behaved completely differently to horse Ig ' s; only 1 h after injection it was possible to observe small brightly green scarce vesicles in vascular endothelium of arteries, interstitial kidney capillaries between nephron tubules and were also scarce in glomeruli endothelium; FITC - IgY appeared only in hepatic sinusoids in the liver.", "output": "FITC, FITC." }, { "input": "No IgY was seen in bronchial and alveolar endothelium, in bile ducts or in hepatocytes.", "output": "There is no related enetity." }, { "input": "Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model.", "output": "There is no related enetity." }, { "input": "Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses.", "output": "There is no related enetity." }, { "input": "Systemic effects ( lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy ) induced by intravenous ( i. v. ) administration of B. caribbaeus venom were studied in mice.", "output": "There is no related enetity." }, { "input": "The role of snake venom metalloproteinases ( SVMPs ) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid ( CaNa ( 2 ) EDTA ).", "output": "calcium disodium ethylenediaminetetraacetic acid, CaNa ( 2 ) EDTA." }, { "input": "A snake C - type lectin - like ( snaclec ) and a type P - III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro.", "output": "There is no related enetity." }, { "input": "Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect.", "output": "There is no related enetity." }, { "input": "Both venom and snaclec induce platelet aggregation / agglutination.", "output": "There is no related enetity." }, { "input": "Moreover, the snaclec binds directly to glycoprotein Ib ( GPIb ) and induces agglutination in washed fixed platelets.", "output": "There is no related enetity." }, { "input": "On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin / fibrinogen degradation products ( FDP ) levels in vivo.", "output": "There is no related enetity." }, { "input": "The negative result for D - dimer ( DD ) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage.", "output": "There is no related enetity." }, { "input": "Likewise, no increments in plasma sE - selectin levels were detected.", "output": "There is no related enetity." }, { "input": "The absence of thrombosis in this murine model suggests that this effect may be species - specific.", "output": "There is no related enetity." }, { "input": "The impact of oxytocin administration and maternal love withdrawal on event - related potential ( ERP ) responses to emotional faces with performance feedback.", "output": "oxytocin." }, { "input": "This is the first experimental study on the effect of oxytocin administration on the neural processing of facial stimuli conducted with female participants that uses event - related potentials ( ERPs ).", "output": "oxytocin." }, { "input": "Using a double - blind, placebo - controlled within - subjects design, we studied the effects of 16 IU of intranasal oxytocin on ERPs to pictures combining performance feedback with emotional facial expressions in 48 female undergraduate students.", "output": "oxytocin." }, { "input": "Participants also reported on the amount of love withdrawal they experienced from their mothers.", "output": "There is no related enetity." }, { "input": "Vertex positive potential ( VPP ) and late positive potential ( LPP ) amplitudes were more positive after oxytocin compared to placebo administration.", "output": "oxytocin." }, { "input": "This suggests that oxytocin increased attention to the feedback stimuli ( LPP ) and enhanced the processing of emotional faces ( VPP ).", "output": "oxytocin." }, { "input": "Oxytocin heightened processing of the happy and disgusted faces primarily for those reporting less love withdrawal.", "output": "Oxytocin." }, { "input": "Significant associations with LPP amplitude suggest that more maternal love withdrawal relates to the allocation of attention toward the motivationally relevant combination of negative feedback with a disgusted face.", "output": "There is no related enetity." }, { "input": "Nanobody - albumin nanoparticles ( NANAPs ) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells.", "output": "17864." }, { "input": "A novel, EGFR - targeted nanomedicine has been developed in the current study.", "output": "There is no related enetity." }, { "input": "Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately 100nm were loaded with the multikinase inhibitor 17864 - L ( x ) - a platinum - bound sunitinib analogue - which couples the drug to methionine residues of albumin and is released in a reductive environment.", "output": "Glutaraldehyde, 17864, platinum, sunitinib, methionine." }, { "input": "Albumin nanoparticles were surface - coated with bifunctional polyethylene glycol 3500 ( PEG ) and a nanobody - the single variable domain of an antibody - ( Ega1 ) against the epidermal growth factor receptor ( EGFR ).", "output": "polyethylene glycol, PEG." }, { "input": "EGa1 - PEG functionalized nanoparticles showed a 40 - fold higher binding to EGFR - positive 14C squamous head and neck cancer cells in comparison to PEGylated nanoparticles.", "output": "PEG, 14C." }, { "input": "17864 - L ( x ) loaded EGa1 - PEG nanoparticles were internalized by clathrin - mediated endocytosis and ultimately digested in lysosomes.", "output": "17864, PEG." }, { "input": "The intracellular routing of EGa1 targeted nanoparticles leads to a successful release of the kinase inhibitor in the cell and inhibition of proliferation whereas the non - targeted formulations had no antiproliferative effects on 14C cells.", "output": "14C." }, { "input": "The drug loaded targeted nanoparticles were as effective as the free drug in vitro.", "output": "There is no related enetity." }, { "input": "These results demonstrate that multikinase inhibitor loaded nanoparticles are interesting nanomedicines for the treatment of EGFR - positive cancers.", "output": "There is no related enetity." }, { "input": "Ex vivo permeation characteristics of venlafaxine through sheep nasal mucosa.", "output": "venlafaxine." }, { "input": "Venlafaxine, a dual acting antidepressant is a new therapeutic option for chronic depression.", "output": "Venlafaxine." }, { "input": "Depression is a common mental disorder associated with the abnormalities in neuronal transport in the brain.", "output": "There is no related enetity." }, { "input": "Since the nose - to - brain pathway has been indicated for delivering drugs to the brain, we analyzed the transport of venlafaxine through sheep nasal mucosa.", "output": "venlafaxine." }, { "input": "Transmucosal permeation kinetics of venlafaxine were examined using sheep nasal mucosa mounted onto static vertical Franz diffusion cells.", "output": "venlafaxine." }, { "input": "Nasal mucosa was treated with venlafaxine in situ gel ( 100 mu l; 1 % w / v ) for 7h.", "output": "venlafaxine." }, { "input": "Amount of venlafaxine diffused through mucosa was measured using validated RP - HPLC method.", "output": "venlafaxine." }, { "input": "After the completion of the study histopathological investigation of mucosa was carried out.", "output": "There is no related enetity." }, { "input": "Ex vivo studies through sheep nasal mucosa showed sustained diffusion of venlafaxine with 66. 5 % permeation in 7h.", "output": "venlafaxine." }, { "input": "Transnasal transport of venlafaxine followed a non - Fickian diffusion process.", "output": "venlafaxine." }, { "input": "Permeability coefficient and steady state flux were found to be 21. 11 x 10 ( - 3 ) cmh ( - 1 ) and 21. 118 mu g cm ( - 2 ) h ( - 1 ) respectively.", "output": "There is no related enetity." }, { "input": "Cumulative amount permeated through mucosa at 7h was found to be 664. 8 mu g through an area of 3. 14 cm ( 2 ).", "output": "There is no related enetity." }, { "input": "Total recovery of venlafaxine at the end of the permeation study was 87. 3 % of initial dose distributed ( i ) at the mucosal surface ( 208. 4 mu g; 20. 8 % ) and ( ii ) through mucosa ( 664. 8 mu g; 66. 5 % ).", "output": "venlafaxine." }, { "input": "Histopathological examinations showed no significant adverse effects confirming that the barrier function of nasal mucosa remains unaffected even after treatment with venlafaxine in situ gel.", "output": "venlafaxine." }, { "input": "Permeation through sheep nasal mucosa using in situ gel demonstrated a harmless nasal delivery of venlafaxine, providing new dimension to the treatment of chronic depression.", "output": "venlafaxine." }, { "input": "Transferrin conjugation does not increase the efficiency of liposomal Foscan during in vitro photodynamic therapy of oesophageal cancer.", "output": "Foscan." }, { "input": "Photodynamic therapy ( PDT ) is based on the delivery of photocytotoxic agents to a target tissue, followed by irradiation.", "output": "There is no related enetity." }, { "input": "In order to increase the efficiency of PDT in oesophageal cancer therapy, polyethylene glycol ( PEG ) - grafted, transferrin ( Tf ) - conjugated liposome formulations of 5, 10, 15, 20 - tetra ( m - hydroxyphenyl ) chlorin ( Foscan ), a second - generation photosensitiser, were prepared.", "output": "polyethylene glycol, PEG, 5 , 10 , 15 , 20 - tetra ( m - hydroxyphenyl ) chlorin, Foscan." }, { "input": "Expression of transferrin receptors ( CD71 ) in the oesophageal cancer cell line, OE21, was confirmed by immunoblot and confocal laser scanning microscopy.", "output": "There is no related enetity." }, { "input": "The anti - proliferative effect of Foscan liposomes was evaluated and compared with plain formulations ( i. e., without Tf ) as well as with free drug.", "output": "Foscan." }, { "input": "In addition, the intracellular accumulation was studied using high content analysis.", "output": "There is no related enetity." }, { "input": "Surprisingly, delivering Foscan by transferrin - conjugated PEG - liposomes to oesophageal cancer cells did not improve the photocytotoxicity or the intracellular accumulation of Foscan when compared to unmodified liposomes or indeed free photosensitiser.", "output": "Foscan, PEG, Foscan." }, { "input": "Tf - targeted drugs and drug delivery systems have shown improved the therapy of many cancers.", "output": "There is no related enetity." }, { "input": "Our study, however, did not corroborate these findings.", "output": "There is no related enetity." }, { "input": "If this is due to the tumour type, the choice of in vitro model or the delivery systems remains to be confirmed.", "output": "There is no related enetity." }, { "input": "A novel approach to improve the pharmacokinetic properties of 8 - chloro - adenosine by the dual combination of lipophilic derivatisation and liposome formulation.", "output": "8 - chloro - adenosine." }, { "input": "8 - Chloro - adenosine ( 8CA ) has shown promise in hematologic and solid tumor models and is in a phase I clinical trial.", "output": "8 - Chloro - adenosine, 8CA." }, { "input": "However, 8CA is intensively metabolized shortly after i. v. administration, with a t ( 1 / 2 beta ) of approximately 1h.", "output": "8CA." }, { "input": "Many carriers have failed to encapsulate 8CA efficiently.", "output": "8CA." }, { "input": "To improve its pharmacokinetic properties, 8 - chloro - adenosine - 5 ' - O - stearate ( 8CAS ), a lipophilic octadecanoyl analogue of 8CA, was synthesized and incorporated into pegylated liposomes.", "output": "8 - chloro - adenosine - 5 ' - O - stearate, 8CAS, octadecanoyl, 8CA." }, { "input": "The liposomes, comprising egg phosphatidylcholine, cholesterol and poly ( ethylene glycol ) 2000 - distearoyl phosphatidylethanolamine ( PEG - DSPE ), had mean diameters of approximately 100 nm and an entrapment efficiency of 69 - 86 %.", "output": "phosphatidylcholine, cholesterol, poly ( ethylene glycol ), distearoyl phosphatidylethanolamine, PEG - DSPE." }, { "input": "MTT assays showed that the cytotoxicity of 8CAS and its pegylated liposomes ( 8CAS - PL ) were retained, with IC ( 50 ) values of 1. 0 mu M and 1. 9 mu M at 72 h on MCF - 7 cells, respectively, slightly higher than that of 8CA ( 0. 6 mu M ).", "output": "MTT, 8CAS, 8CAS, 8CA." }, { "input": "Pharmacokinetic studies in rats after i. v. injection showed that both 8CAS and 8 CAS - PL had increased elimination half - lives ( t ( 1 / 2 ), 128. 4, 249. 2 vs. 74. 7 min ), decreased clearance rates ( Cl, 0. 0135, 0. 00875 vs. 0. 2398 L / min / kg ) and increased area under the concentration - time curve ( AUC ( 0 - infinity ), 741. 4, 1163. 6 vs. 42. 0 mg min / L ) compared to 8CA.", "output": "8CAS, 8CA." }, { "input": "No obvious hematological toxicity was seen for Kunming mice receiving i. v. 8CA or 8CAS - PL at a dosage of 10mg / kg daily.", "output": "8CA, 8CAS." }, { "input": "These results indicate that the lipophilic derivation of 8CA and the incorporation of 8CAS is an effective strategy to improve the bioavailability of 8CA.", "output": "8CA, 8CAS, 8CA." }, { "input": "Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine.", "output": "lidocaine." }, { "input": "The aim of the present study was to prepare and evaluate patches for the controlled release of lidocaine in the oral cavity.", "output": "lidocaine." }, { "input": "Mucoadhesive buccal patches, containing 8 mg / cm ( 2 ) lidocaine base, were formulated and developed by solvent casting method technique, using a number of different bio - adhesive and film - forming semi - synthetic and synthetic polymers ( Carbopol, Poloxamer, different type Methocel ) and plasticizers ( PEG 400, triethyl citrate ); the patches were evaluated for bioadhesion, in vitro drug release and permeation using a modified Franz diffusion cell.", "output": "lidocaine, Carbopol, Poloxamer, PEG 400, triethyl citrate." }, { "input": "A lidocaine / Compritol solid dispersion in the form of microspheres, embedded inside the patch, alone or together with free lidocaine, was also examined to prolong the drug release.", "output": "lidocaine, Compritol, lidocaine." }, { "input": "The effects of the composition were evaluated considering a number of technological parameters and the release of the drug.", "output": "There is no related enetity." }, { "input": "All the formulations tested offer a variety of drug release mechanisms, obtaining a quick or delayed or prolonged anesthetic local activity with simple changes of the formulation parameters.", "output": "There is no related enetity." }, { "input": "Immunotoxic effects of oil sands - derived naphthenic acids to rainbow trout.", "output": "naphthenic acids." }, { "input": "Naphthenic acids are the major organic constituents in waters impacted by oil sands.", "output": "Naphthenic acids." }, { "input": "To investigate their immunotoxicity, rainbow trout ( Oncorhynchus mykiss ) were injected with naphthenic acids extracted from aged oil sands tailings water.", "output": "naphthenic acids." }, { "input": "In two experiments, rainbow trout were injected intraperitoneally with 0, 10, or 100 mg / kg of naphthenic acids, and sampled after 5 or 21 d.", "output": "naphthenic acids." }, { "input": "Half of the fish from the 21 d exposure were co - exposed to inactivated Aeromonas salmonicida ( A. s. ) to induce an immune response.", "output": "There is no related enetity." }, { "input": "A positive control experiment was conducted using an intraperitoneal injection of 100 mg / kg of benzo [ a ] pyrene, a known immune suppressing compound.", "output": "benzo [ a ] pyrene." }, { "input": "T - lymphocytes, B - lymphocytes, thrombocytes, and myeloid cells were counted in blood and lymphatic tissue using flow cytometry.", "output": "There is no related enetity." }, { "input": "In the 5d exposure, there was a reduction in blood leucocytes and spleen thrombocytes at the 100 mg / kg dose.", "output": "There is no related enetity." }, { "input": "However, at 21 d, leucocyte populations showed no effects of exposure with the exception that spleen thrombocyte populations increase at the 100 mg / kg dose.", "output": "There is no related enetity." }, { "input": "In the 21 d exposure, B - and T - lymphocytes in blood showed a significant Dose x A. s. interaction, indicating stimulated blood cell proliferation due to naphthenic acids alone as well as due to A. s.", "output": "naphthenic acids." }, { "input": "Naphthenic acid injections did not result in elevated bile fluorescent metabolites or elevated hepatic EROD activity.", "output": "Naphthenic acid." }, { "input": "In contrast to naphthenic acids exposures, as similar dose of benzo [ a ] pyrene caused a significant decrease in B - and T - lymphocyte absolute counts in blood and relative B - lymphocyte counts in spleen.", "output": "naphthenic acids, benzo [ a ] pyrene." }, { "input": "Results suggest that the naphthenic acids may act via a generally toxic mechanism rather than by specific toxic effects on immune cells.", "output": "naphthenic acids." }, { "input": "The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy.", "output": "methylene blue." }, { "input": "The photosensitizer, methylene blue ( MB ), generates singlet oxygen ( ( 1 ) O2 ) that irreversibly inhibits Torpedo californica acetylcholinesterase ( TcAChE ).", "output": "methylene blue, oxygen, O2." }, { "input": "In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic ' anionic ' subsite ( CAS ), the peripheral ' anionic ' subsite ( PAS ), or bridging them.", "output": "There is no related enetity." }, { "input": "Data concerning both reversible and irreversible inhibition are here reviewed.", "output": "There is no related enetity." }, { "input": "MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ~ 8 degrees C increase in the denaturation temperature.", "output": "There is no related enetity." }, { "input": "The crystal structure of the MB / TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS.", "output": "There is no related enetity." }, { "input": "The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N ' - formylkynurenine ( NFK ); this was indeed confirmed using anti - NFK antibodies.", "output": "N ' - formylkynurenine, NFK, NFK." }, { "input": "Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo - oxidation, both being converted to NFK.", "output": "Trp, Trp84, Trp279, Trp, NFK." }, { "input": "In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented.", "output": "There is no related enetity." }, { "input": "Thus, photo - oxidative damage caused by MB involves targeted release of ( 1 ) O2 by the bound photosensitizer within the aqueous milieu of the active - site gorge.", "output": "O2." }, { "input": "Purification and structural characterisation of phospholipase A1 ( Vespapase, Ves a 1 ) from Thai banded tiger wasp ( Vespa affinis ) venom.", "output": "There is no related enetity." }, { "input": "The Thai banded tiger wasp ( Vespa affinis ) is one of the most dangerous vespid species in Southeast Asia, and stinging accidents involving this species still cause fatalities.", "output": "There is no related enetity." }, { "input": "In the present study, four forms of V. affinis phospholipase A ( 1 ) were identified through a proteomics approach.", "output": "There is no related enetity." }, { "input": "Two of these enzymes were purified by reverse - phase chromatography, and their biochemical properties were characterised.", "output": "There is no related enetity." }, { "input": "These enzymes, designated Ves a 1s, are not glycoproteins and exist as 33441. 5 and 33474. 4 Da proteins, which corresponded with the 34 - kDa band observed via SDS - PAGE.", "output": "There is no related enetity." }, { "input": "The thermal stabilities of these enzymes were stronger than snake venom.", "output": "There is no related enetity." }, { "input": "Using an in vivo assay, no difference was found in the toxicities of the different isoforms.", "output": "There is no related enetity." }, { "input": "Furthermore, the toxicity of these enzymes does not appear to be correlated with their PLA ( 1 ) activity.", "output": "There is no related enetity." }, { "input": "The cDNAs of the full - length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005 - bp ORF, which encodes 334 amino acid residues, and 67 - and 227 - bp 5 ' and 3 ' UTRs, respectively.", "output": "amino acid." }, { "input": "The two isoforms are different by three nucleotide substitutions, resulting in the replacement of two amino acids.", "output": "nucleotide, amino acids." }, { "input": "Through sequence alignment, these enzymes were classified as members of the pancreatic lipase family.", "output": "There is no related enetity." }, { "input": "The structural modelling of Ves a 1 used the rat pancreatic lipase - related protein 2 ( 1bu8A ) as a template because it has PLA ( 1 ) activity, which demonstrated that this enzyme belongs to the alpha / beta hydrolase fold family.", "output": "There is no related enetity." }, { "input": "The Ves a 1 structure, which is composed of seven alpha - helixes and eleven beta - strands, contains the beta - strand / epsilon Ser / alpha - helix structural motif, which contains the Gly - X - Ser - X - Gly consensus sequence.", "output": "Gly, Ser, Gly." }, { "input": "The typical surface structures that play important roles in substrate selectivity ( the lid domain and the beta 9 loop ) were shortened in the Ves a 1 structure, which suggests that this enzyme may only exhibit phospholipase activity.", "output": "There is no related enetity." }, { "input": "Moreover, the observed insertion of proline into the lid domain of the Ves a 1 structure is rare.", "output": "proline." }, { "input": "We therefore propose that this proline residue might be involved in the stability and activity of Ves a 1s.", "output": "proline." }, { "input": "Analysis of mammalian alcohol dehydrogenase 5 ( ADH5 ): characterisation of rat ADH5 with comparisons to the corresponding human variant.", "output": "alcohol." }, { "input": "Alcohol dehydrogenase 5 ( ADH5 ) is a member of the mammalian alcohol dehydrogenase family of yet undefined functions.", "output": "Alcohol, alcohol." }, { "input": "ADH5 was first identified at the DNA level in human and deer mouse.", "output": "There is no related enetity." }, { "input": "A rat alcohol dehydrogenase structure of similar type has been isolated at the cDNA level using human ADH5 as a screening probe, where the rat cDNA structure displayed several atypical properties.", "output": "alcohol." }, { "input": "mRNA for rat ADH5 was found in multiple tissues, especially in the kidney.", "output": "There is no related enetity." }, { "input": "In vitro translation experiments indicated that rat ADH5 is expressed as efficiently as ADH1 and furthermore, rat ADH5 was readily expressed in COS cells fused to Green Fluorescent Protein.", "output": "There is no related enetity." }, { "input": "However, no soluble ADH5 protein could be heterologously expressed in Escherichia coli cells with expression systems successfully used for other mammalian ADHs, including fused to glutathione - S - transferase.", "output": "glutathione, S." }, { "input": "Molecular modelling of the enzyme indicated that the protein does not fold in a productive way, which can be the explanation why no stable and active ADH5 has been isolated.", "output": "There is no related enetity." }, { "input": "These results indicate that ADH5, while readily expressed at the mRNA level, does not behave similarly to other mammalian ADHs investigated.", "output": "There is no related enetity." }, { "input": "The results, in vitro and in silico, suggest an unstable ADH5 structure, which can explain for why no active and stable protein can be isolated.", "output": "There is no related enetity." }, { "input": "Further possibilities are conceivable: the ADH5 protein may have to interact with a stabiliser, or the gene is actually a pseudogene.", "output": "There is no related enetity." }, { "input": "Combining multiple autosomal introns for studying shallow phylogeny and taxonomy of Laurasiatherian mammals: Application to the tribe Bovini ( Cetartiodactyla, Bovidae ).", "output": "There is no related enetity." }, { "input": "Mitochondrial sequences are widely used for species identification and for studying phylogenetic relationships among closely related species or populations of the same species.", "output": "There is no related enetity." }, { "input": "However, many studies of mammals have shown that the maternal history of the mitochondrial genome can be discordant with the true evolutionary history of the taxa.", "output": "There is no related enetity." }, { "input": "In such cases, the analyses of multiple nuclear genes can be more powerful for deciphering interspecific relationships.", "output": "There is no related enetity." }, { "input": "Here, we designed primers for amplifying 13 new exon - primed intron - crossing ( EPIC ) autosomal loci for studying shallow phylogeny and taxonomy of Laurasiatherian mammals.", "output": "There is no related enetity." }, { "input": "Three criteria were used for the selection of the markers: gene orthology, a PCR product length between 600 and 1200 nucleotides, and different chromosomal locations in the bovine genome.", "output": "There is no related enetity." }, { "input": "Positive PCRs were obtained from different species representing the orders Carnivora, Cetartiodactyla, Chiroptera, Perissodactyla and Pholidota.", "output": "There is no related enetity." }, { "input": "The newly developed markers were analyzed in a phylogenetic study of the tribe Bovini ( the group containing domestic and wild cattle, bison, yak, African buffalo, Asian buffalo, and saola ) based on 17 taxa and 18 nuclear genes, representing a total alignment of 13, 095 nucleotides.", "output": "There is no related enetity." }, { "input": "The phylogenetic results were compared to those obtained from analyses of the complete mitochondrial genome and Y chromosomal genes.", "output": "There is no related enetity." }, { "input": "Our analyses support a basal divergence of the saola ( Pseudoryx ) and a sister - group relationship between yak and bison.", "output": "There is no related enetity." }, { "input": "These results contrast with recent molecular studies but are in better agreement with morphology.", "output": "There is no related enetity." }, { "input": "The comparison of pairwise nucleotide distances shows that our nuDNA dataset provides a good signal for identifying taxonomic levels, such as species, genera, subtribes, tribes and subfamilies, whereas the mtDNA genome fails because of mtDNA introgression and higher levels of homoplasy.", "output": "There is no related enetity." }, { "input": "Accordingly, we conclude that the genus Bison should be regarded as a synonym of Bos, with the European bison relegated to a subspecies rank within Bos bison.", "output": "There is no related enetity." }, { "input": "We compared our molecular dating estimates to the fossil record in order to propose a biogeographic scenario for the evolution of Bovini during the Neogene.", "output": "There is no related enetity." }, { "input": "Biomimetic diversity - oriented synthesis of benzannulated medium rings via ring expansion.", "output": "There is no related enetity." }, { "input": "Nature has exploited medium - sized 8 - to 11 - membered rings in a variety of natural products to address diverse and challenging biological targets.", "output": "There is no related enetity." }, { "input": "However, owing to the limitations of conventional cyclization - based approaches to medium - ring synthesis, these structures remain severely underrepresented in current probe and drug discovery efforts.", "output": "There is no related enetity." }, { "input": "To address this problem, we have established an alternative, biomimetic ring expansion approach to the diversity - oriented synthesis of medium - ring libraries.", "output": "There is no related enetity." }, { "input": "Oxidative dearomatization of bicyclic phenols affords polycyclic cyclohexadienones that undergo efficient ring expansion to form benzannulated medium - ring scaffolds found in natural products.", "output": "bicyclic phenols, polycyclic cyclohexadienones." }, { "input": "The ring expansion reaction can be induced using three complementary reagents that avoid competing dienone - phenol rearrangements and is driven by rearomatization of a phenol ring adjacent to the scissile bond.", "output": "dienone - phenol, phenol." }, { "input": "Cheminformatic analysis of the resulting first - generation library confirms that these molecules occupy chemical space overlapping with medium - ring natural products and distinct from that of synthetic drugs and drug - like libraries.", "output": "There is no related enetity." }, { "input": "Two new chromone glycosides from Drynaria fortunei.", "output": "chromone glycosides." }, { "input": "Two new chromone glycosides, drynachromoside A ( 1 ), drynachromoside B ( 2 ), along with three known flavanones, 5, 7, 3 ', 5 ' - tetrahydroxy - flavanone ( 3 ), 5, 7, 3 ', 5 ' - tetrahydroxy - flavanone - 7 - O - beta - d - glucopyranoside ( 4 ), and 5, 7, 3 ', 5 ' - tetrahydroxy - flavanone - 7 - O - neohesperidoside ( 5 ), were isolated from the dry rhizomes of Drynaria fortunei by means of bio - active screening.", "output": "chromone glycosides, drynachromoside A, drynachromoside B, flavanones, 5 , 7 , 3 ' , 5 ' - tetrahydroxy - flavanone, 5 , 7 , 3 ' , 5 ' - tetrahydroxy - flavanone - 7 - O - beta - d - glucopyranoside, 5 , 7 , 3 ' , 5 ' - tetrahydroxy - flavanone - 7 - O - neohesperidoside." }, { "input": "The two former compounds were elucidated on the basis of physico - chemical property and spectroscopic data.", "output": "There is no related enetity." }, { "input": "The osteoblastic proliferation activities of these flavonoids were evaluated by the method of MTT.", "output": "flavonoids, MTT." }, { "input": "The results showed that compound 1 exhibited the biochemical effects on the proliferation of MC3T3 - E1 cells, while Compound 2 showed inhibitory effects against MC3T3 - E1 cells.", "output": "There is no related enetity." }, { "input": "Effects of the extracts and an active compound curcumenone isolated from Curcuma zedoaria rhizomes on alcohol - induced drunkenness in mice.", "output": "curcumenone, alcohol." }, { "input": "The Curcuma zedoaria rhizome has been used traditionally to treat gastrointestinal diseases as an aromatic stomachic drug, and this is currently used to treat alcohol - induced loss of appetite and nausea in Japan.", "output": "alcohol." }, { "input": "We examined the effects of various fractions and isolated compounds on alcohol - induced drunkenness and blood alcohol concentrations in mice.", "output": "alcohol, alcohol." }, { "input": "The 30 % ethanol - extract ( 1000mg / kg ) of C. zedoaria rhizome prevented drunkenness 60 and 120min after 40 % alcohol administration.", "output": "ethanol, alcohol." }, { "input": "The n - hexane - soluble fraction ( 300mg / kg ) and an isolated compound ( 3, 10 or 30mg / kg ) prevented drunkenness at 30, 60 or 120min.", "output": "n - hexane." }, { "input": "The extract, n - hexane - soluble fraction and isolated compound reduced the elevation in blood alcohol concentrations 30 and 60min after 40 % alcohol administration.", "output": "n - hexane, alcohol, alcohol." }, { "input": "The isolated compound ( 10 and 30mg / kg ) enhanced liver ADH activity 30 and 60min after 40 % alcohol administration.", "output": "alcohol." }, { "input": "The compound was identified as curcumenone by a direct comparison of ( 1 ) H - and ( 13 ) C - NMR spectral data.", "output": "curcumenone, ( 1 ) H, ( 13 ) C." }, { "input": "In conclusion, the protective effect of the C. zedoaria extract on drunkenness might be due to an active substance, curcumenone, and decreases in the elevation of blood alcohol concentrations through increased liver alcohol dehydrogenase activity.", "output": "curcumenone, alcohol, alcohol." }, { "input": "Nitrogen dioxide at the air - water interface: trapping, absorption, and solvation in the bulk and at the surface.", "output": "Nitrogen dioxide." }, { "input": "The interaction of NO ( 2 ) with water surfaces in the troposphere is of major interest in atmospheric chemistry.", "output": "NO ( 2 )." }, { "input": "We examined an initial step in this process, the uptake of NO ( 2 ) by water through the use of molecular dynamics simulations.", "output": "NO ( 2 )." }, { "input": "An NO ( 2 ) - H ( 2 ) O intermolecular potential was obtained by fitting to high - level ab initio calculations.", "output": "NO ( 2 ), H ( 2 ) O." }, { "input": "We determined the binding of NO ( 2 ) - H ( 2 ) O to be about two times stronger than that previously calculated.", "output": "NO ( 2 ), H ( 2 ) O." }, { "input": "From scattering simulations of an NO ( 2 ) molecule interacting with a water slab we observed that the majority of the scattering events resulted in outcomes in which the NO ( 2 ) molecule became trapped at the surface or in the interior of the water slab.", "output": "NO ( 2 ), NO ( 2 )." }, { "input": "Typical surface - trapped / adsorbed and bulk - solvated / absorbed trajectories were analyzed to obtain radial distribution functions and the orientational propensity of NO ( 2 ) with respect to the water surface.", "output": "NO ( 2 )." }, { "input": "We observed an affinity of the nitrogen atom for the oxygen in water, rather than hydrogen - bonding which was rare.", "output": "nitrogen, oxygen, hydrogen." }, { "input": "The water solvation shell was less tight for the bulk - absorbed NO ( 2 ) than for the surface - adsorbed NO ( 2 ).", "output": "NO ( 2 ), NO ( 2 )." }, { "input": "Adsorbed NO ( 2 ) demonstrated a marked orientational preference, with the oxygens pointing into the vacuum.", "output": "NO ( 2 ), oxygens." }, { "input": "Such behavior is expected for a mildly hydrophobic and surfactant molecule like NO ( 2 ).", "output": "NO ( 2 )." }, { "input": "Estimates based on our results suggest that at high NO ( 2 ) concentrations encountered, for example, in some sampling systems, adsorption and reaction of NO ( 2 ) at the surface may contribute to the formation of gas - phase HONO.", "output": "NO ( 2 ), NO ( 2 ), HONO." }, { "input": "Liver - specific disruption of the murine glucagon receptor produces alpha - cell hyperplasia: evidence for a circulating alpha - cell growth factor.", "output": "There is no related enetity." }, { "input": "Glucagon is a critical regulator of glucose homeostasis; however, mechanisms regulating glucagon action and alpha - cell function and number are incompletely understood.", "output": "glucose." }, { "input": "To elucidate the role of the hepatic glucagon receptor ( Gcgr ) in glucagon action, we generated mice with hepatocyte - specific deletion of the glucagon receptor.", "output": "There is no related enetity." }, { "input": "Gcgr ( Hep ) ( - / - ) mice exhibited reductions in fasting blood glucose and improvements in insulin sensitivity and glucose tolerance compared with wild - type controls, similar in magnitude to changes observed in Gcgr ( - / - ) mice.", "output": "glucose, glucose." }, { "input": "Despite preservation of islet Gcgr signaling, Gcgr ( Hep ) ( - / - ) mice developed hyperglucagonemia and alpha - cell hyperplasia.", "output": "There is no related enetity." }, { "input": "To investigate mechanisms by which signaling through the Gcgr regulates alpha - cell mass, wild - type islets were transplanted into Gcgr ( - / - ) or Gcgr ( Hep ) ( - / - ) mice.", "output": "There is no related enetity." }, { "input": "Wild - type islets beneath the renal capsule of Gcgr ( - / - ) or Gcgr ( Hep ) ( - / - ) mice exhibited an increased rate of alpha - cell proliferation and expansion of alpha - cell area, consistent with changes exhibited by endogenous alpha - cells in Gcgr ( - / - ) and Gcgr ( Hep ) ( - / - ) pancreata.", "output": "There is no related enetity." }, { "input": "These results suggest that a circulating factor generated after disruption of hepatic Gcgr signaling can increase alpha - cell proliferation independent of direct pancreatic input.", "output": "There is no related enetity." }, { "input": "Identification of novel factors regulating alpha - cell proliferation and mass may facilitate the generation and expansion of alpha - cells for transdifferentiation into beta - cells and the treatment of diabetes.", "output": "There is no related enetity." }, { "input": "HLA - A * 24 is an independent predictor of 5 - year progression to diabetes in autoantibody - positive first - degree relatives of type 1 diabetic patients.", "output": "There is no related enetity." }, { "input": "We investigated whether HLA - A * 24 typing complements screening for HLA - DQ and for antibodies ( Abs ) against insulin, GAD, IA - 2 ( IA - 2A ), and zinc transporter - 8 ( ZnT8A ) for prediction of rapid progression to type 1 diabetes ( T1D ).", "output": "zinc." }, { "input": "Persistently Ab ( + ) siblings / offspring ( n = 288; aged 0 - 39 years ) of T1D patients were genotyped for HLA - DQA1 - DQB1 and HLA - A * 24 and monitored for development of diabetes within 5 years of first Ab ( + ).", "output": "There is no related enetity." }, { "input": "HLA - A * 24 ( P = 0. 009 ), HLA - DQ2 / DQ8 ( P = 0. 001 ), and positivity for IA - 2A +/- ZnT8A ( P < 0. 001 ) were associated with development of T1D in multivariate analysis.", "output": "There is no related enetity." }, { "input": "The 5 - year risk increased with the number of the above three markers present ( n = 0: 6 %; n = 1: 18 %; n = 2: 46 %; n = 3: 100 % ).", "output": "There is no related enetity." }, { "input": "Positivity for one or more markers identified a subgroup of 171 ( 59 % ) containing 88 % of rapid progressors.", "output": "There is no related enetity." }, { "input": "The combined presence of HLA - A * 24 and IA - 2A ( + ) +/- ZnT8A ( + ) defined a subgroup of 18 ( 6 % ) with an 82 % diabetes risk.", "output": "There is no related enetity." }, { "input": "Among IA - 2A ( + ) +/- ZnT8A ( + ) relatives, identification of HLA - A * 24 carriers in addition to HLA - DQ2 / DQ8 carriers increased screening sensitivity for relatives at high Ab - and HLA - inferred risk ( 64 % progression; P = 0. 002 ).", "output": "There is no related enetity." }, { "input": "In conclusion, HLA - A * 24 independently predicts rapid progression to T1D in Ab ( + ) relatives and complements IA - 2A, ZnT8A, and HLA - DQ2 / DQ8 for identifying participants in immunointervention trials.", "output": "There is no related enetity." }, { "input": "Comparison of the structural characteristics of Cu ( 2 + ) - bound and unbound alpha - syn12 peptide obtained in simulations using different force fields.", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "The effects of Cu ( 2 + ) binding and the utilization of different force fields when modeling the structural characteristics of alpha - syn12 peptide were investigated.", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "To this end, we performed extensive temperature replica exchange molecular dynamics ( T - REMD ) simulations on Cu ( 2 + ) - bound and unbound alpha - syn12 peptide using the GROMOS 43A1, OPLS - AA, and AMBER03 force fields.", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "Each replica was run for 300 ns.", "output": "There is no related enetity." }, { "input": "The structural characteristics of alpha - syn12 peptide were studied based on backbone dihedral angle distributions, free - energy surfaces obtained with different reaction coordinates, favored conformations, the formation of different Turn structures, and the solvent exposure of the hydrophobic residues.", "output": "alpha - syn12 peptide." }, { "input": "The findings show that AMBER03 prefers to sample helical structures for the unbound alpha - syn12 peptide and does not sample any beta - hairpin structure for the Cu ( 2 + ) - bound alpha - syn12 peptide.", "output": "alpha - syn12 peptide, Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "In contrast, the central structure of the major conformational clusters for the Cu ( 2 + ) - bound and unbound alpha - syn12 peptide according to simulations performed using the GROMOS 43A1 and OPLS - AA force fields is a beta - hairpin with Turn ( 9 - 6 ).", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "Cu ( 2 + ) can also promote the formation of the beta - hairpin and increase the solvent exposure of hydrophobic residues, which promotes the aggregation of alpha - syn12 peptide.", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "This study can help us to understand the mechanisms through which Cu ( 2 + ) participates in the fibrillation of alpha - syn12 peptide at the atomic level, which in turn represents a step towards elucidating the nosogenesis of Parkinson ' s disease.", "output": "Cu ( 2 + ), alpha - syn12 peptide." }, { "input": "CB ( 1 ) receptor allosteric modulators display both agonist and signaling pathway specificity.", "output": "There is no related enetity." }, { "input": "We have previously identified allosteric modulators of the cannabinoid CB ( 1 ) receptor ( Org 27569, PSNCBAM - 1 ) that display a contradictory pharmacological profile: increasing the specific binding of the CB ( 1 ) receptor agonist [ ( 3 ) H ] CP55940 but producing a decrease in CB ( 1 ) receptor agonist efficacy.", "output": "Org 27569, PSNCBAM - 1, [ ( 3 ) H ] CP55940." }, { "input": "Here we investigated the effect one or both compounds in a broad range of signaling endpoints linked to CB ( 1 ) receptor activation.", "output": "There is no related enetity." }, { "input": "We assessed the effect of these compounds on CB ( 1 ) receptor agonist - induced [ ( 35 ) S ] GTP gamma S binding, inhibition, and stimulation of forskolin - stimulated cAMP production, phosphorylation of extracellular signal - regulated kinases ( ERK ), and beta - arrestin recruitment.", "output": "[ ( 35 ) S ] GTP gamma S, forskolin, cAMP." }, { "input": "We also investigated the effect of these allosteric modulators on CB ( 1 ) agonist binding kinetics.", "output": "There is no related enetity." }, { "input": "Both compounds display ligand dependence, being significantly more potent as modulators of CP55940 signaling as compared with WIN55212 and having little effect on [ ( 3 ) H ] WIN55212 binding.", "output": "CP55940, WIN55212, [ ( 3 ) H ] WIN55212." }, { "input": "Org 27569 displays biased antagonism whereby it inhibits: agonist - induced guanosine 5 ' - O - ( 3 - [ ( 35 ) S ] thio ) triphosphate ( [ ( 35 ) S ] GTP gamma S ) binding, simulation ( G alpha ( s ) - mediated ), and inhibition ( G alpha ( i ) - mediated ) of cAMP production and beta - arrestin recruitment.", "output": "Org 27569, guanosine 5 ' - O - ( 3 - [ ( 35 ) S ] thio ) triphosphate, [ ( 35 ) S ] GTP gamma S, cAMP." }, { "input": "In contrast, it acts as an enhancer of agonist - induced ERK phosphorylation.", "output": "There is no related enetity." }, { "input": "Alone, the compound can act also as an allosteric agonist, increasing cAMP production and ERK phosphorylation.", "output": "cAMP." }, { "input": "We find that in both saturation and kinetic - binding experiments, the Org 27569 and PSNCBAM - 1 appeared to influence only orthosteric ligand maximum occupancy rather than affinity.", "output": "Org 27569, PSNCBAM - 1." }, { "input": "The data indicate that the allosteric modulators share a common mechanism whereby they increase available high - affinity CB ( 1 ) agonist binding sites.", "output": "There is no related enetity." }, { "input": "The receptor conformation stabilized by the allosterics appears to induce signaling and also selectively traffics orthosteric agonist signaling via the ERK phosphorylation pathway.", "output": "There is no related enetity." }, { "input": "Plasma ghrelin is positively associated with body fat, liver fat and milk fat content but not with feed intake of dairy cows after parturition.", "output": "There is no related enetity." }, { "input": "Ghrelin is a gastrointestinal peptide hormone that is present in blood mostly in a non - posttranslationally modified form, with a minor proportion acylated at Ser ( 3 ).", "output": "Ser." }, { "input": "Both ghrelin forms were initially assigned a role in the control of food intake but there is accumulating evidence for their involvement in fat allocation and utilization.", "output": "There is no related enetity." }, { "input": "We investigated changes in the ghrelin system in dairy cows, exhibiting differences in body fat mobilization and fatty liver, from late pregnancy to early lactation.", "output": "There is no related enetity." }, { "input": "Sixteen dairy cows underwent liver biopsy and were retrospectively grouped based on high ( H ) or low ( L ) liver fat content post - partum.", "output": "There is no related enetity." }, { "input": "Both groups had a comparable feed intake in week - 6 ( before parturition ) and week 2 ( after parturition ).", "output": "There is no related enetity." }, { "input": "Only before parturition was preprandial total ghrelin concentration higher in L than in H cows and only after parturition was the basal plasma concentration of non - esterified fatty acids higher in H than in L cows.", "output": "fatty acids." }, { "input": "Both before and after parturition, H cows had higher preprandial plasma concentrations of acyl ghrelin, a higher acyl: total ghrelin ratio, lower plasma triacylglyceride concentrations and a lower respiratory quotient compared with L cows.", "output": "acyl, acyl, triacylglyceride." }, { "input": "These group differences could not be attributed to an allelic variant of the acyl ghrelin receptor.", "output": "acyl." }, { "input": "Rather, the ratio of acyl: total ghrelin correlated with several aspects of fat metabolism and with respiratory quotient but not with feed intake.", "output": "acyl." }, { "input": "These results show that endogenous ghrelin forms are associated with fat allocation, fatty liver, and utilization of fat during the periparturient period.", "output": "There is no related enetity." }, { "input": "1, 25 - Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue.", "output": "1 , 25 - Dihydroxyvitamin D3." }, { "input": "Leptin is an adipose tissue - derived hormone that plays a critical role in energy homeostasis.", "output": "There is no related enetity." }, { "input": "Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear.", "output": "Vitamin D, vitamin D." }, { "input": "Leptin expression and secretion was reduced in vitamin D receptor ( VDR ) - null mice and increased in transgenic ( Tg ) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression.", "output": "vitamin D, vitamin D." }, { "input": "To address this question, we determined the effect of vitamin D on leptin expression in vivo and ex vivo.", "output": "vitamin D." }, { "input": "One - week treatment of WT mice with the vitamin D analog RO - 27 - 5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels.", "output": "vitamin D, RO - 27 - 5646." }, { "input": "Moreover, in adipose tissue cultures, 1, 25 - dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR - null mice, and leptin upregulation induced by 1, 25 - dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice.", "output": "1 , 25 - dihydroxyvitamin D, 1 , 25 - dihydroxyvitamin D." }, { "input": "These data demonstrate that 1, 25 - dihydroxyvitamin D stimulates adipose leptin production in a VDR - dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression.", "output": "1 , 25 - dihydroxyvitamin D, vitamin D." }, { "input": "Suramin decreases injury and improves regeneration of ethanol - induced steatotic partial liver grafts.", "output": "Suramin, ethanol." }, { "input": "Steatotic grafts are excluded for use in partial liver transplantation ( LT ) because of the increased risk of primary nonfunction.", "output": "There is no related enetity." }, { "input": "This study investigated the effects of suramin, a polysulfonated naphthylurea, on the outcome of steatotic partial LT.", "output": "suramin, polysulfonated naphthylurea." }, { "input": "Rat livers were harvested after acute ethanol treatment ( 6 g / kg, intragastric administration ), reduced in size to =~ 1 / 3, and transplanted.", "output": "ethanol." }, { "input": "Serum alanine aminotransferase ( ALT ) and total bilirubin levels as well as hepatic necrosis and apoptosis were significantly higher after transplantation of fatty partial grafts ( FPG ) than lean partial grafts ( LPG ).", "output": "alanine, bilirubin." }, { "input": "Suramin ( 5 mg / kg, i. p. ) decreased ALT by =~ 60 %, hyperbilirubinemia by 75 %, necrosis by 83 %, and apoptosis by 70 % after FPG transplantation.", "output": "Suramin." }, { "input": "Hepatic cellular 5 - bromo - 2 ' - deoxyuridine ( BrdU ) incorporation increased to 28 % in LPG but was only 2 % in FPG at 48 hours, and the mitotic index increased to 7 % in LPG but was only 0. 2 % in FPG, indicating suppressed regeneration in FPG.", "output": "5 - bromo - 2 ' - deoxyuridine, BrdU." }, { "input": "Suramin increased BrdU incorporation and the mitotic index to 43 % and 9 %, respectively, in FPG.", "output": "Suramin, BrdU." }, { "input": "All FPG recipients died within 5 days.", "output": "There is no related enetity." }, { "input": "Suramin recovered survival of FPG to 62 %.", "output": "Suramin." }, { "input": "Tumor necrosis factor - alpha ( TNF - alpha ) mRNA was 2. 2 - fold higher in FPG than in LPG and was associated with activation of caspase - 8 and caspase - 3 in FPG.", "output": "There is no related enetity." }, { "input": "Suramin decreased TNF - alpha and caspase activation in FPG.", "output": "Suramin." }, { "input": "Transforming growth factor - beta ( TGF - beta ), phospho - Smad2 / 3 and p21Cip1 were significantly higher in FPG than in LPG and suramin blocked TGF - beta formation and its down - stream signaling pathway.", "output": "phospho, suramin." }, { "input": "Taken together, suramin improves the outcome of FPG transplantation, most likely by inhibition of TNF - alpha and TGF - beta formation.", "output": "suramin." }, { "input": "Ecological risk assessment in the context of global climate change.", "output": "There is no related enetity." }, { "input": "Changes to sources, stressors, habitats, and geographic ranges; toxicological effects; end points; and uncertainty estimation require significant changes in the implementation of ecological risk assessment ( ERA ).", "output": "There is no related enetity." }, { "input": "Because of the lack of analog systems and circumstances in historically studied sites, there is a likelihood of type III error.", "output": "There is no related enetity." }, { "input": "As a first step, the authors propose a decision key to aid managers and risk assessors in determining when and to what extent climate change should be incorporated.", "output": "There is no related enetity." }, { "input": "Next, when global climate change is an important factor, the authors recommend seven critical changes to ERA.", "output": "There is no related enetity." }, { "input": "First, develop conceptual cause - effect diagrams that consider relevant management decisions as well as appropriate spatial and temporal scales to include both direct and indirect effects of climate change and the stressor of management interest.", "output": "There is no related enetity." }, { "input": "Second, develop assessment end points that are expressed as ecosystem services.", "output": "There is no related enetity." }, { "input": "Third, evaluate multiple stressors and nonlinear responses - include the chemicals and the stressors related to climate change.", "output": "There is no related enetity." }, { "input": "Fourth, estimate how climate change will affect or modify management options as the impacts become manifest.", "output": "There is no related enetity." }, { "input": "Fifth, consider the direction and rate of change relative to management objectives, recognizing that both positive and negative outcomes can occur.", "output": "There is no related enetity." }, { "input": "Sixth, determine the major drivers of uncertainty, estimating and bounding stochastic uncertainty spatially, temporally, and progressively.", "output": "There is no related enetity." }, { "input": "Seventh, plan for adaptive management to account for changing environmental conditions and consequent changes to ecosystem services.", "output": "There is no related enetity." }, { "input": "Good communication is essential for making risk - related information understandable and useful for managers and stakeholders to implement a successful risk - assessment and decision - making process.", "output": "There is no related enetity." }, { "input": "Topoisomerase I inhibitor evodiamine acts as an antibacterial agent against drug - resistant Klebsiella pneumoniae.", "output": "evodiamine." }, { "input": "Topoisomerase inhibitors have been developed in a variety of clinical applications.", "output": "There is no related enetity." }, { "input": "We investigated the inhibitory effect of evodiamine on E. coli topoisomerase I, which may lead to an anti - bacterial effect.", "output": "evodiamine." }, { "input": "Evodiamine inhibits the supercoiled plasmid DNA relaxation that is catalyzed by E. coli topoisomerase I, and computer - aided docking has shown that the Arg161 and Asp551 residues of topoisomerase I interact with evodiamine.", "output": "Evodiamine, Arg161, Asp551, evodiamine." }, { "input": "We investigated the bactericidal effect of evodiamine against multidrug - resistant Klebsiella pneumoniae.", "output": "evodiamine." }, { "input": "Evodiamine showed a significantly lower minimal inhibitory concentration value ( MIC 128 micro g / mL ) compared with antibiotics ( > 512 micro g / mL ) against the clinical isolate of K. pneumoniae.", "output": "Evodiamine." }, { "input": "The results suggested that evodiamine is a potential agent against drug - resistant bacteria.", "output": "evodiamine." }, { "input": "Derivation of a benchmark for freshwater ionic strength.", "output": "There is no related enetity." }, { "input": "Because increased ionic strength has caused deleterious ecological changes in freshwater streams, thresholds for effects are needed to inform resource - management decisions.", "output": "There is no related enetity." }, { "input": "In particular, effluents from surface coal mining raise the ionic strength of receiving streams.", "output": "coal." }, { "input": "The authors developed an aquatic life benchmark for specific conductance as a measure of ionic strength that is expected to prevent the local extirpation of 95 % of species from neutral to alkaline waters containing a mixture of dissolved ions in which the mass of SO ( 4 ) 2 - + HCO ( 3 ) - >= Cl ( - ).", "output": "SO ( 4 ) 2 -, HCO ( 3 ) -, Cl ( - )." }, { "input": "Extirpation concentrations of specific conductance were estimated from the presence and absence of benthic invertebrate genera from 2, 210 stream samples in West Virginia.", "output": "There is no related enetity." }, { "input": "The extirpation concentration is the 95th percentile of the distribution of the probability of occurrence of a genus with respect to specific conductance.", "output": "There is no related enetity." }, { "input": "In a region with a background of 116 micro S / cm, the 5th percentile of the species sensitivity distribution of extirpation concentrations for 163 genera is 300 micro S / cm.", "output": "There is no related enetity." }, { "input": "Because the benchmark is not protective of all genera and protects against extirpation rather than reduction in abundance, this level may not fully protect sensitive species or higher - quality, exceptional waters.", "output": "There is no related enetity." }, { "input": "Hypoxia - response element ( HRE ) - directed transcriptional regulation of the rat lysyl oxidase gene in response to cobalt and cadmium.", "output": "lysyl, cobalt, cadmium." }, { "input": "Lysyl oxidase ( LO ) catalyzes crosslink of collagen, elastin, and histone H1, stabilizing the extracellular matrix and cell nucleus.", "output": "Lysyl." }, { "input": "This enzyme displays dual functions for tumorigenesis, i. e., as a tumor suppressor inactivating the ras oncogene and as a tumor promoter enhancing malignant cell metastasis.", "output": "There is no related enetity." }, { "input": "To elucidate LO transcriptional regulation, we have cloned the 804 base pair region upstream of the translation start site ( ATG ) of the rat LO gene with the maximal promoter activity.", "output": "There is no related enetity." }, { "input": "Computer analysis indicated that at least four hypoxia - response element ( HRE ) consensuses ( 5 ' - ACGTG - 3 ' ) exist in the cloned LO promoter.", "output": "There is no related enetity." }, { "input": "Treatment of rat lung fibroblasts ( RFL6 ) with CoCl2 ( Co, 10 - 100 mu M ), a chemical hypoxia reagent, enhanced LO mRNA expression and promoter activities.", "output": "CoCl2, Co." }, { "input": "Overexpression of LO was associated with upregulation of hypoxia - inducible factor ( HIF ) - 1 alpha at mRNA levels in cobalt ( Co ) - treated cells.", "output": "cobalt, Co." }, { "input": "Thus, LO is a hypoxia - responsive gene.", "output": "There is no related enetity." }, { "input": "Dominant negative - HIF - 1 alpha inhibited LO promoter activities stimulated by Co.", "output": "Co." }, { "input": "Electrophoretic mobility shift, oligonucleotide competition, and in vitro translated HIF - 1 alpha binding assays indicated that only one HRE mapped at - 387 / - 383 relative to ATG was functionally active among four consensuses.", "output": "There is no related enetity." }, { "input": "Site - directed mutation of this HRE significantly diminished the Co - induced and LO promoter - directed expression of the reporter gene.", "output": "Co." }, { "input": "Cadmium ( Cd ), an inducer of reactive oxygen species, inhibited HIF - 1 alpha mRNA expression and HIF - 1 alpha binding to the LO gene in Co - treated cells as revealed by RT - PCR and ChIP assays, respectively.", "output": "Cadmium, Cd, oxygen, Co." }, { "input": "Thus, modulation of the HRE activity by Co and Cd plays a critical role in LO gene transactivation.", "output": "Co, Cd." }, { "input": "Identifying protein interaction subnetworks by a bagging Markov random field - based method.", "output": "There is no related enetity." }, { "input": "Identification of differentially expressed subnetworks from protein - protein interaction ( PPI ) networks has become increasingly important to our global understanding of the molecular mechanisms that drive cancer.", "output": "There is no related enetity." }, { "input": "Several methods have been proposed for PPI subnetwork identification, but the dependency among network member genes is not explicitly considered, leaving many important hub genes largely unidentified.", "output": "There is no related enetity." }, { "input": "We present a new method, based on a bagging Markov random field ( BMRF ) framework, to improve subnetwork identification for mechanistic studies of breast cancer.", "output": "There is no related enetity." }, { "input": "The method follows a maximum a posteriori principle to form a novel network score that explicitly considers pairwise gene interactions in PPI networks, and it searches for subnetworks with maximal network scores.", "output": "There is no related enetity." }, { "input": "To improve their robustness across data sets, a bagging scheme based on bootstrapping samples is implemented to statistically select high confidence subnetworks.", "output": "There is no related enetity." }, { "input": "We first compared the BMRF - based method with existing methods on simulation data to demonstrate its improved performance.", "output": "There is no related enetity." }, { "input": "We then applied our method to breast cancer data to identify PPI subnetworks associated with breast cancer progression and / or tamoxifen resistance.", "output": "tamoxifen." }, { "input": "The experimental results show that not only an improved prediction performance can be achieved by the BMRF approach when tested on independent data sets, but biologically meaningful subnetworks can also be revealed that are relevant to breast cancer and tamoxifen resistance.", "output": "tamoxifen." }, { "input": "G4LDB: a database for discovering and studying G - quadruplex ligands.", "output": "There is no related enetity." }, { "input": "The G - quadruplex ligands database ( G4LDB, http: / / www. g4ldb. org ) provides a unique collection of reported G - quadruplex ligands to streamline ligand / drug discovery targeting G - quadruplexes.", "output": "There is no related enetity." }, { "input": "G - quadruplexes are guanine - rich nucleic acid sequences in human telomeres and gene promoter regions.", "output": "guanine, nucleic acid." }, { "input": "There is a growing recognition for their profound roles in a wide spectrum of diseases, such as cancer, diabetes and cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Ligands that affect the structure and activity of G - quadruplexes can shed light on the search for G - quadruplex - targeting drugs.", "output": "There is no related enetity." }, { "input": "Therefore, we built the G4LDB to ( i ) compile a data set covering various physical properties and 3D structure of G - quadruplex ligands; ( ii ) provide Web - based tools for G - quadruplex ligand design; and ( iii ) to facilitate the discovery of novel therapeutic and diagnostic agents targeting G - quadruplexes.", "output": "There is no related enetity." }, { "input": "G4LDB currently contains > 800 G - quadruplex ligands with ~ 4000 activity records, which, to our knowledge, is the most extensive collection of its kind.", "output": "There is no related enetity." }, { "input": "It offers a user friendly interface that can meet a variety of data inquiries from researchers.", "output": "There is no related enetity." }, { "input": "For example, ligands can be searched for by name, molecular properties, structures, ligand activities and so on.", "output": "There is no related enetity." }, { "input": "Building on the reported data, the database also provides an online ligand design module that can predict ligand binding affinity in real time.", "output": "There is no related enetity." }, { "input": "Laminar silk scaffolds for aligned tissue fabrication.", "output": "There is no related enetity." }, { "input": "3D - biomaterial scaffolds with aligned architecture are of vital importance in tissue regeneration.", "output": "There is no related enetity." }, { "input": "A generic method is demonstrated to produce aligned biomaterial scaffolds using the physics of directional ice freezing.", "output": "There is no related enetity." }, { "input": "Homogeneously aligned 3D silk scaffolds with high porosity and alignment are prepared.", "output": "There is no related enetity." }, { "input": "The method can be adapted to a wide range of polymers and is devoid of any chemical reactions, thus avoiding potential complications associated with by - products.", "output": "There is no related enetity." }, { "input": "Mechanical properties and cellular responses with chondrocytes and bone - marrow - derived hMSCs are studied, assessing survival, proliferation, and differentiation.", "output": "There is no related enetity." }, { "input": "In vivo tests suggest biocompatibility of the matrices for future tissue engineering applications, specifically in areas where high cellular alignment is needed.", "output": "There is no related enetity." }, { "input": "Enantiomeric discrimination of isoxazoline fused beta - amino acid derivatives using ( 18 - crown - 6 ) - 2, 3, 11, 12 - tetracarboxylic acid as a chiral NMR solvating agent.", "output": "isoxazoline, beta - amino acid, ( 18 - crown - 6 ) - 2 , 3 , 11 , 12 - tetracarboxylic acid." }, { "input": "( 18 - Crown - 6 ) - 2, 3, 11, 12 - tetracarboxylic acid is a useful chiral NMR solvating agent for isoxazoline - fused beta - amino acid derivatives.", "output": "( 18 - Crown - 6 ) - 2 , 3 , 11 , 12 - tetracarboxylic acid, isoxazoline, beta - amino acid." }, { "input": "Isoxazoline substrates are analyzed as their hydrochloride salts in methanol - d ( 4 ).", "output": "Isoxazoline, hydrochloride, methanol." }, { "input": "The crown ether and substrate associate through the formation of three hydrogen bonds between the protonated amine and crown ether oxygen atoms.", "output": "hydrogen, amine, crown ether, oxygen." }, { "input": "Enantiomeric discrimination is observed for two or more resonances of every substrate.", "output": "There is no related enetity." }, { "input": "At least one of these resonances is free of overlap with other resonances in the spectrum and has large enough enantiomeric discrimination to enable the determination of enantiomeric purity.", "output": "There is no related enetity." }, { "input": "2D COSY methods can be used to identify additional resonances that exhibit enantiomeric discrimination in the NMR spectrum.", "output": "There is no related enetity." }, { "input": "Effects of mutated pregnancy - associated plasma protein - a on atherosclerotic lesion development in mice.", "output": "There is no related enetity." }, { "input": "Pregnancy - associated plasma protein - A ( PAPP - A ) is a large multidomain metalloprotease involved in cleavage of IGF binding protein ( IGFBP ) - 4 and - 5 thereby causing release of bioactive IGF.", "output": "There is no related enetity." }, { "input": "Individual domains of PAPP - A have been characterized in vitro, including the metzincin proteolytic domain important for IGFBP proteolytic activity, short consensus repeats critical for cell surface association, and Lin - 12 / Notch repeat module demonstrated to determine IGFBP substrate specificity.", "output": "There is no related enetity." }, { "input": "To test the hypothesis that specific cleavage of IGFBP - 4 by PAPP - A in close proximity to the cell surface is required for development of lesions in a murine model of atherosclerosis, the following PAPP - A transgenic ( Tg ) mice were generated: Tg ( E483A ), which lacks all PAPP - A proteolytic activity; Tg ( D1499A ), which selectively lacks proteolytic activity against IGFBP - 4; and Tg ( K1296A / K1316A ), in which cell surface binding is compromised.", "output": "There is no related enetity." }, { "input": "Following cross - breeding with apolipoprotein E ( ApoE ) knockout ( KO ) mice, ApoE KO / Tg mice were fed a high - fat diet to promote aortic lesion development.", "output": "There is no related enetity." }, { "input": "Lesion area was increased 2 - fold in aortas from ApoE KO / Tg wild - type compared with ApoE KO mice ( P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "However, there was no significant increase in the lesion area in any of the ApoE KO / Tg mutant mice.", "output": "There is no related enetity." }, { "input": "We conclude that PAPP - A proteolytic activity is required for the lesion - promoting effect of PAPP - A and that its specificity must be directed against IGFBP - 4.", "output": "There is no related enetity." }, { "input": "Furthermore, our data demonstrate that cleavage of IGFBP - 4 at a distance from the cell surface, and hence from the IGF receptor, is not effective in promoting the development of the atherosclerotic lesions.", "output": "There is no related enetity." }, { "input": "Thus, PAPP - A exerts its effect while bound to the cell surface in vivo.", "output": "There is no related enetity." }, { "input": "Does catch and release affect the mating system and individual reproductive success of wild Atlantic salmon ( Salmo salar L. )?", "output": "There is no related enetity." }, { "input": "In this study, we documented the breeding system of a wild population of Atlantic salmon ( Salmo salar L. ) by genetically sampling every returning adult and assessed the determinants of individual fitness.", "output": "There is no related enetity." }, { "input": "We then quantified the impacts of catch and release ( C & R ) on mating and reproductive success.", "output": "There is no related enetity." }, { "input": "Both sexes showed high variance in individual reproductive success, and the estimated standardized variance was higher for males ( 2. 86 ) than for females ( 0. 73 ).", "output": "There is no related enetity." }, { "input": "We found a weak positive relationship between body size and fitness and observed that fitness was positively correlated with the number of mates, especially in males.", "output": "There is no related enetity." }, { "input": "Mature male parr sired 44 % of the analysed offspring.", "output": "There is no related enetity." }, { "input": "The impact of C & R on the number of offspring was size dependent, as the reproductive success of larger fish was more impaired than smaller ones.", "output": "There is no related enetity." }, { "input": "Also, there was an interactive negative effect of water temperature and air exposure time on reproductive success of C & R salmon.", "output": "There is no related enetity." }, { "input": "This study improves our understanding of the complex reproductive biology of the Atlantic salmon and is the first to investigate the impact of C & R on reproductive success.", "output": "There is no related enetity." }, { "input": "Our study expands the management toolbox of appropriate C & R practices that promote conservation of salmon populations and limit negative impacts on mating and reproductive success.", "output": "There is no related enetity." }, { "input": "Effective targeting of A beta to macrophages by sonochemically prepared surface - modified protein microspheres.", "output": "There is no related enetity." }, { "input": "Imbalanced homeostasis and oligomerization of the amyloid - beta ( A beta ) peptide in the brain are hallmarks of Alzheimer ' s disease ( AD ).", "output": "There is no related enetity." }, { "input": "Microglia and macrophages play a critical role in the etiology of AD either by clearing A beta from the brain or inducing inflammation.", "output": "There is no related enetity." }, { "input": "Recent evidence suggests that clearance of A beta by microglia / macrophages via the phagocytic pathway is defective in AD, which can contribute to the accumulation of A beta in the brain.", "output": "There is no related enetity." }, { "input": "We have recently demonstrated that protein microspheres modified at their surface with multiple copies of an A beta - recognition motif can strongly bind A beta, inhibit its aggregation, and directly reduce its toxicity by sequestering it from the medium.", "output": "There is no related enetity." }, { "input": "Here, we describe how microsphere - bound A beta can stimulate microglial cells and be phagocytosed through a mechanism that is distinct from that of A beta removal and, thus, contribute to the clearance of A beta, even by defective microglial cells.", "output": "There is no related enetity." }, { "input": "The phagocytosis was most effective, with microspheres having a diameter of < 1 mu m.", "output": "There is no related enetity." }, { "input": "The introduction of polyethylene glycol to the surface of the microspheres changed the kinetics of the phagocytosis.", "output": "polyethylene glycol." }, { "input": "Moreover, while aggregated A beta induced a significant inflammatory response that was manifested by the release of TNF - alpha, the microsphere - bound A beta dramatically reduced the amount of cytokine released from microglial cells.", "output": "There is no related enetity." }, { "input": "Diversity patterns of uncultured Haptophytes unravelled by pyrosequencing in Naples Bay.", "output": "There is no related enetity." }, { "input": "Haptophytes are a key phylum of marine protists, including ~ 300 described morphospecies and 80 morphogenera.", "output": "There is no related enetity." }, { "input": "We used 454 pyrosequencing on large subunit ribosomal DNA ( LSU rDNA ) fragments to assess the diversity from size - fractioned plankton samples collected in the Bay of Naples.", "output": "There is no related enetity." }, { "input": "One group - specific primer set targeting the LSU rDNA D1 / D2 region was designed to amplify Haptophyte sequences from nucleic acid extracts ( total DNA or RNA ) of two size fractions ( 0. 8 - 3 or 3 - 20 mu m ) and two sampling depths [ subsurface, at 1 m, or deep chlorophyll maximum ( DCM ) at 23 m ].", "output": "chlorophyll." }, { "input": "454 reads were identified using a database covering the entire Haptophyta diversity currently sequenced.", "output": "There is no related enetity." }, { "input": "Our data set revealed several hundreds of Haptophyte clusters.", "output": "There is no related enetity." }, { "input": "However, most of these clusters could not be linked to taxonomically known sequences: considering OTUs ( 97 % ) ( clusters build at a sequence identity level of 97 % ) on our global data set, less than 1 % of the reads clustered with sequences from cultures, and less than 12 % clustered with reference sequences obtained previously from cloning and Sanger sequencing of environmental samples.", "output": "There is no related enetity." }, { "input": "Thus, we highlighted a large uncharacterized environmental genetic diversity, which clearly shows that currently cultivated species poorly reflect the actual diversity present in the natural environment.", "output": "There is no related enetity." }, { "input": "Haptophyte community appeared to be significantly structured according to the depth.", "output": "There is no related enetity." }, { "input": "The highest diversity and evenness were obtained in samples from the DCM, and samples from the large size fraction ( 3 - 20 mu m ) taken at the DCM shared a lower proportion of common OTUs ( 97 % ) with the other samples.", "output": "There is no related enetity." }, { "input": "Reads from the species Chrysoculter romboideus were notably found at the DCM, while they could be detected at the subsurface.", "output": "There is no related enetity." }, { "input": "The highest proportion of totally unknown OTUs ( 97 % ) was collected at the DCM in the smallest size fraction ( 0. 8 - 3 mu m ).", "output": "There is no related enetity." }, { "input": "Overall, this study emphasized several technical and theoretical barriers inherent to the exploration of the large and largely unknown diversity of unicellular eukaryotes.", "output": "There is no related enetity." }, { "input": "The octadecaneuropeptide stimulates somatolactin release from cultured goldfish pituitary cells.", "output": "There is no related enetity." }, { "input": "The present study aimed to investigate the distribution of the octadecaneuropeptide ( ODN ) in the goldfish brain and to look for a possible effect of ODN on somatolactin ( SL ) release from pituitary cells.", "output": "There is no related enetity." }, { "input": "A discrete population of ODN - immunoreactive neurones was localised in the lateral part of the nucleus lateralis tuberis.", "output": "There is no related enetity." }, { "input": "These neurones sent projections through the neurohypophyseal tract towards the neurohypophysis, and nerve fibres were seen in the close vicinity of SL - producing cells in the pars intermedia.", "output": "There is no related enetity." }, { "input": "Incubation of cultured goldfish pituitary cells with graded concentrations of ODN ( 10 ( - 9 ) - 10 ( - 5 ) m ) induced a dose - dependent stimulation of SL - beta, but not SL - alpha, release.", "output": "There is no related enetity." }, { "input": "ODN - evoked SL release was blocked by the metabotrophic endozepine receptor antagonist cyclo ( 1 - 8 ) [ DLeu ( 5 ) ] OP but was not affected by the central - type benzodiazepine receptor antagonist flumazenil.", "output": "cyclo ( 1 - 8 ) [ DLeu ( 5 ) ] OP, benzodiazepine, flumazenil." }, { "input": "ODN - induced SL release was suppressed by treatment with the phospholipase C ( PLC ) inhibitor U - 73122 but not with the protein kinase A ( PKA ) inhibitor H - 89.", "output": "U - 73122, H - 89." }, { "input": "These results indicate that, in fish, ODN produced by hypothalamic neurones acts as a hypophysiotrophic neuropeptide stimulating SL release.", "output": "There is no related enetity." }, { "input": "The effect of ODN is mediated through a metabotrophic endozepine receptor positively coupled to the PLC / inositol 1, 4, 5 - trisphosphate / protein kinase C - signalling pathway.", "output": "inositol 1 , 4 , 5 - trisphosphate." }, { "input": "Metal - mediated targeting in the body.", "output": "There is no related enetity." }, { "input": "Metal ions are important for many biological processes and are steadily available in the human body.", "output": "There is no related enetity." }, { "input": "Metal concentrations can be extremely high in diseased areas of various pathological conditions.", "output": "There is no related enetity." }, { "input": "Some synthetic and natural drugs need to be activated by metal ions as prodrugs.", "output": "There is no related enetity." }, { "input": "In this review, we provide a few examples to illustrate how metal ions activate and mediate drug targeting in the body.", "output": "There is no related enetity." }, { "input": "This knowledge may be helpful for the development of more effective drugs and pharmaceutical formulations.", "output": "There is no related enetity." }, { "input": "The serotonin receptor 7 promotes neurite outgrowth via ERK and Cdk5 signaling pathways.", "output": "serotonin." }, { "input": "Serotonergic neurotransmission is mediated by at least 14 subtypes of 5 - HT receptors.", "output": "5 - HT." }, { "input": "Among these, the CNS serotonin receptor 7 ( 5 - HTR7 ) is involved in diverse physiological processes.", "output": "serotonin." }, { "input": "Here we show that treatment of murine striatal and cortical neuronal cultures with 5 - HTR7 agonists ( 8 - OH - DPAT and LP - 211 ) significantly enhances neurite outgrowth.", "output": "8 - OH - DPAT, LP - 211." }, { "input": "This effect is abolished by the selective 5 - HTR7 antagonist SB - 269970, by the ERK inhibitor U0126, by the cyclin - dependent kinase 5 ( Cdk5 ) inhibitor roscovitine, as well as by cycloheximide, an inhibitor of protein synthesis.", "output": "SB - 269970, U0126, roscovitine, cycloheximide." }, { "input": "These data indicate that 5 - HTR7 activation stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK and Cdk5 activation, and de novo protein synthesis.", "output": "There is no related enetity." }, { "input": "Two - dimensional ( 2D ) gel electrophoresis coupled to Western blot analyses reveals both qualitative and quantitative expression changes in selected cytoskeletal proteins, following treatment of striatal primary cultures with LP - 211.", "output": "There is no related enetity." }, { "input": "In particular, the 34 kDa isoform of MAP1B is selectively expressed in stimulated cultures, consistent with a role of this protein in tubulin polymerization and neurite elongation.", "output": "There is no related enetity." }, { "input": "In summary, our results show that agonist - dependent activation of the endogenous 5 - HTR7 in CNS neuronal primary cultures stimulates ERK - and Cdk5 - dependent neurite outgrowth, sustained by modifications of cytoskeletal proteins.", "output": "There is no related enetity." }, { "input": "These data support the hypothesis that the 5 - HTR7 might play a crucial role in shaping neuronal morphology and behaviorally relevant neuronal networks, paving the way to new approaches able to modulate CNS connectivity.", "output": "There is no related enetity." }, { "input": "Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds.", "output": "glutamate." }, { "input": "To investigate the role of mGluR8 in modulating the synaptic responses of retinal ganglion cells, we used a recently identified positive allosteric modulator of mGluR8, AZ12216052 ( AZ ) and the mGluR8 - specific orthosteric agonist ( S ) - 3, 4 - dicarboxyphenylglycine ( DCPG ).", "output": "AZ12216052, ( S ) - 3 , 4 - dicarboxyphenylglycine, DCPG." }, { "input": "These agents were applied to whole - cell voltage - clamped ganglion cells from an isolated, superfused mouse retina preparation.", "output": "There is no related enetity." }, { "input": "DCPG reduced OFF - ganglion cell excitatory currents, whereas AZ enhanced the peak excitatory currents in ON -, OFF -, and ON - OFF - ganglion cells.", "output": "DCPG." }, { "input": "The effects on ganglion cell inhibitory currents were more varied.", "output": "There is no related enetity." }, { "input": "The effects of the allosteric modulator were stronger for bright stimuli than for dim stimuli, consistent with receptor stimulation by endogenous glutamate being stronger during bright light stimulation and with mGluR8 receptors mainly being localized away from glutamate release sites, immuno - labeled with VGLUT1.", "output": "glutamate, glutamate." }, { "input": "The differential sensitivity of ganglion cell light responses to DCPG and AZ supports multiple sites where mGluR8 modulates the light responses of ganglion cells.", "output": "DCPG." }, { "input": "Early life exposure to air pollution: how bad is it?", "output": "There is no related enetity." }, { "input": "Increasing concentrations of air pollution have been shown to contribute to an enormity of adverse health outcomes worldwide, which have been observed in clinical, epidemiological, and animal studies as well as in vitro investigations.", "output": "There is no related enetity." }, { "input": "Recently, studies have shown that air pollution can affect the developing fetus via maternal exposure, resulting in preterm birth, low birth weight, growth restriction, and potentially adverse cardiovascular and respiratory outcomes.", "output": "There is no related enetity." }, { "input": "This review will provide a summary of the harmful effects of air pollution exposure on the developing fetus and infant, and suggest potential mechanisms to limit the exposure of pregnant mothers and infants to air pollution.", "output": "There is no related enetity." }, { "input": "On scaffold hopping: challenges in the discovery of sulfated small molecules as mimetics of glycosaminoglycans.", "output": "There is no related enetity." }, { "input": "The design of sulfated, small, nonsaccharide molecules as modulators of proteins is still in its infancy as standard drug discovery tools such as library of diverse sulfated molecules and in silico docking and scoring protocol have not been firmly established.", "output": "There is no related enetity." }, { "input": "Databases, such as ZINC, contain too few sulfate - containing nonsaccharide molecules, which severely limits the identification of new hits.", "output": "ZINC, sulfate." }, { "input": "Lack of a generally applicable protocol for scaffold hopping limits the development of sulfated small molecules as synthetic mimetics of the highly sulfated glycosaminoglycans.", "output": "There is no related enetity." }, { "input": "We explored a sequential ligand - based ( LBVS ) and structure - based virtual screening ( SBVS ) approach starting from our initial discovery of monosulfated benzofurans to discover alternative scaffolds as allosteric modulators of thrombin, a key coagulation enzyme.", "output": "monosulfated benzofurans." }, { "input": "Screening the ZINC database containing nearly 1 million nonsulfated small molecules using a pharmacophore developed from the parent sulfated benzofurans followed by a genetic algorithm - based dual - filter docking and scoring screening identified a group of 10 promising hits, of which three top - scoring hits were synthesized.", "output": "ZINC, sulfated benzofurans." }, { "input": "Each was found to selectively inhibit human alpha - thrombin suggesting the possibility of this approach for scaffold hopping.", "output": "There is no related enetity." }, { "input": "Michaelis - Menten kinetics showed allosteric inhibition mechanism for the best molecule and human plasma studies confirmed good anticoagulation potential as expected.", "output": "There is no related enetity." }, { "input": "Our simple sequential LBVS and SBVS approach is likely to be useful as a general strategy for identification of sulfated small molecules hits as modulators of glycosaminoglycan - protein interactions.", "output": "There is no related enetity." }, { "input": "The perirhinal cortex of rats: an intricate area for microinfusion of anticonvulsants against soman - induced seizures.", "output": "There is no related enetity." }, { "input": "Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide cannula in each hemisphere only invades a small area of this seizure controlling site in rats exposed to soman.", "output": "There is no related enetity." }, { "input": "The purpose of the present study was to examine whether infusions made through 2 cannulas in each perirhinal cortex may produce more efficacious anticonvulsant action against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG - IV and MPEP.", "output": "procyclidine, caramiphen, glutamate, DCG - IV, MPEP." }, { "input": "The results showed that the mere presence of indwelling double cannulas caused proconvulsant effect in response to subsequent systemic administration of soman.", "output": "There is no related enetity." }, { "input": "Both the control and caramiphen groups with double cannulas had significantly shorter latencies to seizure onset than the corresponding groups with single cannula.", "output": "caramiphen." }, { "input": "Procyclidine resulted in anticonvulsant efficacy, even in rats with double cannulas.", "output": "Procyclidine." }, { "input": "In rats that received twin infusions of DCG - IV or MPEP, the anticonvulsant impact was very high, inasmuch as a majority of the rats in each group was protected against seizure activity.", "output": "DCG - IV, MPEP." }, { "input": "Drugs possessing powerful anticonvulsant potency can apparently counteract the proconvulsant effect of double cannulas, and some can even gain enhanced anticonvulsant capacity when invading a larger area of the perirhinal cortex.", "output": "There is no related enetity." }, { "input": "Perirhinal EEG recordings ( electrodes in indwelling cannulas ) in a separate set of rats not exposed to soman or drugs showed no differences in basal electrical activity ( total power 0. 5 - 25Hz or the theta band 4 - 12Hz ) between groups with single or double cannulas.", "output": "There is no related enetity." }, { "input": "The intrinsic excitability and synaptic connectivity of the perirhinal cortex may be associated with the proconvulsant impact observed in rats with double cannulas when exposed to soman.", "output": "There is no related enetity." }, { "input": "Placental concentrations of mercury, lead, cadmium, and arsenic and the risk of neural tube defects in a Chinese population.", "output": "mercury, cadmium, arsenic." }, { "input": "To examine whether in utero exposure to mercury ( Hg ), cadmium ( Cd ), lead ( Pb ) and arsenic ( As ) is associated with an elevated neural tube defects ( NTDs ) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer ( ICP - MS ) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls.", "output": "mercury, Hg, cadmium, Cd, Pb, arsenic, As, Hg, Cd, Pb, As." }, { "input": "The median Hg concentration in the NTD cases ( 2. 25 ng / g ) was higher than that of the controls ( 1. 16 ng / g ).", "output": "Hg." }, { "input": "The odds ratio ( OR ) for an Hg concentration above the median was 8. 80 ( 95 % CI 3. 80 - 20. 36 ) for the NTD cases.", "output": "There is no related enetity." }, { "input": "NTD risks increased for the second and third high levels of the concentrations, with ORs of 2. 70 ( 95 % CI 1. 13 - 6. 43 ) and 18. 20 ( 95 % CI 5. 45 - 60. 73 ), respectively.", "output": "There is no related enetity." }, { "input": "Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs.", "output": "Hg." }, { "input": "Telomere length and dynamics predict mortality in a wild longitudinal study.", "output": "There is no related enetity." }, { "input": "Explaining variation in life expectancy between individuals of the same age is fundamental to our understanding of population ecology and life history evolution.", "output": "There is no related enetity." }, { "input": "Variation in the length and rate of loss of the protective telomere chromosome caps has been linked to cellular lifespan.", "output": "There is no related enetity." }, { "input": "Yet, the extent to which telomere length and dynamics predict organismal lifespan in nature is still contentious.", "output": "There is no related enetity." }, { "input": "Using longitudinal samples taken from a closed population of Acrocephalus sechellensis ( Seychelles warblers ) studied for over 20 years, we describe the first study into life - long adult telomere dynamics ( 1 - 17 years ) and their relationship to mortality under natural conditions ( n = 204 individuals ).", "output": "There is no related enetity." }, { "input": "We show that telomeres shorten with increasing age and body mass, and that shorter telomeres and greater rates of telomere shortening predicted future mortality.", "output": "There is no related enetity." }, { "input": "Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions.", "output": "There is no related enetity." }, { "input": "Merit of quinacrine in the decrease of ingested sulfite - induced toxic action in rat brain.", "output": "quinacrine, sulfite." }, { "input": "We aimed at investigating the effects of sulfite - induced lipid peroxidation and apoptosis mediated by secretory phospholipase A2 ( sPLA2 ) on somatosensory evoked potentials ( SEP ) alterations in rats.", "output": "sulfite." }, { "input": "Thirty male albino Wistar rats were randomized into three experimental groups as follows; control ( C ), sodium metabisulfite treated ( S ), sodium metabisulfite + quinacrine treated ( SQ ).", "output": "sodium metabisulfite, sodium metabisulfite, quinacrine." }, { "input": "Sodium metabisulfite ( 100 mg / kg / day ) was given by gastric gavage for 5 weeks and 10 mg / kg / day quinacrine was applied as a single dose of intraperitoneal injection for the same period.", "output": "Sodium metabisulfite, quinacrine." }, { "input": "The latencies of SEP components were significantly prolonged in the S group and returned to control levels following quinacrine administration.", "output": "quinacrine." }, { "input": "Plasma - S - sulfonate level was increased in S and SQ groups.", "output": "S, sulfonate." }, { "input": "TBARS levels in the S group were significantly higher than those detected in controls.", "output": "There is no related enetity." }, { "input": "Quinacrine significantly decreased brain TBARS levels in the SQ group compared with the S group.", "output": "Quinacrine." }, { "input": "Quinacrine treatment did not have an effect on the increased sPLA2 level of the sulfite administered group.", "output": "Quinacrine, sulfite." }, { "input": "Immunohistochemistry showed that sulfite caused an increase in caspase - 3 and TUNEL positive cells, restored to control levels via quinacrine administration.", "output": "sulfite, quinacrine." }, { "input": "This study showed that sPLA2 might play a role in ingested sulfite - induced SEP alterations, oxidative stress, apoptotic cell death and DNA damage in the brain.", "output": "sulfite." }, { "input": "Bone hemodynamic responses to changes in external pressure.", "output": "There is no related enetity." }, { "input": "Adequate blood supply and circulation to the bones is required to maintain a healthy skeleton.", "output": "There is no related enetity." }, { "input": "Inadequate blood perfusion is associated with numerous bone pathologies and a decrease in bone mineral density, yet bone hemodynamics remains poorly understood.", "output": "There is no related enetity." }, { "input": "This study aims to 1 ) quantify bone hemodynamic responses to changes in external pressure, and 2 ) identify the predominant mechanisms regulating bone hemodynamic responses to pressure changes.", "output": "There is no related enetity." }, { "input": "Photoplethysmography was used to measure bone and skin perfusion in response to changes in external pressure.", "output": "There is no related enetity." }, { "input": "Single - limb pressure chamber experiments were performed over a pressure range of - 50 to + 50mmHg.", "output": "There is no related enetity." }, { "input": "Bone perfusion is decreased at all negative pressures, and larger decrements in perfusion are observed at the more extreme pressure differences.", "output": "There is no related enetity." }, { "input": "At positive pressures we observed an initial increase in perfusion followed by activation of intramuscular pressure receptors at + 30mmHg, which overrides the initial response and results in decreased perfusion at the highest positive pressure levels.", "output": "There is no related enetity." }, { "input": "The myogenic effect is observed and is shown to be the predominant control mechanism in bone over a wide range of pressure exposures.", "output": "There is no related enetity." }, { "input": "Greater understanding of these hemodynamic mechanisms may be important in developing new drugs and therapies to treat various bone disorders.", "output": "There is no related enetity." }, { "input": "Nanostructural transformations during the reduction of hollow and porous nickel oxide nanoparticles.", "output": "nickel oxide." }, { "input": "Size - dependent nanostructural transformations occurring during the H ( 2 ) - mediated reduction of hollow and porous NiO nanoparticles were investigated for controlled nanoparticle sizes of ~ 10 to 100 nm.", "output": "H ( 2 ), NiO." }, { "input": "Transmission electron microscopy reveals that the location and number of reduction sites strongly depend on the nanoparticle size and structure.", "output": "There is no related enetity." }, { "input": "Excited - state proton coupled charge transfer modulated by molecular structure and media polarization.", "output": "There is no related enetity." }, { "input": "Charge and proton transfer reactions in the excited states of organic dyes can be coupled in many different ways.", "output": "There is no related enetity." }, { "input": "Despite the complementarity of charges, they can occur on different time scales and in different directions of the molecular framework.", "output": "There is no related enetity." }, { "input": "In certain cases, excited - state equilibrium can be established between the charge - transfer and proton - transfer species.", "output": "There is no related enetity." }, { "input": "The interplay of these reactions can be modulated and even reversed by variations in dye molecular structures and changes of the surrounding media.", "output": "There is no related enetity." }, { "input": "With knowledge of the mechanisms of these processes, desired rates and directions can be achieved, and thus the multiple emission spectral features can be harnessed.", "output": "There is no related enetity." }, { "input": "These features have found versatile applications in a number of cutting - edge technological areas, particularly in fluorescence sensing and imaging.", "output": "There is no related enetity." }, { "input": "How do the electrical properties of graphene change with its functionalization?", "output": "graphene." }, { "input": "Functionalization of graphene is essential to interface it with other moieties to expand the scope of its electrical / electronic applications.", "output": "graphene." }, { "input": "However, chemical functionalization and / or molecular interactions on graphene sensitively modulate its electrical properties.", "output": "graphene." }, { "input": "To evaluate and take advantage of the properties of functionalized graphene, it is important to understand how its electrical attributes ( such as carrier scattering, carrier concentration, charge polarity, quantum - capacitance enhanced doping, energy levels, transport mechanisms, and orbital hybridization of energy - bands ) are influenced by a change in carbon ' s structural conformation, hybridization state, chemical potential, local energy levels, and dopant / interface coupling induced via functionalization or molecular interactions.", "output": "graphene, carbon." }, { "input": "Here, a detailed and integrated model describes factors influencing these electrical characteristics of functionalized graphene ( covalent bonds, adsorption, pi - pi bonds, and lattice incorporation ).", "output": "graphene." }, { "input": "The electrical properties are governed via three mechanisms: ( a ) conversion of carbon ' s hybridized state, ( b ) dipole interactions enhanced via quantum capacitance, and ( c ) orbital hybridization with an interfacing molecule.", "output": "carbon." }, { "input": "A few graphenic materials are also identified where further studies are essential to understand the effect of their functionalization.", "output": "There is no related enetity." }, { "input": "Global cerebral ischemia: synaptic and cognitive dysfunction.", "output": "There is no related enetity." }, { "input": "Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population.", "output": "There is no related enetity." }, { "input": "Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest.", "output": "There is no related enetity." }, { "input": "These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective.", "output": "There is no related enetity." }, { "input": "Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients.", "output": "There is no related enetity." }, { "input": "A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non - specific targets and numerous cognitive improvements.", "output": "There is no related enetity." }, { "input": "This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia.", "output": "There is no related enetity." }, { "input": "Minocycline mediated mitochondrial cytoprotection: premises for therapy of cerebrovascular and neurodegenerative diseases.", "output": "Minocycline." }, { "input": "In the last decades, emerging molecular targets for ischemic neuroprotection and regeneration have been postulated.", "output": "There is no related enetity." }, { "input": "This fact allowed that classical drugs with well established therapeutic applications might be used in cerebrovascular diseases as well as neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Minocycline is a commonly used antibiotic of the tetracycline family ( 7 - dimethylamino - 6 - dimethyl - 6 - deoxytetracycline ) which reveals cytoprotective capability and potential use in treatment of different diseases.", "output": "Minocycline, tetracycline, 7 - dimethylamino - 6 - dimethyl - 6 - deoxytetracycline." }, { "input": "Here, we discuss the literature concerning minocycline.", "output": "minocycline." }, { "input": "The available data indicate that the antibiotic has multi - faceted effects on cell functions and, consequently, a number of clinical properties that are useful and / or could be useful for treatment of different diseases including bacterial infections, cancer, autoimmune disorders, ischemia as well as neurodegenerative and psychiatric diseases.", "output": "There is no related enetity." }, { "input": "Thus, application of minocycline as a therapeutic agent is the subject of clinical trials for various diseases.", "output": "minocycline." }, { "input": "It is also evident that minocycline - mediated cytoprotection, including neuroprotection, is an important aspect of its clinical application.", "output": "minocycline." }, { "input": "Here, we have reviewed the basis of the minocycline activity as well as different studies indicating that minocycline can be used as potential therapeutic agent in both cerebrovascular and neurodegenerative diseases in human.", "output": "minocycline, minocycline." }, { "input": "Neuroprotection & mechanism of ethanol in stroke and traumatic brain injury therapy: new prospects for an ancient drug.", "output": "ethanol." }, { "input": "Effective efforts to screen for agents that protect against the devastating effects of stroke have not produced viable results thus far.", "output": "There is no related enetity." }, { "input": "As a result this article reviews the possible role of ethanol as a neuroprotective agent in stroke and traumatic brain injury ( TBI ).", "output": "ethanol." }, { "input": "Previous studies have associated ethanol consumption with a decreased risk of ischemic stroke, suggesting a neuroprotective mechanism.", "output": "There is no related enetity." }, { "input": "The translation of this clinical knowledge into basic science research with the goal of new therapy for acute stroke patients remains in its initial stages.", "output": "There is no related enetity." }, { "input": "In a recent study involving rats, we have shown that ethanol administration, in the correct dose after stroke onset, protects against ischemia - induced brain injury.", "output": "ethanol." }, { "input": "The purpose of this paper is to discuss ethanol ' s neuroprotective properties in stroke when consumed as a preconditioning agent, in TBI with a positive blood alcohol content, and finally in stroke treatment, with the goal of using post - ischemia ethanol ( PIE ) therapy to ameliorate brain damage in the future.", "output": "ethanol, ethanol." }, { "input": "Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints.", "output": "There is no related enetity." }, { "input": "Chemical biologists commonly seek out correlations between the physicochemical properties of molecules and their behavior in biological systems.", "output": "There is no related enetity." }, { "input": "However, a new paradigm is emerging for peptides in which conformation is recognized as the primary determinant of bioactivity and bioavailability.", "output": "There is no related enetity." }, { "input": "This review highlights an emerging body of work that directly addresses how a peptide ' s conformation controls its biological effects, cell penetration, and intestinal absorption.", "output": "There is no related enetity." }, { "input": "Based on this work, the dream of mimicking the potency and bioavailability of natural product peptides is getting closer to reality.", "output": "There is no related enetity." }, { "input": "New 2 - ( aryloxy ) - 3 - phenylpropanoic acids as peroxisome proliferator - activated receptor alpha / gamma dual agonists able to upregulate mitochondrial carnitine shuttle system gene expression.", "output": "2 - ( aryloxy ) - 3 - phenylpropanoic acids, carnitine." }, { "input": "The preparation of a series of 2 - ( aryloxy ) - 3 - phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator - activated receptor alpha / gamma ( PPAR alpha / gamma ) dual agonist 1, allowed the identification of new ligands with higher potency on PPAR alpha and fine - tuned moderate PPAR gamma activity.", "output": "2 - ( aryloxy ) - 3 - phenylpropanoic acids, biphenyl." }, { "input": "For the most promising stereoisomer ( S ) - 16, X - ray and calorimetric studies in PPAR gamma revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor.", "output": "There is no related enetity." }, { "input": "On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPAR alpha and PPAR gamma, respectively.", "output": "There is no related enetity." }, { "input": "The effects of ( S ) - 16 on mitochondrial acylcarnitine carrier and carnitine - palmitoyl - transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPAR alpha agonist fibrates currently used in therapy.", "output": "acylcarnitine, carnitine, palmitoyl, carnitine." }, { "input": "Predicting isosteric heats for gas adsorption.", "output": "There is no related enetity." }, { "input": "A method for predicting the isosteric heat of gas adsorption on solid materials is developed which requires the measurement of a single isotherm - where previous methods, such as the Clausius - Clapeyron approach, require either multiple isotherms or complex calorimetric measurement.", "output": "There is no related enetity." }, { "input": "The T o th potential function, stemming from the Polanyi potential function, is evaluated using the Langmuir and T o th isotherm equations to generate new equations for the isosteric heat.", "output": "There is no related enetity." }, { "input": "These new isosteric heat equations share common parameters with the isotherm equations and are determined from isotherm fitting.", "output": "There is no related enetity." }, { "input": "This method is demonstrated in the literature for gas adsorption onto solid adsorbates including zeolites of various surface charge character and non - porous rutile phase titanium dioxide.", "output": "titanium dioxide." }, { "input": "Predictions are made using the new isosteric heat equations and then compared to calorimetric data.", "output": "There is no related enetity." }, { "input": "Elastic CNT - polyurethane nanocomposite: synthesis, performance and assessment of fragments released during use.", "output": "polyurethane." }, { "input": "Intended for use in high performance applications where electrical conductivity is required, we developed a CNT - TPU composite.", "output": "There is no related enetity." }, { "input": "Such a composite can be prepared by melt processing ( extrusion ) on an industrial scale.", "output": "There is no related enetity." }, { "input": "Due to the known hazard upon inhalation of CNTs, we assessed three degradation scenarios that may lead to the release of CNTs from the composite: normal use, machining and outdoor weathering.", "output": "There is no related enetity." }, { "input": "Unexpectedly, we find that the relative softness of the material actually enhances the embedding of CNTs also in its degradation fragments.", "output": "There is no related enetity." }, { "input": "A release of free CNTs was not detected under any condition using several detection methods.", "output": "There is no related enetity." }, { "input": "However, since machining may induce a high acute dose of human exposure, we assessed the cytotoxicity potential of released fragments in the in vitro model of precision - cut lung slices, and found no additional toxicity due to the presence of CNTs.", "output": "There is no related enetity." }, { "input": "At very low rates over years, weathering degrades the polymer matrix as expected for polyurethanes, thus exposing a network of entangled CNTs.", "output": "polyurethanes." }, { "input": "In a preliminary risk assessment, we conclude that this material is safe for humans in professional and consumer use.", "output": "There is no related enetity." }, { "input": "Cardiolipin - dependent reconstitution of respiratory supercomplexes from purified Saccharomyces cerevisiae complexes III and IV.", "output": "Cardiolipin." }, { "input": "Here, we report for the first time in vitro reconstitution of the respiratory supercomplexes from individual complexes III and IV.", "output": "There is no related enetity." }, { "input": "Complexes III and IV were purified from Saccharomyces cerevisiae mitochondria.", "output": "There is no related enetity." }, { "input": "Complex III contained eight molecules of cardiolipin, and complex IV contained two molecules of cardiolipin, as determined by electrospray ionization - mass spectrometry.", "output": "cardiolipin, cardiolipin." }, { "input": "Complex IV also contained Rcf1p.", "output": "There is no related enetity." }, { "input": "No supercomplexes were formed upon mixing of the purified complexes, and low amounts of the supercomplex trimer III ( 2 ) IV ( 1 ) were formed after reconstitution into proteoliposomes containing only phosphatidylcholine and phosphatidylethanolamine.", "output": "phosphatidylcholine, phosphatidylethanolamine." }, { "input": "Further addition of cardiolipin to the proteoliposome reconstitution mixture resulted in distinct formation of both the III ( 2 ) IV ( 1 ) supercomplex trimer and III ( 2 ) IV ( 2 ) supercomplex tetramer.", "output": "There is no related enetity." }, { "input": "No other anionic phospholipid was as effective as cardiolipin in supporting tetramer formation.", "output": "cardiolipin." }, { "input": "Phospholipase treatment of complex IV prevented trimer formation in the absence of cardiolipin.", "output": "cardiolipin." }, { "input": "Both trimer and tetramer formations were restored by cardiolipin.", "output": "cardiolipin." }, { "input": "Analysis of the reconstituted tetramer by single particle electron microscopy confirmed native organization of individual complexes within the supercomplex.", "output": "There is no related enetity." }, { "input": "In conclusion, although some trimer formation occurred dependent only on tightly bound cardiolipin, tetramer formation required additional cardiolipin.", "output": "cardiolipin, cardiolipin." }, { "input": "This is consistent with the high cardiolipin content in the native tetramer.", "output": "cardiolipin." }, { "input": "The dependence on cardiolipin for supercomplex formation suggests that changes in cardiolipin levels resulting from changes in physiological conditions may control the equilibrium between individual respiratory complexes and supercomplexes in vivo.", "output": "cardiolipin, cardiolipin." }, { "input": "Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization.", "output": "There is no related enetity." }, { "input": "Osteopetrosis ( OP ) is an inherited disorder of defective bone resorption, which can be accompanied by impaired skeletal mineralization, a phenotype termed osteopetrorickets ( OPR ).", "output": "There is no related enetity." }, { "input": "Since individuals with dysfunctional osteoclasts often develop osteomyelitis of the jaw, we have analyzed, if dentin and enamel mineralization are differentially affected in OP and OPR.", "output": "There is no related enetity." }, { "input": "Therefore, we have applied non - decalcified histology and quantitative backscattered electron imaging ( qBEI ) to compare the dental phenotypes of Src ( - / - ), oc / oc and Hyp ( - / 0 ) mice, which serve as models for OP, OPR and hypophosphatemic rickets, respectively.", "output": "There is no related enetity." }, { "input": "While both, Src ( - / - ) and oc / oc mice, were characterized by defects of molar root formation, only oc / oc mice displayed a severe defect of dentin mineralization, similar to Hyp ( - / 0 ) mice.", "output": "There is no related enetity." }, { "input": "Most importantly, while enamel thickness was not affected in either mouse model, the calcium content within the enamel phase was significantly reduced in oc / oc, but not in Src ( - / - ) or Hyp ( - / 0 ) mice.", "output": "calcium." }, { "input": "Taken together, these data demonstrate that dentin and enamel mineralization are differentially affected in Src ( - / - ) and oc / oc mice.", "output": "There is no related enetity." }, { "input": "Moreover, since defects of dental mineralization may trigger premature tooth decay and thereby osteomyelitis of the jaw, they further underscore the importance of discriminating between OP and OPR in the respective individuals.", "output": "There is no related enetity." }, { "input": "Mn ( 2 + ) modulates the kinetic properties of an archaeal member of the PLL family.", "output": "Mn ( 2 + )." }, { "input": "Recently we reported on the characterization of an archaeal member of the amidohydrolase superfamily, namely Sulfolobus acidocaldarius lactonase, showing low but significant and extremely thermostable paraoxonase activity.", "output": "There is no related enetity." }, { "input": "This enzyme, that we have named SacPox, is a member of the new described family of phosphotriesterase - like lactonases ( PLLs ).", "output": "There is no related enetity." }, { "input": "In this family the binuclear metal centre, which is involved in the catalytic machinery, has been poorly studied up to now.", "output": "There is no related enetity." }, { "input": "In this work we describe the expression of the protein in presence of different metals showing Mn ( 2 + ) to support the higher activity.", "output": "Mn ( 2 + )." }, { "input": "The enzyme has been over - expressed, purified and characterized as a Mn ( 2 + ) - containing enzyme by inductive plasma coupled mass spectrometry ( ICP - MS ), showing also surprising kinetic differences in comparison with the cadmium - containing enzyme.", "output": "Mn ( 2 + ), cadmium." }, { "input": "The Mn ( 2 + ) containing enzyme was about 30 - fold more efficient with paraoxon as substrate and more stable than the Cd ( 2 + ) counterpart, even though the Mn ( 2 + ) affinity for the binuclear metal centre is apparently lower.", "output": "Mn ( 2 + ), paraoxon, Cd ( 2 + ), Mn ( 2 + )." }, { "input": "These results increase our knowledge of the biochemical characteristics of SacPox mainly with regard to the metal - ions modulation of function.", "output": "There is no related enetity." }, { "input": "Usage patterns of personal care products: important factors for exposure assessment.", "output": "There is no related enetity." }, { "input": "Complete information regarding the use of personal care products ( PCPs ) by consumers is limited, but such information is crucial for realistic consumer exposure assessment.", "output": "There is no related enetity." }, { "input": "To fill this gap, a database was created with person - oriented information regarding usage patterns and circumstances of use for 32 different PCPs.", "output": "There is no related enetity." }, { "input": "Out of 2700 potential participants from the Netherlands, 516 men and women completed a digital questionnaire.", "output": "There is no related enetity." }, { "input": "The prevalence of use varied by gender, age, level of education and skin type.", "output": "There is no related enetity." }, { "input": "A high frequency of use was observed for some products ( e. g. lip care products ), while toothpaste, deodorant and day cream were generally used once or twice a day.", "output": "There is no related enetity." }, { "input": "The frequency of use for other PCPs varied over a wide range.", "output": "There is no related enetity." }, { "input": "The amounts of use varied largely between and within different product groups.", "output": "There is no related enetity." }, { "input": "Body lotion, sunscreen and after sun lotion were often applied on adjacent body parts.", "output": "There is no related enetity." }, { "input": "The majority of PCPs were applied in the morning, but some products, such as night cream and after sun, were predominantly applied in the evening or night.", "output": "There is no related enetity." }, { "input": "As expected, the participants used several PCPs simultaneously.", "output": "There is no related enetity." }, { "input": "The database yields important personalized exposure factors which can be used in aggregate consumer exposure assessment for substances that are components of PCPs.", "output": "There is no related enetity." }, { "input": "An unusual marine envenomation following a rope contact: a report on nine cases of dermatitis caused by Pennaria disticha.", "output": "There is no related enetity." }, { "input": "We would like to present the clinical course of nine patients who had an acute, painful dermatitis following contact with a rope used as a swimming area liner in the sea.", "output": "There is no related enetity." }, { "input": "The macroscopic and microscopic analysis of the fouling on the rope retrospectively, revealed Pennaria disticha as the causative organism.", "output": "There is no related enetity." }, { "input": "To our knowledge, there is no previous report on P. disticha envenomation in medical literature.", "output": "There is no related enetity." }, { "input": "P. disticha is a benthic hydrozoa belonging to Cnidaria phylum.", "output": "There is no related enetity." }, { "input": "Cnidaria are well known for their envenomation with their venomous organelle, \" cnidocyst \".", "output": "There is no related enetity." }, { "input": "The contact with cnidaria can result in a wide range of cytotoxic or anaphylactic reactions.", "output": "There is no related enetity." }, { "input": "While there is a large body of data in the literature from studies at molecular and cellular levels, there is limited data about the in vivo effects of cnidaria toxins.", "output": "There is no related enetity." }, { "input": "We think the clinical aspects of the dermatologic reactions caused by P. disticha and the diagnostic work - up to reveal the contamination on this unusual medium would be of interest to the readers.", "output": "There is no related enetity." }, { "input": "Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre - senescent rats.", "output": "permethrin, monoamine." }, { "input": "Pesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Previous studies investigated the effect of permethrin ( PERM ) administered at 34 mg / kg, a dose close to the no observable adverse effect level ( NOAEL ) from post natal day ( PND ) 6 to PND 21 in rats.", "output": "permethrin, PERM." }, { "input": "Despite the PERM dose did not elicited overt signs of toxicity ( i. e. normal body weight gain curve ), it was able to induce striatal neurodegeneration ( dopamine and Nurr1 reduction, and lipid peroxidation increase ).", "output": "PERM, dopamine." }, { "input": "The present study was designed to characterize the cognitive deficits in the current animal model.", "output": "There is no related enetity." }, { "input": "When during late adulthood PERM treated rats were tested for spatial working memory performances in a T - maze - rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls.", "output": "PERM." }, { "input": "No differences between groups were found in anxiety - like state, locomotor activity, feeding behavior and spatial orientation task.", "output": "There is no related enetity." }, { "input": "Our findings showing a selective effect of PERM treatment on the T - maze task point to an involvement of frontal cortico - striatal circuitry rather than to a role for the hippocampus.", "output": "PERM." }, { "input": "The predominant disturbances concern the dopamine ( DA ) depletion in the striatum and, the serotonin ( 5 - HT ) and noradrenaline ( NE ) unbalance together with a hypometabolic state in the medial prefrontal cortex area.", "output": "dopamine, serotonin, 5 - HT, noradrenaline." }, { "input": "In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls.", "output": "PERM." }, { "input": "The concentration of the most representative marker for pyrethroid exposure ( 3 - phenoxybenzoic acid ) measured in the urine of rodents 12 h after the last treatment was 41. 50 mu g / L and it was completely eliminated after 96 h.", "output": "pyrethroid, 3 - phenoxybenzoic acid." }, { "input": "Orofacial dyskinesia induced by nasal Ritalin ( R ) ( methylphenidate ) sniffing: a rare case report from Switzerland.", "output": "Ritalin, methylphenidate." }, { "input": "Ritalin (R) ( methylphenidate ) is an amphetamine - like prescription stimulant commonly used in the treatment of attention deficit hyperactivity disorder in children and adults.", "output": "Ritalin, methylphenidate, amphetamine." }, { "input": "Recently, the recreational use of Ritalin has increased, particularly among young adults.", "output": "Ritalin." }, { "input": "Well - known symptoms of intoxication include signs of sympathetic nervous stimulation, such as agitation, anxiety, tachycardia, hypertension, headache, tremor, and dizziness.", "output": "There is no related enetity." }, { "input": "This case report describes oral dyskinesia as a rare presentation of Ritalin intoxication, with the review of pathophysiology and some epidemiological data.", "output": "Ritalin." }, { "input": "Oncogenic FGFR3 gene fusions in bladder cancer.", "output": "There is no related enetity." }, { "input": "FGF receptor 3 ( FGFR3 ) is activated by mutation or over - expression in many bladder cancers.", "output": "There is no related enetity." }, { "input": "Here, we identify an additional mechanism of activation via chromosomal re - arrangement to generate constitutively activated fusion genes.", "output": "There is no related enetity." }, { "input": "FGFR3 - transforming acid coiled coil 3 ( TACC3 ) fusions resulting from 4p16. 3 re - arrangements and a t ( 4; 7 ) that generates a FGFR3 - BAI1 - associated protein 2 - like 1 ( BAIAP2L1 ) fusion were identified in 4 of 43 bladder tumour cell lines and 2 of 32 selected tissue samples including the tumour from which one of the cell lines was derived.", "output": "There is no related enetity." }, { "input": "These are highly activated and transform NIH - 3T3 cells.", "output": "There is no related enetity." }, { "input": "The FGFR3 component is identical in all cases and lacks the final exon that includes the phospholipase C gamma 1 ( PLC gamma 1 ) binding site.", "output": "There is no related enetity." }, { "input": "Expression of the fusions in immortalized normal human urothelial cells ( NHUC ) induced activation of the mitogen - activated protein kinase pathway but not PLC gamma 1.", "output": "There is no related enetity." }, { "input": "A protein with loss of the terminal region alone was not as highly activated as the fusion proteins, indicating that the fusion partners are essential.", "output": "There is no related enetity." }, { "input": "The TACC3 fusions retain the TACC domain that mediates microtubule binding and the BAIAP2L1 fusion retains the IRSp53 / MIM domain ( IMD ) that mediates actin binding and Rac interaction.", "output": "There is no related enetity." }, { "input": "As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR - selective agents, the presence of a fusion gene may aid in selection of patients for FGFR - targeted therapy.", "output": "There is no related enetity." }, { "input": "Design, synthesis and biological evaluation of glucose - containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo.", "output": "glucose, scutellarein, scutellarin." }, { "input": "Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by beta - glucuronide enzyme, some glucose - containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C - 7 position of scutellarein via a glucosidic bond.", "output": "scutellarin, scutellarin, scutellarein, glucose, scutellarein, glucose, scutellarein." }, { "input": "Biological activity evaluation showed that these glucose - containing scutellarein derivatives exhibited potent DPPH radical scavenging activities.", "output": "glucose, scutellarein, DPPH." }, { "input": "Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose.", "output": "glucose." }, { "input": "These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.", "output": "glucose, scutellarein." }, { "input": "Pharmacophore identification of c - Myc inhibitor 10074 - G5.", "output": "10074 - G5." }, { "input": "A structure - activity relationship ( SAR ) study of the c - Myc ( Myc ) inhibitor 10074 - G5 ( N - ( [ 1, 1 ' - biphenyl ] - 2 - yl ) - 7 - nitrobenzo [ c ] [ 1, 2, 5 ] oxadiazol - 4 - amine, 1 ) - which targets a hydrophobic domain of the Myc oncoprotein that is flanked by arginine residues - was executed in order to determine its pharmacophore.", "output": "10074 - G5, N - ( [ 1 , 1 ' - biphenyl ] - 2 - yl ) - 7 - nitrobenzo [ c ] [ 1 , 2 , 5 ] oxadiazol - 4 - amine, arginine." }, { "input": "Whilst the 7 - nitrobenzofurazan was found to be critical for inhibitory activity, the ortho - biphenyl could be replaced with a para - carboxyphenyl group to furnish the new inhibitor JY - 3 - 094 ( 3q ).", "output": "7 - nitrobenzofurazan, ortho - biphenyl, para - carboxyphenyl, JY - 3 - 094." }, { "input": "Around five times as potent as the lead with an IC ( 50 ) of 33 mu M for disruption of the Myc - Max heterodimer, JY - 3 - 094 demonstrated excellent selectivity over Max - Max homodimers, with no apparent effect at 100 mu M.", "output": "JY - 3 - 094." }, { "input": "Importantly, the carboxylic acid of JY - 3 - 094 improves the physicochemical properties of the lead compound, which will facilitate the incorporation of additional hydrophobicity that might enhance Myc inhibitory activity further still.", "output": "JY - 3 - 094." }, { "input": "Rigid 5 ' - 6 - locked phenanthroline - derived nucleosides chelated to ruthenium and europium ions.", "output": "phenanthroline, nucleosides, ruthenium, europium." }, { "input": "We describe complexes of ruthenium and europium with rigid, 5 ' - 6 - locked 1, 10 - phenanthroline - containing nucleosides.", "output": "ruthenium, europium, 1 , 10 - phenanthroline, nucleosides." }, { "input": "Both nucleosides were synthesized from condensation of 5 - amino - 2 ' - deoxycytidine with the corresponding diketone.", "output": "5 - amino - 2 ' - deoxycytidine, diketone." }, { "input": "The ruthenium nucleoside displayed fluorescence characteristic of polypyridine ruthenium complexes with a maximum at 616 nm and a quantum yield of 0. 011.", "output": "ruthenium, polypyridine ruthenium." }, { "input": "Binding of europium to the 1, 10 - phenanthroline - 2, 9 - diacid moiety of the lanthanide binding nucleoside showed formation of a 1: 1 complex with emission at 570 - 630 nm, whose emission was enhanced by addition of two phenanthroline ligands.", "output": "europium, 1 , 10 - phenanthroline - 2 , 9 - diacid, lanthanide, nucleoside, phenanthroline." }, { "input": "The lanthanide - binding nucleoside was incorporated into DNA oligonucleotides and shown to selectively bind one equivalent of europium ions.", "output": "lanthanide, nucleoside, europium." }, { "input": "Structure of a Ca ( 2 + ) / CaM: Kv7. 4 ( KCNQ4 ) B - helix complex provides insight into M current modulation.", "output": "Ca ( 2 + )." }, { "input": "Calmodulin ( CaM ) is an important regulator of Kv7. x ( KCNQx ) voltage - gated potassium channels.", "output": "potassium." }, { "input": "Channels from this family produce neuronal M currents and cardiac and auditory I ( KS ) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness.", "output": "There is no related enetity." }, { "input": "Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive.", "output": "There is no related enetity." }, { "input": "Here, we show that both apo - CaM and Ca ( 2 + ) / CaM bind to the C - terminal tail of the neuronal channel Kv7. 4 ( KCNQ4 ), which is involved in both hearing and mechanosensation.", "output": "Ca ( 2 + ), C." }, { "input": "Interactions between apo - CaM and the Kv7. 4 tail involve two C - terminal tail segments, known as the A and B segments, whereas the interaction between Ca ( 2 + ) / CaM and the Kv7. 4 C - terminal tail requires only the B segment.", "output": "C, Ca ( 2 + ), C." }, { "input": "Biochemical studies show that the calcium dependence of the CaM: B segment interaction is conserved in all Kv7 subtypes.", "output": "calcium." }, { "input": "X - ray crystallographic determination of the structure of the Ca ( 2 + ) / CaM: Kv7. 4 B segment complex shows that Ca ( 2 + ) / CaM wraps around the Kv7. 4 B segment, which forms an alpha - helix, in an antiparallel orientation that embodies a variation of the classic 1 - 14 Ca ( 2 + ) / CaM interaction motif.", "output": "Ca ( 2 + ), Ca ( 2 + ), Ca ( 2 + )." }, { "input": "Taken together with the context of prior studies, our data suggest a model for modulation of neuronal Kv7 channels involving a calcium - dependent conformational switch from an apo - CaM form that bridges the A and B segments to a Ca ( 2 + ) / CaM form bound to the B - helix.", "output": "calcium, Ca ( 2 + )." }, { "input": "The structure presented here also provides a context for a number of disease - causing mutations and for further dissection of the mechanisms by which CaM controls Kv7 function.", "output": "There is no related enetity." }, { "input": "Subtle alterations in swimming speed distributions of rainbow trout exposed to titanium dioxide nanoparticles are associated with gill rather than brain injury.", "output": "titanium dioxide." }, { "input": "The effects of engineered nanomaterials on fish behaviours are poorly understood.", "output": "There is no related enetity." }, { "input": "The present study aimed to determine the locomotor behaviours of trout during waterborne exposure to titanium dioxide nanoparticles ( TiO ( 2 ) NPs ) as well as inform on the underlying physiological mechanisms involved.", "output": "titanium dioxide, TiO ( 2 )." }, { "input": "Trout were exposed to either control ( without TiO ( 2 ) ), 1 mg l ( - 1 ) TiO ( 2 ) NPs or 1 mg l ( - 1 ) bulk TiO ( 2 ) for 14 days.", "output": "TiO ( 2 ), TiO ( 2 ), TiO ( 2 )." }, { "input": "Titanium dioxide exposure resulted in 31 ( bulk ) and 22 fold ( nano ) increases in the Ti concentrations of gill tissue compared to controls, but there were no measurable increases of Ti in the internal organs including the brain.", "output": "Titanium dioxide, Ti, Ti." }, { "input": "Gill pathologies were observed in both TiO ( 2 ) treatments.", "output": "TiO ( 2 )." }, { "input": "Locomotor behaviours were quantified using video tracking software and the proportion of time spent swimming at high speed ( > 20 cms ( - 1 ) ) was significantly decreased in fish exposed to TiO ( 2 ) NPs, compared to controls, but not fish exposed to bulk TiO ( 2 ).", "output": "TiO ( 2 ), TiO ( 2 )." }, { "input": "The shift in swimming speed distribution in the TiO ( 2 ) NP - exposed fish was associated with decreased area of red pulp in the spleen, increases in haematocrit and whole blood haemoglobin, all consistent with a compensation for respiratory hypoxia without the accumulation of plasma lactate.", "output": "TiO ( 2 ), lactate." }, { "input": "Fish exposed to TiO ( 2 ) NPs also retained competitive abilities when paired with controls in aggressive social encounters.", "output": "TiO ( 2 )." }, { "input": "The duration of competitive contests, the level of aggression and contest outcome were not affected by NP exposure.", "output": "There is no related enetity." }, { "input": "Neurological injury did not explain the changes in locomotor behaviour, although there was some apparent enlargement of the blood vessels on the brain.", "output": "There is no related enetity." }, { "input": "Whole brain homogenates showed a statistically significant increase in oxidative stress defences such as the total glutathione pool, but without loss of Na ( + ) K ( + ) - ATPase or acetylcholinesterase activities.", "output": "glutathione, Na ( + ) K ( + )." }, { "input": "Inhibition of the thyroid hormone pathway in Xenopus laevis by 2 - mercaptobenzothiazole.", "output": "2 - mercaptobenzothiazole." }, { "input": "Determining the effects of chemicals on the thyroid system is an important aspect of evaluating chemical safety from an endocrine disrupter perspective.", "output": "There is no related enetity." }, { "input": "Since there are numerous chemicals to test and limited resources, prioritizing chemicals for subsequent in vivo testing is critical.", "output": "There is no related enetity." }, { "input": "2 - Mercaptobenzothiazole ( MBT ), a high production volume chemical, was tested and shown to inhibit thyroid peroxidase ( TPO ) enzyme activity in vitro, a key enzyme necessary for the synthesis of thyroid hormone.", "output": "2 - Mercaptobenzothiazole, MBT." }, { "input": "To determine the thyroid disrupting activity of MBT in vivo, Xenopus laevis larvae were exposed using 7 - and 21 - day protocols.", "output": "MBT." }, { "input": "The 7 - day protocol used 18 - 357 mu g / L MBT concentrations and evaluated: metamorphic development, thyroid histology, circulating T4, circulating thyroid stimulating hormone, thyroidal sodium - iodide symporter gene expression, and thyroidal T4, T3, and related iodo - amino acids.", "output": "MBT, sodium - iodide, iodo - amino acids." }, { "input": "The 21 - day protocol used 23 - 435 mu g / L MBT concentrations and evaluated metamorphic development and thyroid histology.", "output": "MBT." }, { "input": "Both protocols demonstrated that MBT is a thyroid disrupting chemical at the lowest concentrations tested.", "output": "MBT." }, { "input": "These studies complement the in vitro study used to identify MBT as a high priority for in vivo testing, supporting the utility / predictive potential of a tiered approach to testing chemicals for TPO activity inhibition.", "output": "MBT." }, { "input": "The 7 - day study, with more comprehensive, sensitive, and diagnostic endpoints, provides information at intermediate biological levels that enables linking various endpoints in a robust and integrated pathway for thyroid hormone disruption associated with TPO inhibition.", "output": "There is no related enetity." }, { "input": "UCCB01 - 125, a dimeric inhibitor of PSD - 95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK - 801.", "output": "UCCB01 - 125, NMDA, MK - 801." }, { "input": "Excessive N - Methyl - d - aspartate receptor ( NMDAR ) - dependent production of nitric oxide ( NO ) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein - 95 ( PSD - 95 ).", "output": "N - Methyl - d - aspartate, nitric oxide, NO." }, { "input": "By binding to both the NMDAR and neuronal NO synthase ( nNOS ), PSD - 95 mediates a specific coupling between NMDAR activation and NO production.", "output": "NO, NO." }, { "input": "NMDAR antagonism shows anti - nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions.", "output": "There is no related enetity." }, { "input": "An alternative approach to modulate the NMDAR - related activity is to perturb the NMDAR / PSD - 95 / nNOS complex by targeting PSD - 95, thereby decreasing NO production without interfering with the NMDAR ion channel function.", "output": "NO." }, { "input": "Here, we compared the effects of a dimeric PSD - 95 inhibitor, UCCB01 - 125, and the NMDAR antagonist, MK - 801, on mechanical hypersensitivity in the complete Freund ' s adjuvant ( CFA ) model of inflammatory pain.", "output": "UCCB01 - 125, MK - 801." }, { "input": "To examine side - effect profiles we also compared the effects of UCCB01 - 125 and MK - 801 in tests of attention, long - term memory, and motor performance.", "output": "UCCB01 - 125, MK - 801." }, { "input": "When administered concurrently with CFA, both MK - 801 and UCCB01 - 125 prevented the development of CFA - induced mechanical hypersensitivity 1 and 24 h after treatment.", "output": "MK - 801, UCCB01 - 125." }, { "input": "Moreover, UCCB01 - 125 was found to reverse CFA - induced hypersensitivity when administered 24 h after CFA treatment, an effect lasting for at least 3 days.", "output": "UCCB01 - 125." }, { "input": "At the dose reducing hypersensitivity, MK - 801 disrupted attention, long - term memory, and motor performance.", "output": "MK - 801." }, { "input": "By contrast, even high doses of UCCB01 - 125 were devoid of side - effects in these tests.", "output": "UCCB01 - 125." }, { "input": "The data suggest that PSD - 95 inhibition is a feasible strategy to prevent both development and maintenance of chronic inflammatory pain, while avoiding NMDAR antagonism - related side - effects.", "output": "There is no related enetity." }, { "input": "Highly regioselective glycosylation of xylosyl - containing taxanes by Enterobacter cloaceae.", "output": "xylosyl - containing taxanes." }, { "input": "Three new diglycoside taxanes ( 4 - 6 ) containing an additional alpha - d - glucose unit were obtained via Enterobacter cloaceae - mediated, highly regioselective glycosylations at OH - 4 of the xylosyl moieties in 7 - xylosyl taxanes ( 1 - 3 ).", "output": "diglycoside taxanes, alpha - d - glucose, OH, xylosyl, 7 - xylosyl taxanes." }, { "input": "Their structures were determined on the basis of extensive spectroscopic analysis and chemical reactivity.", "output": "There is no related enetity." }, { "input": "This is the first report of an enzymatic elongation of the saccharide chain in taxanes, and the glycosylation reaction is the first described example of a transformation effected by E. cloaceae.", "output": "There is no related enetity." }, { "input": "Evaluation of immunohistochemical markers to detect the genotoxic mode of action of fine and ultrafine dusts in rat lungs.", "output": "There is no related enetity." }, { "input": "Data on local genotoxicity after particle exposure are crucial to resolve mechanistic aspects such as the impact of chronic inflammation, types of DNA damage, and their role in lung carcinogenesis.", "output": "There is no related enetity." }, { "input": "We established immunohistochemical methods to quantify the DNA damage markers poly ( ADP - ribose ) ( PAR ), phosphorylated H2AX ( gamma - H2AX ), 8 - hydroxyguanosine ( 8 - OH - dG ), and 8 - oxoguanine DNA glycosylase ( OGG1 ) in paraffin - embedded tissue from particle - exposed rats.", "output": "poly ( ADP - ribose ), PAR, 8 - hydroxyguanosine, 8 - OH - dG, 8 - oxoguanine, paraffin." }, { "input": "The study was based on lungs from a subchronic study that was part of an already published carcinogenicity study where rats had been intratracheally instilled with saline, quartz DQ12, amorphous silica ( Aerosil ( (R) ) 150 ), or carbon black ( Printex ( (R) ) 90 ) at monthly intervals for 3 months.", "output": "silica, Aerosil, carbon black, Printex." }, { "input": "Lung sections were stained immunohistochemically and markers were quantified in alveolar lining cells.", "output": "There is no related enetity." }, { "input": "Local genotoxicity was then correlated with already defined endpoints, i. e. mean inflammation score, bronchoalveolar lavage parameters, and carcinogenicity.", "output": "There is no related enetity." }, { "input": "Genotoxicity was most pronounced in quartz DQ12 - treated rats, where all genotoxicity markers gave statistically significant positive results, indicating considerable genotoxic stress such as occurrence of DNA double - strand breaks ( DSB ), and oxidative damage with subsequent repair activity.", "output": "There is no related enetity." }, { "input": "Genotoxicity was less pronounced for Printex ( (R) ) 90, but significant increases in gamma - H2AX - and 8 - OH - dG - positive nuclei and OGG1 - positive cytoplasm were nevertheless detected.", "output": "Printex, 8 - OH - dG." }, { "input": "In contrast, Aerosil ( (R) ) 150 significantly enhanced only 8 - OH - dG - positive nuclei and oxidative damage - related repair activity ( OGG1 ) in cytoplasm.", "output": "Aerosil, 8 - OH - dG." }, { "input": "In the present study, gamma - H2AX was the most sensitive genotoxicity marker, differentiating best between the three types of particles.", "output": "There is no related enetity." }, { "input": "The mean number of 8 - OH - dG - positive nuclei, however, correlated best with the mean inflammation score at the same time point.", "output": "8 - OH - dG." }, { "input": "This methodological approach enables integration of local genotoxicity testing in subchronic inhalation studies and makes immunohistochemical detection, in particular of gamma - H2AX and 8 - hydroxyguanine, a very promising approach for local genotoxicity testing in lungs, with prognostic value for the long - term outcome of particle exposure.", "output": "8 - hydroxyguanine." }, { "input": "Glucocorticoid receptor concentration and the ability to dimerize influence nuclear translocation and distribution.", "output": "There is no related enetity." }, { "input": "Glucocorticoid receptor ( GR ) concentrations and the ability of the GR to dimerize are factors which influence sensitivity to glucocorticoids.", "output": "There is no related enetity." }, { "input": "Upon glucocorticoid binding, the GR is actively transported into the nucleus, a crucial step in determining GR function.", "output": "There is no related enetity." }, { "input": "We examined the effects of GR concentration and the ability to dimerize on GR nuclear import, export and nuclear distribution using both live cell microscopy of GFP - tagged GR and immunofluorescence of untagged GR, with both wild type GR ( GRwt ) and dimerization deficient GR ( GRdim ).", "output": "There is no related enetity." }, { "input": "We found that the observed rate of GR nuclear import increases significantly at higher GR concentrations, at saturating concentrations of dexamethasone ( 10 ( - 6 ) M ) using GFP - tagged GR, while with untagged GR it is only discernable at sub - saturating ligand concentrations ( 10 ( - 10 ) - 10 ( - 9 ) M ).", "output": "dexamethasone." }, { "input": "Loss of dimerization results in a slower observed rate of nuclear import ( 2. 5 - to 3. 3 - fold decrease for GFP - GRdim ) as well as a decreased extent of GR nuclear localization ( 18 - 27 % decrease for untagged GRdim ).", "output": "There is no related enetity." }, { "input": "These results were linked to an increased rate of GR export at low GR concentrations ( 1. 4 - to 1. 6 - fold increase for untagged GR ) and where GR dimerization is abrogated ( 1. 5 - to 1. 7 - fold increase for GFP - GRdim ).", "output": "There is no related enetity." }, { "input": "Furthermore, GR dimerization was shown to be required for the appearance of discrete GC - dependent GR nuclear foci, the loss of which may explain the increased rate of GR export for the GRdim.", "output": "There is no related enetity." }, { "input": "The reduction in the observed rate of nuclear import and increased rate of nuclear export displayed at low GR concentrations and by the GRdim could explain the lowered glucocorticoid response under these conditions.", "output": "There is no related enetity." }, { "input": "New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles.", "output": "doxorubicin." }, { "input": "This work aimed to develop solid lipid nanoparticles ( SLNs ) loaded with doxorubicin evaluating the influence of docosahexaenoic acid ( DHA ), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency ( EE ).", "output": "doxorubicin, docosahexaenoic acid, DHA, polyunsaturated fatty acid." }, { "input": "The SLN were characterized for size, zeta potential, entrapment efficiency ( EE ) and drug release.", "output": "There is no related enetity." }, { "input": "Studies of in vitro antitumor activity and cellular uptake were also conducted.", "output": "There is no related enetity." }, { "input": "The reduction in particle size ( from 127 +/- 14 to 94 +/- 1 nm ) and negative charges were obtained for SLN loaded with DHA and triethanolamine ( TEA ), amine used to increase the solubility of doxorubicin in melted lipid.", "output": "DHA, triethanolamine, TEA, amine, doxorubicin." }, { "input": "The EE was significantly improved from 36 +/- 4 % to 99 +/- 2 % for SLN without and with DHA at 0. 4 %, respectively.", "output": "DHA." }, { "input": "The doxorubicin release in a slightly acid medium ( pH 5. 0 ) was higher than that observed at physiological pH.", "output": "doxorubicin." }, { "input": "The in vitro studies clearly showed the higher cytotoxicity of doxorubicin - DHA - loaded SLN than free doxorubicin + DHA on human lung tumor cell line ( A549 ) and the improved cellular uptake achieved with the drug encapsulation can be an explanation.", "output": "doxorubicin, DHA, doxorubicin, DHA." }, { "input": "These findings suggest that DHA - doxorubicin - loaded SLN is a promising alternative for the treatment of cancer.", "output": "DHA, doxorubicin." }, { "input": "A novel recombinant fibrinogenase of Agkistrodon acutus venom protects against hyperacute rejection via degradation of complements.", "output": "There is no related enetity." }, { "input": "Hyperacute rejection ( HAR ) is a main barrier in xenotransplantation, which is mediated by the combination of natural antibody to the xenograft and complement activation.", "output": "There is no related enetity." }, { "input": "Current therapies have focus on the inhibition of complement by development of complement inhibitor and transgenic animal organ.", "output": "There is no related enetity." }, { "input": "Here, we investigated the effects of rFII, a recombinant fibrinogenase from Agkistrodon acutus venom, on complement and HAR.", "output": "There is no related enetity." }, { "input": "The degradation effect of rFII on complement was tested by SDS - PAGE, CH50 examination, ELISA Kit and cofocal immunofluorescence microscopy in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "An ex - vivo rat - to - human perfusion model and a vivo guinea - pig - to - rat heat HAR model were used to determine the protection of rFII against HAR.", "output": "There is no related enetity." }, { "input": "Our investigation indicated that rFII could significantly degrade human C5, C6, and C9, decrease the activity of complement, and inhibit the MAC deposition on HUVECs membrane in vitro.", "output": "There is no related enetity." }, { "input": "In addition, serum levels of C1q, C3 and C4 in rat were gradually reduced after infusion of rFII.", "output": "There is no related enetity." }, { "input": "Importantly, in an ex vivo rat - to - human perfusion model, the survival of rat hearts perfused with human serum treated with rFII ( 83. 36 +/- 16. 63 min ) were significantly longer than that of hearts perfused with fresh human serum ( 15. 94 +/- 4. 75 min ).", "output": "There is no related enetity." }, { "input": "At the time of 15 minutes after perfusion, functions of hearts added with 50 ug / ml rFII sustained well with heart rates at 283 +/- 65. 32 beats / minute and LVDP at 13. 70 +/- 5. 45 Kpa, while that of hearts perfused with fresh human serum were severely damaged by HAR with heart rates at 107. 77 +/- 40. 31 beats / minute and LVDP at 1. 01 +/- 0. 83 Kpa.", "output": "There is no related enetity." }, { "input": "We also found that rFII significantly decreased the levels of C1q, C3 and C4 in human fresh serum perfusate.", "output": "There is no related enetity." }, { "input": "In a vivo guinea - pig - to - rat heat HAR model, the survival of rat hearts treated with rFII were significantly longer than that of hearts perfused with normal saline; and relieved heart damage by complete activation.", "output": "There is no related enetity." }, { "input": "Our finding demonstrates the anti - complement property of rFII and its protection against HAR, indicating that rFII might be as a potential therapeutic agent for xenotransplantation.", "output": "There is no related enetity." }, { "input": "Pocketed microneedles for rapid delivery of a liquid - state botulinum toxin A formulation into human skin.", "output": "There is no related enetity." }, { "input": "Botulinum toxin A ( BT ) is used therapeutically for the treatment of primary focal hyperhidrosis, a chronic debilitating condition characterised by over - activity of the eccrine sweat glands.", "output": "There is no related enetity." }, { "input": "Systemic toxicity concerns require BT to be administered by local injection, which in the case of hyperhidrosis means multiple painful intradermal injections by a skilled clinician at 6 - monthly intervals.", "output": "There is no related enetity." }, { "input": "This study investigates the potential of a liquid - loaded pocketed microneedle device to deliver botulinum toxin A into the human dermis with the aim of reducing patient pain, improving therapeutic targeting and simplifying the administration procedure.", "output": "There is no related enetity." }, { "input": "Initially, beta - galactosidase was employed as a detectable model for BT to ( i ) visualise liquid loading of the microneedles, ( ii ) determine residence time of a liquid formulation on the device and ( iii ) quantify loaded doses.", "output": "There is no related enetity." }, { "input": "An array of five stainless steel pocketed microneedles was shown to possess sufficient capacity to deliver therapeutic doses of the potent BT protein.", "output": "There is no related enetity." }, { "input": "Microneedle - mediated intradermal delivery of beta - galactosidase and formaldehyde - inactivated botulinum toxoid revealed effective deposition and subsequent diffusion within the dermis.", "output": "formaldehyde." }, { "input": "This study is the first to characterise pocketed microneedle delivery of a liquid formulation into human skin and illustrates the potential of such systems for the cutaneous administration of potent proteins such as BT.", "output": "There is no related enetity." }, { "input": "A clinically appropriate microneedle delivery system for BT could have a significant impact in both the medical and cosmetic industries.", "output": "There is no related enetity." }, { "input": "Changes of the serum cytokine contents in broilers fed on diets supplemented with nickel chloride.", "output": "nickel chloride." }, { "input": "Cytokines are immunoregulatory proteins which play an important role in the immune system.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to examine the serum cytokine contents including interleukin - 2 ( IL - 2 ), interleukin - 4 ( IL - 4 ), interleukin - 6 ( IL - 6 ), interleukin - 10 ( IL - 10 ), interferon gamma ( IFN - gamma ), and tumor necrosis factor - alpha ( TNF - alpha ) induced by dietary nickel chloride in broilers by enzyme - linked immunospecific assay.", "output": "nickel chloride." }, { "input": "A total of 240 one - day - old avian broilers were divided into four groups and fed on a corn - soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg / kg of nickel chloride.", "output": "nickel chloride." }, { "input": "During the experimental period of 42 days, the results showed that the serum IL - 2, IL - 4, IL - 6, IL - 10, IFN - gamma and TNF - alpha contents were lower ( p < 0. 05 or p < 0. 01 ) in the 300, 600, 900 mg / kg groups than those in the control group.", "output": "There is no related enetity." }, { "input": "It was concluded that dietary nickel chloride in the range of 300 to 900 mg / kg could reduce the serum cytokine contents, which could finally impact the immune function in broilers.", "output": "nickel chloride." }, { "input": "Natures of benzene - water and pyrrole - water interactions in the forms of sigma and pi types: theoretical studies from clusters to liquid mixture.", "output": "benzene, pyrrole." }, { "input": "A combined and sequential use of quantum mechanical ( QM ) calculations and classical molecular dynamics ( MD ) simulations was made to investigate the sigma and pi types of hydrogen bond ( HB ) in benzene - water and pyrrole - water as clusters and as their liquid mixture, respectively.", "output": "hydrogen, benzene, pyrrole." }, { "input": "This paper aims at analyzing similarities and differences of these HBs resulted from QM and MD on an equal footing.", "output": "There is no related enetity." }, { "input": "Based on the optimized geometry at omega b97xD / aug - cc - pVTZ level of theory, the nature and property of sigma and pi types of HBs are unveiled by means of atoms in molecules ( AIM ), natural bond orbital ( NBO ) and energy decomposition analysis ( EDA ).", "output": "There is no related enetity." }, { "input": "In light of the above findings, MD simulation with OPLS - AA and SPC model was applied to study the liquid mixture at different temperatures.", "output": "There is no related enetity." }, { "input": "The MD results further characterize the behavior and structural properties of sigma and pi types HBs, which are somewhat different but reasonable for the clusters by QM.", "output": "There is no related enetity." }, { "input": "Finally, we provide a reasonable explanation for the different solubility between benzene / water and pyrrole / water.", "output": "benzene, pyrrole." }, { "input": "Serotonin - glutamate and serotonin - dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins.", "output": "Serotonin, glutamate, serotonin, dopamine." }, { "input": "The physical and functional interactions between serotonin - glutamate and serotonin - dopamine signaling have been suggested to be involved in psychosis pathophysiology and are supposed to be relevant for antipsychotic treatment.", "output": "serotonin, glutamate, serotonin, dopamine." }, { "input": "Type II metabotropic glutamate receptors ( mGluRs ) and serotonin 5 - HT ( 2A ) receptors have been reported to form heterodimers that modulate G - protein - mediated intracellular signaling differentially compared to mGluR2 and 5 - HT ( 2A ) homomers.", "output": "glutamate, serotonin, 5 - HT, 5 - HT." }, { "input": "Additionally, direct evidence has been provided that D ( 2 ) and 5 - HT ( 2A ) receptors form physical heterocomplexes which exert a functional cross - talk, as demonstrated by studies on hallucinogen - induced signaling.", "output": "5 - HT." }, { "input": "Moving from receptors to postsynaptic density ( PSD ) scenario, the scaffolding protein PSD - 95 is known to interact with N - methyl - D - aspartate ( NMDA ), D ( 2 ) and 5 - HT ( 2 ) receptors, regulating their activation state.", "output": "N - methyl - D - aspartate, NMDA, 5 - HT." }, { "input": "Homer1a, the inducible member of the Homer family of PSD proteins that is implicated in glutamatergic signal transduction, is induced in striatum by antipsychotics with high dopamine receptor affinity and in the cortex by antipsychotics with mixed serotonergic / dopaminergic profile.", "output": "dopamine." }, { "input": "Signaling molecules, such as Akt and glycogen - synthase - kinase - 3 ( GSK - 3 ), could be involved in the mechanism of action of antipsychotics, targeting dopamine, serotonin, and glutamate neurotransmission.", "output": "dopamine, serotonin, glutamate." }, { "input": "Altogether, these proteins stand at the crossroad of glutamate - dopamine - serotonin signaling pathways and may be considered as valuable molecular targets for current and new antipsychotics.", "output": "glutamate, dopamine, serotonin." }, { "input": "The aim of this review is to provide a critical appraisal on serotonin - glutamate and serotonin - dopamine interplay to support the idea that next generation schizophrenia pharmacotherapy should not exclusively rely on receptor targeting strategies.", "output": "serotonin, glutamate, serotonin, dopamine." }, { "input": "Pocket - based drug design: exploring pocket space.", "output": "There is no related enetity." }, { "input": "The identification and application of druggable pockets of targets play a key role in in silico drug design, which is a fundamental step in structure - based drug design.", "output": "There is no related enetity." }, { "input": "Herein, some recent progresses and developments of the computational analysis of pockets have been covered.", "output": "There is no related enetity." }, { "input": "Also, the pockets at the protein - protein interfaces ( PPI ) have been considered to further explore the pocket space for drug discovery.", "output": "There is no related enetity." }, { "input": "We have presented two case studies targeting the kinetic pockets generated by normal mode analysis and molecular dynamics method, respectively, in which we focus upon incorporating the pocket flexibility into the two - dimensional virtual screening with both affinity and specificity.", "output": "There is no related enetity." }, { "input": "We applied the specificity and affinity ( SPA ) score to quantitatively estimate affinity and evaluate specificity using the intrinsic specificity ratio ( ISR ) as a quantitative criterion.", "output": "There is no related enetity." }, { "input": "In one of two cases, we also included some applications of pockets located at the dimer interfaces to emphasize the role of PPI in drug discovery.", "output": "There is no related enetity." }, { "input": "This review will attempt to summarize the current status of this pocket issue and will present some prospective avenues of further inquiry.", "output": "There is no related enetity." }, { "input": "Assessing the sublethal effects of in - river concentrations of parameters contributing to cumulative effects in the athabasca river basin using a fathead minnow bioassay.", "output": "There is no related enetity." }, { "input": "The Athabasca River basin, located in Alberta, Canada, covers 157, 000 km ( 2 ) and holds significant cultural and economic importance.", "output": "There is no related enetity." }, { "input": "Recent research assessed changes in several water quality and quantity parameters that have changed both spatially ( along the river continuum ) and temporally ( pre - development and present day ) in the Athabasca River Basin.", "output": "There is no related enetity." }, { "input": "In particular, parameters such as salinity and dissolved sulphate have changed significantly across the Athabasca River mainstem over the past five decades.", "output": "sulphate." }, { "input": "Further laboratory testing has linked concentrations of these parameters to changes in fathead minnow reproduction.", "output": "There is no related enetity." }, { "input": "Research is required to determine whether these changes observed in the laboratory can be applied to actual in - river conditions.", "output": "There is no related enetity." }, { "input": "The objectives of the present study were to twofold: assess changes in fathead minnow response metrics ( i. e., condition, liver and gonad size, egg production, and gill histology ) associated with increasing concentrations of salinity and dissolved sulphate and determine whether sublethal effect thresholds established in laboratory experiments correspond to actual in - river concentrations using water from the mouth and headwaters of the Athabasca River.", "output": "sulphate." }, { "input": "Three dose - response experiments ( NaCl, SO4, and water sampled from the mouth of the Athabasca River ) were conducted at Jasper National Park, Alberta, Canada.", "output": "NaCl, SO4." }, { "input": "Significant increases in mean eggs per female per day occurred at the 50 % treatment for the mouth experiment and thresholds previously developed in the laboratory were verified.", "output": "There is no related enetity." }, { "input": "Solvated graphenes: an emerging class of functional soft materials.", "output": "graphenes." }, { "input": "From a materials science point of view, graphene is essentially a polymer having a giant, two - dimensional molecular configuration.", "output": "graphene." }, { "input": "In this Progress Report, solvated graphene and its derivatives are illustrated from the perspective of soft matter.", "output": "graphene." }, { "input": "Firstly, the key appealing features of graphene as a molecular building block for assembling bulk soft materials are highlighed.", "output": "graphene." }, { "input": "It is then demonstrated how the intersheet interactions in solution are correlated with the molecular structure of graphene, and how a combination of the unique molecular structure and colloidal interactions can lead to simple, solution - phase approaches for assembling graphenes into a variety of macroscopic nanoarchitectures.", "output": "graphene, graphenes." }, { "input": "A number of new exciting functions and applications are also highlighted, which are enabled by the solvation effect and in particular, it is discussed why and how solvated graphenes can offer exciting functions that are unattainable with the dried, hard counterpart.", "output": "graphenes." }, { "input": "The discussion is concluded with some personal perspectives on the future directions in which this emerging class of functional soft materials could be pursued.", "output": "There is no related enetity." }, { "input": "Stability of pharmaceuticals and other polar organic compounds stored on polar organic chemical integrative samplers and solid - phase extraction cartridges.", "output": "There is no related enetity." }, { "input": "The stability of 24 chemicals, including pharmaceuticals and personal care products, and some agrochemicals on extraction media was evaluated by preloading them onto Oasis hydrophilic lipophilic balanced solid - phase extraction ( SPE ) cartridges and polar organic chemical integrative samplers ( POCIS ) followed by storage at - 20 degrees C over time.", "output": "There is no related enetity." }, { "input": "After 20 months, the average loss was 11 % on POCIS, with only 2, 4 - dichlorophenoxyacetic acid, atrazine, chlorpyrifos, and gemfibrozil showing a statistically significant decline compared with initial concentrations.", "output": "2 , 4 - dichlorophenoxyacetic acid, atrazine, chlorpyrifos, gemfibrozil." }, { "input": "Losses on SPE cartridges were below 19 %, with an average loss of 9 %.", "output": "There is no related enetity." }, { "input": "In addition to laboratory spiked samples, multiple POCIS deployed in wastewater - impacted surface waters and SPE extracts of these waters were stored in their original coextracted matrix for nearly two years with minimal observed losses.", "output": "There is no related enetity." }, { "input": "Errors from typical sampling, handling, and concentration estimates from POCIS sampling rates were typically +/- 15 to 30 % relative standard deviation, so observed storage losses are minimal for most POCIS applications.", "output": "There is no related enetity." }, { "input": "While losses during storage on SPE cartridges for 20 months were small but statistically significant for many compounds, addition of labeled internal standards prior to freezing should correct for such losses.", "output": "There is no related enetity." }, { "input": "Thus, storage of processed water samples for analysis of polar organic pollutants is viable for archival purposes or studies for which samples cannot be analyzed in the short term.", "output": "There is no related enetity." }, { "input": "Mitigating with macrophytes: submersed plants reduce the toxicity of pesticide - contaminated water to zooplankton.", "output": "There is no related enetity." }, { "input": "In ecotoxicology, appreciation is growing for the influence that ecological interactions have on the toxicity of contaminants, such as insecticides, to sensitive species.", "output": "There is no related enetity." }, { "input": "Most previous studies, however, have focused on factors that exacerbate insecticide effects on species, while factors that may mitigate these effects have been relatively ignored.", "output": "There is no related enetity." }, { "input": "In aquatic habitats, a small number of studies have shown that submersed macrophytes can remove some insecticides from the water column via sorption.", "output": "There is no related enetity." }, { "input": "Although examining sorption dynamics is important for understanding the environmental fate of insecticides, whether and to what extent macrophytes actually mitigate insecticide effects on aquatic species remains unknown.", "output": "There is no related enetity." }, { "input": "In the present study, the authors examined how much and how quickly several realistic densities of the macrophyte Elodea canadensis decreased the toxicity of the insecticide malathion to Daphnia magna, a keystone aquatic herbivore.", "output": "malathion." }, { "input": "To do this, the authors quantified Daphnia survival in outdoor test systems ( 0. 95 L ) exposed to a factorial combination of five Elodea densities crossed with five malathion concentrations.", "output": "malathion." }, { "input": "The authors discovered that malathion ' s lethality to Daphnia decreased with increasing Elodea density.", "output": "malathion." }, { "input": "Furthermore, the rate at which Elodea reduced malathion ' s toxicity in the water column increased with macrophyte density.", "output": "malathion." }, { "input": "These results provide strong evidence that submersed macrophytes can mitigate the ecological impacts of a popular insecticide and further support that ecological interactions can strongly influence contaminant environmental effects.", "output": "There is no related enetity." }, { "input": "The nucleoid - associated protein Dan organizes chromosomal DNA through rigid nucleoprotein filament formation in E. coli during anoxia.", "output": "There is no related enetity." }, { "input": "Dan is a transcription factor that regulates the ttd operon encoding tartrate dehydratase.", "output": "tartrate." }, { "input": "During anaerobic conditions, its copy number increases by 100 - fold, making Dan an abundant nucleoid - associated protein.", "output": "There is no related enetity." }, { "input": "However, little is known about the mode of Dan - DNA interaction.", "output": "There is no related enetity." }, { "input": "To understand its cellular functions, we used single - molecule manipulation and imaging techniques to show that Dan binds cooperatively along DNA, resulting in formation of a rigid periodic nucleoprotein filament that strongly restricts accessibility to DNA.", "output": "There is no related enetity." }, { "input": "Furthermore, in the presence of physiologic levels of magnesium, these filaments interact with each other to cause global DNA condensation.", "output": "magnesium." }, { "input": "Overall, these results shed light on the architectural role of Dan in the compaction of Escherichia coli chromosomal DNA under anaerobic conditions.", "output": "There is no related enetity." }, { "input": "Formation of the nucleoprotein filament provides a basis in understanding how Dan may play roles in both chromosomal DNA protection and gene regulation.", "output": "There is no related enetity." }, { "input": "Animal QTLdb: an improved database tool for livestock animal QTL / association data dissemination in the post - genome era.", "output": "There is no related enetity." }, { "input": "The Animal QTL database ( QTLdb; http: / / www. animalgenome. org / QTLdb ) is designed to house all publicly available QTL and single - nucleotide polymorphism / gene association data on livestock animal species.", "output": "There is no related enetity." }, { "input": "An earlier version was published in the Nucleic Acids Research Database issue in 2007.", "output": "There is no related enetity." }, { "input": "Since then, we have continued our efforts to develop new and improved database tools to allow more data types, parameters and functions.", "output": "There is no related enetity." }, { "input": "Our efforts have transformed the Animal QTLdb into a tool that actively serves the research community as a quality data repository and more importantly, a provider of easily accessible tools and functions to disseminate QTL and gene association information.", "output": "There is no related enetity." }, { "input": "The QTLdb has been heavily used by the livestock genomics community since its first public release in 2004.", "output": "There is no related enetity." }, { "input": "To date, there are 5920 cattle, 3442 chicken, 7451 pigs, 753 sheep and 88 rainbow trout data points in the database, and at least 290 publications that cite use of the database.", "output": "There is no related enetity." }, { "input": "The rapid advancement in genomic studies of cattle, chicken, pigs, sheep and other livestock animals has presented us with challenges, as well as opportunities for the QTLdb to meet the evolving needs of the research community.", "output": "There is no related enetity." }, { "input": "Here, we report our progress over the recent years and highlight new functions and services available to the general public.", "output": "There is no related enetity." }, { "input": "Versican 3 ' - untranslated region ( 3 ' - UTR ) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity.", "output": "There is no related enetity." }, { "input": "This study was designed to explore the role of versican in the development of hepatocellular carcinoma ( HCC ).", "output": "There is no related enetity." }, { "input": "Ectopic expression of the versican 3 ' - untranslated region ( 3 ' - UTR ) was studied as a competitive endogenous RNA for regulating miRNA functions.", "output": "There is no related enetity." }, { "input": "We used this approach to modulate the expression of versican and its related proteins in 3 ' - UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3 ' - UTR or a control vector.", "output": "There is no related enetity." }, { "input": "We demonstrated that transgenic mice expressing the versican 3 ' - UTR developed HCC and increased expression of versican isoforms V0 and V1.", "output": "There is no related enetity." }, { "input": "HepG2 cells transfected with versican 3 ' - UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis.", "output": "There is no related enetity." }, { "input": "We found that versican 3 ' - UTR could bind to miRNAs miR - 133a, miR - 199a *, miR - 144, and miR - 431 and also interacted with CD34 and fibronectin.", "output": "There is no related enetity." }, { "input": "As a consequence, expression of versican, CD34, and fibronectin was up - regulated by ectopic transfection of the versican 3 ' - UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild - type controls.", "output": "There is no related enetity." }, { "input": "Transfection with siRNAs targeting the versican 3 ' - UTR abolished the effects of the 3 ' - UTR.", "output": "There is no related enetity." }, { "input": "Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions.", "output": "There is no related enetity." }, { "input": "Conformational landscape of diisopropyl ketone: quantum chemical calculations validated by microwave spectroscopy.", "output": "diisopropyl ketone." }, { "input": "We report on the gas - phase structure of the most abundant conformer of diisopropyl ketone, ( CH ( 3 ) ) ( 2 ) HC - CO - CH ( CH ( 3 ) ) ( 2 ), as observed by molecular beam Fourier transform microwave spectroscopy.", "output": "diisopropyl ketone, ( CH ( 3 ) ) ( 2 ) HC - CO - CH ( CH ( 3 ) ) ( 2 )." }, { "input": "The gas - phase structures of five conformers of diisopropyl ketone were optimized using ab initio calculations at the MP2 / 6 - 311 + + G ( d, p ) level of theory.", "output": "diisopropyl ketone." }, { "input": "The natures of the stationary points were verified using harmonic frequency calculations.", "output": "There is no related enetity." }, { "input": "The only conformer observed in the supersonic jet possesses C ( 2 ) symmetry and appears as an enantiomeric pair.", "output": "There is no related enetity." }, { "input": "From the microwave spectrum, a set of three highly accurate rotational constants, five centrifugal distortion constants, and three sextic centrifugal distortion constants were determined.", "output": "There is no related enetity." }, { "input": "The structure of the observed conformer was optimized again at different levels of theory using the HF, MP2, and B3LYP methods.", "output": "There is no related enetity." }, { "input": "The theoretical constants of the C ( 2 ) conformer were subsequently validated using the experimental constants.", "output": "There is no related enetity." }, { "input": "To understand the transitions of one conformer to the others, the isopropyl groups were rotated against each other.", "output": "isopropyl." }, { "input": "The resulting two - dimensional potential energy surface shows nicely the symmetry of the conformational landscape and also indicates the enantiomeric pairs of the conformers.", "output": "There is no related enetity." }, { "input": "The barriers to internal rotation of the methyl groups were determined to be 1052 and 905 cm ( - 1 ) at the MP2 / 6 - 311 + + G ( d, p ) and the B3LYP / 6 - 311 + + G ( d, p ) levels, respectively.", "output": "methyl." }, { "input": "In agreement with the theoretical predictions, no internal rotation patterns could be observed in the microwave spectrum.", "output": "There is no related enetity." }, { "input": "Progestin effects on expression of AKR1C1 - AKR1C3, SRD5A1 and PGR in the Z - 12 endometriotic epithelial cell line.", "output": "Progestin." }, { "input": "Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity.", "output": "There is no related enetity." }, { "input": "This disease is associated with diminished protective effects of progesterone, which are usually explained by inadequate activation of progesterone receptors and also enhanced pre - receptor metabolism of progesterone.", "output": "progesterone, progesterone, progesterone." }, { "input": "Endometriosis is often treated with progestins, which act as progesterone receptor agonists, although their exact mechanisms of action are not completely understood.", "output": "progestins, progesterone." }, { "input": "The aim of the present study was to investigate how the progestins medroxyprogesterone acetate, dydrogesterone and dienogest, as well as progesterone, impact on the expression of genes of pre - receptor progesterone metabolism in Z - 12 epithelial cell line, a model system of peritoneal endometriosis.", "output": "progestins, medroxyprogesterone acetate, dydrogesterone, dienogest, progesterone, progesterone." }, { "input": "Our data demonstrate that these progestins affect local pre - receptor metabolism to a different extent.", "output": "progestins." }, { "input": "The most favorable effects were seen for dydrogesterone and dienogest, where the first, dydrogesterone, significantly reduced SRD5A1, AKR1C2 and AKR1C3 expression, and additionally had a nonsignificant impact on progesterone receptor B ( PR - B ) protein levels.", "output": "dydrogesterone, dienogest, dydrogesterone, progesterone." }, { "input": "This might slow down the first step of pre - receptor metabolism, the conversion of progesterone to 5 alpha - dihydroprogestrone by SRD5A1, and it might also affect further reduction of 3 - keto and 20 - keto groups catalyzed by AKR1C2 and AKR1C3.", "output": "progesterone, 5 alpha - dihydroprogestrone, 3 - keto, 20 - keto." }, { "input": "Similarly favorable effects were seen for dienogest, which promoted significant reduction of AKR1C1 and AKR1C2 expression and also showed no effect on PR - B protein levels.", "output": "dienogest." }, { "input": "Different effects were seen for progesterone, which significantly decreased SRD5A1, PR - B and HSD17B2 protein levels.", "output": "progesterone." }, { "input": "In contrast, treatment with medroxyprogesterone acetate resulted in increased AKR1C1 expression and decreased levels of PR - B, which might lead to enhanced progesterone metabolism and reduced signaling through progesterone receptors.", "output": "medroxyprogesterone acetate, progesterone, progesterone." }, { "input": "Altogether, our data in this Z - 12 cell model suggest that the beneficial effects of treatment with progestin observed in endometriosis patients might arise from decreased pre - receptor metabolism of the protective progesterone by the SRD5A1 and AKR1C enzymes.", "output": "progestin, progesterone." }, { "input": "Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss - of - function studies.", "output": "There is no related enetity." }, { "input": "Cardiac natriuretic peptides ( NPs ), atrial NP ( ANP ) and B - type NP ( BNP ), and their receptor, guanylyl cyclase ( GC ) - A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions.", "output": "There is no related enetity." }, { "input": "In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses.", "output": "There is no related enetity." }, { "input": "Medaka has two ligands, BNP and C - type NP3 ( CNP3 ) ( but not ANP ), that have greater affinity for the two O. latipes GC - A receptors ( OLGC ), OLGC7 and OLGC2, respectively.", "output": "There is no related enetity." }, { "input": "CNP3 is the ancestral molecule of cardiac NPs.", "output": "There is no related enetity." }, { "input": "Initially, we examined developmental expression of cardiac NP / receptor combinations, BNP / OLGC7 and CNP3 / OLGC2, using quantitative real - time PCR and in situ hybridization.", "output": "There is no related enetity." }, { "input": "BNP and CNP3 mRNA increased at stages 25 ( onset of ventricular formation ) and 22 ( appearance of heart anlage ), respectively, whereas both receptor mRNAs increased at as early as stage 12.", "output": "There is no related enetity." }, { "input": "BNP / OLGC7 transcripts were found in arterial / ventricular tissues and CNP3 / OLGC2 transcripts in venous / atrial tissues by in situ hybridization.", "output": "There is no related enetity." }, { "input": "Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine / autocrine fashion.", "output": "There is no related enetity." }, { "input": "Double knockdown of BNP / OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation.", "output": "There is no related enetity." }, { "input": "CNP3 knockdown induced hypertrophy of atria and activated the renin - angiotensin system.", "output": "There is no related enetity." }, { "input": "Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates.", "output": "There is no related enetity." }, { "input": "The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.", "output": "There is no related enetity." }, { "input": "P21 - activated protein kinase 1 ( Pak1 ) mediates the cross talk between insulin and beta - catenin on proglucagon gene expression and its ablation affects glucose homeostasis in male C57BL / 6 mice.", "output": "glucose." }, { "input": "In gut endocrine L cells, the Wnt signaling pathway effector beta - catenin ( beta - cat ) / transcription factor 7 - like 2 mediates the stimulatory effect of insulin on proglucagon ( gcg ) expression and glucagon - like peptide - 1 ( GLP - 1 ) production.", "output": "There is no related enetity." }, { "input": "In several other cell lineages, insulin is able to stimulate p21 - activated protein kinase 1 ( Pak1 ).", "output": "There is no related enetity." }, { "input": "Here we determined the role of Pak1 in gcg expression and the effect of Pak1 deletion on glucose homeostasis.", "output": "glucose." }, { "input": "Insulin stimulated Pak1 activation through increasing its Thr423 phosphorylation in gut gcg - expressing cell lines, associated with increased gcg mRNA levels.", "output": "Thr423." }, { "input": "This stimulation was attenuated by the Pak inhibitor 2, 2 ' - dihydroxy - 1, 1 ' - dinaphthyldisulfide ( IPA3 ) or dominant - negative Pak1.", "output": "2 , 2 ' - dihydroxy - 1 , 1 ' - dinaphthyldisulfide, IPA3." }, { "input": "Both insulin and cAMP - promoting agents activated beta - cat Ser675 phosphorylation, which was attenuated by IPA3 or protein kinase A inhibition, respectively.", "output": "cAMP, Ser675." }, { "input": "Gut gcg levels were reduced in male Pak1 ( - / - ) mice, associated with impaired glucose tolerance after an ip or oral glucose challenge.", "output": "glucose, glucose." }, { "input": "These mice had lower circulating active GLP - 1 levels after a glucose challenge as well as reduced distal ileum GLP - 1 content after insulin treatment.", "output": "glucose." }, { "input": "Finally, the Pak1 ( - / - ) mice exhibited reduced brainstem gcg level and abolished beta - cat Ser675 phosphorylation in brain neurons after insulin treatment.", "output": "Ser675." }, { "input": "We suggest that Pak1 mediates the cross talk between insulin and Wnt signaling pathways on gut and brain gcg expression, and its ablation impairs glucose homeostasis.", "output": "glucose." }, { "input": "Mortality, bioaccumulation and physiological responses in juvenile freshwater mussels ( Lampsilis siliquoidea ) chronically exposed to copper.", "output": "copper." }, { "input": "Several studies have indicated that the early life stages of freshwater mussels are among the most sensitive aquatic organisms to inorganic chemicals, including copper.", "output": "copper." }, { "input": "However, little is known about the toxic mode of action and sub - lethal effects of copper exposure in this group of imperiled animals.", "output": "copper." }, { "input": "In this study, the physiological effects of long - term copper exposure ( survival, growth, copper bioaccumulation, whole - body ion content, oxygen consumption, filtration rate, ATPase activities, and biomarkers of oxidative stress ) were evaluated in juvenile ( 6 month old ) mussels ( Lampsilis siliquoidea ).", "output": "copper, copper, oxygen." }, { "input": "The mussels ' recovery capacity and their ability to withstand further acute copper challenge were also evaluated in secondary experiments following the 28 day exposure by assessing survival, copper bioaccumulation and whole - body ion content.", "output": "copper, copper." }, { "input": "Mussels chronically exposed to 2 and 12 mu g Cu / L showed significantly higher mortality than those held under control conditions ( mortality 20. 9, 69. 9 and 12. 5 %, respectively ), indicating that juvenile L. siliquoidea is underprotected by the U. S.", "output": "There is no related enetity." }, { "input": "Environmental Protection Agency ( USEPA ) biotic ligand model ( BLM ) - derived chronic water quality criteria ( WQC ) ( 2. 18 mu g Cu / L ) and the hardness - derived USEPA WQC ( 12. 16 mu g Cu / L ).", "output": "There is no related enetity." }, { "input": "Soft tissue copper burden increased equally for both copper exposures, suggesting that chronic toxicity is not associated with copper bioaccumulation.", "output": "copper, copper, copper." }, { "input": "Several physiological disturbances were also observed during chronic copper exposure.", "output": "copper." }, { "input": "Most relevant was a decrease in whole - body sodium content paralleled by an inhibition of Na ( + ) K ( + ) - ATPase activity, indicating a metal - induced ionoregulatory disturbance.", "output": "sodium, Na ( + ), K ( + )." }, { "input": "Filtration and oxygen consumption rates were also affected.", "output": "oxygen." }, { "input": "Redox parameters ( reactive oxygen production, antioxidant capacity against peroxyl radicals, glutathione - S - transferase ( GST ) activity, and glutathione ( GSH ) concentration ) did not show clear responses, but membrane damage as lipid peroxidation ( LPO ) was observed in both copper exposures.", "output": "oxygen, peroxyl, glutathione, S, glutathione, GSH, copper." }, { "input": "Mussels previously held in control conditions or pre - exposed to 2 mu g dissolved Cu / L were able to maintain their ionic homeostasis and did not experience mortality after the 4 - d recovery period.", "output": "Cu." }, { "input": "In contrast, those previously exposed to 12 mu g dissolved Cu / L exhibited 50 % mortality indicating that they had already reached a ' point of no return '.", "output": "Cu." }, { "input": "Pre - exposure to copper did not influence mussel response to the copper challenge test.", "output": "copper, copper." }, { "input": "As observed for the chronic exposure, mortality of mussels held in the absence of copper and submitted to the challenge test was also associated with an ionoregulatory disturbance.", "output": "copper." }, { "input": "These results indicate that ionoregulatory disruption in freshwater mussels chronically exposed to copper is the main mechanism of toxicity and that redox parameters do not appear to be useful as indicators of sub - lethal copper toxicity in these animals.", "output": "copper, copper." }, { "input": "Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host.", "output": "nitrogen." }, { "input": "Alimentary and endogenous proteins are mixed in the small intestinal lumen with the microbiota.", "output": "There is no related enetity." }, { "input": "Although experimental evidences suggest that the intestinal microbiota is able to incorporate and degrade some of the available amino acids, it appears that the microbiota is also able to synthesize amino acids raising the view that amino acid exchange between the microbiota and host can proceed in both directions.", "output": "amino acids, amino acids, amino acid." }, { "input": "Although the net result of such exchanges remains to be determined, it is likely that a significant part of the amino acids recovered from the alimentary proteins are used by the microbiota.", "output": "amino acids." }, { "input": "In the large intestine, where the density of bacteria is much higher than in the small intestine and the transit time much longer, the residual undigested luminal proteins and peptides can be degraded in amino acids by the microbiota.", "output": "amino acids." }, { "input": "These amino acids cannot be absorbed to a significant extent by the colonic epithelium, but are precursors for the synthesis of numerous metabolic end products in reactions made by the microbiota.", "output": "amino acids." }, { "input": "Among these products, some like short - chain fatty acids and organic acids are energy substrates for the colonic mucosa and several peripheral tissues while others like sulfide and ammonia can affect the energy metabolism of colonic epithelial cells.", "output": "fatty acids, sulfide, ammonia." }, { "input": "More work is needed to clarify the overall effects of the intestinal microbiota on nitrogenous compound metabolism and consequences on gut and more generally host health.", "output": "There is no related enetity." }, { "input": "Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide inhibitor siamycin I revealed through synchrotron radiation circular dichroism.", "output": "There is no related enetity." }, { "input": "The suitability of synchrotron radiation circular dichroism spectroscopy ( SRCD ) for studying interactions between the tricyclic peptide inhibitor siamycin I and the intact FsrC membrane sensor kinase in detergent micelles has been established.", "output": "There is no related enetity." }, { "input": "In the present study, tertiary structural changes demonstrate that inhibitor binding occurs at a different, non - overlapping site to the native ligand, GBAP.", "output": "There is no related enetity." }, { "input": "Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?", "output": "There is no related enetity." }, { "input": "Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation.", "output": "There is no related enetity." }, { "input": "Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8 - oxo - dGTP.", "output": "oxidized nucleotides, 8 - oxo - dGTP." }, { "input": "However, many of these show greater activity towards other nucleotides such as ADP - ribose or diadenosine tetraphosphate ( Ap ( 4 ) A ).", "output": "nucleotides, ADP, ribose, diadenosine tetraphosphate, Ap ( 4 ) A." }, { "input": "The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication.", "output": "There is no related enetity." }, { "input": "Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment.", "output": "There is no related enetity." }, { "input": "Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems.", "output": "There is no related enetity." }, { "input": "For example, bacterial Ap ( 4 ) A hydrolases also efficiently remove pyrophosphate from the 5 ' termini of mRNAs, suggesting a potential role for Ap ( 4 ) A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates ( DIPs ) may also be indicative of new regulatory networks in RNA metabolism.", "output": "Ap ( 4 ) A, pyrophosphate, Ap ( 4 ) A, IDP, dIDP, diphosphoinositol polyphosphates, DIPs." }, { "input": "DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation.", "output": "DIP, diadenosine polyphosphates, polyphosphates." }, { "input": "This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.", "output": "There is no related enetity." }, { "input": "ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 ( LGP2 ).", "output": "ATP." }, { "input": "Laboratory of genetics and physiology 2 ( LGP2 ) is a member of the RIG - I - like receptor family of cytoplasmic pattern recognition receptors that detect molecular signatures of virus infection and initiate antiviral signal transduction cascades.", "output": "There is no related enetity." }, { "input": "The ATP hydrolysis activity of LGP2 is essential for antiviral signaling, but it has been unclear how the enzymatic properties of LGP2 regulate its biological response.", "output": "ATP." }, { "input": "Quantitative analysis of the dsRNA binding and enzymatic activities of LGP2 revealed high dsRNA - independent ATP hydrolysis activity.", "output": "ATP." }, { "input": "Biochemical assays and single - molecule analysis of LGP2 and mutant variants that dissociate basal from dsRNA - stimulated ATP hydrolysis demonstrate that LGP2 utilizes basal ATP hydrolysis to enhance and diversify its RNA recognition capacity, enabling the protein to associate with intrinsically poor substrates.", "output": "ATP, ATP." }, { "input": "This property is required for LGP2 to synergize with another RIG - I - like receptor, MDA5, to potentiate IFN beta transcription in vivo during infection with encephalomyocarditis virus or transfection with poly ( I: C ).", "output": "There is no related enetity." }, { "input": "These results demonstrate previously unrecognized properties of LGP2 ATP hydrolysis and RNA interaction and provide a mechanistic basis for a positive regulatory role for LGP2 in antiviral signaling.", "output": "There is no related enetity." }, { "input": "Aminoacyl - tRNA Substrate and Enzyme Backbone Atoms Contribute to Translational Quality Control by YbaK.", "output": "Aminoacyl." }, { "input": "Amino acids are covalently attached to their corresponding transfer RNAs ( tRNAs ) by aminoacyl - tRNA synthetases.", "output": "Amino acids, aminoacyl." }, { "input": "Proofreading mechanisms exist to ensure that high fidelity is maintained in this key step in protein synthesis.", "output": "There is no related enetity." }, { "input": "Prolyl - tRNA synthetase ( ProRS ) can misacylate cognate tRNA ( Pro ) with Ala and Cys.", "output": "Prolyl, Pro, Ala, Cys." }, { "input": "The cis - editing domain of ProRS ( INS ) hydrolyzes Ala - tRNA ( Pro ), whereas Cys - tRNA ( Pro ) is hydrolyzed by a single domain editing protein, YbaK, in trans.", "output": "Ala, Cys, Pro." }, { "input": "Previous studies have proposed a model of substrate - binding by bacterial YbaK and elucidated a substrate - assisted mechanism of catalysis.", "output": "There is no related enetity." }, { "input": "However, the microscopic steps in this mechanism have not been investigated.", "output": "There is no related enetity." }, { "input": "In this work, we carried out biochemical experiments together with a detailed hybrid quantum mechanics / molecular mechanics study to investigate the mechanism of catalysis by Escherichia coli YbaK.", "output": "There is no related enetity." }, { "input": "The results support a mechanism wherein cyclization of the substrate Cys results in cleavage of the Cys - tRNA ester bond.", "output": "Cys, Cys, ester." }, { "input": "Protein side chains do not play a significant role in YbaK catalysis.", "output": "There is no related enetity." }, { "input": "Instead, protein backbone atoms play crucial roles in stabilizing the transition state, while the product is stabilized by the 2 ' - OH of the tRNA.", "output": "2 ' - OH." }, { "input": "Maturation - associated changes in the internal distribution of tetrodotoxin in the female goby Yongeichthys criniger.", "output": "tetrodotoxin." }, { "input": "Maturation - associated changes in the internal distribution of tetrodotoxin ( TTX ) in the goby Yongeichthys criniger were investigated in 29 and 40 female specimens collected from Okinawa, Japan, from August 2008 to June 2009 ( Group I ), and from November 2009 to August 2010 ( Group II ), respectively.", "output": "tetrodotoxin, TTX." }, { "input": "In Group I, based on changes in the gonadosomatic index ( GSI ) and histologic observation of the ovary, the period from October 2008 through January 2009 was estimated to be the ' previtelline - forming period ', February through March 2009 the ' vitelline - forming period ', April through June 2009 the ' spawning period ', and August 2008 the ' end of spawning period ' of the preceding year.", "output": "There is no related enetity." }, { "input": "The TTX content ( mouse unit [ MU ] per gram tissue ) of each Y. criniger tissue ( skin, muscle, liver, and ovary ) quantified by liquid chromatography / mass spectrometry ( LC / MS ) was generally high during the spawning period and continued to rise until the end of spawning period, especially in the ovary.", "output": "TTX." }, { "input": "Total TTX per individual increased considerably during the spawning period, most of which located in the ovary, indicating that Y. criniger obtains a high amount of TTX during the spawning period, and accumulates most of it in the ovary.", "output": "TTX, TTX." }, { "input": "In contrast, the TTX content of the skin was highest at the end of spawning period, and most of the total TTX located in the skin during this period as well as during the previtelline - forming period.", "output": "TTX, TTX." }, { "input": "In Group II, the maturation stage of the ovaries of all specimens was determined, and the specimens were grouped accordingly.", "output": "There is no related enetity." }, { "input": "In the perinucleolus stage, yolk vesicle stage, and yolk globule stage I, most of the TTX was localized in the skin, but the TTX in the ovary greatly increased as the maturation stage advanced from yolk globule stage I to yolk globule stage III.", "output": "TTX, TTX." }, { "input": "Effect of clonidine in mice injected with Tityus discrepans scorpion venom.", "output": "clonidine." }, { "input": "A study was conducted to assess the effect of clonidine ( alpha ( 2 ) - adrenoceptor selective agonist ) on glycemia, serum and urine alpha - amylase, blood urea nitrogen ( BUN ), serum creatinine, white blood cell count, kidney histology and zymogen granule content in pancreatic acini, in mice under the effect of Tityus discrepans ( Td ) scorpion venom.", "output": "clonidine, urea, nitrogen, creatinine." }, { "input": "BALB / c male mice ( 20 +/- 2 g, n = 7 - 11 ) were intraperitoneally ( ip ) injected with a sublethal dose ( 1 mu g / g ) of Td venom, and were treated ( ip ) with 0. 1 mu g / g of clonidine ( Catapresan ( (R) ) ) or 0. 9 % NaCl 30 min after the venom injection, and then every 2 h.", "output": "clonidine, Catapresan, NaCl." }, { "input": "Six hours later, mice were anesthetized with diethylether and urine and blood samples were withdrawn by cystocentesis and cardiocentesis, respectively.", "output": "diethylether." }, { "input": "Tissue samples were obtained and fixed immediately in buffered formalin ( 2 %, pH 7. 4 ) and then processed for stain H & E.", "output": "formalin." }, { "input": "Td venom did not cause hyperglycemia by itself.", "output": "There is no related enetity." }, { "input": "However, clonidine induced hyperglycemia, which was synergized by Td venom.", "output": "clonidine." }, { "input": "Although the venom did not produce hyperamylasemia, clonidine significantly diminished serum alpha - amylase activity in envenomed mice.", "output": "clonidine." }, { "input": "Td venom did not significantly increase urinary alpha - amylase activity, which was unaffected by clonidine.", "output": "clonidine." }, { "input": "Morphometric analysis using microphotographs of pancreata from mice injected with Td venom showed a reduced zymogen granule content as judged by the acidophilic bidimensional area of acini.", "output": "There is no related enetity." }, { "input": "This effect was significantly reduced by clonidine.", "output": "clonidine." }, { "input": "Kidney samples showed histological changes which were partially affected by the drug.", "output": "There is no related enetity." }, { "input": "Clonidine reduced the increase in BUN and serum creatinine concentration in envenomed mice.", "output": "Clonidine, creatinine." }, { "input": "Td venom produced neutrophilia and lymphopenia, which were clonidine - resistant at the assayed dose.", "output": "clonidine." }, { "input": "These results suggest that alpha ( 2 ) - adrenoceptor selective agonists would be able to reduce some scorpion venom - induced renal and pancreatic disturbances, possibly through the inhibition of neurotransmitter release from presynaptic cholinergic and noradrenergic terminals, as well as from adrenal medulla.", "output": "There is no related enetity." }, { "input": "Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines.", "output": "Pyrimidine, halogenated pyrimidines." }, { "input": "African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host.", "output": "pyrimidine, pyrimidines." }, { "input": "However, uptake of pyrimidines in bloodstream form trypanosomes has not been investigated, making it difficult to judge the relative importance of salvage and synthesis or to design a pyrimidine - based chemotherapy.", "output": "pyrimidines, pyrimidine." }, { "input": "Detailed characterization of pyrimidine transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high - affinity uracil transporter ( designated TbU3 ) that is clearly distinct from the procyclic pyrimidine transporters.", "output": "pyrimidine, uracil, pyrimidine." }, { "input": "This transporter had low affinity for uridine and 2 ' deoxyuridine and was the sole pyrimidine transporter expressed in these cells.", "output": "uridine, 2 ' deoxyuridine, pyrimidine." }, { "input": "In addition, thymidine was taken up inefficiently through a P1 - type nucleoside transporter.", "output": "thymidine, nucleoside." }, { "input": "Of importance, the anticancer drug 5 - fluorouracil was an excellent substrate for TbU3, and several 5 - fluoropyrimidine analogs were investigated for uptake and trypanocidal activity; 5F - orotic acid, 5F - 2 ' deoxyuridine displayed activity in the low micromolar range.", "output": "5 - fluorouracil, 5 - fluoropyrimidine, 5F - orotic acid, 5F - 2 ' deoxyuridine." }, { "input": "The metabolism and mode of action of these analogs was determined using metabolomic assessments of T. brucei clonal lines adapted to high levels of these pyrimidine analogs, and of the sensitive parental strains.", "output": "pyrimidine." }, { "input": "The analysis showed that 5 - fluorouracil is incorporated into a large number of metabolites but likely exerts toxicity through incorporation into RNA.", "output": "5 - fluorouracil." }, { "input": "5F - 2 ' dUrd and 5F - 2 ' dCtd are not incorporated into nucleic acids but act as prodrugs by inhibiting thymidylate synthase as 5F - dUMP.", "output": "5F - 2 ' dUrd, 5F - 2 ' dCtd, 5F - dUMP." }, { "input": "We present the most complete model of pyrimidine salvage in T. brucei to date, supported by genome - wide profiling of the predicted pyrimidine biosynthesis and conversion enzymes.", "output": "pyrimidine, pyrimidine." }, { "input": "Impact of thyroid dysfunction on erythropoietin dosage in hemodialysis patients.", "output": "There is no related enetity." }, { "input": "Background: Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis ( HD ).", "output": "There is no related enetity." }, { "input": "Therefore, the impact of thyroid diseases on erythropoietin ( EPO ) dosage in HD patients is not well defined.", "output": "There is no related enetity." }, { "input": "This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients.", "output": "There is no related enetity." }, { "input": "Methods: This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months.", "output": "iron." }, { "input": "Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests.", "output": "There is no related enetity." }, { "input": "Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6 - month period, were collected and analyzed.", "output": "There is no related enetity." }, { "input": "Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status.", "output": "There is no related enetity." }, { "input": "Results: The mean monthly EPO dosages were 77. 7 +/- 37. 0, 70. 2 +/- 40. 6, 90. 8 +/- 68. 4, 78. 5 +/- 46. 7, and 82. 3 +/- 41. 2 mu g, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19. 00 +/- 8. 59 mu g more in hypothyroid patients compared with euthyroid patients ( p = 0. 027 ).", "output": "There is no related enetity." }, { "input": "Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54. 66 +/- 17. 12 mu g ( p = 0. 001 ) and 31. 51 +/- 10. 38 mu g more than that of euthyroid patients, respectively ( p = 0. 002 ).", "output": "There is no related enetity." }, { "input": "Conclusions: In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.", "output": "There is no related enetity." }, { "input": "Phenolic compounds: the role of redox regulation in neurodegenerative disease and cancer.", "output": "Phenolic." }, { "input": "Much work has been carried out in the last two decades on the role of oxidative stress and antioxidants deficiency in the pathophysiology of civilization diseases.", "output": "There is no related enetity." }, { "input": "A considerable amount of chemical, biochemical, epidemiological and clinical evidence indicates that ( poly ) phenolic compounds widely distributed in the plant kingdom, exhibit a wide range effects on biomolecules.", "output": "( poly ) phenolic." }, { "input": "The beneficial effects on human health, many of phenolics have been described to their reactive oxygen ( ROS ) and nitrogen species ( RNS ) scavenging and antioxidant capacity.", "output": "oxygen, nitrogen." }, { "input": "The consumption of vegetables, fruits and flavonoid - rich beverages has been reported to prevent against neurodegenerative diseases, cancer, and ageing.", "output": "flavonoid." }, { "input": "This paper reviews the recent data on ( 1 ) the role oxidative stress in the pathology of civilization diseases; ( 2 ) the protection against oxidative damage due to the toxicity of ROS / RNS; ( 3 ) the cellular and molecular interactions of the ( poly ) phenolic compounds relevant to the prevention of neurodegenerative diseases and cancer, and ( 4 ) the methods for assessing antioxidant capacity.", "output": "( poly ) phenolic." }, { "input": "17 beta - Oestradiol anti - inflammatory effects in primary astrocytes require oestrogen receptor beta - mediated neuroglobin up - regulation.", "output": "17 beta - Oestradiol, oestrogen." }, { "input": "Neuroglobin ( Ngb ), so named after its initial discovery in brain neurones, has received great attention as a result of its neuroprotective effects both in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Recently, we demonstrated that, in neurones, Ngb is a 17 beta - oestradiol ( E ( 2 ) ) inducible protein that is pivotal for hormone - induced anti - apoptotic effects against H ( 2 ) O ( 2 ) toxicity.", "output": "17 beta - oestradiol, H ( 2 ) O ( 2 )." }, { "input": "The involvement of Ngb in other brain cell populations, as well as in other neuroprotective effects of E ( 2 ), is completely unknown at present.", "output": "There is no related enetity." }, { "input": "We demonstrate Ngb immunoreactivity in reactive astrocytes located in the proximity of a penetrating cortical injury in vivo and the involvement of Ngb in the E ( 2 ) - mediated anti - inflammatory effect in primary cortical astrocytes.", "output": "There is no related enetity." }, { "input": "Upon binding to oestrogen receptor ( ER ) beta, E ( 2 ) enhances Ngb levels in a dose - dependent manner.", "output": "oestrogen." }, { "input": "Although with a lesser degree than E ( 2 ), the pro - inflammatory stimulation with lipopolysaccharide ( LPS ) also induces the increase of Ngb protein levels via nuclear factor - ( NF ) kappa B signal ( s ).", "output": "There is no related enetity." }, { "input": "Moreover, a negative cross - talk between ER subtypes and NF kappa B signal ( s ) has been demonstrated.", "output": "There is no related enetity." }, { "input": "In particular, ER alpha - activated signals prevent the NF kappa B - mediated Ngb increase, whereas LPS impairs the ER beta - induced up - regulation of Ngb.", "output": "There is no related enetity." }, { "input": "Therefore, the co - expression of both ER alpha and ER beta is pivotal for mediating E ( 2 ) - induced Ngb expression in the presence of NF kappa B - activated signals.", "output": "There is no related enetity." }, { "input": "Interestingly, Ngb silencing prevents the effect of E ( 2 ) on the expression of inflammatory markers ( i. e. interleukin 6 and interferon gamma - inducible protein 10 ).", "output": "There is no related enetity." }, { "input": "Ngb can be regarded as a key mediator of the different protective effects of E ( 2 ) in the brain, including protection against oxidative stress and the control of inflammation, both of which are at the root of several neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Synthesis and thermal decomposition behaviors of magnesium borohydride ammoniates with controllable composition as hydrogen storage materials.", "output": "magnesium borohydride ammoniates, hydrogen." }, { "input": "An ammonia - redistribution strategy for synthesizing metal borohydride ammoniates with controllable coordination number of NH ( 3 ) was proposed, and a series of magnesium borohydride ammoniates were easily synthesized by a mechanochemical reaction between Mg ( BH ( 4 ) ) ( 2 ) and its hexaammoniate.", "output": "ammonia, metal borohydride ammoniates, NH ( 3 ), magnesium borohydride ammoniates, Mg ( BH ( 4 ) ) ( 2 ), hexaammoniate." }, { "input": "A strong dependence of the dehydrogenation temperature and purity of the released hydrogen upon heating on the coordination number of NH ( 3 ) was elaborated for Mg ( BH ( 4 ) ) ( 2 ). xNH ( 3 ) owing to the change in the molar ratio of H ( delta + ) and H ( delta - ), the charge distribution on H ( delta + ) and H ( delta - ), and the strength of the coordinate bond N: --> Mg ( 2 + ).", "output": "hydrogen, NH ( 3 ), Mg ( BH ( 4 ) ) ( 2 ) . xNH ( 3 ), H ( delta + ), H ( delta - ), H ( delta + ), H ( delta - ), N : --> Mg ( 2 + )." }, { "input": "The monoammoniate of magnesium borohydride ( Mg ( BH ( 4 ) ) ( 2 ). NH ( 3 ) ) was obtained for the first time.", "output": "magnesium borohydride, Mg ( BH ( 4 ) ) ( 2 ) . NH ( 3 )." }, { "input": "It can release 6. 5 % pure hydrogen within 50 minutes at 180 degrees C.", "output": "hydrogen." }, { "input": "The role of prolactin receptor in GH signaling in breast cancer cells.", "output": "There is no related enetity." }, { "input": "GH and prolactin ( PRL ) are structurally related hormones that exert important effects in disparate target tissues.", "output": "There is no related enetity." }, { "input": "Their receptors ( GHR and PRLR ) reside in the cytokine receptor superfamily and share signaling pathways.", "output": "There is no related enetity." }, { "input": "In humans, GH binds both GHR and PRLR, whereas PRL binds only PRLR.", "output": "There is no related enetity." }, { "input": "Both hormones and their receptors may be relevant in certain human and rodent cancers, including breast cancer.", "output": "There is no related enetity." }, { "input": "GH and PRL promote signaling in human T47D breast cancer cells that express both GHR and PRLR.", "output": "There is no related enetity." }, { "input": "Furthermore, GHR and PRLR associate in a fashion augmented acutely by GH, even though GH primarily activates PRLR, rather than GHR, in these cells.", "output": "There is no related enetity." }, { "input": "To better understand PRLR ' s impact, we examined the effects of PRLR knockdown on GHR availability and GH sensitivity in T47D cells.", "output": "There is no related enetity." }, { "input": "T47D - ShPRLR cells, in which PRLR expression was reduced by stable short hairpin RNA ( shRNA ) expression, were compared with T47D - SCR control cells.", "output": "There is no related enetity." }, { "input": "PRLR knockdown decreased the rate of GHR proteolytic turnover, yielding GHR protein increase and ensuing sensitization of these cells to GHR signaling events including phosphorylation of GHR, Janus kinase 2, and signal transducer and activator of transcription 5 ( STAT5 ).", "output": "There is no related enetity." }, { "input": "Unlike in T47D - SCR cells, acute GH signaling in T47D - ShPRLR cells was not blocked by the PRLR antagonist G129R but was inhibited by the GHR - specific antagonist, anti - GHR ( ext - mAb ).", "output": "There is no related enetity." }, { "input": "Thus, GH ' s use of GHR rather than PRLR was manifested when PRLR was reduced.", "output": "There is no related enetity." }, { "input": "In contrast to acute effects, GH incubation for 2 h or longer yielded diminished STAT5 phosphorylation in T47D - ShPRLR cells compared with T47D - SCR, a finding perhaps explained by markedly greater GH - induced GHR down - regulation in cells with diminished PRLR.", "output": "There is no related enetity." }, { "input": "However, when stimulated with repeated 1 - h pulses of GH separated by 3 - h washout periods to more faithfully mimic physiological GH pulsatility, T47D - ShPRLR cells exhibited greater transactivation of a STAT5 - responsive luciferase reporter than did T47D - SCR cells.", "output": "There is no related enetity." }, { "input": "Our data suggest that PRLR ' s presence meaningfully affects GHR use in breast cancer cells.", "output": "There is no related enetity." }, { "input": "MLL histone methylases regulate expression of HDLR - SR - B1 in presence of estrogen and control plasma cholesterol in vivo.", "output": "estrogen, cholesterol." }, { "input": "High - density lipoprotein receptors scavenger receptor class B type I [ HDLR - SR - B1 ( SR - B1 ) ] is a key player in reverse cholesterol transport and maintaining blood cholesterol.", "output": "cholesterol, cholesterol." }, { "input": "We demonstrated that human SR - B1 is transcriptionally activated by 17 beta - estradiol ( E2 ) in HEPG2 and JAR cells.", "output": "17 beta - estradiol." }, { "input": "SR - B1 promoter contains multiple estrogen response elements ( ERE half - sites ) along with some Sp1 binding sites.", "output": "estrogen." }, { "input": "Knockdown of estrogen receptor ( ER ) alpha and ER beta down - regulated E2 - induced SR - B1 expression.", "output": "estrogen." }, { "input": "ERs were bound to SR - B1 promoter EREs in an E2 - dependent manner.", "output": "There is no related enetity." }, { "input": "Along with ERs, mixed - lineage leukemia ( MLL ) histone methylases, especially MLL1 and MLL2, play key roles in E2 - mediated SR - B1 activation.", "output": "There is no related enetity." }, { "input": "MLL1 and MLL2 bind to SR - B1 promoter in an E2 - dependent manner and control the assembly of transcription pre - initiation complex and RNA polymerase II ( RNAPII ) recruitment.", "output": "There is no related enetity." }, { "input": "ERs and MLLs play critical roles in determining the cholesterol uptake by steroidogenic tissues / cells, and their knockdown suppressed the E2 - induced cholesterol uptake efficiencies of the cells.", "output": "cholesterol, cholesterol." }, { "input": "Intriguingly, MLL2 knockdown in mice resulted in a 33 % increase in plasma cholesterol level and also reduced SR - B1 expression in mice liver, demonstrating its crucial functions in controlling plasma cholesterol in vivo.", "output": "cholesterol, cholesterol." }, { "input": "Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study.", "output": "There is no related enetity." }, { "input": "Type 2 diabetes ( T2D ) disproportionally affects African Americans ( AfA ) but, to date, genetic variants identified from genome - wide association studies ( GWAS ) are primarily from European and Asian populations.", "output": "There is no related enetity." }, { "input": "We examined the single nucleotide polymorphism ( SNP ) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2, 806 T2D case subjects with or without end - stage renal disease and 4, 265 control subjects from the Candidate Gene Association Resource Plus Study.", "output": "There is no related enetity." }, { "input": "Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "The strongest association was observed at TCF7L2 rs7903146 ( odds ratio [ OR ] 1. 30; P = 6. 86 x 10 - 8 ).", "output": "There is no related enetity." }, { "input": "Locus - wide analysis demonstrated significant associations ( P ( emp ) < 0. 05 ) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus.", "output": "There is no related enetity." }, { "input": "Of these loci, the regional best SNPs were in differential linkage disequilibrium ( LD ) with the index and adjacent SNPs.", "output": "There is no related enetity." }, { "input": "Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes.", "output": "There is no related enetity." }, { "input": "The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations.", "output": "There is no related enetity." }, { "input": "Clone DB: an integrated NCBI resource for clone - associated data.", "output": "There is no related enetity." }, { "input": "The National Center for Biotechnology Information ( NCBI ) Clone DB ( http: / / www. ncbi. nlm. nih. gov / clone / ) is an integrated resource providing information about and facilitating access to clones, which serve as valuable research reagents in many fields, including genome sequencing and variation analysis.", "output": "There is no related enetity." }, { "input": "Clone DB represents an expansion and replacement of the former NCBI Clone Registry and has records for genomic and cell - based libraries and clones representing more than 100 different eukaryotic taxa.", "output": "There is no related enetity." }, { "input": "Records provide details of library construction, associated sequences, map positions and information about resource distribution.", "output": "There is no related enetity." }, { "input": "Clone DB is indexed in the NCBI Entrez system and can be queried by fields that include organism, clone name, gene name and sequence identifier.", "output": "There is no related enetity." }, { "input": "Whenever possible, genomic clones are mapped to reference assemblies and their map positions provided in clone records.", "output": "There is no related enetity." }, { "input": "Clones mapping to specific genomic regions can also be searched for using the NCBI Clone Finder tool, which accepts queries based on sequence coordinates or features such as gene or transcript names.", "output": "There is no related enetity." }, { "input": "Clone DB makes reports of library, clone and placement data on its FTP site available for download.", "output": "There is no related enetity." }, { "input": "With Clone DB, users now have available to them a centralized resource that provides them with the tools they will need to make use of these important research reagents.", "output": "There is no related enetity." }, { "input": "KEGG OC: a large - scale automatic construction of taxonomy - based ortholog clusters.", "output": "There is no related enetity." }, { "input": "The identification of orthologous genes in an increasing number of fully sequenced genomes is a challenging issue in recent genome science.", "output": "There is no related enetity." }, { "input": "Here we present KEGG OC ( http: / / www. genome. jp / tools / oc / ), a novel database of ortholog clusters ( OCs ).", "output": "There is no related enetity." }, { "input": "The current version of KEGG OC contains 1 176 030 OCs, obtained by clustering 8 357 175 genes in 2112 complete genomes ( 153 eukaryotes, 1830 bacteria and 129 archaea ).", "output": "There is no related enetity." }, { "input": "The OCs were constructed by applying the quasi - clique - based clustering method to all possible protein coding genes in all complete genomes, based on their amino acid sequence similarities.", "output": "amino acid." }, { "input": "It is computationally efficient to calculate OCs, which enables to regularly update the contents.", "output": "There is no related enetity." }, { "input": "KEGG OC has the following two features: ( i ) It consists of all complete genomes of a wide variety of organisms from three domains of life, and the number of organisms is the largest among the existing databases; and ( ii ) It is compatible with the KEGG database by sharing the same sets of genes and identifiers, which leads to seamless integration of OCs with useful components in KEGG such as biological pathways, pathway modules, functional hierarchy, diseases and drugs.", "output": "There is no related enetity." }, { "input": "The KEGG OC resources are accessible via OC Viewer that provides an interactive visualization of OCs at different taxonomic levels.", "output": "There is no related enetity." }, { "input": "An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo W. T.", "output": "isoquinoline alkaloid." }, { "input": "Wang inhibits P - glycoprotein and multidrug resistance - associate protein 1.", "output": "There is no related enetity." }, { "input": "Overexpression of P - glycoprotein ( P - gp ) and multidrug resistance - associate protein 1 ( MRP1 ) is a major mechanism leading to multidrug resistance ( MDR ) of cancer cells.", "output": "There is no related enetity." }, { "input": "These transporters expel anti - cancer drugs and greatly impair therapeutic efficacy of chemotherapy.", "output": "There is no related enetity." }, { "input": "A Chinese herbal plant Yanhusuo ( Corydalis yanhusuo W. T. Wang, YHS ) is frequently used in functional food and traditional Chinese medicine to improve the efficacy of chemotherapy.", "output": "There is no related enetity." }, { "input": "The objective of this work was to study effects of glaucine, an alkaloid component of YHS, on P - gp and MRP1 in resistant cancer cells.", "output": "glaucine." }, { "input": "The resistant cancer cell line, MCF - 7 / ADR and corresponding parental sensitive cells were employed to determine reversal properties of glaucine.", "output": "glaucine." }, { "input": "Glaucine inhibits P - gp and MRP1 - mediated efflux and activates ATPase activities of the transporters, indicating that it is a substrate and inhibits P - gp and MRP1 competitively.", "output": "Glaucine." }, { "input": "Furthermore, glaucine suppresses expression of ABC transporter genes.", "output": "There is no related enetity." }, { "input": "It reverses the resistance of MCF - 7 / ADR to adriamycin and mitoxantrone effectively.", "output": "adriamycin, mitoxantrone." }, { "input": "Antioxidant activity and effective compounds of immature calamondin peel.", "output": "There is no related enetity." }, { "input": "The antioxidant activity and the flavonoids of mature and immature calamondin ( Citrus mitis Blanco ) peel were investigated.", "output": "flavonoids." }, { "input": "The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity ( ORAC ), reducing power, and superoxide scavenging effect.", "output": "oxygen, superoxide." }, { "input": "3 ', 5 ' - Di - C - beta - glucopyranosylphloretin, naringin, hesperidin, nobiletin, and tangeretin are the five major flavonoids found in hot water extract with the levels of 6888 +/- 522, 2333 +/- 157, 1350 +/- 94, 165 +/- 13, and 8 +/- 4 mg / 100 g dry basis, respectively.", "output": "3 ' , 5 ' - Di - C - beta - glucopyranosylphloretin, naringin, hesperidin, nobiletin, tangeretin, flavonoids." }, { "input": "The contents of nobiletin and tangeretin increased after ripening.", "output": "nobiletin, tangeretin." }, { "input": "The hot water extract of immature calamondin peel was fractionated using a semi - preparative HPLC.", "output": "There is no related enetity." }, { "input": "Fraction VI showed the highest ORAC value ( 28. 02 +/- 2. 73 mmol Trolox equivalents ( TE ) / g fraction ) and two compounds, naringin and hesperidin, were identified as the major active components attributed to the antioxidant activity.", "output": "Trolox, naringin, hesperidin." }, { "input": "Fraction V contained 3 ', 5 ' - di - C - beta - glucopyranosylphloretin, which revealed low ORAC value with 7. 43 mmol TE / g fraction.", "output": "3 ' , 5 ' - di - C - beta - glucopyranosylphloretin." }, { "input": "However, it might also contribute to antioxidant activity in immature calamondin peel due to its greatest quantity.", "output": "There is no related enetity." }, { "input": "Temperature - dependent kinetics of grape seed phenolic compounds extraction: experiment and model.", "output": "There is no related enetity." }, { "input": "The kinetics of a batch solid - liquid extraction of total phenolic compounds ( PC ) from milled grape seed ( Vitis vinifera L. cv. \" Frankovka \" ) using 50 % ethanol at different extraction temperatures ( 25 - 80 degrees C ) was studied.", "output": "ethanol." }, { "input": "The maximum yield of PC was 0. 13 kg ( GAE ) / kg ( db ) after 200 min of extraction in agitated vessel at 80 degrees C.", "output": "There is no related enetity." }, { "input": "A new model based on the assumptions of a first order kinetics mechanism for the solid - liquid extraction and a linear equilibrium at the solid - liquid interface was developed.", "output": "There is no related enetity." }, { "input": "The model involves the concept of broken and intact cells in order to describe two successive extraction periods: a very fast surface washing process followed by slow diffusion of phenolic compounds from grape seeds to the solvent.", "output": "There is no related enetity." }, { "input": "The proposed model is suited to fit experimental data and to simulate the extraction of phenolic compounds, which was confirmed by the correlation coefficient ( r >= 0. 965 ), the root mean square error ( RMSE <= 0. 003 kg ( GAE ) / kg ( db ) ) and the mean relative deviation modulus ( E <= 2. 149 % ).", "output": "There is no related enetity." }, { "input": "The temperature influenced both equilibrium partition coefficients of phenolic compounds and transport properties, which is manifested by a relatively high value of activation energy ( 23 - 24 ) kJ / mol and by values of effective diffusivity in seed particles.", "output": "There is no related enetity." }, { "input": "Analysis of Anabaena vaginicola and Nostoc calcicola from Northern Iran, as rich sources of major carotenoids.", "output": "There is no related enetity." }, { "input": "Four major carotenoids of high nutritional significance, including beta - carotene, lycopene, lutein and zeaxanthin were determined in three isolates of heterocystous cyanobacteria, belonging to the genera Anabaena and Nostoc, isolated from Iranian terrestrial and aquatic ecosystems, for the first time.", "output": "beta - carotene, lycopene, lutein, zeaxanthin." }, { "input": "The ultrasonically extracted carotenoids were identified and quantified by a rapid and sensitive isocratic HPLC method and identification was further confirmed by spiking authentic standards and the pattern of the UV - Vis spectra obtained from photo - diode array detector.", "output": "There is no related enetity." }, { "input": "The results showed that these isolates contain large amounts of four major carotenoids, especially lycopene ( up to 24, 570 mu g / g dry weight, DW ) which appears to be the highest reported amount until present; and beta - carotene ( up to 8133 mu g / g DW ) which is comparable with the best natural sources of beta - carotene.", "output": "lycopene, beta - carotene, beta - carotene." }, { "input": "Meanwhile, they are rich in the cis - isomers of lycopene and beta - carotene which is important in their bioavailability and health benefits.", "output": "cis - isomers of lycopene and beta - carotene." }, { "input": "Formation of carcinogenic 4 ( 5 ) - methylimidazole in caramel model systems: a role of sulphite.", "output": "4 ( 5 ) - methylimidazole, sulphite." }, { "input": "Aqueous caramel model systems consisted the D - glucose / NH ( 3 ) / sulphite were heated at 100 degrees C for 2 h and amounts of carcinogenic 4 ( 5 ) - methylimidazole ( 4 - MI ) formed were determined.", "output": "D - glucose, NH ( 3 ), sulphite, 4 ( 5 ) - methylimidazole, 4 - MI." }, { "input": "The amount formed ranged from 7. 0 to 155. 0 ppm.", "output": "There is no related enetity." }, { "input": "A system with 0. 1 M sulphite yielded the greatest amount of 4 - MI, which was 54 % more than that yielded from a system without sulphite.", "output": "sulphite, 4 - MI, sulphite." }, { "input": "When the amount of sulphite increased over 0. 1 M, the amount of 4 - MI reduced.", "output": "sulphite, 4 - MI." }, { "input": "The greatest reduction was achieved with 0. 2 M sulphite by 68 % compared to 0 M sulphite, suggesting that sulphite plays an important role in the formation of carcinogenic 4 - MI in caramel colour.", "output": "sulphite, sulphite, sulphite, 4 - MI." }, { "input": "Also, a system with 0. 1 M sulphite yielded the most intense caramel colour but the other levels of sulphite did not change the colour intensity significantly.", "output": "sulphite, sulphite." }, { "input": "Sulphite contributed slightly to the level of flavour chemicals evaluated using pyrazine formation.", "output": "Sulphite, pyrazine." }, { "input": "The results suggest that sulphite addition at appropriate amount reduces 4 - MI formation in caramel colour without sacrificing flavour and colour formation.", "output": "sulphite, 4 - MI." }, { "input": "Podocarpane, isopimarane, and abietane diterpenoids from Isodon lophanthoides var. graciliflorus.", "output": "Podocarpane, isopimarane, abietane, diterpenoids." }, { "input": "Four new diterpenoids including two podocarpanes, graciliflorins A ( 1 ) and B ( 2 ), an isopimarane acetal, graciliflorin C ( 3 ), and a rearranged abietane, graciliflorin D ( 4 ) were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus ( Lamiaceae ) along with podocarpa - 8, 11, 13 - triene - 3 alpha, 13 - diol ( 5 ) and micranthin B ( 6 ).", "output": "diterpenoids, podocarpanes, graciliflorins A ( 1 ) and B, isopimarane acetal, graciliflorin C, abietane, graciliflorin D, podocarpa - 8 , 11 , 13 - triene - 3 alpha , 13 - diol, micranthin B." }, { "input": "Their structures were elucidated based on the spectroscopic data.", "output": "There is no related enetity." }, { "input": "The in vitro cytotoxicity of compounds 1 - 4 and 6 against human carcinoma A549, MCF - 7, and HeLa cell lines were evaluated using the MTT colourimetric assay.", "output": "MTT." }, { "input": "Micranthin B ( 6 ) showed moderate activity against all the cells with IC ( 50 ) values of 16. 29, 18. 20, and 22. 25 mu M, while compounds 1 - 4 were inactive ( IC ( 50 ) > 50 mu g / ml ).", "output": "Micranthin B." }, { "input": "Oxidative changes during ice storage of rainbow trout ( Oncorhynchus mykiss ) fed different ratios of marine and vegetable feed ingredients.", "output": "There is no related enetity." }, { "input": "Recently fish meal and oil have increasingly been replaced with proteins and oils from vegetable sources in the diets of farmed salmonids, but the consequences for the oxidative stability of the resulting fish products have not been investigated.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the influence of feeding regime on composition of rainbow trout fillets, as well as on lipid and protein oxidation during storage on ice.", "output": "There is no related enetity." }, { "input": "Rainbow trout were fed six different diets, which differed in their levels of marine oil and proteins vs. vegetable oil and protein.", "output": "There is no related enetity." }, { "input": "Fish fillets were characterised by measurement of fatty acid and amino acid composition, primary and secondary lipid oxidation products, astaxanthin and tocopherol content.", "output": "fatty acid, amino acid, astaxanthin, tocopherol." }, { "input": "Protein oxidation was assessed by measuring protein carbonyl content, oxidised amino acids, sulfhydryl groups and immuno - blotting against carbonyl groups.", "output": "carbonyl, amino acids, sulfhydryl, carbonyl." }, { "input": "Feeding regimes significantly influenced fatty acid composition.", "output": "fatty acid." }, { "input": "Replacement of fish oil with vegetable oil reduced formation of primary oxidation products, but the effect on secondary oxidation products differed between different types of volatiles.", "output": "There is no related enetity." }, { "input": "The differences in protein and amino acid composition were not significant, and there were no clear effects of diets on protein oxidation, but data indicated that compounds present in the marine ingredients might have had an effect on protein oxidation.", "output": "amino acid." }, { "input": "Development and characterisation of composite films made of kefiran and starch.", "output": "There is no related enetity." }, { "input": "In this study, new edible composite films were prepared by blending kefiran with corn starch.", "output": "There is no related enetity." }, { "input": "Film - forming solutions of different ratios of kefiran to corn starch ( 100 / 0, 70 / 30, 50 / 50, 30 / 70 ) were cast at room temperature.", "output": "There is no related enetity." }, { "input": "The effects of starch addition on the resulting films ' physical, mechanical and water - vapor permeability ( WVP ) properties were investigated.", "output": "There is no related enetity." }, { "input": "Increasing starch content from 0 % to 50 % ( v / v ) decreased the WVP of films; however, with further starch addition the WVP increased.", "output": "There is no related enetity." }, { "input": "Also, this increase in starch content increased the tensile strength and extensibility of the composite films.", "output": "There is no related enetity." }, { "input": "However, these mechanical properties decreased at higher starch contents.", "output": "There is no related enetity." }, { "input": "Dynamic mechanical thermal analysis ( DMTA ) curves showed that addition of starch at all levels increased the glass transition temperature of films.", "output": "There is no related enetity." }, { "input": "The electron scanning micrograph for the composite film was homogeneous, without signs of phase separation between the components.", "output": "There is no related enetity." }, { "input": "Thus, it was observed that these two film - forming components were compatible, and that an interaction existed between them.", "output": "There is no related enetity." }, { "input": "Binding affinity between dietary polyphenols and beta - lactoglobulin negatively correlates with the protein susceptibility to digestion and total antioxidant activity of complexes formed.", "output": "polyphenols." }, { "input": "Non - covalent interactions between beta - lactoglobulin ( BLG ) and polyphenol extracts of teas, coffee and cocoa were studied by fluorescence and CD spectroscopy at pH values of the gastrointestinal tract ( GIT ).", "output": "polyphenol." }, { "input": "The biological implications of non - covalent binding of polyphenols to BLG were investigated by in vitro pepsin and pancreatin digestibility assay and ABTS radical scavenging activity of complexes formed.", "output": "polyphenols, ABTS." }, { "input": "The polyphenol - BLG systems were stable at pH values of the GIT.", "output": "polyphenol." }, { "input": "The most profound effect of pH on binding affinity was observed for polyphenol extracts rich in phenolic acids.", "output": "polyphenol, phenolic acids." }, { "input": "Stronger non - covalent interactions delayed pepsin and pancreatin digestion of BLG and induced beta - sheet to alpha - helix transition at neutral pH.", "output": "There is no related enetity." }, { "input": "All polyphenols tested protected protein secondary structure at an extremely acidic pH of 1. 2.", "output": "polyphenols." }, { "input": "A positive correlation was found between the strength of protein - polyphenol interactions and ( a ) half time of protein decay in gastric conditions ( R ( 2 ) = 0. 85 ), ( b ) masking of total antioxidant capacity of protein - polyphenol complexes ( R ( 2 ) = 0. 95 ).", "output": "polyphenol, polyphenol." }, { "input": "Recovery and characterisation of coloured phenolic preparations from apple seeds.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate whether complexly constituted phenolic extracts from apple seeds may be utilised for the recovery of natural coloured antioxidant preparations, which might serve as potential food or cosmetic ingredients.", "output": "There is no related enetity." }, { "input": "In a first step, the recovery of phenolic compounds was optimised by varying crucial extraction parameters.", "output": "There is no related enetity." }, { "input": "A single extraction step at 25 degrees C using an acetone - water mixture ( 60: 40, v / v ) and a solid - to - solvent ratio of 1: 8 ( w / v ) for 1 h was found to be appropriate to achieve both high phenolic yields and antioxidant activities.", "output": "acetone." }, { "input": "In a second step, differently produced apple seed extracts and a phloridzin model solution were enzymatically treated by mushroom polyphenol oxidase to investigate the rate of pigment synthesis.", "output": "phloridzin, polyphenol." }, { "input": "Depending on the extraction procedure applied, synthesis rates, pigment yields and colour properties significantly differed.", "output": "There is no related enetity." }, { "input": "Compared to the phloridzin model solution, extracts recovered from the seeds showed comparable and even better results, thus indicating such preparations to be a promising alternative to synthetic yellow dyes.", "output": "phloridzin." }, { "input": "The nutritional supplement Active Hexose Correlated Compound ( AHCC ) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR / MyD88 and NF - kappa B / MAPK activation.", "output": "Hexose." }, { "input": "Active Hexose Correlated Compound ( AHCC ) is an immunostimulatory nutritional supplement.", "output": "Hexose." }, { "input": "AHCC effects and mechanism of action on intestinal epithelial cells or monocytes are poorly described.", "output": "There is no related enetity." }, { "input": "AHCC was added to the culture medium of intestinal epithelial cells ( IEC18 and HT29 cells ) and monocytes ( THP - 1 cells ) and assessed the secretion of proinflammatory cytokines by ELISA.", "output": "There is no related enetity." }, { "input": "Inhibitors of NF kappa B and MAPKs were used to study signal transduction pathways while TLR4 and MyD88 were silenced in IEC18 cells using shRNA.", "output": "There is no related enetity." }, { "input": "It was found that AHCC induced GRO alpha and MCP1 secretion in IEC18 and IL - 8 in HT29 cells.", "output": "There is no related enetity." }, { "input": "These effects depended on NF kappa B activation, and partly on MAPKs activation and on the presence of MyD88 and TLR4.", "output": "There is no related enetity." }, { "input": "In THP - 1 cells AHCC evoked IL - 8, IL - 1 beta and TNF - alpha secretion.", "output": "There is no related enetity." }, { "input": "The induction of IL - 8 depended on JNK and NF kappa B activation.", "output": "There is no related enetity." }, { "input": "Therefore, AHCC exerts immunostimulatory effects on intestinal epithelial cells and monocytes involving TLR4 / MyD88 and NF kappa B / MAPK signal transduction pathways.", "output": "There is no related enetity." }, { "input": "Garlic oil attenuates the cardiac apoptosis in hamster - fed with hypercholesterol diet.", "output": "There is no related enetity." }, { "input": "Hypercholesterolemia is a well established risk factor for cardiac cell apoptosis.", "output": "There is no related enetity." }, { "input": "The purpose of this study is to evaluate the effects of garlic oil on cardiac apoptosis induced by a hypercholesterol diet.", "output": "There is no related enetity." }, { "input": "Twenty - four male Golden - Syrian hamsters at 3 months of age were randomly divided into three groups, control, cholesterol and garlic oil groups received a chow diet, chow diet with 2 % cholesterol, and chow diet with 2 % cholesterol and 1 % garlic oil for 8 weeks, respectively.", "output": "cholesterol, cholesterol, cholesterol." }, { "input": "The TUNEL - positive apoptotic cells, and several apoptotic proteins were significantly induced in the excised left ventricle in cholesterol group, whereas significant reduction was observed in cholesterol plus garlic oil group.", "output": "cholesterol, cholesterol." }, { "input": "The IGFI receptor dependent survival pathway was inhibited in cholesterol group whereas it was obviously reversed in cholesterol plus garlic oil group.", "output": "cholesterol, cholesterol." }, { "input": "Our results suggest that administration of garlic oil shows protective effects on cardiac apoptosis in rats with high cholesterol intake.", "output": "cholesterol." }, { "input": "Characterisation of tequila according to their major volatile composition using multilayer perceptron neural networks.", "output": "There is no related enetity." }, { "input": "Differentiation of silver, gold, aged and extra - aged tequila using 1 - propanol, ethyl acetate, 2 - methyl - 1 - propanol, 3 - methyl - 1 - butanol and 2 - methyl - 1 - butanol and furan derivatives like 5 - ( hydroxymethyl ) - 2 - furaldehyde and 2 - furaldehyde has been carried out.", "output": "silver, 1 - propanol, ethyl acetate, 2 - methyl - 1 - propanol, 3 - methyl - 1 - butanol, 2 - methyl - 1 - butanol, furan, 5 - ( hydroxymethyl ) - 2 - furaldehyde, 2 - furaldehyde." }, { "input": "The content of 1 - propanol, ethyl acetate, 2 - methyl - 1 - propanol, 3 - methyl - 1 - butanol and 2 - methyl - 1 - butanol was determined by means of head space solid phase microextraction gas chromatography mass - spectrometry.", "output": "1 - propanol, ethyl acetate, 2 - methyl - 1 - propanol, 3 - methyl - 1 - butanol, 2 - methyl - 1 - butanol." }, { "input": "5 - ( Hydroxymethyl ) - 2 - furaldehyde and 2 - furaldehyde were determined by high performance liquid chromatography with diode array detection.", "output": "5 - ( Hydroxymethyl ) - 2 - furaldehyde, 2 - furaldehyde." }, { "input": "Kruskal - Wallis test was used to highlight significant differences between types of tequila.", "output": "There is no related enetity." }, { "input": "Principal component analysis was applied as visualisation technique.", "output": "There is no related enetity." }, { "input": "Linear discriminant analysis and multilayer perceptron artificial neural networks were used to construct classification models.", "output": "There is no related enetity." }, { "input": "The best classification performance was obtained when multilayer perceptron model was applied.", "output": "There is no related enetity." }, { "input": "Pulsed - electric - field - assisted extraction of anthocyanins from purple - fleshed potato.", "output": "anthocyanins." }, { "input": "The influence of pulsed electric field ( PEF ) treatment on the anthocyanin extraction yield ( AEY ) from purple - fleshed potato ( PFP ) at different extraction times ( 60 - 480 min ) and temperatures ( 10 - 40 degrees C ) using water and ethanol ( 48 % and 96 % ) as solvents has been investigated.", "output": "anthocyanin, ethanol." }, { "input": "Response surface methodology was used to determine optimal PEF treatment and optimise anthocyanin extraction.", "output": "anthocyanin." }, { "input": "A PEF treatment of 3. 4 kV / cm and 105 mu s ( 35 pulses of 3 mu s ) resulted in the highest cell disintegration index ( Z ( p ) = 1 ) at the lowest specific energy requirements ( 8. 92 kJ / kg ).", "output": "There is no related enetity." }, { "input": "This PEF treatment increased the AEY, the effect being higher at lower extraction temperature with water as solvent.", "output": "There is no related enetity." }, { "input": "After 480 min at 40 degrees C, the AEY obtained for the untreated sample using 96 % ethanol as the solvent ( 63. 9 mg / 100 g fw ) was similar to that obtained in the PEF - treated sample using water ( 65. 8 mg / 100 g fw ).", "output": "ethanol." }, { "input": "Therefore, PEF was possible with water, a more environmental - friendly solvent than ethanol, without decreasing the AEY from PFP.", "output": "ethanol." }, { "input": "Production of medium chain saturated fatty acids with enhanced antimicrobial activity from crude coconut fat by solid state cultivation of Yarrowia lipolytica.", "output": "saturated fatty acids." }, { "input": "Fatty acids profiles and antimicrobial activity of crude coconut fat hydrolysates obtained in solid - state cultivation system with a selected yeast strain Yarrowia lipolytica RO13 were performed.", "output": "Fatty acids." }, { "input": "A preliminary step regarding extracellular lipase production and solid state enzymatic hydrolysis of crude fat at different water activity and time intervals up to 7 days was also applied.", "output": "There is no related enetity." }, { "input": "Gas chromatography - mass spectrometry analysis was used for quantification of medium chain saturated fatty acids ( MCSFAs ) and the results revealed a higher concentration of about 70 % lauric acid from total fatty acids.", "output": "fatty acids, lauric acid, fatty acids." }, { "input": "Further, antimicrobial activity of fatty acids against some food - borne pathogens ( Salmonella enteritidis, Escherichia coli, Listeria monocytogenes and Bacillus cereus ) was evaluated.", "output": "fatty acids." }, { "input": "The minimum inhibitory concentration of the obtained hydrolysates varied from 12. 5 to 1. 56 ppm, significantly lower than values reported in literature.", "output": "There is no related enetity." }, { "input": "The results provide substantial evidence for obtaining biopreservative effects by coconut fat enzymatic hydrolysis.", "output": "There is no related enetity." }, { "input": "Method development and validation for boscalid in blueberries by solid - phase microextraction gas chromatography, and their degradation kinetics.", "output": "There is no related enetity." }, { "input": "Analytical method for the residues of boscalid in blueberries was developed.", "output": "There is no related enetity." }, { "input": "Fungicide residues were determined by solid - phase microextraction ( SPME ) coupled to gas chromatography with micro - electron capture ( mu - ECD ) detector.", "output": "There is no related enetity." }, { "input": "The effect of pH values and fiber coatings were studied.", "output": "There is no related enetity." }, { "input": "The SPME fiber coating selected was 100 mu m PDMS.", "output": "There is no related enetity." }, { "input": "The method is selective with adequate precision and high accuracy and sensitivity.", "output": "There is no related enetity." }, { "input": "Recoveries ranged within the 98 - 104 % range, and detection and quantification limits were 1. 33 and 4. 42 mu g / kg, respectively.", "output": "There is no related enetity." }, { "input": "Statistical parameters indicated the occurrence of matrix effect; consequently calibration was performed on spiked samples.", "output": "There is no related enetity." }, { "input": "Degradation of boscalid was studied in a blueberry field located in Concordia, Argentina, with fruits from Emerald and Jewel varieties.", "output": "boscalid." }, { "input": "The degradation of boscalid in both blueberry varieties studied followed a first order rate kinetics and the half - life for boscalid was 5. 3 and 6. 3 days for Emerald and Jewel cultivars, respectively.", "output": "boscalid, boscalid." }, { "input": "Effect of dry heating with ionic gums on physicochemical properties of starch.", "output": "There is no related enetity." }, { "input": "Corn starch, potato starch, pea starch were impregnated with ionic gums ( sodium alginate, CMC, and xanthan, 1 % based on starch solids ) and heat - treated in a dry state for 0, 2, or 4 h at 130 degrees C.", "output": "sodium." }, { "input": "Effects of the dry heating on paste viscosity ( RVA ), microstructure and thermal properties were examined.", "output": "There is no related enetity." }, { "input": "Dry heat treatment with ionic gums reduced the pasting temperature of the three starches.", "output": "There is no related enetity." }, { "input": "Heating with xanthan increased the paste viscosity of corn and potato starch.", "output": "There is no related enetity." }, { "input": "With heat treatment, the paste viscosity of all the starch - sodium alginate mixtures decreased.", "output": "sodium." }, { "input": "Heating with CMC increased the paste viscosity of potato starch, but decreased that of corn and pea starch.", "output": "There is no related enetity." }, { "input": "After dry - heating, To, Tp and Tc of potato starch with ionic gums decreased significantly.", "output": "There is no related enetity." }, { "input": "SEM of potato starch with CMC showed that the gel structure got compacter after drying - heating.", "output": "There is no related enetity." }, { "input": "Heat treatment obviously improved the functional properties of the three starches.", "output": "There is no related enetity." }, { "input": "Determination of acrylamide in local and commercial cultivar of potatoes from biological farm.", "output": "acrylamide." }, { "input": "This paper reports the results of a preliminary study on the characterization of parameters influencing formation of acrylamide in fried potatoes, from biological cultivation.", "output": "acrylamide." }, { "input": "The formation of acrylamide was investigated in relation to frying in biological extra virgin olive oil and commercial seed oil.", "output": "acrylamide." }, { "input": "Three different cultivars ( Rossa di Colfiorito, Quarantina bianca genovese and Kennebec ) were chosen.", "output": "There is no related enetity." }, { "input": "Asparagine, glucose, fructose and sucrose concentrations were determined in potato slice before frying, while acrylamide content was analysed by LC - ESI - MS / MS in the slices fried in seed and extra virgin olive oil.", "output": "Asparagine, glucose, fructose, sucrose, acrylamide." }, { "input": "The Kennebec cultivar showed differences in its potential for acrylamide formation, which was primarily related to its relatively high asparagine and reducing sugars contents, respect the other local cultivars ( particulary Quarantina ).", "output": "acrylamide, asparagine, sugars." }, { "input": "Values of acrylamide below detection limit ( LOD ) were found in Quarantina bianca genovese cultivar samples fried in extra virgin olive oil and peanuts seed oil and higher in peanuts seed oil fried potatoes of Kennebec cultivar.", "output": "acrylamide." }, { "input": "In vitro antibacterial, cytotoxicity and haemolytic activities and phytochemical analysis of seagrasses from the Gulf of Mannar, South India.", "output": "There is no related enetity." }, { "input": "It is essential to study the phytochemical constituents and toxicological properties of seagrasses when considering their food applications.", "output": "There is no related enetity." }, { "input": "Aqueous methanolic extracts of six seagrasses were evaluated for their antibacterial, cytotoxic ( brine shrimp leathality assay ) and haemolytic activity.", "output": "There is no related enetity." }, { "input": "Thin layer chromatography ( TLC ) and phytochemical analysis were used to compare the phytochemical profiles of six seagrasses.", "output": "There is no related enetity." }, { "input": "Among the six seagrasses examined, Halodule pinifolia and Cymodocea rotundata showed predominant growth inhibitory activity against all the tested human pathogens.", "output": "There is no related enetity." }, { "input": "Cytotoxicity of seagrass extracts against nauplii of Artemia salina revealed that Syringodium isoetifolium exhibited lesser toxicity with LC ( 50 ) value of 699. 096 mu g / ml.", "output": "There is no related enetity." }, { "input": "Of all the seagrasses tested, H. pinifolia recorded the minimum haemolytic activity of 2. 07 +/- 0. 63 % at 1000 mu g / ml concentration.", "output": "There is no related enetity." }, { "input": "Phytochemical analysis showed the presence of common plant chemical constituents which varied with respect to species.", "output": "There is no related enetity." }, { "input": "The present findings suggest the possible pharmacological applications of selected seagrasses that can be used as food ingredients.", "output": "There is no related enetity." }, { "input": "Adsorption kinetics, thermodynamics and isotherm of Hg ( II ) from aqueous solutions using buckwheat hulls from Jiaodong of China.", "output": "Hg ( II )." }, { "input": "The adsorption kinetics and adsorption isotherms of buckwheat hulls in the region of Jiaodong, China ( BHJC ) for Hg ( II ) were investigated.", "output": "Hg ( II )." }, { "input": "Results revealed that the adsorption kinetics of BHJC for Hg ( II ) were well described by a pseudo second - order reaction model, and the adsorption thermodynamic parameters Delta G, Delta H and Delta S were - 5. 83 kJ mol ( - 1 ) ( 35 degrees C ), 73. 1, and 256 JK ( - 1 ) mol ( - 1 ), respectively.", "output": "Hg ( II )." }, { "input": "Moreover, Langmuir, Freundlich and Redlich - Peterson isotherm models were applied to analyse the experimental data and to predict the relevant isotherm parameters.", "output": "There is no related enetity." }, { "input": "The best interpretation for the experimental data was given by the Langmuir isotherm equation, and the maximum adsorption capacity for Hg ( II ) is 243. 90 mg / g at 35 degrees C.", "output": "Hg ( II )." }, { "input": "Furthermore, investigation of the adsorption selectivity showed that BHJC displayed strong affinity for mercury in the aqueous solutions and exhibited 100 % selectivity for mercury in the presence of Zn ( II ) and Cd ( II ).", "output": "mercury, mercury, Zn ( II ), Cd ( II )." }, { "input": "Suitability of elemental fingerprinting for assessing the geographic origin of pumpkin ( Cucurbita pepo var. styriaca ) seed oil.", "output": "There is no related enetity." }, { "input": "An analytical method was developed and validated for the classification of the geographical origin of pumpkin seeds and oil from Austria, China and Russia.", "output": "There is no related enetity." }, { "input": "The distribution of element traces in pumpkin seed and pumpkin seed oils in relation to the geographical origin of soils of several agricultural farms in Austria was studied in detail.", "output": "There is no related enetity." }, { "input": "Samples from several geographic origins were taken from parts of the pumpkin, pumpkin flesh, seeds, the oil extracted from the seeds and the oil - extraction cake as well as the topsoil on which the plants were grown.", "output": "There is no related enetity." }, { "input": "Plants from different geographical origin show variations of the elemental patterns that are significantly large, reproducible over the years and ripeness period and show no significant influence of oil production procedure, to allow to a discrimination of geographical origin.", "output": "There is no related enetity." }, { "input": "A successful differentiation of oils from different regions in Austria, China and Russia classified with multivariate data analysis is demonstrated.", "output": "There is no related enetity." }, { "input": "Comparison of sample preparation methods, validation of an UPLC - MS / MS procedure for the quantification of tetrodotoxin present in marine gastropods and analysis of pufferfish.", "output": "tetrodotoxin." }, { "input": "Tetrodotoxin ( TTX ) is one of the most potent marine neurotoxins reported.", "output": "Tetrodotoxin, TTX." }, { "input": "The global distribution of this toxin is spreading with the European Atlantic coastline now being affected.", "output": "There is no related enetity." }, { "input": "Climate change and increasing pollution have been suggested as underlying causes for this.", "output": "There is no related enetity." }, { "input": "In the present study, two different sample preparation techniques were used to extract TTX from Trumpet shells and pufferfish samples.", "output": "TTX." }, { "input": "Both extraction procedures ( accelerated solvent extraction ( ASE ) and a simple solvent extraction ) were shown to provide good recoveries ( 80 - 92 % ).", "output": "There is no related enetity." }, { "input": "A UPLC - MS / MS method was developed for the analysis of TTX and validated following the guidelines contained in the Commission Decision 2002 / 657 / EC for chemical contaminant analysis.", "output": "TTX." }, { "input": "The performance of this procedure was demonstrated to be fit for purpose.", "output": "There is no related enetity." }, { "input": "This study is the first report on the use of ASE as a mean for TTX extraction, the use of UPLC - MS / MS for TTX analysis, and the validation of this method for TTX in gastropods.", "output": "TTX, TTX, TTX." }, { "input": "Reversible inhibition of vasoconstriction by thiazolidinediones related to PI3K / Akt inhibition in vascular smooth muscle cells.", "output": "thiazolidinediones." }, { "input": "Thiazolidinediones ( also referred to as glitazones ), agonists for Peroxisome Proliferator - Activated Receptor gamma ( PPAR gamma ), are used for treating type 2 diabetes mellitus, where they decrease insulin resistance and cardiovascular risk.", "output": "Thiazolidinediones, glitazones." }, { "input": "Compounds bearing the thiazolidinedione structure have also been shown to inhibit phosphoinositide 3 - kinase ( PI3K ).", "output": "thiazolidinedione." }, { "input": "Here we tried to elucidate the poorly defined role of PI3K / Akt in the physiology of vascular smooth muscle cell contraction and tested the hypothesis that thiazolidinediones, by affecting the PI3K / Akt pathway, may influence vascular physiology.", "output": "thiazolidinediones." }, { "input": "Isolated rat femoral arteries segments were mounted in a wire myograph and challenged with 100mM KCl or phenylephrine ( PE ), in the absence or presence of troglitazone, rosiglitazone, pioglitazone, LY294002 ( PI3K inhibitor ) and 10 - DEBC ( Akt inhibitor ).", "output": "KCl, phenylephrine, troglitazone, rosiglitazone, pioglitazone, LY294002, 10 - DEBC." }, { "input": "All these compounds dose - dependently inhibited vasoconstriction to KCl or PE; their effect was reversible ( after 60 - 120 min washout ) and not affected by GW9662 ( a PPAR gamma antagonist ) or by N ( G ) - nitro - L - arginine ( LNNA, an inhibitor of NO biosynthesis ).", "output": "KCl, GW9662, N ( G ) - nitro - L - arginine, LNNA, NO." }, { "input": "Analysis of phospho - Akt ( ser 473 ) in lysates from rat arteries ( by immunoblot ) revealed that thiazolidinediones, LY294002 and 10 - DEBC, at the same concentration and kinetics inhibiting vasoconstriction, produced a similar decrease of Akt phosphorylation.", "output": "ser, thiazolidinediones, LY294002, 10 - DEBC." }, { "input": "PI3K / Akt pathway therefore appears to be an important, fast acting, modulator of contraction of vascular smooth muscle.", "output": "There is no related enetity." }, { "input": "Thiazolidinediones decrease vasoconstriction of isolated vessels possibly by inhibiting PI3K / Akt pathway.", "output": "Thiazolidinediones." }, { "input": "Such an effect of glitazones, if occurring in vivo, may impact cardiovascular syndromes related to vasospasm in diabetic patients.", "output": "glitazones." }, { "input": "Neurotoxicity of \" ecstasy \" and its metabolites in human dopaminergic differentiated SH - SY5Y cells.", "output": "ecstasy." }, { "input": "\" Ecstasy \" ( 3, 4 - methylenedioxymethamphetamine or MDMA ) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans.", "output": "Ecstasy, 3 , 4 - methylenedioxymethamphetamine, MDMA." }, { "input": "MDMA metabolites can be major contributors for MDMA neurotoxicity.", "output": "MDMA, MDMA." }, { "input": "This work studied the neurotoxicity of MDMA and its catechol metabolites, alpha - methyldopamine ( alpha - MeDA ) and N - methyl - alpha - methyldopamine ( N - Me - alpha - MeDA ) in human dopaminergic SH - SY5Y cells differentiated with retinoic acid and 12 - O - tetradecanoyl - phorbol - 13 - acetate.", "output": "MDMA, catechol, alpha - methyldopamine, alpha - MeDA, N - methyl - alpha - methyldopamine, N - Me - alpha - MeDA, retinoic acid, 12 - O - tetradecanoyl - phorbol - 13 - acetate." }, { "input": "Differentiation led to SH - SY5Y neurons with higher ability to accumulate dopamine and higher resistance towards dopamine neurotoxicity.", "output": "dopamine, dopamine." }, { "input": "MDMA catechol metabolites were neurotoxic to SH - SY5Y neurons, leading to caspase 3 - independent cell death in a concentration - and time - dependent manner.", "output": "MDMA, catechol." }, { "input": "MDMA did not show a concentration - and time - dependent death.", "output": "MDMA." }, { "input": "Pre - treatment with the antioxidant and glutathione precursor, N - acetylcysteine ( NAC ), resulted in strong protection against the MDMA metabolites ' neurotoxicity.", "output": "glutathione, N - acetylcysteine, NAC, MDMA." }, { "input": "Neither the superoxide radical scavenger, tiron, nor the inhibitor of the dopamine ( DA ) transporter, GBR 12909, prevented the metabolites ' toxicity.", "output": "superoxide, dopamine, GBR 12909." }, { "input": "Cells exposed to alpha - MeDA showed an increase in intracellular glutathione ( GSH ) levels, which, at the 48 h time - point, was not dependent in the activity increase of gamma - glutamylcysteine synthetase ( gamma - GCS ), revealing a possible transient effect.", "output": "alpha - MeDA, glutathione, GSH, gamma - glutamylcysteine." }, { "input": "Importantly, pre - treatment with buthionine sulfoximine ( BSO ), an inhibitor of gamma - GCS, prevented alpha - MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity.", "output": "buthionine sulfoximine, BSO, alpha - MeDA, GSH." }, { "input": "Even so, BSO pre - treatment abolished NAC protective effects against alpha - MeDA neurotoxicity, which were, at least partially, due to GSH de novo synthesis.", "output": "BSO, NAC, alpha - MeDA, GSH." }, { "input": "Inversely, pre - treatment of cells with BSO augmented N - Me - alpha - MeDA - induced neurotoxicity, but only slightly affected NAC neuroprotection.", "output": "BSO, N - Me - alpha - MeDA, NAC." }, { "input": "In conclusion, MDMA catechol metabolites promote differential toxic effects to differentiated dopaminergic human SH - SY5Y cells.", "output": "MDMA, catechol." }, { "input": "Brain tumor immunotherapy: seeing the brain in the body.", "output": "There is no related enetity." }, { "input": "Brain tumor immunotherapy is often interpreted in terms of immune privilege and the blood - brain barrier ( BBB ), but a broader view is warranted.", "output": "There is no related enetity." }, { "input": "The delicate regulatory balance of the immune system is relevant at any site, as are the heterogeneity and plasticity of tumor growth.", "output": "There is no related enetity." }, { "input": "Criteria for tumor antigens, and often the antigens themselves, cut across tumor types.", "output": "There is no related enetity." }, { "input": "Here, this broader view, complemented by current understanding of privilege and the BBB, provides the context for review.", "output": "There is no related enetity." }, { "input": "Future success is likely to exploit simplified methods, used in combination; and similarities - more than differences - between the brain and other sites.", "output": "There is no related enetity." }, { "input": "Serine protease activity of calnuc: regulation by Zn2 + and G proteins.", "output": "Serine, Zn2 +." }, { "input": "The functions of calnuc, a novel Ca ( 2 + ) - binding protein with multiple structural domains and diverse interacting partners, are yet unknown.", "output": "Ca ( 2 + )." }, { "input": "We demonstrate unknown facets of calnuc, which is a serine protease in which Ser - 378 of GXSXG motif, Asp - 328 of DTG motif, and His - 339 form the \" catalytic triad, \" locating the enzyme active site in the C - terminal region.", "output": "serine, Ser, Asp, His, C." }, { "input": "Analogous to the active site of Zn ( 2 + ) carboxypeptidases, calnuc has two high affinity ( K ( d ) ~ 20 nm ), well conserved Zn ( 2 + ) - binding sites near its N terminus, although it is inactive as a peptidase.", "output": "Zn ( 2 + ), Zn ( 2 + ), N." }, { "input": "Zn ( 2 + ) binding allosterically and negatively regulates the serine protease activity of calnuc, inhibition being caused by an \" open to close \" change in its conformation not seen upon Ca ( 2 + ) binding.", "output": "Zn ( 2 + ), serine, Ca ( 2 + )." }, { "input": "Most strikingly, interaction with G protein alpha subunit completely inhibits the enzymatic activity of calnuc.", "output": "There is no related enetity." }, { "input": "We thus illustrate that G proteins and Zn ( 2 + ) act as two \" keys \" that control enzymatic activity of calnuc, arresting it in \" locked \" state.", "output": "Zn ( 2 + )." }, { "input": "Calnuc, therefore, exists dynamically in two different forms, ( i ) as a Ca ( 2 + ) - binding protein in Zn ( 2 + ) - bound form and ( ii ) as a protease in Zn ( 2 + ) - free form, commissioning it to perform multiple functions.", "output": "Ca ( 2 + ), Zn ( 2 + ), Zn ( 2 + )." }, { "input": "A specific and essential role for Na, K - ATPase alpha 3 in neurons co - expressing alpha 1 and alpha 3.", "output": "Na, K." }, { "input": "Most neurons co - express two catalytic isoforms of Na, K - ATPase, the ubiquitous alpha 1, and the more selectively expressed alpha 3.", "output": "Na, K." }, { "input": "Although neurological syndromes are associated with alpha 3 mutations, the specific role of this isoform is not completely understood.", "output": "There is no related enetity." }, { "input": "Here, we used electrophysiological and Na ( + ) imaging techniques to study the role of alpha 3 in central nervous system neurons expressing both isoforms.", "output": "Na ( + )." }, { "input": "Under basal conditions, selective inhibition of alpha 3 using a low concentration of the cardiac glycoside, ouabain, resulted in a modest increase in intracellular Na ( + ) concentration ( [ Na ( + ) ] ( i ) ) accompanied by membrane potential depolarization.", "output": "ouabain, Na ( + ), Na ( + )." }, { "input": "When neurons were challenged with a large rapid increase in [ Na ( + ) ] ( i ), similar to what could be expected following suprathreshold neuronal activity, selective inhibition of alpha 3 almost completely abolished the capacity to restore [ Na ( + ) ] ( i ) in soma and dendrite.", "output": "Na ( + ), Na ( + )." }, { "input": "Recordings of Na, K - ATPase specific current supported the notion that when [ Na ( + ) ] ( i ) is elevated in the neuron, alpha 3 is the predominant isoform responsible for rapid extrusion of Na ( + ).", "output": "Na, K, Na ( + ), Na ( + )." }, { "input": "Low concentrations of ouabain were also found to disrupt cortical network oscillations, providing further support for the importance of alpha 3 function in the central nervous system.", "output": "ouabain." }, { "input": "The alpha isoforms express a well conserved protein kinase A consensus site, which is structurally associated with an Na ( + ) binding site.", "output": "Na ( + )." }, { "input": "Following activation of protein kinase A, both the alpha 3 - dependent current and restoration of dendritic [ Na ( + ) ] ( i ) were significantly attenuated, indicating that alpha 3 is a target for phosphorylation and may participate in short term regulation of neuronal function.", "output": "Na ( + )." }, { "input": "Laser synthesis of ligand - free bimetallic nanoparticles for plasmonic applications.", "output": "There is no related enetity." }, { "input": "A picosecond laser ablation approach has been developed for the synthesis of ligand - free AuAg bimetallic NPs where the relative amount of Ag is controlled in situ through a laser shielding effect.", "output": "AuAg, Ag." }, { "input": "Various measurements, such as optical spectroscopy, transmission electron microscopy combined with energy dispersive X - ray spectroscopy and inductively coupled plasma optical emission spectrometry, revealed the generation of homogenous 15 nm average size bimetallic NPs with different compositions and tunable localized surface plasmon resonance.", "output": "There is no related enetity." }, { "input": "Furthermore, ligand - free metallic nanoparticles with respect to chemically synthesized nanoparticles display outstanding properties, i. e. featureless Raman background spectrum, which is a basic requirement in many plasmonic applications such as Surface Enhanced Raman Spectroscopy.", "output": "There is no related enetity." }, { "input": "Various molecules were chemisorbed on the nanoparticle and SERS investigations were carried out, by varying the laser wavelength.", "output": "There is no related enetity." }, { "input": "The SERS enhancement factor for AuAg bimetallic NPs shows an enhancement factor of about 5. 7 x 10 ( 5 ) with respect to the flat AuAg surface.", "output": "AuAg, AuAg." }, { "input": "RNF4 is required for DNA double - strand break repair in vivo.", "output": "There is no related enetity." }, { "input": "Unrepaired DNA double - strand breaks ( DSBs ) cause genetic instability that leads to malignant transformation or cell death.", "output": "There is no related enetity." }, { "input": "Cells respond to DSBs with the ordered recruitment of signaling and repair proteins to the sites of DNA lesions.", "output": "There is no related enetity." }, { "input": "Coordinated protein SUMOylation and ubiquitylation have crucial roles in regulating the dynamic assembly of protein complexes at these sites.", "output": "There is no related enetity." }, { "input": "However, how SUMOylation influences protein ubiquitylation at DSBs is poorly understood.", "output": "There is no related enetity." }, { "input": "We show herein that Rnf4, an E3 ubiquitin ligase that targets SUMO - modified proteins, accumulates in DSB repair foci and is required for both homologous recombination ( HR ) and non - homologous end joining repair.", "output": "There is no related enetity." }, { "input": "To establish a link between Rnf4 and the DNA damage response ( DDR ) in vivo, we generated an Rnf4 allelic series in mice.", "output": "There is no related enetity." }, { "input": "We show that Rnf4 - deficiency causes persistent ionizing radiation - induced DNA damage and signaling, and that Rnf4 - deficient cells and mice exhibit increased sensitivity to genotoxic stress.", "output": "There is no related enetity." }, { "input": "Mechanistically, we show that Rnf4 targets SUMOylated MDC1 and SUMOylated BRCA1, and is required for the loading of Rad51, an enzyme required for HR repair, onto sites of DNA damage.", "output": "There is no related enetity." }, { "input": "Similarly to inactivating mutations in other key regulators of HR repair, Rnf4 deficiency leads to age - dependent impairment in spermatogenesis.", "output": "There is no related enetity." }, { "input": "These findings identify Rnf4 as a critical component of the DDR in vivo and support the possibility that Rnf4 controls protein localization at DNA damage sites by integrating SUMOylation and ubiquitylation events.", "output": "There is no related enetity." }, { "input": "Allosteric modulation of a chemogenetically modified G protein - coupled receptor.", "output": "There is no related enetity." }, { "input": "Designer receptors exclusively activated by designer drugs ( DREADDs ) are chemogenetically modified muscarinic acetylcholine receptors ( mAChRs ) that have minimal responsiveness to acetylcholine ( ACh ) but are potently and efficaciously activated by an otherwise inert synthetic ligand, clozapine - N - oxide ( CNO ).", "output": "acetylcholine, acetylcholine, ACh, clozapine - N - oxide, CNO." }, { "input": "DREADDs have been used as tools for selectively modulating signal transduction pathways in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Recent comprehensive studies have validated how the pharmacology of a CNO - bound DREADD mirrors that of an ACh - bound wild - type ( WT ) mAChR.", "output": "CNO, ACh." }, { "input": "However, nothing is known about whether this equivalence extends to the allosteric modulation of DREADDs by small molecules.", "output": "There is no related enetity." }, { "input": "To address this, we investigated the actions at an M ( 1 ) DREADD of benzyl quinolone carboxylic acid ( BQCA ), a positive allosteric modulator of ACh binding and function that is known to behave according to a simple two - state mechanism at the WT receptor.", "output": "benzyl quinolone carboxylic acid, BQCA, ACh." }, { "input": "We found that allosteric modulation of the CNO - bound DREADD receptor is not equivalent to the corresponding modulation of the ACh - bound WT receptor.", "output": "CNO, ACh." }, { "input": "We also found that BQCA engenders stimulus bias at the M ( 1 ) DREADD, having differential types of cooperativity depending on the signaling pathway.", "output": "BQCA." }, { "input": "Furthermore, the modulation of ACh itself by BQCA at the DREADD is not compatible with the two - state model that we previously applied to the M ( 1 ) WT receptor.", "output": "ACh, BQCA." }, { "input": "Upregulation of Mer receptor tyrosine kinase signaling attenuated lipopolysaccharide - induced lung inflammation.", "output": "tyrosine." }, { "input": "Mer receptor tyrosine kinase ( Mer ) signaling plays a central role in the intrinsic inhibition of the inflammatory response to Toll - like receptor activation.", "output": "tyrosine." }, { "input": "Previously, we found that lung Mer protein expression decreased after lipopolysaccharide ( LPS ) treatment due to enhanced Mer cleavage.", "output": "There is no related enetity." }, { "input": "The purpose of the present study was to examine whether pharmacologically restored membrane - bound Mer expression upregulates the Mer signaling pathways and suppresses lung inflammatory responses.", "output": "There is no related enetity." }, { "input": "Pretreatment with the ADAM17 ( a disintegrin and metalloproteinase - 17 ) inhibitor TAPI - 0 ( tumor necrosis factor alpha protease inhibitor - 0 ) reduced LPS - induced production of soluble Mer protein in bronchoalveolar lavage ( BAL ) fluid, restored membrane - bound Mer expression, and increased Mer activation in alveolar macrophages and lungs after LPS treatment.", "output": "TAPI - 0." }, { "input": "TAPI - 0 also enhanced Mer downstream signaling, including phosphorylation of protein kinase b, focal adhesion kinase, and signal transducer and activator of transcription 1.", "output": "TAPI - 0." }, { "input": "As expected from enhanced Mer signaling, TAPI - 0 also augmented suppressor of cytokine signaling - 1 and - 3 mRNA and protein levels and inhibited nuclear factor kappa B activation at 4 and 24 hours after LPS treatment.", "output": "TAPI - 0." }, { "input": "TAPI - 0 suppressed LPS - induced inflammatory cell accumulation, total protein level elevation in BAL fluid, and production of inflammatory mediators, including tumor necrosis factor - alpha, interleukin - 1 beta, and macrophage inflammatory protein - 2.", "output": "TAPI - 0." }, { "input": "Additionally, the effects of TAPI - 0 on the activation of Mer signaling and the production of inflammatory responses could be reversed by cotreatment with specific Mer - neutralizing antibody.", "output": "TAPI - 0." }, { "input": "Restored Mer protein expression by treatment with TAPI - 0 efficiently prevents the inflammatory cascade during acute lung injury.", "output": "TAPI - 0." }, { "input": "Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1.", "output": "There is no related enetity." }, { "input": "Achieving the vision of identifying and quantifying cancer - related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion.", "output": "There is no related enetity." }, { "input": "Delineated here are the design and evaluation of a newly synthesized turn - on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins.", "output": "There is no related enetity." }, { "input": "Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone - based enzyme substrate.", "output": "naphthalimide, quinone." }, { "input": "Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two - electron reduction of the sterically and conformationally restricted quinone substrate by the cancer - associated human NAD ( P ) H: quinone oxidoreductase isozyme 1 ( hNQO1 ).", "output": "quinone, quinone, quinone." }, { "input": "Successes of the approach include rapid differentiation of NQO1 - expressing and - nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two - photon microscopy.", "output": "There is no related enetity." }, { "input": "The potential for use of the turn - on probe in longer - term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability.", "output": "There is no related enetity." }, { "input": "Bioinspired and highly oriented clay nanocomposites with a xyloglucan biopolymer matrix: extending the range of mechanical and barrier properties.", "output": "There is no related enetity." }, { "input": "The development of clay bionanocomposites requires processing routes with nanostructural control.", "output": "There is no related enetity." }, { "input": "Moreover, moisture durability is a concern with water - soluble biopolymers.", "output": "There is no related enetity." }, { "input": "Here, oriented bionanocomposite coatings with strong in - plane orientation of clay platelets are for the first time prepared by continuous water - based processing.", "output": "There is no related enetity." }, { "input": "Montmorillonite ( MTM ) and a \" new \" unmodified biological polymer ( xyloglucan ( XG ) ) are combined.", "output": "Montmorillonite, MTM." }, { "input": "The resulting nanocomposites are characterized by FE - SEM, TEM, and XRD.", "output": "There is no related enetity." }, { "input": "XG adsorption on MTM is measured by quartz crystal microbalance analysis.", "output": "MTM, quartz." }, { "input": "Mechanical and gas barrier properties are measured, also at high relative humidity.", "output": "There is no related enetity." }, { "input": "The reinforcement effects are modeled.", "output": "There is no related enetity." }, { "input": "XG dimensions in composites are estimated using atomistic simulations.", "output": "There is no related enetity." }, { "input": "The nanostructure shows highly oriented and intercalated clay platelets.", "output": "There is no related enetity." }, { "input": "The reinforcement efficiency and effects on barrier properties are remarkable and are likely to be due to highly oriented and well - dispersed MTM and strong XG - MTM interactions.", "output": "MTM, MTM." }, { "input": "Properties are well preserved in humid conditions and the reasons for this are discussed.", "output": "There is no related enetity." }, { "input": "Hydrogen evolution from Pt / Ru - coated p - type WSe2 photocathodes.", "output": "Hydrogen, Pt, Ru." }, { "input": "Crystalline p - type WSe ( 2 ) has been grown by a chemical vapor transport method.", "output": "There is no related enetity." }, { "input": "After deposition of noble metal catalysts, p - WSe ( 2 ) photocathodes exhibited thermodynamically based photoelectrode energy - conversion efficiencies of > 7 % for the hydrogen evolution reaction under mildly acidic conditions, and were stable under cathodic conditions for at least 2 h in acidic as well as in alkaline electrolytes.", "output": "hydrogen." }, { "input": "The open circuit potentials of the photoelectrodes in contact with the H ( + ) / H ( 2 ) redox couple were very close to the bulk recombination / diffusion limit predicted from the Shockley diode equation.", "output": "H ( + ), H ( 2 )." }, { "input": "Only crystals with a prevalence of surface step edges exhibited a shift in flat - band potential as the pH was varied.", "output": "There is no related enetity." }, { "input": "Spectral response data indicated effective minority - carrier diffusion lengths of ~ 1 mu m, which limited the attainable photocurrent densities in the samples to ~ 15 mA cm ( - 2 ) under 100 mW cm ( - 2 ) of Air Mass 1. 5G illumination.", "output": "There is no related enetity." }, { "input": "Triggered indistinguishable single photons with narrow line widths from site - controlled quantum dots.", "output": "There is no related enetity." }, { "input": "In this Letter, we present narrow line width ( 7 mu eV ), nearly background - free single - photon emission ( g ( ( 2 ) ) ( 0 ) = 0. 02 ) and highly indistinguishable photons ( V = 0. 73 ) from site - controlled In ( Ga ) As / GaAs quantum dots.", "output": "In ( Ga ) As, GaAs." }, { "input": "These excellent properties have been achieved by combining overgrowth on ex situ pit - patterned substrates with vertical stacking of spectrally distinct quantum dot layers.", "output": "There is no related enetity." }, { "input": "Our study paves the way for large - scale integration of quantum dots into quantum photonic circuits as indistinguishable single - photon sources.", "output": "There is no related enetity." }, { "input": "Synthesis, biological evaluation, and molecular modeling of glycyrrhizin derivatives as potent high - mobility group box - 1 inhibitors with anti - heart - failure activity in vivo.", "output": "glycyrrhizin." }, { "input": "Novel glycyrrhizin ( GL ) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C - 30.", "output": "glycyrrhizin, amine, amino acid, carbohydrate." }, { "input": "Their inhibitory effects on high - mobility group box 1 ( HMGB1 ) were evaluated using a cell - based lipopolysaccharide ( LPS ) induced tumor necrosis factor alpha ( TNF - alpha ) release study.", "output": "There is no related enetity." }, { "input": "Compounds 10, 12, 18 - 20, 23, and 24, which had substituents introduced at C - 30, demonstrated moderate HMGB1 inhibition with ED 5 0 values ranging from 337 to 141 mu M, which are values comparable to that of the leading GL compound ( 1 ) ( ED 5 0 = 70 mu M ).", "output": "There is no related enetity." }, { "input": "Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors.", "output": "There is no related enetity." }, { "input": "These compounds were able to extend the survival of mice with chronic heart failure ( CHF ) and acute heart failure ( AHF ), respectively.", "output": "There is no related enetity." }, { "input": "In addition, molecular modeling studies were performed to support the biological data.", "output": "There is no related enetity." }, { "input": "Ultrasensitive broadband probing of molecular vibrational modes with multifrequency optical antennas.", "output": "There is no related enetity." }, { "input": "Optical antennas represent an enabling technology for enhancing the detection of molecular vibrational signatures at low concentrations and probing the chemical composition of a sample in order to identify target molecules.", "output": "There is no related enetity." }, { "input": "However, efficiently detecting different vibrational modes to determine the presence ( or the absence ) of a molecular species requires a multispectral interrogation in a window of several micrometers, as many molecules present informative fingerprint spectra in the mid - infrared between 2. 5 and 10 mu m.", "output": "There is no related enetity." }, { "input": "As most nanoantennas exhibit a narrow - band response because of their dipolar nature, they are not suitable for such applications.", "output": "There is no related enetity." }, { "input": "Here, we propose the use of multifrequency optical antennas designed for operating with a bandwidth of several octaves.", "output": "There is no related enetity." }, { "input": "We demonstrate that surface - enhanced infrared absorption gains in the order of 10 ( 5 ) can be easily obtained in a spectral window of 3 mu m with attomolar concentrations of molecules, providing new opportunities for ultrasensitive broadband detection of molecular species via vibrational spectroscopy techniques.", "output": "There is no related enetity." }, { "input": "Production of 1 - lactulose and lactulose using commercial beta - galactosidase from Kluyveromyces lactis in the presence of fructose.", "output": "1 - lactulose, lactulose, fructose." }, { "input": "Production of 1 - lactulose and lactulose using commercial beta - galactosidase DSM Maxilact (R) 5000 in the presence of fructose was investigated.", "output": "1 - lactulose, lactulose, fructose." }, { "input": "Experiments were performed at 40 degrees C and pH 7. 5.", "output": "There is no related enetity." }, { "input": "Lactose starting concentration was constantly 250 g / l.", "output": "Lactose." }, { "input": "A novel transgalactosylation product 1 - lactulose was detected besides lactulose.", "output": "1 - lactulose, lactulose." }, { "input": "Effects of fructose concentration, reaction time and enzyme concentration on transgalactosylation reactions were discussed.", "output": "fructose." }, { "input": "In all reactions, the yield ratio 1 - lactulose: lactulose was close to 3: 1 due to the regioselectivity of beta - galactosidase.", "output": "1 - lactulose, lactulose." }, { "input": "The maximum production of 1 - lactulose and lactulose was approximately 22 and 8 g / l, respectively, when fructose concentration was increased to 100 g / l.", "output": "1 - lactulose, lactulose, fructose." }, { "input": "Lactose hydrolysis was significantly retarded since fructose strongly attracted water molecules.", "output": "Lactose, fructose." }, { "input": "Higher enzyme concentration can accelerate transgalactosylation reactions without affecting the maximum production of transgalactosylation products.", "output": "There is no related enetity." }, { "input": "Fructose was a more preferred galactosyl acceptor than lactose, since the synthesis of galactooligosacchairdes was found to be absolutely inhibited in the presence of fructose.", "output": "Fructose, galactosyl, lactose, fructose." }, { "input": "Effects of chemical interesterification on the physicochemical, microstructural and thermal properties of palm stearin, palm kernel oil and soybean oil blends.", "output": "stearin." }, { "input": "Blends of palm stearin ( PS ), palm kernel oil ( PKO ) and soybean oil ( SBO ) at certain proportions were formulated using a mixture design based on simplex - lattice ( Design Expert 8. 0. 4 Stat - Ease Inc., Minneapolis, 2010 ).", "output": "stearin." }, { "input": "All the 10 oil blends were subjected to chemical interesterification ( CIE ) using sodium methoxide as the catalyst.", "output": "sodium methoxide." }, { "input": "The solid fat content ( SFC ), triacylglycerol ( TAG ) composition, thermal properties ( DSC ), polymorphism and microstructural properties were studied.", "output": "triacylglycerol, TAG." }, { "input": "Palm - based trans - free table margarine containing ternary mixture of PS / PKO / SBO [ 49 / 20 / 31 ( w / w ) ], was optimally formulated through analysis of multiple isosolid diagrams and was found to have quite similar SMP and SFC profile as compared to the commercial table margarine.", "output": "There is no related enetity." }, { "input": "This study has shown chemical interesterification are effective in modifying the physicochemical properties of palm stearin, palm kernel oil, soybean oil and their mixtures.", "output": "stearin." }, { "input": "Discrimination of cabbage ( Brassica rapa ssp. pekinensis ) cultivars grown in different geographical areas using (1) H NMR - based metabolomics.", "output": "(1) H." }, { "input": "Cabbage ( Brassica rapa ssp. pekinensis ) is one of the most popular foods in Asia and is widely cultivated in many countries for the production of lightly fermented vegetables.", "output": "There is no related enetity." }, { "input": "In this study, metabolomic analysis was performed to distinguish two cultivars of cabbage grown in different geographical areas, Korea and China, using (1) H NMR spectroscopy coupled with multivariate statistical analysis.", "output": "(1) H." }, { "input": "Principal component analysis ( PCA ) showed clear discrimination between extracts of cabbage grown in Korea and China for two different cultivars ( Chunmyeong and Chunjung ).", "output": "There is no related enetity." }, { "input": "The major biochemicals ( metabolites ) that contributed to discrimination between cabbages grown in the two regions were 4 - aminobutyrate ( GABA ), acetate, asparagine, leucine, isoleucine, O - phosphocholine, phenylacetate, phenylalanine, succinate, sucrose, tyrosine, and valine.", "output": "4 - aminobutyrate, GABA, acetate, asparagine, leucine, isoleucine, O - phosphocholine, phenylacetate, phenylalanine, succinate, sucrose, tyrosine, valine." }, { "input": "These results suggest that the levels of the major metabolites that differ significantly between cabbages grown in these two areas were influenced by environmental factors such as climate and geology.", "output": "There is no related enetity." }, { "input": "Our study demonstrates that (1) H NMR based on metabolomics, coupled with multivariate statistics, can be applied to identify the regions of cultivation of various cabbage cultivars.", "output": "(1) H." }, { "input": "Effect of red wines with different in vitro antioxidant activity on oxidative stress of high - fat diet rats.", "output": "There is no related enetity." }, { "input": "It is not known if there is a correlation between in vitro and in vivo antioxidant activity of wines.", "output": "There is no related enetity." }, { "input": "Thus, in the present study, rats were fed with a high - fat diet to induce inflammation and oxidative stress, and received supplementation ( 1. 0 mL / day ) containing water or three red wine samples characterised by high ( 41. 1 mmol TE / L ), medium ( 35. 7 mmol TE / L ) and low ( 14. 4 mmol TE / L ) in vitro antioxidant activity.", "output": "There is no related enetity." }, { "input": "A correlation was observed between in vitro antioxidant activity measured in the wines and in vivo antioxidant activity measured in plasma ( r = + 0. 49, p = 0. 011 ).", "output": "There is no related enetity." }, { "input": "In liver, only the wine containing the highest in vitro antioxidant activity was able to reduce malondialdehyde concentration.", "output": "malondialdehyde." }, { "input": "Groups supplemented with wines containing lower in vitro antioxidant activity showed an increase in antioxidant enzyme activity.", "output": "There is no related enetity." }, { "input": "We concluded that the correlation between in vitro and in vivo antioxidant activity depends on the biomarker selected to evaluate the oxidative stress.", "output": "There is no related enetity." }, { "input": "Determination of mercury in rice by MSFIA and cold vapour atomic fluorescence spectrometry.", "output": "mercury." }, { "input": "In the present paper the use of a MSFIA system for determination of mercury in rice by cold vapour atomic fluorescence spectrometry ( CV AFS ) is proposed.", "output": "mercury." }, { "input": "The sample digestion is performed in a microwave oven using nitric acid and hydrogen peroxide.", "output": "nitric acid, hydrogen peroxide." }, { "input": "The experimental conditions for vapour generation were determined using a full two - level factorial design involving the following factors: nitric acid and tin chloride concentrations and sample flow rate.", "output": "nitric acid, tin chloride." }, { "input": "Employing the conditions optimised, the method allows the determination of mercury using the external calibration technique with aqueous standards.", "output": "mercury." }, { "input": "The reached limits of detection and quantification were 0. 48 and 1. 61 ng g - (1) respectively, and the precision ( as relative standard deviation ) was 3. 28 % and 1. 56 % for rice samples with a mercury content of 3. 63 and 5. 81 ng g - (1), respectively.", "output": "mercury." }, { "input": "The method accuracy was confirmed analysing a certified reference material of rice flour furnished by National Institute of Standard and Technology.", "output": "There is no related enetity." }, { "input": "The interference of nitrous acid and nitrous oxides are removed using potassium dichromate.", "output": "nitrous acid, nitrous oxides, potassium dichromate." }, { "input": "The method was applied to mercury determination in twelve rice samples acquired in Palma de Mallorca ( Spain ) between the months of January and April of 2012.", "output": "mercury." }, { "input": "The mercury content found varied from 2. 15 to 7. 25 ng g - (1).", "output": "mercury." }, { "input": "These results agree with those reported by others authors.", "output": "There is no related enetity." }, { "input": "Composition and distribution of the main active components in selenium - enriched fruit bodies of Cordyceps militaris link.", "output": "selenium." }, { "input": "Selenium - enriched Cordyceps militaris fruit bodies are industrially cultivated as functional food or medicinal food in China and southeast Asia.", "output": "Selenium." }, { "input": "However, composition of selenium compounds and distribution of the main bioactive components are still unknown.", "output": "selenium." }, { "input": "In the selenium - enriched fruit bodies, the main soluble selenium compounds of low molecular weight were identified as SeMet ( selenomethionine ), and the main selenium compounds bound in proteins were identified as SeMet and SeCys ( methylselenocysteine ).", "output": "selenium, selenium, SeMet, selenomethionine, selenium, SeMet, SeCys, methylselenocysteine." }, { "input": "Trace minerals as Se ( selenium ), Zn ( zinc ), Fe ( iron ) and the main active components as adenosine, cordycepin and carotenoids were mostly distributed in the terminal of fruit bodies, while P ( phosphorus ) and K ( potassium ) were evenly distributed in the fruit bodies.", "output": "Se, selenium, Zn, zinc, Fe, iron, adenosine, cordycepin, P, phosphorus, K, potassium." }, { "input": "The results indicated that terminal of the fruit bodies should be the better materials for production of advanced functional food.", "output": "There is no related enetity." }, { "input": "So cultivation of relatively short and thick fruit bodies with bigger terminals deserves further research.", "output": "There is no related enetity." }, { "input": "Detection of trace metal in distilled alcoholic drinks.", "output": "alcoholic." }, { "input": "The presence of trace metal cadmium assay was investigated with a copper immobilized on a graphite carbon electrode ( GPC ), the modified property of which was determined with handheld voltammetric systems.", "output": "cadmium, copper, graphite, carbon." }, { "input": "Following the determination of the analytical stripping conditions of 0. 45 V amplitude, 30 Hz frequency, - 1. 4 V initial potential, and 4. 0 mV increment potential, only a 60 - s experimental accumulation time was used.", "output": "There is no related enetity." }, { "input": "Using these conditions, the analytical detection limit approached the nano range.", "output": "There is no related enetity." }, { "input": "At this condition, the analytical application was performed on distilled alcoholic drinks for food manufacturing systems.", "output": "alcoholic." }, { "input": "This developed technique is faster and less costly than the common voltammetric and spectrophotometric methods.", "output": "There is no related enetity." }, { "input": "Anti - inflammatory norditerpenoids from the soft coral Sinularia maxima.", "output": "norditerpenoids." }, { "input": "Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12 - hydroxy - scabrolide A ( 2 ) and 13 - epi - scabrolide C ( 6 ).", "output": "norditerpenoids, 12 - hydroxy - scabrolide A, 13 - epi - scabrolide C." }, { "input": "The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry ( FTICR - MS ) and both one - and two - dimensional nuclear magnetic resonance ( 1D and 2D NMR, respectively ), in comparison with reported data.", "output": "There is no related enetity." }, { "input": "Compound 6 potently inhibited IL - 12 and IL - 6 production in LPS - stimulated bone marrow derived dendritic ( BMDCs ) with IC ( 50 ) values of 5. 30 +/- 0. 21 and 13. 12 +/- 0. 64 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Compound 1 exhibited moderate inhibitory activity against IL - 12 and IL - 6 production with IC ( 50 ) values of 23. 52 +/- 1. 37 and 69. 85 +/- 4. 11 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Further exploration of M 1 allosteric agonists: subtle structural changes abolish M 1 allosteric agonism and result in pan - mAChR orthosteric antagonism.", "output": "There is no related enetity." }, { "input": "This letter describes the further exploration of two series of M ( 1 ) allosteric agonists, TBPB and VU0357017, previously reported from our lab.", "output": "TBPB, VU0357017." }, { "input": "Within the TPBP scaffold, either electronic or steric perturbations to the central piperidine ring led to a loss of selective M ( 1 ) allosteric agonism and afforded pan - mAChR antagonism, which was demonstrated to be mediated via the orthosteric site.", "output": "TPBP, piperidine." }, { "input": "Additional SAR around a related M ( 1 ) allosteric agonist family ( VU0357017 ) identified similar, subtle ' molecular switches ' that modulated modes of pharmacology from allosteric agonism to pan - mAChR orthosteric antagonism.", "output": "VU0357017." }, { "input": "Therefore, all of these ligands are best classified as bi - topic ligands that possess high affinity binding at an allosteric site to engender selective M ( 1 ) activation, but all bind, at higher concentrations, to the orthosteric ACh site, leading to non - selective orthosteric site binding and mAChR antagonism.", "output": "There is no related enetity." }, { "input": "Interactions of neuropathy inducers and potentiators / promoters with soluble esterases.", "output": "There is no related enetity." }, { "input": "Organophosphorus compounds ( OPs ) cause neurotoxic disorders through interactions with well - known target esterases, such as acetylcholinesterase and neuropathy target esterase ( NTE ).", "output": "Organophosphorus." }, { "input": "However, the OPs can potentially interact with other esterases of unknown significance.", "output": "There is no related enetity." }, { "input": "Therefore, identifying, characterizing and elucidating the nature and functional significance of the OP - sensitive pool of esterases in the central and peripheral nervous systems need to be investigated.", "output": "There is no related enetity." }, { "input": "Kinetic models have been developed and applied by considering multi - enzymatic systems, inhibition, spontaneous reactivation, the chemical hydrolysis of the inhibitor and \" ongoing inhibition \" ( inhibition during the substrate reaction time ).", "output": "There is no related enetity." }, { "input": "These models have been applied to discriminate enzymatic components among the esterases in nerve tissues of adult chicken, this being the experimental model for delayed neuropathy and to identify different modes of interactions between OPs and soluble brain esterases.", "output": "There is no related enetity." }, { "input": "The covalent interaction with the substrate catalytic site has been demonstrated by time - progressive inhibition during ongoing inhibition.", "output": "There is no related enetity." }, { "input": "The interaction of sequential exposure to an esterase inhibitor has been tested in brain soluble fraction where exposure to one inhibitor at a non inhibitory concentration has been seen to modify sensitivity to further exposure to others.", "output": "There is no related enetity." }, { "input": "The effect has been suggested to be caused by interaction with sites other than the inhibition site at the substrate catalytic site.", "output": "There is no related enetity." }, { "input": "This kind of interaction among esterase inhibitors should be considered to study the potentiation / promotion phenomenon, which is observed when some esterase inhibitors enhance the severity of the OP induced neuropathy if they are dosed after a non neuropathic low dose of a neuropathy inducer.", "output": "There is no related enetity." }, { "input": "Selective induction of glutathione S - transferases in round spermatids from the Brown - Norway rat by the chemotherapeutic regimen for testicular cancer.", "output": "glutathione, S." }, { "input": "Chemotherapeutic drugs can affect DNA in male germ cells, thereby impacting on the integrity of the genome transmitted to offspring.", "output": "There is no related enetity." }, { "input": "Drug metabolizing enzymes can protect cells from xenobiotic insult.", "output": "There is no related enetity." }, { "input": "We analyzed the expression pattern of such enzymes in isolated round spermatids from rats exposed to drugs used to treat testicular cancer: bleomycin, etoposide, and cisplatin ( BEP ).", "output": "bleomycin, etoposide, cisplatin, BEP." }, { "input": "The number of isozymes expressed and the overall relative expression values were highest for the glutathione S - transferases ( GSTs ).", "output": "glutathione, S." }, { "input": "Moreover, BEP treatment significantly increased the expression of 8 GSTs and 3 aldehyde dehydrogenases.", "output": "BEP, aldehyde." }, { "input": "Increased expression of GST isozymes was confirmed by qRT - PCR and Western blot analysis.", "output": "There is no related enetity." }, { "input": "Although Gst genes can be targets for epigenetic modifications, promoter DNA methylation was not affected by BEP treatment.", "output": "BEP." }, { "input": "As GSTs are involved in drug resistance mechanisms, we hypothesize that BEP induction of GST expression may lead to the survival of damaged germ cells and the production of abnormal sperm.", "output": "BEP." }, { "input": "Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: investigation of the role of gender.", "output": "Resveratrol." }, { "input": "Resveratrol ( 3, 5, 4 ' - trihydroxy - trans stilbene ) is commonly recognized by its antioxidant properties.", "output": "Resveratrol, 3 , 5 , 4 ' - trihydroxy - trans stilbene." }, { "input": "Despite its beneficial qualities, the toxic effects of this natural compound are still unknown.", "output": "There is no related enetity." }, { "input": "Since mitochondria are essential to support the energy - dependent regulation of several cell functions, the objective of this study was to evaluate resveratrol effects on rat brain and liver mitochondrial fractions from male and females regarding oxidative stress and bioenergetics.", "output": "resveratrol." }, { "input": "No basal differences were observed between mitochondrial fractions from males and females, except in liver mitochondria, the generation of H ( 2 ) O ( 2 ) by the respiratory chain is lower for female preparations.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Resveratrol inhibited lipid peroxidation in preparations from both genders and organs.", "output": "Resveratrol." }, { "input": "Furthermore, brain mitochondria in both gender groups appeared susceptible to resveratrol as seen by a decrease in state 3 respiration and alterations in mitochondrial membrane potential fluctuations during ADP phosphorylation.", "output": "resveratrol, ADP." }, { "input": "As opposed, liver mitochondria were less affected by resveratrol.", "output": "resveratrol." }, { "input": "Our data also demonstrates that resveratrol inhibits complex I activity in all mitochondrial preparations.", "output": "resveratrol." }, { "input": "The results suggest that brain mitochondria appear to be more susceptible to resveratrol effects, and gender appears to play a minor role.", "output": "resveratrol." }, { "input": "It remains to be determined if resveratrol effects on brain mitochondria contribute to deterioration of mitochondrial function or instead to mediate hormesis - mediated events.", "output": "resveratrol." }, { "input": "The role of efflux transporters on the transport of highly toxic aconitine, mesaconitine, hypaconitine, and their hydrolysates, as determined in cultured Caco - 2 and transfected MDCKII cells.", "output": "aconitine, mesaconitine, hypaconitine." }, { "input": "Aconitum alkaloids including aconitine ( AC ), mesaconitine ( MA ), hypaconitine ( HA ), are highly toxic.", "output": "Aconitum alkaloids, aconitine, mesaconitine, hypaconitine." }, { "input": "Their hydrolysates, such as benzoylaconine ( BAC ), benzoylmesaconine ( BMA ), benzoylhypaconine ( BHA ), aconine, and mesaconine, are considerably less toxic.", "output": "benzoylaconine, BAC, benzoylmesaconine, BMA, benzoylhypaconine, BHA, aconine, mesaconine." }, { "input": "Efflux transporters, including P - glycoprotein ( P - gp ), breast cancer resistance protein ( BCRP ), and multidrug resistance - associated protein isoform 2 ( MRP2 ), act as a first line of defence and play key roles in toxicity prevention.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to determine the role of efflux transporters in the transport of Aconitum alkaloids using cultured Caco - 2, MDR1 - MDCKII and BCRP - MDCKII cells.", "output": "Aconitum alkaloids." }, { "input": "Bidirectional transport assays of the Aconitum alkaloids were performed with or without P - gp ( cyclosporine A and verapamil ), BCRP ( Ko143 ) and MRP2 ( MK571 ) inhibitors.", "output": "Aconitum alkaloids, cyclosporine A, verapamil, Ko143, MK571." }, { "input": "The efflux ratios ( Er ) of AC, MA, and HA in Caco - 2 cells were 34. 6 +/- 4. 2, 29. 7 +/- 2. 1, and 15. 6 +/- 2. 1, respectively; those of BAC, BMA, and BHA were approximately 4, and those of aconine and mesaconine were equal to 1.", "output": "BAC, BMA, BHA, aconine, mesaconine." }, { "input": "The Er values of AC, MA, and HA in MDR1 - MDCKII and BCRP - MDCKII cells were significantly higher than those in parental MDCKII cells.", "output": "There is no related enetity." }, { "input": "Taken together the results of Er values and intracellular amounts in the presence of inhibitors, P - gp and BCRP were involved in the transport of AC, MA and HA; and MRP2 might transport AC, MA, HA, BAC, BMA and BHA.", "output": "BAC, BMA, BHA." }, { "input": "Inhibitory effect of 1 alpha, 25 - dihydroxyvitamin D 3 on excretion of JBP485 via organic anion transporters in rats.", "output": "1 alpha , 25 - dihydroxyvitamin D 3, JBP485." }, { "input": "The aim of this study was to investigate the pharmacokinetic mechanism of interaction between JBP485 and 1 alpha, 25 - dihydroxyvitamin D ( 3 ) [ 1, 25 ( OH ) ( 2 ) D ( 3 ) ].", "output": "JBP485, 1 alpha , 25 - dihydroxyvitamin D ( 3 ), 1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "Rats were injected intraperitoneally with 0. 64 nmol / kg / day 1, 25 ( OH ) ( 2 ) D ( 3 ) in 1 ml / kg corn oil for 5 days.", "output": "1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "The plasma and urine concentrations of JBP485 after intravenous administration and the uptake of JBP485 in kidney slices in vitro were determined by liquid chromatography / tandem mass spectrometry.", "output": "JBP485, JBP485." }, { "input": "Quantitative polymerase chain reaction, western blotting, immunohistochemical analysis and immunofluorescence were used to determine the changes in the expression of organic anion transporter ( Oat ) 1 and Oat3 in rat kidney in response to 1, 25 ( OH ) ( 2 ) D ( 3 ) treatment.", "output": "1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "The plasma concentrations and AUCs of JBP485 were significantly increased, while the renal clearance of JBP485 and uptake of JBP485 in kidney slices were significantly decreased after 1, 25 ( OH ) ( 2 ) D ( 3 ) treatment.", "output": "JBP485, JBP485, JBP485, 1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "These results confirmed that 1, 25 ( OH ) ( 2 ) D ( 3 ) inhibited renal excretion of JBP485.", "output": "1 , 25 ( OH ) ( 2 ) D ( 3 ), JBP485." }, { "input": "Moreover, 1, 25 ( OH ) ( 2 ) D ( 3 ) decreased expression of Oat1 and Oat3 in rat kidney.", "output": "1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "Our results are novel in demonstrating an interaction between JBP485 and 1, 25 ( OH ) ( 2 ) D ( 3 ) when they are co - administered.", "output": "JBP485, 1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "The mechanism of interaction between JBP485 and 1, 25 ( OH ) ( 2 ) D ( 3 ) could be explained at least in part by inhibitory effect of 1, 25 ( OH ) ( 2 ) D ( 3 ) on expression of Oats in rat kidney.", "output": "JBP485, 1 , 25 ( OH ) ( 2 ) D ( 3 ), 1 , 25 ( OH ) ( 2 ) D ( 3 )." }, { "input": "Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low - burst release is crucial for efficient CD8 ( + ) T cell activation.", "output": "PLGA." }, { "input": "Overlapping synthetic long peptides ( SLPs ) hold great promise for immunotherapy of cancer.", "output": "There is no related enetity." }, { "input": "Poly ( lactic - co - glycolic acid ) ( PLGA ) nanoparticles ( NPs ) are being developed as delivery systems to improve the potency of peptide - based therapeutic cancer vaccines.", "output": "Poly ( lactic - co - glycolic acid ), PLGA." }, { "input": "Our aim was to optimize PLGA NP for SLP delivery with respect to encapsulation and release, using OVA24, a 24 - residue long synthetic antigenic peptide covering a CTL epitope of ovalbumin ( SIINFEKL ), as a model antigen.", "output": "PLGA." }, { "input": "Peptide - loaded PLGA NPs were prepared by a double emulsion / solvent evaporation technique.", "output": "PLGA." }, { "input": "Using standard conditions ( acidic inner aqueous phase ), we observed that either encapsulation was very low ( 1 - 30 % ), or burst release extremely high ( > 70 % ) upon resuspension of NP in physiological buffers.", "output": "There is no related enetity." }, { "input": "By adjusting formulation and process parameters, we uncovered that the pH of the first emulsion was critical to efficient encapsulation and controlled release.", "output": "There is no related enetity." }, { "input": "In particular, an alkaline inner aqueous phase resulted in circa 330 nm sized NP with approximately 40 % encapsulation efficiency and low ( < 10 % ) burst release.", "output": "There is no related enetity." }, { "input": "These NP showed enhanced MHC class I restricted T cell activation in vitro when compared to high - burst releasing NP and soluble OVA24, proving that efficient entrapment of the antigen is crucial to induce a potent cellular immune response.", "output": "There is no related enetity." }, { "input": "Substrates of IAP ubiquitin ligases identified with a designed orthogonal E3 ligase, the NEDDylator.", "output": "There is no related enetity." }, { "input": "Inhibitors of Apoptosis Protein ( IAPs ) are guardian ubiquitin ligases that keep classic proapoptotic proteins in check.", "output": "There is no related enetity." }, { "input": "Systematic identification of additional IAP substrates is challenged by the heterogeneity and sheer number of ubiquitinated proteins ( > 5, 000 ).", "output": "There is no related enetity." }, { "input": "Here we report a powerful catalytic tagging tool, the NEDDylator, which fuses a NEDD8 E2 - conjugating enzyme, Ubc12, to the ubiquitin ligase, XIAP or cIAP1.", "output": "There is no related enetity." }, { "input": "This permits transfer of the rare ubiquitin homolog NEDD8 to the ubiquitin E3 substrates, allowing them to be efficiently purified for LC - MS / MS identification.", "output": "There is no related enetity." }, { "input": "We have identified > 50 potential IAP substrates of both cytosolic and mitochondrial origin that bear hallmark N - terminal IAP binding motifs.", "output": "N." }, { "input": "These substrates include the recently discovered protein phosphatase PGAM5, which we show is proteolytically processed, accumulates in cytosol during apoptosis, and sensitizes cells to death.", "output": "There is no related enetity." }, { "input": "These studies reveal mechanisms and antagonistic partners for specific IAPs, and provide a powerful technology for labeling binding partners in transient protein - protein complexes.", "output": "There is no related enetity." }, { "input": "Emerging role of primary cilia as mechanosensors in osteocytes.", "output": "There is no related enetity." }, { "input": "The primary cilium is a solitary, immotile microtubule - based extension present on nearly every mammalian cell.", "output": "There is no related enetity." }, { "input": "This organelle has established mechanosensory roles in several contexts including kidney, liver, and the embryonic node.", "output": "There is no related enetity." }, { "input": "Mechanical load deflects the cilium, triggering biochemical responses.", "output": "There is no related enetity." }, { "input": "Defects in cilium function have been associated with numerous human diseases.", "output": "There is no related enetity." }, { "input": "Recent research has implicated the primary cilium as a mechanosensor in bone.", "output": "There is no related enetity." }, { "input": "In this review, we discuss the cilium, the growing evidence for its mechanosensory role in bone, and areas of future study.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled \" The Osteocyte \".", "output": "There is no related enetity." }, { "input": "Selectivity of kinases on the activation of tenofovir, an anti - HIV agent.", "output": "tenofovir." }, { "input": "Nucleoside analogues, used in HIV - therapy, need to be phosphorylated by cellular enzymes in order to become potential substrates for HIV reverse transcriptase.", "output": "Nucleoside." }, { "input": "After incorporation into the viral DNA chain, because of lacking of their 3 ' - hydroxyl groups, they stop the elongation process and lead to the death of the virus.", "output": "3 ' - hydroxyl." }, { "input": "Phosphorylation of the HIV - drug derivative, tenofovir monophosphate was tested with the recombinant mammalian nucleoside diphosphate kinase ( NDPK ), 3 - phosphoglycerate kinase ( PGK ), creatine kinase ( CK ) and pyruvate kinase ( PK ).", "output": "tenofovir monophosphate, nucleoside diphosphate, 3 - phosphoglycerate, creatine, pyruvate." }, { "input": "Among them, only CK was found to phosphorylate tenofovir monophosphate with a reasonable rate ( about 45 - fold lower than with its natural substrate, ADP ), while PK exhibits even lower, but still detectable activity ( about 1000 - fold lower compared to the value with ADP ).", "output": "tenofovir monophosphate, ADP, ADP." }, { "input": "On the other hand, neither NDPK nor PGK has any detectable activity on tenofovir monophosphate.", "output": "tenofovir monophosphate." }, { "input": "The absence of activity with PGK is surprising, since the drug tenofovir competitively inhibits both CK and PGK towards their nucleotide substrates, with similar inhibitory constants, K ( I ) of 2. 9 and 4. 8mM, respectively.", "output": "tenofovir, nucleotide." }, { "input": "Computer modelling ( docking ) of tenofovir mono - or diphosphate forms to these four kinases suggests that the requirement of large - scale domain closure for functioning ( as for PGK ) may largely restrict their applicability for phosphorylation / activation of pro - drugs having a structure similar to tenofovir monophosphate.", "output": "tenofovir mono - or diphosphate, tenofovir monophosphate." }, { "input": "Protective effects of sweroside on human MG - 63 cells and rat osteoblasts.", "output": "sweroside." }, { "input": "Herbal Fructus Corni is a folk medicine with a long history of safe use for treating osteoporosis in postmenopausal women or elderly men in Asia.", "output": "There is no related enetity." }, { "input": "Sweroside is a bioactive herbal ingredient isolated from Fructus Corni, which has been widely used for the treatment of osteoporosis in traditional Chinese medicine ( TCM ).", "output": "Sweroside." }, { "input": "Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unclear.", "output": "There is no related enetity." }, { "input": "The aim of the study was performed to determine the potential molecular mechanism of the anti - osteoporotic effect of sweroside on the human MG - 63 cells and rat osteoblasts.", "output": "sweroside." }, { "input": "3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 - diphenyltetrazolium bromide ( MTT ) test was used to observe the effect of sweroside on cell proliferation.", "output": "3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide, MTT, sweroside." }, { "input": "The activity of alkaline phosphatase ( ALP ) and the amount of osteocalcin were also assayed the cell differentiation.", "output": "There is no related enetity." }, { "input": "Sweroside significantly increased the proliferation of human MG - 63 cells and rat osteoblasts ( P < 0. 01 ).", "output": "Sweroside." }, { "input": "It increased the activity of ALP, and osteocalcin was also elevated in response to sweroside ( P < 0. 05 ).", "output": "sweroside." }, { "input": "Of note, flowcytometer assay showed that sweroside can attenuate and inhibit apoptosis.", "output": "sweroside." }, { "input": "Sweroside has a direct osteogenic effect on the proliferation and differentiation of cultured human MG - 63 cells and rat osteoblasts in vitro.", "output": "Sweroside." }, { "input": "These data will help in understanding the molecular mechanisms of therapeutic efficacy of sweroside, and highlight insights into drug discovery.", "output": "sweroside." }, { "input": "In the current study, sweroside has been suggested to be a promising osteoporosis therapeutic natural product.", "output": "sweroside." }, { "input": "Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric ( Curcuma longa L ).", "output": "There is no related enetity." }, { "input": "The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil ( TEO ) from Curcuma longa L.", "output": "There is no related enetity." }, { "input": "Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0. 1, 0. 25 and 0. 5 g / kg b. wt. in Wistar rats.", "output": "There is no related enetity." }, { "input": "There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies.", "output": "There is no related enetity." }, { "input": "Indicators of hepatic function such as aspartate aminotransferase ( AST ), alanine amino transferase ( ALT ) and alkaline phosphatase ( ALP ) were unchanged in treated animals compared to untreated animals.", "output": "aspartate, alanine, amino." }, { "input": "Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues.", "output": "cholesterol, triglycerides." }, { "input": "TEO did not produce any mutagenicity to Salmonella typhimurium TA - 98, TA - 100, TA - 102 and TA - 1535 with or without metabolic activation.", "output": "There is no related enetity." }, { "input": "Administration of TEO to rats ( 1 g / kg b. wt. ) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.", "output": "There is no related enetity." }, { "input": "New modified beta - cyclodextrin derivatives as detoxifying agents of chemical warfare agents ( I ).", "output": "beta - cyclodextrin." }, { "input": "Synthesis and preliminary screening: evaluation of the detoxification using a half - quantitative enzymatic assay.", "output": "There is no related enetity." }, { "input": "Current treatments of organophosphorus nerve agents poisoning are imperfect, and more efficient medical countermeasures need to be developed.", "output": "organophosphorus." }, { "input": "Chemical scavengers based on beta - cyclodextrin displayed promising results, but further investigations have to be performed to evaluate the possibility of application of substituted cyclodextrins as potential detoxification agents.", "output": "beta - cyclodextrin." }, { "input": "Herein, five new cyclodextrins scavengers were synthesized.", "output": "There is no related enetity." }, { "input": "New optimal conditions for regioselectively monosubstitution of beta - cyclodextrin at O - 2 position were then studied to access to key intermediates.", "output": "beta - cyclodextrin." }, { "input": "After these optimizations, a new series of three permethylated derivatives was developed, and two compounds bearing an alpha - nucleophilic group via a three carbon atoms linker were prepared.", "output": "carbon." }, { "input": "The ability of these five scavengers to detoxify nerve agents ( cyclosarin, soman, tabun and VX ) was evaluated by a semi - quantitative biological assay.", "output": "cyclosarin." }, { "input": "All the modified cyclodextrins significantly decreased the inhibitory effect of chemical warfare G agents on acetylcholinesterase activity.", "output": "There is no related enetity." }, { "input": "For this purpose, we showed that the specific interactions between the organophosphorus compound and the oligosaccharidic moiety of the scavenger played a pivotal role in the detoxification process.", "output": "organophosphorus." }, { "input": "Raloxifene affects fatty acid oxidation in livers from ovariectomized rats by acting as a pro - oxidant agent.", "output": "Raloxifene, fatty acid." }, { "input": "Estrogen deficiency accelerates the development of several disorders including visceral obesity and hepatic steatosis.", "output": "Estrogen." }, { "input": "The predisposing factors can be exacerbated by drugs that affect hepatic lipid metabolism.", "output": "There is no related enetity." }, { "input": "The aim of the present work was to determine if raloxifene, a selective estrogen receptor modulator ( SERM ) used extensively by postmenopausal women, affects hepatic fatty acid oxidation pathways.", "output": "raloxifene, estrogen, fatty acid." }, { "input": "Fatty acids oxidation was measured in the livers, mitochondria and peroxisomes of ovariectomized ( OVX ) rats.", "output": "Fatty acids." }, { "input": "Mitochondrial and peroxisomal beta - oxidation was inhibited by raloxifene at a concentration range of 2. 5 - 25 mu M.", "output": "raloxifene." }, { "input": "In perfused livers, raloxifene reduced the ketogenesis from endogenous and exogenous fatty acids and increased the beta - hydroxybutyrate / acetoacetate ratio.", "output": "raloxifene, fatty acids, beta - hydroxybutyrate, acetoacetate." }, { "input": "An increase in (1) 4 CO 2 production without a parallel increase in the oxygen consumption indicated that raloxifene caused a diversion of NADH from the mitochondrial respiratory chain to another oxidative reaction.", "output": "(1) 4 CO 2, oxygen, raloxifene, NADH." }, { "input": "It was found that raloxifene has a strong ability to react with H 2 O 2 in the presence of peroxidase.", "output": "raloxifene, H 2 O 2." }, { "input": "It is likely that the generation of phenoxyl radical derivatives of raloxifene in intact livers led to the co - oxidation of NADH and a shift of the cellular redox state to an oxidised condition.", "output": "phenoxyl, raloxifene, NADH." }, { "input": "This change can perturb other important liver metabolic processes dependent on cellular NADH / NAD + ratio.", "output": "NADH, NAD +." }, { "input": "Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.", "output": "moniliformin." }, { "input": "Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain - based products worldwide.", "output": "Moniliformin." }, { "input": "In this study, the acute oral toxicity of moniliformin was assessed in Sprague - Dawley male rats according to OECD Guideline 423 with a single - dose exposure.", "output": "moniliformin." }, { "input": "Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography - mass spectrometry method.", "output": "moniliformin." }, { "input": "According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity.", "output": "moniliformin." }, { "input": "Moniliformin can be classified into category 2 ( LD ( 50 ) cut - off value 25 mg / kg b. w. ), according to the Globally Harmonized System for the classification of chemicals.", "output": "Moniliformin." }, { "input": "The clinical observations included muscular weakness, respiratory distress and heart muscle damage.", "output": "There is no related enetity." }, { "input": "Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity.", "output": "moniliformin." }, { "input": "A significant proportion ( about 38 % ) of the administered moniliformin was rapidly excreted in urine in less than 6 h.", "output": "moniliformin." }, { "input": "However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42 %.", "output": "There is no related enetity." }, { "input": "Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human / animal health.", "output": "moniliformin." }, { "input": "Nanoparticle toxicity in Daphnia magna reproduction studies: the importance of test design.", "output": "There is no related enetity." }, { "input": "The increasing use of titanium dioxide nanoparticles ( nTiO ( 2 ) ) inevitably results in their release into the environment, raising concerns about potential adverse effects in wildlife.", "output": "titanium dioxide, nTiO ( 2 )." }, { "input": "By following standard test protocols, several studies investigated the ecotoxicity of nTiO ( 2 ) among others to Daphnia magna.", "output": "nTiO ( 2 )." }, { "input": "These studies indicated a large variability - several orders of magnitude - in the response variables.", "output": "There is no related enetity." }, { "input": "However, other factors, like nanoparticle characteristics and test design, potentially triggering these differences, were largely ignored.", "output": "There is no related enetity." }, { "input": "Therefore, the present study assessed the chronic ecotoxicity of two nTiO ( 2 ) products with varying crystalline structure ( A - 100; P25 ) to D. magna.", "output": "nTiO ( 2 )." }, { "input": "A semi - static and a flow - through exposure scenario were compared, ensuring that both contained environmentally relevant concentrations of dissolved organic carbon.", "output": "carbon." }, { "input": "Utilizing the semi - static test design, a concentration as low as 0. 06 mg / L A - 100 ( ~ 330 nm ) significantly reduced the reproduction of daphnia indicating environmental risk.", "output": "There is no related enetity." }, { "input": "In contrast, no implication in the number of released offspring was observed during the flow - through experiment with A - 100 ( ~ 140 nm ).", "output": "There is no related enetity." }, { "input": "Likewise, P25 ( ~ 130 nm ) did not adversely affect reproduction irrespective of the test design utilized.", "output": "There is no related enetity." }, { "input": "Given the present study ' s results, the particle size, the product composition, i. e. the crystalline structure, and the accumulation of nTiO ( 2 ) at the bottom of the test vessel - the latter is relevant for a semi - static test design - may be suggested as factors potentially triggering differences in nTiO ( 2 ) toxicity to D. magna.", "output": "nTiO ( 2 ), nTiO ( 2 )." }, { "input": "Hence, these factors should be considered to improve environmental risk assessment of nanoparticles.", "output": "There is no related enetity." }, { "input": "The ATPase domain of ISWI is an autonomous nucleosome remodeling machine.", "output": "There is no related enetity." }, { "input": "ISWI slides nucleosomes along DNA, enabling the structural changes of chromatin required for the regulated use of eukaryotic genomes.", "output": "There is no related enetity." }, { "input": "Prominent mechanistic models imply cooperation of the ISWI ATPase domain with a C - terminal DNA - binding function residing in the HAND - SANT - SLIDE ( HSS ) domain.", "output": "C." }, { "input": "Contrary to these models, we show by quantitative biochemical means that all fundamental aspects of nucleosome remodeling are contained within the compact ATPase module of Drosophila ISWI.", "output": "There is no related enetity." }, { "input": "This domain can independently associate with DNA and nucleosomes, which in turn activate ATP turnover by inducing a conformational change in the enzyme, and it can autonomously reposition nucleosomes.", "output": "ATP." }, { "input": "The role of the HSS domain is to increase the affinity and specificity for nucleosomes.", "output": "There is no related enetity." }, { "input": "Nucleosome - remodeling enzymes may thus have evolved directly from ancestral helicase - type motors, and peripheral domains have furnished regulatory capabilities that bias the remodeling reaction toward different structural outcomes.", "output": "There is no related enetity." }, { "input": "Observation of rates and products in the reaction of NO3 with submicron squalane and squalene aerosol.", "output": "NO3, squalane, squalene." }, { "input": "The reactive uptake coefficients gamma, for nitrate radical, NO ( 3 ), on ~ 100 nm diameter squalane and squalene aerosol were measured ( 1 atm pressure of N ( 2 ) and 293 K ).", "output": "nitrate, NO ( 3 ), squalane, squalene, N ( 2 )." }, { "input": "For squalane, a branched alkane, gamma ( NO ( 3 ) ) of 2. 8 x 10 ( - 3 ) was estimated.", "output": "squalane, branched alkane, NO ( 3 )." }, { "input": "For squalene which contains 6 double bonds, gamma ( NO ( 3 ) ) was found to be a function of degree of oxidation with an initial value of 0. 18 +/- 0. 03 on fresh particles increasing to 0. 82 +/- 0. 11 on average of over 3 NO ( 3 ) reactions per squalene molecule in the aerosol.", "output": "squalene, NO ( 3 ), NO ( 3 ), squalene." }, { "input": "Synchrotron VUV - ionization aerosol mass spectrometry was used to detect the particle phase oxidation products that include as many as 3 NO ( 3 ) subunits added to the squalene backbone.", "output": "NO ( 3 ), squalene." }, { "input": "The fraction of squalene remaining in the aerosol follows first order kinetics under oxidation, even at very high oxidation equivalents, which suggests that the matrix remains a liquid upon oxidation.", "output": "squalene." }, { "input": "Our calculation indicates a much shorter chemical lifetime for squalene - like particle with respect to NO ( 3 ) than its atmospheric lifetime to deposition or wet removal.", "output": "squalene, NO ( 3 )." }, { "input": "Metabolism of the plasticizer and phthalate substitute diisononyl - cyclohexane - 1, 2 - dicarboxylate ( DINCH ( (R) ) ) in humans after single oral doses.", "output": "phthalate, diisononyl - cyclohexane - 1 , 2 - dicarboxylate, DINCH." }, { "input": "Hexamoll ( (R) ) DINCH ( (R) ) ( diisononyl - cyclohexane - 1, 2 - dicarboxylate ) is a new high - molecular - weight plasticizer and a phthalate substitute.", "output": "Hexamoll, DINCH, diisononyl - cyclohexane - 1 , 2 - dicarboxylate, phthalate." }, { "input": "In this study, the metabolism of DINCH ( (R) ) was investigated by oral dosage of three male volunteers with approximately 50 mg Hexamoll ( (R) ) DINCH ( (R) ) ( resulting in individual doses between 0. 552 and 0. 606 mg / kg body weight ).", "output": "DINCH, Hexamoll, DINCH." }, { "input": "Their urine samples were consecutively collected over 48 h.", "output": "There is no related enetity." }, { "input": "In analogy to di - iso - nonylphthalate ( DINP ) metabolism, we quantified the simple monoester mono - isononyl - cyclohexane - 1, 2 - dicarboxylate ( MINCH ) and its secondary oxidized metabolites with HPLC - MS / MS via isotope dilution analysis.", "output": "di - iso - nonylphthalate, DINP, monoester, mono - isononyl - cyclohexane - 1 , 2 - dicarboxylate, MINCH." }, { "input": "Additionally, we quantified the unspecific full breakdown product, cyclohexane - 1, 2 - dicarboxylic acid ( CHDA ), via standard addition.", "output": "cyclohexane - 1 , 2 - dicarboxylic acid, CHDA." }, { "input": "All postulated metabolites were present in all samples analyzed.", "output": "There is no related enetity." }, { "input": "The unspecific CHDA was identified as the major urinary metabolite representing 23. 7 % of the dose as the mean of the three volunteers ( range 20. 0 - 26. 5 % ).", "output": "CHDA." }, { "input": "14. 8 % ( 11. 3 - 16. 7 % ) of the dose was excreted as monoesters with oxidative modifications, in particular OH - MINCH 10. 7 % ( 7. 7 - 12. 9 % ), oxo - MINCH 2. 0 % ( 1. 5 - 2. 6 % ) and carboxy - MINCH 2. 0 % ( 1. 8 - 2. 3 % ).", "output": "monoesters, OH, MINCH, oxo, MINCH, carboxy, MINCH." }, { "input": "Less than 1 % was excreted as the simple monoester MINCH.", "output": "monoester, MINCH." }, { "input": "In sum, 39. 2 % ( 35. 9 - 42. 4 % ) of the DINCH ( (R) ) dose was excreted as these metabolites in urine within 48 h.", "output": "DINCH." }, { "input": "Over 90 % of the metabolites investigated were excreted within 24 h after application.", "output": "There is no related enetity." }, { "input": "The secondary oxidized metabolites, with elimination half - times between 10 and 18 h, proved to be apt and specific biomarkers to determine DINCH ( (R) ) exposure.", "output": "DINCH." }, { "input": "With this study, we provide reliable urinary excretion factors to calculate DINCH ( (R) ) intakes based on these metabolites in environmental and occupational studies.", "output": "DINCH." }, { "input": "EENdb: a database and knowledge base of ZFNs and TALENs for endonuclease engineering.", "output": "There is no related enetity." }, { "input": "We report here the construction of engineered endonuclease database ( EENdb ) ( http: / / eendb. zfgenetics. org / ), a searchable database and knowledge base for customizable engineered endonucleases ( EENs ), including zinc finger nucleases ( ZFNs ) and transcription activator - like effector nucleases ( TALENs ).", "output": "zinc." }, { "input": "EENs are artificial nucleases designed to target and cleave specific DNA sequences.", "output": "There is no related enetity." }, { "input": "EENs have been shown to be a very useful genetic tool for targeted genome modification and have shown great potentials in the applications in basic research, clinical therapies and agricultural utilities, and they are specifically essential for reverse genetics research in species where no other gene targeting techniques are available.", "output": "There is no related enetity." }, { "input": "EENdb contains over 700 records of all the reported ZFNs and TALENs and related information, such as their target sequences, the peptide components [ zinc finger protein - / transcription activator - like effector ( TALE ) - binding domains, FokI variants and linker peptide / framework ], the efficiency and specificity of their activities.", "output": "There is no related enetity." }, { "input": "The database also lists EEN engineering tools and resources as well as information about forms and types of EENs, EEN screening and construction methods, detection methods for targeting efficiency and many other utilities.", "output": "There is no related enetity." }, { "input": "The aim of EENdb is to represent a central hub for EEN information and an integrated solution for EEN engineering.", "output": "There is no related enetity." }, { "input": "These studies may help to extract in - depth properties and common rules regarding ZFN or TALEN efficiency through comparison of the known ZFNs or TALENs.", "output": "There is no related enetity." }, { "input": "Identification of LasR ligands through a virtual screening approach.", "output": "There is no related enetity." }, { "input": "With the widespread occurrence of bacterial resistance to antibiotics, the development of new strategies beyond conventional treatments is a pursuit taken by public health institutions worldwide.", "output": "There is no related enetity." }, { "input": "LasR, a transcription factor that controls quorum sensing in Pseudomonas aeruginosa, has emerged as an attractive therapeutic target for the next generation of antimicrobial agents.", "output": "There is no related enetity." }, { "input": "In the present study, a virtual screening workflow combining pharmacophore - and structure - based approaches was used to identify new LasR ligands.", "output": "There is no related enetity." }, { "input": "Five novel inducers and three inhibitors of LasR activity were validated experimentally by use of a cell - based assay.", "output": "There is no related enetity." }, { "input": "Interestingly, these compounds are molecularly distinct from the native signal molecule, N - 3 - oxododecanoyl - L - homoserine lactone ( OHN ), and may serve as lead structures for the design of new drugs.", "output": "N - 3 - oxododecanoyl - L - homoserine lactone, OHN." }, { "input": "The binding modes of these compounds to the OHN binding site in LasR were predicted and used to identify the key interactions that contribute to the induction and inhibition of LasR activity.", "output": "OHN." }, { "input": "Mitogen - inducible gene 6 triggers apoptosis and exacerbates ER stress - induced beta - cell death.", "output": "There is no related enetity." }, { "input": "The increased insulin secretory burden placed on pancreatic beta - cells during obesity and insulin resistance can ultimately lead to beta - cell dysfunction and death and the development of type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Mitogen - inducible gene 6 ( Mig6 ) is a cellular stress - responsive protein that can negatively regulate the duration and intensity of epidermal growth factor receptor signaling and has been classically viewed as a molecular brake for proliferation.", "output": "There is no related enetity." }, { "input": "In this study, we used Mig6 heterozygous knockout mice ( Mig6 ( + / - ) ) to study the role of Mig6 in regulating beta - cell proliferation and survival.", "output": "There is no related enetity." }, { "input": "Surprisingly, the proliferation rate of Mig6 ( + / - ) pancreatic islets was lower than wild - type islets despite having comparable beta - cell mass and glucose tolerance.", "output": "glucose." }, { "input": "We thus speculated that Mig6 regulates cellular death.", "output": "There is no related enetity." }, { "input": "Using adenoviral vectors to overexpress or knockdown Mig6, we found that caspase 3 activation during apoptosis was dependent on the level of Mig6.", "output": "There is no related enetity." }, { "input": "Interestingly, Mig6 expression was induced during endoplasmic reticulum ( ER ) stress, and its protein levels were maintained throughout ER stress.", "output": "There is no related enetity." }, { "input": "Using polyribosomal profiling, we identified that Mig6 protein translation was maintained, whereas the global protein translation was inhibited during ER stress.", "output": "There is no related enetity." }, { "input": "In addition, Mig6 overexpression exacerbated ER stress - induced caspase 3 activation in vitro.", "output": "There is no related enetity." }, { "input": "In conclusion, Mig6 is transcriptionally up - regulated and resistant to global translational inhibition during stressed conditions in beta - cells and mediates apoptosis in the form of caspase 3 activation.", "output": "There is no related enetity." }, { "input": "The sustained production of Mig6 protein exacerbates ER stress - induced beta - cell death.", "output": "There is no related enetity." }, { "input": "Thus, preventing the induction, translation, and / or function of Mig6 is warranted for increasing beta - cell survival.", "output": "There is no related enetity." }, { "input": "Sphingosine 1 - phosphate receptor 1 ( S1P ( 1 ) ) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P ( 1 ) antagonist.", "output": "Sphingosine 1 - phosphate." }, { "input": "Sphingosine 1 - phosphate receptor 1 ( S1P ( 1 ) ) is a G protein - coupled receptor that is critical for proper lymphocyte development and recirculation.", "output": "Sphingosine 1 - phosphate." }, { "input": "Agonists to S1P ( 1 ) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P ( 1 ) expressed on lymphocytes and S1P ( 1 ) expressed within the central nervous system.", "output": "There is no related enetity." }, { "input": "Agonists to S1P ( 1 ) and deficiency in S1P ( 1 ) both cause lymphocyte sequestration in the lymph nodes.", "output": "There is no related enetity." }, { "input": "In the present study, we show that S1P ( 1 ) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P ( 1 ) agonists while upregulating S1P ( 1 ) on lymphocytes and endothelial cells.", "output": "There is no related enetity." }, { "input": "Additionally, we show that S1P ( 1 ) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P ( 1 ) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P ( 1 ) antagonism is sufficient to alleviate autoimmune pathology.", "output": "There is no related enetity." }, { "input": "Design, synthesis and structure - activity relationship of new arginine vasopressin analogues containing proline derivatives in position 2.", "output": "arginine vasopressin, proline." }, { "input": "In this study, we present the synthesis and pharmacological properties of new analogues of arginine vasopressin modified in the N - terminal part of the molecule with proline derivatives: indoline - 2 - carboxylic acid ( Ica ) and ( 2S, 4R ) - 4 - ( naphthalene - 2 - ylmethyl ) pyrrolidine - 2 - carboxylic acid.", "output": "arginine vasopressin, N, proline, indoline - 2 - carboxylic acid, Ica, ( 2S , 4R ) - 4 - ( naphthalene - 2 - ylmethyl ) pyrrolidine - 2 - carboxylic acid." }, { "input": "All the peptides were tested for pressor, antidiuretic and in vitro uterotonic activities.", "output": "There is no related enetity." }, { "input": "We also determined their binding affinity to the human oxytocin receptor.", "output": "oxytocin." }, { "input": "The Ica ( 2 ) substitution resulted in two moderately potent and selective antioxytocic agents: [ Mpa ( 1 ), Ica ( 2 ), D - Arg ( 8 ) ] VP and [ Mpa ( 1 ), Ica ( 2 ), Val ( 4 ), D - Arg ( 8 ) ] VP ( pA ( 2 ) = 7. 09 and 7. 50, respectively ).", "output": "Ica, [ Mpa ( 1 ) , Ica ( 2 ) , D - Arg ( 8 ) ] VP, [ Mpa ( 1 ) , Ica ( 2 ) , Val ( 4 ) , D - Arg ( 8 ) ] VP." }, { "input": "On the other hand, peptides modified with ( 2S, 4R ) - 4 - ( naphthalene - 2 - ylmethyl ) pyrrolidine - 2 - carboxylic acid, apart from their moderate antioxytocic activity, turned out to be weak antagonists of the pressor response to arginine vasopressin.", "output": "( 2S , 4R ) - 4 - ( naphthalene - 2 - ylmethyl ) pyrrolidine - 2 - carboxylic acid, arginine vasopressin." }, { "input": "The results of this study provide useful information about the structure - activity relationship of arginine vasopressin analogues and can help to design compounds with desired biological properties.", "output": "arginine vasopressin." }, { "input": "Magnetic nanoclusters exhibiting protein - activated near - infrared fluorescence.", "output": "There is no related enetity." }, { "input": "Composite nanoclusters with chemical, magnetic, and biofunctionality offer broad opportunities for targeted cellular imaging.", "output": "There is no related enetity." }, { "input": "A key challenge is to load a high degree of targeting, imaging, and therapeutic functionality onto stable metal - oxide nanoparticles.", "output": "metal - oxide." }, { "input": "Here we report a route for producing magnetic nanoclusters ( MNCs ) with alkyne surface functionality that can be utilized as multimodal imaging probes.", "output": "alkyne." }, { "input": "We form MNCs composed of magnetic Fe ( 3 ) O ( 4 ) nanoparticles and poly ( acrylic acid - co - propargyl acrylate ) by the co - precipitation of iron salts in the presence of copolymer stabilizers.", "output": "There is no related enetity." }, { "input": "The MNCs were surface - modified with near - infrared ( NIR ) emitting fluorophore used in photodynamic therapy, an azide - modified indocyanine green.", "output": "azide, indocyanine green." }, { "input": "The fluorophores engaged and complexed with bovine serum albumin, forming an extended coverage of serum proteins on the MNCs.", "output": "There is no related enetity." }, { "input": "These proteins isolated indocyanine green fluorophores from the aqueous environment and induced an effective \" turn - on \" of NIR emission.", "output": "indocyanine green." }, { "input": "Transferable potentials for phase equilibria.", "output": "There is no related enetity." }, { "input": "10.", "output": "There is no related enetity." }, { "input": "Explicit - hydrogen description of substituted benzenes and polycyclic aromatic compounds.", "output": "hydrogen, benzenes, polycyclic aromatic." }, { "input": "The explicit - hydrogen version of the transferable potentials for phase equilibria ( TraPPE - EH ) force field is extended to various substituted benzenes through the parametrization of the exocyclic groups - F, - Cl, - Br, - C = N, and - OH and to polycyclic aromatic hydrocarbons through the parametrization of the aromatic linker carbon atom for multiple rings.", "output": "hydrogen, benzenes, F, Cl, Br, C = N, OH, polycyclic aromatic hydrocarbons, carbon." }, { "input": "The linker carbon together with the TraPPE - EH parameters for aromatic heterocycles constitutes a force field for fused - ring heterocycles.", "output": "carbon, aromatic heterocycles, fused - ring heterocycles." }, { "input": "Configurational - bias Monte Carlo simulations in the Gibbs ensemble were carried out to compute vapor - liquid coexistence curves for fluorobenzene; chlorobenzene; bromobenzene; di -, tri -, and hexachlorobenzene isomers; 2 - chlorofuran; 2 - chlorothiophene; benzonitrile; phenol; dihydroxybenzene isomers; 1, 4 - benzoquinone; naphthalene; naphthalene - 2 - carbonitrile; naphthalen - 2 - ol; quinoline; benzo [ b ] thiophene; benzo [ c ] thiophene; benzoxazole; benzisoxazole; benzimidazole; benzothiazole; indole; isoindole; indazole; purine; anthracene; and phenanthrene.", "output": "fluorobenzene, chlorobenzene, bromobenzene, di - , tri - , and hexachlorobenzene, 2 - chlorofuran, 2 - chlorothiophene, benzonitrile, phenol, dihydroxybenzene, 1 , 4 - benzoquinone, naphthalene, naphthalene - 2 - carbonitrile, naphthalen - 2 - ol, quinoline, benzo [ b ] thiophene, benzo [ c ] thiophene, benzoxazole, benzisoxazole, benzimidazole, benzothiazole, indole, isoindole, indazole, purine, anthracene, phenanthrene." }, { "input": "The agreement with the limited experimental data is very satisfactory, with saturated liquid densities and vapor pressures reproduced to within 1. 5 % and 15 %, respectively.", "output": "There is no related enetity." }, { "input": "The mean unsigned percentage errors in the normal boiling points, critical temperatures, and critical densities are 0. 9 %, 1. 2 %, and 1. 4 %, respectively.", "output": "There is no related enetity." }, { "input": "Additional simulations were carried out for binary systems of benzene / benzonitrile, benzene / phenol, and naphthalene / methanol to illustrate the transferability of the developed potentials to binary systems containing compounds of different polarity and hydrogen - bonding ability.", "output": "benzene, benzonitrile, benzene, phenol, naphthalene, methanol, hydrogen." }, { "input": "A detailed analysis of the liquid - phase structures is provided for selected neat systems and binary mixtures.", "output": "There is no related enetity." }, { "input": "Antiepileptic action of N - palmitoylethanolamine through CB1 and PPAR - alpha receptor activation in a genetic model of absence epilepsy.", "output": "N - palmitoylethanolamine." }, { "input": "N - palmitoylethanolamine ( PEA ), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator - activated receptors ( PPAR - alpha ).", "output": "N - palmitoylethanolamine, PEA, fatty acid ethanolamide." }, { "input": "Endogenous cannabinoids play a protective role in several central nervous system ( CNS ) disorders, particularly those associated with neuronal hyperexcitability.", "output": "cannabinoids." }, { "input": "We investigated the effects of PEA and the role of PPAR - alpha in absence epilepsy using the WAG / Rij rat model.", "output": "PEA." }, { "input": "PEA, anandamide ( AEA ), a PPAR - alpha antagonist ( GW6471 ) and a synthetic CB1 receptor antagonist / inverse agonist ( SR141716 ) were administered to WAG / Rij rats in order to evaluate the effects on epileptic spike - wave discharges ( SWDs ) on EEG recordings.", "output": "PEA, anandamide, AEA, GW6471, SR141716." }, { "input": "We studied also the effects of PEA co - administration with SR141716 and GW6471 and compared these effects with those of AEA to evaluate PEA mechanism of action and focusing on CB1 receptors and PPAR - alpha.", "output": "PEA, SR141716, GW6471, AEA, PEA." }, { "input": "Both PEA and AEA administration significantly decreased SWDs parameters ( absence seizures ).", "output": "PEA, AEA." }, { "input": "In contrast, GW6471 was devoid of effects while SR141716 had pro - absence effects.", "output": "GW6471, SR141716." }, { "input": "The co - administration of SR141716 with PEA or AEA completely blocked the anti - absence effects of these compounds.", "output": "SR141716, PEA, AEA." }, { "input": "GW6471 antagonized PEA ' s effects whereas it did not modify AEA ' s effects.", "output": "GW6471, PEA, AEA." }, { "input": "Furthermore, we have also measured PEA, AEA and 2 - AG ( 2 - arachidonoylglycerol ) brain levels identifying significant differences between epileptic and control rats such as decreased PEA levels in both thalamus and cortex that might contribute to absence epilepsy.", "output": "PEA, AEA, 2 - AG, 2 - arachidonoylglycerol, PEA." }, { "input": "Our data demonstrate that PEA has anti - absence properties in the WAG / Rij rat model and that such properties depend on PPAR - alpha and indirect activation of CB1 receptors.", "output": "PEA." }, { "input": "This article is part of the Special Issue entitled ' New Targets and Approaches to the Treatment of Epilepsy '.", "output": "There is no related enetity." }, { "input": "Tetrahydro - beta - carboline derivatives targeting fatty acid amide hydrolase ( FAAH ) and transient receptor potential ( TRP ) channels.", "output": "Tetrahydro - beta - carboline, fatty acid amide." }, { "input": "A series of twenty - five derivatives of tetrahydro - beta - carbolines 1 - 3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels.", "output": "tetrahydro - beta - carbolines." }, { "input": "Four carbamates, that is, 5a, c, e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b, d, f, and 8a, b were endowed with specific submicromolar TRPV1 modulating activities.", "output": "carbamates." }, { "input": "ESR1 polymorphisms, daily hassles, anger expression, and depressive symptoms in adolescent boys and girls.", "output": "There is no related enetity." }, { "input": "Studies reporting associations between genetic factors and mood - related traits have often been criticized ( i ) for failing to take into account the role of the social environment in which individuals act and ( ii ) for not maintaining a ' transparent narrative connection ' between genes and outcomes.", "output": "There is no related enetity." }, { "input": "In a sample of adolescents, we analyzed whether PvuII and XbaI, two polymorphisms on the ESR1 ( Estrogen Receptor Gene alpha ) were related to depressive symptoms, and considered whether daily hassles moderated this relationship and whether anger expression style mediated this relationship.", "output": "Estrogen." }, { "input": "Analyses suggested that ESR1 polymorphisms are relevant to the intra - sexual variability in depressive symptoms in boys and that the experience of daily hassles moderated this relationship.", "output": "There is no related enetity." }, { "input": "No such relationships were found in girls.", "output": "There is no related enetity." }, { "input": "Additionally, ESR1 polymorphisms are related to anger expression styles in girls.", "output": "There is no related enetity." }, { "input": "Anger - related variables, however, did not mediate the relationship between ESR1 polymorphisms and depressive symptoms, in boys nor in girls.", "output": "There is no related enetity." }, { "input": "Birth defects after exposure to misoprostol in the first trimester of pregnancy: prospective follow - up study.", "output": "misoprostol." }, { "input": "Misoprostol during the first trimester of pregnancy is associated with a specific malformative pattern ( Moebius sequence and limb defects ) whose incidence remains unknown.", "output": "Misoprostol." }, { "input": "Data originate mostly from illegal use for abortion and are mainly retrospective.", "output": "There is no related enetity." }, { "input": "The present prospective controlled study analyses outcomes of first trimester misoprostol exposures after medical prescriptions.", "output": "misoprostol." }, { "input": "Malformation rate was higher among 236 pregnancies exposed before 12 gestational weeks ( 4 % ) than in 255 controls ( 1. 8 % ), although not statistically significant ( OR = 2. 2 [ 95 % CI = 0. 6 - 7. 7 ] ).", "output": "There is no related enetity." }, { "input": "Three malformations ( 2 % ) in the exposed group were consistent with the misoprostol malformative pattern.", "output": "misoprostol." }, { "input": "This is the largest prospective study on first trimester misoprostol exposure and the first one relying on prescriptions.", "output": "misoprostol." }, { "input": "A trend toward a doubling of the overall rate of malformations was observed and for the first time an estimation of the incidence of misoprostol specific spectrum is proposed ( 2 % ).", "output": "misoprostol." }, { "input": "Brainstem injuries including severe trismus might be added to this specific pattern.", "output": "There is no related enetity." }, { "input": "Effects of the herbal medicine composition \" Saiko - ka - ryukotsu - borei - To \" on the function of endothelial progenitor cells in hypertensive rats.", "output": "There is no related enetity." }, { "input": "Endothelial progenitor cells ( EPCs ) are known to repair vascular injuries.", "output": "There is no related enetity." }, { "input": "Recent studies suggest that Saiko - ka - ryukotsu - borei - To ( SKRBT ), a traditional herbal medicine that has been used to treat stress - related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis.", "output": "There is no related enetity." }, { "input": "Spontaneously hypertensive rats ( SHRs ) were fed diets containing lyophilized SKRBT extract for 6 weeks.", "output": "There is no related enetity." }, { "input": "Peripheral blood mononuclear cells ( MNCs ) were isolated and cultured to assay EPC colony formation.", "output": "There is no related enetity." }, { "input": "Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance ( TBARS ) assay and flowcytometric analyses.", "output": "thiobarbituric acid." }, { "input": "Treatment with SKRBT increased EPC colony numbers significantly ( p < 0. 05 ) with decrease in oxidative stress and without affecting blood pressure in SHRs.", "output": "There is no related enetity." }, { "input": "Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidase subunits in cardiovascular organs.", "output": "nicotinamide adenine dinucleotide phosphate, NADPH." }, { "input": "Serum IL - 6 level was significantly reduced.", "output": "There is no related enetity." }, { "input": "SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti - oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to develop a mucoadhesive stimuli - sensitive drug delivery system for nasal administration of zidovudine ( AZT ).", "output": "zidovudine, AZT." }, { "input": "The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior.", "output": "There is no related enetity." }, { "input": "Flow rheology measurements showed that the formulation composed of PPG - 5 - CETETH - 20, oleic acid and water ( 55, 30, 15 % w / w ), denominated P, has Newtonian flow behavior.", "output": "PPG - 5 - CETETH - 20, oleic acid." }, { "input": "Polarized light microscopy ( PLM ) revealed that formulation P is isotropic, whereas its 1: 1 ( w / w ) dilution with artificial nasal mucus ( ANM ) changed the system to an anisotropic lamellar phase ( PD ).", "output": "There is no related enetity." }, { "input": "Oscillatory frequency sweep analysis showed that PD has a high storage modulus ( G ' ) at nasal temperatures.", "output": "There is no related enetity." }, { "input": "Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion.", "output": "There is no related enetity." }, { "input": "Ex vivo permeation studies across porcine nasal mucosa exhibited an 18 - fold rise in the permeability of AZT from the formulation.", "output": "AZT." }, { "input": "The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms.", "output": "AZT." }, { "input": "Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG - 5 - CETETH - 20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT.", "output": "PPG - 5 - CETETH - 20, oleic acid, AZT." }, { "input": "For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT - loaded P formulation ( PA ) and AZT solution, respectively, at a dose of 8mg / kg.", "output": "AZT, AZT, AZT." }, { "input": "The intranasal administration of PA resulted in a fast absorption process ( Tmax = 6. 7min ).", "output": "There is no related enetity." }, { "input": "Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs.", "output": "AZT." }, { "input": "In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS.", "output": "AZT." }, { "input": "Cobalt whole blood concentrations in healthy adult male volunteers following two - weeks of ingesting a cobalt supplement.", "output": "Cobalt, cobalt." }, { "input": "Recently, there has been an increase in the marketing and sales of dietary supplements, energy drinks, and other consumer products that may contain relatively high concentrations of essential elements.", "output": "There is no related enetity." }, { "input": "Cobalt - containing supplements are readily available in the U. S. and have been marketed to consumers as energy enhancers.", "output": "Cobalt." }, { "input": "However, little information is available regarding cobalt ( Co ) body burden and steady - state blood concentrations following the intake of Co dietary supplements.", "output": "cobalt, Co, Co." }, { "input": "We assessed Co whole blood concentrations in four healthy adult male volunteers who ingested a commercially available Co supplement ( 0. 4 mg Co / day ) for 15 or 16 days.", "output": "Co, Co, Co." }, { "input": "Pre - supplementation blood Co concentrations were less than the reporting limit of 0. 5 mu g / L, consistent with background concentrations reported to range between 0. 1 and 0. 4 mu g / L.", "output": "Co." }, { "input": "The mean whole blood Co concentration in the volunteers after 15 or 16 days of dosing was 3. 6 mu g Co / L and ranged from 1. 8 to 5. 1 mu g Co / L.", "output": "Co, Co, Co." }, { "input": "The mean observed concentration in the study group was approximately 9 - 36 times greater than background concentrations.", "output": "There is no related enetity." }, { "input": "Further studies of Co whole blood concentrations following supplementation over longer time periods with additional monitoring of physiological parameters may provide useful information for evaluating the health of persons who take various doses of Co.", "output": "Co, Co." }, { "input": "Polysialic acid enhances the migration and invasion of human cytotrophoblasts.", "output": "There is no related enetity." }, { "input": "Polysialic acid ( polySia ) is a large, cell - surface linear homopolymer composed of alpha 2, 8 - linked sialic acid residues.", "output": "sialic acid." }, { "input": "Most extensively studied in the nervous system, this unique glycan modulates development by enhancing cell migration and regulating differentiation.", "output": "There is no related enetity." }, { "input": "PolySia also functions in developing and adult immune systems and is a signature of many cancers.", "output": "There is no related enetity." }, { "input": "In this study, we demonstrated that human placental trophoblasts, an epithelial lineage, also display this glycan.", "output": "There is no related enetity." }, { "input": "Cytotrophoblasts and syncytiotrophoblasts expressed polySia in the first trimester and downregulated it during the course of pregnancy.", "output": "There is no related enetity." }, { "input": "PolySia promoted cytotrophoblast migration in an explant model of chorionic villous growth.", "output": "There is no related enetity." }, { "input": "Removal of this glycan also reduced cytotrophoblast penetration of basement membranes in an in vitro model of invasion.", "output": "There is no related enetity." }, { "input": "Finally, we showed that polySia was overexpressed in biopsies from patients with gestational trophoblastic diseases, including benign molar pregnancies and malignant choriocarcinomas.", "output": "There is no related enetity." }, { "input": "These results demonstrated, for the first time, functional roles for polySia during normal human placental development and implicated these unusual oligosaccharides in the unrestrained invasion of trophoblast tumors.", "output": "There is no related enetity." }, { "input": "Endocrine - disrupting effects of thioxanthone photoinitiators.", "output": "thioxanthone." }, { "input": "Photoinitiators used in food packaging ink, such as 2 - isopropylthioxanthone ( 2 - ITX ), have been shown to migrate into food and beverages.", "output": "2 - isopropylthioxanthone, 2 - ITX." }, { "input": "Recently, several studies indicated that 2 - ITX might be an endocrine - disrupting chemical.", "output": "2 - ITX." }, { "input": "In this work, the effects of 2 - ITX, 4 - isopropylthioxanthone ( 4 - ITX ), 2, 4 - diethylthio xanthone ( 2, 4 - diethyl - TX ), 2 - chlorothioxanthone ( 2 - chloro - TX ), and 1 - chloro - 4 - propoxythioxanthone ( 1 - chloro - 4 - propoxy - TX ) on steroidogenesis and androgen and estrogen receptor - mediated transcription activation have been studied using human H295R adrenocarcinoma cells and yeast hormone bioassays, respectively.", "output": "2 - ITX, 4 - isopropylthioxanthone, 4 - ITX, 2 , 4 - diethylthio xanthone, 2 , 4 - diethyl - TX, 2 - chlorothioxanthone, 2 - chloro - TX, 1 - chloro - 4 - propoxythioxanthone, 1 - chloro - 4 - propoxy - TX, androgen, estrogen." }, { "input": "None of the compounds showed androgenic or estrogenic activities, but clear antiandrogenic and antiestrogenic activities were observed for 2 - ITX, 4 - ITX, and 2, 4 - diethyl - TX, whereas 2 - chloro - TX showed only antiandrogenic activity.", "output": "2 - ITX, 4 - ITX, 2 , 4 - diethyl - TX, 2 - chloro - TX." }, { "input": "In an adapted version of the H295R steroidogenesis assay, using gas chromatography - tandem mass spectrometry analysis of H295R media, all five compounds increased levels of 17 beta - estradiol and estrone.", "output": "17 beta - estradiol, estrone." }, { "input": "H295R cells incubated with 2 - ITX also showed significantly reduced androgen and increased pregnenolone and progesterone levels.", "output": "2 - ITX, androgen, pregnenolone, progesterone." }, { "input": "Expression of particular steroidogenic genes, including the one encoding for aromatase ( CYP19A1 ), was significantly upregulated after incubation of H295R cells with 2 - ITX, 4 - ITX, and 2, 4 - diethyl - TX.", "output": "2 - ITX, 4 - ITX, 2 , 4 - diethyl - TX." }, { "input": "In line with the increased CYP19A1 mRNA expression, 2 - ITX increased catalytic activity of aromatase in H295R cells as measured by cognate aromatase assays.", "output": "2 - ITX." }, { "input": "The results indicate that thioxanthone derivatives can act as potential endocrine disruptors both at the level of nuclear receptor signaling and steroid hormone production.", "output": "thioxanthone, steroid." }, { "input": "Poly ( 2 - oxazoline ) - derived contact biocides: contributions to the understanding of antimicrobial activity.", "output": "Poly ( 2 - oxazoline )." }, { "input": "A set of poly ( 2 - oxazoline ) - derived ( co - ) polymers was prepared by microwave - assisted polymerizations and acid - mediated hydrolysis and tested for antimicrobial activity in 50 x 50 x 2 mm PP compound plates containing 5 wt % of the polymers.", "output": "poly ( 2 - oxazoline )." }, { "input": "Antimicrobial activity against gram - negative E. coli and P. aeruginosa as well as C. albicans depended only on the degree of hydrolysis, while antimicrobial activity against gram - positive S. aureus was only observed for hydrolyzed poly ( 2 - nonyl - 2 - oxazoline ) s.", "output": "poly ( 2 - nonyl - 2 - oxazoline ) s." }, { "input": "The surface energies of the compound plates compared to pure PP were hardly altered, and the compounds can be considered as alternatives for PP.", "output": "There is no related enetity." }, { "input": "The presence of the biocide additives at the surface of the PP compound plates could be shown by combined ATR - IR, zeta potential, and SEM - EDX measurements.", "output": "There is no related enetity." }, { "input": "Antimicrobial activity was maintained during double incubation as well as for lowered amounts of the biocide additive of 1 % in PP compound plates.", "output": "There is no related enetity." }, { "input": "Genome - wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "output": "There is no related enetity." }, { "input": "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes ( T2D ).", "output": "There is no related enetity." }, { "input": "We conducted a two - stage genome - wide association study of T2D in 12, 535 Indians, a less explored but high - risk group.", "output": "There is no related enetity." }, { "input": "We identified a new type 2 diabetes - associated locus at 2q21, with the lead signal being rs6723108 ( odds ratio 1. 31; P = 3. 32 x 10 - 9 ).", "output": "There is no related enetity." }, { "input": "Imputation analysis refined the signal to rs998451 ( odds ratio 1. 56; P = 6. 3 x 10 - (1) (2) ) within TMEM163 that encodes a probable vesicular transporter in nerve terminals.", "output": "There is no related enetity." }, { "input": "TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion.", "output": "There is no related enetity." }, { "input": "The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders.", "output": "There is no related enetity." }, { "input": "Forty - nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Known loci and the newly identified 2q21 locus altogether explained 7. 65 % variance in the risk of T2D in Indians.", "output": "There is no related enetity." }, { "input": "Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population - specific locus and provides further insights into genetic architecture and etiology of T2D.", "output": "There is no related enetity." }, { "input": "Cotinine in human placenta predicts induction of gene expression in fetal tissues.", "output": "Cotinine." }, { "input": "Maternal cigarette smoking during pregnancy is associated with increased risk of perinatal morbidity and mortality.", "output": "There is no related enetity." }, { "input": "However, the mechanisms underlying adverse birth outcomes following prenatal exposure to cigarette smoke remain unknown due, in part, to the absence or unreliability of information regarding maternal cigarette smoke exposure during pregnancy.", "output": "There is no related enetity." }, { "input": "Our goal was to determine if placental cotinine could be a reliable biomarker of fetal cigarette smoke exposure during pregnancy.", "output": "cotinine." }, { "input": "Cotinine levels were determined in placentas from 47 women who reported smoking during pregnancy and from 10 women who denied cigarette smoke exposure.", "output": "Cotinine." }, { "input": "Cotinine levels were significantly higher in placentas from women reporting cigarette smoking ( median = 27. 2 ng / g ) versus women who reported no smoke exposure ( 2. 3 ng / g, P < 0. 001 ).", "output": "Cotinine." }, { "input": "Receiver operating characteristic curve analysis identified an optimal cut point of 7. 5 ng / g ( sensitivity = 78. 7 %, specificity = 100 % ) to classify placenta samples from mothers who smoked versus those from mothers who did not.", "output": "There is no related enetity." }, { "input": "Among 415 placentas for which maternal cigarette smoking status was unavailable, 167 had cotinine levels > 7. 5 ng / g and would be considered positive for cigarette smoke exposure.", "output": "cotinine." }, { "input": "Data from quantitative reverse - transcription polymerase chain reaction analyses demonstrated that in utero cigarette smoke exposure predicted by cotinine in placenta is associated with changes in the expression of xenobiotic - metabolizing enzymes in fetal tissues.", "output": "cotinine." }, { "input": "CYP1A1 mRNA in fetal lung and liver tissue and CYP1B1 mRNA in fetal lung tissue were significantly induced when cotinine was detected in placenta.", "output": "cotinine." }, { "input": "These findings indicate that cotinine in placenta is a reliable biomarker for fetal exposure and response to maternal cigarette smoking during pregnancy.", "output": "cotinine." }, { "input": "Development of vizantin, a safe immunostimulant, based on the structure - activity relationship of trehalose - 6, 6 ' - dicorynomycolate.", "output": "vizantin, trehalose - 6 , 6 ' - dicorynomycolate." }, { "input": "Vizantin, 6, 6 ' - bis - O - ( 3 - nonyldodecanoyl ) - alpha, alpha ' - trehalose, was developed as a safe immunostimulator on the basis of a structure - activity relationship ( SAR ) study with trehalose 6, 6 ' - dicorynomycolate ( TDCM ).", "output": "Vizantin, 6 , 6 ' - bis - O - ( 3 - nonyldodecanoyl ) - alpha , alpha ' - trehalose, trehalose 6 , 6 ' - dicorynomycolate, TDCM." }, { "input": "It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16 - F0 melanoma cells.", "output": "vizantin, TDCM." }, { "input": "Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.", "output": "vizantin." }, { "input": "Qualitative studies among obese children and adolescents: a systematic review of the literature.", "output": "There is no related enetity." }, { "input": "Childhood obesity is a complex condition involving medical, social, moral and cultural issues.", "output": "There is no related enetity." }, { "input": "Qualitative approaches are of great value in understanding this complexity.", "output": "There is no related enetity." }, { "input": "This meta - synthesis of 45 qualitative studies deals specifically with the issue of obesity in children and adolescents from different perspectives - those of obese children and adolescents, of parents, and of health professionals providing support to the family.", "output": "There is no related enetity." }, { "input": "Our aim was to obtain a coherent view of child and adolescent obesity, focused on clinical and personal experience.", "output": "There is no related enetity." }, { "input": "The themes derived from the synthesis process fall under three main axes: ' Seeing others, seeing oneself ', ' Understanding others, understanding oneself ', and ' Treating others, treating oneself '.", "output": "There is no related enetity." }, { "input": "It emerges that participants in all three groups had equal difficulty in perceiving and labelling obesity, mainly because of their lack of any real common ground.", "output": "There is no related enetity." }, { "input": "The insufficiency of shared representations destabilizes the therapeutic relationship and its construction: an important issue in the doctor - child - parent relationship in this context is the need to exchange their viewpoints of obesity.", "output": "There is no related enetity." }, { "input": "Health workers may also expand their understanding of obesity by incorporating the personal experiences of obese children and their parents in order to match treatment plans to their needs and expectations.", "output": "There is no related enetity." }, { "input": "An explicit formula for optical oscillator strength of excitons in semiconducting single - walled carbon nanotubes: family behavior.", "output": "carbon." }, { "input": "The sensitive structural dependence of the optical properties of single - walled carbon nanotubes, which are dominated by excitons and tunable by changing diameter and chirality, makes them excellent candidates for optical devices.", "output": "carbon." }, { "input": "Because of strong many - electron interaction effects, the detailed dependence of the optical oscillator strength f ( s ) of excitons on nanotube diameter d, chiral angle theta, and electronic subband index P ( the so - called family behavior ), however, has been unclear.", "output": "There is no related enetity." }, { "input": "In this study, based on results from an extended Hubbard Hamiltonian with parameters derived from ab initio GW plus Bethe - Salpeter equation ( GW - BSE ) calculations, we have obtained an explicit formula for the family behavior of the oscillator strengths of excitons in semiconducting single - walled carbon nanotubes ( SWCNTs ), incorporating environmental screening.", "output": "carbon." }, { "input": "The formula explains recent measurements well and is expected to be useful in the understanding and design of possible SWCNT optical and optoelectronic devices.", "output": "There is no related enetity." }, { "input": "Dendronized albumin core - shell transporters with high drug loading capacity.", "output": "There is no related enetity." }, { "input": "We describe the synthesis of a core - shell biohybrid consisting of a human serum albumin ( HSA ) core that serves as a reservoir for lipophilic molecules and a cationized shell region consisting of ethynyl - G2. 0 - PAMAM or ethynyl - G3. 0 - PAMAM dendrons.", "output": "ethynyl, PAMAM, ethynyl, PAMAM." }, { "input": "The binding capacity of lipophilic guests was quantified applying electron paramagnetic resonance ( EPR ) spectroscopy, and five to six out of seven pockets were still available compared with HSA.", "output": "There is no related enetity." }, { "input": "The attachment of ethynyl - G2. 0 - PAMAM dendrons to HSA yielded a nontoxic core - shell macromolecule that was clearly uptaken by A549 human epithelial cells due to the presence of the dendritic PAMAM shell.", "output": "ethynyl, PAMAM, PAMAM." }, { "input": "Significantly higher loading of doxorubicin was observed for dendronized G2 - DHSA compared with the native protein due to the availability of binding pockets of the HSA core, and interaction with the dendritic shell.", "output": "doxorubicin." }, { "input": "Dendronized G2 - DHSA - doxorubicin displayed significant cytotoxicity resulting from high drug loading and high stability under different conditions, thus demonstrating its great potential as a transporter for drug molecules.", "output": "doxorubicin." }, { "input": "Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.", "output": "There is no related enetity." }, { "input": "Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers.", "output": "There is no related enetity." }, { "input": "Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide.", "output": "There is no related enetity." }, { "input": "This disease is caused by autoimmunity - mediated destruction of pancreatic beta - cells, leading to insulin deficiency, hyperglycemia and complications.", "output": "There is no related enetity." }, { "input": "Currently, there is no cure for type 1 diabetes.", "output": "There is no related enetity." }, { "input": "Insulin injection is the only medication; however, it accompanies serious medical complications.", "output": "There is no related enetity." }, { "input": "Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy.", "output": "There is no related enetity." }, { "input": "Despite recent advances in anti - diabetic strategies, no strategy is clinically successful.", "output": "There is no related enetity." }, { "input": "How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development.", "output": "There is no related enetity." }, { "input": "Plants provide an extraordinary source of natural medicines for different diseases.", "output": "There is no related enetity." }, { "input": "Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry.", "output": "There is no related enetity." }, { "input": "Over the past 25 years, 50 % of prescription drugs have been developed from natural products and their derivatives.", "output": "There is no related enetity." }, { "input": "In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type - 1 diabetes.", "output": "There is no related enetity." }, { "input": "Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic beta - cells.", "output": "There is no related enetity." }, { "input": "We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes.", "output": "There is no related enetity." }, { "input": "New views on phytocompound - based strategies for prevention and treatment of type 1 diabetes are also discussed.", "output": "There is no related enetity." }, { "input": "Green factories for biopharmaceuticals.", "output": "There is no related enetity." }, { "input": "Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes.", "output": "There is no related enetity." }, { "input": "Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs.", "output": "There is no related enetity." }, { "input": "Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes.", "output": "There is no related enetity." }, { "input": "Seed - based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution.", "output": "There is no related enetity." }, { "input": "The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix.", "output": "There is no related enetity." }, { "input": "Although the differences between plant and human N - glycans were initially thought to limit the therapeutic potential of plant - derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics.", "output": "There is no related enetity." }, { "input": "In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed.", "output": "There is no related enetity." }, { "input": "Plant metabolomics: from holistic data to relevant biomarkers.", "output": "There is no related enetity." }, { "input": "Metabolomics is playing an increasingly important role in plant science.", "output": "There is no related enetity." }, { "input": "It aims at the comprehensive analysis of the plant metabolome which consists both of primary and secondary metabolites.", "output": "There is no related enetity." }, { "input": "The goal of metabolomics is ultimately to identify and quantify this wide array of small molecules in biological samples.", "output": "There is no related enetity." }, { "input": "This new science is included in several systems biology approaches and is based primarily on the unbiased acquisition of mass spectrometric ( MS ) or nuclear magnetic resonance ( NMR ) data from carefully selected samples.", "output": "There is no related enetity." }, { "input": "This approach provides the most ' ' functional ' ' information of the ' omics ' technologies of a given organism since metabolites are the end products of the cellular regulatory processes.", "output": "There is no related enetity." }, { "input": "The application of state - of - the - art data mining, that includes various untargeted and targeted multivariate data analysis methods, to the vast amount of data generated by this data - driven approach leads to sample classification and the identification of relevant biomarkers.", "output": "There is no related enetity." }, { "input": "The biological areas that have been successfully studied by this holistic approach include global metabolite composition assessment, mutant and phenotype characterisation, taxonomy, developmental processes, stress response, interaction with the environment, quality control assessment, lead finding and mode of action of botanicals.", "output": "There is no related enetity." }, { "input": "This review summarises the main MS - and NMR - based approaches that are used to perform these studies and discusses the potential and current limitations of the various methods.", "output": "There is no related enetity." }, { "input": "The intent is not to provide an exhaustive overview of the field, which has grown considerably over the past decade, but to summarise the main strategies that are used and to discuss the potential and limitations of the different approaches as well as future trends.", "output": "There is no related enetity." }, { "input": "Recent advances in the development of catalytic inhibitors of human DNA topoisomerase II alpha as novel anticancer agents.", "output": "There is no related enetity." }, { "input": "DNA topoisomerases comprise an important family of enzymes that catalyse the induction of topological changes ( e. g. relaxation / supercoiling, catenation / decatenation and knotting / unknotting ) in the DNA molecule.", "output": "There is no related enetity." }, { "input": "These enzymes perform their functions by creating transient either single - stranded or double - stranded breaks in the DNA molecule.", "output": "There is no related enetity." }, { "input": "Due to their ability to modulate the topology of the DNA molecule, DNA topoisomerases play vital roles in replication, transcription, chromosome separation and segregation, and thus represent an important collection of design targets for novel anticancer drugs.", "output": "There is no related enetity." }, { "input": "The aim of this review is to provide an overview of the development of catalytic inhibitors of the human topoisomerase II alpha enzyme - - an important member of the DNA topoisomerase family - - as potential novel anticancer agents.", "output": "There is no related enetity." }, { "input": "The group of catalytic topoII inhibitors is classified into four types according to their molecular mechanism of action: inhibitors that bind to the ATP binding site, inhibitors that prevent the ATP hydrolysis step and trap the enzyme in a closed clamp, inhibitors that block the DNA cleavage and inhibitors that prevent the enzyme binding to the DNA.", "output": "ATP, ATP." }, { "input": "One of the important considerations highlighted throughout this review is the structure - based perspective of inhibitor design, giving the reader a medicinal chemist ' s perspective on this vibrant and active field of drug design research.", "output": "There is no related enetity." }, { "input": "AT1 receptor antagonism is proangiogenic in the brain: BDNF a novel mediator.", "output": "There is no related enetity." }, { "input": "Candesartan is an angiotensin II type 1 receptor blocker ( ARB ) that has been to shown to limit ischemic stroke and improve stroke outcome.", "output": "Candesartan." }, { "input": "In experimental stroke, candesartan induces a proangiogenic effect that is partly attributable to vascular endothelial growth factor.", "output": "candesartan." }, { "input": "Brain - derived neurotrophic factor ( BDNF ) is a member of the neurotrophin family that has been reported to have angiogenic effects and play an important role in recovery after stroke.", "output": "There is no related enetity." }, { "input": "The purpose of this investigation was to determine the role of BDNF in the proangiogenic effect of candesartan in the brain under hypertensive conditions.", "output": "There is no related enetity." }, { "input": "Accordingly, spontaneously hypertensive rats were treated with candesartan, and brain tissue samples were collected for quantification of BDNF expression.", "output": "candesartan." }, { "input": "In addition, human cerebromicrovascular endothelial cells were treated with either low - dose ( 1 f M ) or high - dose ( 1 micro M ) angiotensin II alone or in combination with candesartan ( 0. 16 micro M ) to assess the effect of candesartan treatment and BDNF involvement in the behavior of endothelial cells.", "output": "candesartan, candesartan." }, { "input": "Candesartan significantly increased the expression of BDNF in the SHR ( P < 0. 05 ).", "output": "Candesartan." }, { "input": "In addition, candesartan reversed the antiangiogenic effect of the 1 - micro M dose of AngII ( P = 0. 0001 ).", "output": "candesartan." }, { "input": "The observed effects of candesartan were ablated by neutralizing the effects of BDNF.", "output": "candesartan." }, { "input": "Treatment with the AT2 antagonist PD - 123319 significantly reduced tube - like formation in endothelial cells.", "output": "PD - 123319." }, { "input": "AT2 stimulation induced the BDNF expression and migration ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "In conclusion, candesartan exerts a proangiogenic effect on brain microvascular endothelial cells treated with angiotensin II.", "output": "candesartan." }, { "input": "This response is attributable to increased BDNF expression and is mediated through stimulation of the AT2 receptor.", "output": "There is no related enetity." }, { "input": "Regulation of the human hydroxysteroid sulfotransferase ( SULT2A1 ) by ROR alpha and ROR gamma and its potential relevance to human liver diseases.", "output": "hydroxysteroid." }, { "input": "The retinoid - related orphan receptors ( RORs ) were postulated to have functions in tissue development and circadian rhythm.", "output": "retinoid." }, { "input": "In this study, we revealed a novel function of ROR alpha ( NR1F1 ) and ROR gamma ( NR1F3 ) in regulating the human hydroxysteroid sulfotransferase ( SULT2A1 ), a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens.", "output": "hydroxysteroid, sulfonate bile acids, hydroxysteroid, dehydroepiandrosterone, androgens." }, { "input": "A combination of promoter reporter gene assay and EMSA and chromatin immunoprecipitation ( ChIP ) assays showed that both ROR alpha and ROR gamma transactivated the SULT2A1 gene promoter through their binding to a ROR response element found in the SULT2A1 gene promoter.", "output": "There is no related enetity." }, { "input": "Interestingly, this ROR response element overlaps with a previously reported constitutive androstane receptor response element on the same promoter.", "output": "There is no related enetity." }, { "input": "Down - regulation of ROR alpha and / or ROR gamma by small interfering RNA inhibited the expression of endogenous SULT2A1.", "output": "There is no related enetity." }, { "input": "In primary human hepatocytes and human livers, we found a positive correlation between the expression of SULT2A1 and RORs, which further supported the regulation of SULT2A1 by RORs.", "output": "There is no related enetity." }, { "input": "We also found that the expression of ROR alpha and ROR gamma was impaired in several liver disease conditions, such as steatosis / steatohepatitis, fibrosis, and hepatocellular carcinoma.", "output": "There is no related enetity." }, { "input": "The positive regulation of human SULT2A1 by RORs is opposite to the negative regulation of Sult2a1 by RORs in rodents.", "output": "There is no related enetity." }, { "input": "In summary, our results established SULT2A1 as a novel ROR target gene.", "output": "There is no related enetity." }, { "input": "The expression of RORs is a potential predictor for the expression of SULT2A1 as well as disease conditions.", "output": "There is no related enetity." }, { "input": "Clinical applications for microRNAs in cancer.", "output": "There is no related enetity." }, { "input": "The discovery that noncoding components of the genome, including microRNA ( miRNA or miR ), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making.", "output": "There is no related enetity." }, { "input": "Currently, miRNA signatures are being applied in human clinical trials and miRNA - directed therapy is under way, with miR - 122 targeting in hepatitis C ( HCV ) being the most developed therapy thus far.", "output": "There is no related enetity." }, { "input": "miRNA - based targeting in cancer is not far behind, with several private companies developing therapeutics.", "output": "There is no related enetity." }, { "input": "We are recognizing the potential for miRNA biology to clarify both the molecular pathogenesis of cancer and the inherent complexities in translating its biology to clinics.", "output": "There is no related enetity." }, { "input": "An increased understanding of fundamental miRNA biology, improved bioinformatics, and directed in vivo targeting while minimizing off - target effects and toxicity will be required for successful translational application.", "output": "There is no related enetity." }, { "input": "Here, we provide an overview of miRNAs, with a focus on aspects of translating bench - based discoveries to the clinic.", "output": "There is no related enetity." }, { "input": "Fast screening of authentic ginseng products by surface desorption atmospheric pressure chemical ionization mass spectrometry.", "output": "There is no related enetity." }, { "input": "Surface desorption atmospheric pressure chemical ionization mass spectrometry was developed as a rapid online detection technology for the chemical fingerprints of ginseng products without any sample pretreatment.", "output": "There is no related enetity." }, { "input": "More than 20 ginsenosides were detected in the ginseng tissue and identified by their tandem mass spectrometry.", "output": "ginsenosides." }, { "input": "Data were well matched with their reference compounds.", "output": "There is no related enetity." }, { "input": "Herein, surface desorption atmospheric pressure chemical ionization mass spectrometry was first applied to study the nonvolatile compounds in ginseng.", "output": "There is no related enetity." }, { "input": "White and red ginseng have been successfully differentiated from their counterfeits using some ginsenosides as chemical markers.", "output": "ginsenosides." }, { "input": "Ginsenoside can be used to differentiate between white ginseng, red ginseng, unboiled ginseng, and their counterfeits.", "output": "Ginsenoside." }, { "input": "Ginsenosides Ra1 - 3, Rb2 - 3, and Rc might be used to differentiate between white ginseng and boiled ginseng.", "output": "Ginsenosides Ra1 - 3 , Rb2 - 3 , and Rc." }, { "input": "Our result showed that surface desorption atmospheric pressure chemical ionization mass spectrometry not only could be used for fast screening authentic ginseng products but also might become a useful promising technique for the characterization of nonvolatile compounds in medicinal herbs to save researchers the laborious effort of sample pretreatment.", "output": "There is no related enetity." }, { "input": "Bio - based biodegradable and biocompatible hyperbranched polyurethane: a scaffold for tissue engineering.", "output": "polyurethane." }, { "input": "Hyperbranched polyurethanes are synthesized using TDI, PCL diol, butanediol, and pentaerythritol ( 1 - 5 wt % ) as the B ( 4 ) reactant with and without the monoglyceride of sunflower oil.", "output": "polyurethanes, TDI, PCL diol, butanediol, pentaerythritol, monoglyceride." }, { "input": "The biodegradation, physico - mechanical, and thermal properties are found to be tailored by varying the percentage weight of the branching unit.", "output": "There is no related enetity." }, { "input": "An MTT / hemolytic assay and subcutaneous implantation in Wistar rats followed by cytokine / ALP assay and histopathology studies confirm a better biocompatibility of HBPU with MG than without MG.", "output": "MTT." }, { "input": "HBPU supports the proliferation of dermatocytes with no toxic effect in major organs, in addition the in vitro degraded products are non - toxic.", "output": "There is no related enetity." }, { "input": "Cell adherence and proliferation endorse the bio - based HBPU as a prospective scaffold material in the niche of tissue engineering.", "output": "There is no related enetity." }, { "input": "Poly ( N - vinylpyrrolidone ) - modified surfaces for biomedical applications.", "output": "Poly ( N - vinylpyrrolidone )." }, { "input": "Poly ( N - vinylpyrrolidone ) ( PVP ), an important water soluble synthetic polymer, has many desirable properties including low toxicity, chemical stability, and good biocompatibility.", "output": "Poly ( N - vinylpyrrolidone ), PVP." }, { "input": "Since PVP is hemocompatible and physiologically inactive, it has been used as a blood plasma substitute.", "output": "PVP." }, { "input": "Surface modification with PVP has been investigated extensively over the past few years as a means of preventing nonspecific protein adsorption.", "output": "PVP." }, { "input": "PVP may therefore be seen as a promising antifouling surface modifier comparable to poly ( ethylene glycol ) ( PEG ).", "output": "PVP, poly ( ethylene glycol ), PEG." }, { "input": "In this review, various approaches for the design and preparation of PVP - modified surfaces are summarized and potential biomedical applications of these PVP - modified materials are indicated.", "output": "PVP, PVP." }, { "input": "Finally, some perspectives on future research on PVP for surface modification are discussed.", "output": "PVP." }, { "input": "Design of mixed PEO / PAA brushes with switchable properties toward protein adsorption.", "output": "PEO, PAA." }, { "input": "Adsorption of proteins at interfaces is an ubiquitous phenomenon of prime importance.", "output": "There is no related enetity." }, { "input": "Layers of poly ( ethylene oxide ) ( PEO ) are widely used to repel proteins.", "output": "poly ( ethylene oxide ), PEO." }, { "input": "Conversely, proteins were shown to adsorb deeply into brushes of poly ( acrylic acid ) ( PAA ), and their subsequent partial release could be triggered by a change of pH and / or ionic strength ( I ).", "output": "poly ( acrylic acid ), PAA." }, { "input": "Mixed brushes of these polymers are thus promising candidates to tune protein adsorption onto new smart surfaces.", "output": "There is no related enetity." }, { "input": "In this work, the synthesis of such mixed brushes was performed based on a \" grafting to \" approach, the two polymers being either grafted sequentially or simultaneously.", "output": "There is no related enetity." }, { "input": "Detailed characterization of the obtained brushes using static water contact angle measurements, X - ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and polarization - modulation reflection - absorption infrared spectroscopy is presented.", "output": "There is no related enetity." }, { "input": "While sequential grafting of the two polymers for different reactions times did not give rise to a broad range of composition of mixed brushes, simultaneous grafting of the polymers from solutions with different compositions allows for the synthesis of a range of mixed brushes ( mass fraction of PEO in the mixed brushes from 0. 35 to 0. 65 ).", "output": "PEO." }, { "input": "A key example is then chosen to illustrate the switchable behavior of a selected mixed PEO / PAA brush toward albumin adsorption.", "output": "PEO, PAA." }, { "input": "The adsorption behavior was monitored with a quartz crystal microbalance.", "output": "There is no related enetity." }, { "input": "The mixed brush could adsorb high amounts of albumin, but 86 % of the adsorbed protein could then be desorbed upon pH and I change.", "output": "There is no related enetity." }, { "input": "The obtained properties are thus a combination of the ones of PEO and PAA, and a highly switchable behavior is observed toward protein adsorption.", "output": "PEO, PAA." }, { "input": "Anisotropy of chemical bonding in semifluorinated graphite C2F revealed with angle - resolved X - ray absorption spectroscopy.", "output": "graphite, C2F." }, { "input": "Highly oriented pyrolytic graphite characterized by a low misorientation of crystallites is fluorinated using a gaseous mixture of BrF ( 3 ) with Br ( 2 ) at room temperature.", "output": "graphite, BrF ( 3 ), Br ( 2 )." }, { "input": "The golden - colored product, easily delaminating into micrometer - size transparent flakes, is an intercalation compound where Br ( 2 ) molecules are hosted between fluorinated graphene layers of approximate C ( 2 ) F composition.", "output": "Br ( 2 ), graphene, C ( 2 ) F." }, { "input": "To unravel the chemical bonding in semifluorinated graphite, we apply angle - resolved near - edge X - ray absorption fine structure ( NEXAFS ) spectroscopy and quantum - chemical modeling.", "output": "graphite." }, { "input": "The strong angular dependence of the CK and FK edge NEXAFS spectra on the incident radiation indicates that room - temperature - produced graphite fluoride is a highly anisotropic material, where half of the carbon atoms are covalently bonded with fluorine, while the rest of the carbon atoms preserve pi electrons.", "output": "graphite fluoride, carbon, fluorine." }, { "input": "Comparison of the experimental CK edge spectrum with theoretical spectra plotted for C ( 2 ) F models reveals that fluorine atoms are more likely to form chains.", "output": "C ( 2 ) F, fluorine." }, { "input": "This conclusion agrees with the atomic force microscopy observation of a chain - like pattern on the surface of graphite fluoride layers.", "output": "graphite fluoride." }, { "input": "Structure enhancement factor relationships in single gold nanoantennas by surface - enhanced Raman excitation spectroscopy.", "output": "There is no related enetity." }, { "input": "Determining the existence of any direct spectral relationship between the far - field scattering properties and the near - field Raman - enhancing properties of surface - enhanced Raman spectroscopy ( SERS ) substrates has been a challenging task with only a few significant results to date.", "output": "There is no related enetity." }, { "input": "Here, we prove that hot spot dominated systems show little dependence on the far - field scattering properties because of differences between near - and far - field localized surface plasmon resonance ( LSPR ) effects as well as excitation of new plasmon modes via a localized emitter.", "output": "There is no related enetity." }, { "input": "We directly probe the relationship between the near - and far - field light interactions using a correlated LSPR - transmission electron microscopy ( TEM ) surface - enhanced Raman excitation spectroscopy ( SERES ) technique.", "output": "There is no related enetity." }, { "input": "Fourteen individual SERS nanoantennas, Au nanoparticle aggregates ranging from dimers to undecamers, coated in a reporter molecule and encased in a protective silica shell, were excited using eight laser wavelengths.", "output": "Au, silica." }, { "input": "We observed no correlation between the spectral position of the LSPR maxima and the maximum enhancement factor ( EF ).", "output": "There is no related enetity." }, { "input": "The single nanoantenna data reveal EFs ranging from ( 2. 5 +/- 0. 6 ) x 10 ( 4 ) to ( 4. 5 +/- 0. 6 ) x 10 ( 8 ) with maximum enhancement for excitation wavelengths of 785 nm and lower energy.", "output": "There is no related enetity." }, { "input": "The magnitude of maximum EF was not correlated to the number of cores in the nanoantenna or the spectral position of the LSPR, suggesting a separation between near - field SERS enhancement and far - field Rayleigh scattering.", "output": "There is no related enetity." }, { "input": "Computational electrodynamics confirms the decoupling of maximum SERS enhancement from the peak of the scattering spectrum.", "output": "There is no related enetity." }, { "input": "It also points to the importance of a localized emitter for radiating Raman photons to the far - field which, in nonsymmetric systems, allows for the excitation of radiative plasmon modes that are difficult to excite with plane waves.", "output": "There is no related enetity." }, { "input": "Once these effects are considered, we are able to fully explain the hot spot dominated SERS response of the nanoantennas.", "output": "There is no related enetity." }, { "input": "Fibril formation by pH and temperature responsive silk - elastin block copolymers.", "output": "There is no related enetity." }, { "input": "In this report, we study the self - assembly of two silk - elastin - like proteins: one is a diblock S ( 24 ) E ( 40 ) composed of 24 silk - like ( S ) repeats and 40 elastin - like ( E ) repeats; the other is a triblock S ( 12 ) C ( 4 ) E ( 40 ), in which the S and E blocks are separated by a random coil block ( C ( 4 ) ).", "output": "There is no related enetity." }, { "input": "Upon lowering the pH, the acidic silk - like blocks fold and self - assemble into fibrils by a nucleation - and - growth process.", "output": "There is no related enetity." }, { "input": "While silk - like polymers without elastin - like blocks form fibrils by heterogeneous nucleation, leading to monodisperse populations, the elastin - like blocks allow for homogeneous nucleation, which gives rise to polydisperse length distributions, as well as a concentration - dependent fibril length.", "output": "There is no related enetity." }, { "input": "Moreover, the elastin - like blocks introduce temperature sensitivity: at high temperature, the fibrils become sticky and tend to bundle and aggregate in an irreversible manner.", "output": "There is no related enetity." }, { "input": "Concentrated solutions of S ( 12 ) C ( 4 ) E ( 40 ) form weak gels at low pH that irreversibly lose elasticity in temperature cycling; this is also attributed to fibril aggregation.", "output": "There is no related enetity." }, { "input": "Mechanism of homogeneous reduction of CO2 by pyridine: proton relay in aqueous solvent and aromatic stabilization.", "output": "CO2, pyridine." }, { "input": "We employ quantum chemical calculations to investigate the mechanism of homogeneous CO ( 2 ) reduction by pyridine ( Py ) in the Py / p - GaP system.", "output": "CO ( 2 ), pyridine." }, { "input": "We find that CO ( 2 ) reduction by Py commences with PyCOOH ( 0 ) formation where: ( a ) protonated Py ( PyH ( + ) ) is reduced to PyH ( 0 ), ( b ) PyH ( 0 ) then reduces CO ( 2 ) by one electron transfer ( ET ) via nucleophilic attack by its N lone pair on the C of CO ( 2 ), and finally ( c ) proton transfer ( PT ) from PyH ( 0 ) to CO ( 2 ) produces PyCOOH ( 0 ).", "output": "CO ( 2 ), PyCOOH ( 0 ), PyH ( + ), PyH ( 0 ), PyH ( 0 ), CO ( 2 ), N, C, CO ( 2 ), PyH ( 0 ), CO ( 2 ), PyCOOH ( 0 )." }, { "input": "The predicted enthalpic barrier for this proton - coupled ET ( PCET ) reaction is 45. 7 kcal / mol for direct PT from PyH ( 0 ) to CO ( 2 ).", "output": "PyH ( 0 ), CO ( 2 )." }, { "input": "However, when PT is mediated by one to three water molecules acting as a proton relay, the barrier decreases to 29. 5, 20. 4, and 18. 5 kcal / mol, respectively.", "output": "There is no related enetity." }, { "input": "The water proton relay reduces strain in the transition state ( TS ) and facilitates more complete ET.", "output": "There is no related enetity." }, { "input": "For PT mediated by a three water molecule proton relay, adding water molecules to explicitly solvate the core reaction system reduces the barrier to 13. 6 - 16. 5 kcal / mol, depending on the number and configuration of the solvating waters.", "output": "There is no related enetity." }, { "input": "This agrees with the experimentally determined barrier of 16. 5 +/- 2. 4 kcal / mol.", "output": "There is no related enetity." }, { "input": "We calculate a pK ( a ) for PyH ( 0 ) of 31 indicating that PT preceding ET is highly unfavorable.", "output": "PyH ( 0 )." }, { "input": "Moreover, we demonstrate that ET precedes PT in PyCOOH ( 0 ) formation, confirming PyH ( 0 ) ' s pK ( a ) as irrelevant for predicting PT from PyH ( 0 ) to CO ( 2 ).", "output": "PyCOOH ( 0 ), PyH ( 0 ), PyH ( 0 ), CO ( 2 )." }, { "input": "Furthermore, we calculate adiabatic electron affinities in aqueous solvent for CO ( 2 ), Py, and Py. CO ( 2 ) of 47. 4, 37. 9, and 66. 3 kcal / mol respectively, indicating that the anionic complex PyCOO ( - ) stabilizes the anionic radicals CO ( 2 ) ( - ) and Py ( - ) to facilitate low barrier ET.", "output": "CO ( 2 ), Py . CO ( 2 ), PyCOO ( - ), CO ( 2 ) ( - ), Py ( - )." }, { "input": "As the reduction of CO ( 2 ) proceeds through ET and then PT, the pyridine ring becomes aromatic, and thus Py catalyzes CO ( 2 ) reduction by stabilizing the PCET TS and the PyCOOH ( 0 ) product through aromatic resonance stabilization.", "output": "CO ( 2 ), pyridine, CO ( 2 ), PyCOOH ( 0 )." }, { "input": "Our results suggest that Py catalyzes the homogeneous reductions of formic acid and formaldehyde en route to formation of CH ( 3 ) OH through a series of one - electron reductions analogous to the PCET reduction of CO ( 2 ) examined here, where the electrode only acts to reduce PyH ( + ) to PyH ( 0 ).", "output": "formic acid, formaldehyde, CH ( 3 ) OH, CO ( 2 ), PyH ( + ), PyH ( 0 )." }, { "input": "Total synthesis of AMF - 26, an antitumor agent for inhibition of the Golgi system, targeting ADP - ribosylation factor 1.", "output": "AMF - 26, ADP." }, { "input": "An effective method for the total synthesis of 1 ( AMF - 26 ), a potentially promising new anticancer drug that disrupts the Golgi system by inhibiting the ADP - ribosylation factor 1 ( Arf1 ) activation, has been developed for the first time.", "output": "AMF - 26, ADP." }, { "input": "The construction of the chiral linear precursor ( a key to the synthesis ) was achieved by the asymmetric aldol reaction followed by the computer - assisted predictive stereoselective intramolecular Diels - Alder reaction.", "output": "There is no related enetity." }, { "input": "The global antitumor activity of the totally synthetic 1 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines ( JFCR39 ), and it was shown that the synthetic 1 strongly inhibited the growth of several cancer cell lines at concentrations of less than 0. 04 mu M.", "output": "There is no related enetity." }, { "input": "Biological assays of novel derivatives, 26 and 31, which have different side - chains at the C - 4 positions in the Delta (1), (2) - octalin backbone, disclosed the importance of the suitable structure of the side - chain containing conjugated multidouble bonds.", "output": "Delta (1) , (2) - octalin." }, { "input": "3 - Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models.", "output": "3 - Amido pyrrolopyrazine." }, { "input": "The Janus kinases ( JAKs ) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression.", "output": "There is no related enetity." }, { "input": "We optimized a new inhibitor scaffold, 3 - amido - 5 - cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties.", "output": "3 - amido - 5 - cyclopropylpyrrolopyrazines." }, { "input": "Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3 / JAK1 - dependent IL - 2 stimulated pathway over a JAK1 / JAK2 / Tyk2 - dependent IL - 6 stimulated pathway.", "output": "There is no related enetity." }, { "input": "Protein adsorption mechanisms determine the efficiency of thermally controlled cell adhesion on poly ( N - isopropyl acrylamide ) brushes.", "output": "poly ( N - isopropyl acrylamide )." }, { "input": "This study investigated the impact of the protein adsorption mechanism ( s ) on the efficiency of thermally controlled cell adhesion and release from poly ( N - isopropyl acrylamide ) brushes.", "output": "poly ( N - isopropyl acrylamide )." }, { "input": "Large format polymer gradients were used to screen for grafting densities and substrate chemistries that alter both cell adhesion at 37 degrees C and rapid cell release at 25 degrees C.", "output": "There is no related enetity." }, { "input": "In particular, the grafting conditions investigated allowed protein adsorption to the underlying substrate, penetration of the brush only, or adsorption to the outer edge of the film.", "output": "There is no related enetity." }, { "input": "At an average molecular weight of 30 kDa ( degree of polymerization N ~ 270 ), the results show that robust protein adsorption to polymer brushes impairs rapid cell release below the lower critical solution temperature.", "output": "There is no related enetity." }, { "input": "Conversely, grafting conditions that permit protein penetration of the brush but block strong adsorption to the underlying substrate support cell adhesion above the transition temperature and ensure efficient cell recovery at lower temperature.", "output": "There is no related enetity." }, { "input": "These findings demonstrate the impact of protein adsorption mechanisms, surface chemistry, and polymer properties on thermally controlled cell capture and release.", "output": "There is no related enetity." }, { "input": "Thermochemistry of uracils.", "output": "uracils." }, { "input": "Experimental and computational enthalpies of formation of 5, 6 - dimethyl -, 1, 3, 5 - trimethyl -, and 1, 3, 5, 6 - tetramethyluracils.", "output": "5 , 6 - dimethyl - , 1 , 3 , 5 - trimethyl - , and 1 , 3 , 5 , 6 - tetramethyluracils." }, { "input": "We describe in the current paper an experimental and computational study of three methylated uracils, in particular, the 5, 6 - dimethyl -, 1, 3, 5 - trimethyl -, and 1, 3, 5, 6 - tetramethyl derivatives.", "output": "5 , 6 - dimethyl - , 1 , 3 , 5 - trimethyl - , and 1 , 3 , 5 , 6 - tetramethyl." }, { "input": "The values of the standard ( p ( 0 ) = 0. 1 MPa ) molar enthalpies of formation in the gas phase at T = 298. 15 K have been determined.", "output": "There is no related enetity." }, { "input": "The energies of combustion were measured by static bomb combustion calorimetry, and from the results obtained, the standard molar enthalpies of formation in the crystalline state at T = 298. 15 K were calculated.", "output": "There is no related enetity." }, { "input": "The enthalpies of sublimation were determined using the transpiration method in a saturated N ( 2 ) stream.", "output": "N ( 2 )." }, { "input": "Values of - ( 376. 2 +/- 2. 6 ), - ( 355. 9 +/- 3. 0 ), and - ( 381. 7 +/- 2. 8 ) kJ. mol ( - 1 ) for the gas - phase enthalpies of formation at T = 298. 15 K of 5, 6 - dimethyluracil, 1, 3, 5 - trimethyluracil, and 1, 3, 5, 6 - tetramethyluracil, respectively, were obtained from the experimental thermochemical study.", "output": "5 , 6 - dimethyluracil, 1 , 3 , 5 - trimethyluracil, 1 , 3 , 5 , 6 - tetramethyluracil." }, { "input": "An extended theoretical study with the G3 and the G4 quantum - chemical methods has been carried out for all the possible methylated uracils.", "output": "methylated uracils." }, { "input": "There is a very good agreement between experimental and calculated enthalpies of formation for the three derivatives studied.", "output": "There is no related enetity." }, { "input": "A Free - Wilson analysis on G4 - calculated enthalpies of formation has been carried out, and the contribution of methylation in the different positions of the uracil ring has been estimated.", "output": "There is no related enetity." }, { "input": "Lipid reassembly in asymmetric Langmuir - Blodgett / Langmuir - Schaeffer bilayers.", "output": "There is no related enetity." }, { "input": "Molecular - reorganization - induced morphology alteration in asymmetric substrate - supported lipid bilayers ( SLBs ) was directly visualized by means of atomic force microscopy ( AFM ) and total internal reflection fluorescence ( TIRF ) microscopy.", "output": "There is no related enetity." }, { "input": "SLB samples were fabricated on mica - on - glass and glass substrates by Langmuir - Blodgett ( LB ) / Langmuir - Schaeffer ( LS ) using binary lipid mixtures, namely, 1, 2 - dioleoyl - sn - glycero - 3 - phosphocholine ( DOPC ) / 1, 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine ( DPPC ) and ternary mixtures DOPC / DPPC / 1, 2 - dioleoyl - sn - glycero - 3 - phospho - L - serine ( DOPS ), labeled with 0. 2 mol % Texas Red 1, 2 - dihexadecanoyl - sn - glycero - 3 - phosphoethanolamine triethylammonium salt ( TR - DHPE ) dye.", "output": "1 , 2 - dioleoyl - sn - glycero - 3 - phosphocholine, DOPC, 1 , 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine, DPPC, DOPC, DPPC, 1 , 2 - dioleoyl - sn - glycero - 3 - phospho - L - serine, DOPS, Texas Red, 1 , 2 - dihexadecanoyl - sn - glycero - 3 - phosphoethanolamine triethylammonium, TR - DHPE." }, { "input": "Phase segregations were characterized by TIRF imaging, and DPPC - enriched domain structures were also observed.", "output": "DPPC." }, { "input": "Interestingly for ~ 40 % ( n = 6 ) of the samples with binary mixtures in the LB leaflet and a single component in the LS leaflet, that is, ( DOPC / DPPC ) ( LB ) + DOPC ( LS ), the contrast of the DPPC domains changed from the original dark ( without dye ) to bright ( more TR dye partitioning ) on TIRF images, returning to dark again.", "output": "DOPC, DPPC, DOPC, DPPC." }, { "input": "This contrast reverse was also correlated to AFM height images, where a DPPC - DPPC gel phase was spotted after the TIRF image contrast returned to dark.", "output": "DPPC, DPPC." }, { "input": "The rupture force mapping results measured on these binary mixture samples also confirmed unambiguously the formation of DPPC - DPPC gel domain components during the contrast change.", "output": "DPPC, DPPC." }, { "input": "The samples were tracked over 48 h to investigate the lipid molecule movements in both the DPPC domains and the DOPC fluid phase.", "output": "DPPC, DOPC." }, { "input": "The fluorescence contrast changes from bright to dark in SLBs indicate that the movement of dye molecules was independent of the movement of lipid molecules.", "output": "There is no related enetity." }, { "input": "In addition, correlated multimodal imaging using AFM, force mapping, and fluorescence provides a novel route to uncover the reorganization of lipid molecules at the solid - liquid interface, suggesting that the dynamics of dye molecules is highly structure dependent.", "output": "There is no related enetity." }, { "input": "Chemically tailored dielectric - to - metal transition for the design of metamaterials from nanoimprinted colloidal nanocrystals.", "output": "There is no related enetity." }, { "input": "We demonstrate optical metamaterial design using colloidal gold nanocrystal building blocks.", "output": "There is no related enetity." }, { "input": "In the solid state, chemically exchanging the nanocrystals ' surface - capping molecules provides a tailorable dielectric - to - metal transition exhibiting a 10 ( 10 ) range in DC conductivity and dielectric permittivity ranging from everywhere positive to everywhere negative throughout the visible - to - near - IR.", "output": "There is no related enetity." }, { "input": "Direct, wide - area nanoimprinting of subwavelength superstructures at room temperature, on plastic and glass substrates, affords plasmonic resonances ranging from 660 to 1070 nm, in agreement with numerical simulations.", "output": "There is no related enetity." }, { "input": "Encapsulation of living E. coli cells in hollow polymer microspheres of highly defined size.", "output": "There is no related enetity." }, { "input": "Here, we report the preparation and characterization of hollow polymer microspheres based on the preprecipitation of porous calcium carbonate cores with an average size of 5 mu m and their use for encapsulation of living microorganisms.", "output": "calcium carbonate." }, { "input": "The microspheres filled with individual living E. coli cells were prepared by layer - by - layer ( LbL ) deposition of different polyelectrolytes and proteins onto the porous calcium carbonate cores leading to the formation of matrix - like complexes of the compounds followed by calcium carbonate core dissolution using EDTA.", "output": "calcium carbonate, calcium carbonate, EDTA." }, { "input": "Both the influence of the encapsulation process as well as of the used polyelectrolytes on the survival rate of the cells were determined by confocal laser scanning microscopy ( CLSM ) and microtiter plate fluorescence tests.", "output": "There is no related enetity." }, { "input": "After the encapsulation process ~ 40 % of the cells were alive.", "output": "There is no related enetity." }, { "input": "Cultivation tests indicated that the lag phase of cells treated with polyelectrolytes increases and the encapsulated E. coli cells were able to produce green fluorescent protein inside the microcapsules.", "output": "There is no related enetity." }, { "input": "Recombinant human fibrinogen that produces thick fibrin fibers with increased wound adhesion and clot density.", "output": "There is no related enetity." }, { "input": "Human fibrinogen is a biomaterial used in surgical tissue sealants, scaffolding for tissue engineering, and wound healing.", "output": "There is no related enetity." }, { "input": "Here we report on the post - translational structure and functionality of recombinant human FI ( rFI ) made at commodity levels in the milk of transgenic dairy cows.", "output": "There is no related enetity." }, { "input": "Relative to plasma - derived fibrinogen ( pdFI ), rFI predominately contained a simplified, neutral carbohydrate structure and > 4 - fold higher levels of the gamma ' - chain transcriptional variant that has been reported to bind thrombin and Factor XIII.", "output": "carbohydrate." }, { "input": "In spite of these differences, rFI and pdFI were kinetically similar with respect to the thrombin - catalyzed formation of protofibrils and Factor XIIIa - mediated formation of cross - linked fibrin polymer.", "output": "There is no related enetity." }, { "input": "However, electron microscopy showed rFI produced fibrin with much thicker fibers with less branching than pdFI.", "output": "There is no related enetity." }, { "input": "In vivo studies in a swine liver transection model showed that, relative to pdFI, rFI made a denser, more strongly wound - adherent fibrin clot that more rapidly established hemostasis.", "output": "There is no related enetity." }, { "input": "Platelet - derived microparticles in overweight / obese women with the polycystic ovary syndrome.", "output": "There is no related enetity." }, { "input": "A substantial proportion of women with the polycystic ovary syndrome ( PCOS ) are obese and obesity is considered as a prothrombotic state.", "output": "There is no related enetity." }, { "input": "Platelet - derived microparticles ( PMPs ) might be implicated in the activation of the coagulation cascade.", "output": "There is no related enetity." }, { "input": "We aimed to assess plasma PMPs in overweight / obese women with PCOS.", "output": "There is no related enetity." }, { "input": "We measured plasma PMPs and determined anthropometric, metabolic, hormonal and ultrasonographic features of PCOS in 67 overweight / obese women with PCOS ( with body mass index [ BMI ] > 25. 0 kg / m ( 2 ) ) and in 21 BMI - matched healthy women.", "output": "There is no related enetity." }, { "input": "Circulating androgens and markers of insulin resistance ( IR ) were higher in women with PCOS than in controls.", "output": "androgens." }, { "input": "Plasma PMPs were also higher in women with PCOS than in controls ( p = 0. 046 ).", "output": "There is no related enetity." }, { "input": "In women with PCOS, plasma PMPs correlated with the mean number of follicles in the ovaries ( r = 0. 343; p = 0. 006 ).", "output": "There is no related enetity." }, { "input": "In controls, plasma PMPs did not correlate with any of the studied parameters.", "output": "There is no related enetity." }, { "input": "In conclusion, plasma PMPs are elevated in overweight / obese women with PCOS compared with BMI - matched controls.", "output": "There is no related enetity." }, { "input": "The cause of this increase is unclear but both IR and hyperandrogenemia might be implicated.", "output": "There is no related enetity." }, { "input": "More studies are required to elucidate the pathogenesis of the elevation of PMPs in PCOS and to assess its implications on the cardiovascular risk of these patients.", "output": "There is no related enetity." }, { "input": "Structure - activity relationship study on benzoic acid part of diphenylamine - based retinoids.", "output": "benzoic acid, diphenylamine, retinoids." }, { "input": "Based on structure - activity relationship studies of the benzoic acid part of diphenylamine - based retinoids, the potent RXR agonist 4 was derivatized to obtain retinoid agonists, synergists, and an antagonist.", "output": "benzoic acid, diphenylamine, retinoids, retinoid." }, { "input": "Cinnamic acid derivatives 5 and phenylpropionic acid derivatives 6 showed retinoid agonistic and synergistic activities, respectively.", "output": "Cinnamic acid, phenylpropionic acid, retinoid." }, { "input": "The difference of the activities is considered to be due to differences in the flexibility of the carboxylic acid - containing substituent on the diphenylamine skeleton.", "output": "carboxylic acid, diphenylamine." }, { "input": "Compound 7, bearing a methyl group at the meta position to the carboxyl group, was an antagonist, dose - dependently inhibiting HL - 60 cell differentiation induced by 3. 3 x 10 ( - 10 ) M Am80.", "output": "methyl, carboxyl, Am80." }, { "input": "Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus.", "output": "phenylethyl benzamide." }, { "input": "Novel benzamide derivatives were synthesized and tested at in vitro assay by measuring fold increase of glucokinase activity at 5. 0 mM glucose concentration.", "output": "benzamide, glucose." }, { "input": "Among the prepared compounds, YH - GKA was found to be an active glucokinase activator with EC ( 50 ) of 70 nM.", "output": "YH - GKA." }, { "input": "YH - GKA showed similar glucose AUC reduction of 29. 6 % ( 50 mg / kg ) in an OGTT study with C57BL / J6 mice compared to 29. 9 % for metformin ( 300 mg / kg ).", "output": "YH - GKA, glucose." }, { "input": "Acute treatment of the compound in C57BL / J6 and ob / ob mice elicited basal glucose lowering activity.", "output": "glucose." }, { "input": "In subchronic study with ob / ob mice, YH - GKA showed significant decrease in blood glucose levels and no adverse effects on serum lipids or body weight.", "output": "YH - GKA, glucose." }, { "input": "In addition, YH - GKA exhibited high bioavailability and moderate elimination in preclinical species.", "output": "YH - GKA." }, { "input": "Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors.", "output": "bisulfite." }, { "input": "Noroviruses are the most common cause of acute viral gastroenteritis, accounting for > 21 million cases annually in the US alone.", "output": "There is no related enetity." }, { "input": "Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines.", "output": "There is no related enetity." }, { "input": "In this study, a series of bisulfite adducts derived from representative transition state inhibitors ( dipeptidyl aldehydes and alpha - ketoamides ) was synthesized and shown to exhibit anti - norovirus activity in a cell - based replicon system.", "output": "bisulfite, dipeptidyl aldehydes, alpha - ketoamides." }, { "input": "The ED ( 50 ) of the most effective inhibitor was 60 nM.", "output": "There is no related enetity." }, { "input": "This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C - like protease in vitro and in a cell - based replicon system.", "output": "bisulfite." }, { "input": "The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as alpha - ketoheterocycles and alpha - ketoesters.", "output": "bisulfite, serine, cysteine, alpha - ketoheterocycles, alpha - ketoesters." }, { "input": "Indoleamine 2, 3 - dioxygenase inhibitory activity of derivatives of marine alkaloid tsitsikammamine A.", "output": "Indoleamine, tsitsikammamine A." }, { "input": "Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold.", "output": "Tsitsikammamines, pyrroloiminoquinone." }, { "input": "These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity.", "output": "There is no related enetity." }, { "input": "Indoleamine 2, 3 - dioxygenase ( IDO1 ) is a well - established therapeutic target as an important factor in the tumor immune evasion mechanism.", "output": "Indoleamine." }, { "input": "In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1.", "output": "tsitsikammamine." }, { "input": "Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay.", "output": "Tsitsikammamine A." }, { "input": "A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2, 3 - dioxygenase ( TDO ), a functionally related enzyme.", "output": "tryptophan." }, { "input": "This IDO1 inhibitory activity is rationalized by molecular modeling studies.", "output": "There is no related enetity." }, { "input": "An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.", "output": "There is no related enetity." }, { "input": "Synthesis and insecticidal evaluation of novel N - pyridylpyrazolecarboxamides containing cyano substituent in the ortho - position.", "output": "N - pyridylpyrazolecarboxamides, cyano." }, { "input": "In an attempt to search for potent insecticides targeting the ryanodine receptor ( RyR ), a series of novel N - pyridylpyrazolecarboxamides containing cyano substituent in the ortho - position were designed and synthesized.", "output": "ryanodine, N - pyridylpyrazolecarboxamides, cyano." }, { "input": "Their insecticidal activities of target compounds against oriental armyworm ( Mythimna separata ) and diamondback moth ( Plutella xylostella ) indicated that most of the compounds showed moderate to high activities at the tested concentrations.", "output": "There is no related enetity." }, { "input": "In particular, compound 6l and 6o showed 86 % larvicidal activities against Plutella xylostella at the concentration of 0. 1mg / L, while the activity of compound 6h against Mythimna separate was 80 % at 1mg / L.", "output": "There is no related enetity." }, { "input": "The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ( [ Ca ( 2 + ) ] ( i ) ), experimental results demonstrated that compound 6h stimulates a transient elevation in [ Ca ( 2 + ) ] ( i ) in the absence of external calcium after the central neurons dye loading with fluo - 3 AM.", "output": "calcium, calcium, Ca ( 2 + ), Ca ( 2 + ), calcium, fluo - 3 AM." }, { "input": "However, when the central neurons were dyed with fluo - 5N and incubated with 2 - APB, [ Ca ( 2 + ) ] i decreased transiently by treated of compound 6h.", "output": "2 - APB, Ca ( 2 + )." }, { "input": "All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR.", "output": "calcium, calcium." }, { "input": "DNA polymerase POLQ and cellular defense against DNA damage.", "output": "There is no related enetity." }, { "input": "In mammalian cells, POLQ ( pol theta ) is an unusual specialized DNA polymerase whose in vivo function is under active investigation.", "output": "There is no related enetity." }, { "input": "POLQ has been implicated by different experiments to play a role in resistance to ionizing radiation and defense against genomic instability, in base excision repair, and in immunological diversification.", "output": "There is no related enetity." }, { "input": "The protein is formed by an N - terminal helicase - like domain, a C - terminal DNA polymerase domain, and a large central domain that spans between the two.", "output": "N, C." }, { "input": "This arrangement is also found in the Drosophila Mus308 protein, which functions in resistance to DNA interstrand crosslinking agents.", "output": "There is no related enetity." }, { "input": "Homologs of POLQ and Mus308 are found in multicellular eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs.", "output": "There is no related enetity." }, { "input": "Flies defective in Mus308 are sensitive to DNA interstrand crosslinking agents, while mammalian cells defective in POLQ are primarily sensitive to DNA double - strand breaking agents.", "output": "There is no related enetity." }, { "input": "Cells from Polq ( - / - ) mice are hypersensitive to radiation and peripheral blood cells display increased spontaneous and ionizing radiation - induced levels of micronuclei ( a hallmark of gross chromosomal aberrations ), though mice apparently develop normally.", "output": "There is no related enetity." }, { "input": "Loss of POLQ in human and mouse cells causes sensitivity to ionizing radiation and other double strand breaking agents and increased DNA damage signaling.", "output": "There is no related enetity." }, { "input": "Retrospective studies of clinical samples show that higher levels of POLQ gene expression in breast and colorectal cancer are correlated with poorer outcomes for patients.", "output": "There is no related enetity." }, { "input": "A clear understanding of the mechanism of action and physiologic function of POLQ in the cell is likely to bear clinical relevance.", "output": "There is no related enetity." }, { "input": "Novel cinnoline - based inhibitors of LRRK2 kinase activity.", "output": "cinnoline." }, { "input": "Leucine rich repeat kinase 2 ( LRRK2 ) has been implicated in the pathogenesis of Parkinson ' s disease ( PD ).", "output": "Leucine." }, { "input": "Inhibition of LRRK2 kinase activity is a therapeutic approach that may lead to new treatments for PD.", "output": "There is no related enetity." }, { "input": "Herein we report the discovery of a series of cinnoline - 3 - carboxamides that are potent against both wild - type and mutant LRRK2 kinase activity in biochemical assays.", "output": "cinnoline - 3 - carboxamides." }, { "input": "These compounds are also shown to be potent inhibitors in a cellular assay and to have good to excellent CNS penetration.", "output": "There is no related enetity." }, { "input": "Neuroprotective effects of oxymatrine against excitotoxicity partially through down - regulation of NR2B - containing NMDA receptors.", "output": "oxymatrine, NMDA." }, { "input": "Oxymatrine ( OMT ) is a major bioactive component derived from Sophora flavescens Ait ( kushen ), which is widely used in Chinese medicine.", "output": "Oxymatrine, OMT." }, { "input": "Recent studies have shown that it has neuroprotective effects; however, its underlying mechanisms remain unclear.", "output": "There is no related enetity." }, { "input": "We focus on the mechanisms of pharmacologic action in OMT by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA - induced neurotoxicity in vitro.", "output": "OMT, NMDA." }, { "input": "OMT prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion, in vivo.", "output": "OMT." }, { "input": "In vitro cultured neurons challenged with N - methyl - D - aspartate ( NMDA, 200 mu M ) for 30 min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure.", "output": "N - methyl - D - aspartate, NMDA, OMT, NMDA." }, { "input": "Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro - and anti - apoptotic proteins.", "output": "OMT." }, { "input": "Furthermore, OMT significantly reversed the up - regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA.", "output": "OMT, calcium, NMDA." }, { "input": "OMT showed partial protection in the cortical neurons via down - regulation of NR2B containing NMDA receptors and up - regulation of Bcl - 2 family.", "output": "OMT, NMDA." }, { "input": "Our results provide new insights into the development of natural therapeutic anti - oxidants against ischemia.", "output": "There is no related enetity." }, { "input": "Direct transmembrane interaction between actin and the pore - competent, cholesterol - dependent cytolysin pneumolysin.", "output": "cholesterol." }, { "input": "The eukaryotic actin cytoskeleton is an evolutionarily well - established pathogen target, as a large number of bacterial factors disturb its dynamics to alter the function of the host cells.", "output": "There is no related enetity." }, { "input": "These pathogenic factors modulate or mimic actin effector proteins or they modify actin directly, leading to an imbalance of the precisely regulated actin turnover.", "output": "There is no related enetity." }, { "input": "Here, we show that the pore - forming, cholesterol - dependent cytolysin pneumolysin ( PLY ), a major neurotoxin of Streptococcus pneumoniae, has the capacity to bind actin directly and to enhance actin polymerisation in vitro.", "output": "cholesterol." }, { "input": "In cells, the toxin co - localised with F - actin shortly after exposure, and this direct interaction was verified by F o rster resonance energy transfer.", "output": "There is no related enetity." }, { "input": "PLY was capable of exerting its effect on actin through the lipid bilayer of giant unilamellar vesicles, but only when its pore competence was preserved.", "output": "There is no related enetity." }, { "input": "The dissociation constant of G - actin binding to PLY in a biochemical environment was 170 - 190 nM, which is indicative of a high - affinity interaction, comparable to the affinity of other intracellular actin - binding factors.", "output": "There is no related enetity." }, { "input": "Our results demonstrate the first example of a direct interaction of a pore - forming toxin with cytoskeletal components, suggesting that the cross talk between pore - forming cytolysins and cells is more complex than previously thought.", "output": "There is no related enetity." }, { "input": "Influence of sildenafil and tadalafil on the enzyme - and transporter - inducing effects of bosentan and ambrisentan in LS180 cells.", "output": "sildenafil, bosentan, ambrisentan." }, { "input": "The combinations of the endothelin - 1 receptor antagonists bosentan or ambrisentan with the phosphodiesterase 5 inhibitors sildenafil or tadalafil are current standard therapies of advanced pulmonary arterial hypertension.", "output": "bosentan, ambrisentan, sildenafil, tadalafil." }, { "input": "However, these drugs have a number of drug interactions.", "output": "There is no related enetity." }, { "input": "Changes of bosentan pharmacokinetics by sildenafil are attributed to reduced hepatic uptake as a consequence of inhibition of organic anion transporting polypeptides.", "output": "bosentan, sildenafil." }, { "input": "We therefore tested in vitro the hypothesis that sildenafil and tadalafil reduce the enzyme - and transporter - inducing effects of bosentan or ambrisentan by preventing cellular access.", "output": "sildenafil, tadalafil, bosentan, ambrisentan." }, { "input": "Although intracellular concentrations of bosentan and ambrisentan ( measured by high pressure liquid chromatography coupled with tandem mass - spectrometry ) after four days of incubation of LS180 cells were lower when sildenafil or tadalafil were present, quantification of mRNA expression in these cells by real - time reverse transcription polymerase chain reaction revealed that bosentan and ambrisentan - mediated induction was stable or even increased in combination with sildenafil or tadalafil.", "output": "bosentan, ambrisentan, sildenafil, tadalafil, bosentan, ambrisentan, sildenafil, tadalafil." }, { "input": "For the drug transporter P - glycoprotein this was confirmed at the protein and functional level with highly significant correlations between P - gp mRNA, protein, and function.", "output": "There is no related enetity." }, { "input": "Moreover, using a reporter gene assay in LS180 cells, our study demonstrates for the first time that tadalafil is a potent, ambrisentan a weak, and sildenafil no activator of pregnane X receptor.", "output": "tadalafil, ambrisentan, sildenafil, pregnane." }, { "input": "In conclusion, our study demonstrates that although sildenafil and tadalafil indeed reduce intracellular concentrations of bosentan and ambrisentan in LS180 cells, they do not mitigate the inducing effects of these endothelin - 1 receptor antagonists.", "output": "sildenafil, tadalafil, bosentan, ambrisentan." }, { "input": "Mechanism of maprotiline - induced apoptosis: role of [ Ca2 + ] ( i ), ERK, JNK and caspase - 3 signaling pathways.", "output": "maprotiline, Ca2 +." }, { "input": "Antidepressants are generally used for treatment of various mood and anxiety disorders.", "output": "There is no related enetity." }, { "input": "Several studies have shown the anti - tumor and cytotoxic activities of some antidepressants, but the underlying mechanisms were unclear.", "output": "There is no related enetity." }, { "input": "Maprotiline is a tetracyclic antidepressant and possesses a highly selective norepinephrine reuptake ability.", "output": "Maprotiline, norepinephrine." }, { "input": "We found that maprotiline decreased cell viability in a concentration - and time - dependent manner in Neuro - 2a cells.", "output": "maprotiline." }, { "input": "Maprotiline induced apoptosis and increased caspase - 3 activation.", "output": "Maprotiline." }, { "input": "The activation of caspase - 3 by maprotiline appears to depend on the activation of JNK and the inactivation of ERK.", "output": "maprotiline." }, { "input": "Maprotiline also induced [ Ca ( 2 + ) ] ( i ) increases which involved the mobilization of intracellular Ca ( 2 + ) stored in the endoplasmic reticulum.", "output": "Maprotiline, Ca ( 2 + ), Ca ( 2 + )." }, { "input": "Pretreatment with BAPTA / AM, a Ca ( 2 + ) chelator, suppressed maprotiline - induced ERK phosphorylation, enhanced caspase - 3 activation and increased maprotiline - induced apoptosis.", "output": "BAPTA, Ca ( 2 + ), maprotiline, maprotiline." }, { "input": "In conclusion, maprotiline induced apoptosis in Neuro - 2a cells through activation of JNK - associated caspase - 3 pathways.", "output": "maprotiline." }, { "input": "Maprotiline also evoked an anti - apoptotic response that was both Ca ( 2 + ) - and ERK - dependent.", "output": "Maprotiline, Ca ( 2 + )." }, { "input": "Immunotherapy blocking the tissue plasminogen activator - dependent activation of N - methyl - d - aspartate glutamate receptors improves hemorrhagic stroke outcome.", "output": "N - methyl - d - aspartate, glutamate." }, { "input": "Ischemic and hemorrhagic strokes have different etiologies, but share some pathogenic mechanisms, including a pro - neurotoxic effect of endogenous tissue plasminogen activator ( tPA ) via N - methyl - d - Aspartate ( NMDA ) receptors.", "output": "N - methyl - d - Aspartate, NMDA." }, { "input": "Thus, in a model of intracerebral hemorrhage in rats, we investigated the therapeutic value of a strategy of immunotherapy ( alpha ATD - GluN1 antibody ) preventing the interaction of tPA with NMDA receptors.", "output": "NMDA." }, { "input": "We found that a single intravenous injection of alpha ATD - GluN1 reduced brain edema, neuronal death, microglial activation and functional deficits following intracerebral hemorrhage, without affecting the hematoma volume.", "output": "There is no related enetity." }, { "input": "Do mollusks use vertebrate sex steroids as reproductive hormones?", "output": "steroids." }, { "input": "II.", "output": "There is no related enetity." }, { "input": "Critical review of the evidence that steroids have biological effects.", "output": "steroids." }, { "input": "In assessing the evidence as to whether vertebrate sex steroids ( e. g. testosterone, estradiol, progesterone ) have hormonal actions in mollusks, ca.", "output": "steroids, testosterone, estradiol, progesterone." }, { "input": "85 % of research papers report at least one biological effect; and 18 out of 21 review papers ( published between 1970 and 2012 ) express a positive view.", "output": "There is no related enetity." }, { "input": "However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids ( or modulators of steroids ) on the basis of their effects in vertebrates ( e. g. Bisphenol - A, nonylphenol and sewage treatment effluents ).", "output": "steroids, steroids, steroids, Bisphenol - A, nonylphenol." }, { "input": "Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose - response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within - study repetition.", "output": "steroid." }, { "input": "Furthermore, most studies had very low effect sizes in comparison to fish - based bioassays for steroids ( i. e. they had a very weak ' signal - to - noise ' ratio ).", "output": "steroids." }, { "input": "When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or ' blinding ' procedures ( implying the possibility of ' operator bias ' ) one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks.", "output": "steroids." }, { "input": "The only observation that has been independently validated is the ability of estradiol to trigger rapid ( 1 - 5 min ) lysosomal membrane breakdown in hemocytes of Mytilus spp.", "output": "estradiol." }, { "input": "This is a typical ' inflammatory ' response, however, and is not proof that estradiol is a hormone - especially when taken in conjunction with the evidence ( discussed in a previous review ) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them.", "output": "estradiol, steroids." }, { "input": "Budding yeast Wapl controls sister chromatid cohesion maintenance and chromosome condensation.", "output": "There is no related enetity." }, { "input": "The establishment of stable sister chromatid cohesion during DNA replication requires acetylation of the chromosomal cohesin complex by the replication fork - associated acetyltransferase Eco1.", "output": "There is no related enetity." }, { "input": "Cohesin acetylation is thought to facilitate replication fork progression by counteracting an as yet ill - defined cohesion \" antiestablishment \" activity imposed by the Wapl protein.", "output": "There is no related enetity." }, { "input": "Here, using budding yeast, we find no evidence that cohesin acetylation must overcome Wapl during replication fork progression.", "output": "There is no related enetity." }, { "input": "Instead, Wapl emerges as a negative regulator of cohesion maintenance in G2, a function that it likely exerts through its role as destabilizer of unacetylated, chromosome - bound cohesin.", "output": "There is no related enetity." }, { "input": "Our results suggest that acetylation renders cohesin Wapl - resistant from S phase onward until mitosis.", "output": "There is no related enetity." }, { "input": "In the absence of Wapl, sister chromatid cohesion functions well, suggesting that Wapl partakes in a cohesin function outside of sister chromatid cohesion.", "output": "There is no related enetity." }, { "input": "We find that Wapl is not required for cohesin ' s known role in transcriptional regulation.", "output": "There is no related enetity." }, { "input": "Rather, cells lacking Wapl display increased chromosome condensation in both interphase and mitosis.", "output": "There is no related enetity." }, { "input": "Thus, as a conserved regulator of cohesin dynamics on chromosomes, Wapl controls cohesion maintenance after its establishment in S phase and adjusts the chromosome condensation status.", "output": "There is no related enetity." }, { "input": "Tartary buckwheat improves cognition and memory function in an in vivo amyloid - beta - induced Alzheimer model.", "output": "There is no related enetity." }, { "input": "Protective effects of Tartary buckwheat ( TB ) and common buckwheat ( CB ) on amyloid beta ( A beta ) - induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer ' s disease ( AD ) and its associated progressive memory deficits, cognitive impairment, and personality changes.", "output": "There is no related enetity." }, { "input": "An in vivo mouse model of AD was created by injecting the brains of ICR mice with A beta ( 25 - 35 ), a fragment of the full - length A beta protein.", "output": "There is no related enetity." }, { "input": "Damage of mice recognition ability through following A beta ( 25 - 35 ) brain injections was confirmed using the T - maze test, the object recognition test, and the Morris water maze test.", "output": "There is no related enetity." }, { "input": "Results of behavior tests in AD model showed that oral administration of the methanol ( MeOH ) extracts of TB and CB improved cognition and memory function following A beta ( 25 - 35 ) injections.", "output": "methanol, MeOH." }, { "input": "Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of A beta ( 25 - 35 ), were also decrease.", "output": "MeOH, nitric oxide." }, { "input": "In particular, the MeOH extract of TB exerted a stronger protective activity than CB against A beta ( 25 - 35 ) - induced memory and cognition impairment.", "output": "MeOH." }, { "input": "The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with A beta ( 25 - 35 ) - induced AD.", "output": "There is no related enetity." }, { "input": "Progressive post - yield behavior of human cortical bone in shear.", "output": "There is no related enetity." }, { "input": "Bone fragility depends on its post - yield behavior since most energy dissipation in bone occurs during the post - yield deformation.", "output": "There is no related enetity." }, { "input": "Previous studies have investigated the progressive changes in the post - yield behavior of human cortical bone in tension and compression using a novel progressive loading scheme.", "output": "There is no related enetity." }, { "input": "However, little is known regarding the progressive changes in the post - yield behavior of bone in shear.", "output": "There is no related enetity." }, { "input": "The objective of this short study was to address this issue by testing bone specimens in an inclined double notch shear configuration using the progressive loading protocol.", "output": "There is no related enetity." }, { "input": "The results of this study indicated that the shear modulus of bone decreased with respect to the applied strain, but the rate of degradation was about 50 % less than those previously observed in compression and tension tests.", "output": "There is no related enetity." }, { "input": "In addition, a quasi - linear relationship between the plastic and applied strains was observed in shear mode, which is similar to those previously reported in tension and compression tests.", "output": "There is no related enetity." }, { "input": "However, the viscous responses of bone ( i. e. relaxation time constants and stress magnitude ) demonstrated slight differences in shear compared with those observed in tension and compression tests.", "output": "There is no related enetity." }, { "input": "Nonetheless, the results of this study suggest that the intrinsic mechanism of plastic deformation of human cortical bone may be independent of loading modes.", "output": "There is no related enetity." }, { "input": "Bioactive cis - stilbenoids from the tubers of Scirpus yagara.", "output": "cis - stilbenoids." }, { "input": "Two new cis - stilbenoids, sciryagarol I ( 1 ) and II ( 2 ) were isolated from the EtOAc extract of the tubers of Scirpus yagara, together with four known compounds.", "output": "cis - stilbenoids, sciryagarol I ( 1 ) and II, EtOAc." }, { "input": "The structures of all compounds were determined by comprehensive analyses of their spectroscopic data and comparison with literature information.", "output": "There is no related enetity." }, { "input": "The compounds 3, 4 and 6 were isolated for the first time from this genus.", "output": "There is no related enetity." }, { "input": "Some compounds were tested for their cytotoxicity against human tumor cell lines and antimicrobial activity.", "output": "There is no related enetity." }, { "input": "Compounds 1 - 4 showed significant cytotoxicity against the Hela cell lines with IC ( 50 ) values ranging from 7. 21 to 61. 21 mu M.", "output": "There is no related enetity." }, { "input": "1 and 2 exhibited some antimicrobial activity against Staphylococcus aureus and Candida albicans with uniform MICs of 79. 3 mu l / ml for 2, and 152 mu l / ml for 1, respectively.", "output": "There is no related enetity." }, { "input": "Neuropathy target esterase ( NTE ): overview and future.", "output": "There is no related enetity." }, { "input": "Neuropathy target esterase ( NTE ) was discovered by M. K.", "output": "There is no related enetity." }, { "input": "Johnson in his quest for the entity responsible for the striking and mysterious paralysis brought about by certain organophosphorus ( OP ) esters.", "output": "organophosphorus, esters." }, { "input": "His pioneering work on OP neuropathy led to the view that the biochemical lesion consisted of NTE that had undergone OP inhibition and aging.", "output": "There is no related enetity." }, { "input": "Indeed, nonaging NTE inhibitors failed to produce disease but protected against neuropathy from subsequently administered aging inhibitors.", "output": "There is no related enetity." }, { "input": "Thus, inhibition of NTE activity was not the culprit; rather, formation of an abnormal protein was the agent of the disorder.", "output": "There is no related enetity." }, { "input": "More recently, however, Paul Glynn and colleagues showed that whereas conventional knockout of the NTE gene was embryonic lethal, conditional knockout of central nervous system NTE produced neurodegeneration, suggesting to these authors that the absence of NTE rather than its presence in some altered form caused disease.", "output": "There is no related enetity." }, { "input": "We now know that NTE is the 6th member of a 9 - protein family called patatin - like phospholipase domain - containing proteins, PNPLA1 - 9.", "output": "There is no related enetity." }, { "input": "Mutations in the catalytic domain of NTE ( PNPLA6 ) are associated with a slowly developing disease akin to OP neuropathy and hereditary spastic paraplegia called NTE - related motor neuron disorder ( NTE - MND ).", "output": "There is no related enetity." }, { "input": "Furthermore, the NTE protein from affected individuals has altered enzymological characteristics.", "output": "There is no related enetity." }, { "input": "Moreover, closely related PNPLA7 is regulated by insulin and glucose.", "output": "glucose." }, { "input": "These seemingly disparate findings are not necessarily mutually exclusive, but we need to reconcile recent genetic findings with the historical body of toxicological data indicating that inhibition and aging of NTE are both necessary in order to produce neuropathy from exposure to certain OP compounds.", "output": "There is no related enetity." }, { "input": "Solving this mystery will be satisfying in itself, but it is also an enterprise likely to pay dividends by enhancing our understanding of the physiological and pathogenic roles of the PNPLA family of proteins in neurological health and disease, including a potential role for NTE in diabetic neuropathy.", "output": "There is no related enetity." }, { "input": "Glyoxal and methylglyoxal: autoxidation from dihydroxyacetone and polyphenol cytoprotective antioxidant mechanisms.", "output": "Glyoxal, methylglyoxal, dihydroxyacetone, polyphenol." }, { "input": "Previously, this laboratory had shown that fructose and its downstream metabolites can be enzymatically metabolized to form glyoxal and methylglyoxal.", "output": "fructose, glyoxal, methylglyoxal." }, { "input": "Fructose metabolites, glycoaldehyde, glyceraldehyde and hydroxypyruvate have also been shown to be autoxidizable.", "output": "Fructose, glycoaldehyde, glyceraldehyde, hydroxypyruvate." }, { "input": "In this study, however, fructose did not cause protein carbonylation itself and instead protected against apparent carbonylation by Fenton ' s reagent; fructose did not form significant levels of dicarbonyl compounds over a period of 6 days under standard conditions ( 37 degrees C, pH 7. 4 ).", "output": "fructose, fructose, dicarbonyl." }, { "input": "In contrast, dihydroxyacetone, a fructose metabolite, caused protein carbonylation and autoxidized to form dicarbonyls, which effects were further potentiated under oxidative stress conditions ( Fenton ' s reaction ).", "output": "dihydroxyacetone, fructose, dicarbonyls." }, { "input": "Natural polyphenols were tested for their ability to protect against glyoxal - and methylglyoxal - induced cytotoxicity, reactive oxygen species formation and improved mitochondrial membrane potential maintenance.", "output": "polyphenols, glyoxal, methylglyoxal, oxygen." }, { "input": "The polyphenols investigated were gallic acid, methyl gallate, ethyl gallate, propyl gallate, rutin and curcumin.", "output": "polyphenols, gallic acid, methyl gallate, ethyl gallate, propyl gallate, rutin, curcumin." }, { "input": "The polyphenols were assayed using primary and GSH - depleted hepatocytes.", "output": "polyphenols, GSH." }, { "input": "The polyphenols were also investigated for their rescuing ability and were found to provide greater hepatoprotection when toxins were pre - incubated for 30 min before adding the polyphenols.", "output": "polyphenols, polyphenols." }, { "input": "However, rutin was less protective when rescuing hepatocytes, perhaps, because rutin metabolites may scavenge reactive oxygen species more effectively than rutin itself.", "output": "rutin, rutin, oxygen, rutin." }, { "input": "The longer the alkyl group attached to the gallate compound, the more cytoprotective the polyphenol was.", "output": "alkyl, gallate, polyphenol." }, { "input": "However, the gallates with longer alkyl groups were less able to scavenge reactive oxygen species, and to maintain the mitochondrial membrane potential.", "output": "gallates, alkyl, oxygen." }, { "input": "Aldo - keto reductases in retinoid metabolism: search for substrate specificity and inhibitor selectivity.", "output": "retinoid." }, { "input": "Biological activity of natural retinoids requires the oxidation of retinol to retinoic acid ( RA ) and its binding to specific nuclear receptors in target tissues.", "output": "retinoids, retinol, retinoic acid." }, { "input": "The first step of this pathway, the reversible oxidoreduction of retinol to retinaldehyde, is essential to control RA levels.", "output": "retinol, retinaldehyde." }, { "input": "The enzymes of retinol oxidation are NAD - dependent dehydrogenases of the cytosolic medium - chain ( MDR ) and the membrane - bound short - chain ( SDR ) dehydrogenases / reductases.", "output": "retinol, NAD." }, { "input": "Retinaldehyde reduction can be performed by SDR and aldo - keto reductases ( AKR ), while its oxidation to RA is carried out by aldehyde dehydrogenases ( ALDH ).", "output": "Retinaldehyde, aldehyde." }, { "input": "In contrast to SDR, AKR and ALDH are cytosolic.", "output": "There is no related enetity." }, { "input": "A common property of these enzymes is that they only use free retinoid, but not retinoid bound to cellular retinol binding protein ( CRBP ).", "output": "retinoid, retinoid, retinol." }, { "input": "The relative contribution of each enzyme type in retinoid metabolism is discussed in terms of the different subcellular localization, topology of membrane - bound enzymes, kinetic constants, binding affinity of CRBP for retinol and retinaldehyde, and partition of retinoid pools between membranes and cytoplasm.", "output": "retinoid, retinol, retinaldehyde, retinoid." }, { "input": "The development of selective inhibitors for AKR enzymes 1B1 and 1B10, of clinical relevance in diabetes and cancer, granted the investigation of some structure - activity relationships.", "output": "There is no related enetity." }, { "input": "Kinetics with the 4 - methyl derivatives of retinaldehyde isomers was performed to identify structural features for substrate specificity.", "output": "4 - methyl, retinaldehyde." }, { "input": "Hydrophilic derivatives were better substrates than the more hydrophobic compounds.", "output": "There is no related enetity." }, { "input": "We also explored the inhibitory properties of some synthetic retinoids, known for binding to retinoic acid receptors ( RAR ) and retinoid X receptors ( RXR ).", "output": "retinoids, retinoic acid, retinoid." }, { "input": "Consistent with its substrate specificity towards retinaldehyde, AKR1B10 was more effectively inhibited by synthetic retinoids than AKR1B1.", "output": "retinaldehyde, retinoids." }, { "input": "A RAR beta / gamma agonist ( UVI2008 ) inhibited AKR1B10 with the highest potency and selectivity, and docking simulations predicted that its carboxyl group binds to the anion - binding pocket.", "output": "UVI2008, carboxyl." }, { "input": "Toxicological analysis of limonene reaction products using an in vitro exposure system.", "output": "limonene." }, { "input": "Epidemiological investigations suggest a link between exposure to indoor air chemicals and adverse health effects.", "output": "There is no related enetity." }, { "input": "Consumer products contain reactive chemicals which can form secondary pollutants which may contribute to these effects.", "output": "There is no related enetity." }, { "input": "The reaction of limonene and ozone is a well characterized example of this type of indoor air chemistry.", "output": "limonene, ozone." }, { "input": "The studies described here characterize an in vitro model using an epithelial cell line ( A549 ) or differentiated epithelial tissue ( MucilAir (TM) ).", "output": "There is no related enetity." }, { "input": "The model is used to investigate adverse effects following exposure to combinations of limonene and ozone.", "output": "limonene, ozone." }, { "input": "In A549 cells, exposure to both the parent compounds and reaction products resulted in alterations in inflammatory cytokine production.", "output": "There is no related enetity." }, { "input": "A one hour exposure to limonene + ozone resulted in decreased proliferation when compared to cells exposed to limonene alone.", "output": "limonene, ozone, limonene." }, { "input": "Repeated dose exposures of limonene or limonene + ozone were conducted on MucilAir (TM) tissue.", "output": "limonene, limonene, ozone." }, { "input": "No change in proliferation was observed but increases in cytokine production were observed for both the parent compounds and reaction products.", "output": "There is no related enetity." }, { "input": "Factors such as exposure duration, chemical concentration, and sampling time point were identified to influence result outcome.", "output": "There is no related enetity." }, { "input": "These findings suggest that exposure to reaction products may produce more severe effects compared to the parent compound.", "output": "There is no related enetity." }, { "input": "Brain monoamines and antidepressant - like responses in MRL / MpJ versus C57BL / 6J mice.", "output": "monoamines." }, { "input": "The MRL / MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments.", "output": "There is no related enetity." }, { "input": "This study compared brain monoamine systems between MRL / MpJ and C57BL / 6J mice as a potential basis for strain differences after chronic antidepressant treatment.", "output": "monoamine." }, { "input": "MRL / MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions.", "output": "serotonin, dopamine." }, { "input": "Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains.", "output": "serotonin." }, { "input": "However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL / MpJ mice that was twice as large as achieved in C57BL / 6J mice.", "output": "serotonin, citalopram, serotonin." }, { "input": "The greater effects in MRL / MpJ mice on 5 - HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection.", "output": "5 - HT, citalopram, citalopram." }, { "input": "The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL / MpJ mice.", "output": "serotonin, norepinephrine." }, { "input": "In addition, the expression of 5 - HT ( 1A ) mRNA was lower in the hippocampus, 5 - HT ( 1B ) mRNA was higher in the hippocampus and brainstem and SERT mRNA was higher in the brain stem of MRL / MpJ mice.", "output": "5 - HT, 5 - HT." }, { "input": "The exaggerated neurotransmitter release in MRL / MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine.", "output": "citalopram, desipramine." }, { "input": "These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission.", "output": "serotonin, catecholamine." }, { "input": "Effects of adolescent social defeat on adult amphetamine - induced locomotion and corticoaccumbal dopamine release in male rats.", "output": "amphetamine, dopamine." }, { "input": "Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders.", "output": "dopamine." }, { "input": "Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference following repeated amphetamine treatment.", "output": "dopamine, dopamine, dopamine, amphetamine, amphetamine, amphetamine." }, { "input": "Such changes may reflect altered amphetamine - induced extracellular dopamine release in the corticoaccumbal regions.", "output": "amphetamine, dopamine." }, { "input": "Therefore, we used in vivo microdialysis to measure extracellular dopamine simultaneously within the medial prefrontal cortex and nucleus accumbens core of previously defeated rats and controls, in response to either acute or repeated ( 7 daily injections ) of amphetamine ( 1. 0 mg / kg ).", "output": "dopamine, amphetamine." }, { "input": "Locomotion responses to acute / repeated amphetamine were also assessed the day prior to taking dopamine measurements.", "output": "amphetamine, dopamine." }, { "input": "Adolescent defeat potentiated adult locomotion responses to acute amphetamine, which was negatively correlated with attenuated amphetamine - induced dopamine release in the medial prefrontal cortex, but there was no difference in amphetamine - induced accumbal dopamine release.", "output": "amphetamine, amphetamine, dopamine, amphetamine, dopamine." }, { "input": "However, both locomotion and corticoaccumbal dopamine responses to repeated amphetamine were equivalent between previously defeated rats and controls.", "output": "dopamine, amphetamine." }, { "input": "These data suggest adolescent defeat enhances behavioral responses to initial amphetamine exposure as a function of diminished prefrontal cortex dopamine activity, which may be sufficient to promote subsequently enhanced seeking of drug - associated cues.", "output": "amphetamine, dopamine." }, { "input": "Interestingly, repeated amphetamine treatment appears to normalize amphetamine - elicited locomotion and cortical dopamine responses observed in adult rats exposed to adolescent social defeat, providing implications for treating stress - induced dopamine dysfunction.", "output": "amphetamine, amphetamine, dopamine, dopamine." }, { "input": "Comparative responses of two species of marine phytoplankton to metolachlor exposure.", "output": "metolachlor." }, { "input": "Metolachlor, a chloroacetanilide herbicide, has been frequently detected in coastal waters.", "output": "Metolachlor, chloroacetanilide." }, { "input": "This study examined the growth, photosynthesis, and detoxification responses of chlorophyte Dunaliella tertiolecta ( DT ) and brown tide alga Aureococcus anophagefferens ( AA ) upon 5 - day exposure to 0. 5 - 5 mg L ( - 1 ) metolachlor.", "output": "metolachlor." }, { "input": "Growth was assessed with exponential growth rate, and 5th day in vivo chlorophyll fluorescence, chlorophyll a, b or c, cell density and cell size.", "output": "chlorophyll a , b or c." }, { "input": "The photosynthesis function was assessed with photochemical parameters of photosystem II ( PSII ) during the mid - exponential growth phase ( i. e. 2 - 4 day metolachlor exposure ).", "output": "metolachlor." }, { "input": "The biochemical detoxification was analyzed with glutathione production and metolachlor degradation.", "output": "glutathione, metolachlor." }, { "input": "Results show that metolachlor caused up to ~ 9 % inhibition in growth rate in both species and an expected ~ 35 % and 25 % inhibition in chlorophyll based endpoints in DT and AA respectively.", "output": "metolachlor." }, { "input": "DT had an up to 70 % inhibition in cell density, but AA a 35 % hormesis at 1 mg L ( - 1 ) metolachlor and no significant inhibition, as compared to the controls.", "output": "metolachlor." }, { "input": "Both DT and AA ' s cell sizes were enlarged by metolachlor exposure, but greater in DT ( 1. 2 % per mg L ( - 1 ) ) than in AA ( 0. 68 % per mg L ( - 1 ) ).", "output": "metolachlor." }, { "input": "On PSII photochemistry, maximum quantum yield was not affected in both species; PSII optical cross section and connectivity factor increased in DT but decreased in AA, suggesting species specific impact on PSII function.", "output": "There is no related enetity." }, { "input": "On detoxification responses, glutathione production, when normalized to total chlorophyll a, was not affected by metolachlor in both species; further, despite of heterotrophic capacity of A. anophagefferens metolachlor was not significantly degraded by this alga during the 5 - day incubation.", "output": "glutathione, chlorophyll a, metolachlor, metolachlor." }, { "input": "The species specific effects on algal growth have ecological implications of potential selective inhibition of chlorophytes by metolachlor herbicide.", "output": "metolachlor." }, { "input": "Exposure of zebrafish embryos / larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic - pituitary - thyroid axis.", "output": "TDCPP." }, { "input": "Tris ( 1, 3 - dichloro - 2 - propyl ) phosphate ( TDCPP ) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system.", "output": "Tris ( 1 , 3 - dichloro - 2 - propyl ) phosphate, TDCPP." }, { "input": "In the present study, zebrafish ( Danio rerio ) embryos were exposed to different concentrations of TDCPP ( 10, 50, 100, 300 and 600 mu g / L ) from 2 h post - fertilization ( hpf ) to 144 hpf.", "output": "TDCPP." }, { "input": "Developmental endpoints, and whole - body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic - pituitary - thyroid ( HPT ) axis were examined.", "output": "There is no related enetity." }, { "input": "Exposure to TDCPP caused a dose - dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation ( spinal curvature ).", "output": "TDCPP." }, { "input": "Treatment with the positive control chemical 3, 3 ', 5 - triiodo - l - thyronine ( T3 ) significantly decreased whole - body thyroxin ( T4 ) concentrations, increased whole - body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism.", "output": "3 , 3 ' , 5 - triiodo - l - thyronine, thyroxin ( T4 )." }, { "input": "These results suggested that the HPT axis in 144 - hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system.", "output": "There is no related enetity." }, { "input": "TDCPP exposure significantly decreased whole - body T4 concentrations and increased whole - body T3 concentrations, indicating thyroid endocrine disruption.", "output": "TDCPP." }, { "input": "The upregulation of genes related to thyroid hormone metabolism ( dio1 and ugt1ab ) might be responsible for decreased T4 concentrations.", "output": "There is no related enetity." }, { "input": "Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis ( tsh beta, slc5a5 and tg ) and thyroid development ( hhex, nkx2. 1 and pax8 ) as a compensatory mechanism for decreased T4 concentrations.", "output": "TDCPP." }, { "input": "Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole - body concentrations of thyroid hormones in zebrafish embryos / larvae, thus causing an endocrine disruption of the thyroid system.", "output": "TDCPP." }, { "input": "Methyleugenol hepatocellular cancer initiating effects in rat liver.", "output": "Methyleugenol." }, { "input": "Methyleugenol ( MEG ), a constituent of plants used in the human diet, is hepatocarcinogenic in rodents.", "output": "Methyleugenol, MEG." }, { "input": "In an experiment to elucidate its mode of action in rat liver, male F344 rats were administered MEG intragastrically at 3 doses per week for up to 16 weeks in an initiation phase, after which half the rats were fed 500 ppm phenobarbital ( PB ) in the diet to promote liver neoplasia and the other half were maintained on control diet for 24 weeks.", "output": "MEG, phenobarbital." }, { "input": "At 8 and 16 week interim terminations, ( 32 ) P - nucleotide postlabeling assay revealed 3 adducts in livers of all MEG groups.", "output": "( 32 ) P, MEG." }, { "input": "The hepatocellular replicating fractions, measured by proliferating cell nuclear antigen immunohistochemistry, were doubled or more in all MEG groups.", "output": "MEG." }, { "input": "Hepatocellular altered foci, detected by glutathione S - transferase - placental type ( pi ) immunohistochemistry, were present beginning with the high dose group at 8 weeks and extending to all MEG groups at 16 weeks.", "output": "glutathione, S, MEG." }, { "input": "At the end of maintenance / promotion phase, the incidences, multiplicity and size of foci was similar between control and low dose groups, while those of mid and high dose groups were increased.", "output": "There is no related enetity." }, { "input": "Hepatocellular adenomas occurred in the mid and high dose groups, attaining higher multiplicity and size with PB.", "output": "There is no related enetity." }, { "input": "Thus, MEG had rapid initiating activity, reflecting the formation of DNA adducts and possibly cell proliferation.", "output": "MEG." }, { "input": "Effect of linalool as a component of Humulus lupulus on doxorubicin - induced antitumor activity.", "output": "linalool, doxorubicin." }, { "input": "As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents.", "output": "There is no related enetity." }, { "input": "In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin ( DOX ) permeability in tumor cells and DOX - induced antitumor activity were examined.", "output": "doxorubicin, DOX, DOX." }, { "input": "In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown.", "output": "DOX, linalool, DOX, linalool, DOX." }, { "input": "In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group.", "output": "DOX, linalool, DOX." }, { "input": "The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na ( + ).", "output": "DOX, linalool, Na ( + )." }, { "input": "This promoting effect was suppressed by the presence of S - ( 4 - nitrobenzyl ) - 6 - thioinosine and inhibited dependently on phlorizin concentration.", "output": "S - ( 4 - nitrobenzyl ) - 6 - thioinosine, phlorizin." }, { "input": "It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na ( + ) - dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX.", "output": "linalool, DOX, DOX, Na ( + ), nucleoside, DOX, DOX." }, { "input": "Therefore, linalool as a food component is anticipated to be an effective DOX modulator.", "output": "linalool, DOX." }, { "input": "Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex.", "output": "methylmercury." }, { "input": "We determined the effects of low - level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation.", "output": "MeHg." }, { "input": "We used offspring rats born to dams that had been exposed to saline or various doses of MeHg ( 0. 01 mg / kg / day, 0. 1 mg / kg / day, and 1 mg / kg / day ) from gestational day ( GD ) 11 - 21.", "output": "MeHg." }, { "input": "Immunohistochemical examination of the brains of the offspring was conducted on postnatal day ( PND ) 0, PND3, and PND7.", "output": "There is no related enetity." }, { "input": "Our results showed that prenatal exposure to low levels of MeHg ( 0. 1 mg / kg / day or 1 mg / kg / day ) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats.", "output": "MeHg." }, { "input": "Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells ( NPCs ), induction of apoptosis of NPCs and / or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low - dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself.", "output": "MeHg, MeHg, MeHg." }, { "input": "Moreover, we demonstrated that in utero exposure to low - level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg - induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway.", "output": "MeHg, MeHg." }, { "input": "In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg.", "output": "MeHg." }, { "input": "Attenuated expression of the tight junction proteins is involved in clopidogrel - induced gastric injury through p38 MAPK activation.", "output": "clopidogrel." }, { "input": "Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined.", "output": "clopidogrel." }, { "input": "This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved.", "output": "clopidogrel." }, { "input": "After human gastric epithelial cell line GES - 1 had been treated with clopidogrel ( 0. 5 - 2. 5 mM ), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions ( TJ ) was evaluated by permeability measurement and transmission electron microscopy.", "output": "clopidogrel, MTT, DAPI." }, { "input": "Moreover, expression of the TJ proteins occludin and ZO - 1 and the phosphorylation of the mitogen - activated protein kinases ( MAPK ) p38, ERK, and JNK were examined by western blot.", "output": "There is no related enetity." }, { "input": "In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested.", "output": "There is no related enetity." }, { "input": "Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES - 1 cell viability, and reduced the expression of the TJ proteins ( occludin and ZO - 1 ), acting through p38 MAPK phosphorylation.", "output": "clopidogrel." }, { "input": "Furthermore, these observed effects were partially abolished by SB - 203580 ( a p38 MAPK inhibitor ), rather than by either U - 0126 ( an ERK inhibitor ) or SP - 600125 ( a JNK inhibitor ), suggesting that clopidogrel - induced disruption in the gastric epithelial cells is mediated by the p38 MAPK pathway.", "output": "SB - 203580, U - 0126, SP - 600125, clopidogrel." }, { "input": "It is concluded that attenuated expression of the TJ proteins occludin and ZO - 1 in human gastric epithelial cells could be involved in clopidogrel - induced gastric mucosal injury through activation of the p38 MAPK pathway.", "output": "clopidogrel." }, { "input": "Effect of polyethylene glycol conjugation on the circulatory stability of plasma - derived human butyrylcholinesterase in mice.", "output": "polyethylene glycol." }, { "input": "Exogenously administered human serum butyrylcholinesterase ( Hu BChE ) was demonstrated to function as a bioscavenger of highly toxic organophosphorus ( OP ) compounds in several animal species.", "output": "organophosphorus." }, { "input": "Since the enzyme is isolated from human serum, it is currently the most suitable pretreatment for human use.", "output": "There is no related enetity." }, { "input": "A dose of 200 - 300mg / 70kg human adult is projected to provide protection from 2 X LD50 of soman.", "output": "soman." }, { "input": "Due to the limited supply of Hu BChE, strategies aimed at reducing the dose of enzyme are being explored.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the effect of modification with polyethylene glycol ( PEG ) on the in vivo stability of Hu BChE.", "output": "polyethylene glycol, PEG." }, { "input": "Mice were given two injections of either Hu BChE or Hu BChE modified with PEG - 5K or PEG - 20K, six weeks apart.", "output": "PEG, PEG." }, { "input": "Pharmacokinetic parameters, such as mean residence time ( MRT ), maximal concentration ( Cmax ), elimination half - life ( T1 / 2 ), and area under the plasma concentration time curve extrapolated to infinity ( AUC ), were determined.", "output": "There is no related enetity." }, { "input": "For the first injection, values for MRT, T1 / 2, Cmax, and AUC for PEG - 5K - Hu BChE and PEG - 20K - Hu BChE were similar to those for Hu BChE.", "output": "PEG, PEG." }, { "input": "These values for the second injection of Hu BChE as well as PEG - Hu BChEs were lower as compared to those for the first injections, likely due to antibody - mediated clearance.", "output": "PEG." }, { "input": "Acrolein and chloroacetaldehyde: an examination of the cell and cell - free biomarkers of toxicity.", "output": "Acrolein, chloroacetaldehyde." }, { "input": "Cyclophosphamide and ifosfamide are two commonly used DNA - alkylating agents in cancer chemotherapy that undergo biotransformation to several toxic and non - toxic metabolites, including acrolein and chloroacetaldehyde ( CAA ).", "output": "Cyclophosphamide, ifosfamide, acrolein, chloroacetaldehyde, CAA." }, { "input": "Acrolein and CAA toxicities occur by several different mechanisms, including ROS formation and protein damage ( oxidation ), however, these pathways of toxicity and protecting agents used to prevent them have yet to be compared and ranked in a single study.", "output": "Acrolein, CAA." }, { "input": "This research focused on the molecular targets of acrolein and CAA toxicities and strategies to decrease toxicities.", "output": "acrolein, CAA." }, { "input": "Hepatocyte viability ( cytotoxicity ) was assessed using Trypan blue uptake; formation of reactive oxygen species ( ROS ) and endogenous H2O2 were also assessed in the hepatocyte model.", "output": "Trypan blue, oxygen, H2O2." }, { "input": "In cell - free models ( bovine serum albumin and hepatic microsomes ), protein carbonylation was the measurement of toxicity.", "output": "There is no related enetity." }, { "input": "The present study demonstrated that acrolein was a more potent toxin than CAA for freshly isolated rat hepatocytes, bovine serum albumin and rat hepatic microsomes.", "output": "acrolein, CAA." }, { "input": "Acrolein protein carbonylation was dependent on its concentration; as acrolein concentration increased, protein carbonylation increased in a linear trend, whereas, CAA deviated from the trend and did not cause protein carbonylation at lower concentrations ( < 400 mu M ).", "output": "Acrolein, acrolein, CAA." }, { "input": "Aldehyde dehydrogenase ( ALDH ) is a major pathway for detoxifying pathway for CAA in hepatocytes, as a 3 - fold increase in cytotoxicity occurred when cells were incubated with cyanamide, an ALDH inhibitor.", "output": "Aldehyde, CAA, cyanamide." }, { "input": "Inhibiting ALDH or depleting GSH in hepatocytes increased cytotoxicity by about 3 - fold in acrolein - treated hepatocytes.", "output": "acrolein." }, { "input": "The overall effectiveness of protecting agents to prevent or suppress acrolein or CAA toxicities in cell and cell - free models were ranked in order of most effective to least effective: reducing agents ( sodium borohydride, sodium bisulfite ) > thiol - containing compounds ( N - acetylcysteine, cysteine, glutathione, 2 - mercaptoethane sulfonate [ MESNA ], penicillamine ) > carbonyl scavengers / amines ( aminoguanidine, hydralazine, hydroxylamine ) > antioxidants / ROS scavengers ( ascorbic acid, Trolox; only utilized in hepatocyte system ).", "output": "acrolein, CAA, sodium borohydride, sodium bisulfite, thiol, N - acetylcysteine, cysteine, glutathione, 2 - mercaptoethane sulfonate, MESNA, penicillamine, carbonyl, amines, aminoguanidine, hydralazine, hydroxylamine, ascorbic acid, Trolox." }, { "input": "An understanding of acrolein and CAA toxicities and the ability of protecting agents to protect against toxicities may help to establish or improve existing therapeutic interventions against the side effects associated with acrolein or CAA in cyclophosphamide or ifosfamide treatment.", "output": "acrolein, CAA, acrolein, CAA, cyclophosphamide, ifosfamide." }, { "input": "In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.", "output": "There is no related enetity." }, { "input": "Organophosphorus compounds ( OPC ) were developed as warfare nerve agents.", "output": "Organophosphorus." }, { "input": "They are also widely used as pesticides.", "output": "There is no related enetity." }, { "input": "The drug therapy of intoxication with OPC includes mainly combination of cholinesterase ( ChE ) reactivators and cholinolytics.", "output": "There is no related enetity." }, { "input": "There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors.", "output": "There is no related enetity." }, { "input": "The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication ( tabun, paraoxon and dichlorvos ) in in vitro experiments and to compare their activity to that known for some currently used oximes ( obidoxime, HI - 6, 2 - PAM ).", "output": "tabun, paraoxon, dichlorvos, oximes, obidoxime, HI - 6, 2 - PAM." }, { "input": "Experiments were carried out using rat brain acetylcholinesterase ( AChE ).", "output": "There is no related enetity." }, { "input": "Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition.", "output": "dichlorvos, paraoxon, tabun." }, { "input": "AChE was easier reactivated after paraoxon treatment.", "output": "paraoxon." }, { "input": "The best effect showed BT - 07 - 4M, obidoxime, TMB - 4 and BT - 08 from the group of symmetric oximes, and Toxidin, BT - 05 and BT - 03 from asymmetric compounds.", "output": "BT - 07 - 4M, obidoxime, TMB - 4, BT - 08, oximes, Toxidin, BT - 05, BT - 03." }, { "input": "The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT - 07 - 4M, TMB - 4 and obidoxime from symmetric oximes, and BT - 05 and BT - 03 possessing asymmetric structure.", "output": "BT - 07 - 4M, TMB - 4, obidoxime, oximes, BT - 05, BT - 03." }, { "input": "All compounds showed low activity toward inhibition of AChE caused by dichlorvos.", "output": "dichlorvos." }, { "input": "Comparison of two main structure types ( symmetric / asymmetric ) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones.", "output": "There is no related enetity." }, { "input": "Profiling of oxidized lipid products of marine fish under acute oxidative stress.", "output": "There is no related enetity." }, { "input": "Free radical products including reactive oxygen species are potent to oxidize lipids and reliable measurements have been established mostly in human and rodent.", "output": "oxygen." }, { "input": "To date, robust biomarkers were not used to assess the peroxidation in marine fish.", "output": "There is no related enetity." }, { "input": "The changes of oxidized lipid products from polyunsaturated fatty acids and cholesterol were assessed after exposure of H ( 2 ) O ( 2 ) to fish ( medaka ).", "output": "polyunsaturated fatty acids, cholesterol, H ( 2 ) O ( 2 )." }, { "input": "Oxidized lipid products released by free radical reaction ( F ( 2 ) - isoprostanes and metabolites, F ( 3 ) - isoprostanes, neuroprostanes, 7 - ketocholesterol, 7 beta - hydroxycholesterol ), by lipoxygenase enzymes ( 5 ( S ) -, 8 ( S ) -, 12 ( S ) - and 15 ( S ) - HETE, and resolvin D1 ) and by cytochrome P450 ( 9 ( S ) -, 11 ( S ) - and 20 - HETE, and 27 - hydroxycholestrol ) were measured in fish muscle using LC / MS / MS.", "output": "isoprostanes, isoprostanes, neuroprostanes, 7 - ketocholesterol, 7 beta - hydroxycholesterol, 5 ( S ) - , 8 ( S ) - , 12 ( S ) - and 15 ( S ) - HETE, resolvin D1, 9 ( S ) - , 11 ( S ) - and 20 - HETE, 27 - hydroxycholestrol." }, { "input": "Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels, and antioxidant enzymes activity ( catalase, SOD and gluthathione reductase ) measurement were also determined.", "output": "Arachidonate, docosahexaenoate, eicosapentaenoate, cholesterol, gluthathione." }, { "input": "Activity of antioxidant enzymes especially catalase were elevated in presence of H ( 2 ) O ( 2 ) however longer exposure time suppressed the antioxidant activities.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Arachidonate, docosahexaenoate, eicosapentaenoate and cholesterol levels were reduced in presence of H ( 2 ) O ( 2 ) and oxidized lipid products ( isoprostanes, neuroprostanes 5 ( S ) - HETE, 20 - HETE, 7 - ketocholesterol, 27 - hydroxycholesterol and resolvin D1 ) were rapidly released in the fish muscle.", "output": "Arachidonate, docosahexaenoate, eicosapentaenoate, cholesterol, H ( 2 ) O ( 2 ), isoprostanes, neuroprostanes, 5 ( S ) - HETE, 20 - HETE, 7 - ketocholesterol, 27 - hydroxycholesterol, resolvin D1." }, { "input": "This study validates oxidized lipid products, noticeably isoprostanes are measurable in marine fish muscle and should be considered when assessing oxidative stress especially due to exogenous factors.", "output": "isoprostanes." }, { "input": "Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract.", "output": "There is no related enetity." }, { "input": "In breast cancer patients ( before and during anti - cancer therapy ) oxidative / nitrative damage to various molecules is observed.", "output": "There is no related enetity." }, { "input": "Furthermore, anti - cancer treatments may also influence the hemostatic properties of blood platelets and plasma.", "output": "There is no related enetity." }, { "input": "The aim of our study was to assess the effect of oxidative / nitrative stress ( estimated by measurements of the levels of carbonyl groups and 3 - nitrotyrosine in proteins - - ELISA and C - ELISA methods, respectively; lipid peroxidation and total antioxidant level - - TAS ) on the selected parameters of hemostatic activity of plasma ( the process of fibrin polymerization and lysis ) collected from breast cancer patients after surgery and after various phases of chemotherapy ( doxorubicin and cyclophosphamide ).", "output": "carbonyl, 3 - nitrotyrosine, doxorubicin, cyclophosphamide." }, { "input": "Subsequently, we also evaluated the level of oxidative / nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa ( Aronox (R) ) in vitro.", "output": "There is no related enetity." }, { "input": "Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland.", "output": "There is no related enetity." }, { "input": "We observed increased levels of biomarkers of oxidative / nitrative stress in plasma from patients with breast cancer ( before or after surgery and after various phases of chemotherapy ) in comparison to healthy group.", "output": "There is no related enetity." }, { "input": "Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers.", "output": "There is no related enetity." }, { "input": "We also recognize the existence of a relationship between oxidative stress ( measured by the level of carbonyl groups ) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy.", "output": "There is no related enetity." }, { "input": "Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative / nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy.", "output": "There is no related enetity." }, { "input": "Considering the data presented in this study, we suggest that the oxidative / nitrative stress in plasma obtained from breast cancer patients ( not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy ) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients.", "output": "doxorubicin, cyclophosphamide." }, { "input": "Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients.", "output": "There is no related enetity." }, { "input": "The AhR twist: ligand - dependent AhR signaling and pharmaco - toxicological implications.", "output": "There is no related enetity." }, { "input": "The aryl hydrocarbon receptor ( AhR ) is a transcription factor which is activated by diverse compounds and regulates the expression of xenobiotic metabolism genes.", "output": "aryl hydrocarbon." }, { "input": "Recent studies have unraveled unsuspected physiological roles and novel alternative ligand - specific pathways for this receptor.", "output": "There is no related enetity." }, { "input": "In this review, we discuss these novel aspects and focus on the different responses elicited by the diverse endogenous and / or exogenous AhR ligands.", "output": "There is no related enetity." }, { "input": "In addition to challenging the relevance of the ' agonist / antagonist ' classification of ligands, we introduce the concept of AhR plasticity as a primordial factor in the generation of these pathways.", "output": "There is no related enetity." }, { "input": "Finally, we suggest several promising perspectives for the pharmacological modulation of these responses.", "output": "There is no related enetity." }, { "input": "Optimization of 5 - hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase.", "output": "5 - hydroxytryptamines." }, { "input": "Dual function inhibitors targeting phospholipase A ( 2 ) ( PLA ( 2 ) ) and leukotriene A ( 4 ) hydrolase ( LTA ( 4 ) H ) may balance the arachidonic acid ( AA ) metabolic network and be used as new anti - inflammatory drugs.", "output": "arachidonic acid." }, { "input": "In previous study, we discovered multi - target drugs towards the AA metabolic network, among which a dual - target inhibitor ( JMC08 - 4 ) for human nonpancreatic secretory phospholipase A ( 2 ) ( hnps - PLA ( 2 ) ) and human leukotriene A ( 4 ) hydrolase ( LTA ( 4 ) H - h ) was found.", "output": "JMC08 - 4." }, { "input": "Based on the structure of compound JMC08 - 4, new dual - target inhibitors were designed assisted by molecular docking.", "output": "JMC08 - 4." }, { "input": "In this report, a series of 5 - hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08 - 4 in the in vitro bioassay against these two enzymes.", "output": "5 - hydroxytryptamine, JMC08 - 4." }, { "input": "The best one inhibited hnps - PLA ( 2 ) and LTA ( 4 ) H - h with IC ( 50 ) values of 9. 2 +/- 0. 5 mu M and 2. 4 +/- 1. 4 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.", "output": "benzoheterocyclic." }, { "input": "Human acrosin is an attracting target for the development of novel male contraceptives.", "output": "There is no related enetity." }, { "input": "Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure - activity relationships.", "output": "isoxazolecarbaldehyde." }, { "input": "Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H - indazole, and 5 - phenyl - 1H - pyrazole, were designed and synthesized.", "output": "benzimidazole, benzothiazole, 3H - indazole, 5 - phenyl - 1H - pyrazole." }, { "input": "Most of the synthesized compounds showed potent human acrosin inhibitory activity and their binding modes were investigated by molecular docking.", "output": "There is no related enetity." }, { "input": "The scaffold of the compounds was found to be important for the inhibitory activity.", "output": "There is no related enetity." }, { "input": "Several compounds were more active than the positive control TLCK, suggesting that they can serve as good starting points for the discovery of novel male contraceptive agents.", "output": "TLCK." }, { "input": "Role of organic cation / carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex I respiration in mitochondria.", "output": "carnitine, phenformin." }, { "input": "Phenformin causes lactic acidosis in clinical situations due to inhibition of mitochondrial respiratory chain complex I.", "output": "Phenformin." }, { "input": "It is reportedly taken up by hepatocytes and exhibits mitochondrial toxicity in the liver.", "output": "There is no related enetity." }, { "input": "In this study, uptake of phenformin and [ ( 14 ) C ] tetraethylammonium ( TEA ) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria.", "output": "phenformin, [ ( 14 ) C ] tetraethylammonium, TEA, phenformin." }, { "input": "Uptake of phenformin into isolated rat liver mitochondria was higher than that into heart mitochondria.", "output": "phenformin." }, { "input": "It was inhibited by several cat ionic compounds, which suggests the involvement of multispecific transport system ( s ).", "output": "There is no related enetity." }, { "input": "Similar characteristics were also observed for uptake of TEA; however, uptake of phenformin into mitochondria of organic cation / carnitine transporter 1 ( OCTN1 ) knockout mice was lower than that in wild - type mice, whereas uptake of TEA was comparable between the two strains, suggesting the involvement of distinct transport mechanisms for these two cations in mitochondria.", "output": "TEA, phenformin, carnitine, TEA." }, { "input": "Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside - out structured submitochondrial particles prepared from rat livers and hearts.", "output": "phenformin, oxygen, phenformin." }, { "input": "Lactic acidosis provoked by iv infusion of phenformin was weaker in octn1 ( - / - ) mice than that in wild - type mice.", "output": "phenformin." }, { "input": "These observations suggest that uptake of phenformin into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of complex I respiration.", "output": "phenformin." }, { "input": "This study was, thus, the first to demonstrate OCTN1 - mediated mitochondrial transport and toxicity of biguanide in vivo in rodents.", "output": "There is no related enetity." }, { "input": "Novel Smad proteins localize to IR - induced double - strand breaks: interplay between TGF beta and ATM pathways.", "output": "There is no related enetity." }, { "input": "Cellular damage from ionizing radiation ( IR ) is in part due to DNA damage and reactive oxygen species, which activate DNA damage response ( DDR ) and cytokine signaling pathways, including the ataxia telangiectasia mutated ( ATM ) and transforming growth factor ( TGF ) beta / Smad pathways.", "output": "oxygen." }, { "input": "Using classic double - strand breaks ( DSBs ) markers, we studied the roles of Smad proteins in DDR and the crosstalk between TGF beta and ATM pathways.", "output": "There is no related enetity." }, { "input": "We observed co - localization of phospho - Smad2 ( pSmad2 ) and Smad7 with DSB repair proteins following low and high linear energy transfer ( LET ) radiation in human fibroblasts and epithelial cells.", "output": "phospho." }, { "input": "The decays of both foci were similar to that of gamma H2AX foci.", "output": "There is no related enetity." }, { "input": "Irradiation with high LET particles induced pSmad2 and Smad7 foci tracks indicating the particle trajectory through cells.", "output": "There is no related enetity." }, { "input": "pSmad2 foci were absent in S phase cells, while Smad7 foci were present in all phases of cell cycle.", "output": "There is no related enetity." }, { "input": "pSmad2 ( but not Smad7 ) foci were completely abolished when ATM was depleted or inactivated.", "output": "There is no related enetity." }, { "input": "In contrast, a TGF beta receptor 1 ( TGF beta R1 ) inhibitor abrogated Smad7, but not pSmad2 foci at DSBs sites.", "output": "There is no related enetity." }, { "input": "In summary, we suggest that Smad2 and Smad7 contribute to IR - induced DSB signaling in an ATM or TGF beta R1 - dependent manner, respectively.", "output": "There is no related enetity." }, { "input": "Removal of valproic acid by plasmapheresis in a patient treated for multiple sclerosis.", "output": "valproic acid." }, { "input": "We present a case of a patient with multiple sclerosis who was treated with plasmapheresis and valproic acid.", "output": "valproic acid." }, { "input": "We used therapeutic drug monitoring to determine whether plasma concentrations of valproic acid were kept within the therapeutic window and to determine the amount of valproic acid that was removed by plasmapheresis.", "output": "valproic acid, valproic acid." }, { "input": "Somatic neurofibromatosis type 1 ( NF1 ) inactivation characterizes NF1 - associated pilocytic astrocytoma.", "output": "There is no related enetity." }, { "input": "Low - grade brain tumors ( pilocytic astrocytomas ) arising in the neurofibromatosis type 1 ( NF1 ) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations.", "output": "There is no related enetity." }, { "input": "However, genetically engineered mice ( GEM ) in which mono - allelic germline Nf1 gene loss is coupled with bi - allelic somatic ( glial progenitor cell ) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition.", "output": "There is no related enetity." }, { "input": "These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1 - associated low - grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype.", "output": "There is no related enetity." }, { "input": "To identify these potential cooperating genetic mutations, we performed whole - genome sequencing ( WGS ) analysis of three NF1 - associated pilocytic astrocytoma ( PA ) tumors.", "output": "There is no related enetity." }, { "input": "We found that the mechanism of somatic NF1 loss was different in each tumor ( frameshift mutation, loss of heterozygosity, and methylation ).", "output": "There is no related enetity." }, { "input": "In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50 % - 60 % of cells in the tumor mass exhibited somatic NF1 loss.", "output": "There is no related enetity." }, { "input": "Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment.", "output": "There is no related enetity." }, { "input": "Increase of palmitic acid concentration impairs endothelial progenitor cell and bone marrow - derived progenitor cell bioavailability: role of the STAT5 / PPAR gamma transcriptional complex.", "output": "palmitic acid." }, { "input": "Metabolic profiling of plasma nonesterified fatty acids discovered that palmitic acid ( PA ), a natural peroxisome proliferator - activated receptor gamma ( PPAR gamma ) ligand, is a reliable type 2 diabetes biomarker.", "output": "fatty acids, palmitic acid." }, { "input": "We investigated whether and how PA diabetic ( d - PA ) concentrations affected endothelial progenitor cell ( EPC ) and bone marrow - derived hematopoietic cell ( BM - HC ) biology.", "output": "There is no related enetity." }, { "input": "PA physiologic ( n - PA ) and d - PA concentrations were used.", "output": "There is no related enetity." }, { "input": "Proliferating cell nuclear antigen content and signal transducer and activator of transcription 5 ( STAT5 ), PPAR gamma, cyclin D1, and p21 ( Waf ) expression were evaluated.", "output": "There is no related enetity." }, { "input": "Small interfering RNA technology, gene reporter luciferase assay, electrophoretic mobility shift assay, chromatin immunoprecipitation assay, and coimmunoprecipitation were exploited.", "output": "There is no related enetity." }, { "input": "In vivo studies and migration assays were also performed.", "output": "There is no related enetity." }, { "input": "d - PA, unlike n - PA or physiological and diabetic oleic and stearic acid concentrations, impaired EPC migration and EPC / BM - HC proliferation through a PPAR gamma - mediated STAT5 transcription inhibition.", "output": "oleic and stearic acid." }, { "input": "This event did not prevent the formation of a STAT5 / PPAR gamma transcriptional complex but was crucial for gene targeting, as p21 ( Waf ) gene promoter, unlike cyclin D1, was the STAT5 / PPAR gamma transcriptional target.", "output": "There is no related enetity." }, { "input": "Similar molecular events could be detected in EPCs isolated from type 2 diabetic patients.", "output": "There is no related enetity." }, { "input": "By expressing a constitutively activated STAT5 form, we demonstrated that STAT5 content is crucial for gene targeting and EPC fate.", "output": "There is no related enetity." }, { "input": "Finally, we also provide in vivo data that d - PA - mediated EPC dysfunction could be rescued by PPAR gamma blockade.", "output": "There is no related enetity." }, { "input": "These data provide first insights on how mechanistically d - PA drives EPC / BM - HC dysfunction in diabetes.", "output": "There is no related enetity." }, { "input": "The fidelity of transcription: RPB1 ( RPO21 ) mutations that increase transcriptional slippage in S. cerevisiae.", "output": "There is no related enetity." }, { "input": "The fidelity of RNA synthesis depends on both accurate template - mediated nucleotide selection and proper maintenance of register between template and RNA.", "output": "nucleotide." }, { "input": "Loss of register, or transcriptional slippage, is particularly likely on homopolymeric runs in the template.", "output": "There is no related enetity." }, { "input": "Transcriptional slippage can alter the coding capacity of mRNAs and is used as a regulatory mechanism.", "output": "There is no related enetity." }, { "input": "Here we describe mutations in the largest subunit of Saccharomyces cerevisiae RNA polymerase II that substantially increase the level of transcriptional slippage.", "output": "There is no related enetity." }, { "input": "Alleles of RPB1 ( RPO21 ) with elevated slippage rates were identified among 6 - azauracil - sensitive mutants and were also isolated using a slippage - dependent reporter gene.", "output": "6 - azauracil." }, { "input": "Biochemical characterization of polymerase II isolated from these mutants confirms elevated levels of transcriptional slippage.", "output": "There is no related enetity." }, { "input": "The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial.", "output": "Carbohydrate." }, { "input": "OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain.", "output": "There is no related enetity." }, { "input": "The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate - rich diet ( CARB; similar to the Dietary Approaches to Stop Hypertension [ DASH ] diet ), a protein - rich diet ( PROT; protein predominantly from plant sources ), and an unsaturated fat - rich diet ( UNSAT; predominantly monounsaturated ).", "output": "carbohydrate, CARB." }, { "input": "RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three - period, crossover feeding study.", "output": "There is no related enetity." }, { "input": "The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes.", "output": "There is no related enetity." }, { "input": "Diets were administered for 6 weeks each, with a washout period between diets of 2 - 4 weeks.", "output": "There is no related enetity." }, { "input": "Weight was held constant throughout the study.", "output": "There is no related enetity." }, { "input": "For our primary outcome, we calculated the quantitative insulin sensitivity check index ( QUICKI ) using the end - of - period fasting serum glucose and insulin.", "output": "glucose." }, { "input": "QUICKI is a validated measure of insulin sensitivity.", "output": "There is no related enetity." }, { "input": "The primary analyses used generalized estimating equations.", "output": "There is no related enetity." }, { "input": "RESULTS At baseline, mean ( SD ) BMI was 30. 2 ( 6. 1 ) kg / m ( 2 ), and mean ( SD ) QUICKI was 0. 35 ( 0. 04 ).", "output": "There is no related enetity." }, { "input": "The UNSAT diet increased QUICKI by 0. 005, more than the CARB diet ( P = 0. 04 ).", "output": "CARB." }, { "input": "PROT had no significant effect compared with CARB.", "output": "CARB." }, { "input": "CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease.", "output": "carbohydrate." }, { "input": "Given the well - recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Four - Year Change in Cardiorespiratory Fitness and Influence on Glycemic Control in Adults With Type 2 Diabetes in a Randomized Trial: The Look AHEAD Trial.", "output": "There is no related enetity." }, { "input": "OBJECTIVE To examine an intensive lifestyle intervention ( ILI ) compared with diabetes support and education ( DSE ) on 4 - year change in fitness and physical activity ( PA ), and to examine the effect of change in fitness and PA, adjusting for potential confounders, on glycemic control in the Look AHEAD Trial.", "output": "There is no related enetity." }, { "input": "RESEARCH DESIGN AND METHODS Subjects were overweight / obese adults with type 2 diabetes mellitus ( T2DM ) with available fitness data at 4 years ( n = 3, 942 ). This clinical trial randomized subjects to DSE or ILI.", "output": "There is no related enetity." }, { "input": "DSE subjects received standard care plus information related to diet, PA, and social support three times per year.", "output": "There is no related enetity." }, { "input": "ILI subjects received weekly intervention contact for 6 months, which was reduced over the 4 - year period, and were prescribed diet and PA.", "output": "There is no related enetity." }, { "input": "Measures included weight, fitness, PA, and HbA1c.", "output": "There is no related enetity." }, { "input": "RESULTS The difference in percent fitness change between ILI and DSE at 4 years was significant after adjustment for baseline fitness and change in weight ( 3. 70 vs. 0. 94 %; P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "At 4 years, PA increased by 348 ( 1, 562 ) kcal / week in ILI vs. 105 ( 1, 309 ) kcal / week in DSE ( P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Fitness change at 4 years was inversely related to change in HbA1c after adjustment for clinical site, treatment, baseline HbA1c, prescribed diabetes medication, baseline fitness, and weight change ( P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Change in PA was not related to change in HbA1c.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS A 4 - year ILI increased fitness and PA in overweight / obese individuals with T2DM.", "output": "There is no related enetity." }, { "input": "Change in fitness was associated with improvements in glycemic control, which provides support for interventions to improve fitness in adults with T2DM.", "output": "There is no related enetity." }, { "input": "The chemical synthesis of DNA / RNA: our gift to science.", "output": "There is no related enetity." }, { "input": "It is a great privilege to contribute to the Reflections essays.", "output": "There is no related enetity." }, { "input": "In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by what I have learned from three colleagues ( Robert Letsinger, Gobind Khorana, and George Rathmann ) who molded my career at every important junction.", "output": "There is no related enetity." }, { "input": "To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology.", "output": "There is no related enetity." }, { "input": "Relative to my scientific career, I have focused primarily on two related areas.", "output": "There is no related enetity." }, { "input": "The first is methodologies we developed for chemically synthesizing DNA and RNA.", "output": "There is no related enetity." }, { "input": "Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists.", "output": "There is no related enetity." }, { "input": "The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs.", "output": "There is no related enetity." }, { "input": "Quantum chemical study of the catalytic activation of methane by copper oxide and copper hydroxide cations.", "output": "methane, copper oxide, copper hydroxide." }, { "input": "The activation of methane and its subsequent conversion into more valuable feedstocks under ambient conditions are regarded as one of the major challenges in contemporary catalysis, due to its thermodynamically strong and kinetically inert C - H bond.", "output": "methane, C - H." }, { "input": "Several enzymes and synthetic bioinorganic systems perform the activation of C - H bonds in methane and small hydrocarbons, mediated by transition metal mononuclear centers.", "output": "C - H, methane, hydrocarbons, transition metal." }, { "input": "Among them, monocopper cores and, in particular, CuO ( + ) and CuOH ( + ) have been suggested as efficient catalytic centers; this activity has not been experimentally proven until very recently, mainly due to the difficulty to produce sufficient amounts of active species to demonstrate the bond activation processes.", "output": "CuO ( + ), CuOH ( + )." }, { "input": "The theoretical study presented here provides a thorough quantum chemical description of the activity of both species, together with molecular level insight into the elementary steps of the experimentally observed reactions.", "output": "There is no related enetity." }, { "input": "Post - HF ( CCSD ( T ), CASPT2 ) and Density Functional Theory ( DFT ) methods have been used to unravel detailed electronic and mechanistic aspects of the reaction paths.", "output": "There is no related enetity." }, { "input": "Our study reveals the decisive role of the oxygen - centered radical in the reactivity of both species, and the improvement of the reactivity as a result of the protonation of the active species.", "output": "oxygen." }, { "input": "Patterned polymer nanowire arrays as an effective protein immobilizer for biosensing and HIV detection.", "output": "There is no related enetity." }, { "input": "We report an array of polymeric nanowires for effectively immobilizing biomolecules on biochips owing to the large surface area.", "output": "There is no related enetity." }, { "input": "The nanowires were fabricated in predesigned patterns using an inductively coupled plasma ( ICP ) etching process.", "output": "There is no related enetity." }, { "input": "Microfluidic biochips integrated using the substrates with arrays of nanowires and polydimethylsiloxane channels have been demonstrated to be effective for detecting antigens, and a detection limit of antigens at 0. 2 mu g mL ( - 1 ) has been achieved, which is improved by a factor of 50 compared to that based on flat substrates without the nanowires.", "output": "polydimethylsiloxane." }, { "input": "In addition, the high sensitivity for clinical detection of human immunodeficiency virus ( HIV ) antibody has also been demonstrated, showing a 20 times enhancement in fluorescent signal intensity between the samples with positive and negative HIV.", "output": "There is no related enetity." }, { "input": "Micro - mesoporous materials obtained by zeolite recrystallization: synthesis, characterization and catalytic applications.", "output": "zeolite." }, { "input": "The review covers the recent developments in the field of novel micro - mesoporous materials obtained by zeolite recrystallization.", "output": "zeolite." }, { "input": "The materials are classified into three distinctly different groups depending on the degree of recrystallization: ( i ) coated mesoporous zeolites ( RZEO - 1 ); ( ii ) micro - mesoporous nanocomposites ( RZEO - 2 ); and ( iii ) mesoporous materials with zeolitic fragments in the walls ( RZEO - 3 ).", "output": "zeolites." }, { "input": "The first part of the review is focused on the analysis of the synthetic strategies leading to different types of recrystallized materials.", "output": "There is no related enetity." }, { "input": "In the second part, a comprehensive view on their structure, texture and porosity in connection with acidic and diffusion properties is given.", "output": "There is no related enetity." }, { "input": "The last part is devoted to the catalytic applications of recrystallized materials.", "output": "There is no related enetity." }, { "input": "The advantages and disadvantages with respect to pure micro - and mesoporous molecular sieves and other hierarchical zeolites are critically analyzed and the future opportunities and perspectives are discussed.", "output": "zeolites." }, { "input": "Hydrophobic asymmetric ultrafiltration PVDF membranes: an alternative separator for VFB with excellent stability.", "output": "PVDF." }, { "input": "Polyvinylidene fluoride ( PVDF ) ultrafiltration membranes were investigated for the first time in vanadium redox flow battery ( VFB ) applications.", "output": "Polyvinylidene fluoride, PVDF, vanadium." }, { "input": "Surprisingly, PVDF ultrafiltration membranes with hydrophobic pore walls and relatively large pore sizes of several tens of nanometers proved able to separate vanadium ions and protons efficiently, thus being suitable as a VFB separator.", "output": "PVDF, vanadium." }, { "input": "The ion selectivity of this new type of VFB membrane could be tuned readily by controlling the membrane morphology via changes in the composition of the membrane casting solution, and the casting thickness.", "output": "There is no related enetity." }, { "input": "The results showed that the PVDF membranes offered good performances and excellent stability in VFB applications, where it could, performance - wise, truly substitute Nafion in VFB applications, but at a much lower cost.", "output": "PVDF, Nafion." }, { "input": "Lanthanide - doped luminescent nano - bioprobes: from fundamentals to biodetection.", "output": "Lanthanide." }, { "input": "Trivalent lanthanide ( Ln ( 3 + ) ) - doped luminescent inorganic nanoparticles ( NPs ), characterized by long - lived luminescence, large Stokes and / or anti - Stokes shifts, narrow emission bands and high photochemical stability, are considered to be promising candidates as luminescent bioprobes in biomedicine and biotechnology.", "output": "Trivalent lanthanide, Ln ( 3 + )." }, { "input": "In this feature article, we provide a brief overview of the most recent advances in Ln ( 3 + ) - doped luminescent inorganic NPs as sensors, which covers from their chemical and physical fundamentals to biodetection, such as controlled synthesis methodology, surface modification chemistry, optical physics, and their promising applications in diverse bioassays, with an emphasis on heterogeneous and homogeneous in vitro biodetection.", "output": "Ln ( 3 + )." }, { "input": "Finally, some of the most important emerging trends and future efforts toward this active research field are also proposed.", "output": "There is no related enetity." }, { "input": "Biofunctionalized carbon nanotubes in neural regeneration: a mini - review.", "output": "carbon." }, { "input": "Carbon nanotubes ( CNTs ) have become an intriguing and promising biomaterial platform for the regeneration and functional recovery of damaged nerve tissues.", "output": "Carbon." }, { "input": "The unique electrical, structural and mechanical properties, diversity of available surface chemistry and cell - penetrating ability of CNTs have made them useful implantable matrices or carriers for the delivery of therapeutic molecules.", "output": "There is no related enetity." }, { "input": "Although there are still challenges being faced in the clinical applications of CNTs mainly due to their toxicity, many studies to overcome this issue have been published.", "output": "There is no related enetity." }, { "input": "Modification of CNTs with chemical groups to ensure their dissolution in aqueous media is one possible solution.", "output": "There is no related enetity." }, { "input": "Functionalization of CNTs with biologically relevant and effective molecules ( biofunctionalization ) is also a promising strategy to provide better biocompatibility and selectivity for neural regeneration.", "output": "There is no related enetity." }, { "input": "Here, we review recent advances in the use of CNTs to promote neural regeneration.", "output": "There is no related enetity." }, { "input": "Proteomic and metabolomic responses to connexin43 silencing in primary hepatocyte cultures.", "output": "There is no related enetity." }, { "input": "Freshly established cultures of primary hepatocytes progressively adopt a foetal - like phenotype and display increased production of connexin43.", "output": "There is no related enetity." }, { "input": "The latter is a multifaceted cellular entity with variable subcellular locations, including the mitochondrial compartment.", "output": "There is no related enetity." }, { "input": "Cx43 forms hemichannels and gap junctions that are involved in a plethora of physiological and pathological processes, such as apoptosis.", "output": "There is no related enetity." }, { "input": "The present study was conducted with the goal of shedding more light onto the role of connexin43 in primary hepatocyte cultures.", "output": "There is no related enetity." }, { "input": "Connexin43 expression was suppressed by means of RNA interference technology, and the overall outcome of this treatment on the hepatocellular proteome and metabolome was investigated using tandem mass tag - based differential protein profiling and ( 1 ) H NMR spectroscopy, respectively.", "output": "( 1 ) H." }, { "input": "Global protein profiling revealed a number of targets of the connexin43 knock - down procedure, including mitochondrial proteins ( heat shock protein 60, glucose - regulated protein 75, thiosulphate sulphurtransferase and adenosine triphosphate synthase ) and detoxifying enzymes ( glutathione S - transferase mu 2 and cytochrome P450 2C70 ).", "output": "glucose, thiosulphate, adenosine triphosphate, glutathione, S." }, { "input": "At the metabolomic level, connexin43 silencing caused no overt changes, though there was some evidence for a subtle increase in intracellular glycine quantities.", "output": "glycine." }, { "input": "Collectively, these data could further substantiate the established existence of a mitochondrial connexin pool and could be reconciled with the previously reported involvement of connexin43 signalling in spontaneously occurring apoptosis in primary hepatocyte cultures.", "output": "There is no related enetity." }, { "input": "DFT and TDDFT study on the electronic structure and photoelectrochemical properties of dyes derived from cochineal and lac insects as photosensitizer for dye - sensitized solar cells.", "output": "There is no related enetity." }, { "input": "Essential parameters related to the photoelectrochemical properties, such as ground state geometries, electronic structures, oxidation potential and electron driving force, of cochineal insect dyes were investigated by DFT and TDDFT at the B3LYP / 6 - 31 + G ( d, p ) level of the theory.", "output": "There is no related enetity." }, { "input": "The results show that the major charge flow dynamic for all dyes is the HOMO --> LUMO transition.", "output": "There is no related enetity." }, { "input": "The bi - coordinated binding mode, in which the dye uses one carboxyl - and hydroxyl oxygen bound to Ti ( IV ), is found for all dye - TiO ( 2 ) systems.", "output": "carboxyl - and hydroxyl oxygen, Ti ( IV ), TiO ( 2 )." }, { "input": "Additionally, the doubly bi - coordinated binding mode in which the dye used both carboxyl groups bound to two Ti ( IV ) is also possible due to high energy distribution occupied at anchoring groups.", "output": "carboxyl, Ti ( IV )." }, { "input": "This study highlights that most of these insect dyes can be good photosensitizers in dye - sensitized solar cells based on their strong binding to the TiO ( 2 ) surface, good computed excited state oxidation potential and thermodynamically favored electron driving force.", "output": "TiO ( 2 )." }, { "input": "Molecular vibrational spectroscopy characterization of epoxy graphene oxide from density functional calculations.", "output": "epoxy graphene oxide." }, { "input": "To further understand the structure of graphene oxide, several structures of graphene oxide were systematically investigated using density functional theory ( DFT ).", "output": "graphene oxide, graphene oxide." }, { "input": "Our models consisted of a hexagonal in - plane structure of graphene with epoxy groups, and different oxidation levels.", "output": "graphene, epoxy." }, { "input": "We found that different arrangements of these units yielded a range of vibrational spectra.", "output": "There is no related enetity." }, { "input": "Raman positions of the D and G bands depend sensitively on the local atomic configurations.", "output": "There is no related enetity." }, { "input": "Both structure energy and spectra computations indicate that the oxidation functional groups are energetically favorable to aggregate together and to be close to one another on the opposite side of graphene surface.", "output": "graphene." }, { "input": "Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.", "output": "There is no related enetity." }, { "input": "Amyotrophic lateral sclerosis ( ALS ) is a progressive and fatal degenerative disorder of motor neurons.", "output": "There is no related enetity." }, { "input": "The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms.", "output": "There is no related enetity." }, { "input": "In this study, we have analyzed metal concentrations in cerebrospinal fluid ( CSF ) and blood plasma in a well - defined cohort ( n = 17 ) of ALS patients diagnosed with quantitative electromyography.", "output": "There is no related enetity." }, { "input": "Metal analyses were performed with high - resolution inductively coupled plasma mass spectrometry.", "output": "There is no related enetity." }, { "input": "Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF.", "output": "manganese, aluminium, cadmium, cobalt, copper, zinc, vanadium, uranium." }, { "input": "We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e. g. inward directed transport.", "output": "There is no related enetity." }, { "input": "A pattern of multiple toxic metals is seen in ALS CSF.", "output": "There is no related enetity." }, { "input": "The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.", "output": "There is no related enetity." }, { "input": "Ovariectomy Stimulates Hepatic Fat and Cholesterol Accumulation in High - fat Diet - fed Rats.", "output": "Cholesterol." }, { "input": "This study was designed to determine how estrogens withdrawal during a high - fat ( HF ) diet regimen affects liver triacylglycerol ( TAG ) and cholesterol accumulation.", "output": "estrogens, triacylglycerol, TAG, cholesterol." }, { "input": "Female Sprague - Dawley rats were submitted to a HF ( 42 % energy as fat ) or a standard ( SD ) diet for 6 weeks before being either ovariectomized ( Ovx ) or sham operated ( Sham ).", "output": "There is no related enetity." }, { "input": "Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia.", "output": "There is no related enetity." }, { "input": "Liver TAG content was increased ( p < 0. 01 ) in Ovx rats but not by the HF diet alone.", "output": "TAG." }, { "input": "However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation ( p < 0. 06 ) than that observed in Ovx - SD / SD.", "output": "TAG." }, { "input": "Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation ( CPT - 1 and PGC1; p < 0. 05 ) in rats fed the HF diet.", "output": "There is no related enetity." }, { "input": "This increase was, however, substantially less if HF fed rats were Ovx.", "output": "There is no related enetity." }, { "input": "Liver total cholesterol levels were increased ( p < 0. 01 ) only in the Ovx - HF / HF rats while plasma cholesterol levels were increased in Ovx - SD / SD and in SHAM - HF / HF and Ovx - HF / HF rats.", "output": "cholesterol, cholesterol." }, { "input": "Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis ( CYP7a - 1 ) was reduced in Ovx - SD / SD and Sham - HF / HF rats and even more so in Ovx - HF / HF rats.", "output": "cholesterol, biliary acids." }, { "input": "It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation.", "output": "TAG." }, { "input": "The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation.", "output": "cholesterol." }, { "input": "In vitro antileishmanial activity of resveratrol originates from its cytotoxic potential against host cells.", "output": "resveratrol." }, { "input": "In addition to a range of beneficial pharmacological activities, resveratrol is recently reported to have potential antileishmanial activities in vitro.", "output": "resveratrol." }, { "input": "The present study was conducted to evaluate the effect of resveratrol on promastigotes and amastigotes of transgenic Leishmania major expressing green fluorescent protein in comparison with its direct cytotoxic effects on host cells ( bone marrow - derived and J774 - G8 macrophages, respectively ).", "output": "resveratrol." }, { "input": "As assessed by FACS analysis, resveratrol showed moderate antipromastigote activity at < 35 micro g / mL ( 153. 2 micro M ) and promising effects at higher sample concentrations.", "output": "resveratrol." }, { "input": "In contrast, the green fluorescent protein signal as a measure of the intracellular parasites ' viability was reduced in a concentration - dependent manner.", "output": "There is no related enetity." }, { "input": "Resveratrol strongly inhibited NO production, but did not display direct NO - scavenging activity in sodium nitroprusside solution.", "output": "Resveratrol, NO, NO, sodium nitroprusside." }, { "input": "Western blotting indicated that resveratrol reduced recombinant interferon - gamma / LPS - induced expression of iNOS protein.", "output": "resveratrol." }, { "input": "Microscopic studies, MTT evaluation, and FACS analysis showed significant cytotoxic effects on host cells in a concentration - dependent manner.", "output": "MTT." }, { "input": "This finding suggests that the in vitro antileishmanial activity of resveratrol is due to cytotoxic effects on host cells rather than attributable to a specific antiparasitic potential.", "output": "resveratrol." }, { "input": "Cytotoxic cycloartane triterpenes of the traditional Chinese medicine \" shengma \" ( Cimicifuga dahurica ).", "output": "cycloartane, triterpenes." }, { "input": "Twelve new 9, 19 - cycloartane triterpenes ( 1 - 12 ), together with fourteen known compounds ( 13 - 26 ), were isolated from the roots of Cimicifuga dahurica.", "output": "9 , 19 - cycloartane, triterpenes." }, { "input": "Their structures were determined by application of spectroscopic analyses and chemical methods.", "output": "There is no related enetity." }, { "input": "Biological evaluation of the compounds against human HL - 60, SMMC - 7721, A549, MCF - 7, and SW - 480 cell lines indicated that cimigenol - type glycosides ( 1 - 3, 19, and 20 ) showed broad - spectrum and moderate cytotoxicities, with IC50 values ranging from 4. 2 to 14. 5 micro M.", "output": "cimigenol." }, { "input": "Meanwhile, cimigenol - type aglycones ( 6 - 8, 15, 16, and 18 ) exhibited broad - spectrum and week cytotoxicities, having IC50 values around 20 micro M.", "output": "cimigenol." }, { "input": "In addition, the key points of the structure - activity relationships of aglycones with a cimigenol skeleton were discussed.", "output": "cimigenol." }, { "input": "Combined toxicity of polycyclic aromatic hydrocarbons and heavy metals to biochemical and antioxidant responses of free and immobilized Selenastrum capricornutum.", "output": "polycyclic aromatic hydrocarbons." }, { "input": "The aquatic environment often contains different groups of contaminants, but their combined toxicity on microalgae has seldom been reported.", "output": "There is no related enetity." }, { "input": "The present study compared the toxic effects of combined mixed polycyclic aromatic hydrocarbons ( PAHs ) and heavy metals on growth and antioxidant responses of free and immobilized microalga, Selenastrum capricornutum.", "output": "polycyclic aromatic hydrocarbons, PAHs." }, { "input": "Five PAHs - phenanthrene, fluorene, fluoranthene, pyrene, and benzo [ a ] pyrene - and four heavy metals at different concentrations - 0. 05 to 0. 1 micro g Cd ( 2 + ) ml ( - 1 ), 0. 05 to 1 micro g Cu ( 2 + ) ml ( - 1 ), 0. 05 to 1 micro g Zn ( 2 + ) ml ( - 1 ), and 0. 5 to 2. 5 micro g Ni ( 2 + ) ml ( - 1 ) - were examined.", "output": "PAHs, phenanthrene, fluorene, fluoranthene, pyrene, benzo [ a ] pyrene, Cd ( 2 + ), Cu ( 2 + ), Zn ( 2 + ), Ni ( 2 + )." }, { "input": "Results showed that the chlorophyll a content of free and immobilized S. capricornutum was not affected by PAHs but was significantly inhibited by heavy metals.", "output": "chlorophyll a, PAHs." }, { "input": "Conversely, the antioxidant parameters, including the content of reduced glutathione ( GSH ) and the activities of superoxide dismutase and peroxidase, were significantly induced by both PAHs and metals.", "output": "glutathione, GSH, superoxide, PAHs." }, { "input": "For the combined toxic effects of PAHs and heavy metals, cell growth and antioxidant responses varied with exposure time and contaminants and differed between free and immobilized cells.", "output": "PAHs." }, { "input": "The effects of cocontaminants on the GSH content in free cells were mainly synergistic but changed to antagonistic in immobilized cells.", "output": "GSH." }, { "input": "The toxic effects of cocontamination on free cells were also more obvious than those on immobilized cells.", "output": "There is no related enetity." }, { "input": "These findings suggest that immobilization offers some protection to microalgal cells against toxic contaminants causing differences in the interaction and responses to combined toxicants between free and immobilized cells.", "output": "There is no related enetity." }, { "input": "Immobilized cells might be more suitable for treating wastewater containing toxic contaminants than free cells.", "output": "There is no related enetity." }, { "input": "Multifunctional uniform core - shell Fe3O4 @ mSiO2 mesoporous nanoparticles for bimodal imaging and photothermal therapy.", "output": "Fe3O4." }, { "input": "Multimodal imaging and simultaneous therapy is highly desirable because it can provide complementary information from each imaging modality for accurate diagnosis and, at the same time, afford an imaging - guided focused tumor therapy.", "output": "There is no related enetity." }, { "input": "In this study, indocyanine green ( ICG ), a near - infrared ( NIR ) imaging agent and perfect NIR light absorber for laser - mediated photothermal therapy, was successfully incorporated into superparamagnetic Fe ( 3 ) O ( 4 ) @ mSiO ( 2 ) core - shell nanoparticles to combine the merit of NIR / magnetic resonance ( MR ) bimodal imaging properties with NIR photothermal therapy.", "output": "indocyanine green, ICG, Fe ( 3 ) O ( 4 )." }, { "input": "The resultant nanoparticles were homogenously coated with poly ( allylamine hydrochloride ) ( PAH ) to make the surface of the composite nanoparticles positively charged, which would enhance cellular uptake driven by electrostatic interactions between the positive surface of the nanoparticles and the negative surface of the cancer cell.", "output": "poly ( allylamine hydrochloride ), PAH." }, { "input": "A high biocompatibility of the achieved nanoparticles was demonstrated by using a cell cytotoxicity assay.", "output": "There is no related enetity." }, { "input": "Moreover, confocal laser scanning microscopy ( CLSM ) observations indicated excellent NIR fluorescent imaging properties of the ICG - loaded nanoparticles.", "output": "ICG." }, { "input": "The relatively high r ( 2 ) value ( 171. 6 mM ( - 1 ) s ( - 1 ) ) of the nanoparticles implies its excellent capability as a contrast agent for MRI.", "output": "There is no related enetity." }, { "input": "More importantly, the ICG - loaded nanoparticles showed perfect NIR photothermal therapy properties, thus indicating their potential for simultaneous cancer diagnosis as highly effective NIR / MR bimodal imaging probes and for NIR photothermal therapy of cancerous cells.", "output": "ICG." }, { "input": "Non - ionic dendronized multiamphiphilic polymers as nanocarriers for biomedical applications.", "output": "There is no related enetity." }, { "input": "A new class of non - ionic dendronized multiamphiphilic polymers is prepared from a biodegradable ( AB ) n - type diblock polymer synthesized from 2 - azido - 1, 3 - propanediol ( azido glycerol ) and polyethylene glycol ( PEG ) - 600 diethylester using Novozym - 435 ( Candida antarctica lipase ) as a biocatalyst, following a well - established biocatalytic route.", "output": "2 - azido - 1 , 3 - propanediol, azido glycerol, polyethylene glycol, PEG, diethylester." }, { "input": "These polymers are functionalized with dendritic polyglycerols ( G1 and G2 ) and octadecyl chains in different functionalization levels via click chemistry to generate dendronized multiamphiphilic polymers.", "output": "polyglycerols, octadecyl." }, { "input": "Surface tension measurements and dynamic light scattering studies reveal that all of the multiamphiphilic polymers spontaneously self - assemble in aqueous solution.", "output": "There is no related enetity." }, { "input": "Cryogenic transmission electron microscopy further proves the formation of multiamphiphiles towards monodisperse spherical micelles of about 7 - 9 nm in diameter.", "output": "There is no related enetity." }, { "input": "The evidence from UV - vis and fluorescence spectroscopy suggests the effective solubilization of hydrophobic guests like pyrene and 1 - anilinonaphthalene - 8 - sulfonic acid within the hydrophobic core of the micelles.", "output": "pyrene, 1 - anilinonaphthalene - 8 - sulfonic acid." }, { "input": "These results demonstrate the potential of these dendronized multiamphiphilic polymers for the development of prospective drug delivery systems for the solubilization of poorly water soluble drugs.", "output": "There is no related enetity." }, { "input": "Enhanced nonenzymatic ligation of homopurine miniduplexes: support for greater base stacking in a pre - RNA world.", "output": "There is no related enetity." }, { "input": "The ancestors of RNA?", "output": "There is no related enetity." }, { "input": "There is a long - standing proposal that contemporary nucleic acids might have evolved from RNA - like polymers that utilized only purine - purine base pairs.", "output": "nucleic acids, purine, purine." }, { "input": "Here we demonstrate the great advantage that increased nucleobase stacking area provides for nonenzymatic ligation.", "output": "There is no related enetity." }, { "input": "Preparation of functional water - soluble low - cytotoxic poly ( methacrylate ) s with pendant cationic L - lysines for efficient gene delivery.", "output": "poly ( methacrylate ) s, L - lysines." }, { "input": "In this work, we present the preparation of water - soluble poly ( methacrylate ) s with pendant cationic L - lysines PHMLs ( 6 - 30 K ).", "output": "poly ( methacrylate ) s, L - lysines." }, { "input": "Plasmid DNA binding affinity as well as particle sizes and zeta potentials of the polyplexes were examined for these PHML vectors, and their cytotoxicities were assayed with HeLa cells by CCK - 8 and lactate dehydrogenase kits.", "output": "There is no related enetity." }, { "input": "Gene transfection efficacy and intracellular uptake of the polyplexes by the PHML vectors were also studied with HeLa cells.", "output": "There is no related enetity." }, { "input": "As a result, it was revealed that the low cytotoxic PHMLs tended to exhibit gene transfection efficiencies significantly higher than those of the linear structural PLL ( 15 - 30 K ) control, in particular the molecular weight of a PHML vector remarkably influenced its pDNA binding affinity, transfection efficacy and intracellular uptake of the polyplexes.", "output": "There is no related enetity." }, { "input": "Biocompatible fibrous networks of cellulose nanofibres and collagen crosslinked using genipin: potential as artificial ligament / tendons.", "output": "genipin." }, { "input": "Bio - based fibrous nanocomposites of cellulose nanofibres and non - crosslinked / crosslinked collagen were prepared by in situ pH - induced fibrillation of collagen phase and sterilized using gamma rays at 25 KGy.", "output": "There is no related enetity." }, { "input": "Collagen phase is crosslinked using genipin, a bio - based crosslinker that introduces flexible crosslinks.", "output": "genipin." }, { "input": "Microscopy studies of the prepared materials showed nanostructured fibrous collagen and cellulose dispersed in collagen matrix.", "output": "There is no related enetity." }, { "input": "Mechanical performance of the sterilized nanocomposites was close to that of natural ligament and tendon, in simulated body conditions.", "output": "There is no related enetity." }, { "input": "Cytocompatibility studies indicated that these nanocomposites allowed human ligament cell and human endothelial cell adhesion, growth, and differentiation; which is eminently favourable to ligament tissue engineering.", "output": "There is no related enetity." }, { "input": "N - cyano sulfoximines: COX inhibition, anticancer activity, cellular toxicity, and mutagenicity.", "output": "N - cyano sulfoximines." }, { "input": "From insects to cancer: N - Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines.", "output": "N - Cyano sulfoximines." }, { "input": "The most active compound exhibited potent COX - 2 inhibition, some selectivity for COX - 2 over COX - 1, only slight cytotoxicity towards healthy cells ( HaCaT skin cells ), and no mutagenic potential ( as determined by an Ames assay ).", "output": "There is no related enetity." }, { "input": "Central nervous system disposition and metabolism of Fosdevirine ( GSK2248761 ), a non - nucleoside reverse transcriptase inhibitor: an LC - MS and Matrix - assisted laser desorption / ionization imaging MS investigation into central nervous system toxicity.", "output": "Fosdevirine, GSK2248761, nucleoside." }, { "input": "The CNS disposition and metabolism of Fosdevirine ( FDV ), an HIV non - nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV - 1 treatment experienced study.", "output": "Fosdevirine, FDV, nucleoside." }, { "input": "In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies.", "output": "FDV." }, { "input": "LC - MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid ( seizure patients, rabbit, and monkey ) and brain homogenate ( rabbit, minipig, and monkey ).", "output": "FDV." }, { "input": "The application of matrix - assisted laser desorption / ionization imaging mass spectrometry ( MALDI IMS ) provided the spatial distribution of FDV and its metabolites in brain tissue ( rabbit, minipig, and monkey ).", "output": "FDV." }, { "input": "A cysteine conjugate metabolite resulting from an initial glutathione ( GSH ) Michael addition to the trans - phenyl acrylonitrile moiety of FDV was the predominant drug - related component in the samples from seizure patients, rabbits, and minipigs.", "output": "cysteine, glutathione, GSH, trans - phenyl acrylonitrile, FDV." }, { "input": "This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs.", "output": "There is no related enetity." }, { "input": "Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS.", "output": "There is no related enetity." }, { "input": "In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter.", "output": "FDV." }, { "input": "On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity / seizures observed after FDV dosing.", "output": "FDV." }, { "input": "Epitope - guided engineering of monobody binders for in vivo inhibition of Erk - 2 signaling.", "output": "There is no related enetity." }, { "input": "Although the affinity optimization of protein binders is straightforward, engineering epitope specificity is more challenging.", "output": "There is no related enetity." }, { "input": "Targeting a specific surface patch is important because the biological relevance of protein binders depends on how they interact with the target.", "output": "There is no related enetity." }, { "input": "They are particularly useful to test hypotheses motivated by biochemical and structural studies.", "output": "There is no related enetity." }, { "input": "We used yeast display to engineer monobodies that bind a defined surface patch on the mitogen activated protein kinase ( MAPK ) Erk - 2.", "output": "There is no related enetity." }, { "input": "The targeted area ( \" CD \" domain ) is known to control the specificity and catalytic efficiency of phosphorylation by the kinase by binding a linear peptide ( \" D \" peptide ) on substrates and regulators.", "output": "There is no related enetity." }, { "input": "An inhibitor of the interaction should thus be useful for regulating Erk - 2 signaling in vivo.", "output": "There is no related enetity." }, { "input": "Although the CD domain constitutes only a small percentage of the surface area of the enzyme ( ~ 5 % ), sorting a yeast displayed monobody library with wild type ( wt ) Erk - 2 and a rationally designed mutant led to isolation of high affinity clones with desired epitope specificity.", "output": "There is no related enetity." }, { "input": "The engineered binders inhibited the activity of Erk - 2 in vitro and in mammalian cells.", "output": "There is no related enetity." }, { "input": "Furthermore, they specifically inhibited the activity of Erk - 2 orthologs in yeast and suppressed a mutant phenotype in round worms caused by overactive MAPK signaling.", "output": "There is no related enetity." }, { "input": "The study therefore shows that positive and negative screening can be used to bias the evolution of epitope specificity and predictably design inhibitors of biologically relevant protein - protein interaction.", "output": "There is no related enetity." }, { "input": "Controllable electrical properties of metal - doped In2O3 nanowires for high - performance enhancement - mode transistors.", "output": "In2O3." }, { "input": "In recent years, In ( 2 ) O ( 3 ) nanowires ( NWs ) have been widely explored in many technological areas due to their excellent electrical and optical properties; however, most of these devices are based on In ( 2 ) O ( 3 ) NW field - effect transistors ( FETs ) operating in the depletion mode, which induces relatively higher power consumption and fancier circuit integration design.", "output": "In ( 2 ) O ( 3 ), In ( 2 ) O ( 3 )." }, { "input": "Here, n - type enhancement - mode In ( 2 ) O ( 3 ) NW FETs are successfully fabricated by doping different metal elements ( Mg, Al, and Ga ) in the NW channels.", "output": "In ( 2 ) O ( 3 ), Mg, Al, Ga." }, { "input": "Importantly, the resulting threshold voltage can be effectively modulated through varying the metal ( Mg, Ga, and Al ) content in the NWs.", "output": "Mg, Ga, Al." }, { "input": "A series of scaling effects in the mobility, transconductance, threshold voltage, and source - drain current with respect to the device channel length are also observed.", "output": "There is no related enetity." }, { "input": "Specifically, a small gate delay time ( 0. 01 ns ) and high on - current density ( 0. 9 mA / mu m ) are obtained at 300 nm channel length.", "output": "There is no related enetity." }, { "input": "Furthermore, Mg - doped In ( 2 ) O ( 3 ) NWs are then employed to fabricate NW parallel array FETs with a high saturation current ( 0. 5 mA ), on / off ratio ( > 10 ( 9 ) ), and field - effect mobility ( 110 cm ( 2 ) / V. s ), while the subthreshold slope and threshold voltage do not show any significant changes.", "output": "Mg, In ( 2 ) O ( 3 )." }, { "input": "All of these results indicate the great potency for metal - doped In ( 2 ) O ( 3 ) NWs used in the low - power, high - performance thin - film transistors.", "output": "In ( 2 ) O ( 3 )." }, { "input": "Drug safety evaluation of defibrotide.", "output": "There is no related enetity." }, { "input": "INTRODUCTION: Hepatic veno - occlusive disease ( VOD ), also known as sinusoidal obstruction syndrome ( SOS ), is a potentially life - threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem - cell transplantation ( SCT ).", "output": "There is no related enetity." }, { "input": "Defibrotide ( DF ) has been shown in Phase II and III trials to improve complete response in patients with severe VOD ( sVOD ).", "output": "There is no related enetity." }, { "input": "None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and / or a range of other conditions.", "output": "There is no related enetity." }, { "input": "AREAS COVERED: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases.", "output": "There is no related enetity." }, { "input": "The literature review was conducted using a PubMed search with the fixed term ' defibrotide ' in combination with >= 1 of ' safety ', ' veno - occlusive disease ' ( with and without ' treatment ', ' prevention ' ), ' oncology ', ' myeloma ', ' microangiopathy ', ' anti - thrombotic ' and ' peripheral vascular disorder '.", "output": "There is no related enetity." }, { "input": "Related articles from the EBMT and ASH conference websites were also included.", "output": "There is no related enetity." }, { "input": "EXPERT OPINION: DF was well tolerated in majority of the studies.", "output": "There is no related enetity." }, { "input": "The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.", "output": "There is no related enetity." }, { "input": "A new antibacterial phenanthrenequinone from Dendrobium sinense.", "output": "phenanthrenequinone." }, { "input": "A new phenanthrenequinone, named denbinobin B ( 1 ), together with three known phenanthrenes was isolated from the whole plant of Dendrobium sinense T.", "output": "phenanthrenequinone, denbinobin B, phenanthrenes." }, { "input": "Tang et F. T.", "output": "There is no related enetity." }, { "input": "Wang, an endemic and endangered orchid to Hainan Island.", "output": "There is no related enetity." }, { "input": "The new compound was elucidated using a combination of 1D, 2D NMR ( COSY, HMQC, and HMBC ) techniques, and HR - ESI - MS analyses.", "output": "There is no related enetity." }, { "input": "Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with the diameter of the inhibition zone of 16. 5 mm.", "output": "There is no related enetity." }, { "input": "From a cytotoxic agent to the discovery of a novel antimalarial agent.", "output": "There is no related enetity." }, { "input": "A novel cytotoxin 3, 5 - bis ( 4 - chlorobenzylidene ) - 1 - [ 4 - { 2 - ( 4 - morpholinyl ) ethoxy } phenyl - carbonyl ] - 4 - piperidone hydrochloride 2 demonstrated potent antimalarial properties with IC ( 50 ) values of 0. 60 and 1. 97 mu M against the drug sensitive D6 strain and the C235 drug - resistant strain of Plasmodium falciparum.", "output": "3 , 5 - bis ( 4 - chlorobenzylidene ) - 1 - [ 4 - { 2 - ( 4 - morpholinyl ) ethoxy } phenyl - carbonyl ] - 4 - piperidone hydrochloride." }, { "input": "This compound concentrates in red blood cells, lowers glutathione concentrations in erythrocytes and permeates across CACO - 2 cells.", "output": "glutathione." }, { "input": "These data reveal 2 to be a promising lead compound in the quest for novel antimalarial agents.", "output": "There is no related enetity." }, { "input": "Facile regioselective synthesis of novel bioactive thiazolyl - pyrazoline derivatives via a three - component reaction and their antimicrobial activity.", "output": "thiazolyl - pyrazoline." }, { "input": "A series of novel 2 - ( 3, 5 - diphenyl - 4, 5 - dihydro - 1H - pyrazol - 1 - yl ) - 4 - phenylthiazoles have been prepared by a three - component cyclo - condensation of various chalcones, thiosemicarbazide and phenacyl bromide.", "output": "2 - ( 3 , 5 - diphenyl - 4 , 5 - dihydro - 1H - pyrazol - 1 - yl ) - 4 - phenylthiazoles, chalcones, thiosemicarbazide, phenacyl bromide." }, { "input": "The easy work - up of the products, rapid reaction, and mild conditions are notable features of this protocol.", "output": "There is no related enetity." }, { "input": "The reaction was efficiently catalyzed in one - pot by a few drops of HCl in EtOH under reflux conditions providing the title compounds in moderate to high yields.", "output": "HCl, EtOH." }, { "input": "The antibacterial activity of the selected products was examined.", "output": "There is no related enetity." }, { "input": "Some products exhibit promising activities.", "output": "There is no related enetity." }, { "input": "Cyprodinil as an activator of aryl hydrocarbon receptor.", "output": "Cyprodinil, aryl hydrocarbon." }, { "input": "Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture.", "output": "Cyprodinil, pyrimidinamine." }, { "input": "It is used to protect fruit plants and vegetables from a wide range of pathogens.", "output": "There is no related enetity." }, { "input": "Benzo [ a ] pyrene ( BaP ) and 2, 3, 7, 8 - tetrachlorodibenzo - p - dioxin ( TCDD ) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor ( AHR ) ligands.", "output": "Benzo [ a ] pyrene, BaP, 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin, TCDD, aryl hydrocarbon." }, { "input": "Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element ( AHRE ).", "output": "cyprodinil, BaP, TCDD, cyprodinil, aryl hydrocarbon." }, { "input": "Cyprodinil induced the expression of cytochrome P450 ( CYP ) 1A1, a well - known AHR - targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa - 1c1c7.", "output": "Cyprodinil." }, { "input": "Its induction did not appear in AHR signal - deficient cells, and was blocked by the AHR antagonist, CH - 223191.", "output": "There is no related enetity." }, { "input": "Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9h of treatment in HO23 cells.", "output": "Cyprodinil." }, { "input": "Dexamethasone is a synthetic agonist of glucocorticoids.", "output": "Dexamethasone." }, { "input": "Cyprodinil enhanced dexamethasone - induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter.", "output": "Cyprodinil, dexamethasone, dexamethasone." }, { "input": "In addition to BaP, TCDD, and an AHR agonist, beta - NF, cyprodinil also phosphorylated extracellular signal - regulated kinase ( ERK ) in HO23 and Hepa - 1c1c7 cells, indicating its deregulation of ERK activity.", "output": "BaP, TCDD, cyprodinil." }, { "input": "In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter.", "output": "cyprodinil, BaP." }, { "input": "Metformin - mediated downregulation of p38 mitogen - activated protein kinase - dependent excision repair cross - complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.", "output": "Metformin, paclitaxel." }, { "input": "Metformin, an extensively used and well - tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug.", "output": "Metformin." }, { "input": "On the other hand, paclitaxel ( Taxol ) is a new antineoplastic drug that has shown promise in the treatment of non - small cell lung cancer ( NSCLC ).", "output": "paclitaxel, Taxol." }, { "input": "High expression levels of excision repair cross - complementary 1 ( ERCC1 ) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum - containing chemotherapy.", "output": "platinum." }, { "input": "In this current study, paclitaxel was found to increase phosphorylation of mitogen - activated protein kinase ( MAPK ) kinase 3 / 6 ( MKK3 / 6 ) - p38 MAPK as well as protein and mRNA levels of ERCC1 in H1650 and H1703 cells.", "output": "paclitaxel." }, { "input": "Moreover, paclitaxel - induced ERCC1 protein and mRNA levels significantly decreased via the downregulation of p38 activity by either a p38 MAPK inhibitor SB202190 or p38 knockdown with specific small interfering RNA ( siRNA ).", "output": "paclitaxel, SB202190." }, { "input": "Specific inhibition of ERCC1 with siRNA was found to enhance the paclitaxel - induced cytotoxic effect and growth inhibition.", "output": "paclitaxel." }, { "input": "Furthermore, metformin was able to not only decrease the paclitaxel - induced p38 MAPK - mediated ERCC1 expression, but also augment the cytotoxic effect induced by paclitaxel.", "output": "metformin, paclitaxel, paclitaxel." }, { "input": "Finally, expression of constitutive activate MKK6 or HA - p38 MAPK vectors in lung cancer cells was able to abrogate ERCC1 downregulation by metformin and paclitaxel as well as cell viability and DNA repair capacity.", "output": "metformin, paclitaxel." }, { "input": "Overall, our results suggest that inhibition of the p38 MAPK signaling by metformin coupled with paclitaxel therapy in human NSCLC cells may be a clinically useful combination, which however will require further validation.", "output": "metformin, paclitaxel." }, { "input": "Carboxylesterase - 2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs.", "output": "orlistat." }, { "input": "Orlistat has been the most used anti - obesity drug and the mechanism of its action is to reduce lipid absorption by inhibiting gastrointestinal lipases.", "output": "Orlistat." }, { "input": "These enzymes, like carboxylesterases ( CESs ), structurally belong to the alpha / beta hydrolase fold superfamily.", "output": "There is no related enetity." }, { "input": "Lipases and CESs are functionally related as well.", "output": "There is no related enetity." }, { "input": "Some CESs ( e. g., human CES1 ) have been shown to hydrolyze lipids.", "output": "There is no related enetity." }, { "input": "This study was designed to test the hypothesis that orlistat inhibits CESs with higher potency toward CES1 than CES2, a carboxylesterase with little lipase activity.", "output": "orlistat." }, { "input": "Liver microsomes and recombinant CESs were tested for the inhibition of the hydrolysis of standard substrates and the anticancer prodrugs pentyl carbamate of p - aminobenzyl carbamate of doxazolidine ( PPD ) and irinotecan.", "output": "pentyl carbamate, p - aminobenzyl carbamate, doxazolidine, PPD, irinotecan." }, { "input": "Contrary to the hypothesis, orlistat at 1 nM inhibited CES2 activity by 75 % but no inhibition on CES1, placing CES2 one of the most sensitive targets of orlistat.", "output": "orlistat." }, { "input": "The inhibition varied among some CES2 polymorphic variants.", "output": "There is no related enetity." }, { "input": "Pretreatment with orlistat reduced the cell killing activity of PPD.", "output": "orlistat, PPD." }, { "input": "Certain mouse but not rat CESs were also highly sensitive.", "output": "There is no related enetity." }, { "input": "CES2 is responsible for the hydrolysis of many common drugs and abundantly expressed in the gastrointestinal track and liver.", "output": "There is no related enetity." }, { "input": "Inhibition of this carboxylesterase probably presents a major source for altered therapeutic activity of these medicines if co - administered with orlistat.", "output": "orlistat." }, { "input": "In addition, orlistat has been linked to various types of organ toxicities, and this study provides an alternative target potentially involved in these toxicological responses.", "output": "orlistat." }, { "input": "Microwave synthesis, characterization and bio - efficacy evaluation of novel chalcone based 6 - carbethoxy - 2 - cyclohexen - 1 - one and 2H - indazol - 3 - ol derivatives.", "output": "chalcone, 6 - carbethoxy - 2 - cyclohexen - 1 - one, 2H - indazol - 3 - ol." }, { "input": "Novel chalcone based 6 - carbethoxy - 2 - cyclohexen - 1 - one and 2H - indazol - 3 - ol derivatives were synthesized and characterized by using spectral techniques like IR, ( 1 ) H NMR, ( 13 ) C NMR, COSY, DEPT, and GC - MS.", "output": "chalcone, 6 - carbethoxy - 2 - cyclohexen - 1 - one, 2H - indazol - 3 - ol, ( 1 ) H, ( 13 ) C." }, { "input": "All these compounds were screened for anti - fungal, anti - bacterial and anti - oxidant activity.", "output": "There is no related enetity." }, { "input": "Cyclohexenone derivatives, in general, showed better anti - fungal and anti - bacterial activity than parent chalcones.", "output": "Cyclohexenone, chalcones." }, { "input": "Whereas, all the Indazole derivatives showed very good anti - oxidant activity and some were also found to be active as anti - bacterial agent.", "output": "Indazole." }, { "input": "Among the screened compounds, 15 was found to be most active as anti - fungal agent ( against Rhizoctonia solani, LC ( 50 ) = 2. 36 mu g mL ( - 1 ) ), 15b was found to be most active anti - bacterial agent ( against Klebsiella pneumonia, MIC = 24. 68 mu g mL ( - 1 ) ) and 14b emerged as most active anti - oxidant ( IC ( 50 ) = 19. 81 mu g mL ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "Aryl hydrocarbon receptor is a target of 17 - Allylamino - 17 - demethoxygeldanamycin and enhances its anticancer activity in lung adenocarcinoma cells.", "output": "Aryl hydrocarbon, 17 - Allylamino - 17 - demethoxygeldanamycin." }, { "input": "We have demonstrated that aryl hydrocarbon receptor ( AhR ) is overexpressed in lung adenocarcinoma ( AD ).", "output": "aryl hydrocarbon." }, { "input": "AhR is usually associated with heat shock protein 90 ( Hsp90 ) in the cytoplasm.", "output": "There is no related enetity." }, { "input": "17 - Allylamino - 17 - demethoxygeldanamycin ( 17 - AAG ), an Hsp90 inhibitor, is currently under evaluation for its anticancer activity in clinical trials.", "output": "17 - Allylamino - 17 - demethoxygeldanamycin, 17 - AAG." }, { "input": "Here we investigated whether AhR plays a role in 17 - AAG - mediated anticancer activity by functioning as a downstream target or by modulating its anticancer efficacy.", "output": "17 - AAG." }, { "input": "AhR expression in lung AD cells was modulated by siRNA interference or overexpression.", "output": "There is no related enetity." }, { "input": "Tumor growth was determined with colony formation in vitro or in vivo.", "output": "There is no related enetity." }, { "input": "Anticancer activity of 17 - AAG was determined by measuring cell viability, cell cycle distribution, and expression of cell cycle regulators.", "output": "17 - AAG." }, { "input": "Proteins and mRNA levels were examined by immunoblotting and the real - time reverse transcription - polymerase chain reaction, respectively.", "output": "There is no related enetity." }, { "input": "In this study, AhR overexpression positively modulated growth of lung AD cells, at least partially, via RelA - dependent mechanisms.", "output": "There is no related enetity." }, { "input": "Although treatment with 17 - AAG reduced AhR levels and AhR - regulated gene expression in lung AD cells, AhR expression increased anticancer activity of 17 - AAG.", "output": "17 - AAG, 17 - AAG." }, { "input": "In addition, 17 - AAG treatment reduced cell viability, CDK2, CDK4, cyclin E, cyclin D1, and phosphorylated Rb levels in AhR - expressing lung AD cells.", "output": "17 - AAG." }, { "input": "NAD ( P ) H: quinone oxidoreductase ( NQO1 ), which is regulated by AhR, was shown to increase anticancer activity of 17 - AAG in cells.", "output": "NAD ( P ) H, quinone, 17 - AAG." }, { "input": "Knockdown of NQO1 expression attenuated the reduction of cell cycle regulators by 17 - AAG treatment in AhR overexpressed cells.", "output": "17 - AAG." }, { "input": "We demonstrated that AhR protein not only functions as a downstream target of 17 - AAG, but also enhances anticancer activity of 17 - AAG in lung AD cells.", "output": "17 - AAG, 17 - AAG." }, { "input": "Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction.", "output": "There is no related enetity." }, { "input": "Postoperative cognitive dysfunction ( POCD ) is recognized as a complication after surgery in the elderly.", "output": "There is no related enetity." }, { "input": "The exact pathogenic mechanisms of POCD are still unknown.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the role of iron accumulation within the central nervous system in the development of cognitive dysfunction in rats following splenectomy.", "output": "iron." }, { "input": "Cognitive function was assessed using a Morris water maze on postoperative days 1, 3, and 7.", "output": "There is no related enetity." }, { "input": "Impaired cognitive function was observed on days 1 and 3 after splenectomy, while an anesthesia - alone group showed no significant difference from the control.", "output": "There is no related enetity." }, { "input": "Serum iron levels decreased and brain iron content increased on days 1 and 3 after surgery, which was in parallel with the impairment of cognitive function.", "output": "There is no related enetity." }, { "input": "Furthermore, the levels of proteins involved in the maintenance of brain iron homeostasis, including ferritin, transferrin receptor 1, and iron regulatory protein 2, were significantly different at postoperative days 1 and 3 in the hippocampus of splenectomized animals when compared with those of the control.", "output": "iron, iron." }, { "input": "The alterations in iron homeostasis were accompanied by intensified oxidative stress as measured by increases in the lipid peroxidation product, malondialdehyde, and a decrease in the levels of superoxide dismutase activity.", "output": "iron, malondialdehyde, superoxide." }, { "input": "Overall, these findings suggest that the impaired cognitive function was primarily due to surgical trauma rather than anesthesia.", "output": "There is no related enetity." }, { "input": "Increased iron accumulation and oxidative stress in the brain, especially in the hippocampus, may be involved in the pathogenesis of POCD.", "output": "There is no related enetity." }, { "input": "Pharmacogenomics of gemcitabine metabolism: functional analysis of genetic variants in cytidine deaminase and deoxycytidine kinase.", "output": "gemcitabine, cytidine, deoxycytidine." }, { "input": "Gemcitabine ( dFdC, 2 ', 2 ' - difluorodeoxycytidine ) is metabolized by cytidine deaminase ( CDA ) and deoxycytidine kinase ( DCK ), but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear.", "output": "Gemcitabine, dFdC, 2 ' , 2 ' - difluorodeoxycytidine, cytidine, deoxycytidine." }, { "input": "Wild - type enzymes and variants of CDA ( Lys27Gln and Ala70Thr ) and DCK ( Ile24Val, Ala119Gly, and Pro122Ser ) were expressed in and purified from Escherichia coli, and enzyme kinetic parameters were estimated for cytarabine ( Ara - C ), dFdC, and its metabolite 2 ', 2 ' - difluorodeoxyuridine ( dFdU ) as substrates.", "output": "cytarabine, Ara - C, dFdC, 2 ' , 2 ' - difluorodeoxyuridine, dFdU." }, { "input": "All three CDA proteins showed similar K ( m ) and V ( max ) for Ara - C and dFdC deamination, except for CDA70Thr, which had a 2. 5 - fold lower K ( m ) and 6 - fold lower V ( max ) for Ara - C deamination.", "output": "Ara - C, dFdC, Ara - C." }, { "input": "All four DCK proteins yielded comparable metabolic activity for Ara - C and dFdC monophosphorylation, except for DCK24Val, which demonstrated an approximately 2 - fold increase ( P < 0. 05 ) in the intrinsic clearance of dFdC monophosphorylation due to a 40 % decrease in K ( m ) ( P < 0. 05 ).", "output": "Ara - C, dFdC, dFdC." }, { "input": "DCK did not significantly contribute to dFdU monophosphorylation.", "output": "dFdU." }, { "input": "In conclusion, the Lys27Gln substitution does not significantly modulate CDA activity toward dFdC, and therefore would not contribute to interindividual variability in response to gemcitabine.", "output": "dFdC, gemcitabine." }, { "input": "The higher in vitro catalytic efficiency of DCK24Val toward dFdC monophosphorylation may be relevant to dFdC clinical response.", "output": "dFdC, dFdC." }, { "input": "The substrate - dependent alterations in activities of CDA70Thr and DCK24Val in vitro were observed for the first time, and demonstrate that the in vivo consequences of these genetic variations should not be extrapolated from one substrate of these enzymes to another.", "output": "There is no related enetity." }, { "input": "Stress granules inhibit apoptosis by reducing reactive oxygen species production.", "output": "oxygen." }, { "input": "Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress - induced alterations.", "output": "There is no related enetity." }, { "input": "These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations.", "output": "There is no related enetity." }, { "input": "These two alternative fates are partly controlled by stress granules ( SGs ).", "output": "There is no related enetity." }, { "input": "While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X - ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis.", "output": "arsenite." }, { "input": "However, it is unclear precisely how SGs control apoptosis.", "output": "There is no related enetity." }, { "input": "This study found that SGs suppress the elevation of reactive oxygen species ( ROS ), and this suppression is essential for inhibiting ROS - dependent apoptosis.", "output": "oxygen." }, { "input": "This antioxidant activity of SGs is controlled by two SG components, GTPase - activating protein SH3 domain binding protein 1 ( G3BP1 ) and ubiquitin - specific protease 10 ( USP10 ).", "output": "There is no related enetity." }, { "input": "G3BP1 elevates the steady - state ROS level by inhibiting the antioxidant activity of USP10.", "output": "There is no related enetity." }, { "input": "However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10.", "output": "arsenite." }, { "input": "We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated ( ATM ).", "output": "There is no related enetity." }, { "input": "This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.", "output": "There is no related enetity." }, { "input": "Increased oxidized low - density lipoprotein causes blood - brain barrier disruption in early - onset preeclampsia through LOX - 1.", "output": "There is no related enetity." }, { "input": "Early - onset preeclampsia ( EPE ) is a severe form of preeclampsia that involves life - threatening neurological complications.", "output": "There is no related enetity." }, { "input": "However, the underlying mechanism by which EPE affects the maternal brain is not known.", "output": "There is no related enetity." }, { "input": "We hypothesized that plasma from women with EPE increases blood - brain barrier ( BBB ) permeability vs. plasma from women with late - onset preeclampsia ( LPE ) or normal pregnancy ( NP ) and investigated its underlying mechanism by perfusing cerebral veins from nonpregnant rats ( n = 6 - 7 / group ) with human plasma from women with EPE, LPE, or NP and measuring permeability.", "output": "There is no related enetity." }, { "input": "We show that plasma from women with EPE significantly increased BBB permeability vs. plasma from women with LPE or NP ( P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "BBB disruption in response to EPE plasma was due to a 260 % increase of circulating oxidized LDL ( oxLDL ) binding to its receptor, LOX - 1, and subsequent generation of peroxynitrite ( P < 0. 001 ).", "output": "peroxynitrite." }, { "input": "A rat model with pathologically high lipid levels in pregnancy showed symptoms of preeclampsia, including elevated blood pressure, growth - restricted fetuses, and LOX - 1 - dependent BBB disruption, similar to EPE ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Thus, we have identified LOX - 1 activation by oxLDL and subsequent peroxynitrite generation as a novel mechanism by which disruption of the BBB occurs in EPE.", "output": "peroxynitrite." }, { "input": "As increased BBB permeability is a primary means by which seizure and other neurological symptoms ensue, our findings highlight oxLDL, LOX - 1, and peroxynitrite as important therapeutic targets in EPE.", "output": "peroxynitrite." }, { "input": "Embryonic stem cell - based screen for small molecules: cluster analysis reveals four response patterns in developing neural cells.", "output": "There is no related enetity." }, { "input": "Neural differentiation of embryonic stem cells ( ESC ) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds.", "output": "There is no related enetity." }, { "input": "We studied the potential of a dual reporter murine ESC line to identify bioactive and / or toxic compounds.", "output": "There is no related enetity." }, { "input": "This line expressed firefly luciferase under the control of the neural cell - specific tubulin alpha promoter ( TUBA1A ), and renilla luciferase under the control of the ubiquitous translation elongation factor 1 - alpha - 1 ( EEF1A1 ) promoter.", "output": "There is no related enetity." }, { "input": "During neural differentiation, TUBA1A activity increased, while EEF1A1 activity decreased.", "output": "There is no related enetity." }, { "input": "We first validated our test system using the known neurotoxin methyl mercury.", "output": "methyl mercury." }, { "input": "This compound altered expression of both reporter genes, with ESC - derived neural precursors being affected at markedly lower concentrations than undifferentiated ESCs.", "output": "There is no related enetity." }, { "input": "Analysis of a library of 1040 bioactive compounds picked up 127 compounds with altered EEF1A1 and / or TUBA1A promoter activity, which were classified in 4 clusters.", "output": "There is no related enetity." }, { "input": "Cluster 1 ( low EEF1A1 and TUBA1A ) was the largest cluster, containing many cytostatic drugs, as well as known neurodevelopmental toxicants, psychotropic drugs and endocrine disruptors.", "output": "There is no related enetity." }, { "input": "Cluster 2 ( high EEF1A1, stable TUBA1A ) was limited to three sulfonamides.", "output": "sulfonamides." }, { "input": "Cluster 3 ( high EEF1A1 and TUBA1A ) was small, but markedly enriched in neuroactive and neurotoxic compounds.", "output": "There is no related enetity." }, { "input": "Cluster 4 ( stable EEF1A1, high TUBA1A ) was heterogeneous, containing endocrine disruptors, neurotoxic and cytostatic drugs.", "output": "There is no related enetity." }, { "input": "The dual reporter gene assay described here might be a useful addition to in vitro drug testing panels.", "output": "There is no related enetity." }, { "input": "Our two - dimensional testing strategy provides information on complex response patterns, which could not be achieved by a single marker approach.", "output": "There is no related enetity." }, { "input": "Discovery, synthesis, and structure - based optimization of a series of N - ( tert - butyl ) - 2 - ( N - arylamido ) - 2 - ( pyridin - 3 - yl ) acetamides ( ML188 ) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus ( SARS - CoV ) 3CL protease.", "output": "N - ( tert - butyl ) - 2 - ( N - arylamido ) - 2 - ( pyridin - 3 - yl ) acetamides, ML188." }, { "input": "A high - throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide - like series of severe acute respiratory syndrome ( SARS ) main protease ( 3CLpro ) inhibitors led to the identification of probe compound ML188 ( 16 - ( R ), ( R ) - N - ( 4 - ( tert - butyl ) phenyl ) - N - ( 2 - ( tert - butylamino ) - 2 - oxo - 1 - ( pyridin - 3 - yl ) ethyl ) furan - 2 - carboxamide, Pubchem CID: 46897844 ).", "output": "dipeptide, ML188, ( R ) - N - ( 4 - ( tert - butyl ) phenyl ) - N - ( 2 - ( tert - butylamino ) - 2 - oxo - 1 - ( pyridin - 3 - yl ) ethyl ) furan - 2 - carboxamide, CID : 46897844." }, { "input": "Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16 - ( R ) is a noncovalent SARS - CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity.", "output": "There is no related enetity." }, { "input": "A multicomponent Ugi reaction was utilized to rapidly explore structure - activity relationships within S ( 1 ' ), S ( 1 ), and S ( 2 ) enzyme binding pockets.", "output": "There is no related enetity." }, { "input": "The X - ray structure of SARS - CoV 3CLpro bound with 16 - ( R ) was instrumental in guiding subsequent rounds of chemistry optimization.", "output": "There is no related enetity." }, { "input": "16 - ( R ) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.", "output": "There is no related enetity." }, { "input": "Hydrogel - based scaffolds for enclosing encapsulated therapeutic cells.", "output": "There is no related enetity." }, { "input": "Cell encapsulation technology holds promise for the sustained and controlled delivery of different therapeutic proteins.", "output": "There is no related enetity." }, { "input": "Alginate - poly - L - lysine - alginate ( APA ) microcapsules represent one of the most widely studied alginate - polycation microcapsules.", "output": "poly - L - lysine." }, { "input": "On the basis of this technology, two types of hydrogel - based scaffolds have been developed and analyzed with the aim of improving the retention and the retrieval of erythropoietin ( Epo ) secreting cell - loaded microcapsules in the tissue where they are implanted.", "output": "There is no related enetity." }, { "input": "Furthermore, these hydrogels may help to reduce the post - transplant inflammation and pericapsular fibrotic overgrowth typically observed around capsules.", "output": "There is no related enetity." }, { "input": "The hydrogel - based scaffolds could be administered as implantable forms ( preformed scaffolds ) or injectable forms ( in situ formed scaffolds ).", "output": "There is no related enetity." }, { "input": "The in vitro studies confirmed the correct adaptation of the enclosed cells to the scaffolds in terms of viability and protein expression.", "output": "There is no related enetity." }, { "input": "The posterior implantation of the cell - loaded capsules containing hydrogel - based scaffolds in mice revealed that the hematocrit levels were maintained up to 80 % for at least 2 months.", "output": "There is no related enetity." }, { "input": "The histological analysis of the explanted microcapsules performed at that point showed that pericapsular overgrowth was reduced when cell - loaded microcapsules were enclosed in the hydrogels scaffolds.", "output": "There is no related enetity." }, { "input": "Incorporating microencapsulated cells within hydrogel - based scaffolds may help to improve their administration protocol and retention while reducing post - transplantation inflammation.", "output": "There is no related enetity." }, { "input": "Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors.", "output": "Dopamine, dopamine." }, { "input": "Variations of dopamine ( DA ) levels induced by drugs of abuse or in the context of Parkinson ' s disease modulate the number of dendritic spines in medium spiny neurons ( MSNs ) of the striatum, showing that DA plays a major role in the structural plasticity of MSNs.", "output": "dopamine." }, { "input": "However, little is presently known regarding early spine development in MSNs occurring before the arrival of cortical inputs and in particular about the role of DA and D1 ( D1R ) and D2 ( D2R ) DA receptors.", "output": "There is no related enetity." }, { "input": "A cell culture model reconstituting early cellular interactions between MSNs, intrinsic cholinergic interneurons and DA neurons was used to study the role of DA in spine formation.", "output": "There is no related enetity." }, { "input": "After 5 or 10 days in vitro, the presence of DA neurons increased the number of immature spine - like protrusions.", "output": "There is no related enetity." }, { "input": "In MSN monocultures, chronic activation of D1R or D2R also increased the number of spines and spinophilin expression in MSNs, suggesting a direct role for these receptors.", "output": "There is no related enetity." }, { "input": "In DA - MSN cocultures, chronic blockade of D1R or D2R reduced the number of dendritic spines.", "output": "There is no related enetity." }, { "input": "Interestingly, the combined activation or blockade of both D1R and D2R failed to elicit more extensive spine formation, suggesting that both receptors act through a mechanism that is not additive.", "output": "There is no related enetity." }, { "input": "Finally, we found increased ionotropic glutamate receptor responsiveness and miniature excitatory postsynaptic current ( EPSC ) frequency in DA - MSN co - cultures, in parallel with a higher number of spines containing PSD - 95, suggesting that the newly formed spines present functional post - synaptic machinery preparing the MSNs to receive additional glutamatergic contacts.", "output": "There is no related enetity." }, { "input": "These results represent a first step in the understanding of how dopamine neurons promote the structural plasticity of MSNs during the development of basal ganglia circuits.", "output": "dopamine." }, { "input": "Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N - ( 2, 6 - diarylpyrimidin - 4 - yl ) acetamide scaffold.", "output": "adenosine, methoxyaryl, N - ( 2 , 6 - diarylpyrimidin - 4 - yl ) acetamide." }, { "input": "The influence of diverse methoxyphenyl substitution patterns on the N - ( 2, 6 - diarylpyrimidin - 4 - yl ) acetamide scaffold is herein explored in order to modulate the A ( 3 ) adenosine receptor antagonistic profile.", "output": "methoxyphenyl, N - ( 2 , 6 - diarylpyrimidin - 4 - yl ) acetamide, adenosine." }, { "input": "As a result, novel ligands exhibiting excellent potency ( K ( i ) on A ( 3 ) AR < 20 nM ) and selectivity profiles ( above 100 - fold within the adenosine receptors family ) are reported.", "output": "adenosine." }, { "input": "Moreover, our joint theoretical and experimental approach allows the identification of novel pharmacophoric elements conferring A ( 3 ) AR selectivity, first established by a robust computational model and thereafter characterizing the most salient features of the structure - activity and structure - selectivity relationships in this series.", "output": "There is no related enetity." }, { "input": "Small molecule amides as potent ROR - gamma selective modulators.", "output": "amides." }, { "input": "The structure - activity relationship study of a diphenylpropanamide series of ROR - gamma selective modulators is reported.", "output": "diphenylpropanamide." }, { "input": "Compounds were screened using chimeric receptor Gal4 DNA - binding domain ( DBD ) - NR ligand binding domain cotransfection assay in a two - step format.", "output": "There is no related enetity." }, { "input": "Three different regions of the scaffold were modified to assess the effects on repression of ROR - gamma transcriptional activity and potency.", "output": "There is no related enetity." }, { "input": "The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR - gamma in animal models of disease.", "output": "There is no related enetity." }, { "input": "Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor - kappa B.", "output": "Cynaropicrin." }, { "input": "Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors.", "output": "There is no related enetity." }, { "input": "Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation.", "output": "There is no related enetity." }, { "input": "Nuclear factor kappa B ( NF - kappa B ) is one of the representative transcription factors active in conjunction with inflammation.", "output": "There is no related enetity." }, { "input": "NF - kappa B is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor ( bFGF ) and matrix metalloprotease - 1 ( MMP - 1 ).", "output": "There is no related enetity." }, { "input": "We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF - kappa B.", "output": "There is no related enetity." }, { "input": "One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF - kappa B transactivation.", "output": "There is no related enetity." }, { "input": "As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF - kappa B - mediated transactivation of bFGF and MMP - 1.", "output": "cynaropicrin, sesquiterpene lactone." }, { "input": "Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes.", "output": "cynaropicrin." }, { "input": "These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF - kappa B - mediated transactivation.", "output": "cynaropicrin." }, { "input": "Analysis and characterization of eight estradiol inducible genes and a strong promoter from the steroid degrading marine bacterial strain S19 - 1.", "output": "estradiol, steroid." }, { "input": "Buttiauxella strain S19 - 1 is a new marine bacterium, isolated from the Baltic Sea, which can degrade steroids.", "output": "steroids." }, { "input": "In this report, a meta - genomic approach was used to isolate estradiol inducible genes from S19 - 1.", "output": "estradiol." }, { "input": "SalI - fragments from the chromosomal DNA of S19 - 1 were ligated into plasmid pKEGFP2 bearing an EGFP gene as the reporter system.", "output": "There is no related enetity." }, { "input": "All resulting plasmids harboring SalI - fragments were transformed into Escherichia coli HB101 to measure the relative fluorescent units ( RFU ).", "output": "There is no related enetity." }, { "input": "E. coli cells showing higher RFU after estradiol induction than those without estradiol induction, were selected and the respective plasmids were sequenced.", "output": "estradiol, estradiol." }, { "input": "Sequences of 8 positive plasmids were analyzed and aligned by BLAST.", "output": "There is no related enetity." }, { "input": "Among the predicted genes we found similarities to the major facilitator superfamily, glycerol dehydratase activator, formate acetyltransferase activating enzyme, histidinol - phosphate / aromatic aminotransferase, ABC - transporter, transcriptional regulator nadR, lipoate - protein ligase A, and alcohol phosphatidyl - transferase.", "output": "glycerol, formate, histidinol - phosphate, alcohol." }, { "input": "Interestingly, one of the E. coli cell clones ( containing plasmid p302 ) showed up in green color by normal light microscopy, which indicated that a strong promoter was present in this plasmid.", "output": "There is no related enetity." }, { "input": "Sequencing and deletion - mutagenesis revealed that the putative promoter comprises a 108 bp DNA fragment within p302, from which the putative - 10 and - 35 regions are TTTGAT and TTGGTT, respectively.", "output": "There is no related enetity." }, { "input": "The promoter might be used to construct S19 - 1 mutants in which steroid degradation occurs at high levels.", "output": "steroid." }, { "input": "Energetic constraints and parental care: is corticosterone indicative of energetic costs of incubation in a precocial bird?", "output": "corticosterone." }, { "input": "Suppression of the adrenocortical response ( e. g., corticosterone release ) to an acute stressor is a physiological adjustment thought to decrease the likelihood of avian parents abandoning their nests.", "output": "corticosterone." }, { "input": "However, some periods of parental care, like incubation, are energetically costly, thus corticosterone could increase during these stages to allow incubating parents to utilize energy reserves.", "output": "corticosterone." }, { "input": "Wood ducks ( Aix sponsa ) have ~ 30 day incubation periods and only the female incubates the eggs.", "output": "There is no related enetity." }, { "input": "We hypothesized that corticosterone would be important in regulating energy availability during incubation in this species.", "output": "corticosterone." }, { "input": "Because resources invested in reproduction increase with clutch size, we also hypothesized that clutch size would influence plasma corticosterone during incubation.", "output": "corticosterone." }, { "input": "We measured baseline and stress - induced corticosterone in incubating females during early and late stages of incubation.", "output": "corticosterone." }, { "input": "At both stages of incubation all hens had low baseline corticosterone levels.", "output": "corticosterone." }, { "input": "However, we found that stress - induced corticosterone was 105 % greater late in incubation than early in incubation.", "output": "corticosterone." }, { "input": "We also detected a significant negative correlation between female body mass and stress - induced corticosterone late in incubation, but not during the early stages of incubation.", "output": "corticosterone." }, { "input": "Furthermore, we found a significant positive relationship between stress - induced corticosterone and clutch size.", "output": "corticosterone." }, { "input": "These lines of evidence support the hypothesis that incubation in wood ducks is energetically costly and corticosterone is important in supporting the energetic demands of incubating hens.", "output": "corticosterone." }, { "input": "Our findings suggest that corticosterone ' s role in supporting parental care behaviors are dynamic and are influenced by several factors and that there is a greater physiological cost associated with incubating larger clutches.", "output": "corticosterone." }, { "input": "Toxicity of organotin compounds: shared and unshared biochemical targets and mechanisms in animal cells.", "output": "organotin." }, { "input": "Most biochemical effects of organotin compounds leading to toxicity are astonishingly similar in different animal species.", "output": "organotin." }, { "input": "In vitro tests, designed to explore organotin action modes at cell level by minimizing interfering factors, point out akin responses to these man - made environmental pollutants from prokaryotes to mammals.", "output": "organotin." }, { "input": "On the other hand, a broad susceptibility range to organotin toxicants of animal cells and variegated action mechanisms of these compounds have been reported both in vitro and in vivo studies.", "output": "organotin." }, { "input": "Endocrine and lipid homeostasis perturbations span from mollusks to mammals, in which organotins mainly favor fat accumulation.", "output": "organotins." }, { "input": "Lipid changes were also found in Bacteria.", "output": "There is no related enetity." }, { "input": "Organotin are immunotoxic both in invertebrates and humans.", "output": "Organotin." }, { "input": "Mitochondria and membrane functions seem to be a preferred target of these lipophilic pollutants.", "output": "There is no related enetity." }, { "input": "The inhibition of key membrane - bound enzyme complexes such as Na, K - and F0F1 - ATPases, accompanied by perturbation of hydromineral balance, membrane potential and bioenergetics, has been widely reported.", "output": "Na, K." }, { "input": "Highly conserved mechanisms could be involved in organotin binding to nuclear receptors, membrane components and intracellular proteins as well as in promoting DNA damage, all widely shared action modes of these toxicants.", "output": "organotin." }, { "input": "Accordingly, the different responsiveness / refractoriness to organotins, here overviewed, may mirror the biochemical - physiological selectivity of biomembranes, signalling pathways and intracellular protein components.", "output": "organotins." }, { "input": "Integration of pre - aligned liquid metal electrodes for neural stimulation within a user - friendly microfluidic platform.", "output": "There is no related enetity." }, { "input": "Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research.", "output": "There is no related enetity." }, { "input": "With the increase of optical probes to record neuronal activity, simple and user - friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation.", "output": "There is no related enetity." }, { "input": "Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal.", "output": "There is no related enetity." }, { "input": "We integrated electrode and cell channels into a single poly ( dimethylsiloxane ) ( PDMS ) chip, eliminating entirely the need to align electrodes with microchannels.", "output": "poly ( dimethylsiloxane ), PDMS." }, { "input": "We designed the electrode channels such that the metal can be injected by hand and when the device is non - covalently bound to glass.", "output": "There is no related enetity." }, { "input": "We demonstrated the biocompatibility of the electrodes for long - term cultures ( 12 days ) using hippocampal neurons.", "output": "There is no related enetity." }, { "input": "We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo - 4.", "output": "calcium, Fluo - 4." }, { "input": "We established optimal stimulation parameters that induce neuronal spiking without inducing damage.", "output": "There is no related enetity." }, { "input": "We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters.", "output": "calcium." }, { "input": "Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons.", "output": "There is no related enetity." }, { "input": "In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user - friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations.", "output": "There is no related enetity." }, { "input": "Density functional theory study of the structure and vibrational modes of acrylonitrile adsorbed on Cu ( 100 ).", "output": "acrylonitrile, Cu ( 100 )." }, { "input": "We present a theoretical study of the structure and vibrations of acrylonitrile adsorbed on a Cu ( 100 ) metal surface.", "output": "acrylonitrile, Cu ( 100 )." }, { "input": "Simulations have been carried out by means of the density functional theory adopting periodic boundary conditions and including van der Waals dispersion forces.", "output": "There is no related enetity." }, { "input": "The two most stable structures ( which are almost degenerate in energy ) correspond to the molecule adsorbed parallel to the metal surface.", "output": "There is no related enetity." }, { "input": "In both geometries, the vinyl ( C = C ) and the cyano ( C = N ) groups are the anchorage sites to the surface atoms.", "output": "vinyl, C = C, cyano, C = N." }, { "input": "Low energy transition barriers allow fast isomerization between both structures.", "output": "There is no related enetity." }, { "input": "Molecular adsorption shifts some of their vibrational frequencies with respect to the gas phase, mainly the C = C and the C = N stretching modes, in agreement with recent experimental measurements [ Tornero et al., Phys. Chem. Chem. Phys., 2011, 13, 8475 ].", "output": "C = C, C = N." }, { "input": "Synthesis and NIR optical properties of hollow gold nanospheres with LSPR greater than one micrometer.", "output": "There is no related enetity." }, { "input": "Optical analysis in the near infrared region is of significant biological importance due to better tissue penetration and reduced autofluorescence.", "output": "There is no related enetity." }, { "input": "In this work, an improved synthesis of hollow gold nanospheres ( HGNs ), which provides a tunable localized surface plasmon resonance ( LSPR ) from 610 nm up to 1320 nm, is demonstrated.", "output": "There is no related enetity." }, { "input": "The scattering properties of these nanoparticles are shown using surface enhanced Raman scattering ( SERS ) at 1064 nm excitation wavelength and are compared to citrate reduced gold and silver nanoparticles of similar physical sizes and surface properties.", "output": "citrate, silver." }, { "input": "After the addition of salts, a strong signal was observed from hollow gold with a LSPR of 650 nm and a weaker, yet observable, signal from HGNs with a LSPR of 775 nm.", "output": "There is no related enetity." }, { "input": "However, no obvious signals were observed in the case of standard citrate reduced gold, silver or HGNs with a LSPR of 1080 nm.", "output": "citrate, silver." }, { "input": "The absorption properties of HGNs were investigated by monitoring their photothermal activity.", "output": "There is no related enetity." }, { "input": "In this case, different nanoparticle suspensions including citrate reduced gold, silver, and HGNs were illuminated by a continuous laser at 785 nm excitation wavelength and the absorption efficiency of HGNs with a LSPR of 775 nm was calculated to be 0. 81 % which is more than 5 times higher than the absorption efficiency of citrate reduced gold nanoparticles under similar conditions.", "output": "citrate, silver, citrate." }, { "input": "Determining and reporting purity of organic molecules: why qNMR.", "output": "There is no related enetity." }, { "input": "Although NMR has been routinely used to determine / estimate relative number of protons for structure elucidation, it has been rarely used to determine and report the purity of organic compounds.", "output": "There is no related enetity." }, { "input": "Through this paper, we want to emphasize on routine use of quantitative NMR ( qNMR ) for this purpose.", "output": "There is no related enetity." }, { "input": "The results of qNMR can be routinely considered as documentation of purity much like other established methods ( HPLC, elemental analysis and differential scanning calorimetry ).", "output": "There is no related enetity." }, { "input": "qNMR is a fast, easy, accurate and non - destructive alternate to speed up the whole analytical process and serves the purpose of both identification and purity determination of compounds using single technique.", "output": "There is no related enetity." }, { "input": "In vitro transfection mediated by dendrigraft poly ( L - lysines ): the effect of structure and molecule size.", "output": "poly ( L - lysines )." }, { "input": "Dendritic poly ( L - lysines ) ( DGL ) constitute promising nanomaterials applicable as a nonviral gene - delivery vector.", "output": "Dendritic poly ( L - lysines ), DGL." }, { "input": "In this study, we evaluate the transfection abilities of four DGL generations with special emphasis on the systematic description of the relationship of how generation ( i. e., molecule size ) affects the transfection efficacy.", "output": "DGL." }, { "input": "Using Hep2 cells, we demonstrated that the capability of unmodified DGL to deliver plasmid is of a magnitude lower than that of jetPEI.", "output": "DGL, jetPEI." }, { "input": "On the other hand, employing the Hep2 cell line stably transduced with eGFP, we observed that DGL G5 delivers the siRNA oligonucleotide with the same efficiency as Lipofectamine 2000.", "output": "DGL." }, { "input": "In further experiments, it was shown that DGL affords excellent ability to bind DNA, protect it against DNase I attack, and internalize it into cells.", "output": "DGL." }, { "input": "Synthesis and SAR of novel Re / 99mTc - labeled benzenesulfonamide carbonic anhydrase IX inhibitors for molecular imaging of tumor hypoxia.", "output": "Re, 99mTc, benzenesulfonamide." }, { "input": "Carbonic anhydrase IX ( CA - IX ) is upregulated in cancer in response to the hypoxic tumor microenvironment, making it an attractive molecular target for the detection of hypoxic solid tumors.", "output": "There is no related enetity." }, { "input": "A series of small molecule benzenesulfonamide based CA - IX inhibitors containing novel tridentate chelates complexed with the M ( CO ) ( 3 ) core ( M = Re or ( 99m ) Tc ) were designed and synthesized.", "output": "benzenesulfonamide, M ( CO ) ( 3 ), Re, ( 99m ) Tc." }, { "input": "The in vitro binding affinity of the benzenesulfonamide rhenium complexes yielded IC ( 50 ) values ranging from 3 to 116 nM in hypoxic CA - IX expressing HeLa cells.", "output": "benzenesulfonamide rhenium." }, { "input": "One of the most potent compounds, 3d ( IC ( 50 ) = 9 nM ), was radiolabeled with technetium tricarbonyl ( { ( 99m ) Tc ( CO ) ( 3 ) } ( + ) ) to afford the { ( 99m ) Tc ( CO ) ( 3 ) } ( + ) complex in excellent yield and high purity.", "output": "technetium tricarbonyl, { ( 99m ) Tc ( CO ) ( 3 ) } ( + ), ( 99m ) Tc ( CO ) ( 3 ) } ( + )." }, { "input": "( 99m ) Tc ( CO ) ( 3 ) - 3d bound specifically to CA - IX expressing hypoxic HeLa cells.", "output": "( 99m ) Tc ( CO ) ( 3 )." }, { "input": "This effort led to the identification of a diverse series of promising high affinity { ( 99m ) Tc ( CO ) ( 3 ) } ( + ) radiolabeled CA - IX inhibitors with the potential to significantly impact diagnosis, staging, and treatment selection of hypoxic solid tumors.", "output": "{ ( 99m ) Tc ( CO ) ( 3 ) } ( + )." }, { "input": "Influence of surface groups on poly ( propylene imine ) dendrimers antiprion activity.", "output": "poly ( propylene imine )." }, { "input": "Prion diseases are characterized by the accumulation of PrP ( Sc ), an aberrantly folded isoform of the host protein PrP ( C ).", "output": "There is no related enetity." }, { "input": "Specific forms of synthetic molecules known as dendrimers are able to eliminate protease - resistant PrP ( Sc ) in both an intracellular and in vitro setting.", "output": "There is no related enetity." }, { "input": "The properties of a dendrimer which govern this ability are unknown.", "output": "There is no related enetity." }, { "input": "We addressed the issue by comparing the in vitro antiprion ability of numerous modified poly ( propylene - imine ) dendrimers, which varied in size, structure, charge, and surface group composition.", "output": "poly ( propylene - imine )." }, { "input": "Several of the modified dendrimers, including an anionic glycodendrimer, reduced the level of protease resistant PrP ( Sc ) in a prion strain - dependent manner.", "output": "There is no related enetity." }, { "input": "This led to the formulation of a new working model for dendrimer / prion interactions which proposes dendrimers eliminate PrP ( Sc ) by destabilizing the protein and rendering it susceptible to proteolysis.", "output": "There is no related enetity." }, { "input": "This ability is not dependent on any particular charge of dendrimer, but does require a high density of reactive surface groups.", "output": "There is no related enetity." }, { "input": "Hybrid carbon nanotube networks as efficient hole extraction layers for organic photovoltaics.", "output": "carbon." }, { "input": "Transparent, highly percolated networks of regioregular poly ( 3 - hexylthiophene ) ( rr - P3HT ) - wrapped semiconducting single - walled carbon nanotubes ( s - SWNTs ) are deposited, and the charge transfer processes of these nanohybrids are studied using spectroscopic and electrical measurements.", "output": "poly ( 3 - hexylthiophene ), P3HT, carbon." }, { "input": "The data disclose hole doping of s - SWNTs by the polymer, challenging the prevalent electron - doping hypothesis.", "output": "There is no related enetity." }, { "input": "Through controlled fabrication, high - to low - density nanohybrid networks are achieved, with low - density hybrid carbon nanotube networks tested as hole transport layers ( HTLs ) for bulk heterojunction ( BHJ ) organic photovoltaics ( OPV ).", "output": "carbon." }, { "input": "OPVs incorporating these rr - P3HT / s - SWNT networks as the HTL demonstrate the best large area ( 70 mm ( 2 ) ) carbon nanotube incorporated organic solar cells to date with a power conversion efficiency of 7. 6 %.", "output": "P3HT, carbon." }, { "input": "This signifies the strong capability of nanohybrids as an efficient hole extraction layer, and we believe that dense nanohybrid networks have the potential to replace expensive and material scarce inorganic transparent electrodes in large area electronics toward the realization of low - cost flexible electronics.", "output": "There is no related enetity." }, { "input": "Reporter ligand NMR screening method for 2 - oxoglutarate oxygenase inhibitors.", "output": "2 - oxoglutarate." }, { "input": "The human 2 - oxoglutarate ( 2OG ) dependent oxygenases belong to a family of structurally related enzymes that play important roles in many biological processes.", "output": "2 - oxoglutarate, 2OG." }, { "input": "We report that competition - based NMR methods, using 2OG as a reporter ligand, can be used for quantitative and site - specific screening of ligand binding to 2OG oxygenases.", "output": "2OG, 2OG." }, { "input": "The method was demonstrated using hypoxia inducible factor hydroxylases and histone demethylases, and K ( D ) values were determined for inhibitors that compete with 2OG at the metal center.", "output": "2OG." }, { "input": "This technique is also useful as a screening or validation tool for inhibitor discovery, as exemplified by work with protein - directed dynamic combinatorial chemistry.", "output": "There is no related enetity." }, { "input": "Strontium Ranelate affects signaling from mechanically - stimulated osteocytes towards osteoclasts and osteoblasts.", "output": "Strontium Ranelate." }, { "input": "Strontium Ranelate ( SrRan ) is used to decrease the risk of bone fractures.", "output": "Strontium Ranelate, SrRan." }, { "input": "Any factor that alters the release of paracrine signals by osteocytes in response to mechanical stimuli potentially affects bone mass and structure, and thus fracture resistance.", "output": "There is no related enetity." }, { "input": "We hypothesized that SrRan affects paracrine signaling from mechanically - stimulated osteocytes towards osteoclast - precursors and osteoblasts.", "output": "SrRan." }, { "input": "MLO - Y4 osteocytes were cultured for 24h with SrRan ( 0. 1 - 3mM ) and either or not mechanically stimulated by pulsating fluid flow ( PFF; 0. 7 +/- 0. 3 Pa, 5 Hz ) for 60 min.", "output": "SrRan." }, { "input": "Nitric oxide ( NO ) and prostaglandin E ( 2 ) ( PGE ( 2 ) ) release, and expression of mechanoresponsive genes were quantified.", "output": "Nitric oxide, NO, prostaglandin E ( 2 ), PGE ( 2 )." }, { "input": "Conditioned medium ( CM ) from osteocytes was added to mouse bone marrow cells for 7 days to assess osteoclastogenesis, or MC3T3 - E1 osteoblasts for 4 - 16 days to measure osteogenic gene expression.", "output": "There is no related enetity." }, { "input": "SrRan ( 3mM ) enhanced NO and PGE ( 2 ) release to the same extent in static osteocytes ( NO: 1. 6 - fold; PGE ( 2 ): 2. 8 - fold ) and PFF - stimulated osteocytes ( NO: 1. 3 - fold; PGE ( 2 ): 2. 6 - fold ).", "output": "SrRan, NO, PGE ( 2 ), NO, PGE ( 2 ), NO, PGE ( 2 )." }, { "input": "CM from PFF - treated osteocytes without SrRan enhanced Ki67 expression but reduced Runx2 and Ocn expression in osteoblasts.", "output": "SrRan." }, { "input": "This effect on gene expression was not observed with CM obtained from osteocytes treated with the combination of PFF and 3mM SrRan.", "output": "SrRan." }, { "input": "CM from PFF - treated osteocytes inhibited osteoclastogenesis by 1. 9 - fold.", "output": "There is no related enetity." }, { "input": "The combination of PFF and 3mM SrRan reduced osteocyte - stimulated osteoclastogenesis even more strongly ( 4. 3 - fold ).", "output": "SrRan." }, { "input": "In conclusion, SrRan affects paracrine signaling between mechanically - stimulated MLO - Y4 osteocytes and both osteoblasts and osteoclast precursors.", "output": "SrRan." }, { "input": "The positive effects of SrRan on bone fracture resistance may thus be partly explained by altered paracrine signaling by osteocytes.", "output": "SrRan." }, { "input": "Influence of carboxylic acid functionalities in ruthenium ( II ) polypyridyl complexes on DNA binding, cytotoxicity and antioxidant activity: synthesis, structure and in vitro anticancer activity.", "output": "carboxylic acid, ruthenium ( II ) polypyridyl complexes." }, { "input": "Four new Ru ( II ) complexes [ RuHCl ( bpy ) ( PPh ( 3 ) ) ( CO ) ] ( 1 ), [ RuHCl ( bpy ) ( AsPh ( 3 ) ) ( CO ) ] ( 2 ) ( bpy = 2, 2 ' - bipyridine ), [ RuCl ( HL ) ( PPh ( 3 ) ) ( 2 ) ( CO ) ] ( 3 ) and [ RuCl ( HL ) ( AsPh ( 3 ) ) ( 2 ) ( CO ) ] ( 4 ) ( HL = 2, 2 ' - bipyridine - 4, 4 ' - dicarboxylic acid ) were synthesized and characterized.", "output": "Ru ( II ), [ RuHCl ( bpy ) ( PPh ( 3 ) ) ( CO ) ], [ RuHCl ( bpy ) ( AsPh ( 3 ) ) ( CO ) ], bpy, 2 , 2 ' - bipyridine, [ RuCl ( HL ) ( PPh ( 3 ) ) ( 2 ) ( CO ) ], [ RuCl ( HL ) ( AsPh ( 3 ) ) ( 2 ) ( CO ) ], 2 , 2 ' - bipyridine - 4 , 4 ' - dicarboxylic acid." }, { "input": "X - ray diffraction was used to characterize 3 in solid state.", "output": "There is no related enetity." }, { "input": "The interactions of these complexes with DNA were explored by different techniques which revealed that the complexes could bind to CT - DNA through non - intercalation.", "output": "There is no related enetity." }, { "input": "The in vitro cytotoxic and antioxidant activities of the complexes validated against a panel of cancer cell lines and free radicals showed that 3 and 4 possess quite high anticancer and antioxidant activities over 1, 2 and standard drugs.", "output": "There is no related enetity." }, { "input": "An apparent dependence of biological activities on incorporation of COOH in bipyridine moiety was noticed: Inclusion of COOH caused significant differences in DNA binding, cytotoxicity and antioxidant activity.", "output": "COOH, bipyridine, COOH." }, { "input": "Mast cells produce novel shorter forms of perlecan that contain functional endorepellin: a role in angiogenesis and wound healing.", "output": "There is no related enetity." }, { "input": "Mast cells are derived from hematopoietic progenitors that are known to migrate to and reside within connective and mucosal tissues, where they differentiate and respond to various stimuli by releasing pro - inflammatory mediators, including histamine, growth factors, and proteases.", "output": "histamine." }, { "input": "This study demonstrated that primary human mast cells as well as the rat and human mast cell lines, RBL - 2H3 and HMC - 1, produce the heparan sulfate proteoglycan, perlecan, with a molecular mass of 640 kDa as well as smaller molecular mass species of 300 and 130 kDa.", "output": "sulfate." }, { "input": "Utilizing domain - specific antibodies coupled with N - terminal sequencing, it was confirmed that both forms contained the C - terminal module of the protein core known as endorepellin, which were generated by mast cell - derived proteases.", "output": "N, C." }, { "input": "Domain - specific RT - PCR experiments demonstrated that transcripts corresponding to domains I and V, including endorepellin, were present; however, mRNA transcripts corresponding to regions of domain III were not present, suggesting that these cells were capable of producing spliced forms of the protein core.", "output": "There is no related enetity." }, { "input": "Fractions from mast cell cultures that were enriched for these fragments were shown to bind endothelial cells via the alpha ( 2 ) beta ( 1 ) integrin and stimulate the migration of cells in \" scratch assays, \" both activities of which were inhibited by incubation with either anti - endorepellin or anti - perlecan antibodies.", "output": "There is no related enetity." }, { "input": "This study shows for the first time that mast cells secrete and process the extracellular proteoglycan perlecan into fragments containing the endorepellin C - terminal region that regulate angiogenesis and matrix turnover, which are both key events in wound healing.", "output": "C." }, { "input": "First crystal structure of a fungal high - redox potential dye - decolorizing peroxidase: substrate interaction sites and long - range electron transfer.", "output": "There is no related enetity." }, { "input": "Dye - decolorizing peroxidases ( DyPs ) belong to the large group of heme peroxidases.", "output": "heme." }, { "input": "They utilize hydrogen peroxide to catalyze oxidations of various organic compounds.", "output": "hydrogen peroxide." }, { "input": "AauDyPI from Auricularia auricula - judae ( fungi ) was crystallized, and its crystal structure was determined at 2. 1 A resolution.", "output": "There is no related enetity." }, { "input": "The mostly helical structure also shows a beta - sheet motif typical for DyPs and Cld ( chlorite dismutase ) - related structures and includes the complete polypeptide chain.", "output": "chlorite." }, { "input": "At the distal side of the heme molecule, a flexible aspartate residue ( Asp - 168 ) plays a key role in catalysis.", "output": "heme, aspartate, Asp." }, { "input": "It guides incoming hydrogen peroxide toward the heme iron and mediates proton rearrangement in the process of Compound I formation.", "output": "hydrogen peroxide, heme, iron." }, { "input": "Afterward, its side chain changes its conformation, now pointing toward the protein backbone.", "output": "There is no related enetity." }, { "input": "We propose an extended functionality of Asp - 168, which acts like a gatekeeper by altering the width of the heme cavity access channel.", "output": "Asp, heme." }, { "input": "Chemical modifications of potentially redox - active amino acids show that a tyrosine is involved in substrate interaction.", "output": "amino acids, tyrosine." }, { "input": "Using spin - trapping experiments, a transient radical on the surface - exposed Tyr - 337 was identified as the oxidation site for bulky substrates.", "output": "Tyr." }, { "input": "A possible long - range electron transfer pathway from the surface of the enzyme to the redox cofactor ( heme ) is discussed.", "output": "heme." }, { "input": "Computational study of the spin - state energies and UV - Vis spectra of bis ( 1, 4, 7 - triazacyclononane ) complexes of some first - row transition metal cations.", "output": "bis ( 1 , 4 , 7 - triazacyclononane ), transition metal." }, { "input": "We report here computed spin - state energies and UV - Vis spectra for several transition metal complexes with a triazacyclononane ligand.", "output": "transition metal, triazacyclononane." }, { "input": "Our results show that the spin ground - state is correctly obtained with either OPBE or SSB - D, except for the high - spin ground - state of the Co ( ii ) complex that was properly described only by SSB - D.", "output": "Co ( ii )." }, { "input": "The UV - Vis spectra from TD - DFT reproduce in general rather well the experimental spectra, but in cases of the Cr ( iii ) and Co ( ii ) complexes it clearly failed.", "output": "Cr ( iii ), Co ( ii )." }, { "input": "Better results for the UV - Vis spectra have been obtained by using Ligand Field DFT.", "output": "There is no related enetity." }, { "input": "Particle shape optimization by changing from an isotropic to an anisotropic nanostructure: preparation of highly active and stable supported Pt catalysts in microemulsions.", "output": "Pt." }, { "input": "We recently introduced a new method to synthesize an active and stable Pt catalyst, namely thermo - destabilization of microemulsions ( see R. Y. Parapat, V. Parwoto, M. Schwarze, B. Zhang, D. S. Su and R. Schom a cker, J. Mater. Chem., 2012, 22 ( 23 ), 11605 - 11614 ).", "output": "Pt." }, { "input": "We are able to produce Pt nanocrystals with a small size ( 2. 5 nm ) of an isotropic structure i. e. truncated octahedral and deposit them well on support materials.", "output": "Pt." }, { "input": "Although we have obtained good results, the performance of the catalyst still needed to be improved and optimized.", "output": "There is no related enetity." }, { "input": "We followed the strategy to retain the small size but change the shape to an anisotropic structure of Pt nanocrystals which produces more active sites by means of a weaker reducing agent.", "output": "Pt." }, { "input": "We found that our catalysts are more active than those we reported before and even show the potential to be applied in a challenging reaction such as hydrogenation of levulinic acid.", "output": "levulinic acid." }, { "input": "Influence of glass scaffolds macroporosity on the bioactive process.", "output": "There is no related enetity." }, { "input": "Little is known about the ideal morphology for three - dimensional ( 3D ) porous scaffolds to be used in bone tissue engineering.", "output": "There is no related enetity." }, { "input": "The present study will supply useful data about the dependence of the mineralization process upon macroporous features of bioactive glass scaffolds.", "output": "There is no related enetity." }, { "input": "It also points out the difficulty in distinguishing between the bioactive properties of scaffolds if using common characterization techniques often considered as standard techniques to assess in vitro bioactivity.", "output": "There is no related enetity." }, { "input": "Here, two bioactive glass foams with different porosities ( porous diameters and interconnection sizes ) were successfully synthesized by varying the surfactant quantity in the sol - gel foaming process.", "output": "There is no related enetity." }, { "input": "The two foams had porosities apparently sufficient to serve as a bone tissue engineering scaffold and exhibited no significant difference when studied for the releasing or the taking up of ionic species when immersed in simulated body fluid ( SBF ).", "output": "There is no related enetity." }, { "input": "However, thanks to microion beam analysis, it was possible to highlight key differences in the mineralization reaction taking place at the surface of the pores.", "output": "There is no related enetity." }, { "input": "It is clearly evident that the homogeneity of reaction inside the 3D - scaffolds is particularly dependent upon porosity.", "output": "There is no related enetity." }, { "input": "In particular, it is demonstrated that inadequate porous features can result in limited circulation of the fluid inside the pores.", "output": "There is no related enetity." }, { "input": "Careful attention must be paid to the pore size distribution and interconnection sizes when designing scaffolds for bone tissue engineering, in order to induce homogeneous mineralization inside the porous material and for the scaffold to be efficiently alimented with nutrients or growth factors while allowing a free circulation of the bone cells.", "output": "There is no related enetity." }, { "input": "Tuning the light emission from GaAs nanowires over 290 meV with uniaxial strain.", "output": "GaAs." }, { "input": "Strain engineering has been used to increase the charge carrier mobility of complementary metal - oxide - semiconductor transistors as well as to boost and tune the performance of optoelectronic devices, enabling wavelength tuning, polarization selectivity and suppression of temperature drifts.", "output": "There is no related enetity." }, { "input": "Semiconducting nanowires benefit from enhanced mechanical properties, such as increased yield strength, that turn out to be beneficial to amplify strain effects.", "output": "There is no related enetity." }, { "input": "Here we use photoluminescence ( PL ) to study the effect of uniaxial stress on the electronic properties of GaAs / Al0. 3Ga0. 7As / GaAs core / shell nanowires.", "output": "GaAs, 7As, GaAs." }, { "input": "Both compressive and tensile mechanical stress were applied continuously and reversibly to the nanowire, resulting in a remarkable decrease of the bandgap of up to 296 meV at 3. 5 % of strain.", "output": "There is no related enetity." }, { "input": "Raman spectra were measured and analyzed to determine the axial strain in the nanowire and the Poisson ratio in the < 111 > direction.", "output": "There is no related enetity." }, { "input": "In both PL and Raman spectra, we observe fingerprints of symmetry breaking due to anisotropic deformation of the nanowire.", "output": "There is no related enetity." }, { "input": "The shifts observed in the PL and Raman spectra are well described by bulk deformation potentials for band structure and phonon energies.", "output": "There is no related enetity." }, { "input": "The fact that exceptionally high elastic strain can be applied to semiconducting nanowires makes them ideally suited for novel device applications that require a tuning of the band structure over a broad range.", "output": "There is no related enetity." }, { "input": "Magnetic assembly and patterning of general nanoscale materials through nonmagnetic templates.", "output": "There is no related enetity." }, { "input": "Applied magnetic field represents an effective tool to rapidly assemble micro - and nanoscale magnetic objects into defined structures.", "output": "There is no related enetity." }, { "input": "Ordered assembly is typically achieved by using magnetic micropatterns, for which the downside is that they require advanced microfabrication techniques to produce.", "output": "There is no related enetity." }, { "input": "In addition, most conventional magnetic assembly strategies are restricted to target objects that possess magnetic properties.", "output": "There is no related enetity." }, { "input": "Herein we present a general strategy that allows convenient magnetically driven assembly of nonmagnetic objects in defined locations with high spatial resolution.", "output": "There is no related enetity." }, { "input": "The process involves immersing a polymer relief pattern in a uniformly magnetized ferrofluid, which modulates the local magnetic fields around the pattern.", "output": "There is no related enetity." }, { "input": "Nonmagnetic target objects dispersed in the same ferrofluid can then be magnetically assembled at positions defined by the polymer pattern.", "output": "There is no related enetity." }, { "input": "As the nonmagnetic polymer patterns can be conveniently fabricated at low cost through photolithography and soft - lithography processes, our method provides a general yet very effective means to assemble a wide range of nonmagnetic objects with controlled spatial distribution, paving the way toward patterning functional microstructures.", "output": "There is no related enetity." }, { "input": "Light - triggered biocatalysis using thermophilic enzyme - gold nanoparticle complexes.", "output": "There is no related enetity." }, { "input": "The use of plasmonic nanoparticle complexes for biomedical applications such as imaging, gene therapy, and cancer treatment is a rapidly emerging field expected to significantly improve conventional medical practices.", "output": "There is no related enetity." }, { "input": "In contrast, the use of these types of nanoparticles to noninvasively trigger biochemical pathways has been largely unexplored.", "output": "There is no related enetity." }, { "input": "Here we report the light - induced activation of the thermophilic enzyme Aeropyrum pernix glucokinase, a key enzyme for the decomposition of glucose via the glycolysis pathway, increasing its rate of reaction 60 % with light by conjugating the enzyme onto Au nanorods.", "output": "glucose, Au." }, { "input": "The observed increase in enzyme activity corresponded to a local temperature increase within a calcium alginate encapsulate of ~ 20 degrees C when compared to the bulk medium maintained at standard, nonthermophilic temperatures.", "output": "calcium." }, { "input": "The encapsulated nanocomplexes were reusable and stable for several days, making them potentially useful in industrial applications.", "output": "There is no related enetity." }, { "input": "This approach could significantly improve how biochemical pathways are controlled for in vitro and, quite possibly, in vivo use.", "output": "There is no related enetity." }, { "input": "Slip flow through colloidal crystals of varying particle diameter.", "output": "There is no related enetity." }, { "input": "Slip flow of water through silica colloidal crystals was investigated experimentally for eight different particle diameters, which have hydraulic channel radii ranging from 15 to 800 nm.", "output": "silica." }, { "input": "The particle surfaces were silylated to be low in energy, with a water contact angle of 83 degrees, as determined for a silylated flat surface.", "output": "There is no related enetity." }, { "input": "Flow rates through centimeter lengths of colloidal crystal were measured using a commercial liquid chromatograph for accurate comparisons of water and toluene flow rates using pressure gradients as high as 10 ( 10 ) Pa / m.", "output": "There is no related enetity." }, { "input": "Toluene exhibited no - slip Hagen - Poiseuille flow for all hydraulic channel radii.", "output": "There is no related enetity." }, { "input": "For water, the slip flow enhancement as a function of hydraulic channel radius was described well by the expected slip flow correction for Hagen - Poiseuille flow, and the data revealed a constant slip length of 63 +/- 3 nm.", "output": "There is no related enetity." }, { "input": "A flow enhancement of 20 +/- 2 was observed for the smallest hydraulic channel radius of 15 nm.", "output": "There is no related enetity." }, { "input": "The amount of slip flow was found to be independent of shear rate over a range of fluid velocities from 0. 7 to 5. 8 mm / s.", "output": "There is no related enetity." }, { "input": "The results support the applicability of the slip flow correction for channel radii as small as 15 nm.", "output": "There is no related enetity." }, { "input": "The work demonstrates that packed beds of submicrometer particles enable slip flow to be employed for high - volume flow rates.", "output": "There is no related enetity." }, { "input": "Cycloheximide stimulates suppressor of cytokine signaling - 3 gene expression in 3T3 - L1 adipocytes via the extracellular signal - regulated kinase pathway.", "output": "Cycloheximide." }, { "input": "Suppressor of cytokine signaling ( SOCS ) - 3 can act as a regulator of energy metabolism and cytokine signaling in fat cells.", "output": "There is no related enetity." }, { "input": "It is regulated by hormones and toxicological factors.", "output": "There is no related enetity." }, { "input": "However, the action of cycloheximide on expression of adipocyte SOCS - 3 gene is unknown.", "output": "cycloheximide." }, { "input": "Using 3T3 - L1 adipocytes, we found that cycloheximide up - regulated SOCS - 3 mRNA expression in dose - and time - dependent manners.", "output": "cycloheximide." }, { "input": "Treatment with actinomycin D prevented cycloheximide - stimulated SOCS - 3 mRNA expression, suggesting that the effect of cycloheximide requires new mRNA synthesis.", "output": "actinomycin D, cycloheximide, cycloheximide." }, { "input": "While cycloheximide was shown to increase activities of MEK1 and JNK, signaling was demonstrated to be inhibited by pretreatment with either MEK1 inhibitors U0126 and PD98059, or with the JNK inhibitor SP600125.", "output": "cycloheximide, U0126, PD98059, SP600125." }, { "input": "U0126 and PD98059, respectively, reduced cycloheximide - stimulated SOCS - 3 mRNA expression, but SP600125 did not antagonize cycloheximide effect.", "output": "U0126, PD98059, cycloheximide, SP600125, cycloheximide." }, { "input": "Moreover, cycloheximide was observed to up - regulate expression of other SOCS family members, such as SOCS - 1, - 2, - 4, - 5, - 6, - 7, and cytokine - inducible SH2 - containing protein ( CIS ) - 1 mRNAs.", "output": "cycloheximide." }, { "input": "Such effects varied with the dosage and duration of cycloheximide treatment.", "output": "cycloheximide." }, { "input": "These results imply the functional MEK1 / ERK - mediated pathway is necessary for the cycloheximide stimulation of SOCS - 3 gene expression.", "output": "cycloheximide." }, { "input": "Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non - homologous end - joining.", "output": "There is no related enetity." }, { "input": "In S and G2 phase mammalian cells DNA double strand breaks ( DSBs ) can potentially be repaired by homologous recombination ( HR ) or non - homologous end - joining ( NHEJ ).", "output": "There is no related enetity." }, { "input": "Results of several studies suggest that these two mechanistically distinct repair pathways can compete for DNA ends.", "output": "There is no related enetity." }, { "input": "Because HR and NHEJ differ with respect to error susceptibility, generation of chromosome rearrangements, which are potentially carcinogenic products of DSB repair, may depend on the pathway choice.", "output": "There is no related enetity." }, { "input": "To investigate this hypothesis, the influence of HR and NHEJ inhibition on the frequencies of chromosome aberrations in G2 phase cells was investigated.", "output": "There is no related enetity." }, { "input": "SW - 1573 and RKO cells were treated with mild ( 41 degrees C ) hyperthermia in order to disable HR and / or NU7441 / cisplatin to inactivate NHEJ and frequencies of chromosomal fragments ( resulting from unrepaired DSBs ) and translocations ( products of erroneous DSB rejoining ) were studied using premature chromosome condensation ( PCC ) combined with fluorescence in situ hybridization ( FISH ).", "output": "NU7441, cisplatin." }, { "input": "It is shown here that temporary inhibition of HR by hyperthermia results in increased frequency of ionizing - radiation ( IR ) - induced chromosomal translocations and that this effect is abrogated by NU7441 - or cisplatin - mediated inhibition of NHEJ.", "output": "NU7441, cisplatin." }, { "input": "The results suggest that in the absence of HR, DSB repair is shifted to the error - prone NHEJ pathway resulting in increased frequencies of chromosomal rearrangements.", "output": "There is no related enetity." }, { "input": "These results might be of consequence for clinical cancer treatment approaches that aim at inhibition of one or more DSB repair pathways.", "output": "There is no related enetity." }, { "input": "Lignans from Schisandra sphenathera Rehd.", "output": "Lignans." }, { "input": "et Wils. and semisynthetic schisantherin A analogues: absolute configuration, and their estrogenic and anti - proliferative activity.", "output": "schisantherin A." }, { "input": "A new dibenzocyclooctene - type lignan, named schisandrin A1 ( 1 ), together with nine known lignans ( 2 - 10 ), was isolated from the stems of Schisandra sphenathera.", "output": "dibenzocyclooctene, lignan, schisandrin A1." }, { "input": "The structure of schisandrin A1, which contains a spirocyclic epoxy unit, was established by means of spectroscopic methods.", "output": "schisandrin A1, epoxy." }, { "input": "The absolute configurations of schisandrin A1 ( 1 ) and schisantherin A ( 2 ) were determined by electronic circular dichroism ( CD ) and TDDFT calculations, with 2 further confirmed by X - ray crystallographic data.", "output": "schisandrin A1, schisantherin A." }, { "input": "Ten new schisantherin A derivatives ( 11 - 20 ) and 6, 7 - secoschisantherol A ( 2b ) were synthesized.", "output": "schisantherin A, 6 , 7 - secoschisantherol A." }, { "input": "In addition, natural lignans and semisynthetic schisantherin A derivatives showed the antiproliferative activity on four human cancer cell lines and Id1 ( an inhibitor of DNA binding protein ) and estrogenic potency.", "output": "lignans, schisantherin A." }, { "input": "Compounds 5, 7, and 8 exhibited very potent estrogenic activity.", "output": "There is no related enetity." }, { "input": "Four new triterpenoid saponins from the leaves of Panax japonicus grown in southern Miyazaki Prefecture ( 4 ).", "output": "triterpenoid saponins." }, { "input": "Four new dammarane - type triterpenoid saponins such as chikusetsusaponin LM3 ( 1 ), chikusetsusaponin LM4 ( 2 ), chikusetsusaponin LM5 ( 3 ), chikusetsusaponin LM6 ( 4 ), and twenty known triterpenoid saponins such as ginsenoside Rb3 ( 5 ), ginsenoside Rc ( 6 ), ginsenoside Rd ( 7 ), ginsenoside Re ( 8 ), ginsenoside Rg1 ( 9 ), ginsenoside F3 ( 10 ), ginsenoside F5 ( 11 ), ginsenoside F6 ( 12 ), chikusetsusaponin IVa ( 13 ), chikusetsusaponin V ( 14 ), chikusetsusaponin L5 ( 15 ), chikusetsusaponin L9a ( 16 ), chikusetsusaponin L9bc ( 17 ), chikusetsusaponin L10 ( 18 ), chikusetsusaponin FK2 ( 19 ), chikusetsusaponin FK6 ( 20 ), chikusetsusaponin FK7 ( 21 ), chikusetsusaponin FT1 ( 22 ), chikusetsusaponin LM1 ( 23 ), and chikusetsusaponin LM2 ( 24 ), were isolated from the leaves of Panax japonicus C.", "output": "dammarane, triterpenoid saponins, chikusetsusaponin LM3, chikusetsusaponin LM4, chikusetsusaponin LM5, chikusetsusaponin LM6, triterpenoid saponins, ginsenoside Rb3, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, ginsenoside Rg1, ginsenoside F3, ginsenoside F5, ginsenoside F6, chikusetsusaponin IVa, chikusetsusaponin V, chikusetsusaponin L5, chikusetsusaponin L9a, chikusetsusaponin L9bc, chikusetsusaponin L10, chikusetsusaponin FK2, chikusetsusaponin FK6, chikusetsusaponin FK7, chikusetsusaponin FT1, chikusetsusaponin LM1, chikusetsusaponin LM2." }, { "input": "A.", "output": "There is no related enetity." }, { "input": "MEYER collected in Miyazaki prefecture, Japan.", "output": "There is no related enetity." }, { "input": "The structures of new chikusetsusaponins were elucidated on the basis of spectral and physicochemical evidences.", "output": "chikusetsusaponins." }, { "input": "Mutagenic / recombinogenic effects of four lipid peroxidation products in Drosophila.", "output": "There is no related enetity." }, { "input": "The human diet is an important factor in the development of different diseases.", "output": "There is no related enetity." }, { "input": "Lipid peroxidation during frying in edible vegetable liquid oils of food components is a mechanism leading to the formation of free radicals.", "output": "There is no related enetity." }, { "input": "Such radicals induce tissue damage and are implicated in diverse pathological conditions, including aging, atherosclerosis, brain disorders, cancer, lung disorders and various liver disorders.", "output": "There is no related enetity." }, { "input": "In the present study, we decided to investigate the genotoxic effects of four lipid peroxidation products in the in vivo Drosophila wing somatic mutation and recombination test.", "output": "There is no related enetity." }, { "input": "In this test, point mutation, chromosome breakage and mitotic recombination produce single spots; while twin spots are produced only by mitotic recombination.", "output": "There is no related enetity." }, { "input": "Drosophila is a suitable eukaryotic organism for mutagenicity studies and also its metabolism is quite similar to that of mammalians.", "output": "There is no related enetity." }, { "input": "Since conflicting data exist on the possible risk of several lipid peroxidation products for humans, we have selected four of them, namely acrolein, crotonaldehyde, 4 - hydroxy - hexenal ( 4 - HHE ) and 4 - oxo - 2 - nonenal ( 4 - ONE ).", "output": "acrolein, crotonaldehyde, 4 - hydroxy - hexenal, 4 - HHE, 4 - oxo - 2 - nonenal, 4 - ONE." }, { "input": "Especially at the highest concentrations tested all exert both mutagenic and recombinogenic effects in the Drosophila SMART assay, showing a direct dose - effect relationship.", "output": "There is no related enetity." }, { "input": "This is the first study reporting genotoxicity data in Drosophila for these compounds.", "output": "There is no related enetity." }, { "input": "Chemical assessment and antioxidant capacity of pepper ( Capsicum annuum L. ) seeds.", "output": "There is no related enetity." }, { "input": "Capsicum annuum L.", "output": "There is no related enetity." }, { "input": "is reported to be the most widely cultivated species.", "output": "There is no related enetity." }, { "input": "Recently, waste of vegetable processing, like seeds, has been the subject of many studies as an attempt to find new, alternative and cheap resources of bioactive compounds with application in several industries.", "output": "There is no related enetity." }, { "input": "Despite their chemical, biological and ecological importance, C. annuum seeds are still poorly studied.", "output": "There is no related enetity." }, { "input": "To improve the knowledge on the metabolic profile of this matrix, a targeted metabolite analysis was performed in \" sweet Italian \" and \" Reus long pairal \" pepper seeds.", "output": "There is no related enetity." }, { "input": "Sterols, triterpenes, organic acids, fatty acids and volatile compounds were determined by different chromatographic methods.", "output": "Sterols, triterpenes, fatty acids." }, { "input": "The antioxidant activity was assessed against DPPH (. ), superoxide and nitric oxide radicals.", "output": "DPPH ( . ), superoxide, nitric oxide." }, { "input": "A concentration - dependent activity was noticed against all radicals.", "output": "There is no related enetity." }, { "input": "Acetylcholinesterase inhibitory capacity was also evaluated, but no effect was found.", "output": "There is no related enetity." }, { "input": "Data provide evidence of great similarities between \" sweet Italian \" and \" Reus long pairal \" pepper seeds.", "output": "There is no related enetity." }, { "input": "The present study indicates that C. annuum seeds are a potential source of valuable bioactive compounds that could be used in food industry.", "output": "There is no related enetity." }, { "input": "New insight into the ZnO sulfidation reaction: mechanism and kinetics modeling of the ZnS outward growth.", "output": "ZnO, ZnS." }, { "input": "Zinc oxide based materials are commonly used for the final desulfurization of synthesis gas in Fischer - Tropsch based XTL processes.", "output": "Zinc oxide." }, { "input": "Although the ZnO sulfidation reaction has been widely studied, little is known about the transformation at the crystal scale, its detailed mechanism and kinetics.", "output": "ZnO." }, { "input": "A model ZnO material with well - determined characteristics ( particle size and shape ) has been synthesized to perform this study.", "output": "ZnO." }, { "input": "Characterizations of sulfided samples ( using XRD, TEM and electron diffraction ) have shown the formation of oriented polycrystalline ZnS nanoparticles with a predominant hexagonal form ( wurtzite phase ).", "output": "ZnS, wurtzite." }, { "input": "TEM observations also have evidenced an outward development of the ZnS phase, showing zinc and oxygen diffusion from the ZnO - ZnS internal interface to the surface of the ZnS particle.", "output": "ZnS, zinc, oxygen, ZnO, ZnS, ZnS." }, { "input": "The kinetics of ZnO sulfidation by H ( 2 ) S has been investigated using isothermal and isobaric thermogravimetry.", "output": "ZnO, H ( 2 ) S." }, { "input": "Kinetic tests have been performed that show that nucleation of ZnS is instantaneous compared to the growth process.", "output": "ZnS." }, { "input": "A reaction mechanism composed of eight elementary steps has been proposed to account for these results, and various possible rate laws have been determined upon approximation of the rate - determining step.", "output": "There is no related enetity." }, { "input": "Thermogravimetry experiments performed in a wide range of H ( 2 ) S and H ( 2 ) O partial pressures have shown that the ZnO sulfidation reaction rate has a nonlinear variation with H ( 2 ) S partial pressure at the same time no significant influence of water vapor on reaction kinetics has been observed.", "output": "H ( 2 ) S, H ( 2 ) O, ZnO, H ( 2 ) S." }, { "input": "From these observations, a mixed kinetics of external interface reaction with water desorption and oxygen diffusion has been determined to control the reaction kinetics and the proposed mechanism has been validated.", "output": "oxygen." }, { "input": "However, the formation of voids at the ZnO - ZnS internal interface, characterized by TEM and electron tomography, strongly slows down the reaction rate.", "output": "ZnO, ZnS." }, { "input": "Therefore, the impact of the decreasing ZnO - ZnS internal interface on reaction kinetics has been taken into account in the reaction rate expression.", "output": "ZnO, ZnS." }, { "input": "In this way the void formation at the interface has been modeled considering a random nucleation followed by an isotropic growth of cavities.", "output": "There is no related enetity." }, { "input": "Very good agreement has been observed between both experimental and calculated rates after taking into account the decrease in the ZnO - ZnS internal interface.", "output": "ZnO, ZnS." }, { "input": "Possible presence of hydrophilic SO3H nanoclusters on the surface of dry ultrathin Nafion (R) films: a positron annihilation study.", "output": "SO3H, Nafion." }, { "input": "Solutions of Nafion (R) with an ion exchange capacity ( IEC ) of 0. 91 meq g ( - 1 ), which are on the verge of the formation of SO ( 3 ) H nanoclusters, were spin coated on silicon ( Si ), glassy carbon ( GC ) and platinum / silicon ( Pt / Si ) substrates to form films of up to 256 nm thickness.", "output": "Nafion, SO ( 3 ) H, silicon, Si, glassy carbon, platinum, silicon, Pt, Si." }, { "input": "Nanostructure of the films was studied using Doppler broadening of annihilation radiation ( DBAR ), positron annihilation lifetime ( PAL ), X - ray photoelectron spectroscopy ( XPS ), an atomic force microscope ( AFM ) and contact angle measurements.", "output": "There is no related enetity." }, { "input": "Contact angles as low as 10 degrees indicate that the surface of dry ultrathin Nafion (R) films on Si is highly hydrophilic.", "output": "Nafion, Si." }, { "input": "XPS data of 10 nm thick, ultrathin film on Si show that oxygen concentration is enhanced and the SO ( 3 ) H group concentration, in other words, IEC on the surface is much higher than other films.", "output": "Si, oxygen, SO ( 3 ) H." }, { "input": "The S parameter measured by DBAR of an ultrathin Nafion (R) film on Si is much higher than that of the films on the other substrates.", "output": "Nafion, Si." }, { "input": "We consider that a large number of hydrophilic, reversed micelle like SO ( 3 ) H groups are on the surface of the ultrathin Nafion (R) film on Si but not on the surface of other films.", "output": "SO ( 3 ) H, Nafion, Si." }, { "input": "Positrons implanted into the film are trapped by the SO ( 3 ) H clusters, annihilating with the electrons of oxygen and exhibit the high S parameter.", "output": "SO ( 3 ) H, oxygen." }, { "input": "The SO ( 3 ) H concentration on the surface of thin Nafion (R) films on GC and Pt / Si substrates may not be so high as the threshold for the formation of a large number of SO ( 3 ) H clusters.", "output": "SO ( 3 ) H, Nafion, Pt, Si, SO ( 3 ) H." }, { "input": "Positrons implanted into the films annihilate mostly with fluorine atoms, resulting in a low S parameter.", "output": "fluorine." }, { "input": "The film - substrate interaction plays an essential role in nanostructuring of Nafion (R) thin films, which may also be the case for Nafion (R) on the catalysts of polymer electrolyte fuel cells.", "output": "Nafion, Nafion." }, { "input": "Dietary intake of magnesium may modulate depression.", "output": "magnesium." }, { "input": "Depressive symptoms are frequent in students and may lead to countless problems.", "output": "There is no related enetity." }, { "input": "Several hypotheses associate magnesium with depression because of the presence of this mineral in several enzymes, hormones, and neurotransmitters, which may play a key role in the pathological pathways of depression.", "output": "magnesium." }, { "input": "The aim of this study was to assess whether magnesium intake could modulate depressive symptoms.", "output": "magnesium." }, { "input": "A cross - sectional study was conducted on a convenience sample of 402 Iranian postgraduate students studying in Malaysia to assess the relationship between magnesium intake and depressive symptoms.", "output": "magnesium." }, { "input": "The mean age of the participants was 32. 54 +/- 6. 22 years.", "output": "There is no related enetity." }, { "input": "The results of the study demonstrated an inverse relationship between magnesium intake and depressive symptoms, which persisted even after adjustments for sex, age, body mass index, monthly expenses, close friends, living on campus, smoking ( current and former ), education, physical activity, and marital status.", "output": "magnesium." }, { "input": "Acute Macrovascular Dysfunction in Patients With Type 2 Diabetes Induced by Ingestion of Advanced Glycated beta - Lactoglobulins.", "output": "There is no related enetity." }, { "input": "OBJECTIVE Recent evidence indicates that heat - enhanced food advanced glycation end products ( AGEs ) adversely affect vascular function.", "output": "There is no related enetity." }, { "input": "The aim of this study was to examine the acute effects of an oral load of heat - treated, AGE - modified beta - lactoglobulins ( AGE - BLG ) compared with heat - treated, nonglycated BLG ( C - BLG ) on vascular function in patients with type 2 diabetes mellitus ( T2DM ).", "output": "There is no related enetity." }, { "input": "RESEARCH DESIGN AND METHODS In a double - blind, controlled, randomized, crossover study, 19 patients with T2DM received, on two different occasions, beverages containing either AGE - BLG or C - BLG.", "output": "There is no related enetity." }, { "input": "We measured macrovascular [ brachial ultrasound of flow - mediated dilatation ( FMD ) ] and microvascular ( laser - Doppler measurements of reactive hyperemia in the hand ) functions at baseline ( T0 ), 90 ( T90 ), and 180 ( T180 ) min.", "output": "There is no related enetity." }, { "input": "RESULTS Following the AGE - BLG, FMD decreased at T90 by 80 % from baseline and remained decreased by 42 % at T180 ( P < 0. 05 vs. baseline, P < 0. 05 vs. C - BLG at T90 ).", "output": "There is no related enetity." }, { "input": "By comparison, following C - BLG, FMD decreased by 27 % at T90 and 51 % at T180 ( P < 0. 05 vs. baseline at T180 ).", "output": "There is no related enetity." }, { "input": "A significant decrease in nitrite ( T180 ) and nitrate ( T90 and T180 ), as well as a significant increase in N ( epsilon ) - carboxymethyllisine, accompanied intake of AGE - BLG.", "output": "nitrite, nitrate, N ( epsilon ) - carboxymethyllisine." }, { "input": "There was no change in microvascular function caused by either beverage.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS In patients with T2DM, acute oral administration of a single AGE - modified protein class significantly though transiently impaired macrovascular function in concert with decreased nitric oxide bioavailability.", "output": "nitric oxide." }, { "input": "These AGE - related changes were independent of heat treatment.", "output": "There is no related enetity." }, { "input": "Acute - Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4 / F4 Study.", "output": "There is no related enetity." }, { "input": "OBJECTIVE We sought to investigate whether elevated levels of acute - phase serum amyloid A ( A - SAA ) protein precede the onset of type 2 diabetes independently of other risk factors, including parameters of glucose metabolism.", "output": "glucose." }, { "input": "RESEARCH DESIGN AND METHODS Within the population - based Cooperative Health Research in the Region of Augsburg ( KORA ) S4 study, we measured A - SAA concentrations in 836 initially nondiabetic subjects ( 55 - 74 years of age ) without clinically overt inflammation who participated in a 7 - year follow - up examination including an oral glucose tolerance test.", "output": "glucose." }, { "input": "RESULTS A - SAA concentrations were significantly associated with incident type 2 diabetes ( odds ratio [ OR ] for a one - SD increase of A - SAA adjusted for age and sex = 1. 28 [ 95 % CI 1. 08 - 1. 53 ], P = 0. 005 ), particularly in younger subjects ( P value for interaction = 0. 047 ).", "output": "There is no related enetity." }, { "input": "The association attenuated when adjusting for parameters of glucose metabolism ( fasting glucose, fasting insulin, HbA1c, and 2 - h glucose; OR 1. 16 [ 0. 95 - 1. 42 ], P = 0. 15 ).", "output": "glucose, glucose, glucose." }, { "input": "Similar analyses for high - sensitive C - reactive protein ( hs - CRP ) yielded the following ORs: 1. 39 ( 1. 10 - 1. 68, P = 0. 0006 ) and 1. 13 ( 0. 88 - 1. 45, P = 0. 34 ), respectively.", "output": "There is no related enetity." }, { "input": "In contrast, A - SAA concentrations were significantly associated with 2 - h glucose levels at follow - up even after adjustment for parameters of glucose metabolism ( P = 0. 008, n = 803 ).", "output": "glucose, glucose." }, { "input": "CONCLUSIONS Our findings indicate similarly strong prospective associations with type 2 diabetes for A - SAA and hs - CRP and suggest a potential causal link via postchallenge hyperglycemia.", "output": "There is no related enetity." }, { "input": "The influence of sex, ethnicity, and CYP2B6 genotype on bupropion metabolism as an index of hepatic CYP2B6 activity in humans.", "output": "bupropion." }, { "input": "The effects of sex, ethnicity, and genetic polymorphism on hepatic CYP2B6 ( cytochrome P450 2B6 ) expression and activity were previously demonstrated in vitro.", "output": "There is no related enetity." }, { "input": "Race / ethnic differences in CYP2B6 genotype and phenotype were observed only in women.", "output": "There is no related enetity." }, { "input": "To identify important covariates associated with interindividual variation in CYP2B6 activity in vivo, we evaluated these effects in healthy volunteers using bupropion ( Wellbutrin SR GlaxoSmithKline, Research Triangle Park, NC ) as a CYP2B6 probe substrate.", "output": "bupropion, Wellbutrin SR." }, { "input": "A fixed 150 - mg oral sustained - release dose of bupropion was administered to 100 healthy volunteers comprising four sex / ethnicity cohorts ( n = 25 each ): Caucasian men and Caucasian, African American, and Hispanic women.", "output": "bupropion." }, { "input": "Blood samples were obtained at 0 and 6 hours postdose for the measurement of serum bupropion ( BU ) and hydroxybupropion ( HB ) concentrations.", "output": "bupropion, hydroxybupropion." }, { "input": "Whole blood was obtained at baseline for CYP2B6 genotyping.", "output": "There is no related enetity." }, { "input": "To characterize the relationship between CYP2B6 activity and ethnicity, sex, and genotype when accounting for serum BU concentrations ( dose - adjusted log ( 10 ) - transformed ), analysis of covariance model was fitted in which the dependent variable was CYP2B6 activity represented as the log ( 10 ) - transformed, metabolic ratio of HB to BU concentrations.", "output": "There is no related enetity." }, { "input": "Several CYP2B6 polymorphisms were associated with CYP2B6 activity.", "output": "There is no related enetity." }, { "input": "Evidence of dependence of CYP2B6 activity on ethnicity or genotype - by - ethnicity interactions was not detected in women.", "output": "There is no related enetity." }, { "input": "These results suggest that CYP2B6 genotype is the most important patient variable for predicting the level of CYP2B6 activity in women, when measured by the metabolism of bupropion.", "output": "bupropion." }, { "input": "The bupropion metabolic ratio appears to detect known differences in CYP2B6 activity associated with genetic polymorphism, across different ethnic groups.", "output": "bupropion." }, { "input": "Prospective studies will be needed to validate the use of bupropion as a probe substrate for clinical use.", "output": "bupropion." }, { "input": "Snake ( Walterinnesia aegyptia ) venom - loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells.", "output": "silica." }, { "input": "Prostate cancer ( PCa ) is the most commonly diagnosed cancer in men.", "output": "There is no related enetity." }, { "input": "The progression and invasion of PCa are normally mediated by the overexpression of chemokine receptors ( CKRs ) and the interaction between CKRs and their cognate ligands.", "output": "There is no related enetity." }, { "input": "We recently demonstrated that venom extracted from Walterinnesia aegyptia ( WEV ) either alone or in combination with silica nanoparticles ( WEV + NP ) mediated the growth arrest and apoptosis of breast cancer cells.", "output": "silica." }, { "input": "In the present study, we evaluated the impact of WEV alone and WEV + NP on the migration, invasion, proliferation and apoptosis of prostate cancer cells.", "output": "There is no related enetity." }, { "input": "We found that WEV alone and WEV + NP decreased the viability of all cell types tested ( PCa cells isolated from patient samples, PC3 cells and LNCaP cells ) using an MTT assay.", "output": "MTT." }, { "input": "The IC ( 50 ) values were determined to be 10 and 5 mu g / mL for WEV alone and WEV + NP, respectively.", "output": "There is no related enetity." }, { "input": "WEV + NP decreased the surface expression of the CKRs CXCR3, CXCR4, CXCR5 and CXCR6 to a greater extent than WEV alone and subsequently reduced migration and the invasion response of the cells to the cognate ligands of the CKRs ( CXCL10, CXCL12, CXCL13 and CXCL16, respectively ).", "output": "There is no related enetity." }, { "input": "Using a CFSE proliferation assay, we found that WEV + NP strongly inhibited epidermal growth factor - mediated PCa cell proliferation.", "output": "CFSE." }, { "input": "Furthermore, analysis of the cell cycle indicated that WEV + NP strongly altered the cell cycle of PCa cells and enhanced the induction of apoptosis.", "output": "There is no related enetity." }, { "input": "Finally, we demonstrated that WEV + NP robustly decreased the expression of anti - apoptotic effectors, such as B cell Lymphoma - 2 ( Bcl - 2 ), B cell Lymphoma - extra large ( Bcl - ( XL ) ) and myeloid cell leukemia sequence - 1 ( Mcl - 1 ), and increased the expression of pro - apoptotic effectors, such as Bcl - 2 homologous antagonist / killer ( Bak ), Bcl - 2 - associated X protein ( Bax ) and Bcl - 2 - interacting mediator of cell death ( Bim ).", "output": "There is no related enetity." }, { "input": "WEV + NP also altered the membrane potential of mitochondria in the PCa cells.", "output": "There is no related enetity." }, { "input": "Our data reveal the potential of nanoparticle - sustained delivery of snake venom as effective treatments for prostate cancer.", "output": "There is no related enetity." }, { "input": "Poly - Ortho - Functionalizable Tetraarylporphycene Platform - Synthesis of Octacationic Derivatives Towards the Layer - by - Layer Design of Versatile Graphene Oxide Photoelectrodes.", "output": "Poly - Ortho - Functionalizable Tetraarylporphycene, Octacationic, Graphene Oxide." }, { "input": "The most highly charged water - soluble poly - ortho - substituted tetraarylporphycene ( Pc ( 8 + ) ) has been synthetized.", "output": "poly - ortho - substituted tetraarylporphycene, Pc ( 8 + )." }, { "input": "The latter, which interacts in aqueous solutions with graphene oxide ( GO ) forming a photoactive ensemble Pc ( 8 + ) / GO, is immobilized by means of the Layer - by - Layer ( LbL ) technique onto ITO electrodes to afford novel solar energy conversion devices.", "output": "graphene oxide, Pc ( 8 + )." }, { "input": "Perspectives and potential applications of nanomedicine in breast and prostate cancer.", "output": "There is no related enetity." }, { "input": "Nanomedicine is a branch of nanotechnology that includes the development of nanostructures and nanoanalytical systems for various medical applications.", "output": "There is no related enetity." }, { "input": "Among these applications, utilization of nanotechnology in oncology has captivated the attention of many research endeavors in recent years.", "output": "There is no related enetity." }, { "input": "The rapid development of nano - oncology raises new possibilities in cancer diagnosis and treatment.", "output": "There is no related enetity." }, { "input": "It also holds great promise for realization of point - of - care, theranostics, and personalized medicine.", "output": "There is no related enetity." }, { "input": "In this article, we review advances in nano - oncology, with an emphasis on breast and prostate cancer because these organs are amenable to the translation of nanomedicine from small animals to humans.", "output": "There is no related enetity." }, { "input": "As new drugs are developed, the incorporation of nanotechnology approaches into medicinal research becomes critical.", "output": "There is no related enetity." }, { "input": "Diverse aspects of nano - oncology are discussed, including nanocarriers, targeting strategies, nanodevices, as well as nanomedical diagnostics, therapeutics, and safety.", "output": "There is no related enetity." }, { "input": "The review concludes by identifying some limitations and future perspectives of nano - oncology in breast and prostate cancer management.", "output": "There is no related enetity." }, { "input": "Gold nanoparticles produced in situ mediate bioelectricity and hydrogen production in a microbial fuel cell by quantized capacitance charging.", "output": "hydrogen." }, { "input": "Oppan quantized style: By adding a gold precursor at its cathode, a microbial fuel cell ( MFC ) is demonstrated to form gold nanoparticles that can be used to simultaneously produce bioelectricity and hydrogen.", "output": "hydrogen." }, { "input": "By exploiting the quantized capacitance charging effect, the gold nanoparticles mediate the production of hydrogen without requiring an external power supply, while the MFC produces a stable power density.", "output": "hydrogen." }, { "input": "Synthesis of maleimide - functionalyzed HPMA - copolymers and in vitro characterization of the aRAGE - and human immunoglobulin ( huIgG ) - polymer conjugates.", "output": "maleimide, HPMA." }, { "input": "Herein the synthesis of antibody - polymer conjugates, with a quite narrow dispersity based on the polymer HPMA, are reported.", "output": "HPMA." }, { "input": "These conjugates are synthesized by coupling antibodies to maleimide - functionalized poly ( N - ( 2 - hydroxypropyl ) - methacrylamide ) ( poly - HPMA ) copolymers derived through reversible addition - fragmentation chain transfer ( RAFT ) polymerization of pentafluorophenyl methacrylate via the intermediate step of an activated ester polymer.", "output": "maleimide, poly ( N - ( 2 - hydroxypropyl ) - methacrylamide ), poly - HPMA, pentafluorophenyl methacrylate, ester." }, { "input": "We develop a protocol that allows the attachment of two different model antibodies, monoclonal anti - RAGE ( receptor for advanced glycation end - products ) antibody, and polyclonal human immunoglobulin ( huIgG ).", "output": "There is no related enetity." }, { "input": "Modification of the antibody and conjugation is monitored by SDS - PAGE electrophoresis.", "output": "SDS." }, { "input": "Preserved affinity is demonstrated by Western Blott and cell - uptake analysis, for example, to cells of the immune system.", "output": "There is no related enetity." }, { "input": "Differentiation of opioid drug effects by hierarchical multi - site phosphorylation.", "output": "There is no related enetity." }, { "input": "Differences in the ability of opioid drugs to promote regulated endocytosis of mu - opioid receptors are related to their tendency to produce drug tolerance and dependence.", "output": "There is no related enetity." }, { "input": "Here we show that drug - specific differences in receptor internalization are determined by a conserved, 10 - residue sequence in the receptor ' s carboxyl - terminal cytoplasmic tail.", "output": "carboxyl." }, { "input": "Diverse opioids induce receptor phosphorylation at serine ( S ) 375, present in the middle of this sequence, but opioids differ markedly in their ability to drive higher - order phosphorylation on flanking residues [ threonine ( T ) 370, T376, and T379 ].", "output": "serine, threonine." }, { "input": "Multi - phosphorylation is required for the endocytosis - promoting activity of this sequence and occurs both sequentially and hierarchically, with S375 representing the initiating site.", "output": "There is no related enetity." }, { "input": "Higher - order phosphorylation involving T370, T376, and T379 specifically requires GRK2 / 3 isoforms, and the same sequence controls opioid receptor internalization in neurons.", "output": "There is no related enetity." }, { "input": "These results reveal a biochemical mechanism differentiating the endocytic activity of opioid drugs.", "output": "There is no related enetity." }, { "input": "High performance multilayer MoS2 transistors with scandium contacts.", "output": "MoS2, scandium." }, { "input": "While there has been growing interest in two - dimensional ( 2 - D ) crystals other than graphene, evaluating their potential usefulness for electronic applications is still in its infancy due to the lack of a complete picture of their performance potential.", "output": "graphene." }, { "input": "The focus of this article is on contacts.", "output": "There is no related enetity." }, { "input": "We demonstrate that through a proper understanding and design of source / drain contacts and the right choice of number of MoS ( 2 ) layers the excellent intrinsic properties of this 2 - D material can be harvested.", "output": "MoS ( 2 )." }, { "input": "Using scandium contacts on 10 - nm - thick exfoliated MoS ( 2 ) flakes that are covered by a 15 nm Al ( 2 ) O ( 3 ) film, high effective mobilities of 700 cm ( 2 ) / ( V s ) are achieved at room temperature.", "output": "scandium, MoS ( 2 ), Al ( 2 ) O ( 3 )." }, { "input": "This breakthrough is largely attributed to the fact that we succeeded in eliminating contact resistance effects that limited the device performance in the past unrecognized.", "output": "There is no related enetity." }, { "input": "In fact, the apparent linear dependence of current on drain voltage had mislead researchers to believe that a truly Ohmic contact had already been achieved, a misconception that we also elucidate in the present article.", "output": "There is no related enetity." }, { "input": "Porosity of pillared clays studied by hyperpolarized 129Xe NMR spectroscopy and Xe adsorption isotherms.", "output": "129Xe, Xe." }, { "input": "The influence of the layer charge on the microstructure was studied for a series of three hybrid pillared interlayered clays based on the organic dication Me ( 2 ) DABCO ( 2 + ) and charge reduced synthetic fluorohectorites.", "output": "Me ( 2 ) DABCO ( 2 + )." }, { "input": "To get a detailed picture of the local arrangements within the interlayer space, multinuclear solid - state NMR spectroscopy was performed in conjunction with high - resolution ( 129 ) Xe MAS NMR, temperature - dependent wide - line 1D and 2D ( 129 ) Xe NMR, and Ar / Ar ( l ) and Xe / Xe ( l ) physisorption measurements.", "output": "( 129 ) Xe, ( 129 ) Xe, Ar, Ar ( l ), Xe, Xe ( l )." }, { "input": "The resulting layer charge ( x ) for the three samples are 0. 48, 0. 44, and 0. 39 per formula unit ( pfu ).", "output": "There is no related enetity." }, { "input": "The samples exhibit BET equivalent surfaces between 150 and 220 m ( 2 ) / g and pore volumes which increase from 0. 06 to 0. 11 cm ( 3 ) / g while the layer charge reduces.", "output": "There is no related enetity." }, { "input": "1D and 2D ( 1 ) H, ( 13 ) C, ( 19 ) F, and ( 29 ) Si MAS data reveal that the postsynthetic charge reduction induces regions with higher defect concentrations within the silicate layers.", "output": "( 1 ) H, ( 13 ) C, ( 19 ) F, ( 29 ) Si." }, { "input": "Although the pillars tend to avoid these defect - rich regions, a homogeneous and regular spacing of the Me ( 2 ) DABCO ( 2 + ) pillars is established.", "output": "Me ( 2 ) DABCO ( 2 + )." }, { "input": "Both the Ar / Ar ( l ) physisorption and ( 129 ) Xe NMR measurements reveal comparable pore dimensions.", "output": "Ar, Ar ( l ), ( 129 ) Xe." }, { "input": "The trend of the temperature - dependent wide - line ( 129 ) Xe spectra as well as the exchange in the EXSY spectra is typical for a narrow 2D pore system.", "output": "( 129 ) Xe." }, { "input": "( 129 ) Xe high - resolution experiments allow for a detailed description of the microstructure.", "output": "( 129 ) Xe." }, { "input": "For x = 0. 48 a bimodal distribution with pore diameters between 5. 9 and 6. 4 A is observed.", "output": "There is no related enetity." }, { "input": "Reducing the layer charge leads to a more homogeneous pore structure with a mean diameter of 6. 6 A ( x = 0. 39 ).", "output": "There is no related enetity." }, { "input": "The adsorption enthalpies Delta H ( ads ) determined from the temperature - dependent ( 129 ) Xe chemical shift data fit well to the ones derived from the Xe / Xe ( l ) physisorption measurements in the high - pressure limit while the magnitude of Delta H ( ads ) in the low - pressure limit is significantly larger.", "output": "( 129 ) Xe, Xe, Xe ( l )." }, { "input": "Thus, the ( 129 ) Xe data are influenced by adsorbate - adsorbent as well as adsorbate - adsorbate interactions.", "output": "( 129 ) Xe." }, { "input": "Anharmonic motion in experimental charge density investigations.", "output": "There is no related enetity." }, { "input": "In the charge density study of 9 - diphenylthiophosphinoylanthracene the thermal motion of several atoms needed an anharmonic description via Gram - Charlier coefficients even for data collected at 15 K.", "output": "9 - diphenylthiophosphinoylanthracene." }, { "input": "As several data sets at different temperatures were measured, this anharmonic model could be proved to be superior to a disorder model.", "output": "There is no related enetity." }, { "input": "Refinements against theoretical data showed the resemblance of an anharmonic model and a disorder model with two positions very close to each other ( ~ 0. 2 A ), whereas these two models could be clearly distinguished if the second position is 0. 5 A apart.", "output": "There is no related enetity." }, { "input": "The refined multipole parameters were distorted when the anharmonic motion was not properly refined.", "output": "There is no related enetity." }, { "input": "Therefore, this study reveals the importance of detecting and properly handling anharmonic motion.", "output": "There is no related enetity." }, { "input": "Unrefined anharmonic motion leads to typical shashlik - like residual density patterns.", "output": "There is no related enetity." }, { "input": "Therefore, careful analysis of the residual density and the derived probability density function after the refinement of the Gram - Charlier coefficients proved to be the most useful tools to indicate the presence of anharmonic motion.", "output": "There is no related enetity." }, { "input": "Pseudostatic and dynamic nanomechanics of the tunica adventitia in elastic arteries using atomic force microscopy.", "output": "There is no related enetity." }, { "input": "Tunica adventitia, the outer layer of blood vessels, is an important structural feature, predominantly consisting of collagen fibrils.", "output": "There is no related enetity." }, { "input": "This study uses pseudostatic atomic force microscopy ( AFM ) nanoindentation at physiological conditions to show that the distribution of indentation modulus and viscous creep for the tunica adventitia of porcine aorta and pulmonary artery are distinct.", "output": "There is no related enetity." }, { "input": "Dynamic nanoindentation demonstrates that the viscous dissipation of the tunica adventitia of the aorta is greater than the pulmonary artery.", "output": "There is no related enetity." }, { "input": "We suggest that this mechanical property of the aortic adventitia is functionally advantageous due to the higher blood pressure within this vessel during the cardiac cycle.", "output": "There is no related enetity." }, { "input": "The effects on pulsatile deformation and dissipative energy losses are discussed.", "output": "There is no related enetity." }, { "input": "Biomolecular Interactions of small - molecule inhibitors affecting the YopH protein tyrosine phosphatase.", "output": "tyrosine." }, { "input": "We have developed competitive and direct binding methods to examine small - molecule inhibitors of protein tyrosine phosphatase activity.", "output": "tyrosine." }, { "input": "Focusing on the Yersinia pestis outer protein H, a potent bacterial protein tyrosine phosphatase, we describe how an understanding of the kinetic interactions involving Yersinia pestis outer protein H, peptide substrates, and small - molecule inhibitors of protein tyrosine phosphatase activity can be beneficial for inhibitor screening, and we further translate these results into a microarray assay for high - throughput screening.", "output": "tyrosine, tyrosine." }, { "input": "Information hierarchies optimize patient - centered solutions.", "output": "There is no related enetity." }, { "input": "Enabling science and information technologies has catalyzed a surge of biological, clinical, demographic, health services, and comparative - effectiveness data.", "output": "There is no related enetity." }, { "input": "While accelerating the deconvolution of complex pathophysiological, medical, social, and environmental networks and systems, these platforms have produced informational quanta devoid of contextualization.", "output": "There is no related enetity." }, { "input": "Therapeutic innovation is thus now challenged with moving beyond knowledge generation and curation to integrated solution - seeking paradigms that organize functionally related information, producing system - level insights into health and disease for optimized patient - centered outcomes.", "output": "There is no related enetity." }, { "input": "This annual issue on therapeutics innovations highlights emerging considerations for the generation and hierarchical organization of scientific and clinical information and its translation to advancing next - generation disease management.", "output": "There is no related enetity." }, { "input": "Sponge - like Ni ( OH ) 2 - NiF2 composite film with excellent electrochemical performance.", "output": "Ni ( OH ) 2, NiF2." }, { "input": "Sponge - like porous Ni ( OH ) ( 2 ) - NiF ( 2 ) composite ( PNC ) film was successfully synthesized by the anodization of nickel in a NH ( 4 ) F and H ( 3 ) PO ( 4 ) containing electrolyte.", "output": "Ni ( OH ) ( 2 ), NiF ( 2 ), nickel, NH ( 4 ) F, H ( 3 ) PO ( 4 )." }, { "input": "Thanks to the good conductivity and the highly porous architecture, PNC exhibited not only a high specific capacitance, but also a superior rate capability and a good cyclability ( 2090 F g ( - 1 ) at 10 mV s ( - 1 ), capacitance > 1200 F g ( - 1 ) at 100 A g ( - 1 ) after 2000 cycles ).", "output": "There is no related enetity." }, { "input": "Anodization of nickel is proven to be fast and facile and can be easily scaled up.", "output": "nickel." }, { "input": "The method described here is promising for the fabrication of supercapacitor electrodes with excellent performance.", "output": "There is no related enetity." }, { "input": "Gas - phase dissociative electron attachment to flavonoids and possible similarities to their metabolic pathways.", "output": "flavonoids." }, { "input": "The gas - phase empty - level structures and formation of anion states via resonance attachment of low - energy electrons to the flavonoids naringenin ( III ), quercetin ( IV ) and myricetin ( V ) and the smaller reference molecules chromone ( I ) and flavone ( II ) are investigated experimentally for the first time.", "output": "flavonoids, naringenin, quercetin, myricetin, chromone, flavone." }, { "input": "Dissociative electron attachment spectroscopy ( DEAS ) is used to measure the fragment anion currents generated through dissociative decay channels of the molecular anions of compounds I - V, detected with a mass filter as a function of the incident electron energy in the 0 - 14 eV energy range.", "output": "There is no related enetity." }, { "input": "Due to the insufficient volatility of flavonoids III - V, the energies of vertical electron attachment associated with temporary occupation of the lower - lying virtual orbitals are measured with electron transmission spectroscopy ( ETS ) only in the smaller reference molecules I and II.", "output": "flavonoids." }, { "input": "The experimental findings are interpreted with the support of appropriate density functional theory calculations with the B3LYP functional.", "output": "There is no related enetity." }, { "input": "The experimental vertical electron attachment energies measured in the ET spectra of I and II are compared with the orbital energies of the neutral molecules scaled using an empirically calibrated linear equation.", "output": "There is no related enetity." }, { "input": "The vertical and adiabatic electron affinities are evaluated at the B3LYP / 6 - 31 + G ( d ) level as the anion / neutral total energy difference.", "output": "There is no related enetity." }, { "input": "The latter theoretical method is also used for evaluation of the most stable conformers of the neutral molecules, O - H bond dissociation energies and thermodynamic energy thresholds for production of the anion fragments observed in the DEA spectra.", "output": "O - H." }, { "input": "A possible role played by loss of an H ( 2 ) molecule from the parent molecular anion in vivo in the mitochondrial respiratory chain is briefly discussed.", "output": "H ( 2 )." }, { "input": "Generic methods for micrometer - and nanometer - scale surface derivatization based on photochemical coupling of primary amines to monolayers of aryl azides on gold and aluminum oxide surfaces.", "output": "primary amines, aryl azides, aluminum oxide." }, { "input": "A series of aryl azide terminated thiols and phosphonic acids has been synthesized, and used to prepare self - assembled monolayers on ( respectively ) gold and aluminum oxide surfaces.", "output": "aryl azide, thiols, phosphonic acids, aluminum oxide." }, { "input": "The rates of photoactivation were determined using contact angle measurement and X - ray photoelectron spectroscopy ( XPS ).", "output": "There is no related enetity." }, { "input": "The behavior of a diazirine functionalized aryl thiol was also studied.", "output": "diazirine, aryl thiol." }, { "input": "The rates of activation were found to be similar for all five adsorbates.", "output": "There is no related enetity." }, { "input": "However, the extent of photochemical coupling of a primary amine was significantly greater for the aryl azides than for the diazirine.", "output": "primary amine, aryl azides, diazirine." }, { "input": "A range of primary amines was successfully coupled to all of the azides with high yield.", "output": "primary amines, azides." }, { "input": "Little difference in reactivity was observed following perfluorination of the aromatic ring.", "output": "There is no related enetity." }, { "input": "Micrometer - scale patterns were fabricated by carrying out exposures of the aryl azide terminated SAMs through a mask submerged under a film of primary amine.", "output": "aryl azide, primary amine." }, { "input": "Contrasting amines could be introduced to unreacted regions in a subsequent maskless step.", "output": "amines." }, { "input": "A scanning near - field optical microscope was used to fabricate nanopatterns.", "output": "There is no related enetity." }, { "input": "Exposure of the azides to irradiation at 325 nm in air enabled selective deactivation of azides.", "output": "azides, azides." }, { "input": "The surrounding surface was functionalized with a primary amine in a maskless process; when a protein - resistant oligo ( ethylene glycol ) functionalized amine was used it was possible to produce protein nanopatterns, by adsorbing protein to features defined using near - field exposure.", "output": "primary amine, oligo ( ethylene glycol ), amine." }, { "input": "Medicinal chemistry meets proteomics: fractionation of the human plasma proteome.", "output": "There is no related enetity." }, { "input": "Human plasma and its fractions / derivatives are frequently used materials in biomedicine as it contains thousands and thousands of proteins representing the majority of human proteome.", "output": "There is no related enetity." }, { "input": "Several important methods were developed in the past for the fractionation of this important biological fluid and its use for medicinal purposes.", "output": "There is no related enetity." }, { "input": "One of the greatest challenges is the very large dynamic range of plasma proteins ranging up to 10 - 12 orders of magnitude.", "output": "There is no related enetity." }, { "input": "Early attempts were mainly based on methods such as salting out or cold ethanol precipitation, as well as chromatography utilizing affinity, size exclusion, ion exchange and hydrophobic interaction techniques.", "output": "ethanol." }, { "input": "More recently, fractionation applications started with the depletion of the high abundant plasma components, such as serum albumin and immunoglobulins, before isolating lower abundant proteins of interest.", "output": "There is no related enetity." }, { "input": "Plasma volumes were utilized from the milliliter scale for diagnostic applications to hundreds of liters for industrial scale plasma fractionation ( e. g., medicinal product manufacturing ).", "output": "There is no related enetity." }, { "input": "In this paper we review this important part of medicinal chemistry, highlighting the traditional methods along with some of their variations as well as the most significant recent achievements of the field.", "output": "There is no related enetity." }, { "input": "Proton ion - microbeam elemental analysis for inhaled particle - induced pulmonary diseases: application for diagnosis and assessment of progression.", "output": "There is no related enetity." }, { "input": "Elemental analysis can be applied in the medical field to investigate the causes of disease.", "output": "There is no related enetity." }, { "input": "In patients with some pulmonary diseases, elements can be found in the exogenous dust deposited in the lungs and are also accumulated through the loss of cell homeostasis.", "output": "There is no related enetity." }, { "input": "Diseases induced by inhalation of dust typically affect the lungs.", "output": "There is no related enetity." }, { "input": "Although there are many pulmonary diseases induced by dust inhalation, it is often difficult to clarify the exact cause.", "output": "There is no related enetity." }, { "input": "In - air microparticle induced X - ray emission ( in - air micro - PIXE ) analysis is a method of elemental analysis that employs a proton ion - beam to directly measure the content of elements and their distribution in frozen sections or paraffin sections of tissue.", "output": "There is no related enetity." }, { "input": "We constantly inhale particles while breathing, but most of us do not develop pulmonary disease.", "output": "There is no related enetity." }, { "input": "Because in - air micro - PIXE analysis can determine the two - dimensional localization and content of particles in tissue, we can clarify the relationship between inhaled particles and diseases based on such analysis and the immunohistochemical expression of disease - related proteins.", "output": "There is no related enetity." }, { "input": "Elemental analysis methods like in - air micro - PIXE analysis may be useful for making precise diagnosis amd assesing disease progression to overcome threat such as occupational or environmental exposure.", "output": "There is no related enetity." }, { "input": "Catalase - like and peroxidase - like catalytic activities of silicon nanowire arrays.", "output": "silicon." }, { "input": "Silicon nanowire arrays ( SiNWAs ) were found to have catalytic activities similar to those of biological enzymes catalase and peroxidase.", "output": "Silicon." }, { "input": "Thus not only can these materials catalyze the decomposition reaction of H ( 2 ) O ( 2 ) into water and oxygen, but they can also catalyze the oxidation of o - phenylenediamine ( OPD ), a common substrate for peroxidases, by H ( 2 ) O ( 2 ).", "output": "H ( 2 ) O ( 2 ), oxygen, o - phenylenediamine, OPD, H ( 2 ) O ( 2 )." }, { "input": "The presence of Si - H bonds and the morphology of the SiNWAs are found to be crucial to the occurrence of such catalytic activity.", "output": "Si, H." }, { "input": "When the SiNWAs are reacted with H ( 2 ) O ( 2 ), the data from Raman spectroscopy suggests the formation of ( Si - H ) ( 2 )... ( O species ) ( ( Si - H ) ( 2 )... Os ), which is presumably responsible for the catalytic activity.", "output": "H ( 2 ) O ( 2 ), ( Si - H ) ( 2 ), O, ( Si - H ) ( 2 )." }, { "input": "These findings suggest the potential use of SiNWAs as enzyme mimics in medicine, biotechnology, and environmental chemistry.", "output": "There is no related enetity." }, { "input": "Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties.", "output": "There is no related enetity." }, { "input": "A series of novel glycopyranosyl azides were synthesised wherein the carbohydrate moiety was peracylated with four acetyl, propionyl, butanoyl, pentanoyl ( valeryl ) or 3 - methylbutanoyl ( isovaleryl ) ester linked groups.", "output": "glycopyranosyl azides, carbohydrate, acetyl, propionyl, butanoyl, pentanoyl, valeryl, 3 - methylbutanoyl, isovaleryl, ester." }, { "input": "A panel of glycoconjugates was synthesised from these glycopyranosyl azides using copper - catalysed azide - alkyne cycloaddition.", "output": "glycopyranosyl azides, copper, azide, alkyne." }, { "input": "The in vitro metabolic stability, plasma stability and plasma protein binding was then measured to establish the impact of the different acyl group when presented on a common scaffold.", "output": "acyl." }, { "input": "The acetyl, propionyl and butanoyl esters exhibited metabolism consistent with esterase processing, and various mono -, di - and tri - acylated hydrolysis products as well as the fully hydrolysed compound were detected.", "output": "acetyl , propionyl and butanoyl esters, mono - , di - and tri - acylated." }, { "input": "In contrast, the pentanoyl and 3 - methylbutanoyl esters were stable.", "output": "pentanoyl and 3 - methylbutanoyl esters." }, { "input": "Synthesis of perylene bisimide - centered glycodendrimer and its interactions with concanavalin A.", "output": "perylene bisimide." }, { "input": "A novel glycodendrimer based on 18 peripheral alpha - D - mannoses functionalized perylene bisimide derivative PBI - 18 - Man was synthesized and its selectively binding interactions for Con A were investigated by CD spectra and turbidity assay, which exhibited strong binding affinity for Con A with the binding constant of 1. 3 x 10 ( 8 ) M ( - 1 ) ( 7. 2 x 10 ( 6 ) M ( - 1 ) for monomeric mannose, valency corrected ), 3 orders of magnitude higher affinity than the monovalent mannose ligand.", "output": "alpha - D - mannoses, perylene, PBI - 18 - Man, mannose, mannose." }, { "input": "Furthermore, the inhibitory activity for Con A was studied by ELLA experiment, showed 2 times inhibitor activity than the reference compound ( alpha - MMP ).", "output": "There is no related enetity." }, { "input": "Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF.", "output": "There is no related enetity." }, { "input": "In the past decade, several kinase inhibitors have been approved based on their clinical benefit for cancer patients.", "output": "There is no related enetity." }, { "input": "Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms.", "output": "There is no related enetity." }, { "input": "This review will focus on the cases of acquired resistance to EGFR and ALK inhibitors for non - small cell lung cancer patients and BRAF inhibitors for melanoma patients.", "output": "There is no related enetity." }, { "input": "I will overview the main causes of acquired resistance, and explore the chemical scaffolds as well as combination of drugs, used to tackle these major causes of resistance.", "output": "There is no related enetity." }, { "input": "Exonuclease 1 preferentially repairs mismatches generated by DNA polymerase alpha.", "output": "There is no related enetity." }, { "input": "The Saccharomyces cerevisiae EXO1 gene encodes a 5 ' exonuclease that participates in mismatch repair ( MMR ) of DNA replication errors.", "output": "There is no related enetity." }, { "input": "Deleting EXO1 was previously shown to increase mutation rates to a greater extent when combined with a mutator variant ( pol3 - L612M ) of the lagging strand replicase, DNA polymerase delta ( Pol delta ), than when combined with a mutator variant ( pol2 - M644G ) of the leading strand replicase, DNA polymerase epsilon ( Pol epsilon ).", "output": "There is no related enetity." }, { "input": "Here we confirm that result, and extend the approach to examine the effect of deleting EXO1 in a mutator variant ( pol1 - L868M ) of Pol alpha, the proofreading - deficient and least accurate of the three nuclear replicases that is responsible for initiating Okazaki fragment synthesis.", "output": "There is no related enetity." }, { "input": "We find that deleting EXO1 increases the mutation rate in the Pol alpha mutator strain to a significantly greater extent than in the Pol delta or Pol epsilon mutator strains, thereby preferentially reducing the efficiency of MMR of replication errors generated by Pol alpha.", "output": "There is no related enetity." }, { "input": "Because these mismatches are closer to the 5 ' ends of Okazaki fragments than are mismatches made by Pol delta or Pol epsilon, the results not only support the previous suggestion that Exo1 preferentially excises lagging strand replication errors during mismatch repair, they further imply that the 5 ' ends serve as entry points for 5 ' excision of replication errors made by Pol alpha, and possibly as strand discrimination signals for MMR.", "output": "There is no related enetity." }, { "input": "Nonetheless, mutation rates in the Pol alpha mutator strain are 5 - to 25 - fold lower in an exo1 Delta strain as compared to an msh2 Delta strain completely lacking MMR, indicating that in the absence of Exo1, most replication errors made by Pol alpha can still be removed in an Msh2 - dependent manner by other nucleases and / or by strand displacement.", "output": "There is no related enetity." }, { "input": "Ribonucleotide incorporation, proofreading and bypass by human DNA polymerase delta.", "output": "Ribonucleotide." }, { "input": "In both budding and fission yeast, a large number of ribonucleotides are incorporated into DNA during replication by the major replicative polymerases ( Pols alpha, delta and epsilon ).", "output": "ribonucleotides." }, { "input": "They are subsequently removed by RNase H2 - dependent repair, which if defective leads to replication stress and genome instability.", "output": "There is no related enetity." }, { "input": "To extend these studies to humans, where an RNase H2 defect results in an autoimmune disease, here we compare the ability of human and yeast Pol delta to incorporate, proofread, and bypass ribonucleotides during DNA synthesis.", "output": "ribonucleotides." }, { "input": "In reactions containing nucleotide concentrations estimated to be present in mammalian cells, human Pol delta stably incorporates one rNTP for approximately 2000 dNTPs, a ratio similar to that for yeast Pol delta.", "output": "nucleotide, rNTP, dNTPs." }, { "input": "This result predicts that human Pol delta may introduce more than a million ribonucleotides into the nuclear genome per replication cycle, an amount recently reported to be present in the genome of RNase H2 - defective mouse cells.", "output": "ribonucleotides." }, { "input": "Consistent with such abundant stable incorporation, we show that the 3 ' - exonuclease activity of yeast and human Pol delta largely fails to edit ribonucleotides during polymerization.", "output": "ribonucleotides." }, { "input": "We also show that, like yeast Pol delta, human Pol delta pauses as it bypasses ribonucleotides in DNA templates, with four consecutive ribonucleotides in a DNA template being more problematic than single ribonucleotides.", "output": "ribonucleotides, ribonucleotides, ribonucleotides." }, { "input": "In conjunction with recent studies in yeast and mice, this ribonucleotide incorporation may be relevant to impaired development and disease when RNase H2 is defective in mammals.", "output": "ribonucleotide." }, { "input": "As one tool to investigate ribonucleotide incorporation by Pol delta in human cells, we show that human Pol delta containing a Leu606Met substitution in the polymerase active site incorporates 7 - fold more ribonucleotides into DNA than does wild type Pol delta.", "output": "ribonucleotide, ribonucleotides." }, { "input": "UPLC - Q - TOF / HSMS / MS ( E ) - based metabonomics for adenine - induced changes in metabolic profiles of rat faeces and intervention effects of ergosta - 4, 6, 8 ( 14 ), 22 - tetraen - 3 - one.", "output": "adenine, ergosta - 4 , 6 , 8 ( 14 ) , 22 - tetraen - 3 - one." }, { "input": "Ergosta - 4, 6, 8 ( 14 ), 22 - tetraen - 3 - one ( ergone ), isolated from the medicinal fungus Polyporus umbellatus, has been proven to prevent the progression of renal injury and the subsequent renal fibrosis.", "output": "Ergosta - 4 , 6 , 8 ( 14 ) , 22 - tetraen - 3 - one, ergone." }, { "input": "Ultra performance liquid chromatography coupled with quadrupole time - of - flight high - sensitivity mass spectrometry and a novel mass spectrometry ( Elevated Energy ) ( MS ( E ) ) data collection technique was employed to investigate metabonomic characters of chronic renal failure ( CRF ) induced adenine and the protective effects of ergosta - 4, 6, 8 ( 14 ), 22 - tetraen - 3 - one ( ergone ).", "output": "adenine, ergosta - 4 , 6 , 8 ( 14 ) , 22 - tetraen - 3 - one, ergone." }, { "input": "Coupled with blood biochemistry and kidney histopathology results, the significant difference in metabolic profiling between adenine - induced CRF group and ergone - treated CRF group by using pattern recognition analysis indicated that changes in global faecal metabolites were occurred.", "output": "adenine, ergone." }, { "input": "Seven endogenous metabolites were identified by using metabonomic method combined with multivariate data analysis, the accurate mass, isotopic pattern, MS ( E ) fragments information and MassLynx i - FIT algorithm.", "output": "There is no related enetity." }, { "input": "These biochemical changes in faecal metabolites are related to the perturbations of bile acid metabolism and phospholipid metabolism, which may be helpful to further understand the CRF and therapeutic mechanisms of ergone.", "output": "bile acid, ergone." }, { "input": "This research proved that MS ( E ) can simultaneous acquire precursor ion information and fragment ion data at high and low collision energy in one analytical run, which facilitated the fast structural characterization of metabolites.", "output": "There is no related enetity." }, { "input": "Integration - dependent bacteriophage immunity provides insights into the evolution of genetic switches.", "output": "There is no related enetity." }, { "input": "Genetic switches are critical components of developmental circuits.", "output": "There is no related enetity." }, { "input": "Because temperate bacteriophages are vastly abundant and greatly diverse, they are rich resources for understanding the mechanisms and evolution of switches and the molecular control of genetic circuitry.", "output": "There is no related enetity." }, { "input": "Here, we describe a new class of small, compact, and simple switches that use site - specific recombination as the key decision point.", "output": "There is no related enetity." }, { "input": "The phage attachment site attP is located within the phage repressor gene such that chromosomal integration results in removal of a C - terminal tag that destabilizes the virally encoded form of the repressor.", "output": "C." }, { "input": "Integration thus not only confers prophage stability but also is a requirement for lysogenic establishment.", "output": "There is no related enetity." }, { "input": "The variety of these self - contained integration - dependent immunity systems in different genomic contexts suggests that these represent ancestral states in switch evolution from which more - complex switches have evolved.", "output": "There is no related enetity." }, { "input": "They also provide a powerful toolkit for building synthetic biological circuits.", "output": "There is no related enetity." }, { "input": "The novel delta opioid receptor agonist KNT - 127 produces distinct anxiolytic - like effects in rats without producing the adverse effects associated with benzodiazepines.", "output": "KNT - 127, benzodiazepines." }, { "input": "We previously reported that a delta opioid receptor agonist SNC80 produced potent anxiolytic - like effects in rodents.", "output": "SNC80." }, { "input": "Recently, we succeeded in synthesizing a novel delta opioid receptor agonist KNT - 127.", "output": "KNT - 127." }, { "input": "In this study, we investigated the anxiolytic - like effects of KNT - 127 using three different rat models of innate anxiety.", "output": "KNT - 127." }, { "input": "In an elevated plus - maze test, KNT - 127 ( 0. 3, 1, and 3. 0 mg / kg, s. c. ) significantly and dose - dependently increased the time rats spent in the open arms 30 min after administration.", "output": "KNT - 127." }, { "input": "The magnitude of the KNT - 127 ( 3. 0 mg / kg, s. c. ) - induced anxiolytic - like effects was similar to that produced by diazepam ( 1. 0 mg / kg, s. c. ), a benzodiazepine anxiolytic.", "output": "KNT - 127, diazepam, benzodiazepine." }, { "input": "The anxiolytic - like effects of KNT - 127 ( 3. 0 mg / kg, s. c. ) were abolished by pretreatment with naltrindole ( 0. 1 mg / kg, s. c. ), a selective delta opioid receptor antagonist, suggesting that KNT - 127 - induced anxiolytic - like effects are mediated by delta opioid receptors.", "output": "KNT - 127, naltrindole, KNT - 127." }, { "input": "These findings were supported by results obtained from light / dark and open - field tests.", "output": "There is no related enetity." }, { "input": "Interestingly, in contrast to diazepam ( 1. 0 mg / kg, s. c. ), KNT - 127 ( 3. 0 mg / kg, s. c. ) caused no significant performance changes in the Y - maze test, the ethanol - induced sleeping test, and footprint test.", "output": "diazepam, KNT - 127, ethanol." }, { "input": "This is the first study to demonstrate that the novel delta opioid receptor agonist KNT - 127 produces distinct anxiolytic - like effects in rats, without producing the adverse effects associated with benzodiazepines.", "output": "KNT - 127, benzodiazepines." }, { "input": "Effect of monospecific antibodies against baltergin in myotoxicity induced by Bothrops alternatus venom from northeast of Argentina.", "output": "There is no related enetity." }, { "input": "Role of metalloproteinases in muscle damage.", "output": "There is no related enetity." }, { "input": "Myotoxicity, one of the most relevant local manifestations in envenomation by Bothrops genus, may result from a direct action of myotoxins or be due to an indirect vascular degeneration and ischemia.", "output": "There is no related enetity." }, { "input": "Baltergin, a snake venom metalloproteinase ( SVMP ), isolated from Bothrops alternatus venom has been used to obtain monospecific IgG, in order to determine the relative role of toxin in myotoxicity induced by whole venom.", "output": "There is no related enetity." }, { "input": "Bothrops diporus venom, another medical relevant genus of the northeastern region of Argentina, was also studied.", "output": "There is no related enetity." }, { "input": "Anti - baltergin IgG was able to neutralize completely the hemorrhagic activity of B. alternatus venom at an antibodies: venom ratio of 30: 1 ( w: w ).", "output": "There is no related enetity." }, { "input": "However, mice injected with B. diporus venom showed a small spot remaining even at the highest ratio of IgG: venom assayed ( 50: 1; w: w ).", "output": "There is no related enetity." }, { "input": "Specific antibodies were efficient to neutralize the myotoxicity of B. alternatus venom at ratio 30: 1 ( w: w ) but did not neutralize the same effects in B. diporus venom.", "output": "There is no related enetity." }, { "input": "Anti - baltergin polyclonal antibodies were useful tools for revealing the central role of SVMPs in the development of myotoxicity of B. alternatus venom, as well as, helping to suggest indirectly presence of potent myotoxic phospholipases A2 ( PLA2s ) in B. diporus venom.", "output": "There is no related enetity." }, { "input": "Phthalate and di - ( 2 - ethylhexyl ) adipate ( DEHA ) intake by German infants based on the results of a duplicate diet study and biomonitoring data ( INES 2 ).", "output": "Phthalate, di - ( 2 - ethylhexyl ) adipate, DEHA." }, { "input": "Phthalates as well as di - ( 2 - ethylhexyl ) adipate ( DEHA ) are used as plasticizers in diverse applications and are of toxicological concern.", "output": "Phthalates, di - ( 2 - ethylhexyl ) adipate, DEHA." }, { "input": "The study was conducted with a study population of 25 German subjects aged between 15 and 21 months.", "output": "There is no related enetity." }, { "input": "Overall, 16 phthalates and DEHA were measured by gas chromatography - mass spectrometry in a total of 171 duplicate diet samples collected over 7 consecutive days, and 20 phthalate metabolites were analyzed in the urine samples collected over 7 consecutive days using a liquid chromatography - tandem mass spectrometry method.", "output": "phthalates, DEHA, phthalate." }, { "input": "The median \" high \" daily dietary intake based on 95th percentiles was 4. 66 mu g / kg b. w. for di - 2 - ethylhexyl phthalate ( DEHP ), 1. 03 mu g / kg b. w. for di - isobutyl phthalate ( DiBP ), and 0. 70 mu g / kg b. w. for di - n - butyl phthalate ( DnBP ), and 1. 0 mu g / kg b. w. for DEHA.", "output": "di - 2 - ethylhexyl phthalate, DEHP, di - isobutyl phthalate, DiBP, di - n - butyl phthalate, DnBP, DEHA." }, { "input": "The \" high \" daily total intake from biomonitoring data was 4. 9 mu g / kg b. w. for DEHP, 2. 2 mu g / kg b. w. for DnBP, 3. 9 mu g / kg b. w. for DiBP, and 2. 6 mu g / kg b. w. for di - isononyl phthalate.", "output": "DEHP, DnBP, DiBP, di - isononyl phthalate." }, { "input": "The comparison of the two intake estimates indicates that the dominant intake source of DEHP was food ingestion, whereas other sources considerably contributed to the total intake of other phthalates.", "output": "DEHP, phthalates." }, { "input": "Using our \" high \" intake scenario, none of the analyzed phthalates reached the recommended tolerable daily intake levels.", "output": "phthalates." }, { "input": "The protective role of curcumin on perfluorooctane sulfonate - induced genotoxicity: single cell gel electrophoresis and micronucleus test.", "output": "curcumin, perfluorooctane sulfonate." }, { "input": "Perfluorooctane sulfonate ( PFOS ) is a man - made fluorosurfactant and global pollutant.", "output": "Perfluorooctane sulfonate, PFOS." }, { "input": "PFOS a persistent and bioaccumulative compound, is widely distributed in humans and wildlife.", "output": "PFOS." }, { "input": "Therefore, it was added to Annex B of the Stockholm Convention on Persistent Organic Pollutants in May 2009.", "output": "There is no related enetity." }, { "input": "Curcumin is a natural polyphenolic compound abundant in the rhizome of the perennial herb turmeric.", "output": "Curcumin, polyphenolic." }, { "input": "It is commonly used as a dietary spice and coloring agent in cooking and anecdotally as an herb in traditional Asian medicine.", "output": "There is no related enetity." }, { "input": "In this study, male rats were treated with three different PFOS doses ( 0. 6, 1. 25 and 2. 5 mg / kg ) and one dose of curcumin, from Curcuma longa ( 80 mg / kg ) and combined three doses of PFOS with 80 mg / kg dose of curcumin by gavage for 30 days at 48 h intervals.", "output": "PFOS, curcumin." }, { "input": "Here, we evaluated the DNA damage via single cell gel electrophoresis or comet assay and micronucleus test in bone marrow in vivo.", "output": "There is no related enetity." }, { "input": "PFOS induced micronucleus frequency and decreased the ratio of polychromatic erythrocyte to normochromatic erythrocyte in bone marrow.", "output": "PFOS." }, { "input": "Using the alkaline comet assay, we showed that all doses of the PFOS strongly induced DNA damage in rat bone marrow and curcumin prevented the formation of DNA damage induced by PFOS.", "output": "PFOS, curcumin, PFOS." }, { "input": "Lead - induced neurodegenerative events and abnormal behaviors occur via ORXRergic / GABA ( A ) Rergic mechanisms in a marine teleost.", "output": "GABA." }, { "input": "The hindering effects of metals and in particular lead ( Pb ) are representing a growing threat to aquatic organisms such as fish.", "output": "Pb." }, { "input": "This observation derives from toxic concentrations of Pb accounting for altered neurophysiological activities of some interesting teleost models like Thalassoma pavo, a fish species highly known for its host - cleaning symbiosis.", "output": "Pb." }, { "input": "In this study, the nominal PbNO ( 3 ) concentration of 1. 6 mg / L was capable of reducing feeding and resting bouts as early as 24 h of exposure while hyperactive swimming episodes were also detected.", "output": "PbNO ( 3 )." }, { "input": "Such abnormal behaviors were tightly correlated to up - regulated orexin receptor ( ORXR ) mRNA expression levels in some brain areas such as the lateral thalamic nucleus ( + 213 % ) and the optic tectum ( + 90 % ) with respect to controls.", "output": "There is no related enetity." }, { "input": "Interestingly, these transcriptional effects seemed to be attenuated when Pb - exposed fish received either 100 ng / g of ORX - A ( - 70 % ) or 0. 1 mu g / g of gamma - aminobutyric acid ( A ) receptor ( GABA ( A ) R ) agonist muscimol ( MUS; - 97 % ) compared to fish exposed to Pb alone.", "output": "Pb, gamma - aminobutyric acid, GABA, muscimol, MUS, Pb." }, { "input": "Moreover, a net neurodegenerative process of the different brain areas was reported after Pb exposure as displayed by their marked amino cupric silver stained cells while these cells were devoid of any staining reaction after treatment with MUS only.", "output": "Pb, amino cupric silver, MUS." }, { "input": "Conversely, addition of the GABA ( A ) R antagonist bicuculline ( BIC; 1 mu g / g ) moderately ( p < 0. 05 ) enhanced Pb - dependent behavioral and neurodegenerative actions.", "output": "GABA, bicuculline, BIC, Pb." }, { "input": "Overall, these first indications strongly point to altered ORXR / GABA ( A ) R interactions during neurotoxic events of a metal that by evoking harmful neurobiological dysfunctions may endanger the survival of commercially valuable fish with eventual repercussions on human health.", "output": "GABA." }, { "input": "A p21 - activated kinase ( PAK1 ) signaling cascade coordinately regulates F - actin remodeling and insulin granule exocytosis in pancreatic beta cells.", "output": "There is no related enetity." }, { "input": "Human islet studies implicate an important signaling role for the Cdc42 effector protein p21 - activated kinase ( PAK1 ) in the sustained / second - phase of insulin secretion.", "output": "There is no related enetity." }, { "input": "Because human islets from type 2 diabetic donors lack ~ 80 % of normal PAK1 protein levels, the mechanistic requirement for PAK1 signaling in islet function was interrogated.", "output": "There is no related enetity." }, { "input": "Similar to MIN6 beta cells, human islets elicited glucose - stimulated PAK1 activation that was sensitive to the PAK1 inhibitor, IPA3.", "output": "glucose, IPA3." }, { "input": "Given that sustained insulin secretion has been correlated with glucose - induced filamentous actin ( F - actin ) remodeling, we tested the hypothesis that a Cdc42 - activated PAK1 signaling cascade is required to elicit F - actin remodeling to mobilize granules to the cell surface.", "output": "glucose." }, { "input": "Live - cell imaging captured the glucose - induced cortical F - actin remodeling in MIN6 beta cells; IPA3 - mediated inhibition of PAK1 abolished this remodeling.", "output": "glucose, IPA3." }, { "input": "IPA3 also ablated glucose - stimulated insulin granule accumulation at the plasma membrane, consistent with its role in sustained / second - phase insulin release.", "output": "IPA3, glucose." }, { "input": "Both IPA3 and a selective inhibitor of the Cdc42 GTPase, ML - 141, blunted the glucose - stimulated activation of Raf - 1, suggesting Raf - 1 to be downstream of Cdc42 --> PAK1.", "output": "IPA3, ML - 141, glucose." }, { "input": "IPA3 also inhibited MEK1 / 2 activation, implicating the MEK1 / 2 --> ERK1 / 2 cascade to occur downstream of PAK1.", "output": "IPA3." }, { "input": "Importantly, PD0325901, a new selective inhibitor of MEK1 / 2 --> ERK1 / 2 activation, impaired F - actin remodeling and the sustained / amplification pathway of insulin release.", "output": "PD0325901." }, { "input": "Taken together, these data suggest that glucose - mediated activation of Cdc42 leads to activation of PAK1 and prompts activation of its downstream targets Raf - 1, MEK1 / 2 and ERK1 / 2 to elicit F - actin remodeling and recruitment of insulin granules to the plasma membrane to support the sustained phase of insulin release.", "output": "glucose." }, { "input": "Beta - glucogallin reduces the expression of lipopolysaccharide - induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues.", "output": "Beta - glucogallin, aldose." }, { "input": "Aldose reductase ( AR ) catalyzes the reduction of toxic lipid aldehydes to their alcohol products and mediates inflammatory signals triggered by lipopolysaccharide ( LPS ).", "output": "Aldose, aldehydes, alcohol." }, { "input": "Beta - glucogallin ( BGG ), a recently described AR inhibitor, was purified from extracts of the Indian gooseberry ( Emblica officinalis ).", "output": "Beta - glucogallin, BGG." }, { "input": "In this study, we found that BGG showed low cytotoxicity in Raw264. 7 murine macrophages and effectively inhibited AR activity as measured by a decrease in sorbitol accumulation.", "output": "BGG, sorbitol." }, { "input": "In addition, BGG - mediated inhibition of AR prevented LPS - induced activation of JNK and p38 and lowered ROS levels, which could inhibit LPS - induced apoptosis.", "output": "BGG." }, { "input": "Uveitis is a disease of the eye associated with chronic inflammation.", "output": "There is no related enetity." }, { "input": "In this study, we also demonstrated that treatment with BGG decreased the number of inflammatory cells that infiltrate the ocular media of mice with experimental uveitis.", "output": "BGG." }, { "input": "Accordingly, these results suggest BGG is a potential therapy for inflammatory diseases.", "output": "BGG." }, { "input": "Regulation of human carbonyl reductase 1 ( CBR1, SDR21C1 ) gene by transcription factor Nrf2.", "output": "carbonyl." }, { "input": "Monomeric carbonyl reductase 1 ( CBR1, SDR21C1 ) is a member of the short - chain dehydrogenase / reductase superfamily and is involved in the metabolism of anthracycline anti - cancer drugs, prostaglandins, and isatin, which is an endogenous inhibitor of monoamine oxidases.", "output": "carbonyl, anthracycline, prostaglandins, isatin, monoamine." }, { "input": "Additionally, cancer progression may be partly regulated by CBR1.", "output": "There is no related enetity." }, { "input": "In the present study, we screened more than 10 drugs for the induction of the human CBR1 gene to investigate its regulation.", "output": "There is no related enetity." }, { "input": "Of the drugs, butylated hydroxyanisole ( BHA ) was found to be an inducer.", "output": "butylated hydroxyanisole, BHA." }, { "input": "BHA induced the mRNA and protein expression of CBR1 in hepatoma HepG2 cells.", "output": "BHA." }, { "input": "In a luciferase reporter gene assay, the promoter region between - 2062 bp and the transcription start site of CBR1 was also activated by BHA.", "output": "There is no related enetity." }, { "input": "The transcription factor Nrf2 is known to be activated by BHA.", "output": "BHA." }, { "input": "There are 2 anti - oxidant responsive elements ( ARE ) that are bound by Nrf2 in this region.", "output": "There is no related enetity." }, { "input": "Mutation analyses revealed that one of the AREs participates in the gene regulation of CBR1 by Nrf2.", "output": "There is no related enetity." }, { "input": "Electrophoretic mobility shift assay revealed that Nrf2 binds the site.", "output": "There is no related enetity." }, { "input": "Moreover, to determine whether the functional ARE of CBR1 is conserved with the promoter region of homologues in other species, the nucleotide sequences of the functional AREs of the Chcr1 and Chcr2 genes, which are the Chinese hamster homologues of CBR1, were determined.", "output": "nucleotide." }, { "input": "The region has 2 AREs, and these genes were also induced by the forced expression of Nrf2 ( cotransfection of pNrf2 ) in the luciferase reporter gene assay.", "output": "There is no related enetity." }, { "input": "In conclusion, Nrf2 is a novel transcriptional regulator of CBR1 genes in humans and the Chinese hamster.", "output": "There is no related enetity." }, { "input": "Because the regulation of CBR1 appears to be important for diseases, the induction of CBR1 by Nrf2 may be a therapeutic target.", "output": "There is no related enetity." }, { "input": "Engineering polypeptide coatings to augment gene transduction and in vivo stability of adenoviruses.", "output": "There is no related enetity." }, { "input": "We sought to modify adenoviral ( Ad ) particles by incorporating the advantageous characteristics of non - viral gene delivery vehicles to complement the viral vectors.", "output": "There is no related enetity." }, { "input": "alpha - Amino acid - N - carboxyanhydride chemistry was used to synthesize homopolypeptides and diblock copolypeptides that possess well - defined secondary structures.", "output": "alpha - Amino acid - N - carboxyanhydride." }, { "input": "Using cryo - electron and fluorescence microscopy, we showed that these polypeptides can coat the surfaces of Ad particles in a non - covalent manner to modify their transduction properties.", "output": "There is no related enetity." }, { "input": "The coated Ad particles were found to bind to and be internalized by cells.", "output": "There is no related enetity." }, { "input": "In contrast to reports using covalently PEGylated Ad particles, we found that our physically coated Ad hybrid complexes facilitate gene transfer both in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "We showed that our polypeptide coating was able to shield the Ad particles from the neutralizing effect of antibodies and mitigate the binding of blood coagulation factor ( Factor X ) in vitro.", "output": "There is no related enetity." }, { "input": "The coating also reduced the antigenicity of Ad in immunocompetent mice.", "output": "There is no related enetity." }, { "input": "The biodistribution of the systemically administered hybrid complexes mirrored the behavior of both viral and non - viral vectors, exhibiting liver tropism as well as enhanced lung transduction.", "output": "There is no related enetity." }, { "input": "These data demonstrated that our non - covalent modification was able to alter Ad ' s interactions with cells and organs with retention of transduction efficiency.", "output": "There is no related enetity." }, { "input": "Advantages such as facile coating of the Ad vector, design flexibility and ease of attaching ligands to the polypeptides make this system potentially useful as a platform for adding functionalities to Ad to target cancer metastasis.", "output": "There is no related enetity." }, { "input": "Chirality recognition of the protonated serine dimer and octamer by infrared multiphoton dissociation spectroscopy.", "output": "serine." }, { "input": "Infrared multiphoton dissociation ( IRMPD ) spectroscopy has been used to record IR signatures of chirality recognition in the protonated serine dimer and octamer in the 3200 - 3800 cm ( - 1 ) region.", "output": "serine." }, { "input": "This is the first IRMPD study to investigate the heterochiral biomolecular system by utilizing the isotope - labelled species.", "output": "There is no related enetity." }, { "input": "Noticeable differences in the homo - versus heterochiral IRMPD spectra have been obtained experimentally for both the dimer and octamer.", "output": "There is no related enetity." }, { "input": "Different dissociation patterns have been noted not only between the homo - and heterochiral octamers, but also between the two - OH stretching vibrational bands of the same chirality species.", "output": "OH." }, { "input": "Systematic theoretical searches have been carried out to identify the most stable conformers of both the homo - and heterochiral protonated serine dimer and octamer.", "output": "serine." }, { "input": "The final geometry optimization and harmonic vibrational calculations have been performed at the MP2 / 6 - 311 + + G ( d, p ) level for the homo - and heterochiral protonated serine dimer and at the B3LYP / 6 - 31G ( d ) level for the homo - and heterochiral protonated serine octamer.", "output": "serine." }, { "input": "For the homo - and heterochiral dimer, good agreement between the experimental and theoretical spectra has been achieved and the major conformers have been identified.", "output": "There is no related enetity." }, { "input": "For the homo - and heterochiral octamer, the main IR features observed have been satisfactorily reproduced theoretically and the dominant conformers identified.", "output": "There is no related enetity." }, { "input": "More than one main conformer has been identified for the homochiral octamer.", "output": "There is no related enetity." }, { "input": "This conclusion has been further supported by the analysis of the wavelength specific dissociation products.", "output": "There is no related enetity." }, { "input": "Sophorolipids - functionalized iron oxide nanoparticles.", "output": "iron oxide." }, { "input": "Functional iron oxide nanoparticles ( NP ) have been synthesized in a one and a two - step method using a natural functional glycolipid belonging to the family of sophorolipids ( SL ).", "output": "iron oxide." }, { "input": "These compounds, whose open acidic form is highly suitable for nanoparticle stabilization, are readily obtained by a fermentation process of the yeast Candida bombicola ( polymorph Starmerella bombicola ) in large amounts.", "output": "There is no related enetity." }, { "input": "The final carbohydrate coated iron oxide nanoparticles represent interesting potentially biocompatible materials for biomedical applications.", "output": "carbohydrate, iron oxide." }, { "input": "According to the synthesis strategy, magnetic properties can eventually be tuned, thus putting in evidence the direct effect of the glycolipid on the final material ' s structure ( maghemite and ferrihydrite have been obtained here ).", "output": "maghemite, ferrihydrite." }, { "input": "A combination of FT - IR, Dynamic Light Scattering ( DLS ) and UV - Vis experiments shows that SL complex the nanoparticle surface via their accessible COOH group thus forming stable colloids, whose hydrodynamic diameter mostly varies between 10 nm and 30 nm, both in water and in KCl - containing ( 0. 01 M and 2 M ) solutions.", "output": "COOH, KCl." }, { "input": "The materials can stand multiple filtration steps ( up to 10 ) at different extents, where the largest recorded average aggregate size is 100 nm.", "output": "There is no related enetity." }, { "input": "In general, materials synthesized at T = 80 degrees C display better stability and smaller size distribution than those obtained at room temperature.", "output": "There is no related enetity." }, { "input": "Nicotinic receptors in addiction pathways.", "output": "There is no related enetity." }, { "input": "Neuronal nicotinic acetylcholine receptors ( nAChRs ) are ligand - gated ion channels that consist of pentameric combinations of alpha and beta subunits.", "output": "acetylcholine." }, { "input": "These receptors are widely distributed throughout the brain and are highly expressed in addiction circuitry.", "output": "There is no related enetity." }, { "input": "The role of nAChRs in regulating neuronal activity and motivated behavior is complex and varies both in and among brain regions.", "output": "There is no related enetity." }, { "input": "The rich diversity of central nAChRs has hampered the characterization of their structure and function with use of classic pharmacological techniques.", "output": "There is no related enetity." }, { "input": "However, recent molecular approaches using null mutant mice with specific regional lentiviral re - expression, in combination with neuroanatomical and electrophysiological techniques, have allowed the elucidation of the influence of different nAChR types on neuronal circuit activity and behavior.", "output": "There is no related enetity." }, { "input": "This review will address the influence of nAChRs on limbic dopamine circuitry and the medial habenula - interpeduncular nucleus complex, which are critical mediators of reinforced behavior.", "output": "dopamine." }, { "input": "Characterization of the mechanisms underlying regulation of addiction pathways by endogenous cholinergic transmission and by nicotine may lead to the identification of new therapeutic targets for treating tobacco dependence and other addictions.", "output": "nicotine." }, { "input": "TGF beta receptor signaling is essential for inflammation - induced but not beta - cell workload - induced beta - cell proliferation.", "output": "There is no related enetity." }, { "input": "Protection and restoration of a functional beta - cell mass are fundamental strategies for prevention and treatment of diabetes.", "output": "There is no related enetity." }, { "input": "Consequently, knowledge of signals that determine the functional beta - cell mass is of immense clinical relevance.", "output": "There is no related enetity." }, { "input": "Transforming growth factor beta ( TGF beta ) superfamily signaling pathways play a critical role in development and tissue specification.", "output": "There is no related enetity." }, { "input": "Nevertheless, the role of these pathways in adult beta - cell homeostasis is not well defined.", "output": "There is no related enetity." }, { "input": "Here, we ablated TGF beta receptor I and II genes in mice undergoing two surgical beta - cell replication models ( partial pancreatectomy or partial duct ligation ), representing two triggers for beta - cell proliferation, increased beta - cell workload and local inflammation, respectively.", "output": "There is no related enetity." }, { "input": "Our data suggest that TGF beta receptor signaling is necessary for baseline beta - cell proliferation.", "output": "There is no related enetity." }, { "input": "By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased beta - cell workload are both stimulants for beta - cell proliferation but are TGF beta receptor signaling dependent and independent, respectively.", "output": "glucose." }, { "input": "Collectively, by using a pancreas - specific TGF beta receptor - deleted mouse model, we have identified two distinct pathways that regulate adult beta - cell proliferation.", "output": "There is no related enetity." }, { "input": "Our study thus provides important information for understanding beta - cell proliferation during normal growth and in pancreatic diseases.", "output": "There is no related enetity." }, { "input": "Impact of restricted maternal weight gain on fetal growth and perinatal morbidity in obese women with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "OBJECTIVE Since January 2008, obese women with type 2 diabetes were advised to gain 0 - 5 kg during pregnancy.", "output": "There is no related enetity." }, { "input": "The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women.", "output": "There is no related enetity." }, { "input": "RESEARCH DESIGN AND METHODS A retrospective cohort comprised the records of 58 singleton pregnancies in obese women ( BMI >= 30 kg / m ( 2 ) ) with type 2 diabetes giving birth between 2008 and 2011.", "output": "There is no related enetity." }, { "input": "Birth weight was evaluated by SD z score to adjust for gestational age and sex.", "output": "There is no related enetity." }, { "input": "RESULTS Seventeen women ( 29 % ) gained <= 5 kg, and the remaining 41 gained > 5 kg.", "output": "There is no related enetity." }, { "input": "The median ( range ) gestational weight gains were 3. 7 kg ( - 4. 7 to 5 kg ) and 12. 1 kg ( 5. 5 - 25. 5 kg ), respectively.", "output": "There is no related enetity." }, { "input": "Prepregnancy BMI was 33. 5 kg / m ( 2 ) ( 30 - 53 kg / m ( 2 ) ) vs. 36. 8 kg / m ( 2 ) ( 30 - 48 kg / m ( 2 ) ), P = 0. 037, and median HbA1c was 6. 7 % at first visit in both groups and decreased to 5. 7 and 6. 0 %, P = 0. 620, in late pregnancy, respectively.", "output": "There is no related enetity." }, { "input": "Gestational weight gain <= 5 kg was associated with lower birth weight z score ( P = 0. 008 ), lower rates of large - for - gestational - age ( LGA ) infants ( 12 vs. 39 %, P = 0. 041 ), delivery closer to term ( 268 vs. 262 days, P = 0. 039 ), and less perinatal morbidity ( 35 vs. 71 %, P = 0. 024 ) compared with pregnancies with maternal weight gain > 5 kg.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain <= 5 kg was associated with a more proportionate birth weight and less perinatal morbidity.", "output": "There is no related enetity." }, { "input": "Statins and Risk of Diabetes: An analysis of electronic medical records to evaluate possible bias due to differential survival.", "output": "Statins." }, { "input": "OBJECTIVE Two meta - analyses of randomized trials of statins found increased risk of type 2 diabetes.", "output": "statins." }, { "input": "One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment.", "output": "statin." }, { "input": "RESEARCH DESIGN AND METHODS We used electronic medical records from 500 general practices in the U. K. and included data from 285, 864 men and women aged 50 - 84 years from January 2000 to December 2010.", "output": "There is no related enetity." }, { "input": "We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention - to - treat effect, and adjusted for differential survival bias using inverse - probability weighting.", "output": "statins." }, { "input": "RESULTS During 1. 2 million person - years of follow - up, there were 13, 455 cases of type 2 diabetes and 8, 932 deaths.", "output": "There is no related enetity." }, { "input": "Statin initiation was associated with increased risk of type 2 diabetes.", "output": "Statin." }, { "input": "The hazard ratio ( 95 % CI ) of diabetes was 1. 45 ( 1. 39 - 1. 50 ) before adjusting for potential confounders and 1. 14 ( 1. 10 - 1. 19 ) after adjustment.", "output": "There is no related enetity." }, { "input": "Adjusting for differential survival did not change the estimates.", "output": "There is no related enetity." }, { "input": "Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes.", "output": "atorvastatin, simvastatin." }, { "input": "CONCLUSIONS In this sample of the general population, statin therapy was associated with 14 % increased risk of type 2 diabetes.", "output": "statin." }, { "input": "Differential survival did not explain this increased risk.", "output": "There is no related enetity." }, { "input": "Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.", "output": "glutathione." }, { "input": "Increasing antibiotic resistance makes the identification of new antibacterial principles an urgent task.", "output": "There is no related enetity." }, { "input": "The thioredoxin system including thioredoxin reductase ( TrxR ), thioredoxin ( Trx ), and NADPH plays critical roles in cellular DNA synthesis and defense against oxidative stress.", "output": "NADPH." }, { "input": "Notably, TrxR is very different in structure and mechanism in mammals and bacteria.", "output": "There is no related enetity." }, { "input": "Ebselen [ 2 - phenyl - 1, 2 benzisoselenazol - 3 ( 2H ) - one ], a well - known antioxidant and a substrate for mammalian TrxR and Trx, is rapidly bacteriocidal for methicillin - resistant Staphylococcus aureus by an unknown mechanism.", "output": "Ebselen, 2 - phenyl - 1 , 2 benzisoselenazol - 3 ( 2H ) - one, methicillin." }, { "input": "We have discovered that ebselen is a competitive inhibitor of Escherichia coli TrxR with a Ki of 0. 52 +/- 0. 13 mu M, through reaction with the active site dithiol of the enzyme.", "output": "ebselen, dithiol." }, { "input": "Bacteria lacking glutathione ( GSH ) and glutaredoxin, in which TrxR and Trx are essential for DNA synthesis, were particularly sensitive to ebselen.", "output": "glutathione, GSH." }, { "input": "In growth - inhibited E. coli strains, Trx1 and Trx2 were oxidized, demonstrating that electron transfer via thioredoxin was blocked.", "output": "There is no related enetity." }, { "input": "Ebselen and its sulfur analog ebsulfur were bactericidal for GSH - negative pathogens.", "output": "Ebselen, sulfur, ebsulfur, GSH." }, { "input": "Ebsulfur inhibited a clinically isolated Helicobacter pylori strain with a minimum inhibitory concentration value as low as 0. 39 mu g / ml.", "output": "Ebsulfur." }, { "input": "These results demonstrate that bacterial Trx and TrxR are viable antibacterial drug targets using benzisoselenazol and benzisothiazol derivates. - Lu, J., Vlamis - Gardikas, A., Kandasamy, K., Zhao, R., Gustafsson, T.", "output": "benzisoselenazol, benzisothiazol." }, { "input": "N., Engstrand, L., Hoffner, S., Engman, L., Holmgren, A.", "output": "There is no related enetity." }, { "input": "Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.", "output": "There is no related enetity." }, { "input": "Progress of pharmacological studies on alkaloids from Apocynaceae.", "output": "There is no related enetity." }, { "input": "Alkaloid was a kind of biological active ingredient.", "output": "There is no related enetity." }, { "input": "There were various types of alkaloids in Apocynaceae.", "output": "There is no related enetity." }, { "input": "This paper reviewed the progress on alkaloids from Apocynaceae, which contained origin, structure, and pharmacological activity.", "output": "There is no related enetity." }, { "input": "Multifaceted ultrafast intramolecular charge transfer dynamics of 4 - ( dimethylamino ) benzonitrile ( DMABN ).", "output": "4 - ( dimethylamino ) benzonitrile, DMABN." }, { "input": "Intramolecular charge transfer ( ICT ) of DMABN has been the subject of extensive investigations.", "output": "DMABN." }, { "input": "Through the measurements of highly time - resolved fluorescence spectra ( TRFS ) over the whole emission region, we have examined the ICT dynamics of DMABN in acetonitrile free from the solvation dynamics and vibronic relaxation.", "output": "DMABN, acetonitrile." }, { "input": "The ICT dynamics was found to be characterized by a broad range of time scales; nearly instantaneous ( < 30 fs ), 160 fs, and 3. 3 ps.", "output": "There is no related enetity." }, { "input": "TRFS revealed that an ICT state with partially twisted geometry, ICT ( P ), is formed within a few hundred femtoseconds either directly from the initial photoexcited state or via the locally excited ( LE ) state.", "output": "There is no related enetity." }, { "input": "The ICT ( P ) state undergoes further relaxation along the intramolecular nuclear coordinate to reach the twisted ICT ( TICT ) state with the time constant of 4. 8 ps.", "output": "There is no related enetity." }, { "input": "A conformational diversity along the rotation of the dimethylamino group was speculated to account for the observed diffusive dynamics.", "output": "dimethylamino." }, { "input": "Light - harvesting and ultrafast energy migration in porphyrin - based metal - organic frameworks.", "output": "porphyrin." }, { "input": "Given that energy ( exciton ) migration in natural photosynthesis primarily occurs in highly ordered porphyrin - like pigments ( chlorophylls ), equally highly ordered porphyrin - based metal - organic frameworks ( MOFs ) might be expected to exhibit similar behavior, thereby facilitating antenna - like light - harvesting and positioning such materials for use in solar energy conversion schemes.", "output": "porphyrin, chlorophylls, porphyrin." }, { "input": "Herein, we report the first example of directional, long - distance energy migration within a MOF.", "output": "There is no related enetity." }, { "input": "Two MOFs, namely F - MOF and DA - MOF that are composed of two Zn ( II ) porphyrin struts [ 5, 15 - dipyridyl - 10, 20 - bis ( pentafluorophenyl ) porphinato ] zinc ( II ) and [ 5, 15 - bis [ 4 - ( pyridyl ) ethynyl ] - 10, 20 - diphenylporphinato ] zinc ( II ), respectively, were investigated.", "output": "Zn ( II ), porphyrin, [ 5 , 15 - dipyridyl - 10 , 20 - bis ( pentafluorophenyl ) porphinato ] zinc ( II ), [ 5 , 15 - bis [ 4 - ( pyridyl ) ethynyl ] - 10 , 20 - diphenylporphinato ] zinc ( II )." }, { "input": "From fluorescence quenching experiments and theoretical calculations, we find that the photogenerated exciton migrates over a net distance of up to ~ 45 porphyrin struts within its lifetime in DA - MOF ( but only ~ 3 in F - MOF ), with a high anisotropy along a specific direction.", "output": "porphyrin." }, { "input": "The remarkably efficient exciton migration in DA - MOF is attributed to enhanced pi - conjugation through the addition of two acetylene moieties in the porphyrin molecule, which leads to greater Q - band absorption intensity and much faster exciton - hopping ( energy transfer between adjacent porphyrin struts ).", "output": "acetylene, porphyrin, porphyrin." }, { "input": "The long distance and directional energy migration in DA - MOF suggests promising applications of this compound or related compounds in solar energy conversion schemes as an efficient light - harvesting and energy - transport component.", "output": "There is no related enetity." }, { "input": "Interaction of OH radicals with Arizona Test Dust: uptake and products.", "output": "OH." }, { "input": "Kinetics and products of the interaction of OH radicals with solid films of Arizona Test Dust ( ATD ) were studied using a low pressure flow reactor ( 0. 5 - 3 Torr ) combined with a modulated molecular beam mass spectrometer for monitoring of the gaseous species involved.", "output": "OH." }, { "input": "The reactive uptake coefficient of OH was measured from the kinetics of OH consumption on Pyrex rods coated with ATD as a function of OH concentration ( ( 0. 4 - 5. 2 ) x 10 ( 12 ) molecules cm ( - 3 ) ), relative humidity ( RH = 0. 03 - 25. 9 % ), temperature ( T = 275 - 320 K ), and UV irradiance intensity ( J ( NO ( 2 ) ) = 0 - 0. 012 s ( - 1 ) ).", "output": "OH, OH, OH, NO ( 2 )." }, { "input": "Deactivation of ATD surface upon exposure to OH was observed.", "output": "OH." }, { "input": "The initial uptake coefficient was found to be independent of temperature and irradiation conditions and to decrease with relative humidity: gamma ( 0 ) = 0. 2 / ( 1 + RH ( 0. 36 ) ) ( calculated using geometric surface area, with 30 % estimated conservative uncertainty ).", "output": "There is no related enetity." }, { "input": "H ( 2 ) O ( 2 ) and H ( 2 ) O were observed in the gas phase as products of the OH reaction with ATD surface with yields of ( 10 +/- 3 ) and ( 98 +/- 25 ) %, respectively.", "output": "H ( 2 ) O ( 2 ), H ( 2 ) O, OH." }, { "input": "Quinpirole and 8 - OH - DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit.", "output": "Quinpirole, 8 - OH - DPAT." }, { "input": "This study investigated whether the serotonin 5 - HT1A receptor agonist 8 - hydroxy - 2 - ( di - n - propylamino ) tetralin ( 8 - OH - DPAT ) can induce compulsive checking in a large open field, as does the dopamine D2 / D3 receptor agonist quinpirole.", "output": "serotonin, 8 - hydroxy - 2 - ( di - n - propylamino ) tetralin, 8 - OH - DPAT, dopamine, quinpirole." }, { "input": "To induce compulsive checking, male rats were exposed to eight injections of either 8 - OH - DPAT ( 1 mg / kg ), quinpirole ( 0. 2 mg / kg ), or saline.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "Subsequently, to assess cross - sensitization, rats received an acute challenge of 8 - OH - DPAT or quinpirole.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "The results showed that treatment with 8 - OH - DPAT induces compulsive checking and may have a stronger effect on this behavior compared with quinpirole.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "However, there was no cross - sensitization between 8 - OH - DPAT and quinpirole on measures of compulsive checking and locomotion.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "Moreover, the spatial distribution of locomotor paths in 8 - OH - DPAT animals was more confined and invariant than in quinpirole rats; their rate of locomotor sensitization was also faster than that in quinpirole animals.", "output": "8 - OH - DPAT, quinpirole, quinpirole." }, { "input": "Thus, although 8 - OH - DPAT and quinpirole can induce compulsive checking in a large open field, the results suggest that they do so differently.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "It is suggested that 8 - OH - DPAT and quinpirole probably produce compulsive behavior by acting on different parts of a security motivation circuit underlying obsessive - compulsive disorder.", "output": "8 - OH - DPAT, quinpirole." }, { "input": "Quinpirole may induce compulsive checking behavior by directly driving dopaminergic activity mediating the motivational drive to check.", "output": "Quinpirole." }, { "input": "Conversely, 8 - OH - DPAT may perpetuate the activated motivational state by inhibiting the serotonergic - negative feedback signals that normally deactivate the obsessive - compulsive disorder circuit.", "output": "8 - OH - DPAT." }, { "input": "Antibiotics that bind to the A site of the large ribosomal subunit can induce mRNA translocation.", "output": "There is no related enetity." }, { "input": "In the absence of elongation factor EF - G, ribosomes undergo spontaneous, thermally driven fluctuation between the pre - translocation ( classical ) and intermediate ( hybrid ) states of translocation.", "output": "There is no related enetity." }, { "input": "These fluctuations do not result in productive mRNA translocation.", "output": "There is no related enetity." }, { "input": "Extending previous findings that the antibiotic sparsomycin induces translocation, we identify additional peptidyl transferase inhibitors that trigger productive mRNA translocation.", "output": "sparsomycin." }, { "input": "We find that antibiotics that bind the peptidyl transferase A site induce mRNA translocation, whereas those that do not occupy the A site fail to induce translocation.", "output": "There is no related enetity." }, { "input": "Using single - molecule FRET, we show that translocation - inducing antibiotics do not accelerate intersubunit rotation, but act solely by converting the intrinsic, thermally driven dynamics of the ribosome into translocation.", "output": "There is no related enetity." }, { "input": "Our results support the idea that the ribosome is a Brownian ratchet machine, whose intrinsic dynamics can be rectified into unidirectional translocation by ligand binding.", "output": "There is no related enetity." }, { "input": "Circular RNAs are abundant, conserved, and associated with ALU repeats.", "output": "There is no related enetity." }, { "input": "Circular RNAs composed of exonic sequence have been described in a small number of genes.", "output": "There is no related enetity." }, { "input": "Thought to result from splicing errors, circular RNA species possess no known function.", "output": "There is no related enetity." }, { "input": "To delineate the universe of endogenous circular RNAs, we performed high - throughput sequencing ( RNA - seq ) of libraries prepared from ribosome - depleted RNA with or without digestion with the RNA exonuclease, RNase R.", "output": "There is no related enetity." }, { "input": "We identified > 25, 000 distinct RNA species in human fibroblasts that contained non - colinear exons ( a \" backsplice \" ) and were reproducibly enriched by exonuclease degradation of linear RNA.", "output": "There is no related enetity." }, { "input": "These RNAs were validated as circular RNA ( ecircRNA ), rather than linear RNA, and were more stable than associated linear mRNAs in vivo.", "output": "There is no related enetity." }, { "input": "In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by > 10 - fold.", "output": "There is no related enetity." }, { "input": "By conservative estimate, we identified ecircRNAs from 14. 4 % of actively transcribed genes in human fibroblasts.", "output": "There is no related enetity." }, { "input": "Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs.", "output": "There is no related enetity." }, { "input": "Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice.", "output": "There is no related enetity." }, { "input": "Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes.", "output": "There is no related enetity." }, { "input": "Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs.", "output": "There is no related enetity." }, { "input": "Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats.", "output": "There is no related enetity." }, { "input": "These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.", "output": "There is no related enetity." }, { "input": "The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes.", "output": "bile acid, glucose." }, { "input": "We designed an experiment to examine the effect of bile acid sequestration with Colesevelam on fasting and postprandial glucose metabolism in type 2 diabetes.", "output": "bile acid, Colesevelam, glucose." }, { "input": "To do so, we tested the hypothesis that Colesevelam increases the disposition index ( DI ), and this increase is associated with increased glucagon - like peptide - 1 ( GLP - 1 ) concentrations.", "output": "Colesevelam." }, { "input": "Thirty - eight subjects on metformin monotherapy were studied using a double - blind, placebo - controlled, parallel - group design.", "output": "metformin." }, { "input": "Subjects were studied before and after 12 weeks of Colesevelam or placebo using a labeled triple - tracer mixed meal to measure the rate of meal appearance ( Meal Ra ), endogenous glucose production ( EGP ), and glucose disappearance ( Rd ).", "output": "Colesevelam, glucose, glucose." }, { "input": "Insulin sensitivity and beta - cell responsivity indices were estimated using the oral minimal model and then used to calculate DI.", "output": "There is no related enetity." }, { "input": "Therapy with Colesevelam was associated with a decrease in fasting ( 7. 0 +/- 0. 2 vs. 6. 6 +/- 0. 2 mmol / L; P = 0. 004 ) and postprandial glucose concentrations ( 3, 145 +/- 138 vs. 2, 896 +/- 127 mmol / 6 h; P = 0. 01 ) in the absence of a change in insulin concentrations.", "output": "Colesevelam, glucose." }, { "input": "Minimal model - derived indices of insulin secretion and action were unchanged.", "output": "There is no related enetity." }, { "input": "Postprandial GLP - 1 concentrations were not altered by Colesevelam.", "output": "Colesevelam." }, { "input": "Although EGP and Rd were unchanged, integrated Meal Ra was decreased by Colesevelam ( 5, 191 +/- 204 vs. 5, 817 +/- 204 mu mol / kg / 6 h; P = 0. 04 ), suggesting increased splanchnic sequestration of meal - derived glucose.", "output": "Colesevelam, glucose." }, { "input": "Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations.", "output": "fatty rats, chromium." }, { "input": "Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals.", "output": "There is no related enetity." }, { "input": "While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese ( an insulin resistance and early stage diabetes model ), and Zucker diabetic fatty ( ZDF, a type 2 diabetes model ) have not previously been examined in detail.", "output": "There is no related enetity." }, { "input": "The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined.", "output": "Cu, Zn, Fe, Mg, Ca, Cr." }, { "input": "Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and / or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats.", "output": "Cu, Zn, Fe, Mg." }, { "input": "ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats.", "output": "Cu, Ca." }, { "input": "Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats.", "output": "Fe." }, { "input": "No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified.", "output": "Cr." }, { "input": "Cr ( III ) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats.", "output": "Cr ( III )." }, { "input": "The effects of daily gavage administration of chromium picolinate ( [ Cr ( pic ) ( 3 ) ] ) ( 1 mg Cr / kg body mass ), CrCl ( 3 ) ( 1 mg Cr / kg body mass ), and Cr3 ( [ Cr ( 3 ) O ( propionate ) ( 6 ) ( H ( 2 ) O ) ( 3 ) ] ( + ) ) ( 33 mu g and 1 mg Cr / kg body mass ) on metal concentrations in these tissues were examined.", "output": "chromium picolinate, [ Cr ( pic ) ( 3 ) ], Cr, CrCl ( 3 ), Cr, Cr3 ( [ Cr ( 3 ) O ( propionate ) ( 6 ) ( H ( 2 ) O ) ( 3 ) ] ( + ) ), Cr." }, { "input": "Treatment with CrCl ( 3 ) and Cr3, but not [ Cr ( pic ) ( 3 ) ], at 1 mg Cr / kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes.", "output": "CrCl ( 3 ), Cr3, [ Cr ( pic ) ( 3 ) ], Cr, Cr, Cu." }, { "input": "Curcumin improves TNBS - induced colitis in rats by inhibiting IL - 27 expression via the TLR4 / NF - kappa B signaling pathway.", "output": "Curcumin." }, { "input": "Curcumin is a widely used spice with anti - inflammatory and anticancer properties.", "output": "Curcumin." }, { "input": "It has been reported to have beneficial effects in experimental colitis.", "output": "There is no related enetity." }, { "input": "This study explored whether curcumin improves colonic inflammation in a rat colitis model through inhibition of the TLR4 / NF - kappa B signaling pathway and IL - 27 expression.", "output": "curcumin." }, { "input": "After induction of colitis with 2, 4, 6 - trinitrobenzene sulfonic acid, rats were intragastrically administered with curcumin or sulfasalazine daily for one week.", "output": "2 , 4 , 6 - trinitrobenzene sulfonic acid, curcumin, sulfasalazine." }, { "input": "Rat intestinal mucosa was collected for evaluation of the disease activity index, colonic mucosa damage index, and histological score.", "output": "There is no related enetity." }, { "input": "Myeloperoxidase activity was detected by immunohistochemistry, and mRNA and protein expression levels of TLR4, NF - kappa B, and IL - 27 in colonic mucosa were detected by RT - PCR and Western blot.", "output": "There is no related enetity." }, { "input": "Compared with the untreated colitis group, the curcumin - treated group showed significant decreases in the disease activity index, colonic mucosa damage index, histological score, myeloperoxidase activity, and expressions of NF - kappa B mRNA, IL - 27 mRNA, TLR4 protein, NF - kappa B p65 protein, and IL - 27 p28 protein ( p < 0. 05 ).", "output": "curcumin." }, { "input": "TLR4 mRNA expression did not differ between groups.", "output": "There is no related enetity." }, { "input": "Disease activity index decreased more rapidly in the curcumin - treated group than in the sulfasalazine - treated group ( p < 0. 05 ).", "output": "curcumin, sulfasalazine." }, { "input": "There was no significant difference in TLR4, NF - kappa B, and IL - 27 mRNA and proteins between curcumin - treated and sulfasalazine - treated groups.", "output": "curcumin, sulfasalazine." }, { "input": "Curcumin shows significant therapeutic effects on 2, 4, 6 - trinitrobenzene sulfonic acid - induced colitis that are comparable to sulfasalazine.", "output": "Curcumin, 2 , 4 , 6 - trinitrobenzene sulfonic acid, sulfasalazine." }, { "input": "The anti - inflammatory actions of curcumin on colitis may involve inhibition of the TLR4 / NF - kappa B signaling pathway and of IL - 27 expression.", "output": "curcumin." }, { "input": "Lightweight and strong cellulose materials made from aqueous foams stabilized by nanofibrillated cellulose.", "output": "There is no related enetity." }, { "input": "A lightweight and strong porous cellulose material has been prepared by drying aqueous foams stabilized with surface - modified nanofibrillated cellulose ( NFC ).", "output": "There is no related enetity." }, { "input": "This material differs from other dry, particle stabilized foams in that renewable cellulose is used as stabilizing particles.", "output": "There is no related enetity." }, { "input": "Confocal microscopy and high speed video imaging show that the octylamine - coated, rod - shaped NFC nanoparticles residing at the air - liquid interface prevent the air bubbles from collapsing or coalescing.", "output": "octylamine." }, { "input": "Stable wet foams can be achieved at solids content around 1 % by weight.", "output": "There is no related enetity." }, { "input": "Careful removal of the water results in a cellulose - based material with a porosity of 98 % and a density of 30 mg cm ( - 3 ).", "output": "There is no related enetity." }, { "input": "These porous cellulose materials have a higher Young ' s modulus than porous cellulose materials made from freeze - drying, at comparable densities, and have a compressive energy absorption of 56 kJ m ( - 3 ) at 80 % strain.", "output": "There is no related enetity." }, { "input": "Measurement with the aid of an autoporosimeter revealed that most pores are in the range of 300 to 500 mu m.", "output": "There is no related enetity." }, { "input": "Total synthesis and evaluation of vinblastine analogues containing systematic deep - seated modifications in the vindoline subunit ring system: core redesign.", "output": "vinblastine, vindoline." }, { "input": "The total synthesis of a systematic series of vinblastine analogues that contain deep - seated structural modifications to the core ring system of the lower vindoline subunit is described.", "output": "vinblastine, vindoline." }, { "input": "Complementary to the vindoline 6, 5 DE ring system, compounds with 5, 5, 6, 6, and the reversed 5, 6 membered DE ring systems were prepared.", "output": "vindoline." }, { "input": "Both the natural cis and unnatural trans 6, 6 - membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design.", "output": "There is no related enetity." }, { "input": "Following Fe ( III ) - promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity.", "output": "Fe ( III ), catharanthine, vinblastine, vindoline." }, { "input": "Two potent analogues ( 81 and 44 ) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6, 7 - double bond whose removal in vinblastine leads to a 100 - fold drop in activity.", "output": "vindoline, vinblastine." }, { "input": "Analysis of 4 - Hydroxy - 1 - ( 3 - pyridyl ) - 1 - butanone ( HPB ) - Releasing DNA Adducts in Human Exfoliated Oral Mucosa Cells by Liquid Chromatography - Electrospray Ionization - Tandem Mass Spectrometry.", "output": "4 - Hydroxy - 1 - ( 3 - pyridyl ) - 1 - butanone, HPB." }, { "input": "Quantitation of DNA adducts could provide critical information on the relationship between exposure to tobacco smoke and cancer risk in smokers.", "output": "There is no related enetity." }, { "input": "In this study, we developed a robust and sensitive liquid chromatography - tandem mass spectrometry method for the analysis of 4 - hydroxy - 1 - ( 3 - pyridyl ) - 1 - butanone ( HPB ) - releasing DNA adducts in human oral cells, a noninvasive source of DNA for biomarker studies.", "output": "4 - hydroxy - 1 - ( 3 - pyridyl ) - 1 - butanone, HPB." }, { "input": "Isolated DNA undergoes acid hydrolysis, after which samples are purified by solid - phase extraction and analyzed by LC - ESI - MS / MS.", "output": "There is no related enetity." }, { "input": "The developed method was applied to the analysis of samples obtained via collection with a commercial mouthwash from 30 smokers and 15 nonsmokers.", "output": "There is no related enetity." }, { "input": "In smokers, the levels of HPB - releasing DNA adducts averaged 12. 0 pmol HPB / mg DNA ( detected in 20 out of 28 samples with quantifiable DNA yield ), and in nonsmokers, the levels of adducts averaged 0. 23 pmol / mg DNA ( detected in 3 out of 15 samples ).", "output": "HPB, HPB." }, { "input": "For the 30 smoking subjects, matching buccal brushings were also analyzed, and HPB - releasing DNA adducts were detected in 24 out of 27 samples with quantifiable DNA yield, averaging 44. 7 pmol HPB / mg DNA.", "output": "HPB, HPB." }, { "input": "The levels of adducts in buccal brushings correlated with those in mouthwash samples of smokers ( R = 0. 73, p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Potentially, the method can be applied in studies of individual susceptibility to tobacco - induced cancers in humans.", "output": "There is no related enetity." }, { "input": "Pyrenyl - linker - glucono gelators.", "output": "Pyrenyl, glucono." }, { "input": "Correlations of gel properties with gelator structures and characterization of solvent effects.", "output": "There is no related enetity." }, { "input": "A series of glucono - appended 1 - pyrenesulfonyl derivatives containing alpha, omega - diaminoalkane spacers ( Pn, where n, the number of methylene units separating the amino groups, is 2, 3, 4, 6, 7, and 8 ) have been prepared.", "output": "glucono, 1 - pyrenesulfonyl, alpha , omega - diaminoalkane, methylene, amino." }, { "input": "Careful analyses of correlations between the structures of these molecules and their gels have provided important insights into the factors responsible for one - dimensional aggregation of small molecules containing both lipophilic and hydrophilic parts.", "output": "There is no related enetity." }, { "input": "The gelation behavior has been examined in 30 liquids of diverse structure and polarity, and the properties of their gels and the gelation mechanisms have been investigated using a variety of techniques.", "output": "There is no related enetity." }, { "input": "Possible reasons are discussed regarding why the Pn are better gelators than the corresponding naphthyl analogues ( Nn ) which had been investigated previously.", "output": "naphthyl." }, { "input": "P2 and P3 are ambidextrous gelators ( i. e., they gelate both water and some organic liquids ), and P4 - P8 gelate some organic liquids which are protic and aprotic, but not water.", "output": "There is no related enetity." }, { "input": "In at least one of the liquids examined, P3, P4, P6, P7, and P8 form gels at less than 1 w / v % concentrations, and some of the gels in 1 - decanol are thixotropic.", "output": "1 - decanol." }, { "input": "Analyses of the gelation abilities using Hansen solubility parameters yield both qualitative and quantitative insights into the role of liquid - gelator interactions.", "output": "There is no related enetity." }, { "input": "For example, the critical gelation concentrations increase generally with increasing polar and hydrogen bonding interactions between the gelators and their liquid components.", "output": "hydrogen." }, { "input": "As revealed by FT - IR, ( 1 ) H NMR, UV - vis, and fluorescence spectra, hydrogen - bonding between glucono units and pi - pi stacking between pyrenyl groups are important in the formation and maintenance of the gel networks.", "output": "( 1 ) H, hydrogen, glucono, pyrenyl." }, { "input": "The results from this study, especially those relating the aggregation modes and liquid properties, offer insights for the design of new surfactant - containing low - molecular - mass gelators with predefined gelating abilities.", "output": "There is no related enetity." }, { "input": "Antiproliferative withanolides from Datura wrightii.", "output": "withanolides." }, { "input": "A new withanolide, named withawrightolide ( 1 ), and four known withanolides ( 2 - 5 ) were isolated from the aerial parts of Datura wrightii.", "output": "withanolide, withawrightolide, withanolides." }, { "input": "The structure of compound 1 was elucidated through 2D NMR and other spectroscopic techniques.", "output": "There is no related enetity." }, { "input": "In addition, the structure of withametelin L ( 2 ) was confirmed by X - ray crystallographic analysis.", "output": "withametelin L." }, { "input": "Using MTS viability assays, withanolides 1 - 5 showed antiproliferative activities against human glioblastoma ( U251 and U87 ), head and neck squamous cell carcinoma ( MDA - 1986 ), and normal fetal lung fibroblast ( MRC - 5 ) cells with IC50 values in the range between 0. 56 and 5. 6 mu M.", "output": "MTS, withanolides 1 - 5." }, { "input": "Putative impact of RNA editing on drug discovery.", "output": "There is no related enetity." }, { "input": "Virtually all organisms use RNA editing as a powerful post - transcriptional mechanism to recode genomic information and to increase functional protein diversity.", "output": "There is no related enetity." }, { "input": "The enzymatic editing of pre - mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability.", "output": "There is no related enetity." }, { "input": "However, RNA editing is also an important mechanism for genes expressed outside the brain.", "output": "There is no related enetity." }, { "input": "The fact that RNA editing breaks the ' one gene encodes one protein ' hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the ' wrong ' protein.", "output": "There is no related enetity." }, { "input": "This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets.", "output": "There is no related enetity." }, { "input": "These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology.", "output": "There is no related enetity." }, { "input": "Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high - throughput screens, rational drug design or choosing the right model organism for target validation.", "output": "There is no related enetity." }, { "input": "The discovery of fused oxadiazepines as gamma secretase modulators for treatment of Alzheimer ' s disease.", "output": "oxadiazepines." }, { "input": "In an attempt to further improve overall profiles of the oxadiazine series of GSMs, in particular the hERG activity, conformational modifications of the core structure resulted in the identification of fused oxadiazepines such as 7i which had an improved hERG inhibition profile and was a highly efficacious GSM in vitro and in vivo in rats.", "output": "oxadiazine, oxadiazepines." }, { "input": "These SAR explorations offer opportunities to identify potential drugs to treat Alzheimer ' s disease.", "output": "There is no related enetity." }, { "input": "Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea - induced stalling.", "output": "hydroxyurea." }, { "input": "Human WRN and BLM genes are members of the conserved RECQ helicase family.", "output": "There is no related enetity." }, { "input": "Mutations in these genes are associated with Werner and Bloom syndromes.", "output": "There is no related enetity." }, { "input": "WRN and BLM proteins are implicated in DNA replication, recombination, repair, telomere maintenance, and transcription.", "output": "There is no related enetity." }, { "input": "Using microfluidics - assisted display of DNA for replication track analysis ( ma - RTA ), we show that WRN and BLM contribute additively to normal replication fork progression, and non - additively, in a RAD51 - dependent pathway, to resumption of replication after arrest by hydroxyurea ( HU ), a replication - stalling drug.", "output": "hydroxyurea." }, { "input": "WRN but not BLM is required to support fork progression after HU.", "output": "There is no related enetity." }, { "input": "Resumption of replication by forks may be necessary but is not sufficient for timely completion of the cell cycle after HU arrest, as depletion of WRN or BLM compromises fork recovery to a similar degree, but only BLM depletion leads to extensive delay of cell division after HU, as well as more pronounced chromatin bridging.", "output": "There is no related enetity." }, { "input": "Finally, we show that recovery from HU includes apparent removal of some of the DNA that was synthesized immediately after release from HU, a novel phenomenon that we refer to as nascent strand processing, NSP.", "output": "There is no related enetity." }, { "input": "Phytoestrogen genistein protects against endothelial barrier dysfunction in vascular endothelial cells through PKA - mediated suppression of RhoA signaling.", "output": "genistein." }, { "input": "The soy - derived phytoestrogen genistein has received attention for its potential to improve vascular function, but its mechanism remains unclear.", "output": "genistein." }, { "input": "Here, we report that genistein at physiologically relevant concentrations ( 0. 1 - 10 mu M ) significantly inhibited thrombin - induced increase in endothelial monolayer permeability.", "output": "genistein." }, { "input": "Genistein also reduced the formation of stress fibers by thrombin and suppressed thrombin - induced phosphorylation of myosin light chain ( MLC ) on Ser ( 19 ) / Thr ( 18 ) in endothelial cells ( ECs ).", "output": "Genistein, Ser, Thr." }, { "input": "Genistein had no effect on resting intracellular [ Ca ( 2 + ) ] or thrombin - induced increase in Ca ( 2 + ) mobilization.", "output": "Genistein, Ca ( 2 + ), Ca ( 2 + )." }, { "input": "Addition of the inhibitors of endothelial nitric oxide synthase or estrogen receptor did not alter the protective effect of genistein.", "output": "nitric oxide, estrogen, genistein." }, { "input": "RhoA is a small GTPase that plays an important role in actin - myosin contraction and endothelial barrier dysfunction.", "output": "There is no related enetity." }, { "input": "RhoA inhibitor blocked the protective effect of genistein on endothelial permeability and also ablated thrombin - induced MLC - phosphorylation in ECs.", "output": "genistein." }, { "input": "Inhibition of PKA significantly attenuated the effect of genistein on thrombin - induced EC permeability, MLC phosphorylation, and RhoA membrane translocation in ECs.", "output": "genistein." }, { "input": "Furthermore, thrombin diminished cAMP production in ECs, which were prevented by treatment with genistein.", "output": "cAMP, genistein." }, { "input": "These findings demonstrated that genistein improves thrombin - induced endothelial barrier dysfunction in ECs through PKA - mediated suppression of RhoA signaling.", "output": "genistein." }, { "input": "Intrinsically green iron oxide nanoparticles?", "output": "iron oxide." }, { "input": "From synthesis via ( eco - ) toxicology to scenario modelling.", "output": "There is no related enetity." }, { "input": "Iron oxide nanoparticles ( IONP ) are currently being studied as green magnet resonance imaging ( MRI ) contrast agents.", "output": "Iron oxide." }, { "input": "They are also used in huge quantities for environmental remediation and water treatment purposes, although very little is known on the consequences of such applications for organisms and ecosystems.", "output": "There is no related enetity." }, { "input": "In order to address these questions, we synthesised polyvinylpyrrolidone - coated IONP, characterised the particle dispersion in various media and investigated the consequences of an IONP exposure using an array of biochemical and biological assays.", "output": "polyvinylpyrrolidone." }, { "input": "Several theoretical approaches complemented the measurements.", "output": "There is no related enetity." }, { "input": "In aqueous dispersion IONP had an average hydrodynamic diameter of 25 nm and were stable over six days in most test media, which could also be predicted by stability modelling.", "output": "There is no related enetity." }, { "input": "The particles were tested in concentrations of up to 100 mg Fe per L.", "output": "Fe." }, { "input": "The activity of the enzymes glutathione reductase and acetylcholine esterase was not affected, nor were proliferation, morphology or vitality of mammalian OLN - 93 cells although exposure of the cells to 100 mg Fe per L increased the cellular iron content substantially.", "output": "glutathione, acetylcholine, Fe, iron." }, { "input": "Only at this concentration, acute toxicity tests with the freshwater flea Daphnia magna revealed slightly, yet insignificantly increased mortality.", "output": "There is no related enetity." }, { "input": "Two fundamentally different bacterial assays, anaerobic activated sludge bacteria inhibition and a modified sediment contact test with Arthrobacter globiformis, both rendered results contrary to the other assays: at the lowest test concentration ( 1 mg Fe per L ), IONP caused a pronounced inhibition whereas higher concentrations were not effective or even stimulating.", "output": "There is no related enetity." }, { "input": "Preliminary and prospective risk assessment was exemplified by comparing the application of IONP with gadolinium - based nanoparticles as MRI contrast agents.", "output": "gadolinium." }, { "input": "Predicted environmental concentrations were modelled in two different scenarios, showing that IONP could reduce the environmental exposure of toxic Gd - based particles by more than 50 %.", "output": "Gd." }, { "input": "Application of the Swiss \" Precautionary Matrix for Synthetic Nanomaterials \" rendered a low precautionary need for using our IONP as MRI agents and a higher one when using them for remediation or water treatment.", "output": "There is no related enetity." }, { "input": "Since IONP and ( considerably more reactive ) zerovalent iron nanoparticles are being used in huge quantities for environmental remediation purposes, it has to be ascertained that these particles pose no risk to either human health or to the environment.", "output": "iron." }, { "input": "Low percentage of KRAS mutations revealed by locked nucleic acid polymerase chain reaction: implications for treatment of metastatic colorectal cancer.", "output": "There is no related enetity." }, { "input": "Metastatic colorectal cancer ( mCRC ) is frequently characterized by the presence of mutations of the KRAS oncogene, which are generally associated with a poor response to treatment with anti - epidermal growth factor receptor ( anti - EGFR ) monoclonal antibodies.", "output": "There is no related enetity." }, { "input": "With the methods currently used, a case is classified as KRAS - mutated when approximately 20 % of the cells bear an activating KRAS mutation.", "output": "There is no related enetity." }, { "input": "These considerations raise the question of whether cells with a mutated KRAS can be found in mCRC cases classified as KRAS wild - type when more sensitive methods are used.", "output": "There is no related enetity." }, { "input": "In addition, the issue arises of whether these mCRC cases with low proportion of KRAS - mutated cells could account at least in part for the therapeutic failure of anti - EGFR therapies that occur in 40 - 60 % of cases classified as KRAS wild type.", "output": "There is no related enetity." }, { "input": "In this study, we compared the classical assays with a very sensitive test, a locked nucleic acid ( LNA ) polymerase chain reaction ( PCR ), capable of detecting KRAS - mutated alleles at extremely low frequency ( detection sensitivity limit 0. 25 % mutated DNA / wild - type DNA ).", "output": "There is no related enetity." }, { "input": "By analyzing a cohort of 213 mCRC patients for KRAS mutations, we found a 20. 6 % discordance between the sequencing / TheraScreen methods and the LNA - PCR.", "output": "There is no related enetity." }, { "input": "Indeed, 44 mCRC patients initially considered KRAS wild type were reclassified as KRAS mutated by using the LNA - PCR test.", "output": "There is no related enetity." }, { "input": "These patients were more numerous among individuals displaying a clinical failure to anti - EGFR therapies.", "output": "There is no related enetity." }, { "input": "Failure to respond to these biological treatments occurred even in the absence of mutations in other EGFR pathway components such as BRAF.", "output": "There is no related enetity." }, { "input": "Formation of RNA phosphodiester bond by histidine - containing dipeptides.", "output": "phosphodiester, histidine, dipeptides." }, { "input": "A new scenario for prebiotic formation of nucleic acid oligomers is presented.", "output": "There is no related enetity." }, { "input": "Peptide catalysis is applied to achieve condensation of activated RNA monomers into short RNA chains.", "output": "There is no related enetity." }, { "input": "As catalysts, L - dipeptides containing a histidine residue, primarily Ser - His, were used.", "output": "L - dipeptides, histidine, Ser - His." }, { "input": "Reactions were carried out in self - organised environment, a water - ice eutectic phase, with low concentrations of reactants.", "output": "There is no related enetity." }, { "input": "Incubation periods up to 30 days resulted in the formation of short oligomers of RNA.", "output": "There is no related enetity." }, { "input": "During the oligomerisation, an active intermediate ( dipeptide - mononucleotide ) is produced, which is the reactive species.", "output": "dipeptide - mononucleotide." }, { "input": "Details of the mechanism and kinetics, which were elucidated with a set of control experiments, further establish that the imidazole side chain of a histidine at the carboxyl end of the dipeptide plays a crucial role in the catalysis.", "output": "imidazole, histidine, carboxyl, dipeptide." }, { "input": "These results suggest that this oligomerisation catalysis occurs by a transamination mechanism.", "output": "There is no related enetity." }, { "input": "Because peptides are much more likely products of spontaneous condensation than nucleotide chains, their potential as catalysts for the formation of RNA is interesting from the origin - of - life perspective.", "output": "nucleotide." }, { "input": "Finally, the formation of the dipeptide - mononucleotide intermediate and its significance for catalysis might also be viewed as the tell - tale signs of a new example of organocatalysis.", "output": "dipeptide - mononucleotide." }, { "input": "Structural and stereochemical studies of hydroxyanthraquinone derivatives from the endophytic fungus Coniothyrium sp.", "output": "hydroxyanthraquinone." }, { "input": "Four known hydroxyanthraquinones ( 1 - 4 ) together with four new derivatives having a tetralone moiety, namely coniothyrinones A - D ( 5 - 8 ), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands.", "output": "hydroxyanthraquinones, tetralone, coniothyrinones A - D." }, { "input": "The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data.", "output": "There is no related enetity." }, { "input": "The absolute configurations of coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C ( 7 ) as well.", "output": "coniothyrinones A ( 5 ) , B ( 6 ) , and D, coniothyrinone C." }, { "input": "Coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives.", "output": "Coniothyrinones A ( 5 ) , B ( 6 ) , and D, tetralone." }, { "input": "This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp.", "output": "anthraquinones." }, { "input": "These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.", "output": "There is no related enetity." }, { "input": "Tungsten carbide nanoparticles as efficient cocatalysts for photocatalytic overall water splitting.", "output": "Tungsten carbide." }, { "input": "Tungsten carbide exhibits platinum - like behavior, which makes it an interesting potential substitute for noble metals in catalytic applications.", "output": "Tungsten carbide, platinum." }, { "input": "Tungsten carbide nanocrystals ( =~ 5 nm ) are directly synthesized through the reaction of tungsten precursors with mesoporous graphitic C ( 3 ) N ( 4 ) ( mpg - C ( 3 ) N ( 4 ) ) as the reactive template in a flow of inert gas at high temperatures.", "output": "Tungsten carbide, tungsten, C ( 3 ) N ( 4 ), C ( 3 ) N ( 4 )." }, { "input": "Systematic experiments that vary the precursor compositions and temperatures used in the synthesis selectively generate different compositions and structures for the final nanocarbide ( W ( 2 ) C or WC ) products.", "output": "W ( 2 ) C, WC." }, { "input": "Electrochemical measurements demonstrate that the WC phase with a high surface area exhibits both high activity and stability in hydrogen evolution over a wide pH range.", "output": "WC, hydrogen." }, { "input": "The WC sample also shows excellent hydrogen oxidation activity, whereas its activity in oxygen reduction is poor.", "output": "WC, hydrogen, oxygen." }, { "input": "These tungsten carbides are successful cocatalysts for overall water splitting and give H ( 2 ) and O ( 2 ) in a stoichiometric ratio from H ( 2 ) O decomposition when supported on a Na - doped SrTiO ( 3 ) photocatalyst.", "output": "tungsten carbides, H ( 2 ), O ( 2 ), H ( 2 ) O, Na, SrTiO ( 3 )." }, { "input": "Herein, we present tungsten carbide ( on a small scale ) as a promising and durable catalyst substitute for platinum and other scarce noble - metal catalysts in catalytic reaction systems used for renewable energy generation.", "output": "tungsten carbide, platinum." }, { "input": "Dandelion leaf extract protects against liver injury induced by methionine - and choline - deficient diet in mice.", "output": "methionine, choline." }, { "input": "We investigated the hepatoprotective effects of the extract of dandelion leaves ( EDL ) on a murine model of methionine - and choline - deficient ( MCD ) diet - induced nonalcoholic steatohepatitis ( NASH ).", "output": "methionine, choline." }, { "input": "C57BL / 6 mice were fed for 4 weeks with one of the following diets: control diet ( Cont ), MCD diet ( MCD ), MCD diet supplemented with EDL at 200 mg / kg body weight. daily ( MCD + D200 ), and MCD diet supplemented with EDL at 500 mg / kg body weight. daily ( MCD + D500 ).", "output": "There is no related enetity." }, { "input": "Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase ( ALT ), triglyceride ( TG ), malondialdehyde ( MDA ), and reduced glutathione ( GSH ); expression levels of TNF - alpha and IL - 6; and levels of caspase - 3 and pJNK / JNK protein.", "output": "alanine, triglyceride, malondialdehyde, MDA, reduced glutathione, GSH." }, { "input": "Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH.", "output": "There is no related enetity." }, { "input": "Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF - alpha, and IL - 6; on the contrary, the levels of reduced GSH increased.", "output": "MDA, reduced GSH." }, { "input": "At the post - transcriptional level, EDL significantly decreased the activation of procaspase - 3 to active caspase - 3, and the phosphorylation of JNK.", "output": "There is no related enetity." }, { "input": "These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti - inflammatory activities.", "output": "There is no related enetity." }, { "input": "Trigonelline ameliorates oxidative stress in type 2 diabetic Goto - Kakizaki rats.", "output": "Trigonelline." }, { "input": "Previously, we showed that trigonelline ( TRG ) exerts antidiabetic effects in type 2 diabetic Goto - Kakizaki ( GK ) rats and also lowers blood and liver thiobarbituric acid reactive substances and urinary 8 - hydroxydeoxyguanosine when compared with those levels in GK control rats without TRG.", "output": "trigonelline, TRG, thiobarbituric acid, 8 - hydroxydeoxyguanosine." }, { "input": "These results suggested that TRG also mitigates oxidative stress, which accelerates diabetes.", "output": "TRG." }, { "input": "In this study, the mechanisms of TRG prevention of oxidative stress were determined by measuring erythrocyte and liver antioxidant enzyme activities, and expressions of genes associated with reactive oxygen species production, and carbohydrate and lipid metabolisms by DNA microarray.", "output": "TRG, oxygen, carbohydrate." }, { "input": "Erythrocyte and liver glutathione peroxidase, and liver catalase activities in the GK rats fed with TRG were significantly lower than those of the GK control rats.", "output": "glutathione, TRG." }, { "input": "TRG downregulated the gene expressions involved with NADPH oxidase and mitochondrial electron transfer system when compared with those of the GK control group.", "output": "TRG, NADPH." }, { "input": "These results suggested that mitigation of diabetes by TRG is mediated by its ameliorating effects on oxidative stress.", "output": "TRG." }, { "input": "Metabolic effects of honey in type 1 diabetes mellitus: a randomized crossover pilot study.", "output": "There is no related enetity." }, { "input": "The aim of this study was to evaluate the metabolic effects of 12 - week honey consumption on patients suffering from type 1 diabetes mellitus ( DM ).", "output": "There is no related enetity." }, { "input": "This was a randomized crossover clinical trial done in the National Institute for Diabetes and Endocrinology, Cairo, Egypt.", "output": "There is no related enetity." }, { "input": "Twenty patients of both sexes aged 4 - 18 years with type 1 DM and HbA1C < 10 % participated in the study.", "output": "There is no related enetity." }, { "input": "They were randomized into two equal groups ( intervention to control and control to intervention ).", "output": "There is no related enetity." }, { "input": "The dietary intervention was 12 - week honey consumption in a dose of 0. 5 mL / kg body weight per day.", "output": "There is no related enetity." }, { "input": "The main outcome measures were serum glucose, lipids, and C - peptide, and anthropometric measurements.", "output": "glucose." }, { "input": "None of participants were lost in follow - up.", "output": "There is no related enetity." }, { "input": "The intervention resulted in significant decreases in subscapular skin fold thickness ( SSFT; P =. 002 ), fasting serum glucose ( FSG; P =. 001 ), total cholesterol ( P =. 0001 ), serum triglycerides ( TG; P =. 0001 ), and low - density lipoprotein ( P =. 0009 ), and significant increases in fasting C - peptide ( FCP; P =. 0004 ) and 2 - h postprandial C - peptide ( PCP; P =. 002 ).", "output": "glucose, cholesterol, triglycerides." }, { "input": "As possible long - term effects of honey after its withdrawal, statistically significant reductions in midarm circumference ( P =. 000 ), triceps skin fold thickness ( P =. 006 ), SSFT ( P =. 003 ), FSG ( P =. 005 ), 2 - h postprandial serum glucose ( P =. 000 ), TG ( P =. 003 ), and HbA1C ( P =. 043 ), and significant increases in FCP ( P =. 002 ) and PCP ( P =. 003 ) were observed.", "output": "glucose." }, { "input": "This small clinical trial suggests that long - term consumption of honey might have positive effects on the metabolic derangements of type 1 DM.", "output": "There is no related enetity." }, { "input": "Fit - for - purpose bioanalytical cross - validation for LC - MS / MS assays in clinical studies.", "output": "There is no related enetity." }, { "input": "The paradigm shift of globalized research and conducting clinical studies at different geographic locations worldwide to access broader patient populations has resulted in increased need of correlating bioanalytical results generated in multiple laboratories, often across national borders.", "output": "There is no related enetity." }, { "input": "Cross - validations of bioanalytical methods are often implemented to assure the equivalency of the bioanalytical results is demonstrated.", "output": "There is no related enetity." }, { "input": "Regulatory agencies, such as the US FDA and European Medicines Agency, have included the requirement of cross - validations in their respective bioanalytical validation guidance and guidelines.", "output": "There is no related enetity." }, { "input": "While those documents provide high - level expectations, the detailed implementation is at the discretion of each individual organization.", "output": "There is no related enetity." }, { "input": "At Bristol - Myers Squibb, we practice a fit - for - purpose approach for conducting cross - validations for small - molecule bioanalytical methods using LC - MS / MS.", "output": "There is no related enetity." }, { "input": "A step - by - step proposal on the overall strategy, procedures and technical details for conducting a successful cross - validation is presented herein.", "output": "There is no related enetity." }, { "input": "A case study utilizing the proposed cross - validation approach to rule out method variability as the potential cause for high variance observed in PK studies is also presented.", "output": "There is no related enetity." }, { "input": "Ballistic InAs nanowire transistors.", "output": "There is no related enetity." }, { "input": "Ballistic transport of electrons at room temperature in top - gated InAs nanowire ( NW ) transistors is experimentally observed and theoretically examined.", "output": "There is no related enetity." }, { "input": "From length dependent studies, the low - field mean free path is directly extracted as ~ 150 nm.", "output": "There is no related enetity." }, { "input": "The mean free path is found to be independent of temperature due to the dominant role of surface roughness scattering.", "output": "There is no related enetity." }, { "input": "The mean free path was also theoretically assessed by a method that combines Fermi ' s golden rule and a numerical Schr o dinger - Poisson simulation to determine the surface scattering potential with the theoretical calculations being consistent with experiments.", "output": "There is no related enetity." }, { "input": "Near ballistic transport ( ~ 80 % of the ballistic limit ) is demonstrated experimentally for transistors with a channel length of ~ 60 nm, owing to the long mean free path of electrons in InAs NWs.", "output": "There is no related enetity." }, { "input": "Morphology - dependent trap formation in bulk heterojunction photodiodes.", "output": "There is no related enetity." }, { "input": "We show that local structural variation affects the rate of aging in nanostructured polymer solar cells by comparing time - resolved electrostatic force microscopy ( trEFM ) and conventional device measurements on model polymer blends.", "output": "There is no related enetity." }, { "input": "Specifically, we study photovoltaic devices made from 1: 1 blends of the polyfluorene copolymers poly ( 9, 9 ' - dioctylfluorene - co - bis - N, N ' - ( 4 - butylphenyl ) - bis - N, N ' - phenyl - 1, 4 - phenylene - diamine ) ( PFB ) and poly ( 9, 9 ' - dioctylfluorene - co - benzothiadiazole ) ( F8BT ).", "output": "polyfluorene, poly ( 9 , 9 ' - dioctylfluorene - co - bis - N , N ' - ( 4 - butylphenyl ) - bis - N , N ' - phenyl - 1 , 4 - phenylene - diamine, PFB, poly ( 9 , 9 ' - dioctylfluorene - co - benzothiadiazole, F8BT." }, { "input": "We photooxidize these films in situ using 365, 405, and 455 nm illumination under ambient conditions, with the wavelengths chosen to preferentially excite the different components.", "output": "There is no related enetity." }, { "input": "During photooxidation, we observe a faster loss of photocurrent generation from F8BT - rich domains, leaving the PFB - rich phases to show higher photoresponse even at wavelengths absorbed predominantly by F8BT.", "output": "F8BT, PFB, F8BT." }, { "input": "We propose that this effect is due to the more rapid degradation of PFB hole - transport pathways in the F8BT - rich regions, resulting in a loss of percolation pathways for hole transport in the F8BT - rich phase.", "output": "PFB, F8BT, F8BT." }, { "input": "First - principles prediction of the effects of temperature and solvent selection on the dimerization of benzoic acid.", "output": "benzoic acid." }, { "input": "We introduce a procedure of quantum chemical calculations ( B3P86 / 6 - 31G * * ) to study carboxylic acid dimerization and its correlation with temperature and properties of the solvent.", "output": "carboxylic acid." }, { "input": "Benzoic acid is chosen as a model system for studying dimerization via hydrogen bonding.", "output": "Benzoic acid, hydrogen." }, { "input": "Organic solvents are simulated using the self - consistent reaction field ( SCRF ) method with the polarized continuum model ( PCM ).", "output": "There is no related enetity." }, { "input": "The cyclic dimer is the most stable structure both in gas phase and solution.", "output": "There is no related enetity." }, { "input": "Dimer mono - and dihydrates could be found in the gas phase if acid molecules are in contact with water vapor.", "output": "mono - and dihydrates." }, { "input": "However, the formation of these hydrated conformers is very limited and cyclic dimer is the principal conformer to coexist with monomer acid in solution.", "output": "There is no related enetity." }, { "input": "Solvation of the cyclic dimer is more favorable compared to other complexes, partially due to the diminishing of hydrogen bonding capability and annihilation of dipole moments.", "output": "hydrogen." }, { "input": "Solvents have a strong effect on inducing dimer dissociation and this dependence is more pronounced at low dielectric constants.", "output": "There is no related enetity." }, { "input": "By accounting for selected terms in the total free energy of solvation, the solvation entropy could be incorporated to predict the dimer behavior at elevated temperatures.", "output": "There is no related enetity." }, { "input": "The temperature dependence of benzoic acid dimerization obtained by this technique is in good agreement with available experimental measurements, in which a tendency of dimer to dissociate is observed with increased temperatures.", "output": "benzoic acid." }, { "input": "In addition, dimer breakup is more sensitive to temperature in low dielectric environments rather than in solvents with a higher dielectric constant.", "output": "There is no related enetity." }, { "input": "Universal concept for the implementation of a single cleavable unit at tunable position in functional poly ( ethylene glycol ) s.", "output": "poly ( ethylene glycol ) s." }, { "input": "Poly ( ethylene glycol ) ( PEG ) with acid - sensitive moieties gained attention particularly for various biomedical applications, such as the covalent attachment of PEG ( PEGylation ) to protein therapeutics, the synthesis of stealth liposomes, and polymeric carriers for low - molecular - weight drugs.", "output": "Poly ( ethylene glycol ), PEG, PEG." }, { "input": "Cleavable PEGs are favored over their inert analogues because of superior pharmacodynamic and / or pharmacokinetic properties of their formulations.", "output": "PEGs." }, { "input": "However, synthetic routes to acetal - containing PEGs published up to date either require enormous efforts or result in ill - defined materials with a lack of control over the molecular weight.", "output": "acetal, PEGs." }, { "input": "Herein, we describe a novel methodology to implement a single acetaldehyde acetal in well - defined ( hetero ) functional poly ( ethylene glycol ) s with total control over its position.", "output": "acetaldehyde acetal, ( hetero ) functional poly ( ethylene glycol ) s." }, { "input": "To underline its general applicability, a diverse set of initiators for the anionic polymerization of ethylene oxide ( cholesterol, dibenzylamino ethanol, and poly ( ethylene glycol ) monomethyl ether ( mPEG ) ) was modified and used to synthesize the analogous labile PEGs.", "output": "ethylene oxide, cholesterol, dibenzylamino ethanol, poly ( ethylene glycol ) monomethyl ether, mPEG, PEGs." }, { "input": "The polyether bearing the cleavable lipid had a degree of polymerization of 46, was amphiphilic and exhibited a critical micelle concentration of 4. 20 mg. L ( - 1 ).", "output": "polyether." }, { "input": "From dibenzylamino ethanol, three heterofunctional PEGs with different molecular weights and labile amino termini were generated.", "output": "dibenzylamino ethanol, PEGs, amino." }, { "input": "The transformation of the amino functionality into the corresponding squaric acid ester amide demonstrated the accessibility of the cleavable functional group and activated the PEG for protein PEGylation, which was exemplarily shown by the attachment to bovine serum albumin ( BSA ).", "output": "amino, squaric acid ester amide, PEG." }, { "input": "Furthermore, turning mPEG into a macroinitiator with a cleavable hydroxyl group granted access to a well - defined poly ( ethylene glycol ) derivative bearing a single cleavable moiety within its backbone.", "output": "mPEG, hydroxyl, poly ( ethylene glycol )." }, { "input": "All the acetal - containing PEGs and PEG / protein conjugates were proven to degrade upon acidic treatment.", "output": "acetal, PEGs, PEG." }, { "input": "Enhancing biocompatibility of D - oligopeptide hydrogels by negative charges.", "output": "There is no related enetity." }, { "input": "Oligopeptide hydrogels are emerging as useful matrices for cell culture with commercial products on the market, but L - oligopeptides are labile to proteases.", "output": "There is no related enetity." }, { "input": "An obvious solution is to create D - oligopeptide hydrogels, which lack enzymatic recognition.", "output": "There is no related enetity." }, { "input": "However, D - oligopeptide matrices do not support cell growth as well as L - oligopeptide matrices.", "output": "There is no related enetity." }, { "input": "In addition to chiral interactions, many cellular activities are strongly governed by charge - charge interactions.", "output": "There is no related enetity." }, { "input": "In this work, the effects of chirality and charge on human mesenchymal stem cell ( hMSC ) behavior were studied using hydrogels assembled from oppositely charged oligopeptides.", "output": "There is no related enetity." }, { "input": "It was found that negative charges significantly improved hMSC viability and proliferation in D - oligopeptide gels but had little effect on their interactions with L - oligopeptide gels.", "output": "There is no related enetity." }, { "input": "This result points to the possibility of using charge and other factors to engineer biomaterials whose chirality is distinct from that of natural biomaterials, but whose performance is close to that of natural biomaterials.", "output": "There is no related enetity." }, { "input": "Magnetostructural correlation for rational design of Mn ( II ) hybrid - spin complexes.", "output": "Mn ( II )." }, { "input": "The magnetic properties of a series of manganese ( II ) diacetylacetonate and dihexafluoroacetylacetonate hybrid - spin complexes with neutral pyridine - based organic radicals were characterized theoretically by DFT calculations.", "output": "manganese ( II ) diacetylacetonate and dihexafluoroacetylacetonate, pyridine." }, { "input": "Three stable radicals, in which a radical group is bound in either para or meta position with respect to the pyridine nitrogen atom, were considered.", "output": "pyridine nitrogen." }, { "input": "The correct stable structures and multiplets of the complexes were obtained by full geometry optimization starting from an ideal structure.", "output": "There is no related enetity." }, { "input": "A total of three important geometry descriptors of the complexes were monitored and related to their magnetic characteristics.", "output": "There is no related enetity." }, { "input": "These structural parameters are ( i ) the torsion angle governing the conjugation of the organic radical m - PyNO ( anti versus gauche ), ( ii ) the coordination geometry of the acetyl acetonate ligands around the metal ion ( square versus rhombic ), and ( iii ) the relative orientation of the organic radical with respect to the acetyl acetonate plane ( parallel versus perpendicular ).", "output": "m - PyNO, acetyl acetonate, acetyl acetonate." }, { "input": "It was found that the magnetic properties are not sensitive to the orientation of the radicals with respect to the equatorial plane but do depend on the conformation of the organic radicals.", "output": "There is no related enetity." }, { "input": "Even a spin switch between the ferromagnetic ( S = ( 7 ) / ( 2 ) ) and antiferromagnetic ( S = ( 3 ) / ( 2 ) ) ground state was found to be feasible for one of the complexes upon variation of the organic radical geometry, namely, the dihedral angle between the organic radical moiety and the pyridine ring.", "output": "pyridine." }, { "input": "The pattern of molecular orbital overlap was determined to be the key factor governing the exchange coupling in the modeled systems.", "output": "There is no related enetity." }, { "input": "Bonding pi - type overlap provides antiferromagnetic coupling in all complexes of the para radicals.", "output": "There is no related enetity." }, { "input": "In the meta analogues, the spins are coupled through the sigma orbitals.", "output": "There is no related enetity." }, { "input": "A low - spin ground state occurs whenever a continuous sigma - overlap pathway is present in the complex.", "output": "There is no related enetity." }, { "input": "Ferromagnetic interaction requires sigma - pi orthogonality of the pyridine atomic orbitals and / or pi - antibonding Mn - pyridine natural orbital overlap.", "output": "pyridine, Mn, pyridine." }, { "input": "Using an estimate of the donor - acceptor energy stabilization, the affinity of a given Mn ( II ) d - orbital to mix with the sp ( 2 ) orbital from pyridine can be predicted.", "output": "Mn ( II ), pyridine." }, { "input": "Antioxidants and mucolytics in COPD management: when ( if ever ) and in whom?", "output": "There is no related enetity." }, { "input": "Chronic obstructive pulmonary disease ( COPD ) is a major cause of morbidity and mortality worldwide.", "output": "There is no related enetity." }, { "input": "Oxidative stress is an important mechanism in the pathogenesis of this disease.", "output": "There is no related enetity." }, { "input": "The oxidant / antioxidant imbalance occurring in smokers and patients with COPD is well established.", "output": "There is no related enetity." }, { "input": "Thus, therapeutic strategies targeting oxidative stress with pharmacological antioxidant agents or boosting the endogenous levels of antioxidants is likely to be beneficial as an adjunctive tool in the treatment of COPD patients.", "output": "There is no related enetity." }, { "input": "Thiol compounts such as N - acetyl - L - cysteine ( NAC ), carbocysteine, erdosteine, and fudosteine have been extensively studied.", "output": "Thiol, N - acetyl - L - cysteine, NAC, carbocysteine, erdosteine, fudosteine." }, { "input": "Although some results remain controversial, NAC and carbocysteine seem to have beneficial effect in patients not receiving inhaled corticosteroids who suffer from frequent exacerbations.", "output": "NAC, carbocysteine, corticosteroids." }, { "input": "In addition, other antioxidants like superoxide dismutase ( SOD ) mimetics and nuclear factor - erythroid 2 related factor 2 ( Nrf2 ) are shown to decrease markers of oxidative stress in patients with emphysema, while others like glutathione peroxidase ( GPx ) mimetics and NO synthase ( iNOS ) can prevent both inflammation and oxidative stress in clinical trials in vivo ( or in mouse models ).", "output": "superoxide, glutathione, NO." }, { "input": "In this article we review the effectiveness of various antioxidant factors in COPD and their potential beneficial effect in the treatment of the disease.", "output": "There is no related enetity." }, { "input": "Effect of rehabilitative exercise training on peripheral muscle remodelling in patients with COPD: targeting beyond the lungs.", "output": "There is no related enetity." }, { "input": "Locomotor muscle dysfunction and weakness are frequently observed in patients with Chronic Obstructive Pulmonary Disease ( COPD ).", "output": "There is no related enetity." }, { "input": "In addition to intolerable sensations of dyspnoea which importantly contribute to exercise limitation, intrinsic muscle abnormalities have also been implicated in inducing leg muscle fatigue / discomfort during exercise in these patients.", "output": "There is no related enetity." }, { "input": "It is, however, uncertain whether these intrinsic muscle abnormalities are linked to a specific ' myopathy ' or they constitute a consequence of the disease.", "output": "There is no related enetity." }, { "input": "Besides muscle disuse, other factors which may contribute to peripheral muscle dysfunction include systemic inflammation, oxidative and nitrosative stress, chronic hypoxia, corticosteroid use and malnutrition.", "output": "There is no related enetity." }, { "input": "There is clear evidence that rehabilitative exercise training induces significant skeletal muscle fibre remodelling and improvements in functionality in the absence of changes in lung function.", "output": "There is no related enetity." }, { "input": "The ultimate purpose of this review is to identify and summarize the results of studies implementing diverse types of exercise training on peripheral muscle fibre phenotypic and genotypic modifications in patients with COPD.", "output": "There is no related enetity." }, { "input": "Clonazepam for the treatment of panic disorder.", "output": "Clonazepam." }, { "input": "Clonazepam was initially licensed as an anti - epileptic agent, but its use in a wide variety of psychiatric conditions, including panic disorder ( PD ) has now been well established.", "output": "Clonazepam." }, { "input": "This overview evaluates the current role of clonazepam alone or in combination with antidepressants and / or behavioral therapy in the treatment of PD.", "output": "clonazepam." }, { "input": "We review the data establishing the use of clonazepam in the treatment of PD as well as new information, particularly confirmation of longterm efficacy and safety.", "output": "clonazepam." }, { "input": "We also discuss a regimen for safely tapered withdrawal of clonazepam, the characteristics of the respiratory subtype of PD, and CO2 - induced panic attacks as a diagnostic measure and predictor for therapeutic success.", "output": "clonazepam, CO2." }, { "input": "It has been shown that panic attacks can more readily be induced by CO2 in PD patients with the respiratory subtype than those with the non - respiratory subtype.", "output": "CO2." }, { "input": "More than 25 years after the first report of efficacy in PD in 1984, clonazepam, alone or combined with selective serotonin reuptake inhibitors ( SSRIs ) and / or behavioral therapy, remains an important therapeutic modality for the management of PD.", "output": "clonazepam, serotonin." }, { "input": "Effects of formation conditions on the physicochemical properties, aggregation, and phase transformation of iron oxide nanoparticles.", "output": "iron oxide." }, { "input": "In this work, hematite transformation from a precursor 6 - line ferrihydrite phase was investigated by systematically altering the forced hydrolysis hematite synthesis.", "output": "hematite, ferrihydrite, hematite." }, { "input": "Specifically, we used a combination of in situ and ex situ characterization techniques to examine the effects of varying the Fe ( III ) injection rates and cooling methods on the hematite and 6 - line ferrihydrite nanoparticle size, isoelectric point, mineral phase, and aggregation.", "output": "Fe ( III ), hematite, ferrihydrite." }, { "input": "Finally, As ( V ) adsorption experiments were performed to determine how the two iron oxide phases existed in the reaction system.", "output": "As ( V ), iron oxide." }, { "input": "Nanoparticle synthesis thermodynamics and kinetics were found to control the extent of distinct 6 - line ferrihydrite phases in the iron oxide nanoparticle solutions, as well as the particle size and isoelectric point.", "output": "ferrihydrite, iron oxide." }, { "input": "Conversion of 6 - line ferrihydrite to hematite was greatly influenced by the degree of aggregation ( determined by synthesis conditions ) during drying.", "output": "ferrihydrite, hematite." }, { "input": "As ( V ) adsorption experiments revealed that 6 - line ferrihydrite and hematite exist as a linear combination of two separate phases.", "output": "As ( V ), ferrihydrite, hematite." }, { "input": "These results provide unique information regarding how in situ iron oxide nanoparticle properties can direct their ex situ behavior.", "output": "iron oxide." }, { "input": "The evolution of S100B inhibitors for the treatment of malignant melanoma.", "output": "There is no related enetity." }, { "input": "Malignant melanoma continues to be an extremely fatal cancer due to a lack of viable treatment options for patients.", "output": "There is no related enetity." }, { "input": "The calcium - binding protein S100B has long been used as a clinical biomarker, aiding in malignant melanoma staging and patient prognosis.", "output": "calcium." }, { "input": "However, the discovery of p53 as a S100B target and the consequent impact on cell apoptosis redirected research efforts towards the development of inhibitors of this S100B - p53 interaction.", "output": "There is no related enetity." }, { "input": "Several approaches, including computer - aided drug design, fluorescence polarization competition assays, NMR, x - ray crystallography and cell - based screens have been performed to identify compounds that block the S100B - p53 association, reactivate p53 transcriptional activities and induce cancer cell death.", "output": "There is no related enetity." }, { "input": "Eight promising compounds, including pentamidine, are presented in this review and the potential for future modifications is discussed.", "output": "pentamidine." }, { "input": "Synthesis of compound derivatives will likely exhibit increased S100B affinity and mimic important S100B - target dynamic properties that will result in high specificity.", "output": "There is no related enetity." }, { "input": "HR - MAS NMR Spectroscopy of Reconstructed Human Epidermis: Potential for the in Situ Investigation of the Chemical Interactions between Skin Allergens and Nucleophilic Amino Acids.", "output": "Amino Acids." }, { "input": "High - resolution magic angle spinning ( HR - MAS ) is a nuclear magnetic resonance ( NMR ) technique that enables the characterization of metabolic phenotypes / metabolite profiles of cells, tissues, and organs, under both normal and pathological conditions, without resorting to time - consuming extraction techniques.", "output": "There is no related enetity." }, { "input": "In this article, we explore a new domain of application of HR - MAS, namely, reconstructed human epidermis ( RHE ) and the in situ observation of chemical interactions between skin sensitizers and nucleophilic amino acids.", "output": "amino acids." }, { "input": "First, the preparation, storage, and analysis of RHE were optimized, and this work demonstrated that HR - MAS NMR was well adapted for investigating RHE with spectra of good quality allowing qualitative as well as quantitative studies of metabolites.", "output": "There is no related enetity." }, { "input": "Second, in order to study the response of RHE to chemical sensitizers, the ( ( 13 ) C ) methyldodecanesulfonate was chosen as an NMR probe, and we compared adducts formed on human serum albumin ( HSA ) in solution and adducts formed in RHE.", "output": "( ( 13 ) C ) methyldodecanesulfonate." }, { "input": "Thus, while the modification of proteins or peptides in solution takes several days to lead to a significant amount of modification, in RHE the modifications of nucleophilic amino acids were observable already at 24 h.", "output": "amino acids." }, { "input": "The chemioselectivity also appeared to be different with major modifications taking place on histidine, methionine, and cysteine residues in RHE, while on HSA, significant modifications were observed on lysine residues with the formation of methylated and dimethylated amino groups.", "output": "histidine, methionine, cysteine, lysine, amino." }, { "input": "We thus demonstrated that RHE could be used to investigate in situ chemical interactions taking place between skin sensitizers and nucleophilic amino acids.", "output": "amino acids." }, { "input": "This opens perspectives for the molecular understanding of the skin immune system activation by sensitizing chemicals.", "output": "There is no related enetity." }, { "input": "The RNA polymerase of marine cyanophage Syn5.", "output": "There is no related enetity." }, { "input": "A single subunit DNA - dependent RNA polymerase was identified and purified to apparent homogeneity from cyanophage Syn5 that infects the marine cyanobacteria Synechococcus.", "output": "There is no related enetity." }, { "input": "Syn5 is homologous to bacteriophage T7 that infects Escherichia coli.", "output": "There is no related enetity." }, { "input": "Using the purified enzyme its promoter has been identified by examining transcription of segments of Syn5 DNA and sequencing the 5 ' - termini of the transcripts.", "output": "There is no related enetity." }, { "input": "Only two Syn5 RNAP promoters, having the sequence 5 ' - ATTGGGCACCCGTAA - 3 ', are found within the Syn5 genome.", "output": "There is no related enetity." }, { "input": "One promoter is located within the Syn5 RNA polymerase gene and the other is located close to the right genetic end of the genome.", "output": "There is no related enetity." }, { "input": "The purified enzyme and its promoter have enabled a determination of the requirements for transcription.", "output": "There is no related enetity." }, { "input": "Unlike the salt - sensitive bacteriophage T7 RNA polymerase, this marine RNA polymerase requires 160 mm potassium for maximal activity.", "output": "potassium." }, { "input": "The optimal temperature for Syn5 RNA polymerase is 24 degrees C, much lower than that for T7 RNA polymerase.", "output": "There is no related enetity." }, { "input": "Magnesium is required as a cofactor although some activity is observed with ferrous ions.", "output": "Magnesium, ferrous." }, { "input": "Syn5 RNA polymerase is more efficient in utilizing low concentrations of ribonucleotides than T7 RNA polymerase.", "output": "ribonucleotides." }, { "input": "Super - stable ultrafine beta - tungsten nanocrystals with metastable phase and related magnetism.", "output": "beta - tungsten." }, { "input": "Ultrafine tungsten nanocrystals ( average size of 3 nm ) with a metastable phase ( beta - tungsten with A15 structure, beta - W ) have been prepared by laser ablation of tungsten in liquid nitrogen.", "output": "tungsten, beta - tungsten, W, tungsten, nitrogen." }, { "input": "The as - prepared metastable nanocrystals exhibited super - stablity, and can keep the same metastable structure over a period of 6 months at room temperature.", "output": "There is no related enetity." }, { "input": "This super - stability is attributed to the nanosized confinement effect of ultrafine nanocrystals.", "output": "There is no related enetity." }, { "input": "The magnetism measurements showed that the beta - W nanocrystals have weak ferromagnetic properties at 2 K, which may arise from surface defects and unpaired electrons on the surface of the ultrafine nanocrystals.", "output": "W." }, { "input": "These findings provided useful information for the application of ultrafine beta - W nanocrystals in microelectronics and spintronics.", "output": "W." }, { "input": "The comprehensive epigenome map of piRNA clusters.", "output": "There is no related enetity." }, { "input": "PIWI - interacting RNA ( piRNA ) clusters act as anti - transposon / retrovirus centers.", "output": "There is no related enetity." }, { "input": "Integration of selfish jumping elements into piRNA clusters generates de novo piRNAs, which in turn exert trans - silencing activity against these elements in animal gonads.", "output": "There is no related enetity." }, { "input": "To date, neither genome - wide chromatin modification states of piRNA clusters nor a mode for piRNA precursor transcription have been well understood.", "output": "There is no related enetity." }, { "input": "Here, to understand the chromatin landscape of piRNA clusters and how piRNA precursors are generated, we analyzed the transcriptome, transcription start sites ( TSSs ) and the chromatin landscape of the BmN4 cell line, which harbors the germ - line piRNA pathway.", "output": "There is no related enetity." }, { "input": "Notably, our epigenomic map demonstrated the highly euchromatic nature of unique piRNA clusters.", "output": "There is no related enetity." }, { "input": "RNA polymerase II was enriched for TSSs that transcribe piRNA precursors.", "output": "There is no related enetity." }, { "input": "piRNA precursors possessed 5 ' - cap structures as well as 3 ' - poly A - tails.", "output": "There is no related enetity." }, { "input": "Collectively, we envision that the euchromatic, opened nature of unique piRNA clusters or piRNA cluster - associated TSSs allows piRNA clusters to capture new insertions efficiently.", "output": "There is no related enetity." }, { "input": "A three - generational study of In ovo exposure to PBDE - 99 in the zebra finch.", "output": "PBDE - 99." }, { "input": "Based on a literature review of avian data for polybrominated diphenyl ethers ( PBDEs ), ecologically relevant doses, low ( 10 ng / egg ), medium ( 100 ng / egg ), and high ( 1, 000 ng / egg ) of the 2, 2 ', 4, 4 ', 5 - pentabromodiphenyl ether ( BDE - 99 ) congener along with dimethylsulfoxide ( DMSO ) control were injected into the yolk sac of un - incubated eggs of zebra finch, Taeniopygia guttata.", "output": "polybrominated diphenyl ethers, PBDEs, 2 , 2 ' , 4 , 4 ' , 5 - pentabromodiphenyl ether, BDE - 99, dimethylsulfoxide, DMSO." }, { "input": "Offspring development and adult phenotype were followed over three generations.", "output": "There is no related enetity." }, { "input": "No effects of in ovo PBDE exposure on hatching success, chick growth, thyroid hormone levels, or hematological traits were measured at sexual maturity ( 90 d posthatching ).", "output": "PBDE." }, { "input": "However, the authors did detect significant effects of BDE - 99 treatment on adult phenotype of in ovo - exposed birds by breeding observations, in which clutch size was significantly smaller in all PBDE - dosed birds ( low, medium, and high ) compared with controls.", "output": "BDE - 99, PBDE." }, { "input": "A trend was also seen for longer laying intervals in PBDE - dosed birds ( 13 - 14 d ) compared with control birds ( 8 d ).", "output": "PBDE." }, { "input": "In addition, a significant effect of PBDE was found on growth of the second - generation offspring of in ovo - treated females; body mass was significantly lower in the high - PBDE dosed birds compared with controls from hatch through to fledging ( day 30 ).", "output": "PBDE, PBDE." }, { "input": "The authors found no evidence of effects over the longer term and in successive generations, whether in adult, reproductive phenotype of the second - generation offspring of in ovo - treated birds, or in the growth of their ( third - generation ) offspring.", "output": "There is no related enetity." }, { "input": "Their results suggest that egg levels as low as 10 ng / g BDE - 99 may affect reproduction in small passerines by reducing clutch size.", "output": "BDE - 99." }, { "input": "Assessing ongoing sources of dissolved - phase polychlorinated biphenyls in a contaminated stream.", "output": "polychlorinated biphenyls." }, { "input": "Few studies assess the potential of ongoing sources of \" fresh \" polychlorinated biphenyls ( PCBs ) to aquatic systems when direct discharge to the environment has been eliminated.", "output": "polychlorinated biphenyls, PCBs." }, { "input": "In the present study, the authors used single - layered, low - density polyethylene samplers ( PEs ) to measure total PCB concentrations, congener profiles, and enantiomeric fractions ( EFs ) in a contaminated stream and to provide multiple lines of evidence for assessing ongoing inputs of PCB.", "output": "polyethylene, PCB, PCB." }, { "input": "Concentrations were well above background levels that have been monitored for years.", "output": "There is no related enetity." }, { "input": "Concentrations significantly increased with distance, the farthest downstream PE concentrations being almost five times greater than those at 79 m downstream of a historical point source.", "output": "There is no related enetity." }, { "input": "The PCBs in the PEs at 79 m downstream of the contamination source were dominated by low K ( OW ) congeners, similar to those in the mixture of Aroclors 1016 and 1254 ( 4: 1 v / v ) historically released from the former capacitor manufacturer.", "output": "PCBs, Aroclors 1016 and 1254." }, { "input": "The only two chiral congeners detected in the PEs downstream were PCBs 91 and 95.", "output": "PCBs." }, { "input": "The EF values were nonracemic for PCB 91, while the values were either racemic or near racemic for PCB 95.", "output": "PCB, PCB." }, { "input": "Increased PCB concentrations with distance and a congener composition of predominantly low - weight congeners in the PEs at 79 m downstream of the plant site suggested an ongoing PCB source from the plant site.", "output": "PCB, PCB." }, { "input": "Chiral signatures suggested aerobic biotransformation of dissolved PCBs but did not shed any light on possible ongoing PCB inputs.", "output": "PCBs, PCB." }, { "input": "Photonic modulation of electron transfer with switchable phase inversion.", "output": "There is no related enetity." }, { "input": "Photochromes may be reversibly photoisomerized between two metastable states and their properties can influence, and be influenced by, other chromophores in the same molecule through energy or electron transfer.", "output": "There is no related enetity." }, { "input": "In the photochemically active molecular tetrad described here, a porphyrin has been covalently linked to a fullerene electron acceptor, a quinoline - derived dihydroindolizine photochrome, and a dithienylethene photochrome.", "output": "porphyrin, fullerene, quinoline, dihydroindolizine, dithienylethene." }, { "input": "The porphyrin first excited singlet state undergoes photoinduced electron transfer to the fullerene to generate a charge - separated state.", "output": "porphyrin, fullerene." }, { "input": "The quantum yield of charge separation is modulated by the two photochromes: one isomer of each quenches the porphyrin excited state, reducing the quantum yield of electron transfer to near zero.", "output": "porphyrin." }, { "input": "Interestingly, when the molecule is illuminated with white light, the quantum yield decreases as the white light intensity is increased, generating an out - of - phase response of the quantum yield to white light.", "output": "There is no related enetity." }, { "input": "However, when the same experiment is performed in the presence of additional, steady - state UV illumination, a phase inversion occurs.", "output": "There is no related enetity." }, { "input": "The quantum yield of electron transfer now increases with increasing white light intensity.", "output": "There is no related enetity." }, { "input": "Such effects illustrate emergent complexity in a relatively simple system and could find applications in molecular logic, photochemical labeling and drug delivery, and photoprotection for artificial photosynthetic molecules.", "output": "There is no related enetity." }, { "input": "The photochemistry leading to this behavior is discussed.", "output": "There is no related enetity." }, { "input": "Dendrimer - based multivalent vancomycin nanoplatform for targeting the drug - resistant bacterial surface.", "output": "vancomycin." }, { "input": "Vancomycin represents the preferred ligand for bacteria - targeting nanosystems.", "output": "Vancomycin." }, { "input": "However, it is inefficient for emerging vancomycin - resistant species because of its poor affinity to the reprogrammed cell wall structure.", "output": "vancomycin." }, { "input": "This study demonstrates the use of a multivalent strategy as an effective way for overcoming such an affinity limitation in bacteria targeting.", "output": "There is no related enetity." }, { "input": "We designed a series of fifth generation ( G5 ) poly ( amidoamine ) ( PAMAM ) dendrimers tethered with vancomycin at the C - terminus at different valencies.", "output": "poly ( amidoamine ), PAMAM, vancomycin, C." }, { "input": "We performed surface plasmon resonance ( SPR ) studies to determine their binding avidity to two cell wall models, each made with either a vancomycin - susceptible ( D ) - Ala - ( D ) - Ala or vancomycin - resistant ( D ) - Ala - ( D ) - Lac cell wall precursor.", "output": "vancomycin, ( D ) - Ala - ( D ) - Ala, vancomycin, ( D ) - Ala - ( D ) - Lac." }, { "input": "These conjugates showed remarkable enhancement in avidity in the cell wall models tested, including the vancomycin - resistant model, which had an increase in avidity of four to five orders of magnitude greater than free vancomycin.", "output": "vancomycin, vancomycin." }, { "input": "The tight adsorption of the conjugate to the model surface corresponded with its ability to bind vancomycin - susceptible Staphylococcus aureus bacterial cells in vitro as imaged by confocal fluorescent microscopy.", "output": "vancomycin." }, { "input": "This vancomycin platform was then used to fabricate the surface of iron oxide nanoparticles by coating them with the dendrimer conjugates, and the resulting dendrimer - covered magnetic nanoparticles were demonstrated to rapidly sequester bacterial cells.", "output": "vancomycin, iron oxide." }, { "input": "In summary, this article investigates the biophysical basis of the tight, multivalent association of dendrimer - based vancomycin conjugates to the bacterial cell wall, and proposes a potential new use of this nanoplatform in targeting Gram - positive bacteria.", "output": "vancomycin." }, { "input": "Short - channel transistors constructed with solution - processed carbon nanotubes.", "output": "carbon." }, { "input": "We develop short - channel transistors using solution - processed single - walled carbon nanotubes ( SWNTs ) to evaluate the feasibility of those SWNTs for high - performance applications.", "output": "carbon." }, { "input": "Our results show that even though the intrinsic field - effect mobility is lower than the mobility of CVD nanotubes, the electrical contact between the nanotube and metal electrodes is not significantly affected.", "output": "There is no related enetity." }, { "input": "It is this contact resistance which often limits the performance of ultrascaled transistors.", "output": "There is no related enetity." }, { "input": "Moreover, we found that the contact resistance is lowered by the introduction of oxygen treatment.", "output": "oxygen." }, { "input": "Therefore, high - performance solution - processed nanotube transistors with a 15 nm channel length were obtained by combining a top - gate structure and gate insulators made of a high - dielectric - constant ZrO ( 2 ) film.", "output": "ZrO ( 2 )." }, { "input": "The combination of these elements yields a performance comparable to that obtained with CVD nanotube transistors, which indicates the potential for using solution - processed SWNTs for future aggressively scaled transistor technology.", "output": "There is no related enetity." }, { "input": "Freeze fracture approach to directly visualize wetting transitions on nanopatterned superhydrophobic silicon surfaces: more than a proof of principle.", "output": "silicon." }, { "input": "Freeze fracturing is applied to make the wetting behavior of artificially nanopatterned Si surfaces directly visible.", "output": "Si." }, { "input": "For this purpose, almost hexagonally arranged nanopillars of fixed areal density ( 127 mu m ( - 2 ) ) and diameters ( 35 nm ) but varying heights ( 40 - 150 nm ) were fabricated on silicon.", "output": "silicon." }, { "input": "Measurement of contact angles ( CAs ) including hysteresis allowed to distinguish between the Wenzel ( W ) and the Cassie - Baxter ( CB ) states with droplets completely wetting the pillars or residing on top of them, respectively.", "output": "There is no related enetity." }, { "input": "Providing additional depth contrast by evaporating the ice replica with thin carbon and ( typically 3 nm ) platinum layers under 45 degrees allowed resolving 3D features of 5 nm within the ice replica.", "output": "carbon, platinum." }, { "input": "In this way, laterally sharp transitions from CB - to W - states could be revealed, indicating the formation of zero - curvature water surfaces even on the nanoscale.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of indenoisoquinolines that inhibit both tyrosyl - DNA phosphodiesterase I ( Tdp1 ) and topoisomerase I ( Top1 ).", "output": "indenoisoquinolines." }, { "input": "Tyrosyl - DNA phosphodiesterase I ( Tdp1 ) plays a key role in the repair of damaged DNA resulting from the topoisomerase I ( Top1 ) inhibitor camptothecin and a variety of other DNA - damaging anticancer agents.", "output": "camptothecin." }, { "input": "This report documents the design, synthesis, and evaluation of new indenoisoquinolines that are dual inhibitors of both Tdp1 and Top1.", "output": "indenoisoquinolines." }, { "input": "Enzyme inhibitory data and cytotoxicity data from human cancer cell cultures were used to establish structure - activity relationships.", "output": "There is no related enetity." }, { "input": "The potencies of the indenoisoquinolines against Tdp1 ranged from 5 mu M to 111 mu M, which places the more active compounds among the most potent known inhibitors of this target.", "output": "indenoisoquinolines." }, { "input": "The cytotoxicity mean graph midpoints ranged from 0. 02 to 2. 34 mu M.", "output": "There is no related enetity." }, { "input": "Dual Tdp1 - Top1 inhibitors are of interest because the Top1 and Tdp1 inhibitory activities could theoretically work synergistically to create more effective anticancer agents.", "output": "There is no related enetity." }, { "input": "Morphologies of ABC triblock terpolymer melts containing poly ( cyclohexadiene ): effects of conformational asymmetry.", "output": "poly ( cyclohexadiene )." }, { "input": "We have synthesized linear ABC triblock terpolymers containing poly ( 1, 3 - cyclohexadiene ), PCHD, as an end block and characterized their morphologies in the melt.", "output": "poly ( 1 , 3 - cyclohexadiene ), PCHD." }, { "input": "Specifically, we have studied terpolymers containing polystyrene ( PS ), polybutadiene ( PB ), and polyisoprene ( PI ) as the other blocks.", "output": "polystyrene, polybutadiene, polyisoprene." }, { "input": "Systematically varying the ratio of 1, 2 - / 1, 4 - microstructures of poly ( 1, 3 - cyclohexadiene ), we have studied the effects of conformational asymmetry among the three blocks on the morphologies using transmission electron microscopy ( TEM ), small - angle X - ray scattering ( SAXS ), and self - consistent field theory ( SCFT ) performed with PolySwift + +.", "output": "poly ( 1 , 3 - cyclohexadiene )." }, { "input": "Our work reveals that the triblock terpolymer melts containing a high percentage of 1, 2 - microstructures in the PCHD block are disordered at 110 degrees C for all the samples, independent of sequence and volume fraction of the blocks.", "output": "PCHD." }, { "input": "In contrast, the triblock terpolymer melts containing a high percentage of 1, 4 - microstructure form regular morphologies known from the literature.", "output": "There is no related enetity." }, { "input": "The accuracy of the SCFT calculations depends on calculating the chi parameters that quantify the repulsive interactions between different monomers.", "output": "There is no related enetity." }, { "input": "Simulations using chi values obtained from solubility parameters and group contribution methods are unable to reproduce the morphologies as seen in the experiments.", "output": "There is no related enetity." }, { "input": "However, SCFT calculations accounting for the enhancement of the chi parameter with an increase in the conformational asymmetry lead to an excellent agreement between theory and experiments.", "output": "There is no related enetity." }, { "input": "These results highlight the importance of conformational asymmetry in tuning the chi parameter and, in turn, morphologies in block copolymers.", "output": "There is no related enetity." }, { "input": "Bioreducible polymers as a determining factor for polyplex decomplexation rate and transfection.", "output": "polyplex." }, { "input": "Polyplex formation ( complexation ) and gene release from the polyplexes ( decomplexation ) are major events in polymeric gene delivery; however, the effect of the decomplexation rate on transfection has been rarely investigated.", "output": "Polyplex, polyplexes." }, { "input": "This study employed mixed polymers of poly ( ( L ) - lysine ) ( PLL: MW ~ 7. 4 kDa ) and reducible PLL ( RPLL ) ( MW ~ 6. 7 kDa ) to design decomplexation rate - controllable PLL ( 100 - x ) RPLL ( x ) / pDNA complexes ( PRL ( x ) polyplexes ).", "output": "poly ( ( L ) - lysine ), PLL, PLL, PLL, polyplexes." }, { "input": "The transfection efficiency of a model gene ( luciferase ) in MCF7 and HEK293 cell lines increased with increasing x ( RPLL content ) in the PRL ( x ) polyplexes until peaking at x = 2. 5 and 10, respectively, after which point transfection efficiency declined rapidly.", "output": "polyplexes." }, { "input": "In MCF7 cells, PRL ( 2. 5 ) polyplex produced 3 or 223 times higher gene expression than PLL or RPLL polyplexes, respectively.", "output": "polyplex, PLL, polyplexes." }, { "input": "Similarly, the transfection efficiency of PRL ( 10 ) polyplex - transfected HEK293 cells was 3. 8 or 67 times higher than that of PLL or RPLL polyplexes, respectively.", "output": "polyplex, PLL, polyplexes." }, { "input": "The transfection results were not apparently related to the particle size, surface charge, complexation / compactness, cellular uptake, or cytotoxicity of the tested polyplexes.", "output": "polyplexes." }, { "input": "However, the decomplexation rate varied by RPLL content in the polyplexes, which in turn influenced the gene transfection.", "output": "polyplexes." }, { "input": "The nuclear localization of pDNA delivered by PRL ( x ) polyplexes showed a similar trend to their transfection efficiencies.", "output": "polyplexes." }, { "input": "This study suggests that an optimum decomplexation rate may result in high nuclear localization of pDNA and transfection.", "output": "There is no related enetity." }, { "input": "Understanding in decomplexation and intracellular localization of pDNA may help develop more effective polyplexes.", "output": "polyplexes." }, { "input": "Exploring the Toxicity of a Bismuth - Asparagine Coordination Polymer on the Early Development of Zebrafish Embryos.", "output": "Bismuth, Asparagine." }, { "input": "Nanoparticles are widely used in nanomedicine, raising concerns about their toxicity.", "output": "There is no related enetity." }, { "input": "In this study, the toxicity of bismuth - asparagine coordination polymer spheres ( BACP - 2 ) was assessed in zebrafish embryos.", "output": "bismuth, asparagine." }, { "input": "Injection of 1 - 4 cell stage embryos with BACP - 2 resulted in smaller head size ( particularly smaller eye size ), shorter body length, and pericardial edemas.", "output": "There is no related enetity." }, { "input": "The severity and occurrence of the resulting phenotype were concentration - dependent.", "output": "There is no related enetity." }, { "input": "The expression of genes such as krox20, orthodenticle homeobox 2 ( otx2 ), and cardiac myosin light chain - 2 ( cmlc2 ) indicates that the effects of BACP - 2 on the head and heart were related to changes in gene expression patterns.", "output": "There is no related enetity." }, { "input": "A delay in epiboly was observed, and the expression levels of the no tail ( ntl ) gene indicated that the delay in epiboly resulted both from the effect of BACP - 2 on cell migration during epiboly and from slow growth.", "output": "There is no related enetity." }, { "input": "These findings indicate that BACP - 2 exhibits concentration - dependent developmental toxicity, providing insight into the nanotoxicity of bismuth derivatives, which must be rigorously evaluated with respect to toxicity before their application in nanomedicine.", "output": "bismuth." }, { "input": "Synthesis and evaluation of diphenylphosphinic amides and diphenylphosphine oxides as inhibitors of Kv1. 5.", "output": "diphenylphosphinic amides, diphenylphosphine oxides." }, { "input": "Diphenylphosphinic amides and diphenylphosphine oxides have been synthesized and tested as inhibitors of the Kv1. 5 potassium ion channel as a possible treatment for atrial fibrillation.", "output": "Diphenylphosphinic amides, diphenylphosphine oxides, potassium." }, { "input": "In vitro structure - activity relationships are discussed and several compounds with Kv1. 5 IC ( 50 ) values of < 0. 5 mu M were discovered.", "output": "There is no related enetity." }, { "input": "Selectivity over the ventricular IKs current was monitored and selective compounds were found.", "output": "There is no related enetity." }, { "input": "Results from a rabbit PD - model are included.", "output": "There is no related enetity." }, { "input": "Novel in vivo active anti - malarials based on a hydroxy - ethyl - amine scaffold.", "output": "hydroxy - ethyl - amine." }, { "input": "A novel series of anti - malarials, based on a hydroxy - ethyl - amine scaffold, initially identified as peptidomimetic protease inhibitors is described.", "output": "hydroxy - ethyl - amine." }, { "input": "Combination of the hydroxy - ethyl - amine anti - malarial phramacophore with the known Mannich base pharmacophore of amodiaquine ( 57 ) resulted in promising in vivo active novel derivatives.", "output": "hydroxy - ethyl - amine, Mannich base, amodiaquine." }, { "input": "Live - cell imaging of p53 interactions using a novel Venus - based bimolecular fluorescence complementation system.", "output": "There is no related enetity." }, { "input": "p53 plays an important role in regulating a wide variety of cellular processes, such as cell cycle arrest and / or apoptosis.", "output": "There is no related enetity." }, { "input": "Dysfunction of p53 is frequently associated with several pathologies, such as cancer and neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "In recent years substantial progress has been made in developing novel p53 - activating molecules.", "output": "There is no related enetity." }, { "input": "Importantly, modulation of p53 interaction with its main inhibitor, Mdm2, has been highlighted as a promising therapeutic target.", "output": "There is no related enetity." }, { "input": "In this regard, bimolecular fluorescence complementation ( BiFC ) analysis, by providing direct visualization of protein interactions in living cells, offers a straightforward method to identify potential modulators of protein interactions.", "output": "There is no related enetity." }, { "input": "In this study, we developed a simple and robust Venus - based BiFC system to screen for modulators of p53 - p53 and p53 - Mdm2 interactions in live mammalian cells.", "output": "There is no related enetity." }, { "input": "We used nutlin - 3, a well - known disruptor of p53 - Mdm2 interaction, to validate the specificity of the assay.", "output": "nutlin - 3." }, { "input": "The reduction of BiFC signal mediated by nutlin - 3 was correlated with an increase in Puma transactivation, PARP cleavage, and cell death.", "output": "nutlin - 3." }, { "input": "Finally, this novel BiFC approach was exploited to identify potential modulators of p53 - Mdm2 complex formation among a commercially available chemical library of 33 protein phosphatase inhibitors.", "output": "There is no related enetity." }, { "input": "Our results constitute \" proof - of - concept \" that this model has strong potential as an alternative to traditional target - based drug discovery strategies.", "output": "There is no related enetity." }, { "input": "Identification of new modulators of p53 - p53 and p53 - Mdm2 interactions will be useful to achieve synergistic drug efficacy with currently used anti - tumor therapies.", "output": "There is no related enetity." }, { "input": "Emerging targets in lipid - based therapy.", "output": "There is no related enetity." }, { "input": "The use of prostaglandins and NSAIDS in the clinic has proven that lipid mediators and their associated pathways make attractive therapeutic targets.", "output": "prostaglandins." }, { "input": "When contemplating therapies involving lipid pathways, several basic agents come to mind.", "output": "There is no related enetity." }, { "input": "There are the enzymes and accessory proteins that lead to the metabolism of lipid substrates, provided through diet or through actions of lipases, the subsequent lipid products, and finally the lipid sensors or receptors.", "output": "There is no related enetity." }, { "input": "There is abundant evidence that molecules along this lipid continuum can serve as prognostic and diagnostic indicators and are in fact viable therapeutic targets.", "output": "There is no related enetity." }, { "input": "Furthermore, lipids themselves can be used as therapeutics.", "output": "There is no related enetity." }, { "input": "Despite this, the vernacular dialog pertaining to \" biomarkers \" does not routinely include mention of lipids, though this is rapidly changing.", "output": "There is no related enetity." }, { "input": "Collectively these agents are becoming more appreciated for their respective roles in diverse disease processes from cancer to preterm labor and are receiving their due appreciation after decades of ground work in the lipid field.", "output": "There is no related enetity." }, { "input": "By relating examples of disease processes that result from dysfunction along the lipid continuum, as well as examples of lipid therapies and emerging technologies, this review is meant to inspire further reading and discovery.", "output": "There is no related enetity." }, { "input": "Inhibition of Th1 / Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin.", "output": "flavonoid, icariin." }, { "input": "Inflammatory bowel disease ( IBD ) is a chronic inflammatory disorder in the intestine which involves overproduction of pro - inflammatory cytokines and excessive functions of inflammatory cells.", "output": "There is no related enetity." }, { "input": "However, current treatments for IBD may have potential adverse effects including steroid dependence, infections and lymphoma.", "output": "steroid." }, { "input": "Therefore new therapies or drug candidates for the treatment of IBD are desperately needed.", "output": "There is no related enetity." }, { "input": "In the present study we found that icariin, a major bioactive compound from plants in Epimedium family, exerted protective effect on intestinal inflammation in mice induced by dextran sulfate sodium.", "output": "icariin, sulfate, sodium." }, { "input": "Oral administration of icariin significantly attenuated the disease progression and alleviated the pathological changes of colitis.", "output": "icariin." }, { "input": "It also inhibited the production of pro - inflammatory cytokines and expression of p - p65, p - STAT1 and p - STAT3 in colon tissues.", "output": "There is no related enetity." }, { "input": "Further study showed that icariin dose - dependently inhibited the proliferation and activation of T lymphocytes, and suppressed pro - inflammatory cytokine levels of activated T cells.", "output": "icariin." }, { "input": "Moreover, icariin treatment inhibited the phosphorylations of STAT1 and STAT3 in CD4 ( + ) T cells, which were the crucial transcription factors for Th1 and Th17 respectively.", "output": "icariin." }, { "input": "Taken together, these results indicate that icariin is a potential therapeutic agent for IBD.", "output": "icariin." }, { "input": "Short and long - term exposure of CNS cell lines to BPA - f a radiosensitizer for Boron Neutron Capture Therapy: safety dose evaluation by a battery of cytotoxicity tests.", "output": "Boron." }, { "input": "Despite the current clinical use of boronophenylalanine - fructose ( BPA - f ), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent.", "output": "boronophenylalanine, fructose, BPA - f." }, { "input": "We evaluated the potential risk of primary BPA - f toxicity before neutronic irradiation at different concentrations ( 0 - 100 mu gBeq / ml ) after short - and long - term exposure ( 4 - 48h and 7 - 10 days ), using a battery of tests ( i. e. MTT assay, calcein - AM / Propidium Iodide staining, clonogenic test ) in CNS cell models ( D384 and SH - SY5Y ), and non - neuronal primary human fibroblasts ( F26 ).", "output": "BPA - f, MTT, calcein - AM, Propidium Iodide." }, { "input": "MTT data showed: ( i ) no cytotoxic effects after short - term exposure ( 4h ) to any of BPA - f concentrations tested in all cell models; ( ii ) dose - and time - dependent mitochondrial activity impairment in D384 and SH - SY5Y cells only ( with 60 % and 40 % cell death in D384 and SH - SY5Y, respectively, after 48h exposure to BPA - f 100 mu gBeq / ml ).", "output": "MTT, BPA - f, BPA - f." }, { "input": "By Calcein - AM / PI staining, BPA - f treatment was specific toward SH - SY5Y cells only: a dose - dependent cell density reduction was observed, with a more pronounced effect after 48h exposure ( 15 - 40 % at doses ranging 20 - 100 mu gBeq / ml ).", "output": "Calcein - AM, BPA - f." }, { "input": "Clonogenic data revealed dose - dependent decrease of cell proliferative capacity in all cell lines, still the SH - SY5Y cells were the most sensitive ones: the lowest dose ( 20 mu gBeq / ml ) produced 90 % cell decrease.", "output": "There is no related enetity." }, { "input": "These results indicate dose - and time - dependent cytotoxic effects of BPA - f, with CNS cells showing a lower tolerance compared to fibroblasts.", "output": "BPA - f." }, { "input": "Long - term exposure to BPA - f compromised the proliferative capacity regardless of cell model type ( cell sensitivity being SH - SY5Y > D384 > F26 ).", "output": "BPA - f." }, { "input": "In short - time exposure, BPA - f exhibits a safe dosage up to 40 mu gBeq / ml for the viability of CNS cell lines.", "output": "BPA - f." }, { "input": "Neoechinulin A suppresses amyloid - beta oligomer - induced microglia activation and thereby protects PC - 12 cells from inflammation - mediated toxicity.", "output": "Neoechinulin A." }, { "input": "A pathological hallmark of Alzheimer ' s disease ( AD ), aggregation and deposition of amyloid - beta peptides, has been recognized as a potent activator of microglia - mediated neuroinflammation and neuronal dysfunction.", "output": "There is no related enetity." }, { "input": "Therefore, downregulation of microglial activation has a significant therapeutic demand.", "output": "There is no related enetity." }, { "input": "In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine - derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid - beta 1 - 42 ( A beta 42 ).", "output": "neoechinulin A, indole." }, { "input": "Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in A beta 42 - activated BV - 2 microglia cells.", "output": "Neoechinulin A, oxygen, nitrogen." }, { "input": "In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor - alpha ( TNF - alpha ), interleukin - 1 beta ( IL - 1 beta ), interleukin - 6 ( IL - 6 ), and prostaglandin E2 ( PGE2 ) in activated BV - 2 cells.", "output": "neoechinulin A, prostaglandin E2, PGE2." }, { "input": "Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase ( iNOS ), cyclooxygenase - 2 ( COX - 2 ), TNF - alpha, IL - 1 beta and IL - 6.", "output": "nitric oxide." }, { "input": "Further, activated microglia - mediated apoptosis of PC - 12 pheochromocytoma cells was significantly repressed by neoechinulin A.", "output": "neoechinulin A." }, { "input": "The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen - activated protein kinase ( MAPK ) molecule p38, apoptosis signal - regulating kinase 1 ( ASK - 1 ) and nuclear translocation of nuclear factor - kappa B ( NF - kappa B ) p65 and p50 subunits.", "output": "neoechinulin A." }, { "input": "Regulation of these signalling pathways have most probably contributed to the anti - inflammatory activity of neoechinulin A.", "output": "neoechinulin A." }, { "input": "Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD.", "output": "neoechinulin A." }, { "input": "A comparative performance test of standard, medium - and high - throughput comet assays.", "output": "There is no related enetity." }, { "input": "A serious limitation of the conventional comet assay ( single cell gel electrophoresis ) is the restriction on the number of samples that can be processed in one experiment, imposed by the size of the electrophoresis platform.", "output": "There is no related enetity." }, { "input": "One approach to increasing throughput is to reduce the size of gels.", "output": "There is no related enetity." }, { "input": "We here compare the conventional system of two large gels on a microscope slide, with two recent developments, namely 12 minigels per slide, and a format with 96 minigels on GelBond (R) film.", "output": "There is no related enetity." }, { "input": "We used cells treated with X - rays or methylmethanesulphonate ( MMS ).", "output": "methylmethanesulphonate, MMS." }, { "input": "The level of damage detected ( % tail DNA ) in X - irradiated or MMS - treated cells was not affected by the format used.", "output": "MMS." }, { "input": "Parallel experiments, using all three formats, were performed with MMS - treated cells in two independent laboratories; the difference in results between the two laboratories was of borderline significance.", "output": "MMS." }, { "input": "The potential problem of anomalous comets seen at the border of the gel, the so - called ' edge effects ', has been addressed.", "output": "There is no related enetity." }, { "input": "A reliable, high throughput comet assay has applications in genotoxicity testing ( particularly for in vivo studies with samples from different organs ) as well as ecogenotoxicology and human biomonitoring, where the numbers of samples collected can be considerable.", "output": "There is no related enetity." }, { "input": "The effects of jaspamide on human cardiomyocyte function and cardiac ion channel activity.", "output": "jaspamide." }, { "input": "Jaspamide ( jasplakinolide; NSC - 613009 ) is a cyclodepsipeptide that has antitumor activity.", "output": "Jaspamide, jasplakinolide, NSC - 613009, cyclodepsipeptide." }, { "input": "A narrow margin of safety was observed between doses required for efficacy in mouse tumor models and doses that caused severe acute toxicity in rats and dogs.", "output": "There is no related enetity." }, { "input": "We explored the hypothesis that the observed toxicity was due to cardiotoxicity.", "output": "There is no related enetity." }, { "input": "Jaspamide was tested in a patch clamp assay to determine its effect on selected cardiac ion channels.", "output": "Jaspamide." }, { "input": "Jaspamide ( 10 mu M ) inhibited Kv1. 5 activity by 98. 5 %.", "output": "Jaspamide." }, { "input": "Jaspamide also inhibited other channels including Cav1. 2, Cav3. 2, and HCN2; however, the Kv11. 1 ( hERG ) channel was minimally affected.", "output": "Jaspamide." }, { "input": "Using spontaneously contracting human cardiomyocytes derived from induced pluripotent stem cells, effects on cardiomyocyte contraction and viability were also examined.", "output": "There is no related enetity." }, { "input": "Jaspamide ( 30 nM to 30 mu M ) decreased cardiomyocyte cell indices and beat amplitude, putative measurements of cell viability and cardiac contractility, respectively.", "output": "Jaspamide." }, { "input": "Concentration - dependent increases in rhythmic beating rate were noted at <= 6 h of treatment, followed by dose - dependent decreases after 6 and 72 h exposure.", "output": "There is no related enetity." }, { "input": "The toxic effects of jaspamide were compared with that of the known cardiotoxicant mitoxantrone, and confirmed by multiparameter fluorescence imaging analysis.", "output": "jaspamide, mitoxantrone." }, { "input": "These results support the hypothesis that the toxicity observed in rats and dogs is due to toxic effects of jaspamide on cardiomyocytes.", "output": "jaspamide." }, { "input": "Long - term incubation of adult Nereis virens ( Annelida: Polychaeta ) in copper - spiked sediment: the effects on adult mortality, gametogenesis, spawning and embryo development.", "output": "copper." }, { "input": "Late gametogenic Nereis virens were incubated for up to 2. 5 months in environmentally relevant concentrations of copper - spiked sediment.", "output": "copper." }, { "input": "Sequential extraction confirmed that much more labile copper ( in actual and percentage terms ) was present as spiked concentrations increased, although the residual fractions contained similar amounts across concentrations.", "output": "copper." }, { "input": "This is also reflected in the tissue concentration of the worms which increased in line with the sediment concentrations.", "output": "There is no related enetity." }, { "input": "Adult mortality was not dependent on the exposure time, but higher concentrations usually induced greater mortality for both sexes.", "output": "There is no related enetity." }, { "input": "Oocytes were significantly smaller at higher concentrations although pairwise comparisons did not show specific differences.", "output": "There is no related enetity." }, { "input": "Spawning of males occurred a number of days earlier in the higher concentrations.", "output": "There is no related enetity." }, { "input": "Differences in the number of embryos developing normally after in vitro fertilizations of oocytes fertilized with sperm from exposed males and non - exposed males showed that sperm were more susceptible to toxicity, but oocytes were also affected at the highest concentration.", "output": "There is no related enetity." }, { "input": "These results show that there are direct and indirect reproductive consequences of parental exposure to copper with implications for recruitment and subsequent colonization of polluted sediments for this ecologically and commercially important species.", "output": "copper." }, { "input": "( - ) Epicatechin attenuates mitochondrial damage by enhancing mitochondrial multi - marker enzymes, adenosine triphosphate and lowering calcium in isoproterenol induced myocardial infarcted rats.", "output": "( - ) Epicatechin, adenosine triphosphate, calcium, isoproterenol." }, { "input": "Cardiac mitochondrial damage plays an important role in the pathology of myocardial infarction.", "output": "There is no related enetity." }, { "input": "The protective effects of ( - ) epicatechin on cardiac mitochondrial damage in isoproterenol induced myocardial infarction were evaluated in rats.", "output": "( - ) epicatechin, isoproterenol." }, { "input": "Rats were pretreated with ( - ) epicatechin ( 20 mg / kg body weight ) daily for a period of 21 days.", "output": "( - ) epicatechin." }, { "input": "After the pretreatment period, isoproterenol ( 100 mg / kg body weight ) was injected subcutaneously into rats twice at an interval of 24 h to induce myocardial infarction.", "output": "isoproterenol." }, { "input": "Isoproterenol induced myocardial infarcted rats showed a significant increase in the levels of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, calcium, and a significant decrease in the activities / levels of heart mitochondrial glutathione peroxidase, glutathione reductase, reduced glutathione, isocitrate, succinate, malate, alpha - ketoglutarate and NADH - dehydrogenases, cytochrome - C - oxidase and adenosine triphosphate.", "output": "Isoproterenol, calcium, glutathione, glutathione, reduced glutathione, isocitrate, succinate, malate, alpha - ketoglutarate, NADH, adenosine triphosphate." }, { "input": "( - ) Epicatechin pretreatment showed significant protective effects on all the biochemical parameters evaluated.", "output": "( - ) Epicatechin." }, { "input": "The in vitro study revealed the superoxide and hydroxyl radical scavenging activity of ( - ) epicatechin.", "output": "superoxide, hydroxyl, ( - ) epicatechin." }, { "input": "The possible mechanisms for the beneficial effects of ( - ) epicatechin on cardiac mitochondria could be attributed to scavenging of free radicals, decreasing calcium, increasing multi - enzymes ( antioxidant, tricarboxylic acid cycle and respiratory chain enzymes ), reduced glutathione and adenosine triphosphate.", "output": "( - ) epicatechin, calcium, tricarboxylic acid, glutathione, adenosine triphosphate." }, { "input": "Thus, ( - ) epicatechin attenuated mitochondrial damage in isoproterenol induced myocardial infarcted rats.", "output": "( - ) epicatechin, isoproterenol." }, { "input": "Stimulatory effect of insulin on theca - interstitial cell proliferation and cell cycle regulatory proteins through MTORC1 dependent pathway.", "output": "There is no related enetity." }, { "input": "The present study examined the effect of insulin - mediated activation of the mammalian target of rapamycin complex 1 ( MTORC1 ) signaling network on the proliferation of primary culture of theca - interstitial ( T - I ) cells.", "output": "rapamycin." }, { "input": "Our results show that insulin treatment increased proliferation of the T - I cells through the MTORC1 - dependent signaling pathway by increasing cell cycle regulatory proteins.", "output": "There is no related enetity." }, { "input": "Inhibition of ERK1 / 2 signaling caused partial reduction of insulin - induced phosphorylation of RPS6KB1 and RPS6 whereas inhibition of PI3 - kinase signaling completely blocked the insulin response.", "output": "There is no related enetity." }, { "input": "Pharmacological inhibition of MTORC1 with rapamycin abrogated the insulin - induced phosphorylation of EIF4EBP1, RPS6KB1 and its downstream effector, RPS6.", "output": "rapamycin." }, { "input": "These results were further confirmed by demonstrating that knockdown of Mtor using siRNA reduced the insulin - stimulated MTORC1 signaling.", "output": "There is no related enetity." }, { "input": "Furthermore, insulin - stimulated T - I cell proliferation and the expression of cell cycle regulatory proteins CDK4, CCND3 and PCNA were also blocked by rapamycin.", "output": "rapamycin." }, { "input": "Taken together, the present studies show that insulin stimulates cell proliferation and cell cycle regulatory proteins in T - I cells via activation of the MTORC1 signaling pathway.", "output": "There is no related enetity." }, { "input": "Modulation of activity and inhibitor sensitivity of rabbit aldose reductase - like protein ( AKR1B19 ) by oxidized glutathione and SH - reagents.", "output": "aldose, oxidized glutathione, SH." }, { "input": "Rabbit aldo - keto reductase ( AKR ) 1B19 is an ortholog of human aldose reductase - like protein ( ARLP ), AKR1B10, showing 86 % amino acid sequence identity.", "output": "aldose, amino acid." }, { "input": "AKR1B19 exhibits the highest catalytic efficiency for 4 - oxo - 2 - nonenal, a major product of lipid peroxidation, compared to known reductases of this aldehyde.", "output": "4 - oxo - 2 - nonenal, aldehyde." }, { "input": "In this study, we found that the reductase activity of AKR1B19 was activated to about 5 - fold immediately after the addition of 10 mu M SH - reagents ( p - chloromercuriphenylsulfonic acid and p - chloromercuribenzoic acid ) in the absence or presence of NADPH.", "output": "SH, p - chloromercuriphenylsulfonic acid, p - chloromercuribenzoic acid, NADPH." }, { "input": "In addition, a maximum of 3 - fold activation of AKR1B19 was induced by incubation with glutathione disulfide ( GSSG ) for 1h.", "output": "glutathione disulfide, GSSG." }, { "input": "The activated enzyme was converted into the native enzyme by further incubation with dithiothreitol and glutathione.", "output": "dithiothreitol, glutathione." }, { "input": "The activation was abolished by the C299S mutation of AKR1B19, and the glutathionylated Cys299 was identified by mass spectrometry analysis.", "output": "Cys299." }, { "input": "The Cys299 - modified enzyme displayed different kinetic alterations depending on substrates and inhibitors.", "output": "Cys299." }, { "input": "In the reduction of 4 - oxo - 2 - nonenal, the catalytic efficiency was increased.", "output": "4 - oxo - 2 - nonenal." }, { "input": "Thus, AKR1B10 may be modulated by cellular ratio of GSSG / glutathione and more efficiently act as a detoxifying enzyme for the cytotoxic aldehyde under oxidatively stressed conditions.", "output": "GSSG, glutathione, aldehyde." }, { "input": "Furthermore, such an activity alteration by GSSG was not detected in AKR1B10 and rat ARLPs, suggesting the presence of a GSSG - binding site near Cys299 in AKR1B19.", "output": "GSSG, GSSG, Cys299." }, { "input": "The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat.", "output": "triclosan, ethinyl estradiol." }, { "input": "Triclosan ( TCS ), an antibacterial, has been shown to be an endocrine disruptor in the rat.", "output": "Triclosan, TCS." }, { "input": "We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol ( EE ) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect.", "output": "TCS, ethinyl estradiol, TCS, TCS." }, { "input": "To further characterize this potentiation, we evaluated the effect of co - exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs.", "output": "There is no related enetity." }, { "input": "Changes in uterine weight, epithelial cell growth, and estrogen - sensitive gene expression were assessed.", "output": "estrogen." }, { "input": "TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE.", "output": "TCS." }, { "input": "Similarly, TCS increased the EE - induced stimulation of epithelial cell height following cotreatment.", "output": "TCS." }, { "input": "Cotreatment also enhanced the estrogen - induced change in gene expression, which was reversed with an ER antagonist.", "output": "estrogen." }, { "input": "Furthermore, the TCS - induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay.", "output": "TCS." }, { "input": "Antioxidant cosmeto - textiles: Skin assessment.", "output": "There is no related enetity." }, { "input": "Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals.", "output": "Resveratrol." }, { "input": "This compound could be used in the dermocosmetic field to protect the skin from oxidative stress.", "output": "There is no related enetity." }, { "input": "In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology.", "output": "resveratrol, ethanol." }, { "input": "The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections ( stratum corneum, epidermis, and dermis ).", "output": "resveratrol, trolox, Vitamin E." }, { "input": "Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method.", "output": "resveratrol, trolox, DPPH." }, { "input": "The effective dose ( ED50 ) of compounds and DPPH radical inhibition in each skin layer were evaluated.", "output": "DPPH." }, { "input": "Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers.", "output": "resveratrol, trolox." }, { "input": "The cosmeto - textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries.", "output": "There is no related enetity." }, { "input": "The action of several cosmeto - textiles on the skin was assessed by in vitro and in vivo methodologies.", "output": "There is no related enetity." }, { "input": "Samples of these cosmeto - textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics.", "output": "resveratrol, polyamide." }, { "input": "An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers ( stratum corneum, epidermis, and dermis ).", "output": "resveratrol." }, { "input": "Additionally, these cosmeto - textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles ' efficacy in skin penetration.", "output": "There is no related enetity." }, { "input": "The antioxidant ' s antiradical capacity was evaluated using the DPPH method.", "output": "DPPH." }, { "input": "Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum ( SC ) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method ( stripping ).", "output": "resveratrol." }, { "input": "A smaller amount of resveratrol was penetrated through the skin layers when cosmeto - textiles were used compared to direct topical application of the antioxidant solution.", "output": "resveratrol." }, { "input": "The cosmeto - textiles investigated can act as a reservoir system capable of progressively deliver the active substance to the skin layers.", "output": "There is no related enetity." }, { "input": "From the skin penetration profiles and the antioxidant efficacy assessment of resveratrol, it is possible to ameliorate the inherent antioxidant capacity of skin.", "output": "resveratrol." }, { "input": "Plasmonic photothermal therapy increases the tumor mass penetration of HPMA copolymers.", "output": "HPMA." }, { "input": "Effective drug delivery to tumors requires both transport through the vasculature and tumor interstitium.", "output": "There is no related enetity." }, { "input": "Previously, it was shown that gold nanorod ( GNR ) mediated plasmonic photothermal therapy ( PPTT ) is capable of increasing the overall accumulation of N - ( 2 - hydroxypropyl ) methacrylamide ( HPMA ) copolymers in prostate tumors.", "output": "N - ( 2 - hydroxypropyl ) methacrylamide, HPMA." }, { "input": "In the present study, it is demonstrated that PPTT is also capable of increasing the distribution of these conjugates in tumors.", "output": "There is no related enetity." }, { "input": "Gadolinium labeled HPMA copolymers were administered to mice bearing prostate tumors immediately before treatment of the right tumor with PPTT.", "output": "Gadolinium, HPMA." }, { "input": "The left tumor served as internal, untreated control.", "output": "There is no related enetity." }, { "input": "Magnetic resonance imaging ( MRI ) of both tumors showed that PPTT was capable of improving the tumor mass penetration of HPMA copolymers.", "output": "HPMA." }, { "input": "Thermal enhancement of delivery, roughly 1. 5 - fold, to both the tumor center and periphery was observed.", "output": "There is no related enetity." }, { "input": "Confocal microscopy of fluorescently labeled copolymers corroborates these findings in that PPTT is capable of delivering more HPMA copolymers to the tumor ' s center and periphery.", "output": "HPMA." }, { "input": "These results further demonstrate that PPTT is a useful tool to improve the delivery of polymer - drug conjugates.", "output": "There is no related enetity." }, { "input": "High - throughput identification and characterization of novel, species - selective GPR35 agonists.", "output": "There is no related enetity." }, { "input": "Drugs targeting the orphan receptor GPR35 have potential therapeutic application in a number of disease areas, including inflammation, metabolic disorders, nociception, and cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Currently available surrogate GPR35 agonists identified from pharmacologically relevant compound libraries have limited utility due to the likelihood of off - target effects in vitro and in vivo and the variable potency that such ligands exhibit across species.", "output": "There is no related enetity." }, { "input": "We sought to identify and characterize novel GPR35 agonists to facilitate studies aimed at defining the physiologic role of GPR35.", "output": "There is no related enetity." }, { "input": "PathHunter beta - arrestin recruitment technology was validated as a human GPR35 screening assay, and a high - throughput screen of 100, 000 diverse low molecular weight compounds was conducted.", "output": "There is no related enetity." }, { "input": "Confirmed GPR35 agonists from five distinct chemotypes were selected for detailed characterization using both beta - arrestin recruitment and G protein - dependent assays and each of the human, mouse, and rat GPR35 orthologs.", "output": "There is no related enetity." }, { "input": "These studies identified 4 - { ( Z ) - [ ( 2Z ) - 2 - ( 2 - fluorobenzylidene ) - 4 - oxo - 1, 3 - thiazolidin - 5 - ylidene ] methyl } benzoic acid ( compound 1 ) as the highest potency full agonist of human GPR35 yet described.", "output": "4 - { ( Z ) - [ ( 2Z ) - 2 - ( 2 - fluorobenzylidene ) - 4 - oxo - 1 , 3 - thiazolidin - 5 - ylidene ] methyl } benzoic acid." }, { "input": "As with certain other GPR35 agonists, compound 1 was markedly selective for human GPR35, but displayed elements of signal bias between beta - arrestin - 2 and G protein - dependent assays.", "output": "There is no related enetity." }, { "input": "Compound 1 also displayed competitive behavior when assessed against the human GPR35 antagonist, ML - 145 ( 2 - hydroxy - 4 - [ 4 - ( 5Z ) - 5 - [ ( E ) - 2 - methyl - 3 - phenylprop - 2 - enylidene ] - 4 - oxo - 2 - sulfanylidene - 1, 3 - thiazolidin - 3 - yl ] butanoylamino ] benzoic acid ).", "output": "ML - 145, 2 - hydroxy - 4 - [ 4 - ( 5Z ) - 5 - [ ( E ) - 2 - methyl - 3 - phenylprop - 2 - enylidene ] - 4 - oxo - 2 - sulfanylidene - 1 , 3 - thiazolidin - 3 - yl ] butanoylamino ] benzoic acid." }, { "input": "Of the other chemotypes studied, compounds 2 and 3 were selective for the human receptor, but compounds 4 and 5 demonstrated similar activity at human, rat, and mouse GPR35 orthologs.", "output": "There is no related enetity." }, { "input": "Further characterization of these compounds and related analogs is likely to facilitate a better understanding of GPR35 in health and disease.", "output": "There is no related enetity." }, { "input": "Manganese exposure induces alpha - synuclein aggregation in the frontal cortex of non - human primates.", "output": "Manganese." }, { "input": "Aggregation of alpha - synuclein ( alpha - syn ) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies.", "output": "There is no related enetity." }, { "input": "They include Parkinson ' s disease ( PD ), dementia with Lewy bodies ( DLB ), and multiple system atrophy ( MSA ).", "output": "There is no related enetity." }, { "input": "Occupational and environmental exposure to manganese ( Mn ) is associated with a neurological syndrome consisting of psychiatric symptoms, cognitive impairment and parkinsonism.", "output": "manganese, Mn." }, { "input": "In this study, we examined alpha - syn immunoreactivity in the frontal cortex of Cynomolgus macaques as part of a multidisciplinary assessment of the neurological effects produced by exposure to moderate levels of Mn.", "output": "Mn." }, { "input": "We found increased alpha - syn - positive cells in the gray matter of Mn - exposed animals, typically observed in pyramidal and medium - sized neurons in deep cortical layers.", "output": "Mn." }, { "input": "Some of these neurons displayed loss of Nissl staining with alpha - syn - positive spherical aggregates.", "output": "There is no related enetity." }, { "input": "In the white matter we also observed alpha - syn - positive glial cells and in some cases alpha - syn - positive neurites.", "output": "There is no related enetity." }, { "input": "These findings suggest that Mn exposure promotes alpha - syn aggregation in neuronal and glial cells that may ultimately lead to degeneration in the frontal cortex gray and white matter.", "output": "Mn." }, { "input": "To our knowledge, this is the first report of Mn - induced neuronal and glial cell alpha - syn accumulation and aggregation in the frontal cortex of non - human primates.", "output": "Mn." }, { "input": "Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1.", "output": "glucose, cyclic AMP." }, { "input": "The prototypic second messenger cyclic AMP ( cAMP ) is essential for controlling cellular metabolism, including glucose and lipid homeostasis.", "output": "cyclic AMP, cAMP, glucose." }, { "input": "In mammals, the majority of cAMP functions are mediated by cAMP - dependent protein kinase ( PKA ) and exchange proteins directly activated by cAMP ( Epacs ).", "output": "cAMP, cAMP." }, { "input": "To explore the physiological functions of Epac1, we generated Epac1 knockout mice.", "output": "There is no related enetity." }, { "input": "Here we report that Epac1 null mutants have reduced white adipose tissue and reduced plasma leptin levels but display heightened leptin sensitivity.", "output": "There is no related enetity." }, { "input": "Epac1 - deficient mice are more resistant to high - fat diet - induced obesity, hyperleptinemia, and glucose intolerance.", "output": "glucose." }, { "input": "Furthermore, pharmacological inhibition of Epac by use of an Epac - specific inhibitor reduces plasma leptin levels in vivo and enhances leptin signaling in organotypic hypothalamic slices.", "output": "There is no related enetity." }, { "input": "Taken together, our results demonstrate that Epac1 plays an important role in regulating adiposity and energy balance.", "output": "There is no related enetity." }, { "input": "Molecular diversity of class 2 integrons in antibiotic - resistant gram - negative bacteria found in wastewater environments in China.", "output": "There is no related enetity." }, { "input": "The molecular architecture of class 2 integrons among gram - negative bacteria from wastewater environments was investigated in Jinan, China.", "output": "There is no related enetity." }, { "input": "Out of the 391 antibiotic - resistant bacteria found, 38 isolates harboring class 2 integrons encoding potentially transferrable genes that could confer antibiotic resistance were found.", "output": "There is no related enetity." }, { "input": "These isolates were classified into 19 REP - PCR types.", "output": "There is no related enetity." }, { "input": "These strains were identified using 16S rRNA gene sequencing and found to be as follows: Proteus mirabilis ( 16 ), Escherichia coli ( 7 ), Providencia spp.", "output": "There is no related enetity." }, { "input": "( 7 ), Proteus spp.", "output": "There is no related enetity." }, { "input": "( 2 ), P. vulgaris ( 3 ), Shigella sp.", "output": "There is no related enetity." }, { "input": "( 1 ), Citrobacter freundii ( 1 ), and Acinetobacter sp.", "output": "There is no related enetity." }, { "input": "( 1 ).", "output": "There is no related enetity." }, { "input": "Their class 2 integron cassette arrays were amplified and then either analyzed using PCR - RFLP or sequenced.", "output": "There is no related enetity." }, { "input": "The typical array dfrA1 - sat2 - aadA1 was detected in 27 isolates.", "output": "There is no related enetity." }, { "input": "Six atypical arrays were observed, including three kinds of novel arrangements ( linF2 ( increment attC1 ) - dfrA1 ( increment attC2 ) - aadA1 - orf441 or linF2 ( increment attC1 ) - dfrA1 ( increment attC2 ) - aadA1, dfrA1 - catB2 - sat2 - aadA1, and estX ( Vr ) - sat2 - aadA1 ) and a hybrid with the 3 ' CS of class 1 integrons ( dfrA1 - sat2 - aadA1 - qacH ), and dfrA1 - sat1.", "output": "There is no related enetity." }, { "input": "Twenty - four isolates were also found to carry class 1 integrons with 10 types of gene cassette arrays.", "output": "There is no related enetity." }, { "input": "Several non - integron - associated antibiotic resistance genes were found, and their transferability was investigated.", "output": "There is no related enetity." }, { "input": "Results showed that water sources in the Jinan region harbored a diverse community of both typical and atypical class 2 integrons, raising concerns about the overuse of antibiotics and their careless disposal into the environment.", "output": "There is no related enetity." }, { "input": "Effects of fluoxetine on the swimming and behavioural responses of the Arabian killifish.", "output": "fluoxetine." }, { "input": "The selective serotonin reuptake inhibitor fluoxetine has frequently been detected in surface waters around the world.", "output": "serotonin, fluoxetine." }, { "input": "Fluoxetine modulates levels of serotonin, a neurotransmitter that regulates several important physiological and behavioural processes including fear and anxiety, aggression, locomotion and feeding.", "output": "Fluoxetine, serotonin." }, { "input": "In this study, groups of sub - adult Arabian killifish ( Aphanius dispar ) were exposed to either 0, 0. 03, 0. 3 or 3 mu g / L fluoxetine hydrochloride for 7 days and their swimming behaviour and social interactions videotaped in a circular arena.", "output": "fluoxetine, hydrochloride." }, { "input": "The fish were subsequently exposed to a predator alarm chemical ( from dragonfly larvae fed with A. dispar ) and their short - term responses recorded.", "output": "There is no related enetity." }, { "input": "The video was analysed using the open - sourced software program Ctrax which objectively quantified swimming and social behaviours.", "output": "There is no related enetity." }, { "input": "Aggression ( chasing behaviour was significantly reduced at 3. 0 mu g / L fluoxetine.", "output": "fluoxetine." }, { "input": "After the addition of the predator alarm chemicals fish responded quickly, increasing the percentage of time spent drifting or motionless and reducing average swimming velocity.", "output": "There is no related enetity." }, { "input": "Controls and fish exposed to 0. 03 or 3 mu g / L fluoxetine reduced swimming speed by 20 - 30 % but returned to pre - exposure velocities within 6 min.", "output": "fluoxetine." }, { "input": "Fish exposed to 0. 3 mu g / L fluoxetine reduced swimming speed by 38 % after addition of the predator alarm and did not return to pre - exposure speeds during the recording period ( 19 min ).", "output": "fluoxetine." }, { "input": "Schooling behaviour was also affected by fluoxetine and predator alarm with fish exposed to 0. 3 mu g / L fluoxetine significantly reducing nearest neighbour distance and swimming speed relative to nearest neighbour the following addition of the predator alarm.", "output": "fluoxetine, fluoxetine." }, { "input": "Cortisol and interferon tau regulation of endometrial function and conceptus development in female sheep.", "output": "Cortisol." }, { "input": "During early pregnancy in sheep, the elongating conceptus secretes interferon - tau ( IFNT ) and the conceptus as well as endometrial epithelia produce prostaglandins ( PG ) via PG synthase 2 ( PTGS2 ) and cortisol via hydroxysteroid ( 11 - beta ) dehydrogenase 1 ( HSD11B1 ).", "output": "prostaglandins, cortisol, hydroxysteroid." }, { "input": "Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto - reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation.", "output": "progesterone, keto." }, { "input": "The primary aim of these studies was to test the hypothesis that HSD11B1 - derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep.", "output": "cortisol." }, { "input": "In study 1, cyclic ewes received vehicle, cortisol, PF 915275 ( PF; a selective inhibitor of HSD11B1 ), cortisol and PF, meloxicam ( a selective inhibitor of PTGS2 ), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus.", "output": "cortisol, PF 915275, cortisol, meloxicam, cortisol, meloxicam." }, { "input": "Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up - regulated many conceptus elongation - related genes in the endometrium.", "output": "Cortisol." }, { "input": "Some effects of cortisol and IFNT were mediated by PTGS2 - derived PG.", "output": "cortisol." }, { "input": "In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating.", "output": "PF 915275." }, { "input": "Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF - infused ewes.", "output": "There is no related enetity." }, { "input": "These results suggest that HSD11B1 - derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.", "output": "cortisol, progesterone, cortisol." }, { "input": "Streamlined expressed protein ligation using split inteins.", "output": "There is no related enetity." }, { "input": "Chemically modified proteins are invaluable tools for studying the molecular details of biological processes, and they also hold great potential as new therapeutic agents.", "output": "There is no related enetity." }, { "input": "Several methods have been developed for the site - specific modification of proteins, one of the most widely used being expressed protein ligation ( EPL ) in which a recombinant alpha - thioester is ligated to an N - terminal Cys - containing peptide.", "output": "alpha - thioester, N, Cys." }, { "input": "Despite the widespread use of EPL, the generation and isolation of the required recombinant protein alpha - thioesters remain challenging.", "output": "alpha - thioesters." }, { "input": "We describe here a new method for the preparation and purification of recombinant protein alpha - thioesters using engineered versions of naturally split DnaE inteins.", "output": "alpha - thioesters." }, { "input": "This family of autoprocessing enzymes is closely related to the inteins currently used for protein alpha - thioester generation, but they feature faster kinetics and are split into two inactive polypeptides that need to associate to become active.", "output": "alpha - thioester." }, { "input": "Taking advantage of the strong affinity between the two split intein fragments, we devised a streamlined procedure for the purification and generation of protein alpha - thioesters from cell lysates and applied this strategy for the semisynthesis of a variety of proteins including an acetylated histone and a site - specifically modified monoclonal antibody.", "output": "alpha - thioesters." }, { "input": "Block copolymer modified surfaces for conjugation of biomacromolecules with control of quantity and activity.", "output": "There is no related enetity." }, { "input": "Polymer brush layers based on block copolymers of poly ( oligo ( ethylene glycol ) methacrylate ) ( POEGMA ) and poly ( glycidyl methacrylate ) ( PGMA ) were formed on silicon wafers by activators generated by electron transfer atom transfer radical polymerization ( AGET ATRP ).", "output": "poly ( oligo ( ethylene glycol ) methacrylate ), POEGMA, poly ( glycidyl methacrylate ), PGMA, silicon." }, { "input": "Different types of biomolecule can be conjugated to these brush layers by reaction of PGMA epoxide groups with amino groups in the biomolecule, while POEGMA, which resists nonspecific protein adsorption, provides an antifouling environment.", "output": "PGMA, epoxide, amino, POEGMA." }, { "input": "Surfaces were characterized by water contact angle, ellipsometry, and Fourier transform infrared spectroscopy ( FTIR ) to confirm the modification reactions.", "output": "There is no related enetity." }, { "input": "Phase segregation of the copolymer blocks in the layers was observed by AFM.", "output": "There is no related enetity." }, { "input": "The effect of surface properties on protein conjugation was investigated using radiolabeling methods.", "output": "There is no related enetity." }, { "input": "It was shown that surfaces with POEGMA layers were protein resistant, while the quantity of protein conjugated to the diblock copolymer modified surfaces increased with increasing PGMA layer thickness.", "output": "POEGMA, PGMA." }, { "input": "The activity of lysozyme conjugated on the surface could also be controlled by varying the thickness of the copolymer layer.", "output": "There is no related enetity." }, { "input": "When biotin was conjugated to the block copolymer grafts, the surface remained resistant to nonspecific protein adsorption but showed specific binding of avidin.", "output": "biotin." }, { "input": "These properties, that is, well - controlled quantity and activity of conjugated biomolecules and specificity of interaction with target biomolecules may be exploited for the improvement of signal - to - noise ratio in sensor applications.", "output": "There is no related enetity." }, { "input": "More generally, such surfaces may be useful as biological recognition elements of high specificity for functional biomaterials.", "output": "There is no related enetity." }, { "input": "Electrodeposition of crystalline GaAs on liquid gallium electrodes in aqueous electrolytes.", "output": "GaAs, gallium." }, { "input": "Crystalline GaAs ( c - GaAs ) has been prepared directly through electroreduction of As ( 2 ) O ( 3 ) dissolved in an alkaline aqueous solution at a liquid gallium ( Ga ( l ) ) electrode at modest temperatures ( T >= 80 degrees C ).", "output": "GaAs, GaAs, As ( 2 ) O ( 3 ), gallium, Ga ( l )." }, { "input": "Ga ( l ) pool electrodes yielded consistent electrochemical behavior, affording repetitive measurements that illustrated the interdependences of applied potential, concentration of dissolved As ( 2 ) O ( 3 ), and electrodeposition temperature on the quality of the resultant c - GaAs ( s ).", "output": "Ga ( l ), As ( 2 ) O ( 3 ), GaAs." }, { "input": "Raman spectra indicated the composition of the resultant film was strongly dependent on both the electrodeposition temperature and dissolved concentration of As ( 2 ) O ( 3 ) but not to the applied bias.", "output": "As ( 2 ) O ( 3 )." }, { "input": "For electrodepositions performed either at room temperature or with high ( >= 0. 01 M ) concentrations of dissolved As ( 2 ) O ( 3 ), Raman spectra of the electrodeposited films were consistent with amorphous As ( s ).", "output": "As ( 2 ) O ( 3 ), As." }, { "input": "X - ray diffractograms of As ( s ) films collected after thermal annealing indicated metallurgical alloying occurred only at temperatures in excess of 200 degrees C.", "output": "As." }, { "input": "Optical images and Raman spectra separately showed the composition of the as - electrodeposited film in dilute ( <= 0. 001 M ) solutions of dissolved As ( 2 ) O ( 3 ) ( aq ) was pure c - GaAs ( s ) at much lower temperatures than 200 degrees C.", "output": "as, As ( 2 ) O ( 3 ), GaAs." }, { "input": "Diffractograms and transmission electron microscopy performed on as - prepared films confirmed the identity of c - GaAs ( s ).", "output": "GaAs." }, { "input": "The collective results thus provide the first clear demonstration of an electrochemical liquid - liquid - solid ( ec - LLS ) process involving a liquid metal that serves simultaneously as an electrode, a solvent / medium for crystal growth, and a coreactant for the synthesis of a polycrystalline semiconductor.", "output": "There is no related enetity." }, { "input": "The presented data serve as impetus for the further development of the ec - LLS process as a controllable, simple, and direct route for technologically important optoelectronic materials such as c - GaAs ( s ).", "output": "GaAs." }, { "input": "The determination of phenolic profiles of Serbian unifloral honeys using ultra - high - performance liquid chromatography / high resolution accurate mass spectrometry.", "output": "There is no related enetity." }, { "input": "Polyphenolic profiles of 44 unifloral Serbian honeys were analyzed using ultra - high - performance liquid chromatography ( UHPLC ) coupled with hybrid mass spectrometer which combines the Linear Trap Quadrupole ( LTQ ) and OrbiTrap mass analyzer.", "output": "Polyphenolic." }, { "input": "Rapid UHPLC method was developed in combination with a high sensitivity accurate mass scan and a simultaneous data dependent scan.", "output": "There is no related enetity." }, { "input": "The honey samples were of different botanical origin: acacia ( Robinia pseudoacacia ), sunflower ( Helianthus annuus ), linden ( Tilia cordata ), basil ( Ocimum basilicum ), buckwheat ( Fagopyrum esculentum ), oilseed rape ( Brassica napus ), and goldenrod ( Solidago virgaurea ).", "output": "There is no related enetity." }, { "input": "The presence of 43 compounds, mainly flavonoids, was proven in all honey samples by their characteristic mass spectra and fragmentation pattern.", "output": "flavonoids." }, { "input": "Relatively high amounts of chrysin, pinocembrin and galangin were identified in all honey extracts.", "output": "chrysin, pinocembrin, galangin." }, { "input": "p - Coumaric acid was not detected in basil, buckwheat and goldenrod honey extracts.", "output": "p - Coumaric acid." }, { "input": "A larger amount of gallic acid ( max value 1. 45 mg / kg ) was found in the sunflower honey, while a larger amount of apigenin ( 0. 97 mg / kg ) was determined in the buckwheat honey in comparison with other honeys.", "output": "gallic acid, apigenin." }, { "input": "The samples were classified according to the botanical origin using pattern recognition technique, Principal Component Analysis ( PCA ).", "output": "There is no related enetity." }, { "input": "The LTQ OrbiTrap technique was proven to be reliable for the unambiguous detection of phenolic acids, their derivatives, and flavonoid aglycones based on their molecular masses and fragmentation pattern.", "output": "phenolic acids, flavonoid." }, { "input": "Fast HPLC - DAD quantification of nine polyphenols in honey by using second - order calibration method based on trilinear decomposition algorithm.", "output": "polyphenols." }, { "input": "This paper describes the use of second - order calibration for development of HPLC - DAD method to quantify nine polyphenols in five kinds of honey samples.", "output": "polyphenols." }, { "input": "The sample treatment procedure was simplified effectively relative to the traditional ways.", "output": "There is no related enetity." }, { "input": "Baselines drift was also overcome by means of regarding the drift as additional factor ( s ) as well as the analytes of interest in the mathematical model.", "output": "There is no related enetity." }, { "input": "The contents of polyphenols obtained by the alternating trilinear decomposition ( ATLD ) method have been successfully used to distinguish different types of honey.", "output": "polyphenols." }, { "input": "This method shows good linearity ( r > 0. 99 ), rapidity ( t < 7. 60 min ) and accuracy, which may be extremely promising as an excellent routine strategy for identification and quantification of polyphenols in the complex matrices.", "output": "polyphenols." }, { "input": "Defatted Jatropha curcas flour and protein isolate as materials for protein hydrolysates with biological activity.", "output": "There is no related enetity." }, { "input": "Jatropha curcas L. protein hydrolysates were produced by treatment of a non - toxic genotype with Alcalase as well as the digestive enzymes pepsin and pancreatin.", "output": "There is no related enetity." }, { "input": "The J. curcas protein hydrolysate produced with the pepsin - pancreatin system from protein isolate had the highest TEAC value and was shown to undergo single - electron transfer reactions in the ABTS ( + ) reduction assay, demonstrating its antioxidant capacity.", "output": "ABTS ( + )." }, { "input": "Testing of antimicrobial activity in the J. curcas protein hydrolysates against seven bacterial pathogens showed no growth inhibitory effect in Gram - negative and Gram - positive bacteria.", "output": "There is no related enetity." }, { "input": "More ACE - I inhibitory active peptides were produced in the Alcalase hydrolysates obtained from J. curcas protein isolate.", "output": "There is no related enetity." }, { "input": "The protein hydrolysate obtained with Alcalase from defatted J. curcas flour as well as from the protein isolate showed the highest inhibitory effect of ADP - induced aggregation of human platelets in platelet - rich plasma.", "output": "ADP." }, { "input": "It is expected that the information collated will facilitate new applications of proteins present in Jatropha plant.", "output": "There is no related enetity." }, { "input": "Transepithelial transport of 6 - O - caffeoylsophorose across Caco - 2 cell monolayers.", "output": "6 - O - caffeoylsophorose." }, { "input": "The aim of this study was to clarify the transport behaviour and mechanism of caffeic acid analogue bearing a sugar - moiety, 6 - O - caffeoylsophorose ( CS ), in Caco - 2 cells.", "output": "caffeic acid, sugar, 6 - O - caffeoylsophorose." }, { "input": "The absorption of CS was investigated by its transport across Caco - 2 cell monolayers using a high - performance liquid chromatography - time - of - flight - mass spectrometry ( LC - TOF - MS ).", "output": "There is no related enetity." }, { "input": "The permeation of CS was concentration - dependent and reached the plateau at > 6 mM.", "output": "There is no related enetity." }, { "input": "The apparent permeability ( P ( app ) ) of CS in the apical - to - basolateral direction was 5. 4 x 10 ( - 7 ) cm / s, while in the reversed direction the P ( app ) value was significantly reduced ( 1. 9 x 10 ( - 7 ) cm / s ).", "output": "There is no related enetity." }, { "input": "CS transport was competitively inhibited by phloretin, an inhibitor of monocarboxylic acid transporter ( MCT ).", "output": "phloretin, monocarboxylic acid." }, { "input": "Benzoic acid, an MCT substrate, also reduced CS transport.", "output": "Benzoic acid." }, { "input": "A less significant change of CS transport was observed across Caco - 2 cell monolayers pretreated with quercetin, a suppressor of tight - junction.", "output": "quercetin." }, { "input": "These findings strongly indicate that CS, a caffeic acid analogue bearing sophorose moiety, can be transported across Caco - 2 cell monolayers via the MCT pathway.", "output": "caffeic acid, sophorose." }, { "input": "Sugarcane bagasse treated with hydrous ferric oxide as a potential adsorbent for the removal of As ( V ) from aqueous solutions.", "output": "hydrous ferric oxide, As ( V )." }, { "input": "The mechanism of As ( V ) removal from aqueous solutions by means of hydrated ferric oxide ( HFO ) - treated sugarcane bagasse ( SCB - HFO ) ( Saccharum officinarum L. ) was investigated.", "output": "As ( V ), hydrated ferric oxide, HFO, HFO." }, { "input": "Effects of different parameters, such as pH value, initial arsenic concentration, adsorbent dosage, contact time and ionic strength, on the As ( V ) adsorption were studied.", "output": "arsenic, As ( V )." }, { "input": "The adsorption capacity of SCB - HFO for As ( V ) was found to be 22. 1 mg / g under optimum conditions of pH 4, contact time 3h and temperature 22 degrees C.", "output": "HFO, As ( V )." }, { "input": "Initial As ( V ) concentration influenced the removal efficiency of SCB - HFO.", "output": "As ( V ), HFO." }, { "input": "The desorption of As ( V ) from the adsorbent was 17 % when using 30 % HCl and 85 % with 1M NaOH solution.", "output": "As ( V ), HCl, NaOH." }, { "input": "FTIR analyses evidenced two potential binding sites associated with carboxyl and hydroxyl groups which are responsible for As ( V ) removal.", "output": "carboxyl, hydroxyl, As ( V )." }, { "input": "Adsorption, surface precipitation, ion exchange and complexation can be suggested as mechanisms for the As ( V ) removal from the solution phase onto the surface of SCB - HFO.", "output": "As ( V ), HFO." }, { "input": "Enzymatic synthesis of fructooligosaccharides by inulinases from Aspergillus niger and Kluyveromyces marxianus NRRL Y - 7571 in aqueous - organic medium.", "output": "There is no related enetity." }, { "input": "This work is focused on the synthesis of the fructooligosaccharides ( FOS ) from sucrose and inulin, using free, immobilized and pre - treated immobilized inulinase from Kluyveromyces marxianus NRRL Y 7571 and Aspergillus niger in an aqueous - organic system.", "output": "sucrose." }, { "input": "Initially, the influence of pre - treatment using four different gases, propane, n - butane, CO ( 2 ) and liquefied petroleum gas ( LPG ), was investigated towards FOS production and best results were found when both enzymes were previously treated with LPG.", "output": "propane, n - butane, CO ( 2 )." }, { "input": "The best reaction yields were obtained when the immobilized enzymes were treated with LPG.", "output": "There is no related enetity." }, { "input": "Considering FOS synthesis using the enzyme from A. niger, yields of 26. 62 % of GF2 ( kestose ), 30. 62 % of GF3 ( nystose ) and 8. 47 % of GF4 ( fructosyl nystose ) were achieved using sucrose as substrate.", "output": "kestose, nystose, fructosyl nystose, sucrose." }, { "input": "Using inulinases from K. marxianus NRRL Y 7571, 11. 89 % of GF2 and 20. 83 % of GF3 were obtained, using inulin as substrate.", "output": "There is no related enetity." }, { "input": "However, promising results were achieved using the free form of inulinase from A. niger ( 77. 19 % of GF2; 14. 03 % of GF3 and 0. 07 % of GF4 ) using inulin as substrate.", "output": "There is no related enetity." }, { "input": "Review: on published data and methods for selenium in mushrooms.", "output": "selenium." }, { "input": "Selected data published on selenium in several species of mushrooms are outlined and discussed in light of performance of analytical methods employed.", "output": "selenium." }, { "input": "Data was shown to be either dubious or concentrations too high to be credible and valid in some data reported by authors.", "output": "There is no related enetity." }, { "input": "Examples of methods and specifically the measurement techniques of Se as reported by authors studying mushrooms are outlined.", "output": "Se." }, { "input": "Also examples of valid and incorrect data on Se in a given mushroom species with data by two or more analytical methods are illustrated.", "output": "Se." }, { "input": "Excessive values reported due to selection of improper method of determination of Se in mushrooms relate largely to improper use of flame atomic absorption spectroscopy ( AAS ) and inductively coupled plasma - atomic emission spectroscopy ( ICP - AES ).", "output": "Se." }, { "input": "The biased analytical data published gave a false picture on the composition and nutritional value of mushrooms with respect to selenium.", "output": "selenium." }, { "input": "Rhubarb inhibits hepatocellular carcinoma cell metastasis via GSK - 3 - beta activation to enhance protein degradation and attenuate nuclear translocation of beta - catenin.", "output": "There is no related enetity." }, { "input": "The aim of our study was to investigate the mechanisms by which rhubarb regulates beta - catenin as well as metastasis of hepatocellular carcinomas.", "output": "There is no related enetity." }, { "input": "Our results revealed that rhubarb extract inhibited HA22T cell migration ability in wound healing, migration and invasion assays in a dose - dependent manner.", "output": "There is no related enetity." }, { "input": "Rhubarb also reduced beta - catenin protein level, downregulated its downstream proteins, cyclin D, Tbx3 and c - Myc, and attenuated the expression of MMP9 and contactin - 1 metastatic factors.", "output": "There is no related enetity." }, { "input": "Additionally, rhubarb inhibited beta - catenin nuclear accumulation and induced its degradation via proteasome - mediated pathway.", "output": "There is no related enetity." }, { "input": "Furthermore, we found that rhubarb suppressed the p - ser ( 9 ) GSK - 3 - beta protein level to inactivate Wnt signalling and reduce beta - catenin protein level.", "output": "ser." }, { "input": "Taken together; we found that rhubarb blocked the metastatic process of HA22T hepatocellular carcinoma cells mediated through GSK - 3 - beta activation, and enhancement of protein degradation as well as reduction of the nuclear accumulation of beta - catenin.", "output": "There is no related enetity." }, { "input": "Evaluation of biological activities of a groundnut ( Apios americana Medik ) extract containing a novel isoflavone.", "output": "isoflavone." }, { "input": "Groundnut ( Apios americana Medik ) contains a novel isoflavone, genistein - 7 - O - gentiobioside.", "output": "isoflavone, genistein - 7 - O - gentiobioside." }, { "input": "In the present study, we examined the biological activities of an alcohol extract of groundnut containing genistein - 7 - O - gentiobioside as the main component.", "output": "alcohol, genistein - 7 - O - gentiobioside." }, { "input": "Although the groundnut extract by itself did not show antioxidative activity, it drove the antioxidative system in cells.", "output": "There is no related enetity." }, { "input": "Pretreatment of human breast carcinoma MCF - 7 cells for 24 h with the groundnut extract and soybean isoflavone increased gene expression of heme oxygenase - 1 ( HO - 1 ), a major antioxidative stress enzyme.", "output": "isoflavone." }, { "input": "These groundnut extract - treated cells showed antioxidative activity against free radicals derived from a radical initiator.", "output": "There is no related enetity." }, { "input": "Pretreatment of cells with 100 mu g / mL groundnut extract prevented the depletion of glutathione by the radical initiator; however, treatment with 100 mu g / mL of soybean isoflavone injured the cell membrane, indicating that glutathione might be released to the extracellular environment.", "output": "glutathione, isoflavone, glutathione." }, { "input": "These results suggest that the groundnut extract had isoflavone - like activity.", "output": "isoflavone." }, { "input": "Like soybean, groundnuts are a good source of isoflavones.", "output": "isoflavones." }, { "input": "Three sulphated polysaccharides isolated from the mucilage of mud snail, Bullacta exarata philippi: characterization and antitumour activity.", "output": "There is no related enetity." }, { "input": "Three sulphated polysaccharides, coded as BEMPA, BEMPB ( 1 ), BEMPB ( 2 ), were extracted from the mucilage of mud snail of Bullacta exarata and purified by DEAE - cellulose ion - exchange and size - exclusion chromatography.", "output": "DEAE." }, { "input": "Structural analysis of purified polysaccharides by chemical and biochemical methods revealed BEMPA was a high ( 1 --> 3, 4 ) - linked mannose - containing polysaccharide with molecular weight of 22, 977 Da.", "output": "mannose." }, { "input": "BEMPB ( 1 ), with molecular weight of 64, 117 Da, was a high ( 1 --> 3 ) - linked arabinose - containing polysaccharide.", "output": "arabinose." }, { "input": "BEMPB ( 2 ) was mainly composed of ( 1 --> 3, 4 ) - linked mannose with molecular weight of 47, 507Da.", "output": "mannose." }, { "input": "The comparison between sulphated polysaccharides and their desulphated products showed that sulphate substitutions of BEMPB ( 1 ) were deduced to be at the C - 3 of ( 1 --> 4 ) - linked mannose, while sulphate substitutions of BEMPA and BEMPB ( 2 ) were at C - 4 of ( 1 --> 3 ) - linked mannose.", "output": "sulphate, mannose, sulphate, mannose." }, { "input": "Furthermore, BEMPA exhibited highest inhibitory effects on growth of B - 16 melanoma cells, and IC ( 50 ) were 31. 1 mu g / mL.", "output": "There is no related enetity." }, { "input": "Development and validation of a real - time PCR method for the simultaneous detection of black mustard ( Brassica nigra ) and brown mustard ( Brassica juncea ) in food.", "output": "There is no related enetity." }, { "input": "The paper presents a real - time PCR method allowing the simultaneous detection of traces of black mustard ( Brassica nigra ) and brown mustard ( Brassica juncea ) in food.", "output": "There is no related enetity." }, { "input": "The primers and the probe target the B. nigra partial RT gene for reverse transcriptase from gypsy - like retroelement 13G42 - 26.", "output": "There is no related enetity." }, { "input": "The real - time PCR method does not show any cross - reactivity with other Brassicaceae species with the exception of white mustard.", "output": "There is no related enetity." }, { "input": "Low cross - reactivities with cinnamon, cumin, fenugreek, ginger, rye and turmeric can be ignored because in common mustard containing foodstuffs these biological species are present in very low amounts.", "output": "There is no related enetity." }, { "input": "By analysing serially diluted DNA extracts from black and brown mustard, the DNA of both mustard species could be detected down to 0. 1 pg.", "output": "There is no related enetity." }, { "input": "With 10 ng DNA per PCR tube the real - time PCR method allows the detection of 5 ppm black and brown mustard in brewed sausages.", "output": "There is no related enetity." }, { "input": "Physical attributes and chemical composition of organic strawberry fruit ( Fragaria x ananassa Duch, Cv. Albion ) at six stages of ripening.", "output": "There is no related enetity." }, { "input": "Organic strawberry fruits ( Cv. ' Albion ' ) were harvested at six different ripening stages and evaluated for physical and chemical parameters.", "output": "There is no related enetity." }, { "input": "Biometrical characteristics and moisture content did not change significantly during ripening.", "output": "There is no related enetity." }, { "input": "Total soluble solids, pH and colour development increased while titratable acidity and fruit firmness decreased 14. 7 % and 91 %, respectively.", "output": "There is no related enetity." }, { "input": "Fructose, glucose, and sucrose followed similar tendencies.", "output": "Fructose, glucose, sucrose." }, { "input": "Final contents of these sugars were 2323. 4, 1988. 5, and 1578. 4 mg / 100 g.", "output": "sugars." }, { "input": "Citric, malic, and ascorbic acids followed a descending, irregular, and increasing tendency during ripening, respectively.", "output": "Citric , malic , and ascorbic acids." }, { "input": "Final contents of these acids were 822. 8, 245. 8, and 78. 1 mg / 100 g.", "output": "There is no related enetity." }, { "input": "Total anthocyanins content ( TAC ) increased during ripening, while the opposite was observed for total phenolic content ( TPC ).", "output": "anthocyanins." }, { "input": "TAC and TPC in ripe fruit were 56. 4 mg / 100g and 196 mg gallic acid equivalents ( GAE ) / 100 g.", "output": "gallic acid." }, { "input": "Twenty eight phenolic compounds, mainly glycosides, were identified and quantified by HPLC - DAD - MS analysis.", "output": "There is no related enetity." }, { "input": "The concentration of these compounds was ripening dependent.", "output": "There is no related enetity." }, { "input": "Ascorbic acid, nitrate, and nitrite concentration relationship to the 24hour light / dark cycle for spinach grown in different conditions.", "output": "Ascorbic acid, nitrate, nitrite." }, { "input": "Nitrate, nitrite and ascorbic acid ( vitamin C ) concentrations were determined for spinach ( Spinacia oleracea L. ) over a 24 h period to determine if light intensity ( including dark periods ) at time of harvest impacts concentrations in raw vegetables.", "output": "Nitrate, nitrite, ascorbic acid, vitamin C." }, { "input": "Nitrate, nitrate and ascorbic acid concentrations varied significantly over the 24 h period and appeared to be related to changes in light intensity.", "output": "Nitrate, nitrate, ascorbic acid." }, { "input": "Light intensity at the time an experimental sample is collected may affect the concentration of some constituents that a researcher is studying.", "output": "There is no related enetity." }, { "input": "Also, nitrate and nitrite concentrations in raw spinach can be reduced by harvesting at the best time of day.", "output": "nitrate, nitrite." }, { "input": "The highest nitrate concentrations in spinach occurred in the dark just prior to an increase in light intensity.", "output": "nitrate." }, { "input": "Ascorbic acid was near its highest level for the 24 h period when the light intensity initially increased, then decreased to its lowest level around 3 - 6 h later.", "output": "Ascorbic acid." }, { "input": "Physico - chemical and antioxidant properties of four mango ( Mangifera indica L. ) cultivars in China.", "output": "There is no related enetity." }, { "input": "Four principal mango cultivars ( Tainong No. 1, Irwin, JinHwang and Keitt ) grown in southern China were selected, and their physico - chemical and antioxidant properties were characterized and compared.", "output": "There is no related enetity." }, { "input": "Of all the four cultivars, Tainong No. 1 had highest content of total phenols, rho - coumaric acid, sinapic acid, quercetin, titratable acidity, citric acid, malic acid, fructose, higher antioxidant activities ( DPPH, FRAP ) and L ( * ), lower pH, PPO activity and individual weight.", "output": "phenols, rho - coumaric acid, sinapic acid, quercetin, citric acid, malic acid, fructose, DPPH." }, { "input": "Keitt mangoes showed significantly ( p < 0. 05 ) higher contents of beta - carotene, rho - hydroxybenzoic acid, sucrose, total sugar, total soluble solid, catechin, succinic acid and higher PPO activity.", "output": "beta - carotene, rho - hydroxybenzoic acid, sucrose, sugar, catechin, succinic acid." }, { "input": "JinHwang mangoes exhibited significantly ( p < 0. 05 ) higher individual weight and PPO activity, but had lower content of total phenols, beta - carotene and lower antioxidant activity.", "output": "phenols, beta - carotene." }, { "input": "Principal component analysis ( PCA ) allowed the four mango cultivars to be differentiated clearly based on all these physico - chemical and antioxidant properties determined in the study.", "output": "There is no related enetity." }, { "input": "EC50 estimation of antioxidant activity in DPPH. assay using several statistical programs.", "output": "DPPH .." }, { "input": "DPPH (. ) assay is a reliable method to determine the antioxidant capacity of biological substrates.", "output": "DPPH ( . )." }, { "input": "The DPPH (. ) radical scavenging activity is generally quantified in terms of inhibition percentage of the pre - formed free radical by antioxidants, and the EC ( 50 ) ( concentration required to obtain a 50 % antioxidant effect ) is a typically employed parameter to express the antioxidant capacity and to compare the activity of different compounds.", "output": "DPPH ( . )." }, { "input": "In this study, the EC ( 50 ) estimation was performed using a comparative approach based on various regression models implemented in six specialized computer programs: GraphPad Prism (R) version 5. 01, BLeSq, OriginPro (R) 8. 5. 1, SigmaPlot (R) 12, BioDataFit (R) 1. 02, and IBM SPSS Statistics (R) Desktop 19. 0.", "output": "There is no related enetity." }, { "input": "For this project, quercetin, catechin, ascorbic acid, caffeic acid, chlorogenic acid and acetylcysteine were screened as antioxidant standards with DPPH (. ) assay to define the EC ( 50 ) parameters.", "output": "quercetin, catechin, ascorbic acid, caffeic acid, chlorogenic acid, acetylcysteine, DPPH ( . )." }, { "input": "All the statistical programs gave similar EC ( 50 ) values, but GraphPad Prism (R) five - parameter analysis pointed out a best performance, also showing a minor variance in relation to the actual EC ( 50 ).", "output": "There is no related enetity." }, { "input": "2012: no trans fatty acids in Spanish bakery products.", "output": "trans fatty acids." }, { "input": "Trans fatty acids ( TFA ) are strongly correlated with an increased risk of cardiovascular and other chronic diseases.", "output": "Trans fatty acids, TFA." }, { "input": "Current dietary recommendations exclude bakery products from frequent consumption basically due to their traditionally high content of TFA.", "output": "TFA." }, { "input": "The aim of this work was to analyse the lipid profile of different bakery products currently commercialised in Spain and with a conventionally high fat and TFA content.", "output": "TFA." }, { "input": "Premium and store brands for each product were included in the study.", "output": "There is no related enetity." }, { "input": "No significant amounts of TFA were found in any of the analysed products, regardless the brand.", "output": "TFA." }, { "input": "TFA content ranged between 0. 17 g and 0. 22 g / 100 g product ( mean = 0. 19 g / 100 g product ).", "output": "TFA." }, { "input": "Expressed on percentage of fatty acids, the maximum value was 0. 87 g / 100 g fatty acids and the mean value was 0. 68 %.", "output": "fatty acids, fatty acids." }, { "input": "These data are significantly lower than those observed in previously published papers for these types of products, and highlighted the importance of updating food composition databases in order to accurately estimate the real and current intake of TFA.", "output": "TFA." }, { "input": "Long - term supplementation of high pigmented rice bran oil ( Oryza sativa L. ) on amelioration of oxidative stress and histological changes in streptozotocin - induced diabetic rats fed a high fat diet; Riceberry bran oil.", "output": "streptozotocin." }, { "input": "Diabetes is a serious health problem.", "output": "There is no related enetity." }, { "input": "Searching for alternative natural antioxidants is considered important strategy to manage diabetes.", "output": "There is no related enetity." }, { "input": "This study evaluated the effect of Riceberry bran oil ( RBBO ) supplementation on oxidative stress and organ histology in streptozotocin - induced diabetic rats fed a high fat ( HF ) diet.", "output": "streptozotocin." }, { "input": "Adult male Sprague - Dawley rats with hyperglycemia were divided into four groups: DM group fed a HF diet alone; DMRL group fed a HF diet and 5 % RBBO; DMRM group fed a HF diet and 7. 5 % RBBO; DMRH group fed a HF diet and 15 % RBBO.", "output": "There is no related enetity." }, { "input": "Normal rats were used as normal control and were divided into NC and NR group fed a normal diet containing either 5 % corn oil or 5 % RBBO, respectively.", "output": "There is no related enetity." }, { "input": "After 12 weeks, RBBO significantly decreased malondialdehyde and restored superoxide dismutase, catalase, glutathione peroxidase, coenzyme Q ( 10 ) and ORAC levels in diabetic rats.", "output": "malondialdehyde, superoxide, glutathione." }, { "input": "RBBO additionally improved the regenerative changes of the pancreas, kidneys, heart and liver.", "output": "There is no related enetity." }, { "input": "These findings indicate that pigmented RBBO could provide beneficial effect on diabetes by decreasing oxidative stress and recovering organ histology.", "output": "There is no related enetity." }, { "input": "The antioxidant activity of teas measured by the FRAP method adapted to the FIA system: optimising the conditions using the response surface methodology.", "output": "There is no related enetity." }, { "input": "This study proposes a FRAP assay adapted to FIA system with a merging zones configuration.", "output": "There is no related enetity." }, { "input": "The FIA system conditions were optimised with the response surface methodology using the central composite rotatable design.", "output": "There is no related enetity." }, { "input": "The optimisation parameters studied were: the carrier flow rate, the lengths of the sample and reagent loops, and reactor length.", "output": "There is no related enetity." }, { "input": "The conditions selected in accordance with the results were: carrier flow rate of 1. 00 ml / min, length of the loops 18. 2 cm and length of the reaction coil 210. 1 cm.", "output": "There is no related enetity." }, { "input": "The detection and quantification limits were, respectively, 28. 6 and 86. 8 mu mol / l Fe ( 2 + ), and the precision was 1. 27 %.", "output": "Fe ( 2 + )." }, { "input": "The proposed method had an analytical frequency of 30 samples / h and about 95 % less volume of FRAP reagent was consumed.", "output": "There is no related enetity." }, { "input": "The FRAP assay adapted to the FIA system under the optimised conditions was utilised to determine the antioxidant activity of tea samples.", "output": "There is no related enetity." }, { "input": "Optimization of gas chromatography - single quadrupole mass spectrometry conditions for multiresidue analysis of pesticides in grapes in compliance to EU - MRLs.", "output": "There is no related enetity." }, { "input": "A single quadrupole GC - MS method was optimized for multiresidue determination of 47 pesticides in grapes with limit of quantifications of each compound in compliance with the EU - MRL requirements.", "output": "There is no related enetity." }, { "input": "Sample preparation involved extraction of 10 g sample with 10 ml ethyl acetate ( + 10 g sodium sulphate ) by homogenization at 15, 000 rpm followed by centrifugation at 3000 rpm.", "output": "ethyl acetate, sodium sulphate." }, { "input": "The supernatant was cleaned by dispersive solid phase extraction with primary secondary amine and acidified with 0. 1 % formic acid.", "output": "primary secondary amine, formic acid." }, { "input": "Residues were estimated in selected ion monitoring mode with programmable temperature vaporizer - large volume injection ( 8 mu l ).", "output": "There is no related enetity." }, { "input": "All the GC and MS parameters were thoroughly optimized to achieve satisfactory linearity ( R ( 2 ) > 0. 99 ) within 0. 01 - 0. 25 mg kg ( - 1 ) with minimum matrix interferences.", "output": "There is no related enetity." }, { "input": "Recoveries at 0. 01 and 0. 02 mg kg ( - 1 ) were within 67 - 120 % with associated precision RSD below 19 %.", "output": "There is no related enetity." }, { "input": "The method was successfully applied for analysis of the real world samples for incurred residues.", "output": "There is no related enetity." }, { "input": "Phase behaviour of oat beta - glucan / sodium caseinate mixtures varying in molecular weight.", "output": "sodium." }, { "input": "The isothermal phase behaviour at 5 degrees C of mixtures of sodium caseinate and oat beta - glucan isolates varying in molecular weight ( MW ) was investigated by means of phase diagram construction, rheometry, fluorescence microscopy and electrophoresis.", "output": "sodium." }, { "input": "Phase diagrams indicated that the compatibility of the beta - glucan / sodium caseinate system increases as beta - glucan MW decreases.", "output": "sodium." }, { "input": "Images of mixtures taken at various biopolymer concentrations revealed phase separated domains.", "output": "There is no related enetity." }, { "input": "Results also revealed that at the state of thermodynamic equilibrium, lower MW samples yielded considerable viscosity in the mixture.", "output": "There is no related enetity." }, { "input": "At equivalent hydrodynamic volume of beta - glucan in the mixtures, samples varying in molecular weight exhibited similar flow behaviour.", "output": "There is no related enetity." }, { "input": "A deviation dependent on the protein concentration was observed for the high MW sample in the concentrated regime due to the size of beta - glucan aggregates formed.", "output": "There is no related enetity." }, { "input": "Results demonstrate that by controlling the structural features of beta - glucan in mixtures with sodium caseinate, informed manipulation of rheological properties in these systems can be achieved.", "output": "sodium." }, { "input": "Chemical composition, antimicrobial, cytotoxic and antioxidant activities of the essential oil of Artemisia indica Willd.", "output": "There is no related enetity." }, { "input": "Essential oil from the aerial parts of Artemisia indica was analysed by GC - FID and GC - MS.", "output": "There is no related enetity." }, { "input": "A total of 43 compounds representing 96. 8 % of the oil were identified and the major components were found to be artemisia ketone ( 42. 1 % ), germacrene B ( 8. 6 % ), borneol ( 6. 1 % ) and cis - chrysanthenyl acetate ( 4. 8 % ).", "output": "artemisia ketone, germacrene B, borneol, cis - chrysanthenyl acetate." }, { "input": "Antimicrobial activity of the oil was evaluated against seven clinically significant bacterial and two fungal strains.", "output": "There is no related enetity." }, { "input": "The essential oil and its major constituents exhibited moderate to potent, broad - spectrum antibacterial and antifungal activities targeting both Gram - positive and Gram - negative bacteria.", "output": "There is no related enetity." }, { "input": "In vitro cytotoxicity evaluation against four human cancer cell lines THP - 1 ( leukemia ), A - 549 ( lung ), HEP - 2 ( liver ) and Caco - 2 ( colon ) showed that the essential oil exhibited concentration dependant growth inhibition in the 10 - 100 mu g / ml dilution range, with IC ( 50 ) values of 10 mu g / ml ( THP - 1 ), 25 mu g / ml ( A - 549 ), 15. 5 mu g / ml ( HEP - 2 ) and 19. 5 mu g / ml ( Caco - 2 ).", "output": "There is no related enetity." }, { "input": "It was interesting to note that the essential oil also exhibited potent antioxidant activity.", "output": "There is no related enetity." }, { "input": "Multi - targeted screening of botanicals in food supplements by liquid chromatography with tandem mass spectrometry.", "output": "There is no related enetity." }, { "input": "Safety, quality and composition assessments of food supplements based on botanical ingredients are of major concern, as they have usually not been through a rigorous testing process as required for the approval of therapeutic phytopreparations.", "output": "There is no related enetity." }, { "input": "Therefore, an efficient multi - targeted method was developed to screen selected botanicals of interest in herbal food supplements.", "output": "There is no related enetity." }, { "input": "Liquid chromatography coupled with a hybrid triple quadrupole linear ion trap was used for this purpose.", "output": "There is no related enetity." }, { "input": "Botanicals were characterised by means of appropriate biomarkers, which were unambiguously identified by mass spectrometry using an information dependent acquisition experiment which combined a multiple reaction monitoring survey with dependent enhanced product ion scans.", "output": "There is no related enetity." }, { "input": "During this procedure, product ion scans of targeted analytes were generated at three collision energies and compared with an in - house library of MS / MS spectra acquired from reference standards of all biomarkers.", "output": "There is no related enetity." }, { "input": "This generic method enables detection, identification and quantification of 98 biomarkers intended to characterise 79 selected plants.", "output": "There is no related enetity." }, { "input": "Pattern recognition of peach cultivars ( Prunus persica L. ) from their volatile components.", "output": "There is no related enetity." }, { "input": "The volatile compounds of four peach cultivars ( Prunus persica L. ) were studied: Sudanell, San Lorenzo, Miraflores and Calanda ( two clones, Calante and Jesca ).", "output": "There is no related enetity." }, { "input": "17 - 23 Samples of each cultivar with the same maturity level were analyzed, measuring color, firmness, and soluble solids content.", "output": "There is no related enetity." }, { "input": "The pulp was crushed and mixed with water prior to HS - SPME analysis, and GC - MS was used to determine the volatile compounds.", "output": "There is no related enetity." }, { "input": "Sixty - five compounds were identified using spectral library matching, Kovat ' s indices and, when available, pure standards.", "output": "There is no related enetity." }, { "input": "The main components were lactones and C6 compounds.", "output": "lactones." }, { "input": "From the distribution of these compounds, Principal Component Analysis led to the clustering of the samples according to their different cultivars.", "output": "There is no related enetity." }, { "input": "Finally, Canonical Component Analysis was used to create a classification function that identifies the origin of an unknown sample from its volatile composition.", "output": "There is no related enetity." }, { "input": "The results obtained will help to avoid fraud and protect the European Designation of Origin ' Melocot o n de Calanda '.", "output": "There is no related enetity." }, { "input": "Superomniphobic surfaces for effective chemical shielding.", "output": "There is no related enetity." }, { "input": "Superomniphobic surfaces display contact angles > 150 degrees and low contact angle hysteresis with essentially all contacting liquids.", "output": "There is no related enetity." }, { "input": "In this work, we report surfaces that display superomniphobicity with a range of different non - Newtonian liquids, in addition to superomniphobicity with a wide range of Newtonian liquids.", "output": "There is no related enetity." }, { "input": "Our surfaces possess hierarchical scales of re - entrant texture that significantly reduce the solid - liquid contact area.", "output": "There is no related enetity." }, { "input": "Virtually all liquids including concentrated organic and inorganic acids, bases, and solvents, as well as viscoelastic polymer solutions, can easily roll off and bounce on our surfaces.", "output": "There is no related enetity." }, { "input": "Consequently, they serve as effective chemical shields against virtually all liquids - - organic or inorganic, polar or nonpolar, Newtonian or non - Newtonian.", "output": "There is no related enetity." }, { "input": "Lucidone from Lindera erythrocarpa Makino fruits suppresses adipogenesis in 3T3 - L1 cells and attenuates obesity and consequent metabolic disorders in high - fat diet C57BL / 6 mice.", "output": "Lucidone." }, { "input": "Obesity is associated with an increased risk of development of numerous diseases including type 2 diabetes, hypertension, hyperlipidemia, and cardiovascular disease.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the effects of lucidone in vitro on gene expression during adipogenesis in 3T3 - L1 cells and in vivo on high - fat diet induced obesity in C57BL / 6 mice.", "output": "lucidone." }, { "input": "Lucidone at 40 mu mol / L suppressed adipogenesis in 3T3 - L1 cells by reducing transcription levels of adipogenic genes, including PPAR gamma, C / EBP alpha, LXR - alpha, LPL, aP2, GLUT4 and adiponectin.", "output": "Lucidone." }, { "input": "Five - week - old male C57BL / 6 mice fed a high fat diet ( 60 % energy from fat ) supplemented with lucidone at a dosage of 1250 mg / kg of diet for 12 weeks had reduced body and liver weight, reduced epididymal and perirenal adipose tissue, decreased food efficiency ( percentage of weight gain divided by food intake ), and lowered plasma cholesterol, triglyceride, glucose, and insulin levels.", "output": "lucidone, cholesterol, triglyceride, glucose." }, { "input": "Dissection of adipose tissue from lucidone - treated mice showed a reduction in the average fat - cell size and percentage of large adipocytes.", "output": "lucidone." }, { "input": "These results provide evidence that dietary intake of lucidone alleviates high fat diet - induced obesity in C57BL / 6 mice and reveals the potential of lucidone as a nutraceutical to prevent obesity and consequent metabolic disorders.", "output": "lucidone, lucidone." }, { "input": "A new single - photon emission computed tomography ( SPECT ) imaging agent for serotonin transporters: [ ( 125 ) I ] Flip - IDAM, ( 2 - ( ( 2 - ( ( dimethylamino ) methyl ) - 4 - iodophenyl ) thio ) phenyl ) methanol.", "output": "serotonin, [ ( 125 ) I ] Flip - IDAM, ( 2 - ( ( 2 - ( ( dimethylamino ) methyl ) - 4 - iodophenyl ) thio ) phenyl ) methanol." }, { "input": "New ligands for in vivo brain imaging of serotonin transporter ( SERT ) with single photon emission tomography ( SPECT ) were prepared and evaluated.", "output": "serotonin." }, { "input": "An efficient synthesis and radiolabeling of a biphenylthiol, FLIP - IDAM, 4, was accomplished.", "output": "biphenylthiol, FLIP - IDAM." }, { "input": "The affinity of FLIP - IDAM was evaluated by an in vitro inhibitory binding assay using [ ( 125 ) I ] - IDAM as radioligand in rat brain tissue homogenates ( K ( i ) = 0. 03 nM ).", "output": "FLIP - IDAM, [ ( 125 ) I ] - IDAM." }, { "input": "New [ ( 125 ) I ] Flip - IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30 min post iv injection.", "output": "[ ( 125 ) I ] Flip - IDAM." }, { "input": "The faster in vivo kinetics for brain uptake and a rapid washout from non - specific regions provide excellent signal to noise ratio.", "output": "There is no related enetity." }, { "input": "This new agent, when labeled with ( 123 ) I, may be a useful imaging agent for mapping SERT binding sites in the human brain.", "output": "( 123 ) I." }, { "input": "Structure activity relationship studies of tricyclic bispyran sulfone gamma - secretase inhibitors.", "output": "tricyclic bispyran sulfone." }, { "input": "An investigation is detailed of the structure activity relationships ( SAR ) of two sulfone side chains of compound ( - ) - 1a ( SCH 900229 ), a potent, PS1 - selective gamma - secretase inhibitor and clinical candidate for the treatment of Alzheimer ' s disease.", "output": "sulfone, SCH 900229." }, { "input": "Specifically, 4 - CF ( 3 ) and 4 - Br substituted arylsulfone analogs, ( - ) - 1b and ( - ) - 1c, are equipotent to compound ( - ) - 1a.", "output": "4 - CF ( 3 ), 4 - Br, arylsulfone." }, { "input": "On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.", "output": "sulfone." }, { "input": "Regioselective synthesis of 5 - and 6 - methoxybenzimidazole - 1, 3, 5 - triazines as inhibitors of phosphoinositide 3 - kinase.", "output": "5 - and 6 - methoxybenzimidazole - 1 , 3 , 5 - triazines." }, { "input": "Phosphoinositide 3 - kinases ( PI3K ) hold significant therapeutic potential as novel targets for the treatment of cancer.", "output": "There is no related enetity." }, { "input": "ZSTK474 ( 4a ) is a potent, pan - PI3K inhibitor currently under clinical evaluation for the treatment of cancer.", "output": "ZSTK474." }, { "input": "Structural studies have shown that derivatisation at the 5 - or 6 - position of the benzimidazole ring may influence potency and isoform selectivity.", "output": "benzimidazole." }, { "input": "However, synthesis of these derivatives by the traditional route results in a mixture of the two regioisomers.", "output": "There is no related enetity." }, { "input": "We have developed a straightforward regioselective synthesis that gave convenient access to 5 - and 6 - methoxysubstituted benzimidazole derivatives of ZSTK474.", "output": "5 - and 6 - methoxysubstituted benzimidazole, ZSTK474." }, { "input": "While 5 - methoxy substitution abolished activity at all isoforms, the 6 - methoxy substitution is consistently 10 - fold more potent.", "output": "5 - methoxy, 6 - methoxy." }, { "input": "This synthesis will allow convenient access to further 6 - position derivatives, thus allowing the full scope of the structure - activity relationships of ZSTK474 to be probed.", "output": "ZSTK474." }, { "input": "Synthesis of DNA oligonucleotides containing C5 - ethynylbenzenesulfonamide - modified nucleotides ( EBNA ) by polymerases towards the construction of base functionalized nucleic acids.", "output": "C5 - ethynylbenzenesulfonamide - modified nucleotides, EBNA." }, { "input": "C5 - Ethynylbenzenesulfonamide - modified nucleotide ( EBNA ) was investigated as substrate of various DNA polymerases.", "output": "C5 - Ethynylbenzenesulfonamide - modified nucleotide, EBNA." }, { "input": "The experiments revealed that KOD, Phusion and Klenow DNA polymerases successfully accepted EBNA - T nucleotide as a substrate and yielded the fully extended DNA.", "output": "EBNA, nucleotide." }, { "input": "KOD DNA polymerase was found to be the most efficient enzyme to furnish EBNA - T containing DNA in good yields.", "output": "EBNA." }, { "input": "Phusion DNA polymerase efficiently amplified the template containing EBNA - T nucleotides by PCR.", "output": "EBNA, nucleotides." }, { "input": "Synthesis and evaluation of 8 - oxoadenine derivatives as potent Toll - like receptor 7 agonists with high water solubility.", "output": "8 - oxoadenine." }, { "input": "We report the discovery of novel series of highly potent TLR7 agonists based on 8 - oxoadenines, 1 and 2 by introducing and optimizing various tertiary amines onto the N ( 9 ) - position of the adenine moiety.", "output": "8 - oxoadenines, tertiary amines, N, adenine." }, { "input": "The introduction of the amino group resulted in not only improved water solubility but also enhanced TLR7 agonistic activity.", "output": "amino." }, { "input": "In particular compound 20 ( DSR - 6434 ) indicated an optimal balance between the agonistic potency and high water solubility.", "output": "DSR - 6434." }, { "input": "It also demonstrated a strong antitumor effect in vivo by intravenous administration in a tumor bearing mice model.", "output": "There is no related enetity." }, { "input": "A - ring modification of SCH 900229 and related chromene sulfone gamma - secretase inhibitors.", "output": "SCH 900229, sulfone." }, { "input": "Attempts to block metabolism by incorporating a 9 - fluoro substituent at the A - ring of compound 1 ( SCH 900229 ) using electrophilic Selectfluor (TM) led to an unexpected oxidation of the A - ring to give difluoroquinone analog 1a.", "output": "9 - fluoro, SCH 900229, Selectfluor, difluoroquinone." }, { "input": "Oxidation of other related chromene gamma - secretase inhibitors 2 - 8 resulted in similar difluoroquinone analogs 2a - 8a, respectively.", "output": "difluoroquinone." }, { "input": "These quinone products exhibited comparable in vitro potency in a gamma - scretase membrane assay, but were several fold less potent in a cell - based assay in lowering A beta 40 - 42, compared to their parent compounds.", "output": "quinone." }, { "input": "Inhibition of the beta - carbonic anhydrases from Mycobacterium tuberculosis with C - cinnamoyl glycosides: identification of the first inhibitor with anti - mycobacterial activity.", "output": "C - cinnamoyl glycosides." }, { "input": "A small series of C - cinnamoyl glycoside containing the phenol moiety was tested for the inhibition of the three Mycobacterium tuberculosis beta - carbonic anhydrases ( CAs, EC 4. 2. 1. 1 ) with activities in the low micromolar range detected.", "output": "C - cinnamoyl glycoside, phenol." }, { "input": "The compounds were also tested for the inhibition of growth of M. tuberculosis H ( 37 ) Rv strain, leading to the identification of ( E ) - 1 - ( 2 ', 3 ', 4 ', 6 ' - tetra - O - acetyl - beta - D - glucopyranosyl ) - 4 - ( 3 - hydroxyphenyl ) but - 3 - en - 2 - one ( 1 ) as the first carbonic anhydrase inhibitor with anti - tubercular activity.", "output": "( E ) - 1 - ( 2 ' , 3 ' , 4 ' , 6 ' - tetra - O - acetyl - beta - D - glucopyranosyl ) - 4 - ( 3 - hydroxyphenyl ) but - 3 - en - 2 - one." }, { "input": "Discovery of liver - targeted inhibitors of stearoyl - CoA desaturase ( SCD1 ).", "output": "stearoyl - CoA." }, { "input": "Inhibitors based on a benzo - fused spirocyclic oxazepine scaffold were discovered for stearoyl - coenzyme A ( CoA ) desaturase 1 ( SCD1 ) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model.", "output": "benzo - fused spirocyclic oxazepine, stearoyl - coenzyme A, CoA." }, { "input": "Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties.", "output": "oxazepine, benzylic, piperidine." }, { "input": "After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle - linked amides, and thiazoles.", "output": "piperidine, nitrogen, glycine amides, amides, thiazoles." }, { "input": "Responding to concerns about target localization and potential mechanism - based side effects, an initial effort was also made to improve liver concentration in an available rat PK model.", "output": "There is no related enetity." }, { "input": "An advanced compound 17m with a 5 - carboxy - 2 - thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies.", "output": "5 - carboxy - 2 - thiazole, spirocyclic piperidine." }, { "input": "The venom optimization hypothesis revisited.", "output": "There is no related enetity." }, { "input": "Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non - proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence.", "output": "There is no related enetity." }, { "input": "However, because venoms are protein - rich, they come with a high metabolic price tag.", "output": "There is no related enetity." }, { "input": "The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non - essential to survival of the animal.", "output": "There is no related enetity." }, { "input": "The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure.", "output": "There is no related enetity." }, { "input": "Indeed, various behaviors have been identified that appear consistent with frugality of venom use.", "output": "There is no related enetity." }, { "input": "This has led to formulation of the \" venom optimization hypothesis \" ( Wigger et al. ( 2002 ) Toxicon 40, 749 - 752 ), also known as \" venom metering \", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control.", "output": "There is no related enetity." }, { "input": "Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems.", "output": "There is no related enetity." }, { "input": "We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom.", "output": "There is no related enetity." }, { "input": "However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy.", "output": "There is no related enetity." }, { "input": "We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum.", "output": "There is no related enetity." }, { "input": "Depth - resolved characterization of diffusion properties within and across minimally - perturbed skin layers.", "output": "There is no related enetity." }, { "input": "We examine by both experimental and computational means the diffusion of macromolecules through the skin strata ( both the epidermis and dermis ).", "output": "There is no related enetity." }, { "input": "Using mouse skin as a test case, we present a novel high - resolution technique to characterize the diffusion properties of heterogeneous biomaterials using 3D imaging of fluorescent probes, precisely - deposited in minimally - perturbed in vivo skin layers.", "output": "There is no related enetity." }, { "input": "We find the diffusivity of the delivered macromolecules ( 70 kDa and 2 MDa rhodamine - dextrans ) low within the packed cellular arrangement of the epidermis, while gradually increasing ( by ~ an order of magnitude ) through the dermis - - as pores in the fibrillar network enlarge from the papillary to the reticular dermis.", "output": "rhodamine." }, { "input": "Our experimental and computational approaches for investigating the diffusion through skin strata help in the assessment and optimization of controlled delivery of drugs ( e. g. vaccines ) to specific sites ( e. g. antigen presenting cells ).", "output": "There is no related enetity." }, { "input": "How cationic lipids transfer nucleic acids into cells and across cellular membranes: recent advances.", "output": "There is no related enetity." }, { "input": "Cationic lipid - and polymer - based nanodevices are considered appropriate alternatives for virus - based particles for delivery of nucleic acids, including genes and siRNA, into eukaryotic cells.", "output": "There is no related enetity." }, { "input": "Because of colloidal stability concerns and toxicity issues the potential in vivo application of these so - called non - viral systems, in particular cationic lipids, was met with considerable skepticism.", "output": "There is no related enetity." }, { "input": "However, in recent years, the development of novel ionizable cationic lipid formulations in conjunction with sophisticated procedures to carefully control the size of the nanoparticles has rapidly advanced options for a successful therapeutic application.", "output": "There is no related enetity." }, { "input": "Thus it would appear that cationic lipids have taken a prominent step ahead in their potential use as nanocarriers for siRNA delivery in gene silencing of target genes in a variety of diseases.", "output": "There is no related enetity." }, { "input": "Verification and improvement of delivery efficiency as well as screening of targeting ligands justify further work in revealing underlying mechanisms that are instrumental in efficient crossing of cellular barriers by cationic lipid - based nanocarriers.", "output": "There is no related enetity." }, { "input": "In this regard, triggering entry into specific pathways or modulating trafficking along such pathways, either by targeting of nanoparticles or by affecting specific cellular signaling pathways, may represent promising tools.", "output": "There is no related enetity." }, { "input": "Such options may involve, for example, facilitating nanoparticle transport across endothelial cells by transcytotic mechanisms, or improving delivery efficiency by affecting nanoparticle trafficking that avoids lysosomal delivery.", "output": "There is no related enetity." }, { "input": "Here, recent progress in the field of lipid - based nanocarriers is discussed, with a focus on mechanisms underlying their interactions with cells in vitro.", "output": "There is no related enetity." }, { "input": "Where appropriate, we will include mechanisms for polymer - based systems in our discussion.", "output": "There is no related enetity." }, { "input": "N - acetylgalactosamine functionalized mixed micellar nanoparticles for targeted delivery of siRNA to liver.", "output": "N - acetylgalactosamine." }, { "input": "Due to its efficient and specific gene silencing ability, RNA interference has shown great potential in the treatment of liver diseases.", "output": "There is no related enetity." }, { "input": "However, achieving in vivo delivery of siRNA to critical liver cells remains the biggest obstacle for this technique to be a real clinic therapeutic modality.", "output": "There is no related enetity." }, { "input": "Here, we describe a promising liver targeting siRNA delivery system based on N - acetylgalactosamine functionalized mixed micellar nanoparticles ( Gal - MNP ), which can efficiently deliver siRNA to hepatocytes and silence the target gene expression after systemic administration.", "output": "N - acetylgalactosamine." }, { "input": "The Gal - MNP were assembled in aqueous solution from mixed N - acetylgalactosamine functionalized poly ( ethylene glycol ) - b - poly ( epsilon - caprolactone ) and cationic poly ( epsilon - caprolactone ) - b - poly ( 2 - aminoethyl ethylene phosphate ) ( PCL - b - PPEEA ); the properties of nanoparticles, including particle size, zeta potential and the density of poly ( ethylene glycol ) could be easily regulated.", "output": "N - acetylgalactosamine, poly ( ethylene glycol ) - b - poly ( epsilon - caprolactone ), poly ( epsilon - caprolactone ) - b - poly ( 2 - aminoethyl ethylene phosphate ), PCL - b - PPEEA, poly ( ethylene glycol )." }, { "input": "The hepatocyte - targeting effect of Gal - MNP was demonstrated by significant enriching of fluorescent siRNA in primary hepatocytes in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Successful down - regulation of liver - specific apolipoprotein B ( apoB ) expression was achieved in mouse liver, at both the transcriptional and protein level, following intravenous injection of Gal - MNP / siapoB to BALB / c mice.", "output": "There is no related enetity." }, { "input": "Systemic delivery of Gal - MNP / siRNA did not induce the innate immune response or positive hepatotoxicity.", "output": "There is no related enetity." }, { "input": "The results of this study suggested therapeutic potential for the Gal - MNP / siRNA system in liver disease.", "output": "There is no related enetity." }, { "input": "Targeted adenovirus mediated inhibition of NF - kappa B - dependent inflammatory gene expression in endothelial cells in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration.", "output": "There is no related enetity." }, { "input": "We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor kappa B signal transduction could silence the proinflammatory activation status of endothelial cells.", "output": "There is no related enetity." }, { "input": "For this, an adenovirus encoding dominant - negative I kappa B ( dnI kappa B ) as a therapeutic transgene was employed.", "output": "There is no related enetity." }, { "input": "Selectivity for the endothelial cells was achieved by introduction of antibodies specific for inflammatory endothelial adhesion molecules E - selectin or VCAM - 1 chemically linked to the virus via polyethylene glycol.", "output": "polyethylene glycol." }, { "input": "In vitro, the retargeted adenoviruses selectively infected cytokine - activated endothelial cells to express functional transgene.", "output": "There is no related enetity." }, { "input": "The comparison of transductional capacity of both retargeted viruses revealed that E - selectin based transgene delivery exerted superior pharmacological effects.", "output": "There is no related enetity." }, { "input": "Targeted delivery mediated dnI kappa B transgene expression in endothelial cells inhibited the induced expression of several inflammatory genes, including adhesion molecules, cytokines, and chemokines.", "output": "There is no related enetity." }, { "input": "In vivo, in mice suffering from glomerulonephritis, E - selectin - retargeted adenovirus selectively homed in the kidney to microvascular glomerular endothelium.", "output": "There is no related enetity." }, { "input": "Subsequent downregulation of endothelial adhesion molecule expression 2 days after induction of inflammation demonstrated the pharmacological potential of this gene therapy approach.", "output": "There is no related enetity." }, { "input": "The data justify further studies towards therapeutic virus design and optimization of treatment schedules to investigate their capacity to interfere with inflammatory disease progression.", "output": "There is no related enetity." }, { "input": "In vitro anti - inflammatory effect of apigenin in the Helicobacter pylori - infected gastric adenocarcinoma cells.", "output": "apigenin." }, { "input": "Infection with Helicobacter pylori causes extensive gastric epithelial cell inflammation which may progress to atrophic gastritis, intestinal metaplasia, and even gastric adenocarcinoma.", "output": "There is no related enetity." }, { "input": "Apigenin ( 4 ', 5, 7 - trihydroxyflavone ) is widely distributed in fruits and vegetables, and is a well - known antiinflammatory supplement with low cytotoxicity.", "output": "Apigenin, 4 ' , 5 , 7 - trihydroxyflavone." }, { "input": "In this study, we investigated the anti - inflammatory effects of apigenin in H. pylori - infected MKN45 cells, for which I kappa B alpha, cyclooxygenase - 2 ( COX - 2 ), intercellular adhesion molecule - 1 ( ICAM - 1 ), reactive oxygen species ( ROS ), interleukin - 8 ( IL - 8 ), IL - 6, IL - 1 beta, and mucin - 2 ( MUC - 2 ) expressions were examined.", "output": "apigenin, oxygen." }, { "input": "Apigenin treatments ( 9. 3 - 74 mu M ) significantly increased the I kappa B alpha expression, and thus inhibited nuclear factor kappa B ( NF - kappa B ) activation, and the inflammatory factor ( COX - 2, ICAM - 1, ROS, IL - 6, and IL - 8 ) expressions decreased.", "output": "Apigenin." }, { "input": "The ROS levels decreased partially based on the intrinsic scavenging property of apigenin.", "output": "apigenin." }, { "input": "In summary, apigenin treatments effectively inhibited NF - kappa B activation and the related inflammatory factor expressions, as well as increased MUC - 2 expression in the H. pylori - infected MKN45 cells.", "output": "apigenin." }, { "input": "The compound shows great potential as a candidate agent for the inhibition of H. pylori - induced extensive gastric epithelial cell inflammation.", "output": "There is no related enetity." }, { "input": "Carbamate insecticide methomyl confers cytotoxicity through DNA damage induction.", "output": "Carbamate, methomyl." }, { "input": "Carbamate insecticide methomyl could induce genotoxic effects, including micronuclei, chromosome aberrations and sister - chromatid exchanges.", "output": "Carbamate, methomyl." }, { "input": "However, methomyl induction of cytotoxicity through DNA damage is largely unknown.", "output": "methomyl." }, { "input": "Here we identify cytotoxicity and potential genotoxicity of methomyl in vitro.", "output": "methomyl." }, { "input": "We have employed alkaline comet assay, gamma H2AX foci formation and DNA ladder assay to detected DNA damage and apoptosis of Drosophila S2, HeLa and HEK293 cells.", "output": "There is no related enetity." }, { "input": "The alkaline comet assay was used to evaluate total DNA single strand breaks ( SSBs ) in the target cells exposed in vitro to sublethal concentrations of methomyl.", "output": "methomyl." }, { "input": "As expected, methomyl induced significant concentration - dependent increases in DNA damage of target cells compared with the negative control, as measured by increases in tail length ( mu m ), tail DNA ( percentage of the comet tail ) and tail moment ( arbitrary units ).", "output": "methomyl." }, { "input": "In agreement with the comet assay data, the percentage of gamma H2AX positive reaction in HeLa cells also revealed methomyl caused DNA double strand breaks ( DSBs ) in a time - dependent manner.", "output": "methomyl." }, { "input": "Moreover, methomyl induced a significant increase of apoptosis in Drosophila S2, HeLa and HEK293 cells in a concentration - and time - dependent manner, as determined by Urea PAGE DNA fragmentation analysis.", "output": "methomyl, Urea." }, { "input": "In conclusion, methomyl is a strongly genotoxic agent that induces cell DNA damage and apoptosis in vitro at these sublethal concentrations.", "output": "methomyl." }, { "input": "Inhibition of constitutive aryl hydrocarbon receptor ( AhR ) signaling attenuates androgen independent signaling and growth in ( C4 - 2 ) prostate cancer cells.", "output": "aryl hydrocarbon, androgen." }, { "input": "The aryl hydrocarbon receptor is a member of the basic - helix - loop - helix family of transcription factors.", "output": "aryl hydrocarbon." }, { "input": "AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2, 3, 7, 8, - tetrachloro - dibenzo - p - dioxin ( TCDD ).", "output": "polyaromatic hydrocarbons, 2 , 3 , 7 , 8 , - tetrachloro - dibenzo - p - dioxin, TCDD." }, { "input": "AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450 - 1B1 ( CYP1B1 ).", "output": "There is no related enetity." }, { "input": "Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development.", "output": "There is no related enetity." }, { "input": "Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells.", "output": "androgen." }, { "input": "Immunoblot analysis shows that AhR expression is increased in androgen independent ( C4 - 2 ) prostate cancer cells when compared to androgen sensitive ( LNCaP ) cells.", "output": "androgen, androgen." }, { "input": "RT - PCR studies revealed constitutive AhR signaling in C4 - 2 cells without the ligand induced activation required in LNCaP cells.", "output": "There is no related enetity." }, { "input": "A reduction of AhR activity by short RNA mediated silencing in C4 - 2 cells reduced expression of both AhR and androgen responsive genes.", "output": "androgen." }, { "input": "The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus.", "output": "androgen, androgen, androgen." }, { "input": "Furthermore, the forced decrease in AhR expression resulted in a 50 % decline in the growth rate of C4 - 2 cells.", "output": "There is no related enetity." }, { "input": "These data indicates that AhR is required to maintain hormone independent signaling and growth by the androgen receptor in C4 - 2 cells.", "output": "androgen." }, { "input": "Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer.", "output": "androgen, androgen." }, { "input": "Immunomodulatory properties of multi - walled carbon nanotubes in peripheral blood mononuclear cells from healthy subjects and allergic patients.", "output": "carbon." }, { "input": "In the present study, we investigated the immunomodulatory activity of multi - walled carbon nanotubes ( MWCNTs ) in peripheral blood mononuclear cells ( PBMCs ) from healthy donors and mite - allergic subjects.", "output": "carbon." }, { "input": "Freshly prepared PBMCs, stimulated or not with Toll - like receptor ( TLR ) 1 - 9 agonists, a T cell mitogen ( phytohemagglutinin A ) or mite allergen extract were cultured in the presence or absence of MWCNTs.", "output": "There is no related enetity." }, { "input": "Secretion of TNF - alpha, IL - 2, IL - 5, IL - 6, IL - 12 / 23p40 or IFN - gamma was quantified in the culture supernatants by ELISA.", "output": "There is no related enetity." }, { "input": "Basal secretion of all the cytokines was not altered by MWCNTs in PBMCs from both healthy donors and allergic subjects.", "output": "There is no related enetity." }, { "input": "In PBMCs from healthy donors, TNF - alpha, IL - 6 and IL - 12 / 23p40 secretion in response to the TLR4 agonist, lipopolysaccharide was however increased in a dose - dependent manner by MWCNTs.", "output": "There is no related enetity." }, { "input": "Significant increases in the release of these cytokines were also observed in PBMCs stimulated with a TLR2 or TLR3 agonist.", "output": "There is no related enetity." }, { "input": "MWCNTs also increased the release of IL - 2 and IFN - gamma by PBMCs stimulated with a T cell mitogen.", "output": "There is no related enetity." }, { "input": "In contrast, MWCNTs inhibited allergen - induced IL - 5 secretion by PBMCs from mite - allergic subjects.", "output": "There is no related enetity." }, { "input": "As well, MWCNTs altered the capacity of PBMC - derived monocytes to differentiate into functional dendritic cells.", "output": "There is no related enetity." }, { "input": "All together, our data suggest that according to its immune cell target, MWCNTs may either promote or suppress immune responses in humans.", "output": "There is no related enetity." }, { "input": "Further investigations are necessary to fully understand the complexity behind interactions of engineered nanoparticles with the immune system.", "output": "There is no related enetity." }, { "input": "Non - melanoma skin cancer in mouse and man.", "output": "There is no related enetity." }, { "input": "As a frontier organ, skin is exposed to different environmental and / or occupational chemicals which cause cutaneous cancers in experimental animals.", "output": "There is no related enetity." }, { "input": "In mice, 7, 12 - dimethylbenz [ a ] anthrancene ( DMBA ) and the phorbol ester 12 - O - tetradecanoylphorbol - 13 - acetate ( TPA ) are frequently used as skin model tumor initiator and promoter, respectively.", "output": "7 , 12 - dimethylbenz [ a ] anthrancene, DMBA, phorbol ester, 12 - O - tetradecanoylphorbol - 13 - acetate, TPA." }, { "input": "The sequential administration of DMBA and TPA leads to the appearance of a large number of benign papillomas, of which some convert later into invasive squamous cell carcinomas ( SCC ).", "output": "DMBA, TPA." }, { "input": "At the molecular level, initiation of carcinogenesis in mouse skin consists in the mutational activation of the Ha - ras oncoprotein.", "output": "There is no related enetity." }, { "input": "HA - RAS mutations are rare in human SCC, but HA - RAS - mutated tumors appear in melanoma patients treated with B - raf inhibitors, indicating that initiated, HA - RAS - mutated stem cells also reside in human skin.", "output": "There is no related enetity." }, { "input": "Similarly, UV - induced human SCC show footprint mutations in the tumor suppressor gene TP53 which are also observed in UV - induced mouse SCC.", "output": "There is no related enetity." }, { "input": "Strong species differences exist with respect to phorbol ester - mediated tumor promotion.", "output": "phorbol ester." }, { "input": "While certain mouse strains are very susceptible, other rodent species are much less sensitive.", "output": "There is no related enetity." }, { "input": "Likewise, humans appear to be much more resistant to phorbol ester - mediated skin toxicity.", "output": "phorbol ester." }, { "input": "Papilloma formation as a result of a chemical insult is uncommon in men, questioning the relevance of this preneoplastic lesion for humans.", "output": "There is no related enetity." }, { "input": "However, skin tumorigenesis in the experimental situation and in humans appears to follow common molecular mechanisms, even though there are species differences in the morphological correlates to the preneoplastic state.", "output": "There is no related enetity." }, { "input": "Therefore, we recommend not simply labeling them as irrelevant for human risk assessment.", "output": "There is no related enetity." }, { "input": "Wound - healing plants from TCM: in vitro investigations on selected TCM plants and their influence on human dermal fibroblasts and keratinocytes.", "output": "There is no related enetity." }, { "input": "Wound - healing plants from Traditional Chinese Medicine and described for wound healing in the Pharmacopoeia of People ' s Republic of China ( 2005 ed. ) were investigated by in vitro bioassay on human skin cells.", "output": "There is no related enetity." }, { "input": "Therefore water and EtOH - water extracts ( 6: 4, v / v ) from 12 plants were tested on human primary dermal fibroblasts ( pNHDF ) and human HaCaT keratinocyte cell line by quantification of cell viability ( MTT assay ) and cellular proliferation ( BrdU incorporation ELISA ).", "output": "EtOH, MTT." }, { "input": "No functional activity was found for extracts from Achyranthis bidentatae rhizoma, Cimicifugae rhizoma, Corydalis rhizoma, Gardeniae fructus, Houttuyniae herba, Lonicerae japonicae caulis, Paeoniae rubrae radix and Rehmanniae radix.", "output": "There is no related enetity." }, { "input": "Extracts from Notoginseng radix et rhizoma, Angelicae sinensis radix and Lonicerae japonicae flos showed moderate activity, while extracts from Moutan cortex ( the root bark of Paeonia suffruticosa Andr., Ranunculaceae ) increased cell viability of HaCaT keratinocytes and pNHDF in a dose - dependent manner significantly.", "output": "There is no related enetity." }, { "input": "Bioassay - guided fractionation yielded paeonol 1, the flavan - 3 - ols catechin 2 and epicatechin - 3 - O - gallate 3, the dimeric proanthocyanidin epicatechin - ( 4 beta --> 8 ) - catechin 4, a mixture of trigalloyl - glucoses 5 and 1, 2, 3, 4, 6 - penta - O - galloyl - beta - d - glucose ( PGG ) 6.", "output": "paeonol, flavan - 3 - ols, catechin, epicatechin - 3 - O - gallate, proanthocyanidin, epicatechin - ( 4 beta --> 8 ) - catechin, trigalloyl - glucoses, 1 , 2 , 3 , 4 , 6 - penta - O - galloyl - beta - d - glucose, PGG." }, { "input": "The proanthocyanidin - containing fractions as well as PGG - containing fractions contributed substantially to the stimulating effects.", "output": "proanthocyanidin, PGG." }, { "input": "Especially PGG - containing fractions enhanced cell viability and cellular proliferation of HaCaT keratinocytes at concentration of 100nM.", "output": "PGG." }, { "input": "From these data we conclude that indication claims for TCM herbal materials must be carefully investigated in order to establish evidence - driven use of such plants.", "output": "There is no related enetity." }, { "input": "In case of Moutan cortex skin cell stimulating effects have clearly been proven.", "output": "There is no related enetity." }, { "input": "These effects can be related to the polyphenol fractions of condensed and hydrolysable tannins.", "output": "polyphenol." }, { "input": "Effects of Yerba Mate tea ( Ilex paraguariensis ) on vascular endothelial function and liver lipoprotein receptor gene expression in hyperlipidemic rats.", "output": "There is no related enetity." }, { "input": "Yerba Mate tea ( Mate ), an infusion made from the leaves of the tree Ilex paraguariensis, is a widely consumed beverage in South America.", "output": "There is no related enetity." }, { "input": "This study was performed to investigate the effect of Mate tea on vascular endothelial dysfunction and liver lipoprotein receptor gene expression in hyperlipidemic rats, with the aim of gaining insight into its known lipid - lowering protective mechanisms.", "output": "There is no related enetity." }, { "input": "Sixty male Sprague - Dawley rats were randomly divided into five groups: a normal control group ( NC ), a high - fat diet group ( HC ), and three Mate tea - treated groups.", "output": "There is no related enetity." }, { "input": "In the NC group, rats were fed with standard diet while in the other groups the rats were fed a high - fat diet for 8weeks.", "output": "There is no related enetity." }, { "input": "In the Mate tea - treated groups, the rats were fed a high - fat diet supplemented with low, moderate or high concentrations of aqueous Mate tea extract for the final 4weeks.", "output": "There is no related enetity." }, { "input": "Compared to the HC group, aqueous Mate tea extract significantly reduced endothelin ( ET ) and thromboxane B ( 2 ) ( TXB ( 2 ) ) levels and increased nitric oxide ( NO ) and 6 - keto prostaglandin F ( 1 alpha ) ( 6 - keto - PGF ( 1 alpha ) ) levels in the blood, reduced the pathological damage of vascular endothelial cells, decreased intercellular adhesion molecule - 1 ( ICAM - 1 ) protein expression in the thoracic aorta, and upregulated mRNA expression of hepatic low density lipoprotein receptor ( LDLR ) and scavenger receptor B1 ( SR - B1 ).", "output": "thromboxane B ( 2 ), TXB ( 2 ), nitric oxide, NO, 6 - keto prostaglandin F ( 1 alpha ), 6 - keto - PGF ( 1 alpha )." }, { "input": "These findings indicate that Mate tea administration might have a regulatory effect on blood fat and endothelial function in hyperlipidemia rats.", "output": "There is no related enetity." }, { "input": "The mechanism may involve protecting vascular endothelial cell function and upregulating the expression of LDLR and SR - B1 genes, thereby inhibiting the occurrence of atherosclerosis.", "output": "There is no related enetity." }, { "input": "Triterpenoid saponins from Clematis tangutica and their cardioprotective activities.", "output": "Triterpenoid saponins." }, { "input": "Phytochemical investigation of the whole plants of Clematis tangutica led to the isolation of three new triterpenoid saponins ( 1 - 3 ), together with four known saponins ( 4 - 7 ).", "output": "triterpenoid saponins, saponins." }, { "input": "Their structures were determined by extensive spectral analysis and chemical evidences.", "output": "There is no related enetity." }, { "input": "Compounds 1 - 7 were evaluated for their cardioprotective activities in cardiomyocytes anoxia / reoxygenation ( A / R ) model.", "output": "There is no related enetity." }, { "input": "The results showed that those saponins exhibited cardioprotective effects by decreasing the levels of creatine kinase - MB ( CK - MB ) and lactate dehydrogenase ( LDH ).", "output": "saponins, creatine, lactate." }, { "input": "Anti - tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells.", "output": "There is no related enetity." }, { "input": "Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment.", "output": "There is no related enetity." }, { "input": "Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti - tumor peptide analogs.", "output": "There is no related enetity." }, { "input": "The present study carried out on mouse pheochromocytoma cells ( MPCs ) and a more aggressive mouse tumor tissue - derived ( MTT ) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 ( sst2 ), growth hormone - releasing hormone ( GHRH ) receptor and the luteinizing hormone - releasing hormone ( LHRH ) receptor.", "output": "somatostatin." }, { "input": "We further demonstrated significant anti - tumor effects mediated by cytotoxic somatostatin analogs, AN - 162 and AN - 238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN - 152, and by recently developed GHRH antagonist, MIA - 602, on MPC and for AN - 152 and MIA - 602 on MTT cells.", "output": "somatostatin, Cetrorelix." }, { "input": "Studies of novel anti - tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing.", "output": "There is no related enetity." }, { "input": "The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin.", "output": "metformin." }, { "input": "Interindividual variation in response to metformin, first - line therapy for type 2 diabetes, is substantial.", "output": "metformin." }, { "input": "Given that transporters are determinants of metformin pharmacokinetics, we examined the effects of promoter variants in both multidrug and toxin extrusion protein 1 ( MATE1 ) ( g. - 66T --> C, rs2252281 ) and MATE2 ( g. - 130G --> A, rs12943590 ) on variation in metformin disposition and response.", "output": "metformin, metformin." }, { "input": "The pharmacokinetics and glucose - lowering effects of metformin were assessed in healthy volunteers ( n = 57 ) receiving metformin.", "output": "glucose, metformin, metformin." }, { "input": "The renal and secretory clearances of metformin were higher ( 22 % and 26 %, respectively ) in carriers of variant MATE2 who were also MATE1 reference ( P < 0. 05 ).", "output": "metformin." }, { "input": "Both MATE genotypes were associated with altered post - metformin glucose tolerance, with variant carriers of MATE1 and MATE2 having an enhanced ( P < 0. 01 ) and reduced ( P < 0. 05 ) response, respectively.", "output": "metformin, glucose." }, { "input": "Consistent with these results, patients with diabetes ( n = 145 ) carrying the MATE1 variant showed enhanced metformin response.", "output": "metformin." }, { "input": "These findings suggest that promoter variants of MATE1 and MATE2 are important determinants of metformin disposition and response in healthy volunteers and diabetic patients.", "output": "metformin." }, { "input": "CYP2C19 * 17 gain - of - function polymorphism is associated with peptic ulcer disease.", "output": "There is no related enetity." }, { "input": "Single - nucleotide polymorphisms ( SNPs ) in the CYP2C gene cluster have been extensively investigated as predisposing factors for nonsteroidal anti - inflammatory drug ( NSAID ) - induced peptic ulcer disease ( PUD ) or upper gastrointestinal bleeding ( UGIB ).", "output": "There is no related enetity." }, { "input": "However, results have been inconclusive owing to different study designs, limited genotyping strategies, and small sample sizes.", "output": "There is no related enetity." }, { "input": "We investigated whether eight functional SNPs in the CYP2C family of genes - - CYP2C8 * 3 ( rs11572080 and rs10509681 ), CYP2C8 * 4, CYP2C9 * 2, CYP2C9 * 3, CYP2C19 * 2, CYP2C19 * 3, and CYP2C19 * 17 - - are associated with PUD in 1, 239 Caucasian patients.", "output": "There is no related enetity." }, { "input": "Logistic regression analysis showed that only CYP2C19 * 17 was associated with PUD ( odds ratio additive model: 1. 47 ( 95 % confidence interval ( CI ) 1. 12 to 1. 92 ); P = 0. 005; R ( 2 ) 16 % ), but not UGIB, independent of NSAID use or Helicobacter pylori infection.", "output": "There is no related enetity." }, { "input": "PUD distribution varied ( P = 0. 024 ) according to CYP2C19 * 17 genotype: * 1 / * 1, 490 ( 64. 3 % ); * 1 / * 17, 304 ( 71. 7 % ); and * 17 / * 17, 31 ( 73. 8 % ).", "output": "There is no related enetity." }, { "input": "CYP2C19 * 17, a gain - of - function polymorphism, is associated with PUD irrespective of etiology.", "output": "There is no related enetity." }, { "input": "Simultaneous addition of two ligands: a potential strategy for estimating divalent ion affinities in EF - hand proteins by isothermal titration calorimetry.", "output": "There is no related enetity." }, { "input": "Capable of providing a detailed thermodynamic picture of noncovalent association reactions, isothermal titration calorimetry ( ITC ) has become a popular method for studying protein - ligand interactions.", "output": "There is no related enetity." }, { "input": "We routinely employ the technique to study divalent ion - binding by two - site EF - hand proteins from the parvalbumin - and polcalcin lineages.", "output": "There is no related enetity." }, { "input": "The combination of high Ca ( 2 + ) affinity and relatively low Mg ( 2 + ) affinity, and the attendant complication of parameter correlation, conspire to make the simultaneous extraction of binding constants and - enthalpies for both ions challenging.", "output": "Ca ( 2 + ), Mg ( 2 + )." }, { "input": "Although global analysis of multiple ITC experiments can overcome these hurdles, our current experimental protocol includes upwards of 10 titrations - requiring a substantial investment in labor, machine time, and material.", "output": "There is no related enetity." }, { "input": "This paper explores the potential for using a smaller suite of experiments that includes simultaneous titrations with Ca ( 2 + ) and Mg ( 2 + ) at different ratios of the two ions.", "output": "Ca ( 2 + ), Mg ( 2 + )." }, { "input": "The results obtained for four proteins, differing substantially in their divalent ion - binding properties, suggest that the approach has merit.", "output": "There is no related enetity." }, { "input": "The Ca ( 2 + ) - and Mg ( 2 + ) - binding constants afforded by the streamlined analysis are in reasonable agreement with those obtained from the standard analysis protocol.", "output": "Ca ( 2 + ), Mg ( 2 + )." }, { "input": "Likewise, the abbreviated analysis provides comparable values for the Ca ( 2 + ) - binding enthalpies.", "output": "Ca ( 2 + )." }, { "input": "However, the streamlined analysis can yield divergent values for the Mg ( 2 + ) - binding enthalpies - particularly those for lower affinity sites.", "output": "Mg ( 2 + )." }, { "input": "This shortcoming can be remedied, in large measure, by including data from a direct Ca ( 2 + ) titration in the presence of a high, fixed Mg ( 2 + ) concentration.", "output": "Ca ( 2 + ), Mg ( 2 + )." }, { "input": "On - chip thin film Zernike phase plate for in - focus transmission electron microscopy imaging of organic materials.", "output": "There is no related enetity." }, { "input": "Transmission electron microscopy ( TEM ) is a powerful tool for imaging nanostructures, yet its capability is limited with respect to the imaging of organic materials because of the intrinsic low contrast problem.", "output": "There is no related enetity." }, { "input": "TEM phase plates have been in development for decades, yet a reliable phase plate technique has not been available because the performance of TEM phase plates deteriorates too quickly.", "output": "There is no related enetity." }, { "input": "Such an obstacle prohibits in - focus TEM phase imaging to be routinely achievable, thus limiting the technique being used in practical applications.", "output": "There is no related enetity." }, { "input": "Here we present an on - chip thin film Zernike phase plate which can effectively release charging and allow reliable in - focus TEM images of organic materials with enhanced contrast to be routinely obtained.", "output": "There is no related enetity." }, { "input": "With this stable system, we were able to characterize many polymer solar cell specimens and consequently identified and verified the existence of an unexpected nanoparticle phase.", "output": "There is no related enetity." }, { "input": "Furthermore, we were also able to observe the fine structures of an Escherichia coli specimen, without staining, using this on - chip thin film phase plate.", "output": "There is no related enetity." }, { "input": "Our system, which can be installed on a commercial TEM, opens up exciting possibilities for TEM to characterize organic materials.", "output": "There is no related enetity." }, { "input": "Association between beta cell function and future glycemic control in patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "The aim of this study was to clarify the association between C - peptide immunoreactivity ( CPR ), a marker of beta cell function, and future glycemic control in patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "We conducted a retrospective analysis of 513 consecutive patients with type 2 diabetes who were admitted to our hospital between 2000 and 2007 and followed up for 2 years.", "output": "There is no related enetity." }, { "input": "Serum and urinary CPR levels were measured during admission, and CPR index was calculated as the ratio of CPR to plasma glucose.", "output": "glucose." }, { "input": "The associations between these markers at baseline and glycemic control after 2 years were assessed by means of logistic regression models.", "output": "There is no related enetity." }, { "input": "After 2 years, 167 patients ( 32. 6 % ) showed good glycemic control ( HbA1c < 6. 9 % ).", "output": "There is no related enetity." }, { "input": "Baseline serum and urinary CPR indices were significantly associated with good glycemic control after 2 years, and the postprandial CPR to plasma glucose ratio ( postprandial CPR index ) showed the strongest association ( odds ratio ( OR ) 1. 29, 95 % confidence interval ( CI ) 1. 12 - 1. 50, P = 0. 001 ) among CPR indices.", "output": "glucose." }, { "input": "Multivariate analyses showed consistent results ( OR 1. 23, 95 % CI 1. 03 - 1. 48, P = 0. 021 ).", "output": "There is no related enetity." }, { "input": "In conclusion, preserved beta cell function at baseline was associated with better glycemic control thereafter in patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Recyclable thermoresponsive polymer - cellulase bioconjugates for biomass depolymerization.", "output": "There is no related enetity." }, { "input": "Here we report the construction and characterization of a recoverable, thermoresponsive polymer - endoglucanase bioconjugate that matches the activity of unmodified enzymes on insoluble cellulose substrates.", "output": "There is no related enetity." }, { "input": "Two copolymers exhibiting a thermoresponsive lower critical solution temperature ( LCST ) were created through the copolymerization of an aminooxy - bearing methacrylamide with N - isopropylacrylamide ( NIPAm ) or N - isopropylmethacrylamide ( NIPMa ).", "output": "aminooxy, methacrylamide, N - isopropylacrylamide, NIPAm, N - isopropylmethacrylamide, NIPMa." }, { "input": "The aminooxy group provided a handle through which the LCST was adjusted through small - molecule quenching.", "output": "aminooxy." }, { "input": "This allowed materials with LCSTs ranging from 20. 9 to 60. 5 degrees C to be readily obtained after polymerization.", "output": "There is no related enetity." }, { "input": "The thermostable endoglucanase EGPh from the hypothermophilic Pyrococcus horikoshii was transaminated with pyridoxal - 5 ' - phosphate to produce a ketone - bearing protein, which was then site - selectively modified through oxime linkage with benzylalkoxyamine or 5 kDa - poly ( ethylene glycol ) - alkoxyamine.", "output": "pyridoxal - 5 ' - phosphate, ketone, oxime, benzylalkoxyamine, poly ( ethylene glycol ), alkoxyamine." }, { "input": "These modified proteins showed activity comparable to the controls when assayed on an insoluble cellulosic substrate.", "output": "There is no related enetity." }, { "input": "Two polymer bioconjugates were then constructed using transaminated EGPh and the aminooxy - bearing copolymers.", "output": "aminooxy." }, { "input": "After 12 h, both bioconjugates produced an equivalent amount of free reducing sugars as the unmodified control using insoluble cellulose as a substrate.", "output": "sugars." }, { "input": "The recycling ability of the NIPAm copolymer - EGPh conjugate was determined through three rounds of activity, maintaining over 60 % activity after two cycles of reuse and affording significantly more soluble carbohydrates than unmodified enzyme alone.", "output": "NIPAm, carbohydrates." }, { "input": "When assayed on acid - pretreated Miscanthus, this bioconjugate increased the amount of reducing sugars by 2. 8 - fold over three rounds of activity.", "output": "sugars." }, { "input": "The synthetic strategy of this bioconjugate allows the LCST of the material to be changed readily from a common stock of copolymer and the method of attachment is applicable to a variety of proteins, enabling the same approach to be amenable to thermophile - derived cellulases or to the separation of multiple species using polymers with different recovery temperatures.", "output": "There is no related enetity." }, { "input": "Apocynin and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3 beta - HSD and low testosterone by suppressing endoplasmic reticulum stress and activated p66Shc in rat testes.", "output": "Apocynin, raisanberine, testosterone." }, { "input": "We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase ( NOX ), therefore, APO ( apocynin ) an inhibitor of NOX and raisanberine ( RS ), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis.", "output": "NADPH, APO, apocynin, raisanberine, calcium." }, { "input": "Male Sprague - Dawley rats were exposed to hypoxia ( 10 +/- 0. 5 % O2 ) for 17d and intervened with APO and RS in the last 6d.", "output": "APO." }, { "input": "Histological changes and expression of pro - inflammation factors were evaluated in vivo.", "output": "There is no related enetity." }, { "input": "Biomarkers in isolated Leydig cells incubated with H2O2 were also assayed in vitro.", "output": "H2O2." }, { "input": "Hypoxic rats displayed lower serum testosterone and higher LH and FSH.", "output": "testosterone." }, { "input": "Upregulation of p22 / p47 ( phox ), NOX2, MMP9, PERK and p66Shc was associated with downregulation of StAR, 3 beta - HSD and Cx43 in the hypoxia testis, revealed by Western blot and immunohistochemical assay, respectively.", "output": "There is no related enetity." }, { "input": "APO and RS at least partially normalize hypoxia caused male hypogonadism by suppressing ER stress, and p66Shc in testes.", "output": "APO." }, { "input": "Kynurenic acid as an antagonist of alpha 7 nicotinic acetylcholine receptors in the brain: facts and challenges.", "output": "Kynurenic acid, acetylcholine." }, { "input": "Kynurenic acid ( KYNA ), a major tryptophan metabolite, is a glutamate receptor antagonist, which is also reported to inhibit alpha 7 nicotinic acetylcholine receptors ( alpha 7nAChRs ).", "output": "Kynurenic acid, KYNA, tryptophan, glutamate, acetylcholine." }, { "input": "Due to variations in experimental approaches, controversy has arisen regarding the ability of KYNA to directly influence alpha 7nAChR function.", "output": "KYNA." }, { "input": "Here we summarize current concepts of KYNA neurobiology and review evidence pertaining to the proposed role of KYNA as an endogenous modulator of alpha 7nAChRs and synaptic transmission.", "output": "KYNA, KYNA." }, { "input": "As dysfunction of alpha 7nAChRs plays a major role in the pathophysiology of central nervous system disorders, elucidation of KYNA ' s action on this receptor subtype has significant therapeutic implications.", "output": "KYNA." }, { "input": "Molecular mechanism by which a potent hepatitis C virus NS3 - NS4A protease inhibitor overcomes emergence of resistance.", "output": "There is no related enetity." }, { "input": "Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy.", "output": "There is no related enetity." }, { "input": "This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3 - NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1 - resistant variants.", "output": "acylsulfonamide." }, { "input": "The enhanced potency of this compound versus variants D168V and R155K facilitated x - ray determination of the inhibitor - variant complexes.", "output": "There is no related enetity." }, { "input": "In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms.", "output": "There is no related enetity." }, { "input": "Arsenic suppresses cell survival via Pirh2 - mediated proteasomal degradation of Delta Np63 protein.", "output": "Arsenic." }, { "input": "Transcription factor p63, a member of the p53 family, shares a high degree of sequence similarity with p53.", "output": "There is no related enetity." }, { "input": "Because of transcription from two distinct promoters, the p63 gene encodes two isoforms, TAp63 and Delta Np63.", "output": "There is no related enetity." }, { "input": "Although TAp63 acts as a tumor suppressor, Delta Np63 functions as an oncogene and is often overexpressed in squamous cell carcinomas.", "output": "There is no related enetity." }, { "input": "Thus, therapeutic agents targeting Delta Np63 might be used to manage tumors that overexpress Delta Np63.", "output": "There is no related enetity." }, { "input": "Here we found that arsenic trioxide, a frontline agent for acute promyelocytic leukemia, inhibits Delta Np63 but not TAp63 expression in time - and dose - dependent manners.", "output": "arsenic trioxide." }, { "input": "In addition, we found that arsenic trioxide decreases the stability of Delta Np63 protein via a proteasome - dependent pathway but has little effect on the level of Delta Np63 transcript.", "output": "arsenic trioxide." }, { "input": "Furthermore, we found that arsenic trioxide activates the Pirh2 promoter and consequently induces Pirh2 expression.", "output": "arsenic trioxide." }, { "input": "Consistent with this, we found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, arsenic - induced degradation of Delta Np63 protein.", "output": "arsenic." }, { "input": "Importantly, we found that knockdown of Delta Np63 sensitizes, whereas ectopic expression of Delta Np63 inhibits, growth suppression induced by arsenic.", "output": "arsenic." }, { "input": "Together, these data suggest that arsenic degrades Delta Np63 protein at least in part via Pirh2 - dependent proteolysis and that inhibition of Delta Np63 expression facilitates tumor cells to arsenic - induced death.", "output": "arsenic, arsenic." }, { "input": "Preferred configurations of peptide - peptide interactions.", "output": "There is no related enetity." }, { "input": "The natural and fundamental proclivities of interaction between a pair of peptide units are examined using high - level ab initio calculations.", "output": "There is no related enetity." }, { "input": "The NH... O H - bonded structure is found to be the most stable configuration of the N - methylacetamide ( NMA ) model dimer, but only slightly more so than a stacked arrangement.", "output": "NH, O H, N - methylacetamide, NMA." }, { "input": "The H - bonded geometry is destabilized by only a small amount if the NH group is lifted out of the plane of the proton - accepting amide.", "output": "H, NH, amide." }, { "input": "This out - of - plane motion is facilitated by a stabilizing charge transfer from the CO pi bond to the NH sigma * antibonding orbital.", "output": "CO, NH." }, { "input": "The parallel and antiparallel stacked dimers are nearly equal in energy, both only slightly less stable than the NH... O H - bonded structure.", "output": "NH, O H." }, { "input": "Both are stabilized by a combination of CH... O H - bonding and a pi --> pi * transfer between the two CO bonds.", "output": "CH, O H, CO." }, { "input": "There are no minima on the surface that are associated with O ( lp ) --> pi * ( CO ) transfers, due in large part to strong electrostatic repulsion between the two O atoms, which resists an approach of a carbonyl O from above the C = O bond of the other amide.", "output": "O, CO, O, carbonyl, O, C = O, amide." }, { "input": "Controlling Porphyrin Nanoarchitectures at Solid Interfaces.", "output": "Porphyrin." }, { "input": "Two complementary examples of porphyrin nanoarchitectonics are presented.", "output": "porphyrin." }, { "input": "The fabrication of binary molecular monolayers using two different porphyrin molecules, tetrakis ( 3, 5 - di - t - butyl - 4 - hydroxyphenyl ) porphyrin ( 1 ) and tetrakis ( 4 - pyridyl ) porphyrin ( 2 ), by deposition in ultrahigh vacuum was demonstrated.", "output": "porphyrin, tetrakis ( 3 , 5 - di - t - butyl - 4 - hydroxyphenyl ) porphyrin, tetrakis ( 4 - pyridyl ) porphyrin." }, { "input": "Two unusual heteromolecular monolayer structures were observed, with one exhibiting good separation of 1 molecules within the monolayer.", "output": "There is no related enetity." }, { "input": "Also, a synthetic nanoarchitectonic approach was used to prepare self - assembled molecular nanowires at a mica substrate.", "output": "There is no related enetity." }, { "input": "The nanowires could be observed to grow using atomic force microscopy ( AFM ), and the network structures of the nanowires could be influenced by manipulation using the AFM probe tip.", "output": "There is no related enetity." }, { "input": "Synthesis and antioxidant activity of thymol and carvacrol based Schiff bases.", "output": "thymol, carvacrol, Schiff bases." }, { "input": "Thymol and carvacrol are well known antioxidants found in the extract of the plants of thyme species.", "output": "Thymol, carvacrol." }, { "input": "The Schiff bases of 2 - iso - propyl - 5 - methyl - phenol ( thymol / 1a ), 2 - tert - butyl - 5 - methyl - phenol ( 1b ) and 5 - iso - propyl - 2 - methyl - phenol ( carvacrol / 1c ) exhibited much better antioxidant activity than thymol and carvacrol in DPPH assay.", "output": "Schiff bases, 2 - iso - propyl - 5 - methyl - phenol, thymol, 2 - tert - butyl - 5 - methyl - phenol, 5 - iso - propyl - 2 - methyl - phenol, carvacrol, thymol, carvacrol, DPPH." }, { "input": "Ten compounds ( 4k, 4l, 4r, 5k, 5l, 5q, 5r, 6k, 6l and 6r ) showed better or similar activity as compared to the reference compound ascorbic acid.", "output": "ascorbic acid." }, { "input": "Twenty - four most active compounds were also screened by ABTS method and showed 60 - 90 % inhibition at 5 mu g / mL concentration.", "output": "ABTS." }, { "input": "Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem - cell - like properties.", "output": "There is no related enetity." }, { "input": "Cell - type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor - initiating stem cells and nonstem cells triggered by an inflammatory stroma.", "output": "There is no related enetity." }, { "input": "NF - kappa B represents a key transcription factor within the inflammatory tumor microenvironment.", "output": "There is no related enetity." }, { "input": "However, NF - kappa B ' s function in tumor - initiating cells has not been examined yet.", "output": "There is no related enetity." }, { "input": "Using a genetic model of intestinal epithelial cell ( IEC ) - restricted constitutive Wnt - activation, which comprises the most common event in the initiation of colon cancer, we demonstrate that NF - kappa B modulates Wnt signaling and show that IEC - specific ablation of RelA / p65 retards crypt stem cell expansion.", "output": "There is no related enetity." }, { "input": "In contrast, elevated NF - kappa B signaling enhances Wnt activation and induces dedifferentiation of nonstem cells that acquire tumor - initiating capacity.", "output": "There is no related enetity." }, { "input": "Thus, our data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for dedifferentiation and generation of tumor - initiating cells in vivo.", "output": "There is no related enetity." }, { "input": "Growth inhibition in early life - stage tests predicts full life - cycle toxicity effects of lead in the freshwater pulmonate snail, Lymnaea stagnalis.", "output": "There is no related enetity." }, { "input": "The freshwater pulmonate snail, Lymnaea stagnalis, is the most sensitive freshwater organism tested to date for several metals ( Co, Cu, Pb, Ni ) based on 28 d early life - stage ( ELS ) tests in which growth was the most sensitive endpoint.", "output": "Co, Cu, Pb, Ni." }, { "input": "The United States Environmental Protection Agency ( USEPA ) has expressed concern that growth in 28 d ELS tests with mollusks may overpredict toxicity because of the potential for recovery in a full life - cycle ( LC ) test.", "output": "There is no related enetity." }, { "input": "Consequently, the USEPA only accepts the survival endpoint for these tests in establishing water quality criteria ( WQC ).", "output": "There is no related enetity." }, { "input": "To address this concern, the current study aimed to test the sensitivity of L. stagnalis to Pb in a 56 d full LC test evaluating survival, growth, reproductive and embryonic growth endpoints and compare the estimated effect levels to those established using the 28 d ELS test design.", "output": "There is no related enetity." }, { "input": "The most sensitive endpoints in this study were 28 d growth and 56 d egg mass production, both with a NOEC of < 1. 0 mu g L ( - 1 ) and a LOEC of 1. 0 mu g L ( - 1 ), showing that the ELS growth endpoint is predictive of the 56 d reproduction endpoint.", "output": "There is no related enetity." }, { "input": "Snails exposed to 1. 0 and 2. 7 mu g L ( - 1 ) Pb showed full and partial recovery from growth inhibition between 28 and 56 d.", "output": "Pb." }, { "input": "While this recovery supports the USEPA ' s concern about the 28 d growth endpoint; considering the reproductive lifespan of L. stagnalis and the recovery dose - response, we conclude that the 28 d growth endpoint will be within a factor of 3 of full LC endpoints.", "output": "There is no related enetity." }, { "input": "This is consistent with the level of precision previously determined for fish ELS tests, which the USEPA accepts for WQC derivation, and suggests that tests using 28 d ELS growth endpoint for L. stagnalis may be acceptable for inclusion in WQC derivation.", "output": "There is no related enetity." }, { "input": "Changes in physiological responses of an Antarctic fish, the emerald rock cod ( Trematomus bernacchii ), following exposure to polybrominated diphenyl ethers ( PBDEs ).", "output": "polybrominated diphenyl ethers, PBDEs." }, { "input": "Although polybrominated diphenyl ethers ( PBDEs ) have the ability to undergo long - range atmospheric transport to remote ecosystems like Antarctica, a recent study found evidence for a local source within the Antarctic.", "output": "polybrominated diphenyl ethers, PBDEs." }, { "input": "PBDEs from sewage treatment outfalls of McMurdo Station and Scott Base on Ross Island have been attributed to the high concentrations measured in emerald rock cod ( Trematomus bernacchii ).", "output": "There is no related enetity." }, { "input": "The potential impact of PBDEs on Antarctic fish physiology is unknown and therefore, the aim of this study was to obtain a greater understanding of physiological responses of emerald rock cod for assessing changes in ecosystem quality.", "output": "There is no related enetity." }, { "input": "A PBDE mixture ( Sigma PBDE 8 congeners ) was administered fortnightly over 42 days and physiological changes were observed throughout this period and for a further 14 days thereafter.", "output": "PBDE." }, { "input": "Changes in liver composition, molecular level changes and enzyme activities of selected detoxification - mediated and antioxidant defence markers were measured.", "output": "There is no related enetity." }, { "input": "Changes in total lipid, lipid peroxide and protein carbonyl concentrations in emerald rock cod liver were consistent with increases in nucleus surface area in the PBDE - treated groups, suggesting alterations in cellular function.", "output": "peroxide, carbonyl, PBDE." }, { "input": "Changes in the activities of selected antioxidant enzymes indirectly indicated oxidative stress, possibly resulting in the changes in liver composition.", "output": "There is no related enetity." }, { "input": "Additionally, glutathione - S - transferase ( GST ) activity reached its peak faster than that of ethoxyresorufin - O - deethylase ( EROD ), suggesting that during the early response to PBDE exposures there could be a greater involvement of GST - mediated detoxification.", "output": "glutathione, S, ethoxyresorufin, O, PBDE." }, { "input": "Thus, for at least the species examined here, protein carbonyl and lipid peroxides were useful and informative biomarkers for cellular level responses following PBDE - related exposure.", "output": "carbonyl, PBDE." }, { "input": "Furthermore, our findings suggest that emerald rock cod exposed to PBDEs develop oxidative stress - a condition with potential consequences for fish growth, health and reproduction.", "output": "PBDEs." }, { "input": "Artichoke induces genetic toxicity in the cytokinesis - block micronucleus ( CBMN ) cytome assay.", "output": "There is no related enetity." }, { "input": "Artichoke leaves are used in traditional medicine as an herbal medicament for the treatment of hepatic related diseases, as well as choleretic and diuretic.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the capacity of Cynara scolymus L. leaves extract ( LE ) to cause chromosomal instability and cytotoxicity in Chinese hamster ovary cells ( CHO ) employing the cytokinesis - block micronucleus ( CBMN ) cytome assay.", "output": "There is no related enetity." }, { "input": "Cells were treated with four concentrations of C. scolymus for two exposure times: 1h and 24h.", "output": "There is no related enetity." }, { "input": "Our findings showed that LE did not increase the frequencies of nucleoplasmic bridges ( NPBs ) and nuclear bud ( NBUD ).", "output": "There is no related enetity." }, { "input": "However, all concentrations of the extract produced increments in micronuclei frequencies ( MNi ) in both exposure times, when compared to the negative control.", "output": "There is no related enetity." }, { "input": "No significant differences were observed in the nuclear division cytotoxicity index ( NDCI ), reflecting the absence of cytotoxic effects associated to LE.", "output": "There is no related enetity." }, { "input": "The results demonstrated the ability of C. scolymus LE to promote chromosomal mutations which are, probably, a result of the pro - oxidant activity of LE constituents such as flavonoids and chlorogenic acids.", "output": "flavonoids, chlorogenic acids." }, { "input": "The data obtained in this study suggests that high concentrations of artichoke can pose a risk associated to its consumption.", "output": "There is no related enetity." }, { "input": "Effects of zinc on epithelial barrier properties and viability in a human and a porcine intestinal cell culture model.", "output": "zinc." }, { "input": "Zinc is an essential trace element with a variety of physiological and biochemical functions.", "output": "Zinc." }, { "input": "Piglets are commonly supplemented, during the weaning period, with doses of zinc above dietary requirements with positive effects on health and performance that might be attributed to anti - secretory and barrier - enhancing effects in the intestine.", "output": "zinc." }, { "input": "For a better understanding of these observations increasing zinc sulfate ( ZnSO4; 0 - 200 mu M ) concentrations were used in an in vitro culture model of porcine ( IPEC - J2 ) and human ( Caco - 2 ) intestinal epithelial cells and effects on barrier function, viability, and the mRNA expression of one selected heat shock protein ( Hsp ) were assessed.", "output": "zinc sulfate, ZnSO4." }, { "input": "When treated apically with zinc sulfate, the transepithelial electrical resistance ( TEER ) did not change significantly.", "output": "zinc sulfate." }, { "input": "In contrast, cell viability measured by lactate dehydrogenase ( LDH ) leakage, by ATP and by WST - 1 conversion in postconfluent IPEC - J2 monolayers was affected after a 24 - h treatment with 200 mu M ZnSO4.", "output": "lactate, ATP, ZnSO4." }, { "input": "Caco - 2 cells were more resistant to Zn.", "output": "Zn." }, { "input": "ZnSO4 did not induce any effect on viability, except when it was used at the highest concentration ( 200 mu M ), and only in preconfluent cells.", "output": "ZnSO4." }, { "input": "Furthermore, ZnSO4 induced Hsp70 mRNA expression at 200 mu M and was more pronounced in preconfluent cells.", "output": "ZnSO4." }, { "input": "The observed dose - related effects of zinc are cell - line specific and depended on the differentiation status of the cells.", "output": "zinc." }, { "input": "The IPEC - J2 cell line appears to be a suitable in vitro model to characterize specific effects on porcine intestinal cells.", "output": "There is no related enetity." }, { "input": "The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus.", "output": "There is no related enetity." }, { "input": "Here, we studied the direct contribution of the suprachiasmatic nucleus ( SCN ), the central pacemaker in the circadian system, in the development of insulin resistance.", "output": "There is no related enetity." }, { "input": "Exclusive bilateral SCN lesions in male C57Bl / 6J mice, as verified by immunochemistry, showed a small but significant increase in body weight ( + 17 % ), which was accounted for by an increase in fat mass.", "output": "There is no related enetity." }, { "input": "In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance.", "output": "There is no related enetity." }, { "input": "Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake.", "output": "oxygen." }, { "input": "Hyperinsulinemic - euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham - operated mice ( - 63 % ).", "output": "glucose." }, { "input": "Although insulin potently inhibited endogenous glucose production ( - 84 % ), this was greatly reduced in SCN lesioned mice ( - 7 % ), indicating severe hepatic insulin resistance.", "output": "glucose." }, { "input": "Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance.", "output": "There is no related enetity." }, { "input": "Determination of genotoxicity by the Comet assay applied to murine precision - cut lung slices.", "output": "There is no related enetity." }, { "input": "Precision - cut lung slices ( PCLSs ) are an organotypic lung model that is widely used in pharmacological, physiological, and toxicological studies.", "output": "There is no related enetity." }, { "input": "Genotoxicity testing, as a pivotal part of early risk assessment, is currently established in vivo in various organs including lung, brain, or liver, and in vitro in cell lines or primary cells.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to provide the three - dimensional organ culture PCLS as a new ex vivo model for determination of genotoxicity using the Comet assay.", "output": "There is no related enetity." }, { "input": "Murine PCLS were exposed to increasing concentrations of ethyl methane sulfonate ' EMS ' ( 0. 03 - 0. 4 % ) and formalin ( 0. 5 - 5mM ).", "output": "ethyl methane sulfonate, EMS, formalin." }, { "input": "Tissue was subsequently dissociated, and DNA single - strand breaks were quantified using the Comet assay.", "output": "There is no related enetity." }, { "input": "Number of viable dissociated lung cells was between 4 x 10 ( 5 ) and 6. 7 x 10 ( 5 ) cells / slice.", "output": "There is no related enetity." }, { "input": "Even treatment with EMS did not induce toxicity compared to untreated tissue control.", "output": "EMS." }, { "input": "As expected, DNA single - strand breaks were increased dose - dependently and significantly after exposure to EMS.", "output": "EMS." }, { "input": "Here, tail length rose from 24 mu m to 75 mu m.", "output": "There is no related enetity." }, { "input": "In contrast, formalin resulted in a significant induction of DNA cross - links.", "output": "formalin." }, { "input": "The effects induced by EMS and formalin demonstrate the usefulness of PCLS as a new ex vivo lung model for genotoxicity testing in the early risk assessment of airborne substances in the future.", "output": "EMS, formalin." }, { "input": "PHEA - graft - polymethacrylate supramolecular aggregates for protein oral delivery.", "output": "PHEA - graft - polymethacrylate." }, { "input": "Salmon calcitonin ( sCT ) is characterized by a poor oral availability.", "output": "There is no related enetity." }, { "input": "A new copolymer, beta - poly ( N - 2 - hydroxyethyl ) - graft - { N - 2 - ethylene [ 2 - poly ( methacrylic acid sodium salt ) isobutyrate ] } - d, l - aspartamide ( PHEA - IB - p ( MANa ( + ) ) ), was designed for the oral administration of sCT through the formation of supramolecular aggregates ( SAs ) based on electrostatic interactions.", "output": "beta - poly ( N - 2 - hydroxyethyl ) - graft - { N - 2 - ethylene [ 2 - poly ( methacrylic acid sodium salt ) isobutyrate ] } - d , l - aspartamide, PHEA - IB - p ( MANa ( + ) )." }, { "input": "Several sCT / PHEA - IB - p ( MANa ( + ) ) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis.", "output": "PHEA - IB - p ( MANa ( + ) )." }, { "input": "After the incubation of sCT / PHEA - IB - p ( MANa ( + ) ) complex with digestive enzymes, 10 % ( w / w ) of loaded sCT was released in the native form.", "output": "PHEA - IB - p ( MANa ( + ) )." }, { "input": "In vitro investigation was carried out to determine the copolymer effect on the permeability of sCT in Caco - 2 cell monolayers.", "output": "There is no related enetity." }, { "input": "sCT pharmacokinetic profile and the pharmacodynamic effect on calcium plasma level were determined following an oral administration of the lead sCT / PHEA - IB - p ( MANa ( + ) ) SA ( 1 / 5 ratio ) in rats.", "output": "calcium, PHEA - IB - p ( MANa ( + ) )." }, { "input": "The SA yielded a marked prolongation of the sCT lowering calcium effect.", "output": "calcium." }, { "input": "The maximum decrease, 35 % with respect the basal calcium plasma level at time 0h, was achieved after 4h post - administration, and after 7h, a decrease of 20 % was still present.", "output": "calcium." }, { "input": "Differently, sCT yielded a transient calcium decrease that was completely restored after 5h.", "output": "calcium." }, { "input": "The higher bioavailability of sCT administered as SA was confirmed by the pharmacokinetic studies.", "output": "There is no related enetity." }, { "input": "In fact, the AUC and the Cmax were about 15 times higher for the sCT formulated as SA than the free sCT.", "output": "There is no related enetity." }, { "input": "This study indicates the potentials of PHEA - IB - p ( MANa ( + ) ) as carrier of sCT for oral delivery.", "output": "PHEA - IB - p ( MANa ( + ) )." }, { "input": "Drug release kinetics, cell uptake, and tumor toxicity of hybrid VVVVVVKK peptide - assembled polylactide nanoparticles.", "output": "polylactide." }, { "input": "An exciting approach to tumor delivery is encapsulation of the drug in self - assembled polymer - peptide nanoparticles.", "output": "There is no related enetity." }, { "input": "The objective of this work was to synthesize a conjugate of low molecular weight polylactide ( LMW PLA ) and V6K2 peptide and investigate self - assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin ( DOX ) or paclitaxel ( PTX ).", "output": "polylactide, Doxorubicin, DOX, paclitaxel, PTX." }, { "input": "The results for PLA - V6K2 self - assembled NPs were compared with those of polyethylene glycol stabilized PLA ( PLA - EG ) NPs.", "output": "PLA, polyethylene glycol, PLA, PLA." }, { "input": "The size of PLA - V6K2 and PLA - EG NPs was 100 +/- 20 and 130 +/- 50nm, respectively, with polydispersity index of 1. 04 and 1. 14.", "output": "PLA, PLA." }, { "input": "The encapsulation efficiency of DOX in PLA - V6K2 and PLA - EG NPs was 44 +/- 9 % and 55 +/- 5 %, respectively, and that of PTX was > 90 for both NP types.", "output": "DOX, PLA, PLA, PTX." }, { "input": "The release of DOX and PTX from PLA - V6K2 was slower than that of PLA - EG, and the release rate was relatively constant with time.", "output": "DOX, PTX, PLA, PLA." }, { "input": "Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell, while the hydrophobic PTX was localized mainly to the lactide core.", "output": "DOX, lactide, PTX, lactide." }, { "input": "PLA - V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA - EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane.", "output": "PLA, PLA." }, { "input": "PLA - V6K2 NPs showed no toxicity to marrow stromal cells.", "output": "PLA." }, { "input": "DOX - loaded PLA - V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response, and apoptosis was delayed compared to the free DOX.", "output": "DOX, PLA, DOX." }, { "input": "DOX or PTX encapsulated in PLA - V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA - EG NPs.", "output": "DOX, PTX, PLA, PLA." }, { "input": "Invasion of 4T1 cells treated with DOX in PLA - V6K2 and PLA - EG NPs was 5 +/- 1 % and 30 +/- 5 %, respectively, and that of PTX was 11 +/- 2 % and 40 +/- 7 %.", "output": "DOX, PLA, PLA, PTX." }, { "input": "The AUC of DOX in PLA - V6K2 NPs was 67 % and 21 % higher than those of free DOX and PLA - EG NPs, respectively.", "output": "DOX, PLA, DOX, PLA." }, { "input": "DOX - loaded PLA - V6K2 NPs injected in C3HeB / FeJ mice inoculated with MTCL syngeneic breast cancer cells displayed higher tumor toxicity than PLA - EG NPs and lower host toxicity than the free DOX.", "output": "DOX, PLA, PLA, DOX." }, { "input": "Cationic PLA - V6K2 NPs with higher tumor toxicity than the PLA - EG NPs are potentially useful in chemotherapy.", "output": "PLA, PLA." }, { "input": "Toward a detailed characterization of oil adsorbates as \" solid liquids \".", "output": "There is no related enetity." }, { "input": "Solid lipid formulation systems are used to overcome oral bioavailability problems of poorly water - soluble drugs.", "output": "There is no related enetity." }, { "input": "One promising process is the conversion of a liquid lipid system in a free flowing powder by use of adsorbing excipients.", "output": "There is no related enetity." }, { "input": "The aim of this study was the detailed characterization of solid - liquid interactions in oil adsorbed to Fujicalin (R) and Neusilin (R) which were manufactured by means of dual asymmetric centrifugation or conventional mortar / pestle blending.", "output": "Fujicalin, Neusilin." }, { "input": "The adsorption strength of the excipients was investigated by Benchtop - NMR and ESR spectroscopy revealing the highest adsorption power for the Neusilin (R) products.", "output": "Neusilin." }, { "input": "The adsorbate production methods as well as the storage of the excipients impact their adsorption properties.", "output": "There is no related enetity." }, { "input": "Environmental scanning electron microscopy ( ESEM ) and confocal laser scanning microscopy ( CLSM ) show that dual asymmetric centrifugation leads to a smoothing of the particle surface, whereas the mortar / pestle blending results in an uneven surface and particle destruction.", "output": "There is no related enetity." }, { "input": "The oil distribution at the particles is inhomogeneous for both production methods.", "output": "There is no related enetity." }, { "input": "The micropolarity of the adsorbed oil was investigated by ESR spectroscopy and multispectral fluorescence imaging.", "output": "There is no related enetity." }, { "input": "The adsorbing process on Neusilin (R) leads to an increased micropolarity of the oil component.", "output": "Neusilin." }, { "input": "The release of the oil component in aqueous media could be verified by Benchtop - NMR and multispectral fluorescence imaging.", "output": "There is no related enetity." }, { "input": "Ribosomal protein S25 dependency reveals a common mechanism for diverse internal ribosome entry sites and ribosome shunting.", "output": "There is no related enetity." }, { "input": "During viral infection or cellular stress, cap - dependent translation is shut down.", "output": "There is no related enetity." }, { "input": "Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation.", "output": "There is no related enetity." }, { "input": "This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site ( IRES ) initiation and ribosome shunting, rely on ribosomal protein S25 ( RPS25 ).", "output": "There is no related enetity." }, { "input": "This suggests that they share a mechanism for initiation that is not employed by cap - dependent translation, since cap - dependent translation is not affected by the loss of RPS25.", "output": "There is no related enetity." }, { "input": "Furthermore, we demonstrate that viruses that utilize an IRES or a ribosome shunt, such as hepatitis C virus, poliovirus, or adenovirus, have impaired amplification in cells depleted of RPS25.", "output": "There is no related enetity." }, { "input": "In contrast, viral amplification of a virus that relies solely on cap - dependent translation, herpes simplex virus, is not hindered.", "output": "There is no related enetity." }, { "input": "We present a model that explains how RPS25 can be a nexus for multiple alternative translation initiation pathways.", "output": "There is no related enetity." }, { "input": "Glyconanoparticles - an update.", "output": "There is no related enetity." }, { "input": "This review summarized the progress of glyconanoparticles in the aspects of types, synthesis, and applications for recent five years.", "output": "There is no related enetity." }, { "input": "A major challenge in the development of Au glyconanoparticles for the study of cellular interactions is to span the cellular membrane, which is used for the drug delivery.", "output": "Au." }, { "input": "A majority of glyco - functionalized quantum dots have been utilized as fluorescent probes for biolabeling, imaging and biosensing.", "output": "There is no related enetity." }, { "input": "Recently, magnetic nanoparticles have been more frequently used in biomedical applications.", "output": "There is no related enetity." }, { "input": "The application of these new multivalent systems of glyconanoparticles is to mainly study carbohydrate - mediated interactions, which opens the new field in glycobiology.", "output": "carbohydrate." }, { "input": "Thermodynamically consistent force fields for the assembly of inorganic, organic, and biological nanostructures: the INTERFACE force field.", "output": "There is no related enetity." }, { "input": "The complexity of the molecular recognition and assembly of biotic - abiotic interfaces on a scale of 1 to 1000 nm can be understood more effectively using simulation tools along with laboratory instrumentation.", "output": "There is no related enetity." }, { "input": "We discuss the current capabilities and limitations of atomistic force fields and explain a strategy to obtain dependable parameters for inorganic compounds that has been developed and tested over the past decade.", "output": "There is no related enetity." }, { "input": "Parameter developments include several silicates, aluminates, metals, oxides, sulfates, and apatites that are summarized in what we call the INTERFACE force field.", "output": "silicates, aluminates, oxides, sulfates, apatites." }, { "input": "The INTERFACE force field operates as an extension of common harmonic force fields ( PCFF, COMPASS, CHARMM, AMBER, GROMACS, and OPLS - AA ) by employing the same functional form and combination rules to enable simulations of inorganic - organic and inorganic - biomolecular interfaces.", "output": "There is no related enetity." }, { "input": "The parametrization builds on an in - depth understanding of physical - chemical properties on the atomic scale to assign each parameter, especially atomic charges and van der Waals constants, as well as on the validation of macroscale physical - chemical properties for each compound in comparison to measurements.", "output": "There is no related enetity." }, { "input": "The approach eliminates large discrepancies between computed and measured bulk and surface properties of up to 2 orders of magnitude using other parametrization protocols and increases the transferability of the parameters by introducing thermodynamic consistency.", "output": "There is no related enetity." }, { "input": "As a result, a wide range of properties can be computed in quantitative agreement with experiment, including densities, surface energies, solid - water interface tensions, anisotropies of interfacial energies of different crystal facets, adsorption energies of biomolecules, and thermal and mechanical properties.", "output": "There is no related enetity." }, { "input": "Applications include insight into the assembly of inorganic - organic multiphase materials, the recognition of inorganic facets by biomolecules, growth and shape preferences of nanocrystals and nanoparticles, as well as thermal transitions and nanomechanics.", "output": "There is no related enetity." }, { "input": "Limitations and opportunities for further development are also described.", "output": "There is no related enetity." }, { "input": "Methylation damage to RNA induced in vivo in Escherichia coli is repaired by endogenous AlkB as part of the adaptive response.", "output": "There is no related enetity." }, { "input": "Cytotoxic 1 - methyladenine ( 1 - meA ) and 3 - methylcytosine ( 3 - meC ) lesions induced in DNA and RNA in vitro and in pre - damaged DNA and RNA bacteriophages in vivo are repaired by the Escherichia coli ( E. coli ) protein AlkB and a human homolog, ALKBH3.", "output": "1 - methyladenine, 1 - meA, 3 - methylcytosine, 3 - meC." }, { "input": "However, it is not known whether endogenous RNA is repaired in vivo by repair proteins present at physiological concentrations.", "output": "There is no related enetity." }, { "input": "The concept of RNA repair as a biologically relevant process has therefore remained elusive.", "output": "There is no related enetity." }, { "input": "Here, we demonstrate AlkB - mediated repair of endogenous RNA in vivo by measuring differences in lesion - accumulation in two independent AlkB - proficient and deficient E. coli strains during exposure to methyl methanesulfonate ( MMS ).", "output": "methyl methanesulfonate, MMS." }, { "input": "Repair was observed both in AlkB - overproducing strains and in the wild - type strains after AlkB induction.", "output": "There is no related enetity." }, { "input": "RNA repair appeared to be highest in RNA species below 200 nucleotides in size, mainly comprising tRNAs.", "output": "nucleotides." }, { "input": "Strikingly, at least 10 - fold more lesions were repaired in RNA than in DNA.", "output": "There is no related enetity." }, { "input": "This may be a consequence of some 30 - fold higher levels of aberrant methylation in RNA than in DNA after exposure to MMS.", "output": "MMS." }, { "input": "A high primary kinetic isotope effect ( > 10 ) was measured using a deuterated methylated RNA substrate, D3 - 1me ( rA ), demonstrating that it is the catalytic step, and not the search step that is rate - limiting.", "output": "There is no related enetity." }, { "input": "Our results demonstrate that RNA repair by AlkB takes place in endogenous RNA as part of an adaptive response in wild - type E. coli cells.", "output": "There is no related enetity." }, { "input": "Testosterone metabolites mediate its effects on myocardial damage induced by ischemia / reperfusion in male Wistar rats.", "output": "Testosterone." }, { "input": "The role of testosterone in cardiovascular ( CV ) homeostasis is in controversy, and the exact effects of testosterone on the cardiovascular system remain poorly understood.", "output": "testosterone, testosterone." }, { "input": "Testosterone is metabolized by aromatase into 17 beta - estradiol and by 5 alpha - reductase into dihydrotestosterone ( DHT ).", "output": "Testosterone, 17 beta - estradiol, dihydrotestosterone, DHT." }, { "input": "Thus, identification of these metabolites in the heart may help to explain the controversy regarding the cardiovascular effects of testosterone.", "output": "testosterone." }, { "input": "We analyzed the expression patterns of these testosterone - metabolizing enzymes and assessed the effect of its enzymatic activity inhibition on ischemia ( 40 min ) / reperfusion ( 4h, I / R ) via the left anterior descendent coronary artery in intact and gonadectomized male rats.", "output": "testosterone." }, { "input": "Myocardial damage was measured as percentage of infarcted area vs. area at risk.", "output": "There is no related enetity." }, { "input": "Aromatase and 5 alpha - reductase protein expression was found in the left ventricle of intact and orchidectomized rats.", "output": "There is no related enetity." }, { "input": "Exogenous testosterone had no effect on I / R induced myocardial damage in intact male rats, meanwhile exogenous testosterone protects against I / R injury in orchidectomized rats.", "output": "testosterone, testosterone." }, { "input": "However, enzymatic inhibition of aromatase increased myocardial damage in the presence of testosterone, while enzymatic inhibition of 5 alpha - reductase significantly decreased the level of myocardial damage.", "output": "testosterone." }, { "input": "Our results also showed that sub - chronic inhibition of 5 alpha - reductase resulted in myocardial protection in both groups.", "output": "There is no related enetity." }, { "input": "Furthermore, in orchidectomized and intact male rats IV treatment with DHT induces a significant increase in the myocardial damage induced by I / R.", "output": "There is no related enetity." }, { "input": "Thus, the effect of testosterone on cardiovascular pathophysiology could be related, at least in part to changes in the balance of testosterone 5 alpha - reduction and aromatization.", "output": "testosterone, testosterone." }, { "input": "Identification and expression of multiple CYP1 - like and CYP3 - like genes in the bivalve mollusk Mytilus edulis.", "output": "There is no related enetity." }, { "input": "Various sequencing projects over the last several years have aided the discovery of previously uncharacterized invertebrate sequences, including new cytochrome P450 genes ( CYPs ).", "output": "There is no related enetity." }, { "input": "Here we present data on the identification and characterization of two CYP1 - like and three CYP3 - like genes from the bivalve mollusk Mytilus edulis, and assess their potential as biomarkers based on their responses to several known vertebrate aryl hydrocarbon receptor ( AHR ) agonists.", "output": "aryl hydrocarbon." }, { "input": "Quantitative real - time PCR was used to measure CYP transcript levels in digestive gland, labial palps, adductor muscle, gill, foot, and different regions of the mantle.", "output": "There is no related enetity." }, { "input": "Levels of both CYP1 - like genes were highest in digestive gland, whereas labial palps had the highest expression levels of the three CYP3 - like genes followed by digestive gland and outer margin of the mantle.", "output": "There is no related enetity." }, { "input": "Mussels were exposed by injection to the AHR agonists, beta - naphthoflavone ( BNF; 25 mu g g ( - 1 ) ), 3, 3 ', 4, 4 ', 5 - polychlorinated biphenyl ( PCB126; 2 mu g g ( - 1 ) ), or 6 - formylindolo [ 3, 2 - b ] carbazole ( FICZ; 0. 1 mu g g ( - 1 ) ), or to Aroclor 1254 ( a mixture of PCBs; 50 mu g g ( - 1 ) ) for 24 h, followed by CYP expression analysis.", "output": "beta - naphthoflavone, BNF, 3 , 3 ' , 4 , 4 ' , 5 - polychlorinated biphenyl, PCB126, 6 - formylindolo [ 3 , 2 - b ] carbazole, FICZ, Aroclor 1254, PCBs." }, { "input": "There was no statistically significant change in expression of either of the CYP1 - like genes after exposure to the various AHR agonists.", "output": "There is no related enetity." }, { "input": "The CYP3 - like - 1 gene was significantly up - regulated by BNF in gill tissues and the CYP3 - like - 2 gene was up - regulated in digestive gland by PCB126 and in gill tissue by BNF.", "output": "BNF, PCB126." }, { "input": "These results suggest that distinct mechanisms of CYP gene activation could be present in M. edulis, although the importance of the CYP1 - like and CYP3 - like genes for xenobiotic and endogenous lipids biotransformation requires additional investigation.", "output": "There is no related enetity." }, { "input": "Fisetin averts oxidative stress in pancreatic tissues of streptozotocin - induced diabetic rats.", "output": "Fisetin, streptozotocin." }, { "input": "Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes - associated complications.", "output": "There is no related enetity." }, { "input": "The sensitivity of pancreatic beta - cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues.", "output": "There is no related enetity." }, { "input": "Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress.", "output": "There is no related enetity." }, { "input": "Recently, we have reported that oral administration of fisetin ( 10 mg / Kg b. w. ), a bioflavonoid found to be present in strawberries, persimmon, to STZ - induced experimental diabetic rats significantly improved normoglycemia.", "output": "fisetin, bioflavonoid, STZ." }, { "input": "The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo.", "output": "fisetin." }, { "input": "Diabetes was induced by single intraperitoneal injection of streptozotocin ( 50 mg / kg body weight ).", "output": "streptozotocin." }, { "input": "Fisetin was administered orally for 30 days.", "output": "Fisetin." }, { "input": "At the end of the study, all animals were killed.", "output": "There is no related enetity." }, { "input": "Blood samples were collected for the biochemical estimations.", "output": "There is no related enetity." }, { "input": "The antioxidant status was evaluated.", "output": "There is no related enetity." }, { "input": "Histological examinations were performed on pancreatic tissues.", "output": "There is no related enetity." }, { "input": "Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin ( HbA1c ), NF - kB p65 unit ( in pancreas ) and IL - 1 beta ( plasma ), serum nitric oxide ( NO ) with an elevation in plasma insulin.", "output": "Fisetin, glucose, nitric oxide, NO." }, { "input": "The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin.", "output": "fisetin." }, { "input": "In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin.", "output": "DPPH, ABTS, fisetin." }, { "input": "Histological studies of the pancreas also evidenced the tissue protective nature of fisetin.", "output": "fisetin." }, { "input": "It is concluded that, fisetin possesses antioxidant and anti - inflammatory property and may be considered as an adjunct for the treatment of diabetes.", "output": "fisetin." }, { "input": "X - ray crystallography and computational docking for the detection and development of protein - ligand interactions.", "output": "There is no related enetity." }, { "input": "Amyotrophic lateral sclerosis ( ALS ) is a progressive neurodegenerative disorder characterised by the selective dysfunction and death of the upper and lower motor neurons.", "output": "There is no related enetity." }, { "input": "Median survival rates are between 3 and 5 years after diagnosis.", "output": "There is no related enetity." }, { "input": "Mutations in the gene encoding Cu / Zn superoxide dismutase ( SOD1 ) have been linked to a subset of familial forms of ALS ( fALS ).", "output": "Cu, Zn, superoxide." }, { "input": "Herein, we describe a fragment - based drug discovery ( FBDD ) approach for the investigation of small molecule binding sites in SOD1.", "output": "There is no related enetity." }, { "input": "X - ray crystallography has been used as the primary screening method and has been shown to directly detect protein - ligand interactions which cannot be unambiguously identified using other biophysical methods.", "output": "There is no related enetity." }, { "input": "The structural requirements for effective binding at Trp32 are detailed for a series of quinazoline - containing compounds.", "output": "Trp32, quinazoline." }, { "input": "The investigation of an additional site that binds a range of catecholamines and the use of computational modelling to assist fragment evolution is discussed.", "output": "catecholamines." }, { "input": "This study also highlights the importance of ligand solubility for successful Xray crystallographic campaigns in lead compound design.", "output": "There is no related enetity." }, { "input": "Self - Assembly of N ( 3 ) - Substituted Xanthines in the Solid State and at the Solid - Liquid Interface.", "output": "N ( 3 ) - Substituted Xanthines." }, { "input": "The self - assembly of small molecular modules interacting through noncovalent forces is increasingly being used to generate functional structures and materials for electronic, catalytic, and biomedical applications.", "output": "There is no related enetity." }, { "input": "The greatest control over the geometry in H - bond supramolecular architectures, especially in H - bonded supramolecular polymers, can be achieved by exploiting the rich programmability of artificial nucleobases undergoing self - assembly through strong H bonds.", "output": "H, H, nucleobases, H." }, { "input": "Here N ( 3 ) - functionalized xanthine modules are described, which are capable of self - associating through self - complementary H - bonding patterns to form H - bonded supramolecular ribbons.", "output": "xanthine, H, H." }, { "input": "The self - association of xanthines through directional H bonding between neighboring molecules allows the controlled generation of highly compact 1D supramolecular polymeric ribbons on graphite.", "output": "xanthines, H, graphite." }, { "input": "These architectures have been characterized by scanning tunneling microscopy at the solid - liquid interface, corroborated by dispersion - corrected density functional theory ( DFT ) studies and X - ray diffraction.", "output": "There is no related enetity." }, { "input": "Synthesis and quantum chemical studies of new 4 - aminoquinazoline derivatives as Aurora A / B kinase inhibitors.", "output": "4 - aminoquinazoline." }, { "input": "Nine novel 4 - aminoquinazoline derivatives were designed and synthesized.", "output": "4 - aminoquinazoline." }, { "input": "Biochemical and cellular analyses demonstrated that most of the derivatives exhibited a strong activity to inhibit Aurora A and B kinases and to suppress the proliferation of a panel of human tumor cell lines ( U937, K562, A549, LoVo, and HT29 ).", "output": "There is no related enetity." }, { "input": "Quantum chemical studies were also carried out to determine the structural features of these compounds engaged in the inhibition of Aurora kinases.", "output": "There is no related enetity." }, { "input": "Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats.", "output": "ethanol." }, { "input": "The pathology of a gastric ulcer is complex and multifactorial.", "output": "There is no related enetity." }, { "input": "Gastric ulcers affect many people around the world and its development is a result of the imbalance between aggressive and protective factors in the gastric mucosa.", "output": "There is no related enetity." }, { "input": "In this study, we evaluated the ethanolic extract of Rosmarinus officinalis L.", "output": "There is no related enetity." }, { "input": "( eeRo ); this plant, more commonly known as rosemary, has attracted the interest of the scientific community due to its numerous pharmacological properties and their potential therapeutic applications.", "output": "There is no related enetity." }, { "input": "Here, we tested the preventive effects of eeRo against gastric ulcer induced by 70 % ethanol in male Wistar rats.", "output": "ethanol." }, { "input": "In addition, we aimed to clarify the mechanism involved in the preventive action of the eeRo in gastric ulcers.", "output": "There is no related enetity." }, { "input": "Based on the analysis of markers of oxidative damage and enzymatic antioxidant defense systems, the measurement of nitrite and nitrate levels and the assessment of the inflammatory response, the eeRo exhibited significant antioxidant, vasodilator and antiinflammatory properties.", "output": "nitrite, nitrate." }, { "input": "Protection of the flavonoid fraction from Rosa laevigata Michx fruit against carbon tetrachloride - induced acute liver injury in mice.", "output": "flavonoid, carbon tetrachloride." }, { "input": "Protective effect of the total flavonoids ( TFs ) from Rosa laevigata Michx fruit against carbon tetrachloride ( CCl4 ) - induced hepatotoxicity in mice was investigated.", "output": "flavonoids, carbon tetrachloride, CCl4." }, { "input": "Pretreatment with TFs significantly decreased CCl4 - induced elevation of serum aspartate transaminase ( AST ) and alanine transaminase ( ALT ) activities as well as the relative liver weight.", "output": "CCl4, aspartate, alanine." }, { "input": "Histopathological observation also revealed that TFs reduced the incidence of liver lesions and improved hepatocyte abnormality.", "output": "There is no related enetity." }, { "input": "Moreover, oral administration of TFs significantly enhanced antioxidant enzyme activities ( superoxide dismutase, catalase and glutathione peroxidase ), increased the content of glutathione and decreased the content of malondialdehyde.", "output": "superoxide, glutathione, glutathione, malondialdehyde." }, { "input": "Further research indicated that TFs prevented the DNA fragmentation and mitochondrial ultrastructural alterations caused by CCl4 based on TUNEL and transmission electron microscopy ( TEM ) assays.", "output": "CCl4." }, { "input": "Moreover, pretreatment with TFs down - regulated the protein expressions of CYP2E1, iNOS, NF - kappa B, Bak and Caspase - 3.", "output": "There is no related enetity." }, { "input": "Quantitative Real - time PCR assay suggested that TFs markedly decreased the levels of TNF - alpha, Fas / FasL and Bax gene expressions, and increased the level of Bcl - 2.", "output": "There is no related enetity." }, { "input": "This is the first time to report the significant hepatoprotective effect of TFs from R. laevigata Michx fruit against CCl4 - induced liver injury in mice and the action should be through reducing oxidative stress and suppressing inflammation and apoptosis.", "output": "CCl4." }, { "input": "The significance of low substrate concentration measurements for mechanistic interpretation in cholinesterases.", "output": "There is no related enetity." }, { "input": "Cholinesterases do not follow the Michaelis - Menten kinetics.", "output": "There is no related enetity." }, { "input": "In the past, many reaction schemes were suggested to explain their complex interactions during the substrate turnover.", "output": "There is no related enetity." }, { "input": "Covalent catalysis was recognized very early and therefore, double intermediate traditional reaction scheme for the hydrolysis of good substrates at low concentrations was postulated.", "output": "There is no related enetity." }, { "input": "However, at intermediate and high substrate concentrations homotropic pseudocooperative effects take place in all cholinesterases, due to the nature of their buried active center.", "output": "There is no related enetity." }, { "input": "In this study, the significance and usefulness of experimental data obtained at low substrate concentrations, where only one substrate molecule accesses the active site at a time, are to be specified for the overall mechanistic evaluations.", "output": "There is no related enetity." }, { "input": "Indeed, different interpretations are expected when data are processed with equations derived from different reaction schemes.", "output": "There is no related enetity." }, { "input": "Consequently, the scheme with two substrate binding sites which comprises the structurally evidenced fully occupied active site as ultimate cause for substantially decreased cholinesterase activity at extremely high substrate concentrations is considered here.", "output": "There is no related enetity." }, { "input": "A special emphasis is put on butyrylcholinesterase, the enzyme with the largest active site among cholinesterases, where the pseudocooperative effects appear at much higher concentrations than in acetylcholinesterases.", "output": "There is no related enetity." }, { "input": "Potential prevention and treatment of maifanite for Alzheimer ' s disease based on behavior test, oxidative stress assay, and trace element analysis in hippocampus of A beta ( 2 5 - 3 5 ) - induced AD rats.", "output": "There is no related enetity." }, { "input": "This study aimed to assess whether maifanite can improve the learning and memory, and antioxidant abilities of Alzheimer ' s disease ( AD ) rats.", "output": "There is no related enetity." }, { "input": "The 70 rats were divided into seven groups: [ A ] normal control group, [ B ] AD model group, [ C ] sham group, [ D ] positive control group ( donepezil ), [ E ] low - dose maifanite group, [ F ] middle - dose maifanite group, [ G ] high - dose maifanite group.", "output": "donepezil." }, { "input": "For [ B ], [ D ], [ E ], [ F ], and [ G ] groups, A beta ( 25 - 35 ) ventricle injection was carried out, then respective medicine were administered once a day for 60 consecutive days.", "output": "There is no related enetity." }, { "input": "The step - down and step - through test were used to measure learning and memory ability.", "output": "There is no related enetity." }, { "input": "The hippocampus levels of superoxide dismutase ( SOD ), glutathione peroxidase ( GSH - Px ), and malondialdehyde ( MDA ) were assayed.", "output": "superoxide, glutathione, GSH, malondialdehyde, MDA." }, { "input": "The hippocampus contents of Al, Fe, Cu, Zn, Se, and Mn were analyzed by inductively coupled plasma - atomic emission spectrometer.", "output": "Al, Fe, Cu, Zn, Se, Mn." }, { "input": "Maifanite decreased the acquisition errors and the retention errors while prolonging the step - down latency, and decreased the number of electric shocks while prolonging the first latency of AD rats.", "output": "There is no related enetity." }, { "input": "A beta ( 25 - 35 ) ventricle injection initiated the decrease of SOD and GSH - Px activities and the increase of MDA content, and triggered the rise of Al, Fe, and Cu levels and the decline of Mn, Zn, and Se levels.", "output": "GSH, MDA, Al, Fe, Cu, Mn, Zn, Se." }, { "input": "The SOD and GSH - Px activities were enhanced followed by reduced MDA level, and the levels of Mn, Zn, and Se increased accompanied by Al, Fe, and Cu decreased in the maifanite treat groups.", "output": "GSH, MDA, Mn, Zn, Se, Al, Fe, Cu." }, { "input": "Maifanite could improve the learning and memory, and the antioxidant abilities of AD rats.", "output": "There is no related enetity." }, { "input": "Maifanite had the potential prevention and treatment for AD.", "output": "There is no related enetity." }, { "input": "Initiation of autophagy and apoptosis by sonodynamic therapy in murine leukemia L1210 cells.", "output": "There is no related enetity." }, { "input": "Sonodynamic therapy ( SDT ) has shown great potential in target cancer therapy, but it induced cell death modes has not been fully investigated.", "output": "There is no related enetity." }, { "input": "This study was to examine autophagic and apoptotic responses to protoporphyrin IX ( PpIX ) mediated SDT in murine leukemia L1210 cells.", "output": "protoporphyrin IX, PpIX." }, { "input": "After SDT, the occurrence of autophagy was identified by morphological observation and biochemical analysis.", "output": "There is no related enetity." }, { "input": "Meanwhile, the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death.", "output": "There is no related enetity." }, { "input": "The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies, which indicated that impairment of autophagy enhanced the anti - tumor effect of SDT through induction of apoptosis and necrosis, while caspase inhibition did not affect autophagic vacuoles formation or protect SDT induced cytotoxicity.", "output": "There is no related enetity." }, { "input": "The findings supported that autophagic vacuoles formed upstream and independently from caspase - dependent cell death.", "output": "There is no related enetity." }, { "input": "Additionally, the possible mechanism of SDT - induced autophagy was evaluated by measurement of ROS ( reactive oxygen species ) formation.", "output": "oxygen." }, { "input": "Result suggested ROS play important role in initiating autophagy, possibly through the sono - damaged mitochondria being enclosed by autophagic vacuoles.", "output": "There is no related enetity." }, { "input": "All together, these data indicate that autophagy may be cytoprotective in our experimental system, and point to an important insight into how autophagy inhibitors, in combination with SDT may contribute a regimen for cancer therapy.", "output": "There is no related enetity." }, { "input": "Evidence of impaired health in yellow perch ( Perca flavescens ) from a biological mercury hotspot in northeastern North America.", "output": "mercury." }, { "input": "Few studies have investigated the effects of mercury ( Hg ) on wild fish from remote areas, even though these fish can have high total Hg concentrations.", "output": "mercury, Hg, Hg." }, { "input": "In Kejimkujik National Park and National Historic Site ( KNPNHS ), Nova Scotia, Canada, concentrations of total Hg in many yellow perch ( Perca flavescens ) currently exceed the estimated threshold level for adverse effects in fish ( 0. 2 micro g Hg g ( - 1 ) ( wet wt ), whole body ).", "output": "Hg, Hg." }, { "input": "To determine whether Hg exposure is adversely affecting the general health of these fish, the authors collected male and female perch in the fall of 2009 and 2010 from 12 lakes within KNPNHS.", "output": "Hg." }, { "input": "The health endpoints condition, liver somatic index ( LSI ), and macrophage aggregates ( MAs; indicators of oxidative stress and tissue damage ) in the liver, kidney, and spleen were examined, and in female perch were compared between lakes and related to Hg concentrations measured in the muscle and liver tissue.", "output": "Hg." }, { "input": "No negative relationships between fish condition or LSI and Hg were found.", "output": "Hg." }, { "input": "However, within the liver, kidney, and spleen tissues of females, the relative area occupied by MAs was positively related to both muscle and liver Hg concentrations, indicating the health of these perch was adversely affected at the cellular level.", "output": "Hg." }, { "input": "These findings raise concerns for the health of these perch as well as for other wild fish populations known to have similarly elevated Hg concentrations.", "output": "Hg." }, { "input": "Comparing the effectiveness of chronic water column tests with the crustaceans Hyalella azteca ( order: Amphipoda ) and Ceriodaphnia dubia ( order: Cladocera ) in detecting toxicity of current - use insecticides.", "output": "There is no related enetity." }, { "input": "Standard U. S.", "output": "There is no related enetity." }, { "input": "Environmental Protection Agency laboratory tests are used to monitor water column toxicity in U. S. surface waters.", "output": "There is no related enetity." }, { "input": "The water flea Ceriodaphnia dubia is among the most sensitive test species for detecting insecticide toxicity in freshwater environments. Its usefulness is limited, however, when water conductivity exceeds 2, 000 micro S / cm ( approximately 1 ppt salinity ) and test effectiveness is insufficient.", "output": "There is no related enetity." }, { "input": "Water column toxicity tests using the euryhaline amphipod Hyalella azteca could complement C. dubia tests; however, standard chronic protocols do not exist.", "output": "There is no related enetity." }, { "input": "The present study compares the effectiveness of two water column toxicity tests in detecting the toxicity of two organophosphate ( OP ) and two pyrethroid insecticides: the short - term chronic C. dubia test, which measures mortality and fecundity, and a 10 - d H. azteca test, which measures mortality and growth.", "output": "organophosphate, pyrethroid." }, { "input": "Sensitivity was evaluated by comparing effect data, and end point variability was evaluated by comparing minimum significant differences.", "output": "There is no related enetity." }, { "input": "Tests were performed in synthetic water and filtered ambient water to quantify the influence of water matrix on effect concentrations.", "output": "There is no related enetity." }, { "input": "The H. azteca test detected pyrethroid toxicity far more effectively, while the C. dubia test was more sensitive to OPs.", "output": "pyrethroid." }, { "input": "Among endpoints, H. azteca mortality was most robust.", "output": "There is no related enetity." }, { "input": "The results demonstrate that the H. azteca test is preferable when conductivity of water samples is 2, 000 to 10, 000 micro S / cm or if contaminants of concern include pyrethroid insecticides.", "output": "pyrethroid." }, { "input": "The impact of structure on oxidatively generated DNA damage products resulting from the C3 ' - thymidinyl radical.", "output": "C3 ' - thymidinyl." }, { "input": "What ' s the damage?", "output": "There is no related enetity." }, { "input": "Trapping the C3 ' - thymidinyl radical in biologically significant architectures delivers both the repaired oligomer and 1 - ( 2 ' - deoxy - beta - D - threo - pentofuranosyl ) thymidine - containing substrates.", "output": "C3 ' - thymidinyl, 1 - ( 2 ' - deoxy - beta - D - threo - pentofuranosyl ) thymidine." }, { "input": "The stereoselectivity of the reduction was found to be dependent upon the DNA structure.", "output": "There is no related enetity." }, { "input": "Spectroscopic fingerprints of toroidal nuclear quantum delocalization via ab initio path integral simulations.", "output": "There is no related enetity." }, { "input": "We investigate the quantum - mechanical delocalization of hydrogen in rotational symmetric molecular systems.", "output": "hydrogen." }, { "input": "To this purpose, we perform ab initio path integral molecular dynamics simulations of a methanol molecule to characterize the quantum properties of hydrogen atoms in a representative system by means of their real - space and momentum - space densities.", "output": "methanol, hydrogen." }, { "input": "In particular, we compute the spherically averaged momentum distribution n ( k ) and the pseudoangular momentum distribution n ( k theta ).", "output": "There is no related enetity." }, { "input": "We interpret our results by comparing them to path integral samplings of a bare proton in an ideal torus potential.", "output": "There is no related enetity." }, { "input": "We find that the hydroxyl hydrogen exhibits a toroidal delocalization, which leads to characteristic fingerprints in the line shapes of the momentum distributions.", "output": "hydroxyl hydrogen." }, { "input": "We can describe these specific spectroscopic patterns quantitatively and compute their onset as a function of temperature and potential energy landscape.", "output": "There is no related enetity." }, { "input": "The delocalization patterns in the projected momentum distribution provide a promising computational tool to address the intriguing phenomenon of quantum delocalization in condensed matter and its spectroscopic characterization.", "output": "There is no related enetity." }, { "input": "As the momentum distribution n ( k ) is also accessible through Nuclear Compton Scattering experiments, our results will help to interpret and understand future measurements more thoroughly.", "output": "There is no related enetity." }, { "input": "Electrophoretic deposition of CdSe / ZnS quantum dots for light - emitting devices.", "output": "CdSe, ZnS." }, { "input": "The electrophoretic deposition of thin films of colloidal quantum dots is an alternative to spin - casting and printing for large - area, high - throughput processing of quantum - dot ( QD ) optoelectronics.", "output": "There is no related enetity." }, { "input": "In this study, QD light - emitting diodes ( QD - LEDs ) fabricated with electrophoretically deposited films of CdSe / ZnS core / shell QDs are demonstrated for the first time.", "output": "CdSe, ZnS." }, { "input": "Synthesis and biological evaluation of diaryl - substituted carboranes as inhibitors of hypoxia inducible factor ( HIF ) - 1 transcriptional activity.", "output": "diaryl - substituted carboranes." }, { "input": "Diaromatic - substituted ortho - and meta - carboranes were synthesized as mimics of manassantin A.", "output": "Diaromatic - substituted ortho - and meta - carboranes, manassantin A." }, { "input": "Among the carboranes synthesized, compounds 1 and 2 showed significant inhibition of hypoxia - induced HIF - 1 transcriptional activity, with IC ( 50 ) values of 3. 2 and 2. 2 mu M, respectively.", "output": "carboranes." }, { "input": "Compounds 1 and 2 similarly suppressed hypoxia - induced HIF - 1 alpha accumulation in a concentration - dependent manner without affecting the expression level of HIF - 1 alpha mRNA.", "output": "There is no related enetity." }, { "input": "The hypoxia - induced accumulation and translocation of HIF - 1 alpha into nuclei were not observed in HeLa cells treated with compounds 1 and 2 by immunofluorescence analysis, revealing that the inhibition of hypoxia - induced HIF - 1 transcriptional activity is induced by compounds 1 and 2 through a degradation pathway of the HIF - 1 alpha protein under hypoxic conditions.", "output": "There is no related enetity." }, { "input": "Butyltin ( IV ) benzoates: inhibition of thioredoxin reductase, tumor cell growth inhibition, and interactions with proteins.", "output": "Butyltin ( IV ) benzoates." }, { "input": "Thioredoxin reductase ( TrxR ) is overexpressed in cancer cells and is therefore a putative cancer target.", "output": "There is no related enetity." }, { "input": "Inhibition of this enzyme is considered an important strategy for the development of new chemotherapeutic agents with a specific mechanism of action.", "output": "There is no related enetity." }, { "input": "Organotin compounds have been described as experimental antitumor agents, yet their mechanism of action remains largely unknown.", "output": "Organotin." }, { "input": "Based on the outcome of a virtual screening study, various di - and tri - n - butyltin ( IV ) carboxylates were synthesized, and their biological properties were evaluated.", "output": "di - and tri - n - butyltin ( IV ) carboxylates." }, { "input": "All synthesized compounds were able to inhibit TrxR selectively within the micromolar range and showed potent antitumor activity against HT - 29 and MCF - 7 cancer cell lines.", "output": "There is no related enetity." }, { "input": "Moreover, tin ( IV ) organometallics were found to strongly induce apoptosis in the BJAB lymphoma cell line.", "output": "tin ( IV )." }, { "input": "Mass spectrometry and atomic absorption spectroscopy experiments revealed metal binding to proteins, and efficient cellular uptake was observed using a di - n - butyltin ( IV ) complex as an example.", "output": "di - n - butyltin ( IV )." }, { "input": "Correct Spectral Conversion between Surface - Enhanced Raman and Plasmon Resonance Scattering from Nanoparticle Dimers for Single - Molecule Detection.", "output": "There is no related enetity." }, { "input": "Simultaneous measurement of surface - enhanced Raman scattering ( SERS ) and localized surface plasmon resonance ( LSPR ) in nanoparticle dimers presents outstanding opportunities in molecular identification and in the elucidation of physical properties, such as the size, distance, and deformation of target species.", "output": "There is no related enetity." }, { "input": "SERS - LSPR instrumentation exists and has been used under limited conditions, but the extraction of SERS and LSPR readouts from a single measurement is still a challenge.", "output": "There is no related enetity." }, { "input": "Herein, the extraction of LSPR spectra from SERS signals is reported and a tool for measuring the interparticle distance from Raman enhancement data by the standardization of the SERS signal is proposed.", "output": "There is no related enetity." }, { "input": "The SERS nanoruler mechanism incorporates two important aspects ( the LSPR scattering peak shift and the Raman shift for measuring interparticle distance ), and signifies their exact one - to - one correspondence after spectral correction.", "output": "There is no related enetity." }, { "input": "The developed methodology is applied to calculate the interparticle distance between nanoparticle dimers from SERS signals, to detect and quantify DNA at the single - molecule level in a base - pair - specific manner.", "output": "There is no related enetity." }, { "input": "It is also shown that the SERS nanoruler concept can be used in structural analysis for the specific detection of the interaction of immunoglobulin G ( IgG ) with its target from bianalyte Raman signals with identical shaping at single - molecule resolution.", "output": "There is no related enetity." }, { "input": "The SERS profile shaping approach not only offers a new detection mechanism for single molecules, but also has excellent potential for studying protein interactions and the intracellular detection of mRNA.", "output": "There is no related enetity." }, { "input": "Mesoporous metallic cells: design of uniformly sized hollow mesoporous pt - ru particles with tunable shell thicknesses.", "output": "pt, ru." }, { "input": "A new class of hollow mesoporous Pt - Ru and Pt particles with uniform size, named ' mesoporous metallic cells ', are synthesized through a dual - templating approach using colloidal silica particles and non - ionic surfactants.", "output": "Pt, Ru, Pt, silica." }, { "input": "To realize the full potential of mesoporous metals as electrocatalysts, the shell thicknesses, compositions, and hollow cavity sizes are precisely controlled.", "output": "There is no related enetity." }, { "input": "Production of hybrid diesel fuel precursors from carbohydrates and petrochemicals using formic acid as a reactive solvent.", "output": "carbohydrates, formic acid." }, { "input": "We report the one - pot alkylation of mesitylene with carbohydrate - derived 5 - ( hydroxymethyl ) furfural ( HMF ) as a step toward diesel - range liquids.", "output": "mesitylene, carbohydrate, 5 - ( hydroxymethyl ) furfural, HMF." }, { "input": "Using FeCl ( 3 ) as a catalyst, HMF is shown to alkylate toluene, xylene, and mesitylene in high yields in CH ( 2 ) Cl ( 2 ) and MeNO ( 2 ) solvents.", "output": "FeCl ( 3 ), HMF, toluene, xylene, mesitylene, CH ( 2 ) Cl ( 2 ), MeNO ( 2 )." }, { "input": "Efforts to extend this reaction to greener or safer solvents showed that most ether - based solvents are unsatisfactory.", "output": "ether." }, { "input": "Acid catalysts ( e. g, p - TsOH ) also proved to be ineffective.", "output": "p - TsOH." }, { "input": "Using formic acid as a reactive solvent, mesitylene could be alkylated to give mesitylmethylfurfural ( MMF ) starting from fructose with yields up to approximately 70 %.", "output": "formic acid, mesitylene, mesitylmethylfurfural, MMF, fructose." }, { "input": "The reaction of fructose with formic acid in the absence of mesitylene gave rise to low yields of the formate ester of HMF, which indicates the stabilizing effect of replacing the hydroxyl substituent with mesityl.", "output": "fructose, formic acid, mesitylene, formate ester, HMF, hydroxyl, mesityl." }, { "input": "The arene also serves as a second phase into which the product is extracted.", "output": "arene." }, { "input": "Even by using formic acid, the mesitylation of less expensive precursors such as glucose and cellulose proceeded only in modest yields ( ca. 20 % ).", "output": "formic acid, glucose." }, { "input": "These simpler substrates were found to undergo mesitylation by using hydrogen chloride / formic acid via the intermediate chloromethylfurfural.", "output": "hydrogen chloride, formic acid, chloromethylfurfural." }, { "input": "Chemerin and vaspin: possible targets to treat obesity?", "output": "There is no related enetity." }, { "input": "Obesity is one of the main human epidemics today.", "output": "There is no related enetity." }, { "input": "The increase in fat accumulation, which is associated with obesity, may significantly change the expression of several bioactive molecules known as adipokines.", "output": "There is no related enetity." }, { "input": "These adipokines interact not only with adipose tissue, but also with metabolically relevant organs such as liver and muscle.", "output": "There is no related enetity." }, { "input": "Understanding the molecular basics of potential novel targets might help to improve the therapeutic treatment of people who suffer from obesity.", "output": "There is no related enetity." }, { "input": "Herein we summarize the state of the art of two novel adipokines and their impaired or protective action in obesity: chemerin and vaspin.", "output": "There is no related enetity." }, { "input": "Their expression patterns, signal transduction activity, and resulting functions within the human body are introduced.", "output": "There is no related enetity." }, { "input": "We also discuss various possibilities to target these adipokines, which may represent promising new targets for the treatment of obesity by small and synthetic compounds.", "output": "There is no related enetity." }, { "input": "Glycofullerenes inhibit viral infection.", "output": "Glycofullerenes." }, { "input": "Water - soluble glycofullerenes based on a hexakis - adduct of [ 60 ] fullerene with an octahedral addition pattern are very attractive compounds providing a spherical presentation of carbohydrates.", "output": "hexakis - adduct of [ 60 ] fullerene, carbohydrates." }, { "input": "These tools have been recently described and they have been used to interact with lectins in a multivalent manner.", "output": "There is no related enetity." }, { "input": "Here, we present the use of these glycofullerenes, including new members with 36 mannoses, as compounds able to inhibit a DC - SIGN - dependent cell infection by pseudotyped viral particles.", "output": "glycofullerenes, mannoses." }, { "input": "The results obtained in these experiments demonstrate for the first time that these glycoconjugates are adequate to inhibit efficiently an infection process, and therefore, they can be considered as very promising and interesting tools to interfere in biological events where lectins such as DC - SIGN are involved.", "output": "There is no related enetity." }, { "input": "Two new ent - 3, 4 - seco - labdane diterpenoids from Callicarpa nudiflora.", "output": "ent - 3 , 4 - seco - labdane diterpenoids." }, { "input": "Two new ent - 3, 4 - seco - labdane diterpenoids, methylcallicarpate ( 1 ) and callicarpic acid ( 2 ), were isolated from the leaves of Callicarpa nudiflora Hook et Arn.", "output": "ent - 3 , 4 - seco - labdane diterpenoids, methylcallicarpate, callicarpic acid." }, { "input": "Their structures and relative configurations were established by analysis of spectroscopic data.", "output": "There is no related enetity." }, { "input": "Their absolute configurations were assigned by the application of the CD technique for the first time among the ent - 3, 4 - seco - labdane - type diterpenes.", "output": "ent - 3 , 4 - seco - labdane, diterpenes." }, { "input": "Paeoniflorin acts as a liver X receptor agonist.", "output": "Paeoniflorin." }, { "input": "Paeoniflorin is one of the active ingredients of Paeonia lactiflora Pall., a novel traditional herbal medicine exerting pharmacological effects including antihyperlipidemic, neuroprotective, and anti - hepatofibrosis effects.", "output": "Paeoniflorin." }, { "input": "Liver X receptor ( LXR ) acts as a ligand - activated transcription factor to exhibit antihyperlipidemic and neuroprotective effects.", "output": "There is no related enetity." }, { "input": "In this study, the activity of paeoniflorin against LXR was evaluated by the mammalian one - hybrid and transient transfection reporter assays.", "output": "paeoniflorin." }, { "input": "The results showed that paeoniflorin transactivated GAL4, rat cholesterol 7 alpha - hydroxylase, phospholipid transfer protein, and ATP - binding cassette A1 gene promoters in dose - dependent manner.", "output": "paeoniflorin, cholesterol, ATP." }, { "input": "Furthermore, the docking study demonstrated that paeoniflorin resided in the LXR ligand - binding pocket in the similar manner as GSK 3987, a novel LXR agonist.", "output": "paeoniflorin, GSK 3987." }, { "input": "These results indicated that paeoniflorin might exert pharmacological effects through LXR pathway.", "output": "paeoniflorin." }, { "input": "Spreading and structuring of water on superhydrophilic polyelectrolyte brush surfaces.", "output": "There is no related enetity." }, { "input": "The wetting behavior of superhydrophilic polyelectrolyte brushes was investigated.", "output": "There is no related enetity." }, { "input": "Reflection interference contrast microscopy demonstrated that the contact angles of water on the polyelectrolyte brushes were extremely low but remained finite in the range of < 3 degrees.", "output": "There is no related enetity." }, { "input": "The presence of water molecules was evident, even outside the macroscopic water droplet.", "output": "There is no related enetity." }, { "input": "These water molecules were confined to the thin brush layers and contained a highly ordered hydrogen bond network, which was identified as structural water.", "output": "hydrogen." }, { "input": "The presence of the thin film and the structural water changed the surface energies, which prevented the complete wetting of the surface.", "output": "There is no related enetity." }, { "input": "Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir.", "output": "acyclovir." }, { "input": "The objective of this investigation was to design and develop water - in - oil - in - water type multiple emulsions ( w / o / w emulsions ) entrapping acyclovir for improving its oral bioavailability.", "output": "acyclovir." }, { "input": "Multiple emulsions ( MEs ) were prepared and optimized using Span - 80 and Span - 83 as lipophilic surfactant and Brij - 35 as hydrophilic surfactant.", "output": "Span - 80, Span - 83, Brij - 35." }, { "input": "The physio - chemical properties of the w / o / w emulsions - particle size, viscosity, phase separation ( centrifugation test ) and entrapment efficiency were measured and evaluated along with macroscopic and microscopic observations to confirm multiple nature, homogeneity and globule size.", "output": "There is no related enetity." }, { "input": "Stability study, in vitro and ex vivo release studies were performed followed by in vivo studies in rats.", "output": "There is no related enetity." }, { "input": "Stable w / o / w emulsions with a particle size of 33. 098 +/- 2. 985 micro m and 85. 25 +/- 4. 865 % entrapment efficiency were obtained.", "output": "There is no related enetity." }, { "input": "Stability studies showed that the concentration of lipophilic surfactant was very important for stability of MEs.", "output": "There is no related enetity." }, { "input": "Drug release from the prepared formulations showed initial rapid release followed by a much slower release.", "output": "There is no related enetity." }, { "input": "In vivo studies in rats indicated prolonged release and better oral bioavailability as compared to drug solution.", "output": "There is no related enetity." }, { "input": "The overall results of this study show the potential of the w / o / w emulsions as promising drug delivery systems for acyclovir.", "output": "acyclovir." }, { "input": "Structural studies of mixed glass former 0. 35Na2O + 0. 65 [ xB2O3 + ( 1 - x ) P2O5 ] glasses by Raman and 11B and 31P magic angle spinning nuclear magnetic resonance spectroscopies.", "output": "35Na2O, [ xB2O3 + ( 1 - x ) P2O5 ], 11B, 31P." }, { "input": "The mixed glass former ( MGF ) effect ( MGFE ) is defined as a nonlinear and nonadditive change in the ionic conductivity with changing glass former composition at constant modifier composition.", "output": "There is no related enetity." }, { "input": "In this study, sodium borophosphate 0. 35Na ( 2 ) O + 0. 65 [ xB ( 2 ) O ( 3 ) + ( 1 - x ) P ( 2 ) O ( 5 ) ], 0 <= x <= 1, glasses which have been shown to exhibit a positive MGFE have been prepared and examined using Raman and ( 11 ) B and ( 31 ) P magic angle spinning nuclear magnetic resonance ( MAS NMR ) spectroscopies.", "output": "sodium borophosphate, 35Na ( 2 ) O, [ xB ( 2 ) O ( 3 ) + ( 1 - x ) P ( 2 ) O ( 5 ) ], ( 11 ) B, ( 31 ) P." }, { "input": "Through examination of the short - range order ( SRO ) structures found in the ternary glasses, it was determined that the minority glass former, B for 0. 1 <= x <= 0. 7 and P for 0. 7 <= x <= 0. 9, is \" overmodified \" and contains more Na ( + ) ions than would be expected from simple linear mixing of the binary sodium borate, x = 1, and sodium phosphate, x = 0, glasses, respectively.", "output": "B, P, Na ( + ), sodium borate, sodium phosphate." }, { "input": "Changes in the intermediate range order ( IRO ) structures were suggested by changes in the NMR spectral chemical shifts and Raman spectra wavenumber shifts over the full composition range x in the Raman and MAS NMR spectra.", "output": "There is no related enetity." }, { "input": "The changes observed in the chemical shifts of ( 31 ) P MAS NMR spectra with x are found to be too large to be caused solely by changing sodium modification of the phosphate SRO structural groups, and this indicates that internetwork bonding between phosphorus and boron through bridging oxygens ( BOs ), P - O - B, must be a major contributor to the IRO structure of these glasses.", "output": "( 31 ) P, sodium, phosphorus, boron, oxygens, P - O - B." }, { "input": "While not fully developed, a first - order thermodynamic analysis based upon the Gibbs free energies of formation of the various SRO structural units in this system has been developed and can be used to account for the preferential formation of tetrahedral boron groups, B ( 4 ), by the reaction of B ( 3 ) with P ( 2 ) groups to form B ( 4 ) and P ( 3 ) groups, respectively, where the superscript denotes the number of BOs on these units, in these glasses.", "output": "boron, B, B, P, B, P." }, { "input": "This preference for B ( 4 ) units appears to be a predominate cause of the changing modifier to glass former ratio with composition x in these ternary MGF glasses and appears to be associated with the large negative value of the Gibbs free energy of formation of this group.", "output": "B." }, { "input": "X - ray absorption near edge structure spectroscopy to resolve the in vivo chemistry of the redox - active indazolium trans - [ Tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ] ( KP1019 ).", "output": "indazolium trans - [ Tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ], KP1019." }, { "input": "Indazolium trans - [ tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ] ( 1, KP1019 ) and its analogue sodium trans - [ tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ] ( 2, KP1339 ) are promising redox - active anticancer drug candidates that were investigated with X - ray absorption near edge structure spectroscopy.", "output": "Indazolium trans - [ tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ], KP1019, sodium trans - [ tetrachlorobis ( 1H - indazole ) ruthenate ( III ) ], KP1339." }, { "input": "The analysis was based on the concept of the coordination charge and ruthenium model compounds representing possible coordinations and oxidation states in vivo.", "output": "ruthenium." }, { "input": "1 was investigated in citrate saline buffer ( pH 3. 5 ) and in carbonate buffer ( pH 7. 4 ) at 37 degrees C for different time intervals.", "output": "citrate, carbonate." }, { "input": "Interaction studies on 1 with glutathione in saline buffer and apo - transferrin in carbonate buffer were undertaken, and the coordination of 1 and 2 in tumor tissues was studied too.", "output": "glutathione, carbonate." }, { "input": "The most likely coordinations and oxidation states of the compound under the above mentioned conditions were assigned.", "output": "There is no related enetity." }, { "input": "Microprobe X - ray fluorescence of tumor thin sections showed the strong penetration of ruthenium into the tumor tissue, with the highest concentrations near blood vessels and in the edge regions of the tissue samples.", "output": "ruthenium." }, { "input": "Evaluation of animal models for intestinal first - pass metabolism of drug candidates to be metabolized by CYP3A enzymes via in vivo and in vitro oxidation of midazolam and triazolam.", "output": "midazolam, triazolam." }, { "input": "Abstract 1.", "output": "There is no related enetity." }, { "input": "To search an appropriate evaluation methodology for the intestinal first - pass metabolism of new drug candidates, grapefruit juice ( GFJ ) - and vehicle ( tap water ) - pretreated mice or rats were orally administered midazolam ( MDZ ) or triazolam ( TRZ ), and blood levels of the parent compounds and their metabolites were measured by liquid chromatography / MS / MS.", "output": "midazolam, MDZ, triazolam, TRZ." }, { "input": "A significant effect of GFJ to elevate the blood levels was observed only for TRZ in mice.", "output": "TRZ." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "In vitro experiments using mouse, rat and human intestinal and hepatic microsomal fractions demonstrated that GFJ suppressed the intestinal microsomal oxidation of MDZ and especially TRZ.", "output": "MDZ, TRZ." }, { "input": "Substrate inhibition by MDZ caused reduction in 1 ' - hydroxylation but not 4 - hydroxylation in both intestinal and hepatic microsomal fractions.", "output": "MDZ." }, { "input": "The kinetic profiles of MDZ oxidation and the substrate inhibition in mouse intestinal and hepatic microsomal fractions were very similar to those in human microsomes but were different from those in rat microsomes.", "output": "MDZ." }, { "input": "Furthermore, MDZ caused mechanism - based inactivation of cytochrome P450 3A - dependent TRZ 1 ' - hydroxylation in mouse, rat and human intestinal microsomes with similar potencies.", "output": "MDZ, TRZ." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "These results are useful information in the analysis of data obtained in mouse and rat for the evaluation of first - pass effects of drug candidates to be metabolized by CYP3A enzymes.", "output": "There is no related enetity." }, { "input": "Catalytic enantioselective cyclization and C3 - fluorination of polyenes.", "output": "polyenes." }, { "input": "( Xylyl - phanephos ) Pt ( 2 + ) in combination with XeF ( 2 ) mediates the consecutive diastereoselective cation - olefin cyclization / fluorination of polyene substrates.", "output": "( Xylyl - phanephos ) Pt ( 2 + ), XeF ( 2 ), olefin, polyene." }, { "input": "Isolated yields were typically in the 60 - 69 % range while enantioselectivities reached as high as 87 %.", "output": "There is no related enetity." }, { "input": "The data are consistent with a stereoretentive fluorination of a P ( 2 ) Pt - alkyl cation intermediate.", "output": "P ( 2 ) Pt - alkyl." }, { "input": "A micro - cantilever sensor chip based on contact angle analysis for a label - free troponin I immunoassay.", "output": "There is no related enetity." }, { "input": "Cantilever sensors have been extensively explored as a promising technique for real - time and label - free analyses in biological systems.", "output": "There is no related enetity." }, { "input": "A major sensing principle utilized by state - of - the - art cantilever sensors is based on analyte - induced surface stress changes, which result in static bending of a cantilever.", "output": "There is no related enetity." }, { "input": "The sensor performance, however, suffers from the intrinsically small change in surface stress induced by analytes, especially for molecular recognition such as antigen - antibody binding.", "output": "There is no related enetity." }, { "input": "Through the contact angle change on a tailored solid surface, it is possible to convert a tiny surface stress into a capillary force - a much larger physical quantity needed for a practical sensor application.", "output": "There is no related enetity." }, { "input": "In this work, a micro - cantilever sensor based on contact angle analysis ( CAMCS ) was proposed to effectively enhance the sensitivity of a sensor in proportion to the square of the length to thickness ratio of the cantilever structure.", "output": "There is no related enetity." }, { "input": "CAMCS chips were fabricated using a standard complementary - metal - oxide - semiconductor ( CMOS ) process to demonstrate a 1250 - fold enhancement in the sensitivity of surface stress to bioanalyte adsorption using a piezoresistive sensing method.", "output": "metal - oxide." }, { "input": "A real - time and label - free troponin I ( cTnI ) immunoassay, which is now widely used in clinics and considered a gold standard for the early diagnosis and prognosis of cardiovascular disease, was performed to demonstrate cTnI detection levels as low as 1 pg mL ( - 1 ).", "output": "There is no related enetity." }, { "input": "The short detection time of this assay was within several minutes, which matches the detection time of commercially available instruments that are based on fluorescence - labeling techniques.", "output": "There is no related enetity." }, { "input": "Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats.", "output": "Zinc sulphate, vitamin E, aluminium sulphate." }, { "input": "This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium ( Al ) in male albino rats.", "output": "aluminium sulphate, zinc sulphate, vitamin E, aluminium, Al." }, { "input": "The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate ( 50 mg / kg body weight ( b. w. ) ); group 3 received aluminium sulphate ( 50 mg / kg b. w. ) plus zinc sulphate ( 50 mg / kg b. w. ); group 4 received aluminium sulphate ( 50 mg / kg b. w. ) and vitamin E ( 15 mg / kg b. w. ); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above.", "output": "aluminium sulphate, aluminium sulphate, zinc sulphate, aluminium sulphate, vitamin E, aluminium sulphate, zinc sulphate, vitamin E." }, { "input": "Doses were administered orally once daily for 45 consecutive days.", "output": "There is no related enetity." }, { "input": "The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats.", "output": "aluminium sulphate, Al." }, { "input": "Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment.", "output": "Al." }, { "input": "In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al - treated rats was recorded.", "output": "cholesterol, Al." }, { "input": "The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al - intoxicated rats.", "output": "testosterone, Al." }, { "input": "Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals.", "output": "aluminium sulphate." }, { "input": "Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues.", "output": "zinc sulphate, vitamin E, Al." }, { "input": "We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with zinc sulphate and / or vitamin E alleviated these toxic effects.", "output": "aluminium sulphate, zinc sulphate, vitamin E." }, { "input": "In some cases, vitamin E exerted a more potent effect, while in other cases, the more potent effect is related to zinc sulphate and the combination of both at most of the recorded data.", "output": "vitamin E, zinc sulphate." }, { "input": "Trichostatin A inhibits transforming growth factor - beta - induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF - E2 - related factor 2 - antioxidant response element signaling.", "output": "Trichostatin A, oxygen." }, { "input": "Trichostatin A ( TSA ) has been shown to prevent fibrosis in vitro and in vivo.", "output": "Trichostatin A, TSA." }, { "input": "The present study aimed at investigating the role of reactive oxygen species ( ROS ) scavenging by TSA on transforming growth factor - beta ( TGF - beta ) - induced myofibroblast differentiation of corneal fibroblasts in vitro.", "output": "oxygen, TSA." }, { "input": "Human immortalized corneal fibroblasts were treated with TGF - beta in the presence of TSA, the NAD ( P ) H oxidase inhibitor diphenyleneiodonium ( DPI ), the antioxidant N - acetyl - cysteine ( NAC ), the NF - E2 - related factor 2 - antioxidant response element ( Nrf2 - ARE ) activator sulforaphane, or small interfering RNA.", "output": "TSA, NAD ( P ) H, diphenyleneiodonium, DPI, N - acetyl - cysteine, NAC, sulforaphane." }, { "input": "Myofibroblast differentiation was assessed by alpha - smooth muscle actin ( alpha - SMA ) expression, F - actin bundle formation, and collagen gel contraction.", "output": "There is no related enetity." }, { "input": "ROS, H ( 2 ) O ( 2 ), intracellular glutathione ( GSH ) level, cellular total antioxidant capacity, and the activation of Nrf2 - ARE signaling were determined with various assays.", "output": "H ( 2 ) O ( 2 ), glutathione, GSH." }, { "input": "Treatment with TSA and the Nrf2 - ARE activator resulted in increased inhibition of the TGF - beta - induced myofibroblast differentiation as compared with treatment with DPI or NAC.", "output": "TSA, DPI, NAC." }, { "input": "Furthermore, TSA also decreased cellular ROS and H ( 2 ) O ( 2 ) accumulation induced by TGF - beta, whereas it elevated intracellular GSH level and cellular total antioxidant capacity.", "output": "TSA, H ( 2 ) O ( 2 ), GSH." }, { "input": "In addition, TSA induced Nrf2 nuclear translocation and up - regulated the expression of Nrf2 - ARE downstream antioxidant genes, whereas Nrf2 knockdown by RNA interference blocked the inhibition of TSA on myofibroblast differentiation.", "output": "TSA, TSA." }, { "input": "In conclusion, this study provides the first evidence implicating that TSA inhibits TGF - beta - induced ROS accumulation and myofibroblast differentiation via enhanced Nrf2 - ARE signaling.", "output": "TSA." }, { "input": "Amide hydrolysis of a novel chemical series of microsomal prostaglandin E synthase - 1 inhibitors induces kidney toxicity in the rat.", "output": "Amide, prostaglandin E." }, { "input": "A novel microsomal prostaglandin E synthase 1 ( mPGES - 1 ) inhibitor induced kidney injury at exposures representing less than 4 times the anticipated efficacious exposure in man during a 7 - day toxicity study in rats.", "output": "prostaglandin E." }, { "input": "The findings consisted mainly of tubular lesions and the presence of crystalline material and increases in plasma urea and creatinine.", "output": "urea, creatinine." }, { "input": "In vitro and in vivo metabolic profiling generated a working hypothesis that a bis - sulfonamide metabolite ( determined M1 ) formed by amide hydrolysis caused this toxicity.", "output": "bis - sulfonamide, amide." }, { "input": "To test this hypothesis, rats were subjected to a 7 - day study and were administered the suspected metabolite and two low - potency mPGES - 1 inhibitor analogs, where amide hydrolysis was undetectable in rat hepatocyte experiments.", "output": "amide." }, { "input": "The results suggested that compounds with a reduced propensity to undergo amide hydrolysis, thus having less ability to form M1, reduced the risk of inducing kidney toxicity.", "output": "amide." }, { "input": "Rats treated with M1 alone showed no histopathologic change in the kidney, which was likely related to underexposure to M1.", "output": "There is no related enetity." }, { "input": "To circumvent rat kidney toxicity, we identified a potent mPGES - 1 inhibitor with a low propensity for amide hydrolysis and superior rat pharmacokinetic properties.", "output": "amide." }, { "input": "A subsequent 14 - day rat toxicity study showed that this compound was associated with kidney toxicity at 42, but not 21, times the anticipated efficacious exposure in humans.", "output": "There is no related enetity." }, { "input": "In conclusion, by including metabolic profiling and exploratory rat toxicity studies, a new and active mPGES - 1 inhibitor with improved margins to chemically induced kidney toxicity in rats has been identified.", "output": "There is no related enetity." }, { "input": "Using binary surfactant mixtures to simultaneously improve the dimensional tunability and monodispersity in the seeded growth of gold nanorods.", "output": "There is no related enetity." }, { "input": "We report a dramatically improved synthesis of colloidal gold nanorods ( NRs ) using a binary surfactant mixture composed of hexadecyltrimethylammonium bromide ( CTAB ) and sodium oleate ( NaOL ).", "output": "hexadecyltrimethylammonium bromide, CTAB, sodium oleate, NaOL." }, { "input": "Both thin ( diameter < 25 nm ) and thicker ( diameter > 30 nm ) gold NRs with exceptional monodispersity and broadly tunable longitudinal surface plasmon resonance can be synthesized using seeded growth at reduced CTAB concentrations ( as low as 0. 037 M ).", "output": "CTAB." }, { "input": "The CTAB - NaOL binary surfactant mixture overcomes the difficulty of growing uniform thick gold NRs often associated with the single - component CTAB system and greatly expands the dimensions of gold NRs that are accessible through a one - pot seeded growth process.", "output": "CTAB, NaOL, CTAB." }, { "input": "Gold NRs with large overall dimensions and thus high scattering / absorption ratios are ideal for scattering - based applications such as biolabeling as well as the enhancement of optical processes.", "output": "There is no related enetity." }, { "input": "Antiproliferative and antiplasmodial dimeric phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest ( 1 ).", "output": "dimeric phloroglucinols." }, { "input": "Bioassay - guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B ( 1 ) and C ( 2 ), together with the known mallotophenone ( 3 ).", "output": "ethanol, dimeric phloroglucinols, mallotojaponins B ( 1 ) and C ( 2 ), mallotophenone." }, { "input": "The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D - and 2D - NMR spectra, mass spectrometry, and an X - ray crystal structure.", "output": "There is no related enetity." }, { "input": "Compounds 1 and 2 showed potent antimalarial activity against chloroquine - resistant Plasmodium falciparum, with IC50 values of 0. 75 +/- 0. 30 and 0. 14 +/- 0. 04 mu M, while 3 was inactive in this assay.", "output": "chloroquine." }, { "input": "Compounds 1 - 3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line ( IC50 1. 10 +/- 0. 05, 1. 3 +/- 0. 1 and 6. 3 +/- 0. 4 mu M, respectively ).", "output": "There is no related enetity." }, { "input": "Delayed frost growth on jumping - drop superhydrophobic surfaces.", "output": "There is no related enetity." }, { "input": "Self - propelled jumping drops are continuously removed from a condensing superhydrophobic surface to enable a micrometric steady - state drop size.", "output": "There is no related enetity." }, { "input": "Here, we report that subcooled condensate on a chilled superhydrophobic surface are able to repeatedly jump off the surface before heterogeneous ice nucleation occurs.", "output": "There is no related enetity." }, { "input": "Frost still forms on the superhydrophobic surface due to ice nucleation at neighboring edge defects, which eventually spreads over the entire surface via an interdrop frost wave.", "output": "There is no related enetity." }, { "input": "The growth of this interdrop frost front is shown to be up to 3 times slower on the superhydrophobic surface compared to a control hydrophobic surface, due to the jumping - drop effect dynamically minimizing the average drop size and surface coverage of the condensate.", "output": "There is no related enetity." }, { "input": "A simple scaling model is developed to relate the success and speed of interdrop ice bridging to the drop size distribution.", "output": "There is no related enetity." }, { "input": "While other reports of condensation frosting on superhydrophobic surfaces have focused exclusively on liquid - solid ice nucleation for isolated drops, these findings reveal that the growth of frost is an interdrop phenomenon that is strongly coupled to the wettability and drop size distribution of the surface.", "output": "There is no related enetity." }, { "input": "A jumping - drop superhydrophobic condenser minimized frost formation relative to a conventional dropwise condenser in two respects: preventing heterogeneous ice nucleation by continuously removing subcooled condensate, and delaying frost growth by limiting the success of interdrop ice bridge formation.", "output": "There is no related enetity." }, { "input": "Toxicity of copper salts is dependent on solubility profile and cell type tested.", "output": "copper salts." }, { "input": "Copper ( Cu ) is considered an essential metal for living organisms.", "output": "Copper, Cu." }, { "input": "However, disruption of Cu homeostasis is toxic and can lead to disorders such as Menkes and Wilson ' s diseases.", "output": "Cu." }, { "input": "The brain appears to be a vulnerable target organ.", "output": "There is no related enetity." }, { "input": "This study investigated the toxicity of Cu based on its solubility profile and cell type tested.", "output": "Cu." }, { "input": "Human A - 172 ( glioblastoma ), SK - N - SH ( neuroblastoma ) and CCF - STTG1 ( astrocytoma ) cells were assessed after exposure to different concentrations ( 0. 5 - 500 mu M ) of copper sulfate ( CuSO4 ) or copper ( II ) oxide ( CuO ).", "output": "copper sulfate, CuSO4, copper ( II ) oxide, CuO." }, { "input": "Since Cu is a redox active transition metal, we hypothesized that oxidative stress would be the main mechanism underlying cell toxicity.", "output": "Cu, transition metal." }, { "input": "Therefore, cell viability was correlated with the extent of reactive oxygen species ( ROS ) formation.", "output": "oxygen." }, { "input": "Cell viability decreased at the higher concentrations of the Cu salts and CuO was more toxic compared to CuSO4.", "output": "Cu salts, CuO, CuSO4." }, { "input": "The astrocytoma and glioblastoma cells were more vulnerable compared to the neuronal cells.", "output": "There is no related enetity." }, { "input": "Furthermore, it appears that oxidative stress only partially accounts for Cu - induced cell toxicity.", "output": "Cu." }, { "input": "Further studies are needed to better understand the unique susceptibility of glial cells and determine the physicochemical properties of insoluble Cu which accounts for its enhanced toxicity.", "output": "Cu." }, { "input": "Synthesis and biological evaluation of new N - alkylcarbazole derivatives as STAT3 inhibitors: preliminary study.", "output": "N - alkylcarbazole." }, { "input": "The signalling pathway of Janus tyrosine Kinases - Signal Transducers and Activators of Transcription ( JAK - STAT ) is activated by a number of cytokines, hormones ( GH, erythropoietin and prolactin ), and growth factors.", "output": "tyrosine." }, { "input": "JAK - STAT signalling is involved in regulation of cell proliferation, differentiation and apoptosis.", "output": "There is no related enetity." }, { "input": "These activities are due to different members of JAK - STAT family consisting of: JAK1, JAK2, JAK3, Tyk2 and STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6.", "output": "There is no related enetity." }, { "input": "Recent studies suggest a key role for STAT family proteins, in particular for STAT3, in selectively inducing and maintaining a pro - carcinogenic inflammatory microenvironment, that promote tumour cells transformation.", "output": "There is no related enetity." }, { "input": "Moreover, a striking correlation between cancer development / progression and STAT3 persistent activation exists, probably due to STAT3 promoting of the pro - oncogenic inflammatory pathways, like NF - kB, IL - 6 and JAK family kinases.", "output": "There is no related enetity." }, { "input": "Recent study demonstrated that carbazoles can inhibit STAT3 mediated transcription.", "output": "carbazoles." }, { "input": "From these evidences, STAT3 represents a therapeutic target, so we have synthesized a new set of N - alkylcarbazole derivatives substituted in positions 2, 4 and 6, to evaluate their activity on STAT3.", "output": "N - alkylcarbazole." }, { "input": "Some of these compounds showed an interesting activity as STAT3 selective inhibitors; in particular, compounds 9a 9b and 9c revealed to inhibit the STAT3 activation for the 50 %, 90 % and 95 %, respectively.", "output": "There is no related enetity." }, { "input": "Adult dose - dependent behavioral and cognitive disturbances after a single neonatal PFHxS dose.", "output": "PFHxS." }, { "input": "Perfluoroalkyl acids, including perfluorohexane sulfonate ( PFHxS ), are fluorinated organic compounds used as surfactants and water and stain repellents in carpets, paper, and textiles, with characteristics to bioaccumulate and biomagnify in the food chain.", "output": "Perfluoroalkyl acids, perfluorohexane sulfonate, PFHxS." }, { "input": "PFHxS is found in umbilical cord blood, human milk and child serum from all over the world.", "output": "PFHxS." }, { "input": "We have recently reported that neonatal exposure to certain perfluoroalkyl acids, PFOS and PFOA, can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal.", "output": "perfluoroalkyl acids, PFOS, PFOA." }, { "input": "The present study indicates that a single exposure to PFHxS on postnatal day 10, during a vulnerable period of brain development can alter adult spontaneous behavior and cognitive function in both male and female mice, effects that are both dose - response related and long - lasting / irreversible.", "output": "PFHxS." }, { "input": "PFHxS affected the cholinergic system, manifested as altered nicotine - induced behavior in adult animals.", "output": "PFHxS, nicotine." }, { "input": "This is also in agreement with earlier studies on neonatal exposure to PFOS and PFOA.", "output": "PFOS, PFOA." }, { "input": "The present findings show that PFHxS, a member of the perfluoroalkyl acid group, can act as a developmental neurotoxicant and affect the cholinergic system and cognitive function and the effects show similarities with effects earlier reported after neonatal exposure to other POPs, such as bisphenol A, PBDEs and PCBs.", "output": "PFHxS, perfluoroalkyl acid, bisphenol A, PBDEs, PCBs." }, { "input": "Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens.", "output": "There is no related enetity." }, { "input": "Adolescent alcohol binge drinking constitutes a major vulnerability factor to develop alcoholism.", "output": "There is no related enetity." }, { "input": "However, mechanisms underlying this susceptibility remain unknown.", "output": "There is no related enetity." }, { "input": "We evaluated the effect of adolescent binge - like ethanol intoxication on vulnerability to alcohol abuse in Sprague - Dawley rats.", "output": "ethanol." }, { "input": "To model binge - like ethanol intoxication, every 2 days, rats received an ethanol injection ( 3. 0 g / kg ) for 2 consecutive days across 14 days either from postnatal day 30 ( PND30 ) to 43 ( early adolescence ) or from PND 45 to PND 58 ( late adolescence ).", "output": "ethanol, ethanol." }, { "input": "In young adult animals, we measured free ethanol consumption in the two - bottle choice paradigm, motivation for ethanol in the operant self - administration task and both ethanol ' s rewarding and aversive properties in the conditioned place preference ( CPP ) and taste aversion ( CTA ) paradigms.", "output": "ethanol, ethanol, ethanol." }, { "input": "While intermittent ethanol intoxications ( IEI ) during late adolescence had no effect on free - choice 10 % ethanol consumption, we found that IEI during early adolescence promoted free - choice 10 % ethanol consumption, enhanced motivation for ethanol in the self - administration paradigm and induced a loss of both ethanol - induced CPP and CTA in young adults.", "output": "ethanol, ethanol, ethanol, ethanol, ethanol." }, { "input": "No modification in either sucrose self - administration or amphetamine - induced CPP was observed.", "output": "sucrose, amphetamine." }, { "input": "As the nucleus accumbens ( Nac ) is particularly involved in addictive behavior, we analyzed IEI - induced long - term neuroadaptations in the Nac using c - Fos immunohistochemistry and an array of neurotransmission - related genes.", "output": "There is no related enetity." }, { "input": "This vulnerability to ethanol abuse was associated with a lower c - Fos immunoreactivity in the Nac and enduring alterations of the expression of Penk and Slc6a4, 2 neurotransmission - related genes that have been shown to play critical roles in the behavioral effects of ethanol and alcoholism.", "output": "ethanol, ethanol." }, { "input": "Cannabinoid discrimination and antagonism by CB ( 1 ) neutral and inverse agonist antagonists.", "output": "Cannabinoid." }, { "input": "Cannabinoid receptor 1 ( CB ( 1 ) ) inverse agonists ( e. g., rimonabant ) have been reported to produce adverse effects including nausea, emesis, and anhedonia that limit their clinical applications.", "output": "Cannabinoid, rimonabant." }, { "input": "Recent laboratory studies suggest that the effects of CB ( 1 ) neutral antagonists differ from those of such inverse agonists, raising the possibility of improved clinical utility.", "output": "There is no related enetity." }, { "input": "However, little is known regarding the antagonist properties of neutral antagonists.", "output": "There is no related enetity." }, { "input": "In the present studies, the CB ( 1 ) inverse agonist SR141716A ( rimonabant ) and the CB ( 1 ) neutral antagonist AM4113 were compared for their ability to modify CB ( 1 ) receptor - mediated discriminative stimulus effects in nonhuman primates trained to discriminate the novel CB ( 1 ) full agonist AM4054.", "output": "SR141716A, rimonabant, AM4113, AM4054." }, { "input": "Results indicate that AM4054 serves as an effective CB ( 1 ) discriminative stimulus, with an onset and time course of action comparable with that of the CB ( 1 ) agonist Delta ( 9 ) - tetrahydrocannabinol, and that the inverse agonist rimonabant and the neutral antagonist AM4113 produce dose - related rightward shifts in the AM4054 dose - effect curve, indicating that both drugs surmountably antagonize the discriminative stimulus effects of AM4054.", "output": "AM4054, Delta ( 9 ) - tetrahydrocannabinol, rimonabant, AM4113, AM4054, AM4054." }, { "input": "Schild analyses further show that rimonabant and AM4113 produce highly similar antagonist effects, as evident in comparable pA ( 2 ) values ( 6. 9 ).", "output": "rimonabant, AM4113." }, { "input": "Taken together with previous studies, the present data suggest that the improved safety profile suggested for CB ( 1 ) neutral antagonists over inverse agonists is not accompanied by a loss of antagonist action at CB ( 1 ) receptors.", "output": "There is no related enetity." }, { "input": "Dose dependent molecular effects of acrylamide and glycidamide in human cancer cell lines and human primary hepatocytes.", "output": "acrylamide, glycidamide." }, { "input": "Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer.", "output": "acrylamide." }, { "input": "However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of low level acrylamide exposure as seen by dietary intake are not well understood.", "output": "acrylamide, acrylamide." }, { "input": "Therefore, we analyzed in ovarian and endometrial cancer cell lines as well as in primary hepatocytes the expression of genes involved in cancer development and xenobiotic metabolism after high and low dose exposure ( 1 - 0. 001mM ) of acrylamide and its metabolite glycidamide.", "output": "acrylamide, glycidamide." }, { "input": "In conclusion our in vitro results demonstrate that exposure to high doses of glycidamide / acrylamide - exceeding the dietary exposure of the general population by far - can induce genes with growth promoting potential like the oncogene cMYC and genes involved in the MAPK pathway.", "output": "glycidamide, acrylamide." }, { "input": "However, low - dose exposure seems to activate primarily genes involved in the elimination of the toxicant.", "output": "There is no related enetity." }, { "input": "Cloning and characterization of an antibacterial L - amino acid oxidase from Crotalus durissus cumanensis venom.", "output": "L - amino acid." }, { "input": "An L - amino acid oxidase ( LAAO ) from Crotalus durissus cumanensis venom ( CdcLAAO ) was purified to homogeneity using a combination of size - exclusion and ion exchange chromatographies.", "output": "L - amino acid." }, { "input": "CdcLAAO is a monomeric protein exhibiting an apparent molecular mass of 55 kDa and a calculated pI of 8.", "output": "There is no related enetity." }, { "input": "Its complete 498 - amino - acid sequence was deduced through cDNA and protein sequencing.", "output": "amino - acid." }, { "input": "The enzyme oxidized L - Leu with K ( m ) and a V ( Max ) of 9. 23 mu M and 0. 46 mu M / min respectively, and exhibited Kcat and a Kcat / K ( m ) of 1. 8 s ( - 1 ) and 195 mM ( - 1 ) s ( - 1 ).", "output": "L - Leu." }, { "input": "CdcLAAO inhibited in a dose - dependent manner the growth of Staphylococcus aureus and Acinetobacter baumannii.", "output": "There is no related enetity." }, { "input": "The inhibitory effect was more significant on S. aureus, with a Minimal Inhibitory Concentration ( MIC ) of 8 mu g / mL and Minimal Bactericidal Concentration ( MBC ) of 16 mu g / mL, than against A. baumannii, with a MIC of 16 mu g / mL and MBC of 32 mu g / mL.", "output": "There is no related enetity." }, { "input": "However, against Escherichia coli CdcLAAO did not show inhibitory capacity at the concentrations tested ( 2 - 128 mu g / mL ).", "output": "There is no related enetity." }, { "input": "CdcLAAO did not exhibit cytotoxic activity on the mouse myoblast cell line C ( 2 ) C ( 12 ) and on peripheral blood mononuclear cell ( PBMC ).", "output": "There is no related enetity." }, { "input": "Toxicity of the flame - retardant BDE - 49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN - deficient background.", "output": "BDE - 49." }, { "input": "Polybrominated diphenyl ethers ( PBDEs ) represent an important group of flame retardants extensively used, tonnage of which in the environment has been steadily increasing over the past 25 years.", "output": "Polybrominated diphenyl ethers, PBDEs." }, { "input": "PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction ( MD ) through a variety of mechanisms.", "output": "PBDEs." }, { "input": "Recently, PBDEs with < 5 Br substitutions ( i. e., 2, 2 ', 4, 4 ' - tetrabromodiphenyl ether [ BDE - 47 ] and 2, 2 ', 4, 5 ' - tetrabromodiphenyl ether [ BDE - 49 ] ) have gained interest because of their high bioaccumulation.", "output": "PBDEs, Br, 2 , 2 ' , 4 , 4 ' - tetrabromodiphenyl ether, BDE - 47, 2 , 2 ' , 4 , 5 ' - tetrabromodiphenyl ether, BDE - 49." }, { "input": "In particular, congeners such as BDE - 49 arise as one of the most biologically active, with concentrations typically lower than those observed for BDE - 47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown.", "output": "BDE - 49, BDE - 47." }, { "input": "To this end, the effect of BDE - 49 was studied in brain mitochondria and neuronal progenitor striatal cells ( NPC ).", "output": "BDE - 49." }, { "input": "BDE - 49 uncoupled mitochondria at concentrations < 0. 1 nM, whereas at > 1 nM, it inhibited the electron transport at Complex V ( mixed type inhibition; IC ( 50 ) = 6 nM ) and Complex IV ( noncompetitive inhibition; IC ( 50 ) = 40 nM ).", "output": "BDE - 49." }, { "input": "These concentrations are easily achieved in plasma concentrations considering that BDE - 49 ( this study, 400 - fold ) and other PBDEs accumulate 1 - 3 orders of magnitude in the cells, particularly in mitochondria and microsomes.", "output": "BDE - 49, PBDEs." }, { "input": "Similar effects were observed in NPC and exacerbated with PTEN ( negative modulator of the PI3K / Akt pathway ) deficiency, background associated with autism - like behavior, schizophrenia, and epilepsy.", "output": "There is no related enetity." }, { "input": "PBDE - mediated MD per se or enhanced by a background that confers susceptibility to this exposure may have profound implications in the energy balance of brain.", "output": "PBDE." }, { "input": "Molecular mechanisms of fibrosis - associated promotion of liver carcinogenesis.", "output": "There is no related enetity." }, { "input": "Hepatocellular carcinoma ( HCC ) mostly develops in patients with advanced fibrosis; however, the mechanisms of interaction between a genotoxic insult and fibrogenesis are not well understood.", "output": "There is no related enetity." }, { "input": "This study tested a hypothesis that fibrosis promotes HCC via a mechanism that involves activation of liver stem cells.", "output": "There is no related enetity." }, { "input": "First, B6C3F1 mice were administered diethylnitrosamine ( DEN; single ip injection of 1mg / kg at 14 days of age ).", "output": "diethylnitrosamine, DEN." }, { "input": "Second, carbon tetrachloride ( CCl ( 4 ); 0. 2ml / kg, 2 / week ip starting at 8 weeks of age ) was administered for 9 or 14 weeks to develop advanced liver fibrosis.", "output": "carbon tetrachloride, CCl ( 4 )." }, { "input": "In animals treated with DEN as neonates, presence of liver fibrosis led to more than doubling ( to 100 % ) of the liver tumor incidence as early as 5 months of age.", "output": "DEN." }, { "input": "This effect was associated with activation of cells with progenitor features in noncancerous liver tissue, including markers of replicative senescence ( p16 ), oncofetal transformation ( Afp, H19, and Bex1 ), and increased \" stemness \" ( Prom1 and Epcam ).", "output": "There is no related enetity." }, { "input": "In contrast, the dose of DEN used did not modify the extent of liver inflammation, fibrogenesis, oxidative stress, proliferation, or apoptosis induced by subchronic CCl ( 4 ) administration.", "output": "DEN, CCl ( 4 )." }, { "input": "This study demonstrates the potential role of liver stem - like cells in the mechanisms of chemical - induced, fibrosis - promoted HCC.", "output": "There is no related enetity." }, { "input": "We posit that the combination of genotoxic and fibrogenic insults is a sensible approach to model liver carcinogenesis in experimental animals.", "output": "There is no related enetity." }, { "input": "These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue.", "output": "There is no related enetity." }, { "input": "Therapeutic drug monitoring of antiepileptic drugs by use of saliva.", "output": "There is no related enetity." }, { "input": "Blood ( serum / plasma ) antiepileptic drug ( AED ) therapeutic drug monitoring ( TDM ) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy.", "output": "There is no related enetity." }, { "input": "Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM.", "output": "There is no related enetity." }, { "input": "The advantages of saliva include the fact that for many AEDs it reflects the free ( pharmacologically active ) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly.", "output": "There is no related enetity." }, { "input": "For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum.", "output": "There is no related enetity." }, { "input": "Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting.", "output": "There is no related enetity." }, { "input": "Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide.", "output": "carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, zonisamide." }, { "input": "Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.", "output": "valproic acid, clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin." }, { "input": "A new hematite photoanode doping strategy for solar water splitting: oxygen vacancy generation.", "output": "hematite, oxygen." }, { "input": "The enhancement of the electrical conductivity by doping is important in hematite ( alpha - Fe ( 2 ) O ( 3 ) ) photoanodes for efficient solar water oxidation.", "output": "hematite, alpha - Fe ( 2 ) O ( 3 )." }, { "input": "However, in spite of many successful demonstrations using extrinsic dopants, such as Sn, Ti, and Si, the achieved photocurrent is still lower than the practical requirement.", "output": "Sn, Ti, Si." }, { "input": "There is still lack of our understanding of how intrinsic oxygen defects can change the photocurrent and interact with the extrinsic dopants.", "output": "oxygen." }, { "input": "In this study, we systematically investigate the interplay of oxygen vacancies and extrinsic Sn dopants in the context of photoanodic properties.", "output": "oxygen, Sn." }, { "input": "As a result, we demonstrate that the controlled generation of oxygen vacancies can activate the photoactivity of pure hematite remarkably and further enhance the Sn doping effects synergistically.", "output": "oxygen, hematite, Sn." }, { "input": "Furthermore, the correlated behavior of oxygen vacancies and Sn dopants is closely linked to the variation of electrical conductance and results in the optimum concentration region to show the high photocurrent and low onset voltage.", "output": "oxygen, Sn." }, { "input": "A popular engagement at the ends.", "output": "There is no related enetity." }, { "input": "Three recent studies converged on a specific protein - protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells.", "output": "There is no related enetity." }, { "input": "An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regulation.", "output": "There is no related enetity." }, { "input": "Electrolyte - gated organic field - effect transistor sensors based on supported biotinylated phospholipid bilayer.", "output": "There is no related enetity." }, { "input": "Anchored, biotinylated phospholipids forming the capturing layers in an electrolyte - gated organic field - effect transistor ( EGOFET ) allow label - free electronic specific detection at a concentration level of 10 nM in a high ionic strength solution.", "output": "There is no related enetity." }, { "input": "The sensing mechanism is based on a clear capacitive effect across the PL layers involving the charges of the target molecules.", "output": "There is no related enetity." }, { "input": "P - glycoprotein increases portal bioavailability of loperamide in mouse by reducing first - pass intestinal metabolism.", "output": "loperamide." }, { "input": "P - glycoprotein ( P - gp ) and CYP3A ( cytochrome P450 3A, generally; Cyp3a, rodent enzyme ) in the intestine can attenuate absorption of orally administered drugs.", "output": "There is no related enetity." }, { "input": "While some suggest that P - gp enhances intestinal metabolism by CYP3A / Cyp3a during absorption of a dual substrate, others suggest that P - gp reduces the metabolism in the intestine when substrates are at subsaturating concentrations.", "output": "There is no related enetity." }, { "input": "Hence, to elucidate the cellular mechanisms that can address these divergent reports, we studied intestinal absorption of the dual substrate loperamide in portal vein - cannulated P - gp - competent and P - gp - deficient mice.", "output": "loperamide." }, { "input": "These studies showed that at low doses of loperamide, which produced intestinal concentrations near the apparent K ( m ) for oxidative metabolism, the bioavailability across the intestine ( F ( G ) ) was 6 - fold greater in the P - gp - competent mice than in P - gp - deficient mice.", "output": "loperamide." }, { "input": "The higher F ( G ) of loperamide in the presence of P - gp was attributed to lower loperamide intestinal metabolism.", "output": "loperamide, loperamide." }, { "input": "However, at high doses of loperamide, the sparing of first - pass metabolism by P - gp was balanced against the attenuation of absorption by apical efflux, resulting in no net effect on F ( G ).", "output": "loperamide." }, { "input": "In vitro studies with intestinal tissue from P - gp - competent and - deficient mice confirmed that P - gp reduced the metabolic rate of loperamide during absorptive flux at concentrations near K ( m ) but had little effect on metabolism at higher ( saturating ) concentrations.", "output": "loperamide." }, { "input": "Further, studies in which Cyp3a was chemically inactivated by aminobenzotriazole in P - gp - competent and - deficient mice, showed that P - gp and Cyp3a individually attenuated F ( G ) by 8 - fold and 70 - fold, respectively.", "output": "aminobenzotriazole." }, { "input": "These results confirmed that P - gp effectively protects loperamide at low doses from intestinal first - pass metabolism during intestinal absorption.", "output": "loperamide." }, { "input": "Influence of polyelectrolyte film stiffness on bacterial growth.", "output": "There is no related enetity." }, { "input": "Photo - cross - linkable polyelectrolyte films, whose nanomechanical properties can be varied under UV light illumination, were prepared from poly ( l - lysine ) ( PLL ) and a hyaluronan derivative modified with photoreactive vinylbenzyl groups ( HAVB ).", "output": "poly ( l - lysine ), PLL, vinylbenzyl." }, { "input": "The adhesion and the growth of two model bacteria, namely Escherichia coli and Lactococcus lactis, were studied on non - cross - linked and cross - linked films to investigate how the film stiffness influences the bacterial behavior.", "output": "There is no related enetity." }, { "input": "While the Gram positive L. lactis was shown to grow slowly on both films, independently of their rigidity, the Gram negative E. coli exhibited a more rapid growth on non - cross - linked softer films compared to the stiffer ones.", "output": "There is no related enetity." }, { "input": "Experiments performed on photopatterned films showing both soft and stiff regions, confirmed a faster development of E. coli colonies on softer regions.", "output": "There is no related enetity." }, { "input": "Interestingly, this behavior is opposite to the one reported before for mammalian cells.", "output": "There is no related enetity." }, { "input": "Therefore, the photo - cross - linked ( PLL / HAVB ) films are interesting coatings for tissue engineering since they promote the growth of mammalian cells while limiting the bacterial colonization.", "output": "There is no related enetity." }, { "input": "Novel 1H - 1, 2, 3 -, 2H - 1, 2, 3 -, 1H - 1, 2, 4 - and 4H - 1, 2, 4 - triazole derivatives: a patent review ( 2008 - 2011 ).", "output": "1H - 1 , 2 , 3 - , 2H - 1 , 2 , 3 - , 1H - 1 , 2 , 4 - and 4H - 1 , 2 , 4 - triazole." }, { "input": "INTRODUCTION: The triazoles represent a class of five - membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms.", "output": "triazoles, carbon, nitrogen." }, { "input": "Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds.", "output": "triazoles." }, { "input": "In this review, the authors explored aspects of patents for the 1H - 1, 2, 3 -, 2H - 1, 2, 3 -, 1H - 1, 2, 4 - and 4H - 1, 2, 4 - triazole families, including prototypes being considered in clinical studies between 2008 and 2011.", "output": "1H - 1 , 2 , 3 - , 2H - 1 , 2 , 3 - , 1H - 1 , 2 , 4 - and 4H - 1 , 2 , 4 - triazole." }, { "input": "AREAS COVERED: The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities.", "output": "triazoles." }, { "input": "More recently, there has been considerable interest in the development of novel triazoles with anti - inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases.", "output": "triazoles." }, { "input": "This review emphasizes recent perspective and advances in the therapeutically active 1H - 1, 2, 3 -, 2H - 1, 2, 3 -, 1H - 1, 2, 4 - and 4H - 1, 2, 4 - triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals.", "output": "1H - 1 , 2 , 3 - , 2H - 1 , 2 , 3 - , 1H - 1 , 2 , 4 - and 4H - 1 , 2 , 4 - triazole." }, { "input": "Many studies have focused on these compounds as target structures and evaluated them in several biological targets.", "output": "There is no related enetity." }, { "input": "EXPERT OPINION: The preparation of 1H - 1, 2, 3 -, 2H - 1, 2, 3 -, 1H - 1, 2, 4 - and 4H - 1, 2, 4 - triazole derivatives brings to light several issues.", "output": "1H - 1 , 2 , 3 - , 2H - 1 , 2 , 3 - , 1H - 1 , 2 , 4 - and 4H - 1 , 2 , 4 - triazole." }, { "input": "There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability.", "output": "triazoles." }, { "input": "New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these new diseases.", "output": "There is no related enetity." }, { "input": "Of great urgency is finding prototypes against bacteria that continue to increase resistance and for neglected diseases that affect a large part of humanity, especially the poor and vulnerable.", "output": "There is no related enetity." }, { "input": "Infrared multiple photon dissociation action spectroscopy of deprotonated DNA mononucleotides: gas - phase conformations and energetics.", "output": "mononucleotides." }, { "input": "The gas phase structures of the deprotonated 2 ' - deoxymononucleotides including 2 ' - deoxyadenosine - 5 ' - monophosphate ( dA5 ' p ), 2 ' - deoxycytidine - 5 ' - monophosphate ( dC5 ' p ), 2 ' - deoxyguanosine - 5 ' - monophosphate ( dG5 ' p ), and thymidine - 5 ' - monophosphate ( T5 ' p ) are examined via infrared multiple photon dissociation ( IRMPD ) action spectroscopy and theoretical electronic structure calculations.", "output": "2 ' - deoxymononucleotides, 2 ' - deoxyadenosine - 5 ' - monophosphate, dA5 ' p, 2 ' - deoxycytidine - 5 ' - monophosphate, dC5 ' p, 2 ' - deoxyguanosine - 5 ' - monophosphate, dG5 ' p, thymidine - 5 ' - monophosphate, T5 ' p." }, { "input": "The measured IRMPD action spectra of all four deprotonated DNA mononucleotides exhibit unique spectral features in the region extending from ~ 600 to 1800 cm ( - 1 ) such that they can be readily differentiated from one another.", "output": "mononucleotides." }, { "input": "The measured IRMPD action spectra are compared to the linear IR spectra calculated at the B3LYP / 6 - 311 + G ( d, p ) level of theory to determine the conformations of these species accessed in the experiments.", "output": "There is no related enetity." }, { "input": "On the basis of these comparisons and the computed energetic information, the most stable conformations of the deprotonated forms of dA5 ' p, dC5 ' p, and T5 ' p are conformers where the ribose moiety adopts a C3 ' endo conformation and the nucleobase is in an anti conformation.", "output": "dA5 ' p, dC5 ' p, T5 ' p, ribose, nucleobase." }, { "input": "By contrast, the most stable conformations of the deprotonated form of dG5 ' p are conformers where the ribose adapts a C3 ' endo conformation and the nucleobase is in a syn conformation.", "output": "dG5 ' p, nucleobase." }, { "input": "In addition to the ground - state conformers, several stable low - energy excited conformers that differ slightly in the orientation of the phosphate ester moiety were also accessed in the experiments.", "output": "phosphate ester." }, { "input": "Freezing continuous - flow self - assembly in a microfluidic device: toward imaging of liposome formation.", "output": "There is no related enetity." }, { "input": "A new method is described that combines a microfluidic device for the controlled formation of liposomes with instantaneous immobilization by means of ultrarapid cooling.", "output": "There is no related enetity." }, { "input": "The microfluidic device is composed of capillaries to hydrodynamically focus a stream of lipids dissolved in 2 - propanol by two adjacent aqueous buffer streams before rapidly cooling by propane jet - freezing.", "output": "2 - propanol." }, { "input": "The capillary containing the frozen sheath - flow is subsequently separated from the flow - focusing unit and trimmed with cryo - ultramicrotomy for imaging with cryo - scanning electron microscopy ( SEM ).", "output": "There is no related enetity." }, { "input": "The emergence of liposomes could be visualized by cryo - SEM without the need for chemical fixation or labeling.", "output": "There is no related enetity." }, { "input": "We demonstrate that the method is capable of revealing in more detail the formation of nonequilibrium liposomes.", "output": "There is no related enetity." }, { "input": "Partially and completely formed liposomes were observed at the miscible alcohol - buffer interface.", "output": "alcohol." }, { "input": "The number density of lipid vesicles varied along the focused interface, and we frequently found clusters of liposomes.", "output": "There is no related enetity." }, { "input": "Additionally, evidence for the formation of disclike transient intermediates is presented.", "output": "There is no related enetity." }, { "input": "The method is not limited to studying self - assembly processes only.", "output": "There is no related enetity." }, { "input": "It can be extended to other biochemical reactions, crystallization processes, and even systematic interfacial mixing studies between different solvents.", "output": "There is no related enetity." }, { "input": "Distribution and seasonal variation in hypothalamic RF - amide peptides in a semi - desert rodent, the jerboa.", "output": "amide." }, { "input": "The jerboa is a semi - desert rodent, in which reproductive activity depends on the seasons, being sexually active in the spring - summer.", "output": "There is no related enetity." }, { "input": "The present study aimed to determine whether the expression of two RF - amide peptides recently described to regulate gonadotrophin - releasing hormone neurone activity, kisspeptin ( Kp ) and RF - amide - related peptide ( RFRP ) - 3, displays seasonal variation in jerboa.", "output": "amide, amide." }, { "input": "Kp and / or RFRP - 3 immunoreactivity was investigated in the hypothalamus of jerboas captured in the field of the Middle Atlas mountain ( Morocco ), either in the spring or autumn.", "output": "There is no related enetity." }, { "input": "As in other rodents, the Kp - immunoreactive ( - IR ) neurones were found in the anteroventro - periventricular and arcuate nuclei.", "output": "There is no related enetity." }, { "input": "RFRP - 3 neurones were noted within the dorso / ventromedial hypothalamus.", "output": "There is no related enetity." }, { "input": "A marked sexual dimorphism in the expression of Kp ( but not RFRP - 3 ) was observed.", "output": "There is no related enetity." }, { "input": "The number of Kp - IR neurones was nine - fold higher, and the density of Kp - IR fibres and terminal - like elements in the median eminence was two - fold higher in females than in males.", "output": "There is no related enetity." }, { "input": "Furthermore, a significant seasonal variation in peptide expression was obtained with an increase in both Kp - and RFRP - 3 - IR cell bodies in sexually active male jerboas captured in the spring compared to sexually inactive autumn animals.", "output": "There is no related enetity." }, { "input": "In the arcuate nucleus, the level of Kp - IR cells and fibres was significant higher during the sexually active period in the spring than during the autumnal sexual quiescence.", "output": "There is no related enetity." }, { "input": "Similarly, the number of RFRP - 3 - IR neurones in the ventro / dorsomedial hypothalamus was approximately three - fold higher in sexually active jerboa captured in the spring compared to sexually inactive autumn animals.", "output": "There is no related enetity." }, { "input": "Altogether, the present study reports the distribution of Kp and RFRP - 3 neurones in the hypothalamus of a desert species and reveals a seasonal difference in their expression that correlates with sexual activity.", "output": "There is no related enetity." }, { "input": "These findings suggest that these two RF - amide peptides may act in concert to synchronise the gonadotrophic activity of jerboas with the seasons.", "output": "There is no related enetity." }, { "input": "Living unimodal growth of polyion complex vesicles via two - dimensional supramolecular polymerization.", "output": "There is no related enetity." }, { "input": "Understanding the dynamic behavior of molecular self - assemblies with higher - dimensional structures remains a key challenge to obtaining well - controlled and monodispersed structures.", "output": "There is no related enetity." }, { "input": "Nonetheless, there exist few systems capable of realizing the mechanism of supramolecular polymerization at higher dimensions.", "output": "There is no related enetity." }, { "input": "Herein, we report the unique self - assembling behavior of polyion complexes ( PICs ) consisting of poly ( ethylene glycol ) - polyelectrolyte block copolymer as an example of two - dimensional supramolecular living polymerization.", "output": "poly ( ethylene glycol )." }, { "input": "Monodispersed and submicrometer unilamellar PIC vesicles ( nano - PICsomes ) displayed time - dependent growth while maintaining a narrow size distribution and a unilamellar structure.", "output": "There is no related enetity." }, { "input": "Detailed analysis of the system revealed that vesicle growth proceeded through the consumption of unit PICs ( uPICs ) composed of a single polycation / polyanion pair and was able to restart upon the further addition of isolated uPICs.", "output": "There is no related enetity." }, { "input": "Interestingly, the resulting vesicles underwent dissociation into uPICs in response to mechanical stress.", "output": "There is no related enetity." }, { "input": "These results clearly frame the growth as a two - dimensional supramolecular living polymerization of uPICs.", "output": "There is no related enetity." }, { "input": "Mammalian Trit1 is a tRNA ( [ Ser ] Sec ) - isopentenyl transferase required for full selenoprotein expression.", "output": "Ser, Sec, isopentenyl." }, { "input": "Selenoproteins are proteins carrying the rare amino acid Sec ( selenocysteine ).", "output": "amino acid, Sec, selenocysteine." }, { "input": "Full expression of selenoproteins requires modification of tRNA ( [ Ser ] Sec ), including N ( 6 ) - isopentenylation of base A ( 37 ).", "output": "Ser, Sec." }, { "input": "We show that Trit1 is a dimethylallyl: tRNA ( [ Ser ] Sec ) transferase.", "output": "dimethylallyl, Ser, Sec." }, { "input": "Knockdown of Trit1 reduces expression of selenoproteins.", "output": "There is no related enetity." }, { "input": "Incubation of in vitro transcribed tRNA [ Ser ] Sec with recombinant Trit1 transfers [ ( 14 ) C ] dimethylallyl pyrophosphate to tRNA ( [ Ser ] Sec ).", "output": "Ser, Sec, [ ( 14 ) C ] dimethylallyl pyrophosphate, Ser, Sec." }, { "input": "37A > G tRNA ( [ Ser ] Sec ) is resistant to isopentenylation by Trit1.", "output": "Ser, Sec." }, { "input": "Engagement of CF3 group in N - H... F - C hydrogen bond in the solution state: NMR spectroscopy and MD simulation studies.", "output": "CF3, N - H, F - C, hydrogen." }, { "input": "Unambiguous evidence for the engagement of CF ( 3 ) group in N - H... F - C hydrogen bond in a low polarity solvent, the first observation of its kind, is reported.", "output": "CF ( 3 ), N - H, F - C, hydrogen." }, { "input": "The presence of such weak molecular interactions in the solution state is convincingly established by one and two - dimensional ( 1 ) H, ( 19 ) F, and natural abundant ( 15 ) N NMR spectroscopic studies.", "output": "( 1 ) H, ( 19 ) F, ( 15 ) N." }, { "input": "The strong and direct evidence is derived by the observation of through - space couplings, such as, ( 1h ) J ( FH ), ( 1h ) J ( FN ), and ( 2h ) J ( FF ), where the spin polarization is transmitted through hydrogen bond.", "output": "FH, FN, FF, hydrogen." }, { "input": "In an interesting example of a molecule containing two CF ( 3 ) groups getting simultaneously involved in hydrogen bond, where hydrogen bond mediated couplings are not reflected in the NMR spectrum, ( 19 ) F - ( 19 ) F NOESY experiment yielded confirmatory evidence.", "output": "CF ( 3 ), hydrogen, hydrogen, ( 19 ) F, ( 19 ) F." }, { "input": "Significant deviations in the strengths of ( 1 ) J ( NH ), variable temperature, and the solvent induced perturbations yielded additional support.", "output": "NH." }, { "input": "The NMR results are corroborated by both DFT calculations and MD simulations, where the quantitative information on different ways of involvement of fluorine in two and three centered hydrogen bonds, their percentage of occurrences, and geometries have been obtained.", "output": "fluorine, hydrogen." }, { "input": "The hydrogen bond interaction energies have also been calculated.", "output": "hydrogen." }, { "input": "On the preparation of indoxyl red from indican and some new characteristics.", "output": "indoxyl red." }, { "input": "An indole compound with a strong purple - red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE - 650S Toyopearl TSK - gel and silica - gel columns.", "output": "indole, silica." }, { "input": "The purple - red compound purified was identified as indoxyl red, on the basis of FAB Mass, ( 13 ) C NMR, ( 1 ) H NMR, UV - visible spectra, and IR spectra.", "output": "indoxyl red, ( 13 ) C, ( 1 ) H." }, { "input": "Although indoxyl red was first synthesized by Seidel ( 9 ) 70 years ago, very little information has been available on its characteristics.", "output": "indoxyl red." }, { "input": "We repot here that the compound was purple - red colored at acidic pH and green at pH 13, and showed antiproliferative and cytotoxic activities to the mouse B cell lymphoma cell line NSF202.", "output": "There is no related enetity." }, { "input": "Alkyladenine DNA glycosylase ( AAG ) localizes to mitochondria and interacts with mitochondrial single - stranded binding protein ( mtSSB ).", "output": "Alkyladenine." }, { "input": "Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts.", "output": "There is no related enetity." }, { "input": "While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria.", "output": "There is no related enetity." }, { "input": "Alkyladenine DNA glycosylase ( AAG ) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG.", "output": "Alkyladenine." }, { "input": "Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria.", "output": "There is no related enetity." }, { "input": "We identify mitochondrial single - stranded binding protein ( mtSSB ) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate ( MMS ) treatment.", "output": "methyl methanesulfonate, MMS." }, { "input": "The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single - stranded DNA ( ssDNA ), but not a double - stranded DNA ( dsDNA ) substrate.", "output": "There is no related enetity." }, { "input": "By inhibiting AAG - initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA.", "output": "There is no related enetity." }, { "input": "In summary, our findings suggest the existence of AAG - initiated BER in mitochondria and further support a role for mtSSB in DNA repair.", "output": "There is no related enetity." }, { "input": "Zinc drives a tertiary fold in the prion protein with familial disease mutation sites at the interface.", "output": "Zinc." }, { "input": "The cellular prion protein PrP ( C ) consists of two domains - - a flexible N - terminal domain, which participates in copper and zinc regulation, and a largely helical C - terminal domain that converts to beta sheet in the course of prion disease.", "output": "N, copper, zinc, C." }, { "input": "These two domains are thought to be fully independent and noninteracting.", "output": "There is no related enetity." }, { "input": "Compelling cellular and biophysical studies, however, suggest a higher order structure that is relevant to both PrP ( C ) function and misfolding in disease.", "output": "There is no related enetity." }, { "input": "Here, we identify a Zn (2) + - driven N - terminal to C - terminal tertiary interaction in PrP ( C ).", "output": "Zn (2) +, N, C." }, { "input": "The C - terminal surface participating in this interaction carries the majority of the point mutations that confer familial prion disease.", "output": "C." }, { "input": "Investigation of mutant PrPs finds a systematic relationship between the type of mutation and the apparent strength of this domain structure.", "output": "There is no related enetity." }, { "input": "The structural features identified here suggest mechanisms by which physiologic metal ions trigger PrP ( C ) trafficking and control prion disease.", "output": "There is no related enetity." }, { "input": "Syntheses and evaluation of the antioxidant activity of novel methoxypsoralen derivatives.", "output": "methoxypsoralen." }, { "input": "A series of 5 - and 8 - methoxypsoralen ( MOP ) analogs, suitable for structure - antioxidative / anti - inflammatory activity relationship studies, were synthesized using as key - reactions the selective monobromination of MOPs with N - bromosaccharin and either a Heck reaction or a Suzuki coupling or a Suzuki coupling followed by a Wittig reaction to install side - chains of the acrylate - or benzoate - or cinnamate - type, respectively.", "output": "5 - and 8 - methoxypsoralen, MOP, MOPs, N - bromosaccharin, acrylate, benzoate, cinnamate." }, { "input": "The 8 - MOP analogs 19 and 24, incorporating at position 5 of the psoralen nucleus a butyl acrylate or a tert - butyl cinnamate moiety, were the most powerful inhibitors of soybean LOX and inhibited effectively lipid peroxidation.", "output": "8 - MOP, psoralen, butyl acrylate, tert - butyl cinnamate." }, { "input": "Analog 19 was a more potent anti - inflammatory agent than the reference compound indomethacin and of comparable cytocompatibility to 8 - MOP whereas analog 24 was a weaker inhibitor of inflammation than indomethacin and significantly more cytotoxic than 8 - MOP.", "output": "indomethacin, 8 - MOP, indomethacin, 8 - MOP." }, { "input": "The results of the biological tests are discussed in terms of structural characteristics.", "output": "There is no related enetity." }, { "input": "Urinary chemokine ( C - C motif ) ligand 2 ( monocyte chemotactic protein - 1 ) as a tubular injury marker for early detection of cisplatin - induced nephrotoxicity.", "output": "cisplatin." }, { "input": "Because of the difficulty in detecting segment - specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin ( cis - diamminedichloroplatinum II ) - induced nephrotoxicity.", "output": "cisplatin, cis - diamminedichloroplatinum II." }, { "input": "Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin - 1beta, chemokine ( C - C motif ) ligand ( CCL ) 2, CCL20, chemokine ( C - X - C motif ) ligand ( CXCL ) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney.", "output": "cisplatin." }, { "input": "Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased.", "output": "cisplatin." }, { "input": "Levels of both CCL2 and kidney injury molecule - 1 ( KIM - 1 ) in the whole kidney increased after cisplatin administration.", "output": "cisplatin." }, { "input": "Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium.", "output": "There is no related enetity." }, { "input": "Urinary CCL2 excretion significantly increased approximately 3 - fold compared with controls the day after cisplatin administration ( 5mg / kg ), when no changes were observed plasma creatinine and blood urea nitrogen levels.", "output": "cisplatin, creatinine, urea, nitrogen." }, { "input": "Urinary levels of KIM - 1 also increased 3 - fold after cisplatin administration.", "output": "cisplatin." }, { "input": "In addition, urinary CCL2 rather than KIM - 1 increased in chronic renal failure rats after administration of low - dose cisplatin ( 2mg / kg ), suggesting that urinary CCL2 was selective for cisplatin - induced nephrotoxicity in renal impairment.", "output": "cisplatin, cisplatin." }, { "input": "These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin - induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin - induced tubular injury.", "output": "cisplatin, cisplatin." }, { "input": "Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10.", "output": "There is no related enetity." }, { "input": "Association between autoimmune thyroid diseases ( AITD ) and hepatitis C is controversial, but may occur or worsen during alpha - interferon treatment.", "output": "There is no related enetity." }, { "input": "The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated.", "output": "There is no related enetity." }, { "input": "This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of CXCL10 and AITD.", "output": "There is no related enetity." }, { "input": "One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine - binding globulin ( TBG ) and CXCL10 measurements and hepatic biopsies.", "output": "There is no related enetity." }, { "input": "The frequency of AITD among infected subjects was similar to controls.", "output": "There is no related enetity." }, { "input": "TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them.", "output": "There is no related enetity." }, { "input": "Thyroid heterogeneity and hypoechogenicity were associated with AITD.", "output": "There is no related enetity." }, { "input": "Increased vascularization was more prevalent in chronic hepatitis C. CXCL10 was higher in infected patients ( p = 0. 007 ) but was not related to thyroid dysfunction.", "output": "There is no related enetity." }, { "input": "Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity ( p = 0. 011 ).", "output": "There is no related enetity." }, { "input": "In summary, no association was found between chronic hepatitis C and AITD.", "output": "There is no related enetity." }, { "input": "Infected subjects had higher TT3 and TT4 which were correlated to TBG.", "output": "There is no related enetity." }, { "input": "Increased CXCL10 was not associated to thyroid dysfunction in HCV - infected population.", "output": "There is no related enetity." }, { "input": "Embryonic stem cell - derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms.", "output": "There is no related enetity." }, { "input": "The development of the placenta is imperative for successful pregnancy establishment, yet the earliest differentiation events of the blastocyst - derived trophectoderm that forms the placenta remain difficult to study in humans.", "output": "There is no related enetity." }, { "input": "Human embryonic stem cells ( hESC ) display a unique ability to form trophoblast cells when induced to differentiate either by the addition of exogenous BMP4 or by the formation of cellular aggregates called embryoid bodies.", "output": "There is no related enetity." }, { "input": "While mouse trophoblast stem cells ( TSC ) have been isolated from blastocyst outgrowths, mouse ESC do not spontaneously differentiate into trophoblast cells.", "output": "There is no related enetity." }, { "input": "In this review, we focus on addressing the similarities and differences between mouse TSC differentiation and hESC - derived trophoblast differentiation.", "output": "There is no related enetity." }, { "input": "We discuss the functional and mechanistic diversity that is found in different species models.", "output": "There is no related enetity." }, { "input": "Of central importance are the unique signaling events that trigger downstream gene expression that create specific cellular fate decisions.", "output": "There is no related enetity." }, { "input": "We support the idea that we must understand the nuances that hESC differentiation models display so that investigators can choose the appropriate model system to fit experimental needs.", "output": "There is no related enetity." }, { "input": "Small - scale heat detection using catalytic microengines irradiated by laser.", "output": "There is no related enetity." }, { "input": "We demonstrate a novel approach to modulating the motion speed of catalytic microtubular engines via laser irradiation / heating with regard to small - scale heat detection.", "output": "There is no related enetity." }, { "input": "Laser irradiation on the engines leads to a thermal heating effect and thus enhances the engine speed.", "output": "There is no related enetity." }, { "input": "During a laser on / off period, the motion behaviour of a microengine can be repeatable and reversible, demonstrating a regulation of motion speeds triggered by laser illumination.", "output": "There is no related enetity." }, { "input": "Also, the engine velocity exhibits a linear dependence on laser power in various fuel concentrations, which implies an application potential as local heat sensors.", "output": "There is no related enetity." }, { "input": "Our work may hold great promise in applications such as lab on a chip, micro / nano factories, and environmental detection.", "output": "There is no related enetity." }, { "input": "The evolution of RuBisCO stability at the thermal limit of photoautotrophy.", "output": "There is no related enetity." }, { "input": "A long - standing question in evolutionary biology is how organisms adapt to novel environments.", "output": "There is no related enetity." }, { "input": "In North American hot springs, diversification of a clade of the cyanobacterium Synechococcus into hotter environments has resulted in the unique innovation of a light - driven ecosystem at temperatures up to 74 degrees C, and temperature adaptation of photosynthetic carbon fixation with the Calvin cycle contributed to this process.", "output": "There is no related enetity." }, { "input": "Here, we investigated the evolution of thermostability of the Calvin cycle enzyme ribulose - 1, 5 - bisphosphate carboxylase / oxygenase ( RuBisCO ) during Synechococcus divergence.", "output": "ribulose - 1 , 5 - bisphosphate." }, { "input": "Circular dichroism thermal scans revealed that the RuBisCO of the most thermotolerant Synechococcus lineage is more stable than those of other lineages or of resurrected ancestral enzymes.", "output": "There is no related enetity." }, { "input": "Using site - directed mutagenesis, we next identified four amino acid substitutions that together increased stability and activity of this enzyme at higher temperatures.", "output": "amino acid." }, { "input": "These are clustered near critical subunit interfaces distant from the active site.", "output": "There is no related enetity." }, { "input": "Each of the four amino acids is also observed in a less thermostable Synechococcus RuBisCO, and the impact on stability of three of these appears to be epistatic.", "output": "amino acids." }, { "input": "Recombination analyses that allow for recurrent mutation as well as patterns of synonymous variation surrounding these sites suggest that the evolution of a more thermostable RuBisCO may have involved homologous recombination.", "output": "There is no related enetity." }, { "input": "Our results provide insights on the molecular evolutionary processes that shape niche differentiation and ecosystem function.", "output": "There is no related enetity." }, { "input": "New oral anticoagulants: comparative pharmacology with vitamin K antagonists.", "output": "vitamin K." }, { "input": "New oral anticoagulants ( OACs ) that directly inhibit Factor Xa ( FXa ) or thrombin have been developed for the long - term prevention of thromboembolic disorders.", "output": "There is no related enetity." }, { "input": "These novel agents provide numerous benefits over older vitamin K antagonists ( VKAs ) due to major pharmacological differences.", "output": "vitamin K." }, { "input": "VKAs are economical and very well characterized, but have important limitations that can outweigh these advantages, such as slow onset of action, narrow therapeutic window and unpredictable anticoagulant effect.", "output": "There is no related enetity." }, { "input": "VKA - associated dietary precautions, monitoring and dosing adjustments to maintain international normalized ratio ( INR ) within therapeutic range, and bridging therapy, are inconvenient for patients, expensive, and may result in inappropriate use of VKA therapy.", "output": "There is no related enetity." }, { "input": "This may lead to increased bleeding risk or reduced anticoagulation and increased risk of thrombotic events.", "output": "There is no related enetity." }, { "input": "The new OACs have rapid onset of action, low potential for food and drug interactions, and predictable anticoagulant effect that removes the need for routine monitoring.", "output": "There is no related enetity." }, { "input": "FXa inhibitors, e. g. rivaroxaban and apixaban, are potent, oral direct inhibitors of prothrombinase - bound, clot - associated or free FXa.", "output": "rivaroxaban, apixaban." }, { "input": "Both agents have a rapid onset of action, a wide therapeutic window, little or no interaction with food and other drugs, minimal inter - patient variability, and display similar pharmacokinetics in different patient populations.", "output": "There is no related enetity." }, { "input": "Since both are substrates, co - administration of rivaroxaban and apixaban with strong cytochrome P450 ( CYP ) 3A4 and permeability glycoprotein ( P - gp ) inhibitors and inducers can result in substantial changes in plasma concentrations due to altered clearance rates; consequently, their concomitant use is contraindicated and caution is required when used concomitantly with strong CYP3A4 and P - gp inducers.", "output": "rivaroxaban, apixaban." }, { "input": "Although parenteral oral direct thrombin inhibitors ( DTIs ), such as argatroban and bivalirudin, have been on the market for years, DTIs such as dabigatran are novel synthetic thrombin antagonists.", "output": "argatroban, dabigatran." }, { "input": "Dabigatran etexilate is a low - molecular - weight non - active pro - drug that is administered orally and converted rapidly to its active form, dabigatran - - a potent, competitive and reversible DTI.", "output": "Dabigatran etexilate, dabigatran." }, { "input": "Dabigatran has an advantage over the indirect thrombin inhibitors, unfractionated heparin and low - molecular - weight heparin, in that it inhibits free and fibrin - bound thrombin.", "output": "Dabigatran." }, { "input": "The reversible binding of dabigatran may provide safer and more predictable anticoagulant treatment than seen with irreversible, non - covalent thrombin inhibitors, e. g. hirudin.", "output": "dabigatran." }, { "input": "Dabigatran shows a very low potential for drug - drug interactions.", "output": "Dabigatran." }, { "input": "However, co - administration of dabigatran etexilate with other anticoagulants and antiplatelet agents can increase the bleeding risk.", "output": "dabigatran etexilate." }, { "input": "Although the new agents are pharmacologically better than VKAs - - particularly in terms of fixed dosing, rapid onset of action, no INR monitoring and lower risk of drug interactions - - there are some differences between them: the bioavailability of dabigatran is lower than rivaroxaban and apixaban, and so the dabigatran dosage required is higher; lower protein binding of dabigatran reduces the variability related to albuminaemia.", "output": "dabigatran, rivaroxaban, apixaban, dabigatran, dabigatran." }, { "input": "The risk of metabolic drug - drug interactions also appears to differ between OACs: VKAs > rivaroxaban > apixaban > dabigatran.", "output": "rivaroxaban, apixaban, dabigatran." }, { "input": "The convenience of the new OACs has translated into improvements in efficacy and safety as shown in phase III randomized trials.", "output": "There is no related enetity." }, { "input": "The new anticoagulants so far offer the greatest promise and opportunity for the replacement of VKAs.", "output": "There is no related enetity." }, { "input": "Fluorescent live - cell imaging of metabolically incorporated unnatural cyclopropene - mannosamine derivatives.", "output": "cyclopropene, mannosamine." }, { "input": "Sugar coated: We recently developed methylcyclopropenes as low - molecular - weight tetrazine coupling partners.", "output": "Sugar, methylcyclopropenes, tetrazine." }, { "input": "Here, we demonstrate that methylcyclopropenes can meet the stringent steric demands required for metabolic imaging of unnatural mannosamines on live cells.", "output": "methylcyclopropenes, mannosamines." }, { "input": "Using sequential azide - alkyne chemistry, we also demonstrate multicolor imaging of two different metabolically incorporated unnatural sugars.", "output": "azide, alkyne, sugars." }, { "input": "Microwave spectroscopic and atoms in molecules theoretical investigations on the Ar... propargyl alcohol complex: Ar... H - O, Ar... pi, and Ar... C interactions.", "output": "propargyl alcohol, H - O, C." }, { "input": "The structure of the Ar... propargyl alcohol ( Ar... PA ) complex is determined from the rotational spectra of the parent complex and its two deuterated isotopologues, namely Ar... PA - D ( OD ) and Ar... PA - D ( CD ).", "output": "propargyl alcohol, D, OD, D, CD." }, { "input": "The spectra confirm a geometry in which PA exists in the gauche form with Ar located in between - OH and - C = C - H groups.", "output": "OH, C = C - H." }, { "input": "All a, b and c types of transitions show small splitting due to some large - amplitude motion dominated by C - OH torsion, as in the monomer.", "output": "C - OH." }, { "input": "Splittings in a - and b - type transitions are of the order of a few kilohertz, whereas splitting in the c - type transitions is relatively larger ( 0. 9 - 2. 6 MHz ) and decreases in the order Ar... PA > Ar... PA - D ( CD ) > Ar... PA - D ( OD ).", "output": "D, CD, D, OD." }, { "input": "The assignments are well supported by ab initio calculations.", "output": "There is no related enetity." }, { "input": "Atoms in molecules ( AIM ) and electrostatic potential calculations are used to explore the nature of the interactions in this complex.", "output": "There is no related enetity." }, { "input": "AIM calculations not only reveal the expected O - H... Ar and pi... Ar interactions in the Ar... gauche - PA complex, but also novel C... Ar ( of CH2OH group ) and O - H... Ar interactions in the Ar... trans - PA complex.", "output": "O - H, C, CH2OH, O - H." }, { "input": "Similar interactions are also present in the Ar... methanol complex.", "output": "methanol." }, { "input": "Smoothened is a fully competent activator of the heterotrimeric G protein G ( i ).", "output": "There is no related enetity." }, { "input": "Smoothened ( Smo ) is a 7 - transmembrane protein essential to the activation of Gli transcription factors ( Gli ) by hedgehog morphogens.", "output": "There is no related enetity." }, { "input": "The structure of Smo implies interactions with heterotrimeric G proteins, but the degree to which G proteins participate in the actions of hedgehogs remains controversial.", "output": "There is no related enetity." }, { "input": "We posit that the G ( i ) family of G proteins provides to hedgehogs the ability to expand well beyond the bounds of Gli.", "output": "There is no related enetity." }, { "input": "In this regard, we evaluate here the efficacy of Smo as it relates to the activation of G ( i ), by comparing Smo with the 5 - hydroxytryptamine ( 1A ) ( 5 - HT ( 1A ) ) receptor, a quintessential G ( i ) - coupled receptor.", "output": "5 - hydroxytryptamine, 5 - HT." }, { "input": "We find that with use of [ ( 35 ) S ] guanosine 5 ' - ( 3 - O - thio ) triphosphate, first, with forms of G ( i ) endogenous to human embryonic kidney ( HEK ) - 293 cells made to express epitope - tagged receptors and, second, with individual forms of G alpha ( i ) fused to the C terminus of each receptor, Smo is equivalent to the 5 - HT ( 1A ) receptor in the assay as it relates to capacity to activate G ( i ).", "output": "[ ( 35 ) S ] guanosine 5 ' - ( 3 - O - thio ) triphosphate, 5 - HT." }, { "input": "This finding is true regardless of subtype of G ( i ) ( e. g., G ( i2 ), G ( o ), and G ( z ) ) tested.", "output": "There is no related enetity." }, { "input": "We also find that Smo endogenous to HEK - 293 cells, ostensibly through inhibition of adenylyl cyclase, decreases intracellular levels of cAMP.", "output": "adenylyl, cAMP." }, { "input": "The results indicate that Smo is a receptor that can engage not only Gli but also other more immediate effectors.", "output": "There is no related enetity." }, { "input": "3D nanoscale chemical imaging of the distribution of aluminum coordination environments in zeolites with soft X - ray microscopy.", "output": "aluminum, zeolites." }, { "input": "Which side are you on?", "output": "There is no related enetity." }, { "input": "Scanning transmission X - ray microscopy is used for the first time to elucidate the coordination and distribution of aluminum in industrial - relevant zeolites at the single - particle level.", "output": "aluminum, zeolites." }, { "input": "Extended regions of a few hundred nanometers, rich in higher aluminum coordination environments, are heterogeneously embedded within the zeolite particle, before and after a steaming post - treatment.", "output": "aluminum, zeolite." }, { "input": "Structural aspects of gut peptides with therapeutic potential for type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Gut hormones represent a niche subset of pharmacologically active agents that are rapidly gaining importance in medicine.", "output": "There is no related enetity." }, { "input": "Due to their exceptional specificity for their receptors, these hormones along with their analogues have attracted considerable pharmaceutical interest for the treatment of human disorders including type 2 diabetes.", "output": "There is no related enetity." }, { "input": "With the recent advances in the structural biology, a significant amount of structural information for these hormones is now available.", "output": "There is no related enetity." }, { "input": "This Minireview presents an overview of the structural aspects of these hormones, which have roles in physiological processes such as insulin secretion, as well as a discussion on the relevant structural modifications used to improve these hormones for the treatment of type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Electron doping by charge transfer at LaFeO3 / Sm2CuO4 epitaxial interfaces.", "output": "LaFeO3, Sm2CuO4." }, { "input": "Using X - ray absorption spectroscopy and electron energy loss spectroscopy with atomic - scale spatial resolution, experimental evidence for charge transfer at the interface between the Mott insulators Sm2 CuO4 and LaFeO3 is obtained.", "output": "Sm2 CuO4, LaFeO3." }, { "input": "As a consequence of the charge transfer, the Sm2 CuO4 is doped with electrons and thus epitaxial Sm2 CuO4 / LaFeO3 heterostructures become metallic.", "output": "Sm2 CuO4, Sm2 CuO4, LaFeO3." }, { "input": "Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale.", "output": "There is no related enetity." }, { "input": "The human telomeric DNA sequence with four repeats can fold into a parallel - stranded propeller - type topology.", "output": "There is no related enetity." }, { "input": "NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal - packing interactions that are effectively equivalent to molecular crowding.", "output": "There is no related enetity." }, { "input": "This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state.", "output": "There is no related enetity." }, { "input": "Although G - quartet stems have been well characterized, the interactions of the TTA loop with the G - quartets are much less defined.", "output": "There is no related enetity." }, { "input": "To better understand the conformational variability and structural dynamics of the propeller - type topology, we performed molecular dynamics simulations in explicit solvent up to 1. 5 mu s.", "output": "There is no related enetity." }, { "input": "The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G - quartets including formation of an A: A base pair, triad, pentad and hexad.", "output": "There is no related enetity." }, { "input": "The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar - phosphate backbone in formation of unusual architecture within the topology.", "output": "sugar, phosphate." }, { "input": "Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.", "output": "There is no related enetity." }, { "input": "ParseCNV integrative copy number variation association software with quality tracking.", "output": "There is no related enetity." }, { "input": "A number of copy number variation ( CNV ) calling algorithms exist; however, comprehensive software tools for CNV association studies are lacking.", "output": "There is no related enetity." }, { "input": "We describe ParseCNV, unique software that takes CNV calls and creates probe - based statistics for CNV occurrence in both case - control design and in family based studies addressing both de novo and inheritance events, which are then summarized based on CNV regions ( CNVRs ).", "output": "There is no related enetity." }, { "input": "CNVRs are defined in a dynamic manner to allow for a complex CNV overlap while maintaining precise association region.", "output": "There is no related enetity." }, { "input": "Using this approach, we avoid failure to converge and non - monotonic curve fitting weaknesses of programs, such as CNVtools and CNVassoc, and although Plink is easy to use, it only provides combined CNV state probe - based statistics, not state - specific CNVRs.", "output": "There is no related enetity." }, { "input": "Existing CNV association methods do not provide any quality tracking information to filter confident associations, a key issue which is fully addressed by ParseCNV.", "output": "There is no related enetity." }, { "input": "In addition, uncertainty in CNV calls underlying CNV associations is evaluated to verify significant results, including CNV overlap profiles, genomic context, number of probes supporting the CNV and single - probe intensities.", "output": "There is no related enetity." }, { "input": "When optimal quality control parameters are followed using ParseCNV, 90 % of CNVs validate by polymerase chain reaction, an often problematic stage because of inadequate significant association review.", "output": "There is no related enetity." }, { "input": "ParseCNV is freely available at http: / / parsecnv. sourceforge. net.", "output": "There is no related enetity." }, { "input": "Dietary exposure of mink ( Mustela vison ) to fish from the upper Hudson River, New York, USA: effects on reproduction and offspring growth and mortality.", "output": "There is no related enetity." }, { "input": "The effects of feeding farm - raised mink ( Mustela vison ) diets containing polychlorinated biphenyl ( PCB ) - contaminated fish from the upper Hudson River ( New York, USA ) on adult reproductive performance and kit growth and mortality were evaluated.", "output": "polychlorinated biphenyl, PCB." }, { "input": "Diets contained 2. 5 to 20 % Hudson River fish, providing 0. 72 to 6. 1 micro g sum PCBs / g feed ( 4. 8 - 38 pg toxic equivalents [ TEQWHO 2005 ] / g feed ).", "output": "There is no related enetity." }, { "input": "The percentage of stillborn kits per litter was significantly increased by dietary concentrations of 4. 5 micro g sum PCBs / g feed ( 28 pg TEQWHO 2005 / g feed ) and greater.", "output": "There is no related enetity." }, { "input": "All offspring exposed to dietary concentrations of 4. 5 and 6. 1 micro g sum PCBs / g feed ( 28 and 38 pg TEQWHO 2005 / g feed ) died by 10 weeks of age, and all offspring exposed to 1. 5 and 2. 8 micro g sum PCBs / g feed ( 10 and 18 pg TEQWHO 2005 / g feed ) died by 31 weeks of age, leaving juveniles in the control and 0. 72 micro g sum PCBs / g feed ( 0. 41 - and 4. 8 pg TEQWHO 2005 / g feed ) groups only.", "output": "There is no related enetity." }, { "input": "The dietary concentration predicted to result in 20 % kit mortality ( LC20 ) at six weeks of age was 0. 34 micro g sum PCBs / g feed ( 2. 6 pg TEQWHO 2005 / g feed ).", "output": "There is no related enetity." }, { "input": "The corresponding maternal hepatic concentration was 0. 80 micro g sum PCBs / g liver, wet weight ( 13 pg TEQWHO 2005 / g liver, wet wt ).", "output": "There is no related enetity." }, { "input": "Mink residing in the upper Hudson River would be expected to consume species of fish that contain an average of 4. 0 micro g sum PCBs / g tissue.", "output": "There is no related enetity." }, { "input": "Thus, a daily diet composed of less than 10 % Hudson River fish could provide a dietary concentration of sum PCBs that resulted in 20 % kit mortality in the present study.", "output": "There is no related enetity." }, { "input": "Clinal variation in colony breeding structure and level of inbreeding in the subterranean termites Reticulitermes flavipes and R. grassei.", "output": "There is no related enetity." }, { "input": "Social insects exhibit remarkable variation in their colony breeding structures, both within and among species.", "output": "There is no related enetity." }, { "input": "Ecological factors are believed to be important in shaping reproductive traits of social insect colonies, yet there is little information linking specific environmental variables with differences in breeding structure.", "output": "There is no related enetity." }, { "input": "Subterranean termites ( Rhinotermitidae ) show exceptional variation in colony breeding structure, differing in the number of reproductives and degree of inbreeding; colonies can be simple families headed by a single pair of monogamous reproductives ( king and queen ) or they can be extended families headed by multiple inbreeding neotenic reproductives ( wingless individuals ).", "output": "There is no related enetity." }, { "input": "Using microsatellite markers, we characterized colony breeding structure and levels of inbreeding in populations over large parts of the range of the subterranean termites Reticulitermes flavipes in the USA and R. grassei in Europe.", "output": "There is no related enetity." }, { "input": "Combining these new data with previous results on populations of both species, we found that latitude had a strong effect on the proportion of extended - family colonies in R. flavipes and on levels of inbreeding in both species.", "output": "There is no related enetity." }, { "input": "We examined the effect of several environmental variables that vary latitudinally; while the degree of inbreeding was greatest in cool, moist habitats in both species, seasonality affected the species differently.", "output": "There is no related enetity." }, { "input": "Inbreeding in R. flavipes was most strongly associated with climatic variables ( mean annual temperature and seasonality ), whereas nonclimatic variables, including the availability of wood substrate and soil composition, were important predictors of inbreeding in R. grassei.", "output": "There is no related enetity." }, { "input": "These results are the first showing that termite breeding structure is shaped by local environmental factors and that species can vary in their responses to these factors.", "output": "There is no related enetity." }, { "input": "Analytical model for the deformation of a fluid - fluid interface beneath an AFM probe.", "output": "There is no related enetity." }, { "input": "We present an analytical solution for the shape of a fluid - fluid interface near a nanoscale solid sphere, which is a configuration motivated by common measurements with an atomic force microscope.", "output": "There is no related enetity." }, { "input": "The forces considered are surface tension, gravity, and the van der Waals attraction.", "output": "There is no related enetity." }, { "input": "The nonlinear governing equation has been solved previously using the method of matched asymptotic expansions, and this requires that the surface tension forces far exceed those of gravity, i. e., the Bond number is much less than one.", "output": "There is no related enetity." }, { "input": "We first present this method using a physically relevant scaling of the equations, then offer a new analytical solution valid for all Bond numbers.", "output": "There is no related enetity." }, { "input": "We show that one configuration with a large effective Bond number, and thus one requiring our new solution, is a nanothick liquid film spread over a solid substrate.", "output": "There is no related enetity." }, { "input": "The scaling implications of both analytical methods are considered, and both are compared with numerical solutions of the full equation.", "output": "There is no related enetity." }, { "input": "Luminescence enhancement of pyrene / dispersant nanoarrays driven by the nanoscale spatial effect on mixing.", "output": "pyrene." }, { "input": "This work presents a simple method to generate ordered chromophore / dispersant nanoarrays through a pore - filling process for a nanoporous polymer template to enhance chromophore luminescence.", "output": "There is no related enetity." }, { "input": "Fluorescence results combining with the morphological evolution examined by scanning probe microscopy reveal that the enhanced luminescence intensity reaches the maximum intensity as the nanopores of the template are completely filled by the chromophore / dispersant mixture.", "output": "There is no related enetity." }, { "input": "The variation is attributed to nanoscale spatial effect on the enhanced mixing efficiency of chromophore and dispersant, that is, the alleviation of self - quenching problem, as evidenced by the results of attenuated total reflection Fourier transform IR spectroscopy combining with grazing incident wide - angle X - ray diffraction.", "output": "There is no related enetity." }, { "input": "The enhanced luminescence of the chromophore / dispersant nanoarrays driven by the nanoscale spatial effect is highly promising for use in designing luminescent nanodevices.", "output": "There is no related enetity." }, { "input": "Hepatocyte growth factor activator inhibitor type 2 ( HAI - 2 ) modulates hepcidin expression by inhibiting the cell surface protease matriptase - 2.", "output": "There is no related enetity." }, { "input": "Matriptase - 2, a recently identified cell surface protease, is the key enzyme of iron homoeostasis modulating the expression of the liver peptide hormone hepcidin.", "output": "iron." }, { "input": "HAI ( hepatocyte growth factor activator inhibitor ) types 1 and 2 ( HAI - 1 and HAI - 2 respectively ) have been shown to inhibit the close homologue, i. e. matriptase.", "output": "There is no related enetity." }, { "input": "By co - expressing matriptase - 2 and the inhibitor HAI - 2 we have identified HAI - 2 displaying high inhibitory potential against matriptase - 2 at the cell surface as well as in conditioned medium.", "output": "There is no related enetity." }, { "input": "Accordingly, complex formation between matriptase - 2 and HAI - 2 was demonstrated by isolation of the complex via immobilizing either HAI - 2 or matriptase - 2 from lysates and conditioned medium of co - expressing cells.", "output": "There is no related enetity." }, { "input": "Furthermore, HAI - 2 indirectly influences the expression of the hepcidin - encoding gene HAMP.", "output": "There is no related enetity." }, { "input": "The inhibitor abrogates the matriptase - 2 - mediated suppression of HAMP expression, presumably by inhibiting the supposed potential of matriptase - 2 to cleave membrane - bound HJV ( haemojuvelin ).", "output": "There is no related enetity." }, { "input": "Taken together, the results of the present study have characterized HAI - 2 as an inhibitor of matriptase - 2 that modulates the synthesis of hepcidin and provides new insights into the regulatory mechanism of iron homoeostasis, with clinical importance for a treatment of iron overload diseases.", "output": "iron, iron." }, { "input": "Single - molecule force spectroscopy identifies a small cold shock protein as being mechanically robust.", "output": "There is no related enetity." }, { "input": "Single - molecule force spectroscopy has emerged as a powerful approach to examine the stability and dynamics of single proteins.", "output": "There is no related enetity." }, { "input": "We have completed force extension experiments on the small cold shock protein B from Thermotoga maritima, using a specially constructed chimeric polyprotein.", "output": "There is no related enetity." }, { "input": "The protein ' s simple topology, which is distinct from the mechanically well - characterized beta - grasp and immunoglobulin ( Ig ) - like folds, in addition to the wide range of structural homologues resulting from its ancient origin, provides an attractive model protein for single - molecule force spectroscopy studies.", "output": "There is no related enetity." }, { "input": "We have determined that the protein has mechanical stability, unfolding at greater than 70 pN at a pulling velocity of 100 nm s ( - 1 ).", "output": "There is no related enetity." }, { "input": "We reveal features of the unfolding energy landscape by measuring the dependence of the mechanical stability on pulling velocity, in combination with Monte Carlo simulations.", "output": "There is no related enetity." }, { "input": "We show that the cold shock protein has mechanically robust, yet malleable, features that may be important in providing the protein with stability and flexibility to function over a range of environmental conditions.", "output": "There is no related enetity." }, { "input": "These results provide insights into the relationship between the secondary structure and topology of a protein and its mechanical strength.", "output": "There is no related enetity." }, { "input": "This lays the foundation for the investigation of the effects of changes in environmental conditions on the mechanical and dynamic properties of cold shock proteins.", "output": "There is no related enetity." }, { "input": "Synthesis and characterization of quarteranthene: elucidating the characteristics of the edge state of graphene nanoribbons at the molecular level.", "output": "quarteranthene, graphene." }, { "input": "The characteristics of the edge state, which is a peculiar magnetic state in zigzag - edged graphene nanoribbons ( ZGNRs ) that originates from electron - electron correlation in an edge - localized pi - state, are investigated by preparing and characterizing quarteranthene molecules.", "output": "graphene, quarteranthene." }, { "input": "The molecular geometry that was determined from the X - ray analysis is consistent with a zigzag - edge - localized structure of unpaired electrons.", "output": "There is no related enetity." }, { "input": "The localized electrons are responsible for the peculiar magnetic ( room - temperature ferromagnetic correlation ), optical ( the lowest - lying doubly excited state ), and chemical ( peroxide bond formation ) behaviors.", "output": "peroxide." }, { "input": "On the basis of these distinguishing properties and a careful consideration of the valence bonding, insight into the edge state of ZGNRs can be gained.", "output": "There is no related enetity." }, { "input": "Tobacco smoke modulates ozone - induced toxicity in rat lungs and central nervous system.", "output": "ozone." }, { "input": "Adult Sprague - Dawley ( SD ) male rats were exposed for a single 3 h period to air, ozone ( O 3 ) or O 3 ) followed by tobacco smoke ( O 3 / TS ).", "output": "ozone, O 3, O 3, O 3." }, { "input": "For pulmonary effects, bronchoalveolar lavage ( BAL ) cells and fluid were analyzed.", "output": "There is no related enetity." }, { "input": "Data revealed a significant increase in polymorphonuclear leukocytes ( PMN ), total protein and albumin concentrations in the O 3 group, reflecting inflammatory and toxic responses.", "output": "O 3." }, { "input": "A subsequent exposure to TS attenuated PMN infiltration into the airspaces and their recovery in the BAL.", "output": "There is no related enetity." }, { "input": "A similar reduction was observed for BAL protein and albumin in the O 3 / TS group, but it was not statistically significant.", "output": "O 3." }, { "input": "We also observed a significant increase in BAL total antioxidant capacity following O 3 exposure, suggesting development of protective mechanisms for oxidative stress damage from O 3.", "output": "O 3, O 3." }, { "input": "Exposure to TS attenuated the levels of total antioxidant capacity.", "output": "There is no related enetity." }, { "input": "Lung tissue protein analysis showed a significant reduction of extracellular superoxide dismutase ( EC - SOD ) in the O 3 or O 3 / TS group and catalase in the O 3 / TS group.", "output": "superoxide, O 3, O 3, O 3." }, { "input": "TS further altered O 3 - induced EC - SOD and catalase protein expression, but the reductions were not significant.", "output": "O 3." }, { "input": "For effects in the central nervous system ( CNS ), we measured striatal dopamine levels by HPLC with electrochemical detection.", "output": "dopamine." }, { "input": "O 3 exposure produced a nonsignificant decrease in the striatal dopamine content.", "output": "O 3." }, { "input": "The effect was partially reversed in the O 3 / TS group.", "output": "O 3." }, { "input": "Overall, the results show that the toxicity of O 3 in the lung is modulated by TS exposure, and the attenuating trend, though nonsignificant in many cases, is contrary to the synergistic toxicity predicted for TS and O 3, suggesting limited cross - tolerance following such exposures.", "output": "O 3, O 3." }, { "input": "Comparison of dose - response relations between 4 - week inhalation and intratracheal instillation of NiO nanoparticles using polimorphonuclear neutrophils in bronchoalveolar lavage fluid as a biomarker of pulmonary inflammation.", "output": "NiO." }, { "input": "Inhalation studies and intratracheal instillation studies using laboratory animals are commonly conducted for pulmonary toxicity tests of nanomaterials.", "output": "There is no related enetity." }, { "input": "In our study, male Wister rats were exposed to nickel oxide ( NiO ) particles including a nano - scale, even for aerosols and suspensions, in a 4 - week inhalation and intratracheal instillation.", "output": "nickel oxide, NiO." }, { "input": "Using polymorphonuclear neutrophils ( PMNs ) in bronchoalveolar lavage fluid as a biomarker of inflammation, we attempted to quantify the relationship between responses to inhalation and intratracheal instillation of the nanoparticles, based on surface area doses.", "output": "There is no related enetity." }, { "input": "Four kinds of NiO suspension samples with different specific surface areas were singly injected via the tracheas of the rats.", "output": "NiO." }, { "input": "The relationship between the instilled doses and PMN production was examined 3 days and 1 month after the instillation.", "output": "There is no related enetity." }, { "input": "In parallel, 4 - week inhalation studies, using two of the suspensions, were conducted for aerosols generated by a pressurized nebulizer.", "output": "There is no related enetity." }, { "input": "NiO samples induced PMN responses 3 days after instillation according to the surface area doses, but not the mass doses, as has been reported in many studies.", "output": "NiO." }, { "input": "When the same NiO samples were tested in a 4 - week inhalation and intratracheal instillation, the amount of pulmonary deposition of the sample after the 4 - week inhalation, and an intratracheally instilled dose about ten - times higher, induced similar PMN responses 3 days after termination of inhalation and instillation.", "output": "NiO." }, { "input": "Using the relationship between these responses to 4 - week inhalation and intratracheal instillation, it may be possible to estimate what aerosol concentrations of other nanomaterials might cause the same responses of PMN production as intratracheal instillation tests.", "output": "There is no related enetity." }, { "input": "Hedgehog pathway inhibitors: a patent review ( 2009 - - present ).", "output": "There is no related enetity." }, { "input": "INTRODUCTION: The hedgehog ( Hh ) pathway is a developmental signaling pathway that plays a key role in directing cellular growth and tissue patterning during embryonic development.", "output": "There is no related enetity." }, { "input": "Dysregulation of Hh signaling has been linked to the development of a variety of human tumors, and numerous drug development programs in both academia and industry are actively exploring inhibitors of the pathway as anti - cancer agents.", "output": "There is no related enetity." }, { "input": "AREAS COVERED: This review surveys the recent patent literature ( 2009 - 2012 ) for Hh pathway inhibitors as treatments for a variety of human malignancies.", "output": "There is no related enetity." }, { "input": "EXPERT OPINION: To date, all of the pathway inhibitors that have entered clinical trials and the majority of compounds identified via high - throughput screens target smoothened ( Smo ), a transmembrane protein that is essential for pathway signaling.", "output": "There is no related enetity." }, { "input": "While these compounds have shown initial promise in preclinical and clinical trials, several mechanisms of resistance to Smo inhibitors have been identified.", "output": "There is no related enetity." }, { "input": "Even with this knowledge, the majority of small - molecule pathway inhibitors disclosed in the recent patent literature directly target Smo.", "output": "There is no related enetity." }, { "input": "The continued identification of Hh pathway inhibitors that function either upstream or downstream is warranted not only to combat these emerging resistance mechanisms, but also to help elucidate the various cellular mechanisms that control both normal and oncogenic pathway signaling.", "output": "There is no related enetity." }, { "input": "Density of GM1 in nanoclusters is a critical factor in the formation of a spherical assembly of amyloid beta - protein on synaptic plasma membranes.", "output": "There is no related enetity." }, { "input": "The deposition of amyloid beta - protein ( A beta ) is a pathological hallmark of Alzheimer ' s disease ( AD ).", "output": "There is no related enetity." }, { "input": "We previously found that the ganglioside - enriched microdomains ( ganglioside clusters ) in presynaptic neuronal membranes play a key role in the initiation of the A beta assembly process.", "output": "ganglioside, ganglioside." }, { "input": "However, not all ganglioside clusters accelerate A beta assembly.", "output": "ganglioside." }, { "input": "In the present study, we directly observed a spherical A beta in an atomic force microscopic study on the morphology of a reconstituted lipid bilayer composed of lipids that were extracted from a detergent - resistant membrane microdomain ( DRM ) fraction of synaptosomes prepared from aged mouse brain.", "output": "There is no related enetity." }, { "input": "The A beta assembly was generated on a distinctive GM1 domain, which was characterized as the A beta - sensitive ganglioside nanocluster ( ASIGN ).", "output": "ganglioside." }, { "input": "By using an artificial GM1 cluster - binding peptide, ASIGN was found to have a high density of GM1; therefore, there would be a critical density of GM1 in nanoclusters to induce A beta binding and assembly.", "output": "There is no related enetity." }, { "input": "These results suggest that ganglioside - bound A beta ( GA beta ), which acts as an endogenous seed for A beta fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes.", "output": "ganglioside." }, { "input": "Anterior gradient 2 and 3 - - two prototype androgen - responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells.", "output": "androgen, androgens, oestrogens." }, { "input": "Androgens and oestrogens have been implicated in prostatic carcinogenesis and tumour progression.", "output": "Androgens, oestrogens." }, { "input": "Although the actions of androgens have been studied extensively, the mechanisms underlying oestrogen signalling in prostate cancer are not fully understood.", "output": "androgens, oestrogen." }, { "input": "In the present study, we analyzed the effect of androgens and oestrogens on the expression of anterior gradient 2 ( AGR2 ) and anterior gradient 3 ( AGR3 ), comprising two highly - related genes encoding secretory proteins that are expressed in prostate cancer and one of which ( AGR2 ) has been associated with tumour metastasis.", "output": "androgens, oestrogens." }, { "input": "Quantitative reverse - transcriptase PCR and western blot analysis showed androgen induction of AGR2 and AGR3 in three androgen receptor positive cell lines, starting at concentrations of 0. 1 nm.", "output": "androgen, androgen." }, { "input": "Both AGR genes were also transcriptionally activated by >= 5 nM oestradiol but not by isotype selective or nonselective oestrogen receptor agonists in DUCaP cells that harbour a high - level of wild - type androgen receptor.", "output": "oestradiol, oestrogen, androgen." }, { "input": "A functional androgen receptor but not oestrogen receptor turned out to be required for both androgen and oestrogen regulation.", "output": "androgen, oestrogen, androgen, oestrogen." }, { "input": "This pattern of androgen and oestrogen regulation was confirmed in VCaP cells and was also observed for FKBP5, a well - characterized androgen - regulated gene.", "output": "androgen, oestrogen, androgen." }, { "input": "Genome - wide chromatin - immunoprecipitation studies coupled with deep sequencing identified androgen receptor binding sites localized in the distal promoter and intron regions of the AGR2 and AGR3 genes, respectively.", "output": "androgen." }, { "input": "The androgen responsiveness of these enhancers was verified by luciferase reporter gene assays and site - directed mutagenesis analysis.", "output": "androgen." }, { "input": "Androgen treatment also induced p300 and RNA Pol II recruitment to androgen receptor enhancers of AGR2 and initiated local chromatin remodelling and the formation of RNA Pol II - containing androgen receptor transcription complexes.", "output": "Androgen, androgen, androgen." }, { "input": "Pentacyclic hemiacetal sterol with antifouling and cytotoxic activities from the soft coral Nephthea sp.", "output": "Pentacyclic hemiacetal sterol." }, { "input": "A novel unusual pentacyclic hemiacetal sterol nephthoacetal ( 1 ), was isolated from soft coral Nephthea sp.", "output": "pentacyclic hemiacetal sterol, nephthoacetal." }, { "input": "The structure of this sterol was inferred from its two acetyl derivatives ( 2 ) and ( 3 ), by means of spectroscopic methods, and quantum chemical calculations.", "output": "sterol, acetyl." }, { "input": "Anti - fouling activity of compounds 1 - 3 against Bugula neritina larvae was evaluated, sterol ( 1 ) exhibited significant inhibitory effect with EC ( 50 ) value of 2. 5 mu g / mL, while having low toxicity with LC ( 50 ) > 25. 0 mu g / mL.", "output": "sterol." }, { "input": "The in vitro cytotoxic activity of compounds 1 - 3 against HeLa cells was also evaluated, all of them exhibited moderate cytotoxicity with IC ( 50 ) values of 12. 3 ( 1 ), 10. 1 ( 2 ), and 19. 6 mu g / mL ( 3 ), respectively.", "output": "There is no related enetity." }, { "input": "Aspirin and aspirin resistance in coronary artery disease.", "output": "Aspirin, aspirin." }, { "input": "Aspirin is still the mainstay of antiplatelet therapy in the secondary prevention of coronary artery disease.", "output": "Aspirin." }, { "input": "However certain patients do not benefit from the antithrombotic effects of aspirin.", "output": "aspirin." }, { "input": "The phenomenon of so - called aspirin resistance can be considered from the clinical and laboratory perspective.", "output": "aspirin." }, { "input": "A variety of methods have emerged for the laboratory diagnosis of aspirin resistance.", "output": "aspirin." }, { "input": "None of them is considered ideal as they provide conflicting information with significant inter - individual variability and weak correlation between them.", "output": "There is no related enetity." }, { "input": "With the mechanisms of aspirin resistance not fully understood and the phenomenon commonly observed in individuals with poor compliance, the existence of aspirin resistance has been challenged.", "output": "aspirin, aspirin." }, { "input": "The aim of this review is to present recent data on the impact of aspirin resistance in primary and secondary prevention of coronary artery disease.", "output": "aspirin." }, { "input": "L - Carnitine protects against arterial hypertension - related cardiac fibrosis through modulation of PPAR - gamma expression.", "output": "L - Carnitine." }, { "input": "Cardiac fibrosis is a pathogenic factor in a variety of cardiovascular diseases and is characterized by an abnormal accumulation of extracellular matrix protein that leads to cardiac dysfunction.", "output": "There is no related enetity." }, { "input": "l - Carnitine ( LC ) plays an essential role in the beta - oxidation of long - chain fatty acids in lipid metabolism.", "output": "l - Carnitine, fatty acids." }, { "input": "We have previously demonstrated the beneficial effects of LC in hypertensive rats.", "output": "There is no related enetity." }, { "input": "The aim of this study was to analyze the effect of LC on arterial hypertension - associated cardiac fibrosis and to explore the mechanisms of LC action.", "output": "There is no related enetity." }, { "input": "To this end, four groups of rats were used: Wistar ( control ), rats treated with 400mg / kg / day of LC, rats treated with 25mg / kg / day of l - NAME ( to induce hypertension ), and rats treated with LC + l - NAME simultaneously.", "output": "l - NAME, l - NAME." }, { "input": "We found an elevation in the myocardial expression of profibrotic factors ( TGF - beta 1 and CTGF ), types I and III of collagen, and NADPH oxidase subunits ( NOX2 and NOX4 ), in hypertensive rats when compared with normotensive ones.", "output": "NADPH." }, { "input": "In addition, an increase in myocardial fibrosis was also found in the l - NAME group.", "output": "l - NAME." }, { "input": "These results were accompanied by a down - regulation of PPAR - gamma in the heart of hypertensive animals.", "output": "There is no related enetity." }, { "input": "When hypertensive rats were treated with LC, all these alterations were reversed.", "output": "There is no related enetity." }, { "input": "Moreover, a significant negative correlation was observed between myocardial interstitial fibrosis and mRNA expression of PPAR - gamma.", "output": "There is no related enetity." }, { "input": "In conclusion, the reduction of cardiac fibrosis and the down - regulation of NOX2, NOX4, TGF - beta 1 and CTGF induced by LC might be, at least in part, mediated by an upregulation of PPAR - gamma, which leads to a reduction on hypertension - related cardiac fibrosis.", "output": "There is no related enetity." }, { "input": "Anti - human VWF monoclonal antibody SZ - 123 prevents arterial thrombus formation by inhibiting VWF - collagen and VWF - platelet interactions in Rhesus monkeys.", "output": "There is no related enetity." }, { "input": "The interactions between collagen, von Willebrand factor ( VWF ), and glycoprotein Ib ( GPIb ) are crucial for hemostasis and thrombosis.", "output": "There is no related enetity." }, { "input": "This axis represents a promising target for the development of new antithrombotic agents.", "output": "There is no related enetity." }, { "input": "In this study, we investigate the in vivo antithrombotic efficacy of an anti - VWF monoclonal antibody SZ - 123 and its potential underlying mechanisms.", "output": "There is no related enetity." }, { "input": "Cyclic flow reductions ( CFRs ), an indicator of arterial thrombosis, were measured in the femoral artery of anesthetized Rhesus monkeys before and after intravenous administration of SZ - 123.", "output": "There is no related enetity." }, { "input": "Ex vivo VWF binding to collagen, platelet agglutination, platelet count, and template bleeding time were used as measurements of antithrombotic activity.", "output": "There is no related enetity." }, { "input": "In addition, plasma VWF and SZ - 123 levels, and VWF occupancy were measured by ELISA.", "output": "There is no related enetity." }, { "input": "Administration of 0. 1, 0. 3, and 0. 6 mg / kg SZ - 123 resulted in 45. 3 %, 78. 2 %, and 100 % reductions in CFRs, respectively.", "output": "There is no related enetity." }, { "input": "When 0. 3 and 0. 6 mg / kg SZ - 123 were administered, 100 % of VWF was occupied by the antibody.", "output": "There is no related enetity." }, { "input": "Moreover, 100 % ex vivo inhibition of VWF - collagen binding and 60 - 95 % inhibition of platelet agglutination were observed from 15 min to 1 h.", "output": "There is no related enetity." }, { "input": "None of the doses resulted in significant prolongation of bleeding time.", "output": "There is no related enetity." }, { "input": "In vitro experiments revealed that SZ - 123 not only blocks the collagen - VWF A3 interaction but also indirectly inhibits VWF A1 binding to GPIb alpha induced by ristocetin.", "output": "There is no related enetity." }, { "input": "Thus, we demonstrate that SZ - 123 prevents in vivo arterial thrombus formation under high shear conditions by inhibiting VWF A3 - collagen and VWF A1 - platelet interactions and does not significantly prolong bleeding time.", "output": "There is no related enetity." }, { "input": "A novel transcriptional repressor PhaR for the steroid - inducible expression of the 3, 17 beta - hydroxysteroid dehydrogenase gene in Comamonas testosteroni ATCC11996.", "output": "steroid, 3 , 17 beta - hydroxysteroid." }, { "input": "Comamonas testosteroni is able to catabolize a variety of steroids and polycyclic aromatic hydrocarbons and might be used in the bioremediation of contaminated environments.", "output": "steroids, polycyclic aromatic hydrocarbons." }, { "input": "3, 17 beta - Hydroxysteroid dehydrogenase ( 3, 17 beta - HSD ) from C. testosteroni is a member of the short - chain dehydrogenase / reductase ( SDR ) superfamily and a key enzyme in steroid degradation.", "output": "3 , 17 beta - Hydroxysteroid, steroid." }, { "input": "The genome of C. testosteroni ATCC11996 was sequenced in our previous work.", "output": "There is no related enetity." }, { "input": "In addition to the gene coding for 3, 17 beta - HSD ( beta hsd ), a novel transcriptional repressor phaR gene ( phaR ) which locates 2290 bp upstream of the beta hsd gene was found.", "output": "There is no related enetity." }, { "input": "PhaR knock - out mutants of C. testosteroni were prepared and shown to grow better than wild - type C. testosteroni in the presence of 1 mM testosterone, 0. 5 mM estradiol or 0. 5 mM cholesterol in both Standard 1 Nutrient ( SIN ) medium and 1: 10 diluted SIN medium.", "output": "testosterone, estradiol, cholesterol." }, { "input": "After 1 mM testosterone induction, 3, 17 beta - HSD expression in the mutant was 2. 5 times higher than in wild type C. testosteroni.", "output": "testosterone." }, { "input": "Accordingly, PhaR is a repressor that controls 3, 17 beta - HSD expression.", "output": "There is no related enetity." }, { "input": "Moreover, phaR knock - out mutants grow at higher rates and produce more protein in the presence of steroids as carbon source.", "output": "steroids, carbon." }, { "input": "However, ELISA results showed that 0. 5 mM estradiol and cholesterol could not induce beta hsd gene expression in both wild - type and mutant C. testosteroni.", "output": "estradiol, cholesterol." }, { "input": "Probably, in addition to the beta hsd gene, PhaR regulates some other genes that relate to steroid degradation.", "output": "steroid." }, { "input": "The genes coding for PhaR and 3, 17 beta - HSD together with their promoter domains were cloned into plasmids pK18 and pUC19.", "output": "There is no related enetity." }, { "input": "Escherichia coli HB101 was co - transformed with these plasmids.", "output": "There is no related enetity." }, { "input": "The results suggest that PhaR is a repressor, which might bind on a special beta hsd promoter domain ( 214 bp ).", "output": "There is no related enetity." }, { "input": "A 2509 bp DNA fragment that contained a putative promoter for the beta hsd gene ( without the phaR gene ) was cloned into plasmid pUC2. 5 - 3.", "output": "There is no related enetity." }, { "input": "The plasmid was transformed into HB101 ( E. coli ) and induced with testosterone.", "output": "testosterone." }, { "input": "As a result, 3, 17 beta - HSD expression was at a high level, but could not be further enhanced by testosterone.", "output": "testosterone." }, { "input": "Taken together, phaR knock - out mutants have better ability to degrade steroids than wild - type C. testosteroni ATCC11996 and might therefore be used in bioremediation.", "output": "steroids." }, { "input": "Biocatalytic production of alpha - hydroxy ketones and vicinal diols by yeast and human aldo - keto reductases.", "output": "alpha - hydroxy ketones, vicinal diols." }, { "input": "The alpha - hydroxy ketones are used as building blocks for compounds of pharmaceutical interest ( such as antidepressants, HIV - protease inhibitors and antitumorals ).", "output": "alpha - hydroxy ketones." }, { "input": "They can be obtained by the action of enzymes or whole cells on selected substrates, such as diketones.", "output": "diketones." }, { "input": "We have studied the enantiospecificities of several fungal ( AKR3C1, AKR5F and AKR5G ) and human ( AKR1B1 and AKR1B10 ) aldo - keto reductases in the production of alpha - hydroxy ketones and diols from vicinal diketones.", "output": "alpha - hydroxy ketones, diols, vicinal diketones." }, { "input": "The reactions have been carried out with pure enzymes and with an NADPH - regenerating system consisting of glucose - 6 - phosphate and glucose - 6 - phosphate dehydrogenase.", "output": "NADPH, glucose - 6 - phosphate, glucose - 6 - phosphate." }, { "input": "To ascertain the regio and stereoselectivity of the reduction reactions catalyzed by the AKRs, we have separated and characterized the reaction products by means of a gas chromatograph equipped with a chiral column and coupled to a mass spectrometer as a detector.", "output": "There is no related enetity." }, { "input": "According to the regioselectivity and stereoselectivity, the AKRs studied can be divided in two groups: one of them showed preference for the reduction of the proximal keto group, resulting in the S - enantiomer of the corresponding alpha - hydroxy ketones.", "output": "keto, alpha - hydroxy ketones." }, { "input": "The other group favored the reduction of the distal keto group and yielded the corresponding R - enantiomer.", "output": "keto." }, { "input": "Three of the AKRs used ( AKR1B1, AKR1B10 and AKR3C1 ) could produce 2, 3 - butanediol from acetoin.", "output": "2 , 3 - butanediol, acetoin." }, { "input": "We have explored the structure / function relationships in the reactivity between several yeast and human AKRs and various diketones and acetoin.", "output": "diketones, acetoin." }, { "input": "In addition, we have demonstrated the utility of these AKRs in the synthesis of selected alpha - hydroxy ketones and diols.", "output": "alpha - hydroxy ketones, diols." }, { "input": "Fluorescence lifetime analysis and effect of magnesium ions on binding of NADH to human aldehyde dehydrogenase 1.", "output": "magnesium, NADH, aldehyde." }, { "input": "Aldehyde dehydrogenase 1 ( ALDH1A1 ) catalyzes the oxidation of toxic aldehydes to carboxylic acids.", "output": "Aldehyde, aldehydes, carboxylic acids." }, { "input": "Physiologic levels of Mg ( 2 + ) ions decrease ALDH1 activity in part by increasing NADH binding affinity to the enzyme.", "output": "Mg ( 2 + ), NADH." }, { "input": "By using time - resolved fluorescence spectroscopy, we have resolved the fluorescent lifetimes ( tau ) of free NADH in solution ( tau = 0. 4 ns ) and two enzyme - bound NADH states ( tau = 2. 0 ns and tau = 7. 7 ns ).", "output": "NADH, NADH." }, { "input": "We used this technique to investigate the effects of Mg ( 2 + ) ions on the ALDH1A1 - NADH binding characteristics and enzyme catalysis.", "output": "Mg ( 2 + ), NADH." }, { "input": "From the resolved free and bound NADH fluorescence signatures, the KD values for both NADH conformations in ALDH1A1 ranged from about 24 mu M to 1 mu M for Mg ( 2 + ) ion concentrations of 0 - 6000 mu M, respectively.", "output": "NADH, NADH, Mg ( 2 + )." }, { "input": "The rate constants for dissociation of the enzyme - NADH complex ranged from 0. 03 s ( - 1 ) ( 6000 mu M Mg ( 2 + ) ) to 0. 30s ( - 1 ) ( 0 mu M Mg ( 2 + ) ) as determined by addition of excess NAD ( + ) to prevent re - association of NADH and resolving the real - time NADH fluorescence signal.", "output": "NADH, Mg ( 2 + ), Mg ( 2 + ), NAD ( + ), NADH, NADH." }, { "input": "During the initial reaction of enzyme with NAD ( + ) and butyraldehyde, there was an immediate rise in the NADH fluorescence, due to the formation of bound NADH complexes, with a constant steady - state rate of production of free NADH.", "output": "NAD ( + ), butyraldehyde, NADH, NADH, NADH." }, { "input": "As the Mg ( 2 + ) ion concentration was increased, there was a consistent decrease of the enzyme catalytic turnover from 0. 31 s ( - 1 ) ( 0 mu M Mg ( 2 + ) ) to 0. 050 s ( - 1 ) ( 6000 mu M Mg ( 2 + ) ) and a distinct shift in steady - state conformational population from one that favors the ALDH1 - NADH complex with the shorter fluorescence lifetime ( 33 % excess ) in the absence of magnesium ion to one that favors the ALDH1 - NADH complex with the longer fluorescence lifetime ( 13 % excess ) at 6000 mu M Mg ( 2 + ).", "output": "Mg ( 2 + ), Mg ( 2 + ), Mg ( 2 + ), NADH, magnesium, NADH, Mg ( 2 + )." }, { "input": "This shift in conformational population at higher Mg ( 2 + ) ion concentrations and to lower enzyme activity may be due to longer residence time of the NADH in the ALDH1 pocket.", "output": "Mg ( 2 + ), NADH." }, { "input": "The results from monitoring enzyme catalysis in the absence of magnesium suggests that the ALDH1 - NADH complex with the shorter fluorescence lifetime is the form initially produced, and the complex with the longer fluorescence lifetime is produced through isomerization.", "output": "magnesium, NADH." }, { "input": "Novel topical formulations of Terbinafine - HCl for treatment of onychomycosis.", "output": "Terbinafine, HCl." }, { "input": "Terbinafine hydrochloride ( TBF - HCl ) is an active substance that is using for treatment of onychomycosis.", "output": "Terbinafine hydrochloride, TBF, HCl." }, { "input": "Onychomycosis is a fungal infection which is the most common disease of nail plate.", "output": "There is no related enetity." }, { "input": "The nail plate is a barrier which prevents effective topical treatment of ungual disorders.", "output": "There is no related enetity." }, { "input": "In this study, TBF - HCl loaded liposome and ethosome formulations and also gel form of these formulations were prepared.", "output": "TBF, HCl." }, { "input": "The formulations were characterized and in vitro and ex vivo release studies were performed.", "output": "There is no related enetity." }, { "input": "Nail characterization studies were also performed to examine the effect of formulations and experimental conditions on nail surface.", "output": "There is no related enetity." }, { "input": "As a result, all formulations can serve as efficient formulations for ungual application of TBF - HCl.", "output": "TBF, HCl." }, { "input": "By the way, the results of the accumulation studies suggested that liposome poloxamer gel formulation could be promising system for ungual drug delivery due to the better accumulation and easier application of the formulation.", "output": "poloxamer gel." }, { "input": "The interplay between environmental and genetic factors in Parkinson ' s disease susceptibility: The evidence for pesticides.", "output": "There is no related enetity." }, { "input": "Parkinson ' s disease ( PD ) is a common neurodegenerative disorder characterized by dopaminergic neuron loss in the substantia nigra.", "output": "There is no related enetity." }, { "input": "Several genetic and environmental factors have been implicated in the pathogenesis of PD.", "output": "There is no related enetity." }, { "input": "Single risk factors are likely to exert relatively minor effects, whereas their interaction may prove to be sufficient to cause PD.", "output": "There is no related enetity." }, { "input": "In the present review we summarize current knowledge from human genetic association studies regarding the interaction between gene polymorphisms and pesticide exposure in the risk of PD.", "output": "There is no related enetity." }, { "input": "A number of genetic association studies have investigated joint effects between genes and pesticides on PD risk.", "output": "There is no related enetity." }, { "input": "They have provided some evidence that genetic susceptibility either in metabolism, elimination and transport of pesticides or in the extent of mitochondrial dysfunction, oxidative stress and neuronal loss may predispose individuals to PD if they have been exposed to pesticides.", "output": "There is no related enetity." }, { "input": "These findings confirm the importance of considering pesticide - gene interactions in future studies in order to gain a better understanding of the pathogenic mechanisms of PD.", "output": "There is no related enetity." }, { "input": "Adaptive changes in basal and stress - induced HPA activity in lactating and post - lactating female rats.", "output": "There is no related enetity." }, { "input": "Lactation represents a period of marked adaptation of the hypothalamo - pituitary - adrenal HPA axis.", "output": "There is no related enetity." }, { "input": "We characterized basal and stress - induced HPA activity during lactation and experimental weaning using dynamic blood sampling in rats.", "output": "There is no related enetity." }, { "input": "Pulsatile and diurnal corticosterone release occurred at all reproductive stages studied ( virgin; day 10 of lactation; 3 and 14 days after experimental weaning on day 10 of lactation ).", "output": "corticosterone." }, { "input": "However, in lactating rats the diurnal peak was significantly reduced, resulting in a flattened rhythm, and three days after weaning, basal HPA activity was markedly suppressed: the number of pulses and underlying basal levels of corticosterone were reduced and the diurnal rise phase delayed.", "output": "corticosterone." }, { "input": "Marked changes in the HPA response to 10 min noise stress also occurred at these times: being completely absent in lactating animals, but restored and highly prolonged in early weaned animals.", "output": "There is no related enetity." }, { "input": "Injection of methylprednisolone ( 2 mg, iv ) was used to determine whether changes in fast glucocorticoid suppression correlated with these adaptive changes.", "output": "methylprednisolone." }, { "input": "Methylprednisolone induced a rapid suppression of corticosterone in virgin animals, but this effect was markedly attenuated in lactating and early weaned animals and was accompanied by significant changes in relative expression of hippocampal glucocorticoid and mineralocorticoid receptor mRNA.", "output": "Methylprednisolone, corticosterone." }, { "input": "All effects were reversed or partially reversed 14 days after experimental weaning.", "output": "There is no related enetity." }, { "input": "Thus, the presence of the pups has an important influence on regulation of the HPA axis, and while postpartum adaptations are reversible, acute weaning evokes marked reorganisation of basal and stress - induced HPA activity.", "output": "There is no related enetity." }, { "input": "Tamoxifen represses miR - 200 microRNAs and promotes epithelial - to - mesenchymal transition by up - regulating c - Myc in endometrial carcinoma cell lines.", "output": "Tamoxifen." }, { "input": "Although tamoxifen ( TAM ), a selective estrogen receptor modulator, has been widely used in the treatment of hormone - responsive breast cancer, its estrogen - like effect increases the risk of endometrial cancer.", "output": "tamoxifen, TAM, estrogen, estrogen." }, { "input": "However, the molecular mechanisms of TAM - induced endometrial carcinoma still remain unclear.", "output": "TAM." }, { "input": "In this report, we explored the role of microRNAs ( miRNAs ) in TAM - induced epithelial - mesenchymal transition ( EMT ) in ECC - 1 and Ishikawa endometrial cancer cell lines and found miR - 200 is involved in this process via the regulation of c - Myc.", "output": "TAM." }, { "input": "When treated with TAM, ECC - 1 and Ishikawa cells were characterized by higher invasiveness and motility and underwent EMT.", "output": "TAM." }, { "input": "miR - 200, a miRNA family with tumor suppressive functions in a wide range of cancers, was found reduced in response to TAM treatment.", "output": "TAM." }, { "input": "Consistent with zinc finger E - box binding homeobox 2, which was confirmed as a direct target of miR - 200b in endometrial cancer cell lines, some other key factors of EMT such as Snail and N - cadherin increased, whereas E - cadherin decreased in the TAM - treated cells, contributing to TAM - induced EMT in these endometrial cancer cells.", "output": "zinc, TAM, TAM." }, { "input": "In addition, we showed that c - Myc directly binds to and represses the promoter of miR - 200 miRNAs, and its up - regulation in TAM - treated endometrial cancer cells leads to the down - regulation of miR - 200 and eventually to EMT.", "output": "TAM." }, { "input": "Collectively, our data suggest that TAM can repress the miR - 200 family and induce EMT via the up - regulation of c - Myc in endometrial cancer cells.", "output": "TAM." }, { "input": "These findings describe a possible mechanism of TAM - induced EMT in endometrial cancer and provide a potential new therapeutic strategy for it.", "output": "TAM." }, { "input": "Apoptotic transcriptional profile remains activated in late remodeled left ventricle after myocardial infarction in swine infarcted hearts with preserved ejection fraction.", "output": "There is no related enetity." }, { "input": "Apoptosis is involved in both acute and chronic loss of cardiomyocytes after myocardial infarction ( MI ).", "output": "There is no related enetity." }, { "input": "To date, the pathophysiological significance of an apoptotic transcriptional profile activated in the post - ischemic remodeled myocardium, in the absence of hemodynamic factors secondary to left ventricular ( LV ) dysfunction, still remains to be determined.", "output": "There is no related enetity." }, { "input": "The mRNA expression of pro - and anti - apoptotic factors was determined in a swine model of non - reperfused MI with preserved LV ejection fraction.", "output": "There is no related enetity." }, { "input": "The extent of cell death was evaluated by histological analysis.", "output": "There is no related enetity." }, { "input": "Male adult farm pigs with MI ( n = 5 ), induced by permanent surgical ligation of the left anterior descending coronary artery and sham - operated adult farm pigs as control ( n = 7 ) were studied.", "output": "There is no related enetity." }, { "input": "Tissue samples were collected from the border ( BZ ) and remote zone ( RZ ) of the infarcted area to identify possible regional effects.", "output": "There is no related enetity." }, { "input": "After 4 weeks post - MI, the infarct size was 13 +/- 1 % of the LV wall mass in absence of contractile dysfunction.", "output": "There is no related enetity." }, { "input": "In BZ, there was increased mRNA expression of Casp - 3 ( BZ vs Controls: 0. 51 +/- 0. 15 vs 1. 39 +/- 0. 04, p < 0. 001 ), a significant decrease in Bcl - 2 ( by 63 % ), associated with an increase in apoptotic cells, as revealed by TUNEL staining and cleaved - Casp - 3 presence.", "output": "There is no related enetity." }, { "input": "In contrast, in the RZ there was a significant reduction of pro - apoptotic factors compared to BZ ( by 80 % for Casp - 3 ), in presence of scattered apoptotic cells, increased gene expression of Hsp72 ( 1. 82 +/- 0. 21 vs 1. 34 +/- 0. 08, p = 0. 037 ) and iNOS ( 1. 51 +/- 0. 14 vs 1. 19 +/- 0. 05, p < 0. 05 ) compared to control.", "output": "There is no related enetity." }, { "input": "In conclusion, the LV distribution of apoptotic transcriptional profile revealed that apoptotic cell death is highly detectable in BZ, possibly explaining the local abnormalities of myocardial cell survival in a porcine model of MI with normal overall function.", "output": "There is no related enetity." }, { "input": "Poor definitions threaten drug trial safety in India.", "output": "There is no related enetity." }, { "input": "India has become a hotbed of clinical trials, but recent reports of safety lapses have prompted calls for better regulation in this area.", "output": "There is no related enetity." }, { "input": "Currently, trial requirements can be relaxed if doing so is in the ' public interest ', but a clearer definition of what this means is needed before this provision should be used.", "output": "There is no related enetity." }, { "input": "Combined analytical ultracentrifugation, light scattering and fluorescence spectroscopy studies on the functional associations of the bacterial division FtsZ protein.", "output": "There is no related enetity." }, { "input": "The combined application of different biophysical techniques - analytical ultracentrifugation, light scattering and fluorescence - based assays - to study the ligand - linked self - association and assembly properties of the cell division protein FtsZ from Escherichia coli is described.", "output": "There is no related enetity." }, { "input": "These reactions are thought to be important for the formation of the dynamic division ring that drives bacterial cytokinesis.", "output": "There is no related enetity." }, { "input": "In addition, the use of this orthogonal experimental approach to measure the interactions between FtsZ oligomers ( GDP forms ) and polymers ( GTP forms ) with two variants ( a soluble form and a full - length protein incorporated in phospholipid bilayer nanodiscs ) of the ZipA protein, which provides membrane tethering to FtsZ, is described as well.", "output": "GDP, GTP." }, { "input": "The power of a global analysis of the results obtained from complementary biophysical methods to discriminate among alternative self - and hetero - associating schemes and to propose a more robust description of the association reactions involved is emphasized.", "output": "There is no related enetity." }, { "input": "This orthogonal approach will contribute to complete our quantitative understanding of the initial events of bacterial division.", "output": "There is no related enetity." }, { "input": "Manganese - induced oxidative DNA damage in neuronal SH - SY5Y cells: attenuation of thymine base lesions by glutathione and N - acetylcysteine.", "output": "Manganese, thymine, glutathione, N - acetylcysteine." }, { "input": "Manganese ( Mn ) is an essential trace element required for normal function and development.", "output": "Manganese, Mn." }, { "input": "However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson ' s disease ( IPD ).", "output": "There is no related enetity." }, { "input": "Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns.", "output": "Mn." }, { "input": "The underlying mechanism of Mn neurotoxicity remains unclear.", "output": "Mn." }, { "input": "Accordingly, the present study was designed to investigate the toxic effects of Mn ( 2 + ) in human neuroblastoma SH - SY5Y cells.", "output": "Mn ( 2 + )." }, { "input": "Mn ( 2 + ) caused a concentration dependent decrease in SH - SY5Y cellular viability compared to controls.", "output": "Mn ( 2 + )." }, { "input": "The LD50 value was 12. 98 mu M Mn ( 2 + ) ( p < 0. 001 for control vs. 24h Mn treatment ).", "output": "Mn ( 2 + ), Mn." }, { "input": "Both TUNEL and annexin V / propidium iodide ( PI ) apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn ( 2 + ) ( 2 mu M, 62 mu M or 125 mu M ).", "output": "propidium iodide, Mn ( 2 + )." }, { "input": "In addition, Mn ( 2 + ) induced both the formation and accumulation of DNA single strand breaks ( via alkaline comet assay analysis ) and oxidatively modified thymine bases ( via gas chromatography / mass spectrometry analysis ).", "output": "Mn ( 2 + ), thymine." }, { "input": "Pre - incubation of the cells with characteristic antioxidants, either 1mM N - acetylcysteine ( NAC ) or 1mM glutathione ( GSH ) reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage.", "output": "N - acetylcysteine, NAC, glutathione, GSH, thymine." }, { "input": "Our findings indicate that ( 1 ) exposure of SH - SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA damage, ( 2 ) SH - SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and ( 3 ) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants.", "output": "Mn." }, { "input": "This is the first known report of Mn ( 2 + ) - induction and antioxidant protection of thymine lesions in this SH - SY5Y cell line and contributes new information to the potential use of antioxidants as a therapeutic strategy for protection against Mn ( 2 + ) - induced oxidative DNA damage.", "output": "Mn ( 2 + ), thymine, Mn ( 2 + )." }, { "input": "Acrolein induces Alzheimer ' s disease - like pathologies in vitro and in vivo.", "output": "Acrolein." }, { "input": "The pathologic mechanisms of Alzheimer ' s disease ( AD ) have not been fully uncovered.", "output": "There is no related enetity." }, { "input": "Acrolein, a ubiquitous dietary pollutant and by - product of oxidative stress, can induce cytotoxicity in neurons, which might play an important role in the etiology of AD.", "output": "Acrolein." }, { "input": "Here, we examined the effects of Acrolein on the AD pathologies in vitro and in vivo.", "output": "Acrolein." }, { "input": "We found Acrolein induced HT22 cells death in concentration - and time - dependent manners.", "output": "Acrolein." }, { "input": "Interestingly, Acrolein increased proteins ' levels of amyloid precursor protein ( APP ), beta - secretase ( BACE - 1 ) and the amyloid beta - peptide transporter receptor for advanced glycation end products, and decreased A - disintegrin and metalloprotease ( ADAM ) 10 levels.", "output": "Acrolein." }, { "input": "In vivo, chronic oral exposure to Acrolein ( 2. 5 mg / kg / day by intragastric gavage for 8 weeks ) induced mild cognitive declination and pyknosis / atrophy of hippocampal neurons.", "output": "Acrolein." }, { "input": "The activity of superoxide dismutase was down - regulated while the level of malondialdehyde was up - regulated in rat brain.", "output": "superoxide, malondialdehyde." }, { "input": "Moreover, Acrolein resulted in activation of astrocytes, up - regulation of BACE - 1 in cortex and down - regulation of ADAM - 10 in hippocampus and cortex.", "output": "Acrolein." }, { "input": "Taken together, our findings suggest that exposure to Acrolein induces AD - like pathology in vitro and in vivo.", "output": "Acrolein." }, { "input": "Scavenging Acrolein might be beneficial for the therapy of AD.", "output": "Acrolein." }, { "input": "Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats.", "output": "uranium." }, { "input": "Uranium nanoparticles ( < 100 nm ) can be released into the atmosphere during industrial stages of the nuclear fuel cycle and during remediation and decommissioning of nuclear facilities.", "output": "Uranium." }, { "input": "Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols.", "output": "uranium." }, { "input": "The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account.", "output": "uranium." }, { "input": "In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally.", "output": "uranium." }, { "input": "For this purpose, rats were exposed to an aerosol containing 10 7 particles of uranium per cm (3) ( CMD = 38 nm ) for 1h in a nose - only inhalation exposure system.", "output": "uranium." }, { "input": "Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP - MS.", "output": "Uranium." }, { "input": "Twenty - seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract.", "output": "uranium." }, { "input": "One - fifth of UO 2 nanoparticles were rapidly cleared from lung ( T ( (1/2) ) = 2. 4 h ) and translocated to extrathoracic organs.", "output": "UO 2." }, { "input": "However, the majority of the particles were cleared slowly ( T ( (1/2) ) = 141. 5 d ).", "output": "There is no related enetity." }, { "input": "Future long - term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure.", "output": "uranium." }, { "input": "A RASSCF study of free base, magnesium and zinc porphyrins: accuracy versus efficiency.", "output": "magnesium and zinc porphyrins." }, { "input": "The restricted - active - space self - consistent - field methodology is successfully applied to the study of free base - and regular metalloporphyrins, the latter containing magnesium and zinc central ions.", "output": "metalloporphyrins, magnesium, zinc." }, { "input": "It is shown that inclusion of all excitations involving the Gouterman frontier orbitals in the RAS2 subspace results in a numerically stable approach, producing highly accurate results at a fraction of the computational cost of the complete - active - space self - consistent - field method, whereas increasing RAS2 beyond this size leads to only modest improvement.", "output": "There is no related enetity." }, { "input": "Topological and orbital analysis shows that the approach is also able to give a highly accurate description of the electronic wavefunction.", "output": "There is no related enetity." }, { "input": "Inclusion of the entire pi - conjugated subsystem in the active space results in more accurate excitation energies and a reduction in the dependence on the exact form of the perturbational Hamiltonian used to include dynamic correlation.", "output": "There is no related enetity." }, { "input": "The larger active space also resolves a quantitative disagreement in results obtained with and without the inclusion of dynamic correlation.", "output": "There is no related enetity." }, { "input": "Role of immunoglobulin G fragment C receptor polymorphism - mediated antibody - dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy.", "output": "There is no related enetity." }, { "input": "Antibody - dependent cellular cytotoxicity ( ADCC ), which is activated by effector cells via immunoglobulin G ( IgG ) fragment C receptors ( FcRs ), was proposed as a mechanism of cetuximab efficacy.", "output": "There is no related enetity." }, { "input": "Peripheral blood mononuclear cells ( PBMCs ) from 23 healthy donors and 13 patients with metastatic colorectal cancer ( mCRC ) treated with cetuximab were tested for Fc gamma R polymorphisms and cetuximab - mediated ADCC.", "output": "There is no related enetity." }, { "input": "ADCC was measured by chromium - 51 release on a epidermal growth factor receptor ( EGFR ) - positive human colon cancer cell line.", "output": "chromium - 51." }, { "input": "Overall, 86 mCRC patients were genotyped for study purposes.", "output": "There is no related enetity." }, { "input": "PBMCs harbouring the Fc gamma RIIIa 158 V / V genotype had a significantly higher cetuximab - mediated ADCC.", "output": "There is no related enetity." }, { "input": "No correlation was found between Fc gamma R polymorphisms and response rate or time to progression after cetuximab - based therapy.", "output": "There is no related enetity." }, { "input": "Despite the in vitro analysis showing that the Fc gamma RIIIa 158 V / V genotype is associated with higher ADCC, clinical data do not support a predictive role of Fc gamma RIIIa polymorphisms in mCRC treated with cetuximab. The Pharmacogenomics Journal advance online publication, 8 January 2013; doi: 10. 1038 / tpj. 2012. 54.", "output": "There is no related enetity." }, { "input": "Inborn errors of metabolism with 3 - methylglutaconic aciduria as discriminative feature: proper classification and nomenclature.", "output": "3 - methylglutaconic." }, { "input": "Increased urinary 3 - methylglutaconic acid excretion is a relatively common finding in metabolic disorders, especially in mitochondrial disorders.", "output": "3 - methylglutaconic acid." }, { "input": "In most cases 3 - methylglutaconic acid is only slightly elevated and accompanied by other ( disease specific ) metabolites.", "output": "3 - methylglutaconic acid." }, { "input": "There is, however, a group of disorders with significantly and consistently increased 3 - methylglutaconic acid excretion, where the 3 - methylglutaconic aciduria is a hallmark of the phenotype and the key to diagnosis.", "output": "3 - methylglutaconic acid, 3 - methylglutaconic." }, { "input": "Until now these disorders were labelled by roman numbers ( I - V ) in the order of discovery regardless of pathomechanism.", "output": "There is no related enetity." }, { "input": "Especially, the so called \" unspecified \" 3 - methylglutaconic aciduria type IV has been ever growing, leading to biochemical and clinical diagnostic confusion.", "output": "3 - methylglutaconic." }, { "input": "Therefore, we propose the following pathomechanism based classification and a simplified diagnostic flow chart for these \" inborn errors of metabolism with 3 - methylglutaconic aciduria as discriminative feature \".", "output": "3 - methylglutaconic." }, { "input": "One should distinguish between \" primary 3 - methylglutaconic aciduria \" formerly known as type I ( 3 - methylglutaconyl - CoA hydratase deficiency, AUH defect ) due to defective leucine catabolism and the - currently known - three groups of \" secondary 3 - methylglutaconic aciduria \".", "output": "3 - methylglutaconic, 3 - methylglutaconyl - CoA, leucine, 3 - methylglutaconic." }, { "input": "The latter should be further classified and named by their defective protein or the historical name as follows: i ) defective phospholipid remodelling ( TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome ) and ii ) mitochondrial membrane associated disorders ( OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect ).", "output": "There is no related enetity." }, { "input": "The remaining patients with significant and consistent 3 - methylglutaconic aciduria in whom the above mentioned syndromes have been excluded, should be referred to as \" not otherwise specified ( NOS ) 3 - MGA - uria \" until elucidation of the underlying pathomechanism enables proper ( possibly extended ) classification.", "output": "3 - methylglutaconic, 3 - MGA." }, { "input": "Neuroprotective and anti - inflammatory properties of a coffee component in the MPTP model of Parkinson ' s disease.", "output": "MPTP." }, { "input": "Consumption of coffee is associated with reduced risk of Parkinson ' s disease ( PD ), an effect that has largely been attributed to caffeine.", "output": "There is no related enetity." }, { "input": "However, coffee contains numerous components that may also be neuroprotective.", "output": "There is no related enetity." }, { "input": "One of these compounds is eicosanoyl - 5 - hydroxytryptamide ( EHT ), which ameliorates the phenotype of alpha - synuclein transgenic mice associated with decreased protein aggregation and phosphorylation, improved neuronal integrity and reduced neuroinflammation.", "output": "eicosanoyl - 5 - hydroxytryptamide, EHT." }, { "input": "Here, we sought to investigate if EHT has an effect in the MPTP model of PD.", "output": "EHT, MPTP." }, { "input": "Mice fed a diet containing EHT for four weeks exhibited dose - dependent preservation of nigral dopaminergic neurons following MPTP challenge compared to animals given control feed.", "output": "EHT, MPTP." }, { "input": "Reductions in striatal dopamine and tyrosine hydroxylase content were also less pronounced with EHT treatment.", "output": "dopamine, tyrosine, EHT." }, { "input": "The neuroinflammatory response to MPTP was markedly attenuated, and indices of oxidative stress and JNK activation were significantly prevented with EHT.", "output": "MPTP, EHT." }, { "input": "In cultured primary microglia and astrocytes, EHT had a direct anti - inflammatory effect demonstrated by repression of lipopolysaccharide - induced NF kappa B activation, iNOS induction, and nitric oxide production.", "output": "EHT, nitric oxide." }, { "input": "EHT also exhibited a robust anti - oxidant activity in vitro.", "output": "EHT." }, { "input": "Additionally, in SH - SY5Y cells, MPP ( + ) - induced demethylation of phosphoprotein phosphatase 2A ( PP2A ), the master regulator of the cellular phosphoregulatory network, and cytotoxicity were ameliorated by EHT.", "output": "MPP ( + ), EHT." }, { "input": "These findings indicate that the neuroprotective effect of EHT against MPTP is through several mechanisms including its anti - inflammatory and antioxidant activities as well as its ability to modulate the methylation and hence activity of PP2A.", "output": "EHT, MPTP." }, { "input": "Our data, therefore, reveal a strong beneficial effect of a novel component of coffee in multiple endpoints relevant to PD.", "output": "There is no related enetity." }, { "input": "Urinary chromium excretion in response to an insulin challenge is not a biomarker for chromium status.", "output": "chromium, chromium." }, { "input": "Over 50 years ago, chromium ( Cr ) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional.", "output": "chromium, Cr, Cr." }, { "input": "The pharmacological basis for Cr ' s effects can explain the inability of investigators to discover a biomarker for Cr status.", "output": "Cr, Cr." }, { "input": "One potential biomarker has not been examined to date.", "output": "There is no related enetity." }, { "input": "Cr is known to be mobilized in the body in response to insulin ( or insulin release in response to a glucose challenge ), resulting in an increase in urinary Cr excretion.", "output": "Cr, glucose, Cr." }, { "input": "The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr.", "output": "Cr, Cr, Cr." }, { "input": "Zucker lean rats housed in carefully controlled metal - free conditions were provided a series of purified diets containing variable Cr contents ( from 16 mu g / kg diet to 2, 000 mu g / kg ) for 23 weeks.", "output": "Cr." }, { "input": "The 16 mu g / kg diet contained less Cr than any diet examined to date.", "output": "Cr." }, { "input": "Urine samples were collected before and after insulin and glucose challenges ( 0, 2, 6, and 12 h postinjection ).", "output": "glucose." }, { "input": "Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption.", "output": "Cr, graphite." }, { "input": "The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats ' diets.", "output": "Cr, glucose, Cr." }, { "input": "Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status.", "output": "iron, Cr, iron." }, { "input": "The Cr content of the diet was found to have no affect on blood iron levels.", "output": "Cr, iron." }, { "input": "Overall, the study demonstrated that insulin - stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.", "output": "Cr, Cr." }, { "input": "Chrysin and Luteolin Attenuate Diabetes - Induced Impairment in Endothelial - Dependent Relaxation: Effect on Lipid Profile, AGEs and NO Generation.", "output": "Chrysin, Luteolin, NO." }, { "input": "Chrysin and luteolin are two important plant flavonoids.", "output": "Chrysin, luteolin, flavonoids." }, { "input": "In the present study, we hypothesized that they protect against deleterious vascular effects of diabetes.", "output": "There is no related enetity." }, { "input": "Diabetes was induced in rats by streptozotocin ( STZ ) injection, while chrysin and luteolin were administered two weeks after STZ administration for 6 weeks.", "output": "streptozotocin, STZ, chrysin, luteolin, STZ." }, { "input": "Then, blood pressure ( BP ) and serum levels of glucose, advanced glycation end products ( AGEs ), triglycerides ( TGs ), total cholesterol and low density lipoprotein - cholesterol ( LDL - C ) were determined.", "output": "glucose, triglycerides, TGs, cholesterol, cholesterol." }, { "input": "Concentration response curves for KCl, phenylephrine ( PE ), acetylcholine ( ACh ) and ACh - induced NO generation were obtained in isolated aorta.", "output": "KCl, phenylephrine, acetylcholine, ACh, ACh, NO." }, { "input": "Compared with control, diabetes increased diastolic and systolic BP, while chrysin and luteolin attenuated diastolic BP elevation without affecting the developed hyperglycemia.", "output": "chrysin, luteolin." }, { "input": "Diabetes increased contractile response of aorta to KCl, PE, decreased relaxation response to ACh, while chrysin and luteolin prevented the impaired response to ACh.", "output": "KCl, ACh, chrysin, luteolin, ACh." }, { "input": "In addition, diabetes was accompanied by elevated levels of TGs, total and LDL cholesterol, while both chrysin and luteolin prevented this dyslipidemia.", "output": "TGs, cholesterol, chrysin, luteolin." }, { "input": "Furthermore, chrysin decreased the elevated AGEs level in serum of diabetic animals, while luteolin abrogated the impaired NO generation in diabetic aorta.", "output": "chrysin, luteolin, NO." }, { "input": "Collectively, chrysin and luteolin attenuate diabetes - evoked impairment in endothelial - dependent relaxation possibly via ameliorating detrimental changes in lipid profile, AGEs and NO generation.", "output": "chrysin, luteolin, NO." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Anti - platelet Activity of Erythro - ( 7S, 8R ) - 7 - acetoxy - 3, 4, 3 `, 5 ` - tetramethoxy - 8 - O - 4 ` - neolignan from Myristica fragrans.", "output": "Erythro - ( 7S , 8R ) - 7 - acetoxy - 3 , 4 , 3 ` , 5 ` - tetramethoxy - 8 - O - 4 ` - neolignan." }, { "input": "Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes.", "output": "There is no related enetity." }, { "input": "The inhibition of platelet function is beneficial for the treatment and prevention of these diseases.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the anti - platelet activity of erythro - ( 7S, 8R ) - 7 - acetoxy - 3, 4, 3 `, 5 ` - tetramethoxy - 8 - O - 4 ` - neolignan ( EATN ), a neolignan isolated from Myristica fragrans, using human platelets.", "output": "erythro - ( 7S , 8R ) - 7 - acetoxy - 3 , 4 , 3 ` , 5 ` - tetramethoxy - 8 - O - 4 ` - neolignan, EATN, neolignan." }, { "input": "EATN preferentially inhibited thrombin - and platelet - activating factor ( PAF ) - induced platelet aggregation without affecting platelet damage in a concentration - dependent manner with IC ( 50 ) values of 3. 2 +/- 0. 4 and 3. 4 +/- 0. 3 mu M, respectively.", "output": "EATN." }, { "input": "However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid.", "output": "EATN, arachidonic acid." }, { "input": "EATN also inhibited thrombin - induced serotonin and ATP release, and thromboxane B ( 2 ) formation in human platelets.", "output": "EATN, serotonin, ATP, thromboxane B ( 2 )." }, { "input": "Moreover, EATN caused an increase in cyclic AMP ( cAMP ) levels and attenuated intracellular Ca ( 2 + ) mobilization in thrombin - activated human platelets.", "output": "EATN, cyclic AMP, cAMP, Ca ( 2 + )." }, { "input": "Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca ( 2 + ) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors.", "output": "EATN, cAMP, Ca ( 2 + )." }, { "input": "This is the first report of the anti - platelet activity of EATN isolated from M. fragrans.", "output": "EATN." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Materiomics: an - omics approach to biomaterials research.", "output": "There is no related enetity." }, { "input": "The past fifty years have seen a surge in the use of materials for clinical application, but in order to understand and exploit their full potential, the scientific complexity at both sides of the interface - - the material on the one hand and the living organism on the other hand - - needs to be considered.", "output": "There is no related enetity." }, { "input": "Technologies such as combinatorial chemistry, recombinant DNA as well as computational multi - scale methods can generate libraries with a very large number of material properties whereas on the other side, the body will respond to them depending on the biological context.", "output": "There is no related enetity." }, { "input": "Typically, biological systems are investigated using both holistic and reductionist approaches such as whole genome expression profiling, systems biology and high throughput genetic or compound screening, as already seen, for example, in pharmacology and genetics.", "output": "There is no related enetity." }, { "input": "The field of biomaterials research is only beginning to develop and adopt these approaches, an effort which we refer to as \" materiomics \".", "output": "There is no related enetity." }, { "input": "In this review, we describe the current status of the field, and its past and future impact on the biomedical sciences.", "output": "There is no related enetity." }, { "input": "We outline how materiomics sets the stage for a transformative change in the approach to biomaterials research to enable the design of tailored and functional materials for a variety of properties in fields as diverse as tissue engineering, disease diagnosis and de novo materials design, by combining powerful computational modelling and screening with advanced experimental techniques.", "output": "There is no related enetity." }, { "input": "Hydrogen sulfide, the next potent preventive and therapeutic agent in aging and age - associated diseases.", "output": "Hydrogen sulfide." }, { "input": "Hydrogen sulfide ( H ( 2 ) S ) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide.", "output": "Hydrogen sulfide, H ( 2 ) S, nitric oxide, carbon monoxide." }, { "input": "It is physiologically generated by cystathionine - gamma - lyase, cystathionine - beta - synthase, and 3 - mercaptopyruvate sulfurtransferase.", "output": "cystathionine, cystathionine, 3 - mercaptopyruvate." }, { "input": "H ( 2 ) S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems.", "output": "H ( 2 ) S." }, { "input": "Substantial evidence shows that H ( 2 ) S is involved in aging by inhibiting free - radical reactions, activating SIRT1, and probably interacting with the age - related gene Klotho.", "output": "H ( 2 ) S." }, { "input": "Moreover, H ( 2 ) S has been shown to have therapeutic potential in age - associated diseases.", "output": "H ( 2 ) S." }, { "input": "This article provides an overview of the physiological functions and effects of H ( 2 ) S in aging and age - associated diseases, and proposes the potential health and therapeutic benefits of H ( 2 ) S.", "output": "H ( 2 ) S, H ( 2 ) S." }, { "input": "Chemical composition and antibacterial activities of the essential oils isolated from Juniperus thurifera L. var.", "output": "There is no related enetity." }, { "input": "Africana.", "output": "There is no related enetity." }, { "input": "This study describes the chemical composition and antibacterial activities of essential oils of Moroccan Juniperus thurifera L. var.", "output": "There is no related enetity." }, { "input": "Africana ( Cupressaceae ).", "output": "There is no related enetity." }, { "input": "The essential oil of dried leaves was isolated by hydrodistillation, vapohydrodistillation and microwaves.", "output": "There is no related enetity." }, { "input": "Sixty - four compounds in J. thurifera L. var.", "output": "There is no related enetity." }, { "input": "Africana oils were identified ( 79. 9 %, 92. 4 % and 98. 4 % of the oil, respectively ).", "output": "There is no related enetity." }, { "input": "The most abundant compound in J. thurifera L. var.", "output": "There is no related enetity." }, { "input": "Africana oils is sabinene ( 38 %, 36. 2 % and 39. 4 % ).", "output": "sabinene." }, { "input": "Antibacterial activities of J. thurifera essential oils was tested against bacteria Gram ( - ) and Gram ( + ).", "output": "There is no related enetity." }, { "input": "The oil is very active against all bacteria tested except Pseudomonas, which turned out to be very resistant.", "output": "There is no related enetity." }, { "input": "Composition and evaluation of the anti - inflammatory and anticancer activities of the essential oil from Annona sylvatica A.", "output": "There is no related enetity." }, { "input": "St. - Hil.", "output": "There is no related enetity." }, { "input": "The essential oil from the leaves of Annona sylvatica ( EOAS ) was extracted by hydrodistillation, and the analysis was performed by gas chromatography - mass spectrometry.", "output": "There is no related enetity." }, { "input": "The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z - caryophyllene, beta - maaliene, gamma - gurjunene, silphiperfol - 5 - en - 3 - ol, ledol, cubecol - 1 - epi, and muurola - 3, 5 - diene.", "output": "sesquiterpenes, hinesol, z - caryophyllene, beta - maaliene, gamma - gurjunene, silphiperfol - 5 - en - 3 - ol, ledol, cubecol - 1 - epi, muurola - 3 , 5 - diene." }, { "input": "Oral administration of the EOAS ( 20 and 200 mg / kg ) and subcutaneous injection of dexamethasone ( 0. 5 mg / kg, reference drug ) significantly inhibited carrageenan - and complete Freund ' s adjuvant - induced mouse paw edema.", "output": "dexamethasone." }, { "input": "The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration.", "output": "There is no related enetity." }, { "input": "The EOAS inhibited the growth of human cancer cell lines with GI ( 50 ) values in the range of 36. 04 - 45. 37 mu g / mL on all of the cell lines tested.", "output": "There is no related enetity." }, { "input": "This work describes for the first time the anti - inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition.", "output": "There is no related enetity." }, { "input": "Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side - effects, the present results may have clinical relevance and open new possibilities for the development of novel anti - inflammatory and anticancer drugs.", "output": "There is no related enetity." }, { "input": "Topical wound - healing effects and phytochemical composition of heartwood essential oils of Juniperus virginiana L., Juniperus occidentalis Hook., and Juniperus ashei J.", "output": "There is no related enetity." }, { "input": "Buchholz.", "output": "There is no related enetity." }, { "input": "Ethnobotanical surveys indicated that in the traditional medicines worldwide, several Juniperus species are utilized as antihelmintic, diuretic, stimulant, antiseptic, carminative, stomachic, antirheumatic, antifungal, and for wound healing.", "output": "There is no related enetity." }, { "input": "In the present study, essential oils obtained from heartwood samples of Juniperus virginiana L., Juniperus occidentalis Hook. and Juniperus ashei J.", "output": "There is no related enetity." }, { "input": "Buchholz were evaluated for wound healing and anti - inflammatory activities by using in vivo experimental methods.", "output": "There is no related enetity." }, { "input": "The essential oils were obtained by the supercritical carbon dioxide extraction method.", "output": "carbon dioxide." }, { "input": "Linear incision and circular excision wound models were performed for the wound - healing activity assessment.", "output": "There is no related enetity." }, { "input": "The tissues were also evaluated for the hydroxyproline content as well as histopathologically.", "output": "hydroxyproline." }, { "input": "To evaluate the anti - inflammatory activity of the essential oils, the test used was an acetic acid - induced increase in capillary permeability.", "output": "acetic acid." }, { "input": "The essential oil of J. occidentalis showed the highest activity on the in vivo biological activity models.", "output": "There is no related enetity." }, { "input": "Additionaly, the oil of J. virginiana was found highly effective in the anti - inflammatory activity method.", "output": "There is no related enetity." }, { "input": "The experimental data demonstrated that essential oil of J. occidentalis displayed significant wound - healing and anti - inflammatory activities.", "output": "There is no related enetity." }, { "input": "Isolation and anti - HIV - 1 activity of a new sesquiterpene lactone from Calocephalus brownii F.", "output": "sesquiterpene lactone." }, { "input": "Muell.", "output": "There is no related enetity." }, { "input": "As part of our ongoing collaborative effort to discover potential anti - HIV - 1 agents from plants, the CH ( 2 ) Cl ( 2 ) extract of Calocephalus brownii F.", "output": "CH ( 2 ) Cl ( 2 )." }, { "input": "Muell. was phytochemically investigated, which resulted in the isolation of two sesquiterpene lactones of the cis - fused guaianolides type, one new identified as 1 alpha - hydroxy - 3 beta H - 3 alpha, 4 alpha - epoxy - 4, 10 - dimethyl - 5 alpha H, 7 alpha H, 8 beta H, 10 alpha H - guai - 11 ( 13 ) - ene - 7, 8 - olide ( 1 ) and one known identified 1 alpha H - 4 alpha - hydroxy - 4, 10 - dimethyl - 5 alpha H, 7 alpha H, 8 beta H, 10 alpha H - guai - 11 ( 13 ) - ene - 7, 8 - olide ( 2 ).", "output": "sesquiterpene lactones, cis - fused guaianolides, 1 alpha - hydroxy - 3 beta H - 3 alpha , 4 alpha - epoxy - 4 , 10 - dimethyl - 5 alpha H , 7 alpha H , 8 beta H , 10 alpha H - guai - 11 ( 13 ) - ene - 7 , 8 - olide, 1 alpha H - 4 alpha - hydroxy - 4 , 10 - dimethyl - 5 alpha H , 7 alpha H , 8 beta H , 10 alpha H - guai - 11 ( 13 ) - ene - 7 , 8 - olide." }, { "input": "Their structures were elucidated on the bases of IR, UV, 1D - NMR, 2D - NMR, DIFNOE and high - resolution ESI - TOF - MS.", "output": "There is no related enetity." }, { "input": "The anti - HIV - 1 activity was evaluated and revealed that STLs ( 1 and 2 ) caused a reduction for the viability of mock - infected MT - 4 cells by CC ( 50 ) = 29. 1 and 0. 5 mu g / mL, respectively, and caused 50 % protection of MT - 4 cells against HIV - 1 induced cytopathogeneticy by EC ( 50 ) = 29. 1 and 0. 5 mu g / mL, respectively, as compared with Efavirenz ( EFV ) as positive control that showed a CC ( 50 ) = 11. 6 and EC ( 50 ) = 0. 0006 mu g / mL, using the 3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 - diphenyltetrazolium bromide method.", "output": "Efavirenz, EFV, 3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide." }, { "input": "Risk of completed suicide after bariatric surgery: a systematic review.", "output": "There is no related enetity." }, { "input": "Bariatric surgery is one of the most effective treatments for morbid obesity, and a large body of research indicates significant long - term weight loss.", "output": "There is no related enetity." }, { "input": "While overall mortality decreases in patients who received bariatric surgery, a number of studies have shown that suicide rates are higher in bariatric patients than in control groups.", "output": "There is no related enetity." }, { "input": "The objective of this study was to present a systematic review of suicide mortality after bariatric surgery and calculate an estimate for the suicide rate.", "output": "There is no related enetity." }, { "input": "Literature researches of the databases PubMed, Web of Knowledge, PsychInfo, ScienceDirect and Google Scholar were conducted.", "output": "There is no related enetity." }, { "input": "Thirty studies concerning bariatric surgery and completed suicides met the inclusion criteria.", "output": "There is no related enetity." }, { "input": "We included 28 studies in the estimation of a suicide rate for the bariatric population.", "output": "There is no related enetity." }, { "input": "Only one study ( Tindle et al. ) put a main focus on suicide after bariatric surgery; this was therefore chosen as an adequate reference figure for comparison.", "output": "There is no related enetity." }, { "input": "The other 27 chosen studies were compared with World Health Organization data and the suicide rate reported by Tindle et al.", "output": "There is no related enetity." }, { "input": "Twenty - three thousand eight hundred eighty - five people were included in the analysis.", "output": "There is no related enetity." }, { "input": "In the literature, we found a total of 95 suicides when examining 190, 000 person - years of post - bariatric surgery data.", "output": "There is no related enetity." }, { "input": "Little information was provided describing the reasons for suicide and the time - point of these events after surgery.", "output": "There is no related enetity." }, { "input": "We estimated a suicide rate of 4. 1 / 10, 000 person - years ( 95 % confidence interval [ 3. 2, 5. 1 ] / 10, 000 person - years ).", "output": "There is no related enetity." }, { "input": "A comparison with Tindle et al. demonstrates that their rate is significantly higher than our estimate ( P = 0. 03 ).", "output": "There is no related enetity." }, { "input": "Bariatric surgery patients show higher suicide rates than the general population.", "output": "There is no related enetity." }, { "input": "Therefore, there is a great need to identify persons at risk and post - operative psychological monitoring is recommended.", "output": "There is no related enetity." }, { "input": "CO oxidation on colloidal Au ( 0. 80 ) Pd ( 0. 20 ) - Fe ( x ) O ( y ) dumbbell nanocrystals.", "output": "CO, Au ( 0 . 80 ) Pd ( 0 . 20 ) - Fe ( x ) O ( y )." }, { "input": "We report a colloidal synthesis of Au ( 0. 80 ) Pd ( 0. 20 ) - Fe ( x ) O ( y ) dumbbell nanocrystals ( NCs ) derived from Au ( 0. 75 ) Pd ( 0. 25 ) NCs by metal oxide overgrowth.", "output": "Au ( 0 . 80 ) Pd ( 0 . 20 ) - Fe ( x ) O ( y ), Au ( 0 . 75 ) Pd ( 0 . 25 ), metal oxide." }, { "input": "We compared the catalytic activity of the two types of NCs in the CO oxidation reaction ( CO + 1 / 2O ( 2 ) --> CO ( 2 ) ), after they had been dispersed on an alumina nanopowder support.", "output": "CO, CO, 1 / 2O ( 2 ), CO ( 2 ), alumina." }, { "input": "In both cases, the surface active sites were identified by means of in situ diffuse reflectance infrared Fourier transform spectroscopy ( DRIFTS ).", "output": "There is no related enetity." }, { "input": "The enhanced catalytic performance of the dumbbell NCs ( Au ( 0. 80 ) Pd ( 0. 20 ) - Fe ( x ) O ( y ) ) catalyst over that of the initial Au ( 0. 75 ) Pd ( 0. 25 ) NCs could be correlated to the presence of the epitaxial connection between the Fe ( x ) O ( y ) and the Au ( 0. 80 ) Pd ( 0. 20 ) domains ( as the main factor ).", "output": "Au ( 0 . 80 ) Pd ( 0 . 20 ) - Fe ( x ) O ( y ), Au ( 0 . 75 ) Pd ( 0 . 25 ), Fe ( x ) O ( y ), Au ( 0 . 80 ) Pd ( 0 . 20 )." }, { "input": "Such connection should result in an electron flow from the metal oxide ( Fe ( x ) O ( y ) ) domain to the noble metal ( Au ( 0. 80 ) Pd ( 0. 20 ) ) domain and appears to influence favorably the nature and composition of the catalytically active surface sites of the dumbbells.", "output": "metal oxide, Fe ( x ) O ( y ), Au ( 0 . 80 ) Pd ( 0 . 20 )." }, { "input": "Our experiments indicate indeed that, when the metal alloy domain is attached to the metal oxide domain ( that is, in the dumbbell ), surface Pd species are more active than in the case of the initial Au ( 0. 75 ) Pd ( 0. 25 ) NCs and also Au ( delta - ) sites are formed that were not present on the initial Au ( 0. 75 ) Pd ( 0. 25 ) NCs.", "output": "metal oxide, Pd, Au ( 0 . 75 ) Pd ( 0 . 25 ), Au, Au ( 0 . 75 ) Pd ( 0 . 25 )." }, { "input": "Honey as a source of dietary antioxidants: structures, bioavailability and evidence of protective effects against human chronic diseases.", "output": "There is no related enetity." }, { "input": "In the long human tradition honey has been used not only as a nutrient but also as a medicine.", "output": "There is no related enetity." }, { "input": "Its composition is rather variable and depends on the floral source and on external factors, such as seasonal, environmental conditions and processing.", "output": "There is no related enetity." }, { "input": "In this review, specific attention is focused on absorption, metabolism, and beneficial biological activities of honey compounds in human.", "output": "There is no related enetity." }, { "input": "Honey is a supersaturated solution of sugars, mainly composed of fructose ( 38 % ) and glucose ( 31 % ), containing also minerals, proteins, free amino acids, enzymes, vitamins and polyphenols.", "output": "sugars, fructose, glucose, free amino acids, polyphenols." }, { "input": "Among polyphenols, flavonoids are the most abundant and are closely related to its biological functions.", "output": "polyphenols, flavonoids." }, { "input": "Honey positively affects risk factors for cardiovascular diseases by inhibiting inflammation, improving endothelial function, as well as the plasma lipid profile, and increasing low - density lipoprotein resistance to oxidation.", "output": "There is no related enetity." }, { "input": "Honey also displays an important antitumoral capacity, where polyphenols again are considered responsible for its complementary and overlapping mechanisms of chemopreventive activity in multistage carcinogenesis, by inhibiting mutagenesis or inducing apoptosis.", "output": "polyphenols." }, { "input": "Moreover, honey positively modulates the glycemic response by reducing blood glucose, serum fructosamine or glycosylated hemoglobin concentrations and exerts antibacterial properties caused by its consistent amount of hydrogen peroxide and non - peroxide factors as flavonoids, methylglyoxal and defensin - 1 peptide.", "output": "glucose, fructosamine, hydrogen peroxide, peroxide, flavonoids, methylglyoxal." }, { "input": "In conclusion, the evidence of the biological actions of honey can be ascribed to its polyphenolic contents which, in turn, are usually associated to its antioxidant and anti - inflammatory actions, as well as to its cardiovascular, antiproliferative and antimicrobial benefits.", "output": "There is no related enetity." }, { "input": "Enhanced Electrical Conductivity in Poly ( 3 - hexylthiophene ) / Fluorinated Tetracyanoquinodimethane Nanowires Grown with a Porous Alumina Template.", "output": "Poly ( 3 - hexylthiophene ), Fluorinated Tetracyanoquinodimethane, Alumina." }, { "input": "We report on improved electrical conductivity in poly ( 3 - hexylthiophene ) ( P3HT ) / 2, 3, 5, 6 - tetrafluoro - 7, 7, 8, 8 - tetracyanoquinodimethane ( F4 - TCNQ ) composite nanowires grown using an anodized aluminum oxide ( AAO ) template.", "output": "poly ( 3 - hexylthiophene ), P3HT, 2 , 3 , 5 , 6 - tetrafluoro - 7 , 7 , 8 , 8 - tetracyanoquinodimethane, F4 - TCNQ, aluminum oxide." }, { "input": "The electrical conductivity of individual nanowire measured by four - probe scanning tunneling microscopy shows that F4 - TCNQ molecules are effectively doped into P3HT by capillary force.", "output": "F4 - TCNQ, P3HT." }, { "input": "The resistivity is tuned in the 0. 1 - 10 Omega cm range by changing the F4 - TCNQ concentration from 10 to 0. 1 wt % and is 2 - 4 orders of magnitude smaller than that of the corresponding P3HT / F4 - TNCQ thin film composites.", "output": "F4 - TCNQ, P3HT, F4 - TNCQ." }, { "input": "The AAO template - assisted synthesis approach thus appears to be effective for high chemical doping and for improving the electrical conductivity of the molecular wires.", "output": "There is no related enetity." }, { "input": "Timed - release polymer nanoparticles.", "output": "There is no related enetity." }, { "input": "Triggered - release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work.", "output": "There is no related enetity." }, { "input": "Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA.", "output": "There is no related enetity." }, { "input": "The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self - assembly and disassembly.", "output": "There is no related enetity." }, { "input": "At temperatures below the second block ' s LCST ( i. e., below 37 degrees C for in vitro assays ), the diblock copolymer was fully water - soluble, and when heated to 37 degrees C, the polymer self - assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm.", "output": "There is no related enetity." }, { "input": "The thermoresponsive nature of the second block could be manipulated in situ by the self - catalyzed degradation of cationic 2 - ( dimethylamino ) ethyl acrylate ( DMAEA ) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 degrees C.", "output": "2 - ( dimethylamino ) ethyl acrylate, DMAEA, acrylic acid." }, { "input": "The disassembly of the nanoparticles could be controlled from 10 to 70 h.", "output": "There is no related enetity." }, { "input": "The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.", "output": "There is no related enetity." }, { "input": "Advancements in the field of intravaginal siRNA delivery.", "output": "There is no related enetity." }, { "input": "The vaginal tract is a suitable site for the administration of both local and systemic acting drugs.", "output": "There is no related enetity." }, { "input": "There are numerous vaginal products on the market such as those approved for contraception, treatment of yeast infection, hormonal replacement therapy, and feminine hygiene.", "output": "There is no related enetity." }, { "input": "Despite the potential in drug delivery, the vagina is a complex and dynamic organ that requires greater understanding.", "output": "There is no related enetity." }, { "input": "The recent discovery that injections of double stranded RNA ( dsRNA ) in Caenorhabditis elegans ( C. elegans ) results in potent gene specific silencing, was a major scientific revolution.", "output": "There is no related enetity." }, { "input": "This phenomenon known as RNA interference ( RNAi ), is believed to protect host genome against invasion by mobile genetic elements such as transposons and viruses.", "output": "There is no related enetity." }, { "input": "Gene silencing or RNAi has opened new potential opportunities to study the function of a gene in an organism.", "output": "There is no related enetity." }, { "input": "Furthermore, its therapeutic potential is being investigated in the field of sexually transmitted infections such as human immunodeficiency virus ( HIV ) and other diseases such as age - related macular degeneration ( AMD ), diabetes, hypercholesterolemia, respiratory disease, and cancer.", "output": "There is no related enetity." }, { "input": "This review will focus on the therapeutic potential of siRNA for the treatment and / or prevention of infectious diseases such as HIV, HPV, and HSV within the vaginal tract.", "output": "There is no related enetity." }, { "input": "Specifically, formulation design parameters to improve siRNA stability and therapeutic efficacy in the vaginal tract will be discussed along with challenges, advancements, and future directions of the field.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES - 1: use of a conformation - based hypothesis to facilitate compound design.", "output": "benzoxazoles." }, { "input": "Microsomal prostaglandin E ( 2 ) synthase - 1 ( mPGES - 1 ) is a novel therapeutic target for the treatment of inflammation and pain.", "output": "prostaglandin E ( 2 )." }, { "input": "In the preceding letter, we detailed the discovery of clinical candidate PF - 04693627, a potent mPGES - 1 inhibitor possessing a novel benzoxazole structure.", "output": "PF - 04693627, benzoxazole." }, { "input": "While PF - 04693627 was undergoing further preclinical profiling, we sought to identify a back - up mPGES - 1 inhibitor that differentiated itself from PF - 04693627.", "output": "PF - 04693627, PF - 04693627." }, { "input": "The design, synthesis, mPGES - 1 activity and in vivo PK of a novel set of substituted benzoxazoles are described herein.", "output": "benzoxazoles." }, { "input": "Also described is a conformation - based hypothesis for mPGES - 1 activity based on the preferred conformation of the cyclohexane ring within this class of inhibitors.", "output": "cyclohexane." }, { "input": "Effects of asymmetric dimethylarginine on inflammatory cytokines ( TNF - alpha, IL - 6 and IL - 10 ) in rats.", "output": "dimethylarginine." }, { "input": "This study is intended to examine the effects of administration of asymmetric dimethylarginine ( ADMA ) on the levels of tumor necrosis factor - alpha ( TNF - alpha ), interleukin - 6 ( IL - 6 ) and IL - 10.", "output": "dimethylarginine." }, { "input": "A total of 30 Wistar adult albino rats were used.", "output": "There is no related enetity." }, { "input": "Group I was administrated ( n = 10 ) with 1 mg / kg / day of ADMA, group II ( n = 10 ) was administrated with 2 mg / kg / day of ADMA and the control group was administrated ( n = 10 ) with 0. 9 % sodium chloride.", "output": "sodium chloride." }, { "input": "ADMA was intraperitoneally administrated for 7 days.", "output": "There is no related enetity." }, { "input": "The serum levels of IL - 6, TNF - alpha and IL - 10 were measured.", "output": "There is no related enetity." }, { "input": "There was a significant decrease in the levels of TNF - alpha, IL - 6 and IL - 10 in group I compared with that of the control group ( p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "There was also a significant decrease in the levels of IL - 10 in group II compared with that of the control group ( p < 0. 05 ) but the increase was much more distinct in the levels of IL - 6 and TNF - alpha ( p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "When comparing the groups by the doses given, no difference between the levels of IL - 6 and IL - 10 in groups I and II ( p > 0. 05 ) was observed; the levels of TNF - alpha in group II were significantly lower than those of group I ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "A significant decrease in the serum levels of inflammatory cytokines IL - 6, TNF - alpha and IL - 10, after administration of 1 mg / kg / day and 2 mg / kg / day of ADMA, indicates that ADMA has an effect on inflammation.", "output": "There is no related enetity." }, { "input": "Increase in ADMA levels in the rats shows that the effects of inflammatory cytokines were suppressed.", "output": "There is no related enetity." }, { "input": "Protective effect of Lygodium flexuosum ( family: Lygodiaceae ) against excision, incision and dead space wounds models in experimental rats.", "output": "There is no related enetity." }, { "input": "Ethnopharmacological relevance: Lygodium flexuosum ( Linn ) Sw.", "output": "There is no related enetity." }, { "input": "is a climbing fern, and it is the sole genus in the family Lygodiaceae.", "output": "There is no related enetity." }, { "input": "It commonly grows epiphytically on moss covered tree trunks and branches as lithophytes on shady boulders along with moss.", "output": "There is no related enetity." }, { "input": "It has been reported as a traditional folkloric medicine for a variety of ailments particularly useful for carbuncles, inflammation, ulcer, various respiratory diseases, general disorders, muscle sprains and acts as panacea for wounds.", "output": "There is no related enetity." }, { "input": "However, there are no scientific reports on wound healing activity of the plant L. flexuosum ( Linn ) Sw. Aim of the study: To explore the protective effect of L. flexuosum against excision, incision and dead space wounds models in experimental rats.", "output": "There is no related enetity." }, { "input": "METHODS: Wistar albino rats of either sex weighing between 180 and 220 g were topically treated with extract formulated in ointment using simple ointment BP as base.", "output": "There is no related enetity." }, { "input": "Ointments, 4 % and 5 % ( w / w ), were applied once daily in excision wound model.", "output": "There is no related enetity." }, { "input": "L. flexuosum ethanolic extract was given orally at a dose of 100, 200 and 400 mg / kg in incision and dead space wound healing models.", "output": "There is no related enetity." }, { "input": "Rats of standard groups were treated with 0. 2 % nitrofurazone ointment topically.", "output": "nitrofurazone." }, { "input": "The percentage wound contraction, epithelization time in excision wound model; breaking strength in incision wound model and wet and dry granulation weight, hydroxyproline content were measured.", "output": "hydroxyproline." }, { "input": "RESULTS: Topical application of L. flexuosum in excision wound model increased the percentage of wound contraction, and the epithelization time was decreased.", "output": "There is no related enetity." }, { "input": "In the incision wound model, the breaking strength of wounds increased and in dead space model the weight of dry and wet granuloma of wounds and hydroxyproline was increased.", "output": "hydroxyproline." }, { "input": "Conclusively, the data of present study indicated that the leaf extract of L. flexuosum accelerated wound healing in rats and thus supports its traditional use.", "output": "There is no related enetity." }, { "input": "Gender differences in drug bioequivalence: time to rethink practices.", "output": "There is no related enetity." }, { "input": "Currently, bioequivalence ( BE ) studies are carried out exclusively in males, assuming that intrasubject variabilities are similar between the sexes.", "output": "There is no related enetity." }, { "input": "This article challenges this hypothesis on the basis of available evidence and urges that studies of BE of sufficient power be undertaken in women also for all generic drugs aimed at women.", "output": "There is no related enetity." }, { "input": "Spatial modeling for refining and predicting surface potential mapping with enhanced resolution.", "output": "There is no related enetity." }, { "input": "Quantitatively mapping surface properties with nanometer or even subnanometer resolutions is critical for advanced scanning probe microscopy ( SPM ) characterization.", "output": "There is no related enetity." }, { "input": "However, the characterization performance often suffers from noises and artifacts due to instrumentation or environmental limitations.", "output": "There is no related enetity." }, { "input": "In this paper, we proposed a novel statistical approach with bivariate spatial modeling to efficiently refine and predict surface property mapping.", "output": "There is no related enetity." }, { "input": "Scanning Kelvin probe microscopy ( SKPM ) was selected as a representative example to test our proposed method on lateral nanowire assemblies.", "output": "There is no related enetity." }, { "input": "We revealed that the proposed method can effectively retrieve the artifact - free surface potential distribution by automatically identifying topological artifacts from surface potential maps.", "output": "There is no related enetity." }, { "input": "Furthermore, the statistical model built upon low spatial resolution was successfully used to predict the potential values from higher - resolution topography data.", "output": "There is no related enetity." }, { "input": "Compared to conventional regression model, our model is able to predict the surface potential distribution from less raw data but yields much higher accuracy.", "output": "There is no related enetity." }, { "input": "Through this means, the spatial resolution of SKPM surface potential maps can be significantly improved.", "output": "There is no related enetity." }, { "input": "This statistics - enabled predictive method opens a new route toward high - precision and high - resolution SPM characterizations without the enhancement of instrumentation capabilities.", "output": "There is no related enetity." }, { "input": "Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART Body Composition substudy.", "output": "There is no related enetity." }, { "input": "Bone mineral density ( BMD ) declines significantly in HIV patients on antiretroviral therapy ( ART ).", "output": "There is no related enetity." }, { "input": "We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy ( SMART ) trial and determined whether early changes in markers predicted subsequent change in BMD.", "output": "There is no related enetity." }, { "input": "For 202 participants ( median age 44 years, 17 % female, 74 % on ART ) randomised to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline, months 4 and 12; BMD at the spine ( dual X - ray absorptiometry [ DXA ] and computed tomography ) and hip ( DXA ) was evaluated annually.", "output": "There is no related enetity." }, { "input": "Compared to the continuous ART group, mean bone - specific alkaline phosphatase ( bALP ), osteocalcin, procollagen type 1 N - terminal propeptide ( P1NP ), N - terminal cross - linking telopeptide of type 1 collagen ( NTX ), and C - terminal cross - linking telopeptide of type 1 collagen ( beta CTX ) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL: osteoprotegerin ( OPG ) ratio increased ( all p < 0. 002 at month 4 and month 12 ).", "output": "N, N." }, { "input": "Increases in bALP, osteocalcin, P1NP, NTX, and beta CTX at month 4 predicted decrease in hip BMD at month 12, while increases in RANKL and the RANKL: OPG ratio at month 4 predicted increase in hip and spine BMD at month 12.", "output": "There is no related enetity." }, { "input": "This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Influence of rare earth elements on metabolism and related enzyme activity and isozyme expression in Tetrastigma hemsleyanum cell suspension cultures.", "output": "There is no related enetity." }, { "input": "The effects of rare earth elements ( REEs ) not only on cell growth and flavonoid accumulation of Tetrastigma hemsleyanum suspension cells but also on the isoenzyme patterns and activities of related enzymes were studied in this paper.", "output": "flavonoid." }, { "input": "There were no significant differences in enhancement of flavonoid accumulation in T. hemsleyanum suspension cells among La ( 3 + ), Ce ( 3 + ), and Nd ( 3 + ).", "output": "flavonoid, La ( 3 + ), Ce ( 3 + ), Nd ( 3 + )." }, { "input": "Whereas their inductive effects on cell proliferation varied greatly.", "output": "There is no related enetity." }, { "input": "The most significant effects were achieved with 100 mu M Ce ( 3 + ) and Nd ( 3 + ).", "output": "Ce ( 3 + ), Nd ( 3 + )." }, { "input": "Under treatment over a 25 - day culture period, the maximal biomass levels reached 1. 92 - and 1. 74 - fold and the total flavonoid contents are 1. 45 - and 1. 49 - fold, than that of control, respectively.", "output": "flavonoid." }, { "input": "Catalase, phenylalanine ammonia - lyase ( PAL ), and peroxidase ( POD ) activity was activated significantly when the REE concentration range from 0 to 300 mu M, whereas no significant changes were found in superoxide dismutase activity.", "output": "phenylalanine, ammonia, superoxide." }, { "input": "Differences of esterase isozymes under REE treatment only laid in expression level, and there were no specific bands.", "output": "There is no related enetity." }, { "input": "The expression level of some POD isozymes strengthened with increasing concentration of REEs within the range of 50 - 200 mu M.", "output": "There is no related enetity." }, { "input": "When REE concentration was higher than 300 mu M, the expression of some POD isozymes was inhibited; meanwhile, some other new POD isozymes were induced.", "output": "There is no related enetity." }, { "input": "Our results also showed REEs did not directly influence PAL activity.", "output": "There is no related enetity." }, { "input": "So, we speculated that 50 - 200 mu M REEs could activate some of antioxidant enzymes, adjust some isozymes expression, trigger the defense responses of T. hemsleyanum suspension cells, and stimulate flavonoid accumulation by inducing PAL activity.", "output": "There is no related enetity." }, { "input": "Determination of key receptor - ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model.", "output": "arylpiperazines, dopamine." }, { "input": "Interest in structure - based G - protein - coupled receptor ( GPCR ) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds.", "output": "There is no related enetity." }, { "input": "The GPCR family includes the dopamine receptor subtype D2 ( D2DR ), but unfortunately - - as is true of most GPCRs - - no experimental structures are available for these receptors.", "output": "dopamine." }, { "input": "In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor ( D3DR ).", "output": "dopamine." }, { "input": "A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand.", "output": "arylpiperazine." }, { "input": "The observed binding modes and receptor - ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.", "output": "There is no related enetity." }, { "input": "A G protein - biased ligand at the mu - opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine.", "output": "morphine." }, { "input": "The concept of ligand bias at G protein - coupled receptors broadens the possibilities for agonist activities and provides the opportunity to develop safer, more selective therapeutics.", "output": "There is no related enetity." }, { "input": "Morphine pharmacology in beta - arrestin - 2 knockout mice suggested that a ligand that promotes coupling of the mu - opioid receptor ( MOR ) to G proteins, but not beta - arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine.", "output": "Morphine, morphine." }, { "input": "Here we report the discovery of TRV130 ( [ ( 3 - methoxythiophen - 2 - yl ) methyl ] ( { 2 - [ ( 9R ) - 9 - ( pyridin - 2 - yl ) - 6 - oxaspiro [ 4. 5 ] decan - 9 - yl ] ethyl } ) amine ), a novel MOR G protein - biased ligand.", "output": "TRV130, [ ( 3 - methoxythiophen - 2 - yl ) methyl ] ( { 2 - [ ( 9R ) - 9 - ( pyridin - 2 - yl ) - 6 - oxaspiro [ 4 . 5 ] decan - 9 - yl ] ethyl } ) amine." }, { "input": "In cell - based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less beta - arrestin recruitment and receptor internalization.", "output": "TRV130, morphine." }, { "input": "In mice and rats, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses.", "output": "TRV130, morphine." }, { "input": "TRV130 successfully translates evidence that analgesic and adverse MOR signaling pathways are distinct into a biased ligand with differentiated pharmacology.", "output": "TRV130." }, { "input": "These preclinical data suggest that TRV130 may be a safer and more tolerable therapeutic for treating severe pain.", "output": "TRV130." }, { "input": "The Akt DUBbed InAktive.", "output": "There is no related enetity." }, { "input": "Akt is a central node in the phosphoinositide - 3 kinase - Akt - mammalian target of rapamycin pathway and is activated by a multistep process in response to growth factor stimulation.", "output": "rapamycin." }, { "input": "An additional layer of posttranslational modification has emerged as a new paradigm in the regulation of Akt.", "output": "There is no related enetity." }, { "input": "The identification of an E3 ligase for Lys ( 63 ) - linked ubiquitination of Akt has now been complemented with the discovery of the tumor suppressor cylindromatosis as a deubiquitinating enzyme ( DUB ) for Akt.", "output": "Lys." }, { "input": "Thus, like phosphorylation and dephosphorylation, cycles of ubiquitination and deubiquitination provide additional on - off switches that keep Akt activity in balance, and disturbances in this balance have pathological consequences.", "output": "There is no related enetity." }, { "input": "Dye sensitised solar cells with nickel oxide photocathodes prepared via scalable microwave sintering.", "output": "nickel oxide." }, { "input": "Photoactive NiO electrodes for cathodic dye - sensitised solar cells ( p - DSCs ) have been prepared with thicknesses ranging between 0. 4 and 3. 0 mu m by spray - depositing pre - formed NiO nanoparticles on fluorine - doped tin oxide ( FTO ) coated glass substrates.", "output": "NiO, NiO, fluorine, tin oxide, FTO." }, { "input": "The larger thicknesses were obtained in sequential sintering steps using a conventional furnace ( CS ) and a newly developed rapid discharge sintering ( RDS ) method.", "output": "There is no related enetity." }, { "input": "The latter procedure is employed for the first time for the preparation of p - DSCs.", "output": "There is no related enetity." }, { "input": "In particular, RDS represents a scalable procedure that is based on microwave - assisted plasma formation that allows the production in series of mesoporous NiO electrodes with large surface areas for p - type cell photocathodes.", "output": "NiO." }, { "input": "RDS possesses the unique feature of transmitting heat from the bulk of the system towards its outer interfaces with controlled confinement of the heating zone.", "output": "There is no related enetity." }, { "input": "The use of RDS results in a drastic reduction of processing times with respect to other deposition methods that involve heating / calcination steps with associated reduced costs in terms of energy.", "output": "There is no related enetity." }, { "input": "P1 - dye sensitized NiO electrodes obtained via the RDS procedure have been tested in DSC devices and their performances have been analysed and compared with those of cathodic DSCs derived from CS - deposited samples.", "output": "NiO." }, { "input": "The largest conversion efficiencies ( 0. 12 % ) and incident photon - to - current conversion efficiencies, IPCEs ( 50 % ), were obtained with sintered NiO electrodes having thicknesses of ~ 1. 5 - 2. 0 mu m.", "output": "NiO." }, { "input": "In all the devices, the photogenerated holes in NiO live significantly longer ( tau ( h ) ~ 1 s ) than have previously been reported for P1 - sensitized NiO photocathodes.", "output": "NiO, NiO." }, { "input": "In addition, P1 - sensitised sintered electrodes give rise to relatively high photovoltages ( up to 135 mV ) when the triiodide - iodide redox couple is used.", "output": "triiodide, iodide." }, { "input": "Cyanide antidotes for mass casualties: water - soluble salts of the dithiane ( sulfanegen ) from 3 - mercaptopyruvate for intramuscular administration.", "output": "Cyanide, dithiane, sulfanegen, 3 - mercaptopyruvate." }, { "input": "Current cyanide antidotes are administered by IV infusion, which is suboptimal for mass casualties.", "output": "There is no related enetity." }, { "input": "Therefore, in a cyanide disaster, intramuscular ( IM ) injectable antidotes would be more appropriate.", "output": "cyanide." }, { "input": "We report the discovery of the highly water - soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote.", "output": "sulfanegen, triethanolamine, cyanide." }, { "input": "Effects of water concentration on the structural and diffusion properties of imidazolium - based ionic liquid - water mixtures.", "output": "imidazolium." }, { "input": "We have used molecular dynamics simulations to study the properties of three ionic liquid ( IL ) - water systems: 1 - butyl - 3 - methylimidazolium chloride ( [ bmim ] Cl ), 1 - ethyl - 3 - methylimidazolium acetate ( [ emim ] [ Ac ] ), and 1, 3 - dimethylimidazolium dimethylphosphate ( [ dmim ] [ DMP ] ).", "output": "1 - butyl - 3 - methylimidazolium chloride, [ bmim ] Cl, 1 - ethyl - 3 - methylimidazolium acetate, [ emim ] [ Ac ], 1 , 3 - dimethylimidazolium dimethylphosphate, [ dmim ] [ DMP ]." }, { "input": "We observe the transition of those mixtures from pure IL to aqueous solution by analyzing the changes in important bulk properties ( density ) and structural and bonding properties ( radial distribution functions, water clustering, hydrogen bonding, and cationic stacking ) as well as dynamical properties ( diffusion coefficients ) at 12 different concentration samplings of each mixture, ranging from 0. 0 to 99. 95 mol % water.", "output": "There is no related enetity." }, { "input": "Our simulations revealed across all of the different structural, bonding, and dynamical properties major structural changes consistent with a transition from IL - water mixture to aqueous solution in all three ILs at water concentrations around 75 mol %.", "output": "There is no related enetity." }, { "input": "Among the structural changes observed were rapid increase in the frequency of hydrogen bonds, both water - water and water - anion.", "output": "hydrogen." }, { "input": "Similarly, at these critical concentrations, the water clusters formed begin to span the entire simulation box, rather than existing as isolated networks of molecules.", "output": "There is no related enetity." }, { "input": "At the same time, there is a sudden decrease in cationic stacking at the transition point, followed by a rapid increase near 90 mol % water.", "output": "There is no related enetity." }, { "input": "Finally, the diffusion coefficients of individual cations and anions show a rapid transition from rates consistent with diffusion in IL ' s to rates consistent with diffusion in water beginning at 75 mol % water.", "output": "There is no related enetity." }, { "input": "The location of this transition is consistent, for [ bmim ] Cl and [ dmim ] [ DMP ], with the water concentration limit above which the ILs are unable to dissolve cellulose.", "output": "[ bmim ] Cl, [ dmim ] [ DMP ]." }, { "input": "Benzoquinones and terphenyl compounds as phosphodiesterase - 4B inhibitors from a fungus of the order Chaetothyriales ( MSX 47445 ).", "output": "Benzoquinones, terphenyl." }, { "input": "Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales ( MSX 47445 ) using bioactivity - directed fractionation as part of a search for anticancer leads from filamentous fungi.", "output": "There is no related enetity." }, { "input": "Of these, two were benzoquinones [ betulinan A ( 1 ) and betulinan C ( 3 ) ], and the third was a terphenyl compound, BTH - II0204 - 207: A ( 2 ).", "output": "benzoquinones, betulinan A, betulinan C, terphenyl, BTH - II0204 - 207 : A." }, { "input": "The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound ( 3 ) was confirmed via single - crystal X - ray diffraction.", "output": "There is no related enetity." }, { "input": "Compounds 1 - 3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase ( PDE4B2 ) inhibitory activities.", "output": "There is no related enetity." }, { "input": "The putative binding mode of 1 - 3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated.", "output": "There is no related enetity." }, { "input": "Spectral marker for C alpha damage in beta peptides.", "output": "There is no related enetity." }, { "input": "The work in this article describes a spectral signature for the detection of a C ( alpha ) radical damaged peptide, which should enable the use of infrared spectroscopic methods to directly monitor oxidative events.", "output": "There is no related enetity." }, { "input": "Spectra for radical damaged peptides are computed with ab initio methods.", "output": "There is no related enetity." }, { "input": "The amide bands A, I, II, and III are analyzed for trends in the damage site.", "output": "amide." }, { "input": "The spectral signature is found in a region ( i. e., 1700 - 1620 cm ( - 1 ) ) normally void of vibrational absorption bands from stable undamaged beta peptides.", "output": "There is no related enetity." }, { "input": "An analysis of the vibrational motions of the spectral signature is described.", "output": "There is no related enetity." }, { "input": "The uniqueness of the spectral signature is explored by an examination and comparison with C ( alpha ) monoradicals and polyradicals, as well as with other bioradicals that could act as spectral interferences.", "output": "There is no related enetity." }, { "input": "The identification of unique infrared spectral features for C ( alpha ) damage could have important implications in diagnostics for beta conformational peptides damaged by oxidative stress processes.", "output": "There is no related enetity." }, { "input": "Design, synthesis and biological evaluation of novel 7 - mercaptocoumarin derivatives as alpha ( 1 ) - adrenoceptor antagonists.", "output": "7 - mercaptocoumarin." }, { "input": "Study on the pharmacophore model of alpha ( 1 ) - adrenoceptor ( alpha ( 1 ) - AR ) antagonists led to design a series of novel 7 - mercaptocoumarin derivatives as alpha ( 1 ) - AR antagonists.", "output": "7 - mercaptocoumarin." }, { "input": "All designed compounds have been synthesized and biologically evaluated.", "output": "There is no related enetity." }, { "input": "The results showed that most of them exhibited strong antagonistic activity.", "output": "There is no related enetity." }, { "input": "Especially compound 6 showed excellent activity, which was better than that of the reference compound prazosin.", "output": "prazosin." }, { "input": "Structure - activity relationship studies revealed that small hydrophobic group at the terminal heterocyclic ring and ortho substituents on the phenyl ring of phenylpiperazine moiety were the essential structural factors for alpha ( 1 ) - AR antagonistic activity.", "output": "phenylpiperazine." }, { "input": "The pharmacophore modeling studies further clarified their structural contributions to antagonistic activity and also demonstrated that 7 - mercaptocoumarin moiety could be a useful scaffold for design of alpha ( 1 ) - AR antagonists.", "output": "7 - mercaptocoumarin." }, { "input": "Himeic acids E - G, new 4 - pyridone derivatives from a culture of Aspergillus sp.", "output": "Himeic acids E - G, 4 - pyridone." }, { "input": "Three new himeic acids E - G were isolated from a marine - derived fungus, Aspergillus sp., and their structures were determined by spectroscopic analysis.", "output": "himeic acids E - G." }, { "input": "Although himeic acid A inhibited the activity of ubiquitin - activating enzyme ( E1 ), the three new derivatives did not.", "output": "himeic acid A." }, { "input": "Hyaluronan synthase 1 ( HAS1 ) requires higher cellular UDP - GlcNAc concentration than HAS2 and HAS3.", "output": "UDP, GlcNAc." }, { "input": "Mammals have three homologous genes encoding proteins with hyaluronan synthase activity ( Has1 - 3 ), all producing an identical polymer from UDP - N - acetylglucosamine and UDP - glucuronic acid.", "output": "UDP, N - acetylglucosamine, UDP, glucuronic acid." }, { "input": "To compare the properties of these isoenzymes, COS - 1 cells, with minor endogenous hyaluronan synthesis, were transfected with human Has1 - 3 isoenzymes.", "output": "There is no related enetity." }, { "input": "HAS1 was almost unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3.", "output": "There is no related enetity." }, { "input": "This failure of HAS1 to synthesize hyaluronan was compensated by increasing the cellular content of UDP - N - acetyl glucosamine by ~ 10 - fold with 1 mm glucosamine in the growth medium.", "output": "UDP, N - acetyl glucosamine, glucosamine." }, { "input": "Hyaluronan synthesis driven by HAS2 was less affected by glucosamine addition, and HAS3 was not affected at all.", "output": "glucosamine." }, { "input": "Glucose - free medium, leading to depletion of the UDP - sugars, markedly reduced hyaluronan synthesis by all HAS isoenzymes while raising its concentration from 5 to 25 mm had a moderate stimulatory effect.", "output": "Glucose, UDP, sugars." }, { "input": "The results indicate that HAS1 is almost inactive in cells with low UDP - sugar supply, HAS2 activity increases with UDP - sugars, and HAS3 produces hyaluronan at high speed even with minimum substrate content.", "output": "UDP, sugar, UDP, sugars." }, { "input": "Transfected Has2 and particularly Has3 consumed enough UDP - sugars to reduce their content in COS - 1 cells.", "output": "UDP, sugars." }, { "input": "Comparison of different human cell types revealed ~ 50 - fold differences in the content of UDP - N - acetylhexosamines and UDP - glucuronic acid, correlating with the expression level of Has1, suggesting cellular coordination between Has1 expression and the content of UDP - sugars.", "output": "UDP, N - acetylhexosamines, UDP, glucuronic acid, UDP, sugars." }, { "input": "Antihypertensive and metabolic effects of high - dose olmesartan and telmisartan in type 2 diabetes patients with hypertension.", "output": "olmesartan, telmisartan." }, { "input": "We performed a crossover study in hypertensive patients with type 2 diabetes to compare olmesartan ( 40 mg / day ) with telmisartan ( 80 mg / day ) in terms of their antihypertensive and metabolic effects.", "output": "olmesartan, telmisartan." }, { "input": "The subjects were 36 patients ( 20 men and 16 women ) with type 2 diabetes who did not achieve a blood pressure < 130 / 80 mmHg following treatment with olmesartan at 40 mg / day or telmisartan at 80 mg / day for 8 weeks or more.", "output": "olmesartan, telmisartan." }, { "input": "The primary endpoint was the blood pressure reduction rate, while the secondary endpoints were BMI, parameters of glucose metabolism, HMW - adiponectin, hs - CRP and lipids metabolism.", "output": "glucose." }, { "input": "All parameters were measured in Weeks 0, 12, and 24.", "output": "There is no related enetity." }, { "input": "Treatments were switched in Week 0, and Week 12 and the following results were obtained.", "output": "There is no related enetity." }, { "input": "There were 1 ) no significant differences in baseline characteristics; 2 ) no significant difference of the blood pressure reduction rate; 3 ) significant reductions of HbA1c ( NGSP ), FPG and HOMA - IR in olmesartan group; 4 ) a significant increase of HDL - C in olmesartan group; 5 ) a decrease of hs - CRP and a increase of HMW - adiponectin in olmesartan group; and 6 ) a positive correlation between the percent changes of HOMA - IR and hs - CRP in olmesartan group.", "output": "olmesartan, olmesartan, olmesartan, olmesartan." }, { "input": "In conclusion, there was no difference of the blood pressure reduction achieved at the highest dose in olmesartan group and telmisartan group.", "output": "olmesartan, telmisartan." }, { "input": "But improvement of glycemic control and insulin resistance was only observed in olmesartan group.", "output": "olmesartan." }, { "input": "Because there was a correlation between the percent changes of HOMA - IR and hs - CRP, these effects of olmesartan might be mediated by an anti - inflammatory action.", "output": "olmesartan." }, { "input": "Global CNS gene delivery and evasion of anti - AAV - neutralizing antibodies by intrathecal AAV administration in non - human primates.", "output": "There is no related enetity." }, { "input": "Injection of adeno - associated virus ( AAV ) into the cerebrospinal fluid ( CSF ) offers a means to achieve widespread transgene delivery to the central nervous system, where the doses can be readily translated from small to large animals.", "output": "There is no related enetity." }, { "input": "In contrast to studies with other serotypes ( AAV2, AAV4 and AAV5 ) in rodents, we report that a naturally occurring capsid ( AAV9 ) and rationally engineered capsid ( AAV2. 5 ) are able to achieve broad transduction throughout the brain and spinal cord parenchyma following a single injection into the CSF ( via cisterna magna or lumbar cistern ) in non - human primates ( NHP ).", "output": "There is no related enetity." }, { "input": "Using either vector at a dose of ~ 2 x 10 ( 12 ) vector genome ( vg ) per 3 - 6 kg animal, approximately 2 % of the entire brain and spinal cord was transduced, covering all regions of the central nervous system ( CNS ).", "output": "There is no related enetity." }, { "input": "AAV9 in particular displayed efficient transduction of spinal cord motor neurons.", "output": "There is no related enetity." }, { "input": "The peripheral organ biodistribution was highly reduced compared with intravascular delivery, and the presence of circulating anti - AAV - neutralizing antibodies up to a 1: 128 titer had no inhibitory effect on CNS gene transfer.", "output": "There is no related enetity." }, { "input": "Intra - CSF delivery effectively translates from rodents to NHPs, which provides encouragement for the use of this approach in humans to treat motor neuron and lysosomal storage diseases.", "output": "There is no related enetity." }, { "input": "Evaluation of hepatic disposition of paroxetine using sandwich - cultured rat and human hepatocytes.", "output": "paroxetine." }, { "input": "Paroxetine, a selective serotonin reuptake inhibitor, is metabolized in the liver and excreted into bile and urine as metabolites, but species differences have been observed in hepatic disposition between rats and humans.", "output": "Paroxetine." }, { "input": "A major metabolite in rats is M1 - glucuronide, whereas M1 - glucuronide and M1 - sulfate are found in humans.", "output": "sulfate." }, { "input": "The primary excretion route of paroxetine - derived radioactivity in rats and humans is bile and urine, respectively.", "output": "paroxetine." }, { "input": "The aim of this study was to examine the usefulness of sandwich - cultured hepatocytes ( SCH ) to evaluate in vivo species differences of the hepatic disposition of paroxetine between rats and humans.", "output": "paroxetine." }, { "input": "The metabolite profile of [ ( 3 ) H ] paroxetine in SCH was similar to that in hepatocytes in suspension, and the in vitro metabolite profiles were similar to the published in vivo metabolic pathways for both species.", "output": "[ ( 3 ) H ] paroxetine." }, { "input": "Furthermore, the biliary excretion index ( BEI ) of formed M1 - glucuronide in rat SCH ( 25. 8 - 50. 9 % ) was higher than that in human SCH ( 15. 1 - 16. 7 % ).", "output": "There is no related enetity." }, { "input": "The BEI of formed M1 - sulfate ( 16. 4 - 29. 1 % ) was comparable to that of M1 - glucuronide in human SCH, whereas the BEIs of paroxetine were negligible in SCH of both species.", "output": "sulfate, paroxetine." }, { "input": "Moreover, M1 - glucuronide was demonstrated to be a multidrug resistance - associated protein 2 substrate in both species, as determined by its uptake into ATP - binding cassette transporter - expressing membrane vesicles.", "output": "ATP." }, { "input": "SCH should prove to be useful to evaluate the processes of hepatic uptake and metabolism of parent drugs and the simultaneous examination of the biliary excretion of both parent drug and liver - derived metabolites.", "output": "There is no related enetity." }, { "input": "Synthetic strategies for the biotinylation of bioactive small molecules.", "output": "There is no related enetity." }, { "input": "Biotinylation, the functional appendage of a biotin moiety to a bioactive compound ( including small molecules and biological macromolecules ), represents a common technique for identification of the intracellular binding partners that underlie the foundation of observed biological activity.", "output": "biotin." }, { "input": "Introduction of an attachment tether to the framework of a compound of interest must be planned at an early stage of development, and many considerations apply: 1 ) region of attachment, so as not to impede the pharmacophore; 2 ) stability of the parent molecular architecture to biotinylation conditions; 3 ) regioselectivity for the chosen tethering location over other reactive functionalities; 4 ) toxicity of reagents if biotinylation is to be performed in vitro; and 5 ) overall ease of synthesis.", "output": "There is no related enetity." }, { "input": "This review is intended to serve as a guide for the selection of appropriate tethering modalities.", "output": "There is no related enetity." }, { "input": "Examples of the common techniques used to affix biotin, including amide bond formation, [ 3 + 2 ] cycloadditions through \" click \" chemistry, Staudinger ligation, and thioether formation will be discussed, along with analysis of the wider applications of synthetic methodology that have been applied toward the biotinylation of small molecules.", "output": "biotin, amide, thioether." }, { "input": "The marine polyketide myriaporone 3 / 4 stalls translation by targeting the elongation phase.", "output": "myriaporone 3 / 4." }, { "input": "Myriaporone 3 / 4, a cytotoxic polyketide, has been reported as an inhibitor of eukaryotic protein synthesis.", "output": "Myriaporone 3 / 4." }, { "input": "However, the mechanism by which it inhibits translation was unknown.", "output": "There is no related enetity." }, { "input": "Here we show that myriaporone 3 / 4 stalls protein synthesis in the elongation phase by inducing phosphorylation of eukaryotic elongation factor 2.", "output": "myriaporone 3 / 4." }, { "input": "The phosphorylation results from direct binding of myriaporone 3 / 4 to eukaryotic elongation factor 2 kinase.", "output": "myriaporone 3 / 4." }, { "input": "Our study also shows that myriaporone 3 / 4 in the nanomolar range inhibits in vitro tube formation by endothelial cells without being cytotoxic.", "output": "myriaporone 3 / 4." }, { "input": "In general, myriaporone 3 / 4 was at least 300 times less toxic to primary cells than to tumor cells.", "output": "myriaporone 3 / 4." }, { "input": "A Myc - microRNA network promotes exit from quiescence by suppressing the interferon response and cell - cycle arrest genes.", "output": "There is no related enetity." }, { "input": "The transition of mammalian cells from quiescence to proliferation is accompanied by the differential expression of several microRNAs ( miRNAs ) and transcription factors.", "output": "There is no related enetity." }, { "input": "However, the interplay between transcription factors and miRNAs in modulating gene regulatory networks involved in human cell proliferation is largely unknown.", "output": "There is no related enetity." }, { "input": "Here we show that the miRNA miR - 22 promotes proliferation in primary human cells, and through a combination of Argonaute - 2 immunoprecipitation and reporter assays, we identified multiple novel targets of miR - 22, including several cell - cycle arrest genes that mediate the effects of the tumor - suppressor p53.", "output": "There is no related enetity." }, { "input": "In addition, we found that miR - 22 suppresses interferon gene expression by directly targeting high mobility group box - 1 and interferon regulatory factor ( IRF ) - 5, preventing activation of IRF3 and NF - kappa B, which are activators of interferon genes.", "output": "There is no related enetity." }, { "input": "The expression of interferon genes is elevated in quiescent cells and their expression is inhibitory for cell proliferation.", "output": "There is no related enetity." }, { "input": "In addition, we find that miR - 22 is activated by the transcription factor Myc when quiescent cells enter proliferation and that miR - 22 inhibits the Myc transcriptional repressor MXD4, mediating a feed - forward loop to elevate Myc expression levels.", "output": "There is no related enetity." }, { "input": "Our results implicate miR - 22 in downregulating the anti - proliferative p53 and interferon pathways and reveal a new transcription factor - miRNA network that regulates the transition of primary human cells from quiescence to proliferation.", "output": "There is no related enetity." }, { "input": "Space exploration by the promoter of a long human gene during one transcription cycle.", "output": "There is no related enetity." }, { "input": "An RNA polymerase has been thought to transcribe by seeking out a promoter, initiating and then tracking down the template.", "output": "There is no related enetity." }, { "input": "We add tumor necrosis factor alpha to primary human cells, switch on transcription of a 221 - kb gene and monitor promoter position during the ensuing transcription cycle ( using RNA fluorescence in situ hybridization coupled to super - resolution localization, chromosome conformation capture and Monte Carlo simulations ).", "output": "There is no related enetity." }, { "input": "Results are consistent with a polymerase immobilized in a ' factory ' capturing a promoter and reeling in the template, as the transcript and promoter are extruded.", "output": "There is no related enetity." }, { "input": "Initially, the extruded promoter is tethered close to the factory and so likely to re - initiate; later, the tether becomes long enough to allow re - initiation in another factory.", "output": "There is no related enetity." }, { "input": "We suggest close tethering underlies enhancer function and transcriptional ' bursting '.", "output": "There is no related enetity." }, { "input": "Anomalous high mobility in LaAlO3 / SrTiO3 nanowires.", "output": "LaAlO3, SrTiO3." }, { "input": "Nanoscale control of the metal - insulator transition at the interface between LaAlO ( 3 ) and SrTiO ( 3 ) provides a pathway for reconfigurable, oxide - based nanoelectronics.", "output": "LaAlO ( 3 ), SrTiO ( 3 )." }, { "input": "Four - terminal transport measurements of LaAlO ( 3 ) / SrTiO ( 3 ) nanowires at room temperature ( T = 300 K ) reveal an equivalent 2D Hall mobility greatly surpassing that of bulk SrTiO ( 3 ) and approaching that of n - type Si nanowires of comparable dimensions.", "output": "LaAlO ( 3 ), SrTiO ( 3 ), SrTiO ( 3 ), Si." }, { "input": "This large enhancement of mobility is relevant for room - temperature device applications.", "output": "There is no related enetity." }, { "input": "Enhanced redifferentiation of chondrocytes on microperiodic silk / gelatin scaffolds: toward tailor - made tissue engineering.", "output": "There is no related enetity." }, { "input": "Direct - write assembly allows rapid fabrication of complex three - dimensional ( 3D ) architectures, such as scaffolds simulating anatomical shapes, avoiding the need for expensive lithographic masks.", "output": "There is no related enetity." }, { "input": "However, proper selection of polymeric ink composition and tailor - made viscoelastic properties are critically important for smooth deposition of ink and shape retention.", "output": "There is no related enetity." }, { "input": "Deposition of only silk solution leads to frequent clogging due to shear - induced beta - sheet crystallization, whereas optimized viscoelastic property of silk - gelatin blends facilitate the flow of these blends through microcapillary nozzles of varying diameter.", "output": "There is no related enetity." }, { "input": "This study demonstrates that induction of controlled changes in scaffold surface chemistry, by optimizing silk - gelatin ratio, can govern cell proliferation and maintenance of chondrocyte morphology.", "output": "There is no related enetity." }, { "input": "Microperiodic silk - gelatin scaffolds can influence postexpansion redifferentiation of goat chondrocytes by enhancing Sox - 9 gene expression, aggregation, and driving cartilage matrix production, as evidenced by upregulation of collagen type II and aggrecan expression.", "output": "There is no related enetity." }, { "input": "The strategy for optimizing redifferentiation of chondrocytes can offer valuable consideration in scaffold - based cartilage repair strategies.", "output": "There is no related enetity." }, { "input": "Anomalous high ionic conductivity of nanoporous beta - Li3PS4.", "output": "There is no related enetity." }, { "input": "Lithium - ion - conducting solid electrolytes hold promise for enabling high - energy battery chemistries and circumventing safety issues of conventional lithium batteries.", "output": "Lithium, lithium." }, { "input": "Achieving the combination of high ionic conductivity and a broad electrochemical window in solid electrolytes is a grand challenge for the synthesis of battery materials.", "output": "There is no related enetity." }, { "input": "Herein we show an enhancement of the room - temperature lithium - ion conductivity by 3 orders of magnitude through the creation of nanostructured Li ( 3 ) PS ( 4 ).", "output": "lithium, Li ( 3 ) PS ( 4 )." }, { "input": "This material has a wide electrochemical window ( 5 V ) and superior chemical stability against lithium metal.", "output": "lithium." }, { "input": "The nanoporous structure of Li ( 3 ) PS ( 4 ) reconciles two vital effects that enhance the ionic conductivity: ( 1 ) the reduction of the dimensions to a nanometer - sized framework stabilizes the high - conduction beta phase that occurs at elevated temperatures, and ( 2 ) the high surface - to - bulk ratio of nanoporous beta - Li ( 3 ) PS ( 4 ) promotes surface conduction.", "output": "Li ( 3 ) PS ( 4 ), Li ( 3 ) PS ( 4 )." }, { "input": "Manipulating the ionic conductivity of solid electrolytes has far - reaching implications for materials design and synthesis in a broad range of applications, including batteries, fuel cells, sensors, photovoltaic systems, and so forth.", "output": "There is no related enetity." }, { "input": "Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6 - Hydroxy - benzofuran - 5 - carboxylic acid scaffold.", "output": "tyrosine, 6 - Hydroxy - benzofuran - 5 - carboxylic acid." }, { "input": "Mycobacterium tuberculosis ( Mtb ) protein tyrosine phosphatase B ( mPTPB ) is a virulence factor secreted by the pathogen and mediates mycobacterial survival in macrophages by targeting host cell immune responses.", "output": "There is no related enetity." }, { "input": "Consequently, mPTPB represents an exciting new target to combat tuberculosis ( TB ) infection.", "output": "There is no related enetity." }, { "input": "We describe a medicinal chemistry oriented approach that transforms a benzofuran salicylic acid scaffold into a highly potent ( IC ( 50 ) = 38 nM ) and selective mPTPB inhibitor ( > 50 fold against a large panel of PTPs ).", "output": "benzofuran salicylic acid." }, { "input": "Importantly, the inhibitor is capable of reversing the altered host immune responses induced by the bacterial phosphatase and restoring the macrophage ' s full capacity to secrete IL - 6 and undergo apoptosis in response to interferon - gamma stimulation, validating the concept that chemical inhibition of mPTPB may be therapeutically useful for novel TB treatment.", "output": "There is no related enetity." }, { "input": "The study further demonstrates that bicyclic salicylic acid pharmacophores can be used to deliver PTP inhibitors with high potency, selectivity, and cellular efficacy.", "output": "salicylic acid." }, { "input": "Meroterpenoid pigments from the basidiomycete Albatrellus ovinus.", "output": "Meroterpenoid." }, { "input": "Eight grifolin derivatives, involving three new monomers, albatrelins A - C ( 1 - 3 ), three novel dimers ( meroterpenoid pigments ), albatrelins D - F ( 4 - 6 ), and two known ones, 6a, 7, 8, 9, 10, 10a - hexahydro - 3, 6, 9 - trimethyl - 6 - ( 4 - methyl - 3 - penten - 1 - yl ) - 1, 9 - epoxy - 6H - dibenzo [ b, d ] pyran ( 7 ) and confluentin ( 8 ), were isolated from Albatrellus ovinus.", "output": "grifolin, albatrelins A - C, meroterpenoid, albatrelins D - F, 6a , 7 , 8 , 9 , 10 , 10a - hexahydro - 3 , 6 , 9 - trimethyl - 6 - ( 4 - methyl - 3 - penten - 1 - yl ) - 1 , 9 - epoxy - 6H - dibenzo [ b , d ] pyran, confluentin." }, { "input": "Their structures were established by extensive spectroscopic analysis.", "output": "There is no related enetity." }, { "input": "The absolute configurations of compounds 2 - 4 were determined as 9R by comparing their optical rotations with data reported in the literature.", "output": "There is no related enetity." }, { "input": "Albatrelin F ( 6 ) was isolated as a pair of C - 2 ' tautomers with a ratio of 1. 3: 1.", "output": "Albatrelin F." }, { "input": "Confluentin ( 8 ) showed weak cytotoxicity against four human tumor cell lines, HL - 60, SMMC - 7712, A - 549, and MCF - 7, in vitro.", "output": "Confluentin." }, { "input": "Neolignans from leaves of Miliusa mollis.", "output": "Neolignans." }, { "input": "From the leaves of Miliusa mollis Pierre ( Annonaceae ), five new dihydrobenzofuran neolignans, namely miliumollin, 7 - methoxymiliumollin, 3 ' - methoxymiliumollin, 4 ' - O - methylmiliumollin and miliumollinone, and a new 8 - O - 4 ' neolignan named miliusamollin were isolated, and their structures were elucidated through analysis of spectroscopic data.", "output": "dihydrobenzofuran neolignans, miliumollin, 7 - methoxymiliumollin, 3 ' - methoxymiliumollin, 4 ' - O - methylmiliumollin, miliumollinone, 8 - O - 4 ' neolignan, miliusamollin." }, { "input": "Miliumollin, 3 ' - methoxymiliumollin, miliumollinone and decurrenal exhibited weak cytotoxicity against KB, MCF7 and NCI - H187 cells.", "output": "Miliumollin, 3 ' - methoxymiliumollin, miliumollinone." }, { "input": "Miliumollinone possessed weak inhibitory effects against herpes simplex virus types 1 and 2.", "output": "Miliumollinone." }, { "input": "None of the isolates displayed inhibitory activity against avian influenza H5N1 neuraminidase.", "output": "There is no related enetity." }, { "input": "Prophylactic effect of resveratrol against ethinylestradiol - induced liver cholestasis.", "output": "resveratrol, ethinylestradiol." }, { "input": "Estrogens, and particularly glucuronides such as ethinylestradiol ( EE ), have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes.", "output": "Estrogens, ethinylestradiol, bile acid." }, { "input": "The aim of the present article was to investigate anticholestatic activity of resveratrol ( RES ) against liver cholestasis induced by EE in adult female rats.", "output": "resveratrol, RES." }, { "input": "The daily oral administration of the RES at a concentration of 25 mg / kg body weight for 15 days to rats treated with EE ( 100 mu g / kg body weight for 5 days ) resulted in a significant protection against EE - induced decrease in both serum cholesterol and bile acid levels as well as against an increase of serum bilirubin concentration.", "output": "RES, bile acid, bilirubin." }, { "input": "The treatment also resulted in a significant increase in hepatic superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities as well as hepatic protein - bound and nonprotein sulfhydryl groups.", "output": "superoxide, glutathione, glutathione, sulfhydryl." }, { "input": "RES inhibited serum alkaline phosphatase, alanine aminotransferase, pi - glutathione - S - transferase, gamma - glutamyl transpeptidase, and alpha - glutathione - S - transferase activities, as well as reduced serum tumor necrosis factor - alpha, nitric oxide, and hepatic malondialdehyde as compared to EE - treated rats.", "output": "RES, alanine, glutathione, S, glutamyl, glutathione, nitric oxide, malondialdehyde." }, { "input": "The results clearly suggest that RES has a powerful prophylactic action in cholestasis induced by EE.", "output": "RES." }, { "input": "Taken together, RES has potential as a preventive and therapeutic agent for cholestasis and deserves clinical trial in the near future as an adjuvant therapy in women treated with estrogen.", "output": "RES, estrogen." }, { "input": "The first total synthesis and biological evaluation of marine natural products ma ' edamines A and B.", "output": "ma ' edamines A and B." }, { "input": "We have developed the first total syntheses of marine natural products ma ' edamines A ( 18 ) and B ( 20 ).", "output": "ma ' edamines A ( 18 ) and B." }, { "input": "Structurally, they contain a pyrazine - 2 - ( 1H ) - one core and were screened for antiproliferative activity on several cancer cell lines.", "output": "pyrazine - 2 - ( 1H ) - one." }, { "input": "Out of the six cell lines tested, ma ' edamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 ( IC ( 50 ) 7. 9 and 10. 3 mu M, respectively ), breast cancer cell line MCF - 7 ( IC ( 50 ): 6. 9 and 10. 5 mu M, respectively ) and human lung adenocarcinoma cell line A549 ( IC ( 50 ): 12. 2 and 15. 4 mu M, respectively ).", "output": "ma ' edamines A and B." }, { "input": "The apoptotic effect of ma ' edamines was confirmed by comet assay.", "output": "ma ' edamines." }, { "input": "Hence ma ' edamines are likely to be useful as leads for development of a new class of anti - cancer agents.", "output": "ma ' edamines." }, { "input": "Chemical synthesis, docking studies and biological effects of a pan peroxisome proliferator - activated receptor agonist and cyclooxygenase inhibitor.", "output": "There is no related enetity." }, { "input": "The compound ( 5Z ) - 5 - [ ( 5 - bromo - 1H - indol - 3 - yl ) methylene ] - 3 - ( 4 - chlorobenzyl ) - thiazolidine - 2, 4 - dione ( LYSO - 7 ) was synthesised in order to obtain a new type of anti - inflammatory drug, designed with hybrid features to inhibit cyclooxygenase ( COX ) and also to activate peroxisome proliferator - activated receptor ( PPAR ).", "output": "( 5Z ) - 5 - [ ( 5 - bromo - 1H - indol - 3 - yl ) methylene ] - 3 - ( 4 - chlorobenzyl ) - thiazolidine - 2 , 4 - dione, LYSO - 7." }, { "input": "Results obtained from docking ( in silico ) studies corroborated with experimental data, showing the potential affinity between the studied ligand and targets.", "output": "There is no related enetity." }, { "input": "The specificity of LYSO - 7 for COX - enzymes was detected by the inhibition of COX - 1 and COX - 2 activities by 30 % and 20 %, respectively.", "output": "LYSO - 7." }, { "input": "In transactivation reporter gene assays LYSO - 07 showed a pan partial agonist effect on the three PPAR subtypes ( PPAR gamma, PPAR alpha and PPAR beta / delta ).", "output": "LYSO - 07." }, { "input": "The agonist action on PPAR gamma was also observed by a pharmacological approach, as the reduction in the Escherichia coli lipopolysaccharide ( LPS ) - induced interleukin 1 beta ( IL - 1 beta ) secretion and nitric oxide ( NO ) production by mouse neutrophils was blocked by GW9962, a specific PPAR gamma antagonist.", "output": "nitric oxide, NO, GW9962." }, { "input": "Additionally, the in vivo effect was measured by reduced carrageenan - induced neutrophil influx into the subcutaneous tissue of mice.", "output": "There is no related enetity." }, { "input": "Taken together, these data show that LYSO - 7 displays a potent in vivo anti - inflammatory effect during the innate acute response, which is dependent on its associated COX inhibitory activities and PPAR activation.", "output": "LYSO - 7." }, { "input": "A new spatane diterpenoid from the cultured soft coral Sinularia leptoclados.", "output": "spatane, diterpenoid." }, { "input": "A new spatane diterpenoid, leptoclalin A ( 1 ), along with two previously reported known norcembranoid diterpenes ( 2 and 3 ), were isolated from a cultured soft coral Sinularia leptoclados.", "output": "spatane, diterpenoid, leptoclalin A, norcembranoid, diterpenes." }, { "input": "The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds.", "output": "There is no related enetity." }, { "input": "Metabolite 1 is rarely found in spatane skeletons reported from soft corals.", "output": "There is no related enetity." }, { "input": "In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T - 47 D and K - 562.", "output": "There is no related enetity." }, { "input": "Antibacterial polyketides from the marine alga - derived endophitic Streptomyces sundarbansensis: a study on hydroxypyrone tautomerism.", "output": "hydroxypyrone." }, { "input": "Polyketide 13 [ = 2 - hydroxy - 5 - ( ( 6 - hydroxy - 4 - oxo - 4H - pyran - 2 - yl ) methyl ) - 2 - propylchroman - 4 - one ] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp.", "output": "2 - hydroxy - 5 - ( ( 6 - hydroxy - 4 - oxo - 4H - pyran - 2 - yl ) methyl ) - 2 - propylchroman - 4 - one." }, { "input": "Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation.", "output": "There is no related enetity." }, { "input": "Due to tautomeric equilibrium, 13 in CD ( 3 ) OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI - MS / MS analysis.", "output": "CD ( 3 ) OD, deuterium." }, { "input": "The 2 - hydroxy - gamma - pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4 - hydroxy - alpha - pyrone and 2 - hydroxy - gamma - pyrone forms.", "output": "2 - hydroxy - gamma - pyrone, 4 - hydroxy - alpha - pyrone, 2 - hydroxy - gamma - pyrone." }, { "input": "During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin - resistant S. aureus ( MRSA, MIC = 6 mu Mu ), with a bacteriostatic effect.", "output": "methicillin." }, { "input": "Verrucarin A enhances TRAIL - induced apoptosis via NF - kappa B - mediated Fas overexpression.", "output": "Verrucarin A." }, { "input": "We investigated whether verrucarin A ( VA ) sensitizes HepG2 hepatoma cells to tumor necrosis factor - related apoptosis inducing ligand ( TRAIL ) - mediated apoptosis.", "output": "verrucarin A." }, { "input": "We found that VA alone induces little apoptosis, but when combined with TRAIL ( VA / TRAIL ), it triggered significant apoptosis, causing little or no toxicity in normal mouse splenocytes.", "output": "There is no related enetity." }, { "input": "VA / TRAIL - induced cell death is involved in the loss of mitochondrial transmembrane potential and the consequent activation of caspases.", "output": "There is no related enetity." }, { "input": "Because nuclear factor ( NF ) - kappa B inhibition has been known as a critical target in TRAIL - mediated apoptosis, we also investigated the role of NF - kappa B in VA / TRAIL treatment.", "output": "There is no related enetity." }, { "input": "We found that VA upregulated the DNA binding activity of NF - kappa B, but that the antioxidants glutathione and N - acetyl - l - cysteine, as well as NF - kappa B inhibitor MG132, and mutant - I kappa B ( m - I kappa B ) transfection, significantly downregulated VA / TRAIL - induced cell death by inhibiting caspase - 3 and NF - kappa B activities.", "output": "glutathione, N - acetyl - l - cysteine, MG132." }, { "input": "Transfection of mutant - eIF2 alpha also resulted in a decrease in VA / TRAIL - induced cell death by inhibiting of caspase - 3, but not NF - kappa B activity.", "output": "There is no related enetity." }, { "input": "Although VA / TRAIL treatment led to an increase of DR5 expression, transfection of m - I kappa B had no influence on the DR5 expressional level.", "output": "There is no related enetity." }, { "input": "Finally, we showed that NF - kappa B - mediated Fas expression is critical to VA / TRAIL - induced apoptosis.", "output": "There is no related enetity." }, { "input": "Taken together, these results indicate that VA / TRAIL sensitizes HepG2 cells to apoptosis via NF - kappa B - mediated overexpression of Fas.", "output": "There is no related enetity." }, { "input": "Polyethylene glycol - g - polyvinyl alcohol grafted copolymer: Reproductive toxicity study in Wistar rats.", "output": "Polyethylene glycol, polyvinyl alcohol." }, { "input": "Polyethylene glycol - g - polyvinyl alcohol ( PEG - PVA ) grafted copolymer was administered by gavage to groups of 25 male and 25 female young Wistar rats at doses of 0 ( vehicle control ), 100, 300, or 1000mg / kg bw / day for one generation ( F0 ).", "output": "Polyethylene glycol, polyvinyl alcohol, PEG - PVA." }, { "input": "The study followed the treated F0 generation through mating, gestation, lactation, and weaning of the F1 generation.", "output": "There is no related enetity." }, { "input": "F1 animals were mated and followed to gestation day ( GD ) 15 - 17 at which time F2 implants were evaluated.", "output": "There is no related enetity." }, { "input": "There were no indications from the various clinical and gross pathological examinations that the oral administration of PEG - PVA grafted copolymer to the F0 - parental rats produced any signs of general, reproductive, or developmental toxicity in the F0 or F1 animals or F2 implants.", "output": "PEG - PVA." }, { "input": "Based on the lack of any dose - related or biologically relevant effects on fertility, reproduction, development, and overall health of rats gavaged with PEG - PVA grafted copolymer and their progeny, the no - observed - adverse effect level ( NOAEL ) was determined to be the highest dose tested of 1000mg / kg bw / day.", "output": "PEG - PVA." }, { "input": "Protease - activated receptor ( PAR ) 1 and PAR4 differentially regulate factor V expression from human platelets.", "output": "There is no related enetity." }, { "input": "With the recent interest of protease - activated receptors ( PAR ) 1 and PAR4 as possible targets for the treatment of thrombotic disorders, we compared the efficacy of protease - activated receptor ( PAR ) 1 and PAR4 in the generation of procoagulant phenotypes on platelet membranes.", "output": "There is no related enetity." }, { "input": "PAR4 - activating peptide ( AP ) - stimulated platelets promoted thrombin generation in plasma up to 5 minutes earlier than PAR1 - AP - stimulated platelets.", "output": "There is no related enetity." }, { "input": "PAR4 - AP - mediated factor V ( FV ) association with the platelet surface was 1. 6 - fold greater than for PAR1 - AP.", "output": "There is no related enetity." }, { "input": "Moreover, PAR4 stimulation resulted in a 3 - fold greater release of microparticles, compared with PAR1 stimulation.", "output": "There is no related enetity." }, { "input": "More robust FV secretion and microparticle generation with PAR4 - AP was attributable to stronger and more sustained phosphorylation of myosin light chain at serine 19 and threonine 18.", "output": "serine, threonine." }, { "input": "Inhibition of Rho - kinase reduced PAR4 - AP - mediated FV secretion and microparticle generation to PAR1 - AP - mediated levels.", "output": "There is no related enetity." }, { "input": "Thrombin generation assays measuring prothrombinase complex activity demonstrated 1. 5 - fold higher peak thrombin levels on PAR4 - AP - stimulated platelets, compared with PAR1 - AP - stimulated platelets.", "output": "There is no related enetity." }, { "input": "Rho - kinase inhibition reduced PAR4 - AP - mediated peak thrombin generation by 25 % but had no significant effect on PAR1 - AP - mediated thrombin generation.", "output": "There is no related enetity." }, { "input": "In conclusion, stimulation of PAR4 on platelets leads to faster and more robust thrombin generation, compared with PAR1 stimulation.", "output": "There is no related enetity." }, { "input": "The greater procoagulant potential is related to more efficient FV release from intracellular stores and microparticle production driven by stronger and more sustained myosin light chain phosphorylation.", "output": "There is no related enetity." }, { "input": "These data have implications about the role of PAR4 during hemostasis and are clinically relevant in light of recent efforts to develop PAR antagonists to treat thrombotic disorders.", "output": "There is no related enetity." }, { "input": "Natalizumab therapy for multiple sclerosis.", "output": "There is no related enetity." }, { "input": "The treatment of relapsing remitting multiple sclerosis has witnessed major progress since the first effective disease modifying treatment, beta - interferon, became available in 1993.", "output": "There is no related enetity." }, { "input": "One of the most remarkable new treatments has been natalizumab.", "output": "There is no related enetity." }, { "input": "This review describes the evolution of this humanized anti - alpha 4 beta 1 monoclonal antibody, from preclinical experimental research through proof - of - concept ( phase 1 / 2 ) and pivotal ( phase 3 ) clinical trials to the now extensive experience of its use in clinical practice.", "output": "There is no related enetity." }, { "input": "The future potential and challenges of natalizumab and oral therapies with a similar mechanism of action are also discussed.", "output": "There is no related enetity." }, { "input": "Ambulatory blood pressure monitoring: recent evidence and clinical pharmacy applications.", "output": "There is no related enetity." }, { "input": "Conventional office blood pressure readings are a well - established surrogate for the prediction of cardiovascular risk.", "output": "There is no related enetity." }, { "input": "It is assumed that these readings reflect an underlying average level of blood pressure exposure occurring in an individual over a period of time.", "output": "There is no related enetity." }, { "input": "But because blood pressure is not static, important additional prognostic information about the diurnal blood pressure profile, including within - day and between - day variability, is not easily ascertained from conventional measurements.", "output": "There is no related enetity." }, { "input": "Ambulatory blood pressure monitoring provides a more thorough depiction of the underlying blood pressure level and predicts cardiovascular risk more robustly than do conventional blood pressure measurements.", "output": "There is no related enetity." }, { "input": "Although the technology has been available for more than 30 years, there has been an expansion of the research base in the past decade supporting its role in the evaluation and management of patients with hypertension and as an important surrogate in research trials.", "output": "There is no related enetity." }, { "input": "This review summarizes recent evidence supporting the predictive ability of ambulatory blood pressure monitoring and briefly highlights opportunities for clinical pharmacists to adopt this important clinical and research tool.", "output": "There is no related enetity." }, { "input": "Improper Selection of a Pre - specified Primary Dose - Response Analysis Delays Regulatory Drug Approval.", "output": "There is no related enetity." }, { "input": "Dose - response analysis is one of the accepted efficacy endpoints to establish effectiveness.", "output": "There is no related enetity." }, { "input": "The purpose of this research was to inform selection of an appropriate pre - specified primary dose - response analysis to demonstrate drug efficacy in a registration trial.", "output": "There is no related enetity." }, { "input": "The power and the type I error rate of the placebo - corrected ( i. e., simply adjusting the observed treatment value by subtracting the placebo mean ) and the placebo - anchored ( i. e., including the placebo data as dose 0 in the regression ) slope analyses were assessed based on regulatory submission data for two antihypertensive drugs and simulated data from hypothetical clinical trials.", "output": "There is no related enetity." }, { "input": "In the simulated hypothetical trials, the impact of different dosing strategies ( i. e., the fixed dose versus the weight - based per kilogram dose ), sample size, and scenarios governing the drug exposure - response relationship ( e. g., E max, ED 50, and SD ) was also evaluated.", "output": "There is no related enetity." }, { "input": "For each scenario, a total 300 replications were simulated.", "output": "There is no related enetity." }, { "input": "The placebo - anchored slope analysis is always more powerful to demonstrate effectiveness in all plausible scenarios.", "output": "There is no related enetity." }, { "input": "The difference between the placebo - anchored and the placebo - corrected analyses was maximum when the studied doses were too high.", "output": "There is no related enetity." }, { "input": "However, the dose - response analysis is not sensitive to the dosing strategies.", "output": "There is no related enetity." }, { "input": "Furthermore, the type I error rate of these two methods was also found to be comparable.", "output": "There is no related enetity." }, { "input": "The design of dose - response studies should carefully consider these results to justify the inclusion of placebo and the analysis method.", "output": "There is no related enetity." }, { "input": "The pharmaceutical industry and the regulatory agencies are equally responsible for using the appropriate methods of primary analysis and providing justification in the protocol.", "output": "There is no related enetity." }, { "input": "Fueling open - source drug discovery: 177 small - molecule leads against tuberculosis.", "output": "There is no related enetity." }, { "input": "With the aim of fuelling open - source, translational, early - stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible.", "output": "There is no related enetity." }, { "input": "A set of 177 potent non - cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics / proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead - generation activities.", "output": "There is no related enetity." }, { "input": "Two additional drug - discovery - relevant datasets are included: a ) a drug - like property analysis reflecting the latest lead - like guidelines and b ) an early lead - generation package of the most promising hits within the clusters identified.", "output": "There is no related enetity." }, { "input": "Calorie - restricted weight loss reverses high - fat diet - induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin - dependent manner.", "output": "There is no related enetity." }, { "input": "Twelve weeks of high - fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y ( NPY ) / agouti - related protein ( AgRP ) neurons.", "output": "There is no related enetity." }, { "input": "In the current study, we investigated whether diet - induced weight loss could restore NPY / AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie - restricted ( CR ) weight loss.", "output": "There is no related enetity." }, { "input": "Diet - induced obese ( DIO ) mice were allocated to one of two dietary interventions until they reached the weight of age - matched lean controls.", "output": "There is no related enetity." }, { "input": "DIO mice received chow diet ad libitum or chow diet with 40 % CR.", "output": "There is no related enetity." }, { "input": "Chow - fed and high - fat - fed mice served as controls.", "output": "There is no related enetity." }, { "input": "Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin.", "output": "glucose." }, { "input": "We show that diet - induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression.", "output": "There is no related enetity." }, { "input": "We propose that long - term DIO creates a higher body weight set - point and that weight loss induced by CR, as seen in the high - fat CR group, provokes the brain to protect the new higher set - point.", "output": "There is no related enetity." }, { "input": "This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin - responsive neuronal populations in the hypothalamic arcuate nucleus.", "output": "There is no related enetity." }, { "input": "Indeed, we also show that DIO ghrelin - knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild - type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.", "output": "There is no related enetity." }, { "input": "Loss and gain of Drosophila TDP - 43 impair synaptic efficacy and motor control leading to age - related neurodegeneration by loss - of - function phenotypes.", "output": "There is no related enetity." }, { "input": "Cytoplasmic accumulation and nuclear clearance of TDP - 43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP - 43 function, or both, cause disease formation.", "output": "There is no related enetity." }, { "input": "Here we have systematically compared loss - and gain - of - function of Drosophila TDP - 43, TAR DNA Binding Protein Homolog ( TBPH ), in synaptic function and morphology, motor control, and age - related neuronal survival.", "output": "There is no related enetity." }, { "input": "Both loss and gain of TBPH severely affect development and result in premature lethality.", "output": "There is no related enetity." }, { "input": "TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction ( NMJ ) and in the adult.", "output": "There is no related enetity." }, { "input": "Tissue - specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre - synaptic efficacy, suggesting that impaired pre - synaptic transmission is one of the earliest events in TDP - 43 - related pathogenesis.", "output": "There is no related enetity." }, { "input": "Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age - related, progressive degeneration of neurons involved in motor control.", "output": "There is no related enetity." }, { "input": "Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant - negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH.", "output": "There is no related enetity." }, { "input": "Together these data suggest that dysfunction of Drosophila TDP - 43 triggers a cascade of events leading to loss - of - function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age - related neurodegeneration.", "output": "There is no related enetity." }, { "input": "Characterization of bundled and individual triple - walled carbon nanotubes by resonant Raman spectroscopy.", "output": "carbon." }, { "input": "The optical characterization of bundled and individual triple - walled carbon nanotubes was studied for the first time in detail by using resonant Raman spectroscopy.", "output": "carbon." }, { "input": "In our approach, the outer tube of a triple - walled carbon nanotube system protects the two inner tubes ( or equivalently the inner double - walled carbon nanotube ) from external environment interactions making them a partially isolated system.", "output": "carbon, carbon." }, { "input": "Following the spectral changes and line - widths of the radial breathing modes and G - band by performing laser energy dependent Raman spectroscopy, it is possible to extract important information as regards to the electronic and vibrational properties, tube diameters, wall - to - wall distances, radial breathing mode, and G - band resonance evolutions as well as high - curvature intertube interactions in isolated double - and triple - walled carbon nanotube systems.", "output": "carbon." }, { "input": "Time - resolved single molecule fluorescence spectroscopy of an alpha - chymotrypsin catalyzed reaction.", "output": "There is no related enetity." }, { "input": "Single molecule fluorescence spectroscopy offers great potential for studying enzyme kinetics.", "output": "There is no related enetity." }, { "input": "A number of fluorescence reporter systems allow for monitoring the sequence of individual reaction events with a confocal microscope.", "output": "There is no related enetity." }, { "input": "When using a time - correlated single photon counting ( TCSPC ) detection scheme, additional information about the fluorescence lifetimes of the fluorophores can be obtained.", "output": "There is no related enetity." }, { "input": "We have applied a TCSPC detection scheme for studying the kinetics of alpha - chymotrypsin hydrolyzing a double - substituted rhodamine 110 - based fluorogenic substrate in a two - step reaction.", "output": "There is no related enetity." }, { "input": "On the basis of the lifetime information, it was possible to discriminate the intermediate and the final product.", "output": "There is no related enetity." }, { "input": "At the high substrate concentration used, only the formation of the intermediate was observed.", "output": "There is no related enetity." }, { "input": "No rebinding of the intermediate followed by rhodamine 110 formation occurred at these high concentrations.", "output": "There is no related enetity." }, { "input": "We have further found no alterations in the fluorescence lifetime of this intermediate that would indicate changes in the local environment of the fluorophore originating from strong interactions with the enzyme.", "output": "There is no related enetity." }, { "input": "Our results clearly show the power of using lifetime - resolved measurements for investigating enzymatic reactions at the single molecule level.", "output": "There is no related enetity." }, { "input": "Poorly differentiated thyroid carcinoma presenting with gross extrathyroidal extension: 1986 - 2009 Memorial Sloan - Kettering Cancer Center experience.", "output": "There is no related enetity." }, { "input": "To describe the outcome of patients with poorly differentiated thyroid cancer ( PDTC ) presenting with gross extrathyroidal extension ( ETE ).", "output": "There is no related enetity." }, { "input": "After IRB approval we performed retrospective review of consecutive series of thyroid cancer patients treated by primary surgical resection with or without adjuvant therapy at MSKCC from 1986 - 2009.", "output": "There is no related enetity." }, { "input": "Out of 91 PDTC patients, 27 ( 30 % ) had gross ETE ( T4a ) and they formed the basis of our study.", "output": "There is no related enetity." }, { "input": "Of 27 patients, 52 % were female.", "output": "There is no related enetity." }, { "input": "The median age was 70 ( range 27 - 87 ).", "output": "There is no related enetity." }, { "input": "Ten patients ( 37 % ) presented with distant metastases; four to the bone, three to lung and three had both bone and lung metastases.", "output": "There is no related enetity." }, { "input": "All patients had extended total thyroidectomy except two who had subtotal thyroidectomy.", "output": "There is no related enetity." }, { "input": "20 patients ( 74 % ) had central compartment neck dissection and 11 also had lateral neck dissection.", "output": "There is no related enetity." }, { "input": "Four patients had pN0, 6 ( 30 % ) pN1a and 10 ( 50 % ) pN1b neck disease.", "output": "There is no related enetity." }, { "input": "21 patients ( 77 % ) had adjuvant therapy: 15 ( 55 % ) RAI only, 3 ( 11 % ) postoperative external beam radiation ( PORT ) only and 3 ( 11 % ) had both RAI and PORT.", "output": "RAI, RAI." }, { "input": "Overall survival ( OS ), disease specific survival ( DSS ), local recurrence free survival ( LRFS ) and regional recurrence free survival ( RRFS ) were calculated by the Kaplan Meier method.", "output": "There is no related enetity." }, { "input": "Median follow - up time was 57 months ( range 1 - 197 months ).", "output": "There is no related enetity." }, { "input": "The 5 year OS and DSS were 47 % and 49 % respectively.", "output": "There is no related enetity." }, { "input": "This poor outcome was due to distant metastatic disease; 10 patients had distant metastases at presentation and a further 6 developed distant metastases during follow up.", "output": "There is no related enetity." }, { "input": "Locoregional control was good with 5 year LRFS and RRFS of 70 % and 62 % respectively.", "output": "There is no related enetity." }, { "input": "Overall, 8 patients ( 30 % ) had recurrences: 2 had distant alone, 2 regional, 2 regional and distant, 1 local and distant, and 1 had local, regional and distant recurrence.", "output": "There is no related enetity." }, { "input": "Aggressive surgery in patients with PDTC showing gross ETE resulted in satisfactory locoregional control.", "output": "There is no related enetity." }, { "input": "Due to the small proportion of patients who received PORT ( 22 % ), it is not possible to analyze its benefit on locoregional control.", "output": "There is no related enetity." }, { "input": "Of significance is the observation that the majority of patients ( 60 % ) who presented with or subsequently developed distant metastases eventually died of distant disease.", "output": "There is no related enetity." }, { "input": "New systemic therapies to target distant metastatic disease are required for improvements in outcome.", "output": "There is no related enetity." }, { "input": "Phase boundaries, structural characteristics, and NMR spectra of ionic liquid - in - oil microemulsions containing double chain surface active ionic liquid: a comparative study.", "output": "There is no related enetity." }, { "input": "A method developed for the first time, to create a huge number of ionic liquid ( IL ) - in - oil microemulsions has been discussed in our earlier publication ( Rao, V. G.; Ghosh, S.; Ghatak, C.; Mandal, S.; Brahmachari, U.; Sarkar, N. J. Phys. Chem. B 2012, 116, 2850 - 2855 ).", "output": "There is no related enetity." }, { "input": "Here, we present facile methods to adjust the structural parameters of microemulsions using different ionic liquids ( ILs ) as additives ( polar phase ).", "output": "There is no related enetity." }, { "input": "We have characterized ILs / [ C ( 4 ) mim ] [ AOT ] / benzene ternary system by performing a phase behavior study, dynamic light scattering ( DLS ) measurements, and ( 1 ) H NMR measurements.", "output": "[ C ( 4 ) mim ] [ AOT ], benzene, ( 1 ) H." }, { "input": "The IL loading capacity of microemulsions ( area of single phase region ) ( i ) increases with increase in alkyl chain length of cation of ILs and follows the trend [ C ( 6 ) mim ] [ TF ( 2 ) N ] > [ C ( 4 ) mim ] [ TF ( 2 ) N ] > [ C ( 2 ) mim ] [ TF ( 2 ) N ], ( ii ) increases with decrease in cation anion interaction strength of added ILs and follows the trend [ C ( 4 ) mim ] [ TF ( 2 ) N ] > [ C ( 4 ) mim ] [ PF ( 6 ) ] > [ C ( 4 ) mim ] [ BF ( 4 ) ].", "output": "[ C ( 6 ) mim ] [ TF ( 2 ) N ], [ C ( 4 ) mim ] [ TF ( 2 ) N ], [ C ( 2 ) mim ] [ TF ( 2 ) N ], [ C ( 4 ) mim ] [ TF ( 2 ) N ], [ C ( 4 ) mim ] [ PF ( 6 ) ], [ C ( 4 ) mim ] [ BF ( 4 ) ]." }, { "input": "So depending on the IL used, the amount of IL within the core of microemulsions can be easily manipulated to directly affect the size of aggregates in microemulsions.", "output": "There is no related enetity." }, { "input": "The size increase with increasing R value ( R value is defined as the molar ratio of RTILs to [ C ( 4 ) mim ] [ AOT ] ) was found to be maximum in the case of [ C ( 2 ) mim ] [ TF ( 2 ) N ] / [ C ( 4 ) mim ] [ AOT ] / benzene microemulsions and follows the trend [ C ( 2 ) mim ] [ TF ( 2 ) N ] > [ C ( 4 ) mim ] [ TF ( 2 ) N ] > [ C ( 6 ) mim ] [ TF ( 2 ) N ].", "output": "[ C ( 4 ) mim ] [ AOT ], [ C ( 2 ) mim ] [ TF ( 2 ) N ], [ C ( 4 ) mim ] [ AOT ], benzene, [ C ( 2 ) mim ] [ TF ( 2 ) N ], [ C ( 4 ) mim ] [ TF ( 2 ) N ], [ C ( 6 ) mim ] [ TF ( 2 ) N ]." }, { "input": "However, the size increase was almost the same with increase in R value in the case of ILs with different anions.", "output": "There is no related enetity." }, { "input": "The most promising fact about IL - in - oil microemulsions is their high thermal stability compared to that of aqueous microemulsions, so we investigated the effect of temperature on size of aggregates in microemulsions at R = 1. 0.", "output": "There is no related enetity." }, { "input": "It is evident from dynamic light scattering measurements that the aggregates in microemulsions remain monodisperse in nature with increasing temperature, and in all the cases, the size of aggregates in microemulsions decreases with increasing temperature.", "output": "There is no related enetity." }, { "input": "The effect of water addition on IL - in - oil ( IL / O ) microemulsions was also studied in detail.", "output": "There is no related enetity." }, { "input": "By far, this is the first report where the effect of water addition on microemulsions containing hydrophobic ILs is being reported and compared with microemulsions containing hydrophilic ILs.", "output": "There is no related enetity." }, { "input": "We observed that the added water has a prominent effect on the microstructure of the microemulsions.", "output": "There is no related enetity." }, { "input": "In all the cases, ( 1 ) H NMR spectra provide more detailed information about intra / intermolecular interactions thus affording a clear picture of locations of ( i ) the RTILs in RTILs / [ C ( 4 ) mim ] [ AOT ] / benzene microemulsions and ( ii ) the added water molecules in microemulsions.", "output": "( 1 ) H, [ C ( 4 ) mim ] [ AOT ], benzene." }, { "input": "Cucumber - like V2O5 / poly ( 3, 4 - ethylenedioxythiophene ) & MnO2 nanowires with enhanced electrochemical cyclability.", "output": "V2O5, poly ( 3 , 4 - ethylenedioxythiophene ), MnO2." }, { "input": "Inspired by the cucumber - like structure, by combining the in situ chemical oxidative polymerization with facile soaking process, we designed the heterostructured nanomaterial with PEDOT as the shell and MnO ( 2 ) nanoparticles as the protuberance and synthesized the novel cucumber - like MnO ( 2 ) nanoparticles enriched vanadium pentoxide / poly ( 3, 4 - ethylenedioxythiophene ) ( PEDOT ) coaxial nanowires.", "output": "PEDOT, MnO ( 2 ), MnO ( 2 ), vanadium pentoxide, poly ( 3 , 4 - ethylenedioxythiophene ), PEDOT." }, { "input": "This heterostructured nanomaterial exhibits enhanced electrochemical cycling performance with the decreases of capacity fading during 200 cycles from 0. 557 to 0. 173 % over V ( 2 ) O ( 5 ) nanowires at the current density of 100 mA / g.", "output": "V ( 2 ) O ( 5 )." }, { "input": "This method is proven to be an effective technique for improving the electrochemical cycling performance and stability of nanowire electrodes especially at low rate for application in rechargeable lithium batteries.", "output": "lithium." }, { "input": "Damned if you do, damned if you don ' t: the conundrum of adipose tissue vascularization.", "output": "There is no related enetity." }, { "input": "The plasticity of adipose tissue requires highly regulated changes in accompanying blood vessels.", "output": "There is no related enetity." }, { "input": "In obesity, adipose tissue angiogenesis plays a complex role to support tissue growth and promote metabolic disease.", "output": "There is no related enetity." }, { "input": "Emerging research ( Sung et al., 2013 ) indicates that exploiting the mediators of adipose tissue angiogenesis may offer the possibility for therapeutic interventions.", "output": "There is no related enetity." }, { "input": "Vascular complications of diabetes: mechanisms of injury and protective factors.", "output": "There is no related enetity." }, { "input": "In patients with diabetes, atherosclerosis is the main reason for impaired life expectancy, and diabetic nephropathy and retinopathy are the largest contributors to end - stage renal disease and blindness, respectively.", "output": "There is no related enetity." }, { "input": "An improved therapeutic approach to combat diabetic vascular complications might include blocking mechanisms of injury as well as promoting protective or regenerating factors, for example by enhancing the action of insulin - regulated genes in endothelial cells, promoting gene programs leading to induction of antioxidant or anti - inflammatory factors, or improving the sensitivity to vascular cell survival factors.", "output": "There is no related enetity." }, { "input": "Such strategies could help prevent complications despite suboptimal metabolic control.", "output": "There is no related enetity." }, { "input": "Specific chlorination of isoquinolines by a fungal flavin - dependent halogenase.", "output": "isoquinolines, flavin." }, { "input": "Rdc2 is the first flavin - dependent halogenase identified from fungi.", "output": "flavin." }, { "input": "Based on the reported structure of the bacterial halogenase CmlS, we have built a homology model for Rdc2.", "output": "There is no related enetity." }, { "input": "The model suggests an open substrate binding site that is capable of binding the natural substrate, monocillin II, and possibly other molecules such as 4 - hydroxyisoquinoline ( 1 ) and 6 - hydroxyisoquinoline ( 2 ).", "output": "monocillin II, 4 - hydroxyisoquinoline, 6 - hydroxyisoquinoline." }, { "input": "In vitro and in vivo halogenation experiments confirmed that 1 and 2 can be halogenated at the position ortho to the hydroxyl group, leading to the synthesis of the chlorinated isoquinolines 1a and 2a, respectively, which further expands the spectrum of identified substrates of Rdc2.", "output": "hydroxyl, isoquinolines." }, { "input": "This work revealed that Rdc2 is a useful biocatalyst for the synthesis of various halogenated compounds.", "output": "There is no related enetity." }, { "input": "Injectable nanomaterials for drug delivery: Carriers, targeting moieties, and therapeutics.", "output": "There is no related enetity." }, { "input": "Therapeutics such as nucleic acids, proteins / peptides, vaccines, anti - cancer, and other drugs have disadvantages of low bio - availability, rapid clearance, and high toxicity.", "output": "There is no related enetity." }, { "input": "Thus, there is a significant need for the development of efficient delivery methods and carriers.", "output": "There is no related enetity." }, { "input": "Injectable nanocarriers have received much attention due to their vast range of structures and ability to contain multiple functional groups, both within the bulk material and on the surface of the particles.", "output": "There is no related enetity." }, { "input": "Nanocarriers may be tailored to control drug release and / or increase selective cell targeting, cellular uptake, drug solubility, and circulation time, all of which lead to a more efficacious delivery and action of therapeutics.", "output": "There is no related enetity." }, { "input": "The focus of this review is injectable, targeted nanoparticle drug delivery carriers highlighting the diversity of nanoparticle materials and structures as well as highlighting current therapeutics and targeting moieties.", "output": "There is no related enetity." }, { "input": "Structures and materials discussed include liposomes, polymersomes, dendrimers, cyclodextrin - containing polymers ( CDPs ), carbon nanotubes ( CNTs ), and gold nanoparticles.", "output": "dendrimers, carbon." }, { "input": "Additionally, current clinical trial information and details such as trial phase, treatment, active drug, carrier sponsor, and clinical trial identifier for different materials and structures are presented and discussed.", "output": "There is no related enetity." }, { "input": "Novel diaryl ureas with efficacy in a mouse model of malaria.", "output": "diaryl ureas." }, { "input": "Exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug - resistant and drug - sensitive strains of the human malaria parasite Plasmodium falciparum.", "output": "diaryl ureas." }, { "input": "Compound 18 demonstrated EC ( 50 ) values of 37 and 55 nM versus in vitro cultured parasite strains and promising in vivo efficacy in a Plasmodium berghei antimalarial mouse model, with > 50 % survival at day 31 post - treatment when administered subcutaneously at 256 mg / kg.", "output": "There is no related enetity." }, { "input": "This series of compounds provides a chemical scaffold of novel architecture, as validated by cheminformatics analysis, to pursue antimalarial drug discovery efforts.", "output": "There is no related enetity." }, { "input": "Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2 / STAT3 signaling pathway.", "output": "Pterostilbene." }, { "input": "Osteosarcoma is a high - grade malignant bone tumor.", "output": "There is no related enetity." }, { "input": "Pterostilbene ( PTE ) is a natural, dimethylated analog of resveratrol with higher bioavailability.", "output": "Pterostilbene, PTE, resveratrol." }, { "input": "While PTE has been shown to have potent antitumor activity against various types of cancer, the molecular mechanisms underlying the effects of PTE remain largely unknown.", "output": "PTE, PTE." }, { "input": "The Janus kinase 2 / Signal Transducer and Activator of Transcription 3 ( JAK2 / STAT3 ) signaling pathway plays a crucial role in tumorigenesis and immune development.", "output": "There is no related enetity." }, { "input": "In this study, we assessed the antitumor activity of PTE against human osteosarcoma cells and explored the role of JAK2 / STAT3 and apoptosis - related signaling pathways on the activity of PTE.", "output": "PTE, PTE." }, { "input": "PTE treatment resulted in a dose - and time - dependent inhibition of osteosarcoma cell viability.", "output": "PTE." }, { "input": "Additionally, PTE exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration and mitochondrial membrane potential ( MMP ) but also by increases in the apoptotic index, reactive oxygen species ( ROS ) and several biochemical parameters.", "output": "PTE, oxygen." }, { "input": "Furthermore, PTE treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of STAT3.", "output": "PTE, Tyr." }, { "input": "PTE also down - regulated the expression of STAT3 target genes, including the anti - apoptotic proteins Bcl - xL and Mcl - 1, leading to the up - regulation of mitochondrial apoptosis pathway - related proteins ( Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3 ) and cyclin - dependent kinase inhibitors such as p21 and p27.", "output": "PTE." }, { "input": "PTE, used in combination with a known JAK2 / STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells.", "output": "PTE, AG490." }, { "input": "Taken together, PTE is a potent inhibitor of osteosarcoma cell growth that targets the JAK2 / STAT3 signaling pathway.", "output": "PTE." }, { "input": "These data suggest that inhibition of JAK2 / STAT3 signaling is a novel mechanism of action for PTE during therapeutic intervention in osteosarcoma cancers.", "output": "PTE." }, { "input": "The effects of natural disturbances, reef state, and herbivorous fish densities on ciguatera poisoning in Rarotonga, southern Cook Islands.", "output": "There is no related enetity." }, { "input": "Ciguatera poisoning is a critical public - health issue among Pacific island nations.", "output": "There is no related enetity." }, { "input": "Accurately predicting ciguatera outbreaks has become a priority, particularly in Rarotonga in the southern Cook Islands, which has reported the highest incidence of ciguatera poisoning globally.", "output": "There is no related enetity." }, { "input": "Since 2006, however, cases of ciguatera poisoning have declined, and in 2011 ciguatera cases were the lowest in nearly 20 years.", "output": "There is no related enetity." }, { "input": "Here we examined the relationships between cases of ciguatera poisoning, from 1994 to 2011, and: ( i ) coral cover, used as a proxy of reef state, ( ii ) the densities of herbivorous fishes, and ( iii ) reef disturbances.", "output": "There is no related enetity." }, { "input": "We found that coral cover was not a good predictor of cases of ciguatera poisoning, but high densities of the herbivorous fish Ctenochaetus striatus and reef disturbances were both strong predictors of ciguatera poisoning.", "output": "There is no related enetity." }, { "input": "Yet these two predictors were correlated, because the densities of C. striatus increased only after major cyclones had disturbed the reefs.", "output": "There is no related enetity." }, { "input": "Since 2006, the number of cyclones has decreased considerably in Rarotonga, because of the climatic shift toward the negative phase of the Pacific Decadal Oscillation.", "output": "There is no related enetity." }, { "input": "We suggest that fewer cyclones have led to decreases in both the densities of C. striatus and of the number of reported cases of ciguatera poisoning in Rarotonga.", "output": "There is no related enetity." }, { "input": "Preclinical assessment of a polyspecific antivenom against the venoms of Cerrophidion sasai, Porthidium nasutum and Porthidium ophryomegas: Insights from combined antivenomics and neutralization assays.", "output": "There is no related enetity." }, { "input": "A polyspecific antivenom is used in Central America for the treatment of envenomings by viperid snakes.", "output": "There is no related enetity." }, { "input": "This antivenom is generated in horses hyperimmunized with a mixture of venoms from Bothrops asper, Crotalus simus and Lachesis stenophrys.", "output": "There is no related enetity." }, { "input": "The present study analyzed the ability of this antivenom to neutralize the venoms of three Central American viperid species of the ' Porthidium group ', i. e. Porthidium nasutum, Porthidium ophryomegas and Cerrophidion sasai, formerly classified as Cerrophidion godmani.", "output": "There is no related enetity." }, { "input": "In addition, the immunorecognition of the components of these venoms was assessed by immunoaffinity antivenomics.", "output": "There is no related enetity." }, { "input": "The antivenom proved effective in neutralizing the lethal, hemorrhagic, myotoxic, phospholipase A ( 2 ) ( PLA ( 2 ) ) and proteinase activities of the three venoms, albeit exhibiting quantitative differences in the values of the Median Effective Doses ( ED ( 50 ) ).", "output": "There is no related enetity." }, { "input": "Excepting for certain low molecular mass bands corresponding to disintegrins, and some PLA ( 2 ) s and PI - metalloproteinases, Western blotting and immunoaffinity chromatography revealed immunorecognition of most Porthidium and Cerrophidion venom proteins.", "output": "There is no related enetity." }, { "input": "In agreement with in vivo neutralization assays, immobilized antivenom IgGs showed higher immunocapturing activity of toxins from both Porthidium taxa than from C. sasai.", "output": "There is no related enetity." }, { "input": "Overall our results demonstrate a significant paraspecific protection of the Costa Rican polyspecific antivenom against the three venoms sampled.", "output": "There is no related enetity." }, { "input": "They also stress the need to search for novel ways to enhance the immune response of horses against several weakly immunogenic venom components.", "output": "There is no related enetity." }, { "input": "cDNA cloning of a snake venom metalloproteinase from the eastern diamondback rattlesnake ( Crotalus adamanteus ), and the expression of its disintegrin domain with anti - platelet effects.", "output": "There is no related enetity." }, { "input": "A 5 ' truncated snake venom metalloproteinase was identified from a cDNA library constructed from venom glands of an eastern diamondback rattlesnake ( Crotalus adamanteus ).", "output": "There is no related enetity." }, { "input": "The 5 ' - rapid amplification of cDNA ends ( RACE ) was used to obtain the 1865 bp full - length cDNA sequence of a snake venom metalloproteinase ( CamVMPII ).", "output": "There is no related enetity." }, { "input": "CamVMPII encodes an open reading frame of 488 amino acids, which includes a signal peptide, a pro - domain, a metalloproteinase domain, a spacer, and an RGD - disintegrin domain.", "output": "amino acids." }, { "input": "The predicted amino acid sequence of CamVMPII showed a 91 %, 90 %, 83 %, and 82 % sequence homology to the P - II class enzymes of C. adamanteus metalloproteinase 2, Crotalus atrox CaVMP - II, Gloydius halys agkistin, and Protobothrops jerdonii jerdonitin, respectively.", "output": "There is no related enetity." }, { "input": "Disintegrins are potent inhibitors of both platelet aggregation and integrin - dependent cell adhesion.", "output": "There is no related enetity." }, { "input": "Therefore, the disintegrin domain ( Cam - dis ) of CamVMPII was amplified by PCR, cloned into a pET - 43. 1a vector, and expressed in Escherichia coli BL21.", "output": "There is no related enetity." }, { "input": "Affinity purified recombinantly modified Cam - dis ( r - Cam - dis ) with a yield of 8. 5 mg / L culture medium was cleaved from the fusion tags by enterokinase cleavage.", "output": "There is no related enetity." }, { "input": "r - Cam - dis was further purified by two - step chromatography consisting of HiTrap (TM) Benzamidine FF column, followed by Talon Metal affinity column with a final yield of 1 mg / L culture.", "output": "There is no related enetity." }, { "input": "r - Cam - dis was able to inhibit all three processes of platelet thrombus formation including platelet adhesion with an estimated IC ( 50 ) of 1 nM, collagen - and ADP - induced platelet aggregation with the estimated IC ( 50 ) s of 18 and 6 nM, respectively, and platelet function on clot retraction.", "output": "ADP." }, { "input": "It is a potent anti - platelet inhibitor, which should be further investigated for drug discovery to treat stroke patients or patients with thrombotic disorders.", "output": "There is no related enetity." }, { "input": "Vasorelaxant effects of 1 - nitro - 2 - phenylethane, the main constituent of the essential oil of Aniba canelilla, in superior mesenteric arteries from spontaneously hypertensive rats.", "output": "1 - nitro - 2 - phenylethane." }, { "input": "The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla ( EOAC ) and its main constituent 1 - nitro - 2 - phenylethane ( NP ) in isolated superior mesenteric artery from spontaneously hypertensive rats ( SHRs ).", "output": "1 - nitro - 2 - phenylethane." }, { "input": "At 0. 1 - 1000 mu g / mL, EOAC and NP relaxed SMA preparations pre - contracted with 75 mMKCl with IC ( 50 ) ( geometric mean [ 95 % confidence interval ] ) values of 294. 19 [ 158. 20 - 94. 64 ] and 501. 27 [ 378. 60 - 624. 00 ] mu g / mL, respectively ); or with phenylephrine ( PHE ) ( IC ( 50 ) s = 11. 07 [ 6. 40 - 15. 68 ] and 7. 91 [ 4. 08 - 11. 74 ) mu g / mL, respectively ).", "output": "mMKCl, phenylephrine, PHE." }, { "input": "All these effects were reversible and remained unaltered by vascular endothelium removal.", "output": "There is no related enetity." }, { "input": "In preparations maintained under Ca ( 2 + ) - free conditions, EOAC and NP ( both at 600 mu g / mL ) reduced the PHE -, but not the caffeine - induced contraction.", "output": "Ca ( 2 + ), caffeine." }, { "input": "In Ca ( 2 + ) - free and high K ( + ) ( 75 mM ) medium, the contractions produced by CaCl ( 2 ) or BaCl ( 2 ) were reduced or even abolished by EOAC and NP at 100 and 600 mu g / mL, respectively.", "output": "Ca ( 2 + ), K ( + ), CaCl ( 2 ), BaCl ( 2 )." }, { "input": "EOAC and NP ( both at 10 - 1000 mu g / mL ) also relaxed the contraction evoked by phorbol dibutyrate ( IC ( 50 ) = 52. 66 [ 10. 82 - 94. 64 ] and 39. 13 [ 31. 55 - 46. 72 ] mu g / mL, respectively ).", "output": "phorbol dibutyrate." }, { "input": "It is concluded that NP has a myogenic endothelium - independent vasorelaxant effects and appears to be the active principle of the EOAC.", "output": "There is no related enetity." }, { "input": "Vasorelaxant effect induced by both EOAC and NP is preferential to receptor - activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel.", "output": "There is no related enetity." }, { "input": "Total synthesis of bicyclic depsipeptides spiruchostatins C and D and investigation of their histone deacetylase inhibitory and antiproliferative activities.", "output": "spiruchostatins C and D." }, { "input": "The bicyclic depsipeptide histone deacetylase ( HDAC ) inhibitors spiruchostatins C and D were synthesized for the first time in a highly convergent and unified manner.", "output": "spiruchostatins C and D." }, { "input": "The method features the amide coupling of a D - leucine - D - cysteine - or D - valine - D - cysteine - containing segment with a D - alanine - or D - valine - containing segment to directly assemble the corresponding seco - acids, key precursors of macrolactonization.", "output": "amide, D - leucine - D - cysteine, D - valine - D - cysteine, D - alanine, D - valine." }, { "input": "The HDAC inhibitory assay and cell - growth inhibition analysis of the synthesized depsipeptides determined the order of potency of spiruchostatins A - D in comparison with the clinically approved depsipeptide FK228 ( romidepsin ).", "output": "spiruchostatins A - D, FK228, romidepsin." }, { "input": "Novel aspects of structure - activity relationships ( SAR ) were revealed.", "output": "There is no related enetity." }, { "input": "Design and synthesis of biaryl aryl stilbenes / ethylenes as antimicrotubule agents.", "output": "biaryl aryl stilbenes, ethylenes." }, { "input": "Two new series of compounds E - 2, 3, 4 - trimethoxy - 6 - styrylbiphenyls and 2, 3, 4 - trimethoxy - 6 - ( 1 - phenylvinyl ) biphenyls were designed, synthesized and evaluated for antitubulin activity.", "output": "E - 2 , 3 , 4 - trimethoxy - 6 - styrylbiphenyls, 2 , 3 , 4 - trimethoxy - 6 - ( 1 - phenylvinyl ) biphenyls." }, { "input": "A common intermediate 4, 5, 6 - trimethoxybiphenyl - 2 - carbaldehydes was employed to generate the two scaffolds.", "output": "4 , 5 , 6 - trimethoxybiphenyl - 2 - carbaldehydes." }, { "input": "Majority of the analogs inhibited cell proliferation and those functionalized with 3, 4 - ( 1, 3 - dioxolane ) and 3, 4 - difluoro groups were identified as effective inhibitors in both the series.", "output": "3 , 4 - ( 1 , 3 - dioxolane ), 3 , 4 - difluoro." }, { "input": "Treatments with 19b, 19c, 22b and 22c arrested cells at G2 / M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2 / M marker, Cyclin B1.", "output": "There is no related enetity." }, { "input": "Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.", "output": "colchicine." }, { "input": "Interaction of polyhexamethylene biguanide hydrochloride ( PHMB ) with phosphatidylcholine containing o / w emulsion and consequences for microbicidal efficacy and cytotoxicity.", "output": "polyhexamethylene biguanide hydrochloride, PHMB, phosphatidylcholine." }, { "input": "Oil - in - water ( o / w ) emulsions containing egg yolk phosphatidylcholine ( EPC ) were combined with aqueous polyhexamethylene biguanide hydrochloride ( PHMB ).", "output": "phosphatidylcholine, polyhexamethylene biguanide hydrochloride, PHMB." }, { "input": "The PHMB concentration in the aqueous phase was estimated by filtration centrifugation experiments.", "output": "PHMB." }, { "input": "In parallel, PHMB concentration was assessed utilizing cytotoxicity assays ( neutral red ) on cultured murine fibroblasts ( L929 cells ) and tests of bactericidal efficacy on either Pseudomonas aeruginosa or Staphylococcus aureus.", "output": "PHMB, neutral red." }, { "input": "Biological tests were performed in cell culture medium.", "output": "There is no related enetity." }, { "input": "Filtration centrifugation experiments demonstrated much higher aqueous PHMB concentrations than did the assays for biologically effective PHMB.", "output": "PHMB, PHMB." }, { "input": "Therefore, biological test systems should preferably be used to verify effective PHMB concentrations.", "output": "PHMB." }, { "input": "Tests of microbicidal efficacy in which the same 0. 05 % PHMB o / w emulsion was re - used 8 times revealed a drug delivery system activated by the presence of test bacteria.", "output": "PHMB." }, { "input": "Neuroprotective effects of resveratrol on embryonic dorsal root ganglion neurons with neurotoxicity induced by ethanol.", "output": "resveratrol, ethanol." }, { "input": "Studies have established that ethanol ( EtOH ) consumption results in damage to the peripheral nervous systems.", "output": "ethanol, EtOH." }, { "input": "Although the pathobiological mechanism is still unclear, oxidative stress is known to play an important role in EtOH - induced neurotoxicity.", "output": "EtOH." }, { "input": "Because resveratrol ( Res ) is attracting increased attention due to its antioxidative properties, we investigated the neuroprotective efficacy of Res in ethanol - treated embryonic dorsal root ganglion ( DRG ) neurons in vitro.", "output": "resveratrol, Res, Res, ethanol." }, { "input": "Organotypic DRG explants and a dispersed cell culture model were used to evaluate the effects of Res on EtOH - induced neurotoxicity.", "output": "Res, EtOH." }, { "input": "Res increased the number of extended nerve fibers and neurons that migrated from the DRG explants.", "output": "Res." }, { "input": "Hoechst 33342 staining and terminal deoxynucleotidyl - transferase - mediated dUTP nick - end - labeling analysis showed that the EtOH - induced apoptosis was inhibited by Res.", "output": "Hoechst 33342, dUTP, EtOH, Res." }, { "input": "The effects of Res were blocked by the 5 ' - adenosine monophosphate - activated protein kinase inhibitor Compound C and the sirtuin 1 inhibitor nicotinamide.", "output": "Res, 5 ' - adenosine monophosphate, nicotinamide." }, { "input": "The elevation of oxidative / nitrosative stress, as measured by the amount of reactive oxygen species, malondialdehyde, nitrite, glutathione and superoxide dismutase activity, was also attenuated by Res.", "output": "oxygen, malondialdehyde, nitrite, glutathione, superoxide, Res." }, { "input": "The data from the present study indicate that Res protects DRG neurons from EtOH - induced neurotoxicity.", "output": "Res, EtOH." }, { "input": "Res and its derivative may be effective for the treatment of diseases characterized by axonopathy and neuron loss induced by EtOH.", "output": "Res, EtOH." }, { "input": "Specific uptake of folate - decorated triamcinolone - encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity.", "output": "folate, triamcinolone." }, { "input": "We are proposing folate - decorated polymeric nanoparticles as carriers of poorly soluble drug molecules for intracellular and prolonged delivery to retinal pigment epithelium ( RPE ) cells.", "output": "folate." }, { "input": "RPE is a monolayer of epithelial cells that forms the outer blood - retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of, such as neovascularization in age - related macular degeneration ( AMD ).", "output": "There is no related enetity." }, { "input": "In this study, folate - functionalized poly ( ethylene glycol ) - b - polycaprolactone ( folate - PEG - b - PCL ) were synthesized for assembling into nanoparticles of ~ 130nm.", "output": "folate, poly ( ethylene glycol ), polycaprolactone, folate, PEG, PCL." }, { "input": "These nanoparticles were internalized into ARPE - 19 ( human RPE cell line ) via receptor - mediated endocytosis, and the cellular uptake was significantly higher than particles without folate modification.", "output": "folate." }, { "input": "Triamcinolone acetonide ( TA ) was efficiently encapsulated ( > 97 % ) into the folate - decorated nanoparticles and was slowly released over a period of 4 weeks at pH 5. 5 and 8 weeks at pH 7. 4.", "output": "Triamcinolone acetonide, folate." }, { "input": "The enhanced uptake and controlled release resulted in prolonged anti - angiogenic gene expression of RPE cells.", "output": "There is no related enetity." }, { "input": "In cell culture, the down - regulation of vascular endothelial growth factor ( VEGF ) and up - regulation of pigment epithelium derived factor ( PEDF ) lasted for at least 3 weeks.", "output": "There is no related enetity." }, { "input": "Unlike benzyl alcohol, the surfactant found in commercial formulation, folate - modified nanoparticles were non - toxic.", "output": "benzyl alcohol, folate." }, { "input": "Furthermore, TA became less cytotoxic by being encapsulated in the nanoparticles.", "output": "There is no related enetity." }, { "input": "Our findings suggest that folate - PEG - PCL nanoparticles are promising drug carriers for RPE targeting.", "output": "folate, PEG, PCL." }, { "input": "Pharmacokinetics of temoporfin - loaded liposome formulations: correlation of liposome and temoporfin blood concentration.", "output": "temoporfin, temoporfin." }, { "input": "Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility - related problems associated with the current therapy scheme.", "output": "temoporfin." }, { "input": "We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size.", "output": "temoporfin, cholesterol." }, { "input": "Specifically, two phosphatidyl oligoglycerols were compared to PEG2000 - DSPE with respect to the ability to prolong circulation half life of the liposomal carrier.", "output": "PEG2000 - DSPE." }, { "input": "We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and ( 14 ) C - temoporfin.", "output": "temoporfin, ( 14 ) C - temoporfin." }, { "input": "The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two - compartment model.", "output": "temoporfin." }, { "input": "This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components ( e. g. plasma proteins ) before being eliminated from the blood.", "output": "temoporfin, temoporfin." }, { "input": "We therefore additionally analyzed the data based on two separate one - compartment models for the liposomes and temoporfin.", "output": "temoporfin." }, { "input": "The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins.", "output": "temoporfin, temoporfin." }, { "input": "Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood.", "output": "temoporfin." }, { "input": "In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel - phase liposomes to e. g. plasma proteins.", "output": "temoporfin, temoporfin." }, { "input": "Interestingly, liposomes carrying either one of the three investigated surface - modifying agents did not adhere to the tendencies observed for unmodified liposomes.", "output": "There is no related enetity." }, { "input": "Although surface - modified liposomes exhibited improved pharmacokinetic properties with regard to the liposomal carrier, an enhanced temoporfin loss and elimination from the PEGylated - liposomes was observed.", "output": "temoporfin." }, { "input": "This effect was more pronounced for PEGylated liposomes than for the two oligo - glycerols.", "output": "glycerols." }, { "input": "Our combined experimental - theoretical approach for in vivo plasma re - distribution of liposomal drugs may help to optimize colloidal drug carrier systems.", "output": "There is no related enetity." }, { "input": "Inhibition of protein glycation by urea and thiourea derivatives of glycine / proline conjugated benzisoxazole analogue - synthesis and structure - activity studies.", "output": "urea, thiourea, glycine, proline, benzisoxazole." }, { "input": "Synthesis of a new series of urea / thiourea derivatives of Gly / Pro conjugated benzisoxazole has been reported.", "output": "urea, thiourea, Gly, Pro, benzisoxazole." }, { "input": "Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity.", "output": "There is no related enetity." }, { "input": "Several compounds showed promising activity with IC ( 50 ) < 5 mu M compared to standard rutin ( IC ( 50 ) = 41. 9 mu M ).", "output": "rutin." }, { "input": "Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity.", "output": "methoxy, bromine." }, { "input": "Thus, the title compounds represent novel class of potent antiglycating agents.", "output": "There is no related enetity." }, { "input": "Effects of 17 beta - trenbolone on Eastern and Western mosquitofish ( Gambusia holbrooki and G. affinis ) anal fin growth and gene expression patterns.", "output": "17 beta - trenbolone." }, { "input": "The Eastern and Western mosquitofish ( Gambusia holbrooki and G. affinis ) are potential bioindicator organisms for endocrine disruptors.", "output": "There is no related enetity." }, { "input": "Male mosquitofish have an elongated anal fin ( gonopodium ) used for internal fertilization whose formation is driven by androgens.", "output": "androgens." }, { "input": "Normal female mosquitofish have a normal, rounded anal fin which undergoes elongation into a gonopodium structure when female mosquitofish are exposed to androgenic chemicals.", "output": "There is no related enetity." }, { "input": "Significant issues with using mosquitofish as a bioindicator include the lack of knowledge on how anal fin growth in females corresponds to endpoints relevant to biological integrity and the lack of information on the molecular pathways that regulate anal fin growth.", "output": "There is no related enetity." }, { "input": "The objectives of this study were to understand how androgen - induced anal fin elongation relates to changes in endpoints related to the female reproductive system and to understand how anal fin elongation occurs in androgen - exposed female mosquitofish.", "output": "androgen, androgen." }, { "input": "To achieve these objectives, adult female G. holbrooki were exposed to a vehicle control or one of three doses of the androgen 17 beta - trenbolone ( TB ) at nominal concentrations of 0. 1, 1 or 10 mu g TB / L.", "output": "androgen, 17 beta - trenbolone." }, { "input": "Anal fin measurements were taken and livers were used for quantitative polymerase chain reaction analysis of vitellogenin ( vtg ) mRNA expression at multiple time points.", "output": "There is no related enetity." }, { "input": "10 mu g TB / L induced anal fin elongation after 7 days of treatment ( one - way ANOVA, p < 0. 05 ) as did 0. 1 and 1 mu g TB / L at later time points ( one - way ANOVA, p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "10 mu g TB / L significantly reduced hepatic vtg gene expression at all time points assessed ( one - way ANOVA, p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "There was no correlation between anal fin elongation levels and vtg gene expression ( Spearman ' s rho, p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "In a separate experiment, female G. holbrooki and G. affinis were exposed to the vehicle control or 1 mu g TB / L.", "output": "There is no related enetity." }, { "input": "Anal fins were used for qualitative gene expression analysis of the genes sonic hedgehog ( shh ), muscle segment homeobox C ( msxC ), and fibroblast growth factor receptor 1 ( fgfr1 ) by in situ hybridization.", "output": "There is no related enetity." }, { "input": "Shh was expressed in the distal tip of the gonopodium while msxC and fgfr1 were more widely expressed along the same anal fin rays during androgen exposure.", "output": "androgen." }, { "input": "These data provide insight into the molecular pathways involved in anal fin elongation and pave the way for future work toward developing the mosquitofish into a bioindicator organism for endocrine disruptors.", "output": "There is no related enetity." }, { "input": "Biochemical and metabolic effects of a short - term exposure to nanoparticles of titanium silicate in tadpoles of Pelophylax perezi ( Seoane ).", "output": "titanium silicate." }, { "input": "This study aimed to evaluate sublethal effects of a short - term exposure ( 96 h ) to titanium silicate nanoparticles ( TiSiO ( 4 ) - NP ) on Pelophylax perezi tadpoles.", "output": "titanium silicate, TiSiO ( 4 )." }, { "input": "Tadpoles were exposed to five concentrations of TiSiO ( 4 ) - NP ( 8. 2, 10. 2, 12. 8, 16 and 20 mg / L ) plus a control.", "output": "TiSiO ( 4 )." }, { "input": "Effect criteria were: mortality, cholinesterases, glutathione S - transferases, lactate dehydrogenase, and catalase activities, and alanine and lactate contents.", "output": "glutathione, S, lactate, alanine, lactate." }, { "input": "Light scattering was used for physical characterization of TiSiO ( 4 ) - NP suspensions, revealing a high aggregation state of the NP, consistent with low z - potential values ( < 30 mV ).", "output": "TiSiO ( 4 )." }, { "input": "Mortality among TiSiO ( 4 ) - NP treatments was < 11 %.", "output": "TiSiO ( 4 )." }, { "input": "Significant differences relatively to the control were observed at the biochemical level ( for CAT and LDH ) and in lactate and alanine contents, which may end - up in increased oxidative stress.", "output": "There is no related enetity." }, { "input": "Overall, some of the monitored endpoints suggest metabolic alterations in TiSiO ( 4 ) - NP exposed tadpoles, highlighting the potential of TiSiO ( 4 ) - NP long - term effects on these organisms.", "output": "TiSiO ( 4 ), TiSiO ( 4 )." }, { "input": "Copper induced upregulation of apoptosis related genes in zebrafish ( Danio rerio ) gill.", "output": "Copper." }, { "input": "Copper ( Cu ) is an essential micronutrient that, when present in high concentrations, becomes toxic to aquatic organisms.", "output": "Copper, Cu." }, { "input": "It is known that Cu toxicity may induce apoptotic cell death.", "output": "Cu." }, { "input": "However, the precise mechanism and the pathways that are activated, in fish, are still unclear.", "output": "There is no related enetity." }, { "input": "Thus, this study aimed to assess which apoptotic pathways are triggered by Cu, in zebrafish ( Danio rerio ) gill, the main target of waterborne pollutants.", "output": "Cu." }, { "input": "Fish where exposed to 12. 5 and 100 mu g / L of Cu during 6, 12, 24 and 48 h.", "output": "Cu." }, { "input": "Fish gills were collected to TUNEL assay and mRNA expression analysis of selected genes by real time PCR.", "output": "There is no related enetity." }, { "input": "An approach to different apoptosis pathways was done selecting p53, caspase - 8, caspase - 9 and apoptosis inducing factor ( AIF ) genes.", "output": "There is no related enetity." }, { "input": "The higher incidence of TUNEL - positive cells, in gill epithelia of the exposed fish, proved that Cu induced apoptosis.", "output": "Cu." }, { "input": "The results suggest that different apoptosis pathways are triggered by Cu at different time points of the exposure period, as the increase in transcripts was sequential, instead of simultaneous.", "output": "Cu." }, { "input": "Apoptosis seems to be initiated via intrinsic pathway ( caspase - 9 ), through p53 activation; then followed by the extrinsic pathway ( caspase - 8 ) and finally by the caspase - independent pathway ( AIF ).", "output": "There is no related enetity." }, { "input": "A possible model for Cu - induce apoptosis pathways is proposed.", "output": "Cu." }, { "input": "Forming double layer - encapsulated quantum dots for bio - imaging and cell targeting.", "output": "There is no related enetity." }, { "input": "We report a simple and effective approach for the preparation of double layer - encapsulated quantum dots ( DL - Qdots ) composed of alkyl - capping ligands to interdigitate with hydrophobic, protective agents on the surface of AgInS ( 2 ) / ZnS quantum dots ( Qdots ), which allow phase transfer of hydrophobic Qdots from the organic phase into the aqueous phase.", "output": "AgInS ( 2 ), ZnS." }, { "input": "The alkyl - capping ligands consist of a hydrophobic, aliphatic chain and different functional terminal groups ( e. g., carboxyl, amine, hydroxyl, and thiol groups ) that can serve as reactive sites to chemically couple with other materials.", "output": "carboxyl, amine, hydroxyl, thiol." }, { "input": "The resulting DL - Qdots bearing various functional groups retain good fluorescence properties and show excellent solubility as well as stability over a range of pH in the aqueous phase.", "output": "There is no related enetity." }, { "input": "Cytotoxicity studies of DL - Qdots bearing carboxyl groups ( DL - Qdots - COOH ) were carried out against human cervical ( HeLa ) cancer cells to elicit no apparent toxicity even at high concentrations of 300 mu g mL ( - 1 ) and 24 h of incubation.", "output": "carboxyl, COOH." }, { "input": "To demonstrate their potential biomedical application, DL - Qdots - COOH were further conjugated with folate for staining in HeLa, human liver carcinoma ( HepG2 ), and human breast ( MCF - 7 ) cancer cells.", "output": "COOH, folate." }, { "input": "Confocal imaging characterization revealed that folate - conjugated DL - Qdots could target most specifically and effectively HeLa cells via folate receptor - mediated targeted delivery compared to HepG2 and MCF - 7 cells.", "output": "folate, folate." }, { "input": "The generality and simplicity of this newly developed strategy can possibly be extended to a large variety of hydrophobic Qdots and nanocrystals whose surface protective agents have a long aliphatic chain.", "output": "There is no related enetity." }, { "input": "Epigenetic and small RNA regulation of senescence.", "output": "There is no related enetity." }, { "input": "Leaf senescence is regulated through a complex regulatory network triggered by internal and external signals for the reprogramming of gene expression.", "output": "There is no related enetity." }, { "input": "In plants, the major developmental phase transitions and stress responses are under epigenetic control.", "output": "There is no related enetity." }, { "input": "In this review, the underlying molecular mechanisms are briefly discussed and evidence is shown that epigenetic processes are also involved in the regulation of leaf senescence.", "output": "There is no related enetity." }, { "input": "Changes in the chromatin structure during senescence, differential histone modifications determining active and inactive sites at senescence - associated genes and DNA methylation are addressed.", "output": "There is no related enetity." }, { "input": "In addition, the role of small RNAs in senescence regulation is discussed.", "output": "There is no related enetity." }, { "input": "Hypolipidemic effect of fruit fibers in rats fed with high dietary fat.", "output": "There is no related enetity." }, { "input": "The hypolipidemic effect of 10 % fruit fibers in rats fed with high - fat diet ( HFD ) was evaluated.", "output": "There is no related enetity." }, { "input": "This study was conducted on a total of 50 male Albino rats divided into 10 equal groups fed with different types of dietary fruits.", "output": "There is no related enetity." }, { "input": "The feeding period lasted for 24 weeks.", "output": "There is no related enetity." }, { "input": "Fasting blood samples were collected and sera separated and subjected to lipid profile assay and atherogenic index.", "output": "There is no related enetity." }, { "input": "In addition, total antioxidant activity of different fruits was determined.", "output": "There is no related enetity." }, { "input": "The results obtained showed that pomegranate had higher content of antioxidants followed by apple, strawberry and guava compared with other fruits.", "output": "There is no related enetity." }, { "input": "Rats fed with 20 % coconut oil showed a highly significant elevation in the levels of serum total cholesterol, low - density lipoprotein cholesterol and atherogenic factor while the level of high - density lipoprotein cholesterol was significantly decreased when compared with control rats.", "output": "cholesterol, cholesterol, cholesterol." }, { "input": "Histological examination revealed that there was a large lipid and cholesterol deposition in the livers of rats fed with HFD.", "output": "cholesterol." }, { "input": "The potential in lowering the levels of plasma total cholesterol and triglyceride is in the following order: pomegranate > apple > strawberry > guava > papaya > mandarin and orange.", "output": "cholesterol, triglyceride." }, { "input": "Accumulation of hepatic lipid droplets was diminished when compared with the HFD group.", "output": "There is no related enetity." }, { "input": "Also, antiatherogenic is better than the untreated groups.", "output": "There is no related enetity." }, { "input": "Accordingly these hypolipidemic effects may be due to high - fiber content and antioxidant activity of these fruits.", "output": "There is no related enetity." }, { "input": "Transaldolase deficiency: report of 12 new cases and further delineation of the phenotype.", "output": "There is no related enetity." }, { "input": "PURPOSE: Transaldolase deficiency is a recently described inborn error of pentose phosphate pathway.", "output": "pentose phosphate." }, { "input": "We conducted this study to further delineate the associated phenotype.", "output": "There is no related enetity." }, { "input": "METHODS AND RESULTS: We report on 12 new cases representing six families with this metabolic defect that were observed over an 8 year span.", "output": "There is no related enetity." }, { "input": "None of these cases received the correct diagnosis initially because of significant overlap in the presenting symptoms ( growth retardation, dysmorphic features, cutis laxa, congenital heart disease, hepatosplenomegaly, pancytopenia, and bleeding tendency ) with a wide range of genetic disorders.", "output": "There is no related enetity." }, { "input": "However, the consanguineous nature of these families allowed us to pursue autozygome analysis, which highlighted TALDO as the likely candidate gene and sequencing confirmed segregation of a novel homozygous mutation with the disease in all the studied families.", "output": "There is no related enetity." }, { "input": "Biochemical analysis was also consistent with transaldolase deficiency.", "output": "There is no related enetity." }, { "input": "CONCLUSION: This study expands the clinical definition of transaldolase deficiency, and adds to its allelic heterogeneity.", "output": "There is no related enetity." }, { "input": "In addition, we emphasize the diagnostic challenge posed by this rare and pleiotropic metabolic disorder.", "output": "There is no related enetity." }, { "input": "Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection.", "output": "ATP." }, { "input": "The lymphocytic ionotropic purinergic P2X receptors ( P2X1R - P2X7R, or P2XRs ) sense ATP released during cell damage - activation, thus regulating T - cell activation.", "output": "ATP." }, { "input": "We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti - P2XRs strategy to achieve long - term islet allograft function.", "output": "There is no related enetity." }, { "input": "Our data demonstrate that P2X1R and P2X7R are induced in islet allograft - infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation.", "output": "There is no related enetity." }, { "input": "In vivo short - term P2X7R targeting ( using periodate - oxidized ATP [ oATP ] ) delays islet allograft rejection, reduces the frequency of Th1 / Th17 cells, and induces hyporesponsiveness toward donor antigens.", "output": "ATP, oATP." }, { "input": "oATP - treated mice displayed preserved islet grafts with reduced Th1 transcripts.", "output": "oATP." }, { "input": "P2X7R targeting and rapamycin synergized in inducing long - term islet function in 80 % of transplanted mice and resulted in reshaping of the recipient immune system.", "output": "rapamycin." }, { "input": "In vitro P2X7R targeting using oATP reduced T - cell activation and diminished Th1 / Th17 cytokine production.", "output": "oATP." }, { "input": "Peripheral blood mononuclear cells obtained from long - term islet - transplanted patients showed an increased percentage of P2X7R ( + ) CD4 ( + ) T cells compared with controls.", "output": "There is no related enetity." }, { "input": "The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long - term islet allograft function.", "output": "oATP." }, { "input": "Low - level domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: role of glutathione.", "output": "domoic acid, glutathione." }, { "input": "Domoic acid ( DomA ) is a potent marine neurotoxin.", "output": "Domoic acid, DomA." }, { "input": "By activating alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazoleproprionic acid / kainate receptors, DomA induces oxidative stress - mediated apoptotic cell death in neurons.", "output": "alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazoleproprionic acid, kainate, DomA." }, { "input": "The effect of prolonged ( 10 days ) exposure to a low, nontoxic concentration ( 5nM ) of DomA on acute ( intermediate concentration ) neurotoxicity of this toxin was investigated in cerebellar granule neurons ( CGNs ) from wild - type mice and mice lacking the glutamate cysteine ligase ( GCL ) modifier subunit ( Gclm ( / ) ).", "output": "DomA, glutamate, cysteine." }, { "input": "CGNs from Gclm ( / ) mice have very low glutathione ( GSH ) levels and are very sensitive to DomA toxicity.", "output": "glutathione, GSH, DomA." }, { "input": "In CGNs from wild - type mice, prolonged exposure to 5nM DomA did not cause any overt toxicity but reduced oxidative stress - mediated apoptotic cell death induced by exposure to an intermediate concentration ( 100nM for 24h ) of DomA.", "output": "DomA, DomA." }, { "input": "This protection was not observed in CGNs from Gclm ( / ) mice.", "output": "There is no related enetity." }, { "input": "Prolonged DomA exposure increased GSH levels in CGNs of wild - type but not Gclm ( / ) mice.", "output": "DomA, GSH." }, { "input": "Levels of GCLC ( the catalytic subunit of GCL ) protein and mRNA were increased in CGNs of both mouse strains, whereas levels of GCLM protein and mRNA, activity of GCL, and levels of GCL holoenzyme were only increased in CGNs of wild - type mice.", "output": "There is no related enetity." }, { "input": "Chronic DomA exposure also protected wild - type CGNs from acute toxicity of other oxidants.", "output": "DomA." }, { "input": "The results indicate that CGNs from Gclm ( / ) mice, which are already more sensitive to DomA toxicity, are unable to upregulate their GSH levels.", "output": "DomA, GSH." }, { "input": "As Gclm ( / ) mice may represent a model for a common human polymorphism in GCLM, such individuals may be at particular risk for DomA - induced neurotoxicity.", "output": "DomA." }, { "input": "One - Hour Glucose During an Oral Glucose Challenge Prospectively Predicts beta - Cell Deterioration and Prediabetes in Obese Hispanic Youth.", "output": "Glucose, Glucose." }, { "input": "OBJECTIVEIn adults, 1 - h glucose during an oral glucose tolerance test ( OGTT ) predicts the development of type 2 diabetes independent of fasting and 2 - h glucose concentrations.", "output": "glucose, glucose, glucose." }, { "input": "The purpose of the current investigation was to examine the utility of elevated 1 - h glucose levels to prospectively predict deterioration in beta - cell function and the development of prediabetes in high - risk youth. RESEARCH DESIGN AND METHODSObese Latino youth with a family history of type 2 diabetes ( 133 male and 100 female; age 11. 1 +/- 1. 7 years ) completed a baseline OGTT and were divided into two groups based upon a 1 - h glucose threshold of 155 mg / dL ( < 155 mg / dL, n = 151, or >= 155 mg / dL, n = 82 ).", "output": "glucose, glucose." }, { "input": "Youth were followed annually for up to 8 years for assessment of glucose tolerance, body composition by dual - energy X - ray absorptiometry, and insulin sensitivity, insulin secretion, and the disposition index by the frequently sampled intravenous glucose tolerance test. RESULTSOver time, the >= 155 mg / dL group exhibited a significantly greater decline in beta - cell function compared with youth with a 1 - h glucose < 155 mg / dL ( beta = - 327. 8 +/- 126. 2, P = 0. 01 ).", "output": "glucose, glucose, glucose." }, { "input": "Moreover, this decline was independent of fasting or 2 - h glucose and body composition.", "output": "glucose." }, { "input": "When the data were restricted to only participants with normal glucose tolerance at baseline, a 1 - h glucose >= 155 mg / dL was independently associated with a 2. 5 times greater likelihood of developing prediabetes during follow - up ( 95 % CI 1. 6 - 4. 1, P = 0. 0001 ). CONCLUSIONSThese data suggest that a 1 - h glucose >= 155 mg / dL during an OGTT is an independent predictor of beta - cell deterioration and progression to prediabetes among obese Latino youth.", "output": "glucose, glucose, glucose." }, { "input": "Exciton Dissociation and Charge - Transport Enhancement in Organic Solar Cells with Quantum - Dot / N - doped CNT Hybrid Nanomaterials.", "output": "There is no related enetity." }, { "input": "The incorporation of InP quantum - dot / N - doped multiwalled carbon nanotube ( QD: NCNT ) nanohybrids in the active layer of poly ( 3 - hexylthiophene ) / indene - C60 bisadduct ( P3HT / ICBA ) bulk - heterojuction solar cells enhances VOC and JSC.", "output": "InP, N, carbon, poly ( 3 - hexylthiophene ), indene, C60, bisadduct, P3HT, ICBA." }, { "input": "The QDs encourage exciton dissociation by promoting electron transfer, while the NCNTs enhance the transport of the separated electrons and eventual charge collection.", "output": "There is no related enetity." }, { "input": "Such a synergistic effect successfully improves the power conversion efficiency ( PCE ) from 4. 68 % ( reference cells ) to 6. 11 %.", "output": "There is no related enetity." }, { "input": "N - Boc - protected 1, 2 - diphenylethylenediamine - based dendritic organogels with multiple - stimulus - responsive properties.", "output": "N - Boc - protected 1 , 2 - diphenylethylenediamine." }, { "input": "A new class of poly ( benzyl ether ) dendrimers, decorated in their cores with N - Boc - protected 1, 2 - diphenylethylenediamine groups, were synthesized and fully characterized.", "output": "poly ( benzyl ether ), N - Boc - protected 1 , 2 - diphenylethylenediamine." }, { "input": "It was found that the gelation capability of these dendrimers was highly dependent on dendrimer generation, and the second - generation dendrimer ( R, R ) - G ( 2 ) DPENBoc proved to be a highly efficient organogelator.", "output": "( R , R ) - G ( 2 ) DPENBoc." }, { "input": "A number of experiments ( SEM, TEM, FTIR spectroscopy, ( 1 ) H NMR spectroscopy, rheological measurements, UV / Vis absorption spectroscopy, CD, and XRD ) revealed that these dendritic molecules self - assembled into elastically interpenetrating one - dimensional nanostructures in organogels.", "output": "( 1 ) H." }, { "input": "The hydrogen bonding, pi - pi, and solvophobic interactions were found to be the main driving forces for formation of the gels.", "output": "hydrogen." }, { "input": "Most interestingly, these dendritic organogels exhibited smart multiple - stimulus - responsive behavior upon exposure to environmental stimuli such as temperature, anions, and mechanical stress.", "output": "There is no related enetity." }, { "input": "Research resource: tissue - and pathway - specific metabolomic profiles of the steroid receptor coactivator ( SRC ) family.", "output": "steroid." }, { "input": "The rapidly growing family of transcriptional coregulators includes coactivators that promote transcription and corepressors that harbor the opposing function.", "output": "There is no related enetity." }, { "input": "In recent years, coregulators have emerged as important regulators of metabolic homeostasis, including the p160 steroid receptor coactivator ( SRC ) family.", "output": "steroid." }, { "input": "Members of the SRC family have been ascribed important roles in control of gluconeogenesis, fat absorption and storage in the liver, and fatty acid oxidation in skeletal muscle.", "output": "fatty acid." }, { "input": "To provide a deeper and more granular understanding of the metabolic impact of the SRC family members, we performed targeted metabolomic analyses of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockouts ( KOs ) of SRC - 1, SRC - 2, or SRC - 3.", "output": "glucose, fatty acid, amino acid." }, { "input": "We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions ( liver, heart, skeletal muscle, brain, plasma ) isolated from SRC - 1, - 2, or - 3 KO mice and their wild - type littermates under fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC.", "output": "amino acids, acyl carnitines." }, { "input": "Specifically, SRC - 1 ablation revealed the most significant impact on hepatic metabolism, whereas SRC - 2 appeared to impact cardiac metabolism.", "output": "There is no related enetity." }, { "input": "Conversely, ablation of SRC - 3 primarily affected brain and skeletal muscle metabolism.", "output": "There is no related enetity." }, { "input": "Surprisingly, we identified very few metabolites that changed universally across the three SRC KO models.", "output": "There is no related enetity." }, { "input": "The findings of this Research Resource demonstrate that coactivator function has very limited metabolic redundancy even within the homologous SRC family.", "output": "There is no related enetity." }, { "input": "Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.", "output": "There is no related enetity." }, { "input": "The pH Taxis of an Intelligent Catalytic Microbot.", "output": "There is no related enetity." }, { "input": "A Pd nanoparticle - containing polymer microsphere moves with increasing speed across a pH gradient, following differential catalytic decomposition of aqueous hydrogen peroxide.", "output": "Pd, hydrogen peroxide." }, { "input": "The directional motion is akin to the pH taxis of living microorganisms.", "output": "There is no related enetity." }, { "input": "The artificial pH taxis exhibits random walk, translation, vertical, hopping, and pulsed motion, when the size of the motor and the imposed pH gradient are modulated.", "output": "There is no related enetity." }, { "input": "Gadolinium - and manganite - based contrast agents with fluorescent probes for both magnetic resonance and fluorescence imaging of pancreatic islets: a comparative study.", "output": "Gadolinium." }, { "input": "Three magnetic resonance ( MR ) / fluorescence imaging probes were tested for visualization, cellular distribution, and survival of labeled pancreatic islets in vitro and following transplantation.", "output": "There is no related enetity." }, { "input": "As T ( 1 ) contrast agents ( CAs ), gadolinium ( III ) complexes linked to beta - cyclodextrin ( Gd - F - beta CD ) or bound to titanium dioxide ( TiO2 @ RhdGd ) were tested.", "output": "gadolinium ( III ), beta - cyclodextrin, Gd - F - beta CD, titanium dioxide, TiO2." }, { "input": "As a T ( 2 ) CA, perovskite manganite nanoparticles ( LSMO @ siF @ si ) were examined.", "output": "There is no related enetity." }, { "input": "Fluorescein or rhodamine was incorporated as a fluorescent marker in all probes.", "output": "Fluorescein, rhodamine." }, { "input": "Islets labeled with gadolinium ( III ) CAs were visible as hyperintense spots on MR in vitro, but detection in vivo was inconclusive.", "output": "gadolinium ( III )." }, { "input": "Islets labeled with LSMO @ siF @ si CA were clearly visible as hypointense spots or areas on MR scans in vitro as well as in vivo.", "output": "There is no related enetity." }, { "input": "All CAs were detected inside the islet cells by fluorescence.", "output": "There is no related enetity." }, { "input": "Although the vitality and function of the labeled islets was not impaired by any of the tested CAs, results indicate that LSMO @ siF @ si CA is a superior marker for islet labeling, as it provides better contrast enhancement within a shorter scan time.", "output": "There is no related enetity." }, { "input": "Improved quantum efficiency of highly efficient perovskite BaSnO 3 - based dye - sensitized solar cells.", "output": "perovskite, BaSnO 3." }, { "input": "Ternary oxides are potential candidates as an electron - transporting material that can replace TiO 2 in dye - sensitized solar cells ( DSSCs ), as their electronic / optical properties can be easily controlled by manipulating the composition and / or by doping.", "output": "oxides, TiO 2." }, { "input": "Here, we report a new highly efficient DSSC using perovskite BaSnO 3 ( BSO ) nanoparticles.", "output": "perovskite, BaSnO 3, BSO." }, { "input": "In addition, the effects of a TiCl 4 treatment on the physical, chemical, and photovoltaic properties of the BSO - based DSSCs are investigated.", "output": "TiCl 4, BSO." }, { "input": "The TiCl 4 treatment was found to form an ultrathin TiO 2 layer on the BSO surface, the thickness of which increases with the treatment time.", "output": "TiCl 4, TiO 2, BSO." }, { "input": "The formation of the TiO 2 shell layer improved the charge - collection efficiency by enhancing the charge transport and suppressing the charge recombination.", "output": "TiO 2." }, { "input": "It was also found that the TiCl 4 treatment significantly reduces the amount of surface OH species, resulting in reduced dye adsorption and reduced light - harvesting efficiency.", "output": "TiCl 4, OH." }, { "input": "The trade - off effect between the charge - collection and light - harvesting efficiencies resulted in the highest quantum efficiency ( i. e., short - circuit photocurrent density ), leading to the highest conversion efficiency of 5. 5 % after a TiCl 4 treatment of 3 min ( cf. 4. 5 % for bare BSO ).", "output": "TiCl 4, BSO." }, { "input": "The conversion efficiency could be increased further to 6. 2 % by increasing the thickness of the BSO film, which is one of the highest efficiencies from non - TiO 2 - based DSSCs.", "output": "BSO, TiO 2." }, { "input": "Matrix metalloproteinases as drug targets in preeclampsia.", "output": "There is no related enetity." }, { "input": "Preeclampsia is an important syndrome complicating pregnancy.", "output": "There is no related enetity." }, { "input": "While the pathogenesis of preeclampsia is not entirely known, poor placental perfusion leading to widespread maternal endothelial dysfunction is accepted as a major mechanism.", "output": "There is no related enetity." }, { "input": "It has been suggested that altered placental expression of matrix metalloproteinases ( MMPs ) may cause shallow cytotrophoblastic invasion and incomplete remodeling of the spiral arteries.", "output": "There is no related enetity." }, { "input": "MMPs are also thought to link placental ischemia to the cardiovascular alterations of preeclampsia.", "output": "There is no related enetity." }, { "input": "In fact, MMPs may promote vasoconstriction and surface receptors cleavage affecting the vasculature.", "output": "There is no related enetity." }, { "input": "Therefore, the overall goal of this review article is to provide an overview of the pathophisiology of preeclampsia, more specifically regarding the role of MMPs in the pathogenesis of preeclampsia and the potential of MMP inhibitors as therapeutic options.", "output": "There is no related enetity." }, { "input": "Inhibition of matrix metalloproteinases ( MMPs ) as a potential strategy to ameliorate hypertension - induced cardiovascular alterations.", "output": "There is no related enetity." }, { "input": "A group of proteases, the matrix metalloproteinases ( MMPs ) are well known for their capacity to degrade extracellular matrix ( ECM ) proteins.", "output": "There is no related enetity." }, { "input": "Particularly MMP - 2 and MMP - 9 contribute to the degradation and reorganization of the ECM components and are involved in the pathophysiology of cardiovascular remodeling.", "output": "There is no related enetity." }, { "input": "Imbalanced MMP activity promotes vascular smooth muscle cells and migration and proliferation and endothelial dysfunction, thus resulting in increased cardiovascular stiffness and hypertrophy.", "output": "There is no related enetity." }, { "input": "Furthermore, MMP - 2 cleaves non - ECM protein substrates including cellular receptors and intracellular proteins, thus causing cardiac and vascular dysfunction.", "output": "There is no related enetity." }, { "input": "It is now becoming clear that increased MMP activity promotes long - lasting cardiovascular structural and functional alterations in both experimental and clinical hypertension, and this alteration may contribute to sustained hypertension and its complications.", "output": "There is no related enetity." }, { "input": "Other pathogenic mechanisms including activation of the renin - angiotensin - aldosterone system and oxidative stress activate and upregulate MMPs.", "output": "There is no related enetity." }, { "input": "Therefore, MMP inhibition may prevent the deleterious consequences of hypertension to the cardiovascular system.", "output": "There is no related enetity." }, { "input": "This review article will focus on growing evidence supporting the relevance of MMPs in hypertension and the effects of MMP inhibitors.", "output": "There is no related enetity." }, { "input": "Particularly, the effects of doxycycline used as a non selective MMP inhibitor in experimental and clinical studies will be discussed.", "output": "doxycycline." }, { "input": "Matrix metalloproteinases as drug targets in acute pulmonary embolism.", "output": "There is no related enetity." }, { "input": "Acute pulmonary embolism is a critical condition associated with increased mortality.", "output": "There is no related enetity." }, { "input": "Lung embolization causes acute pulmonary hypertension and right ventricle afterload.", "output": "There is no related enetity." }, { "input": "Global heart ischemia supervenes and may lead to severe shock and death.", "output": "There is no related enetity." }, { "input": "In this article, we reviewed current literature supporting the idea that abnormal matrix metalloproteinase ( MMP ) activity contributes to acute pulmonary embolism - induced hemodynamic changes.", "output": "There is no related enetity." }, { "input": "While low MMP levels are usually found in normal lung tissues, it is well known that inflammation and lung injury increase MMP expression and activity.", "output": "There is no related enetity." }, { "input": "This is probably due to recruitment and migration of inflammatory cells from the circulation to lung tissues.", "output": "There is no related enetity." }, { "input": "In addition, recent studies have shown increased MMP levels and activity in the right ventricle from animals with acute pulmonary embolism.", "output": "There is no related enetity." }, { "input": "Such increases in proteolytic activity were associated with increased cardiac troponin I in serum, suggesting a possible role for MMPs in cardiomyocyte injury during acute pulmonary embolism.", "output": "There is no related enetity." }, { "input": "These alterations have justified the use of doxycycline as an MMP inhibitor in acute pulmonary embolism.", "output": "doxycycline." }, { "input": "We review current evidence indicating that MMPs are targets in this critical condition.", "output": "There is no related enetity." }, { "input": "MMP inhibition apparently exerts antihypertensive effects and protects against cardiomyocyte injury caused by acute pulmonary embolism.", "output": "There is no related enetity." }, { "input": "A Novel Marine Drug, SZ - 685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR - 200c.", "output": "SZ - 685C." }, { "input": "Objective: We found a novel marine drug, SZ - 685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus ( No. 1403 ) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells.", "output": "SZ - 685C." }, { "input": "However, its anticancer mechanism remains unknown.", "output": "There is no related enetity." }, { "input": "The aims of this study were to observe the effectiveness of SZ - 685C on pituitary adenoma cells and determine the underlying mechanisms of action.", "output": "SZ - 685C." }, { "input": "Methods: A rat prolactinoma cell line, MMQ, was used in this study.", "output": "There is no related enetity." }, { "input": "A dose escalation of SZ - 685C was performed on this cell line, and cell viability was assessed using an MTT assay.", "output": "SZ - 685C, MTT." }, { "input": "Hoechst 33342, Annexin V - FITC / PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ - 685C.", "output": "FITC, SZ - 685C." }, { "input": "The effect of SZ - 685C on prolactin expression was also evaluated using RT - PCR and immunoblotting.", "output": "SZ - 685C." }, { "input": "Quantitative RT - PCR was used to detect the expression of miR - 200c in SZ - 685C - stimulated MMQ cells and pituitary adenoma tissues.", "output": "SZ - 685C." }, { "input": "This miRNA was then overexpressed in MMQ cells via transfection of a miR - 200c mimic to identify the mechanism underling the anti - tumor effect of SZ - 685C.", "output": "SZ - 685C." }, { "input": "Results: SZ - 685C inhibited MMQ cell growth in a dose - dependent manner but showed little toxicity toward rat pituitary cells ( RPCs ).", "output": "SZ - 685C." }, { "input": "The IC50s of SZ - 685C in MMQ cells and RPCs were 13. 2 +/- 1. 3 mM and 49. 1 +/- 11. 5 mM, respectively, which was statistically significant.", "output": "SZ - 685C." }, { "input": "Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ - 685C, and the expression level of prolactin ( PRL ) was inhibited.", "output": "SZ - 685C." }, { "input": "Nevertheless, the level of PRL mRNA was unchanged.", "output": "There is no related enetity." }, { "input": "Additionally, miR - 200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR - 200c was observed in SZ - 685C - treated MMQ cells.", "output": "SZ - 685C." }, { "input": "Furthermore, the overexpression of miR - 200c weakened the effect of SZ - 685C - induced apoptosis of MMQ cells.", "output": "SZ - 685C." }, { "input": "Conclusions: Our results suggest that SZ - 685C induces MMQ cell apoptosis in a miR - 200c - dependent manner.", "output": "SZ - 685C." }, { "input": "Therefore, SZ - 685C might be a useful alternative treatment for pituitary adenoma.", "output": "SZ - 685C." }, { "input": "JAK inhibitors: pharmacology and clinical activity in chronic myeloprolipherative neoplasms.", "output": "There is no related enetity." }, { "input": "The Janus family kinases ( JAKs ), JAK1, JAK2, JAK3, and TYK2, are involved in cell growth, survival, development, and differentiation of a variety of cells, particularly immune cells and hematopoietic cells.", "output": "There is no related enetity." }, { "input": "They form a subgroup of the non - receptor protein tyrosine kinases.", "output": "tyrosine." }, { "input": "Activating mutations within each of the JAKs is associated with malignant transformations; the most common are mutations of JAK2 in polycythemia vera ( PV ) and other myeloproliferative neoplasms ( MPN ).", "output": "There is no related enetity." }, { "input": "Identification of the V617F mutation of the JAK2 gene ( JAK2 V617F ) led to an important breakthrough in the understanding of MPN disease pathogenesis.", "output": "There is no related enetity." }, { "input": "The JAK2 V617F mutation is present in the majority of PV patients, and about 50 % of patients with essential thrombocythemia ( ET ) and primary myelofibrosis ( PMF ) are affected.", "output": "There is no related enetity." }, { "input": "This mutation leads to hyperactivation of JAK2, cytokine - independent signaling, and subsequent activation of downstream signaling networks.", "output": "There is no related enetity." }, { "input": "JAK2 ATP - competitive inhibitors that indirectly inhibit the JAK - STAT pathway are new candidates for the treatment of MPN.", "output": "ATP." }, { "input": "JAK2 inhibitors in development for the treatment of MPN have demonstrated clinical activity with minimal toxicity.", "output": "There is no related enetity." }, { "input": "These agents consistently alleviate constitutional symptoms and reduce spleen size in PMF and other MPN.", "output": "There is no related enetity." }, { "input": "However, some of these inhibitors have additional unique effects.", "output": "There is no related enetity." }, { "input": "Ruxolitinib causes a significant reduction in the level of pro - inflammatory cytokines.", "output": "Ruxolitinib." }, { "input": "Another inhibitor, CYT387, improves anemia.", "output": "There is no related enetity." }, { "input": "Many other JAK2 inhibitors such as TG101348 or SAR302503, SB1518, CEP701 and LY2784544 are now under investigation for MPN development.", "output": "TG101348, SAR302503, SB1518, CEP701, LY2784544." }, { "input": "In contrast tasocitinib, a predominantly JAK3 inhibitor, is being evaluated in a number of inflammatory and immunological diseases, including rheumatoid arthritis, psoriasis, ulcerative colitis, dry eye disease and in kidney transplant patients.", "output": "tasocitinib." }, { "input": "In conclusion the use of JAK inhibitors in MPN and some of the immune - mediated disorders is a promising new strategy for therapy.", "output": "There is no related enetity." }, { "input": "However, definitive data from ongoing and future preclinical and clinical trials will aid in better defining the status of these drugs in the treatment of these diseases.", "output": "There is no related enetity." }, { "input": "Cellular signaling crosstalk between multiple receptors for investigation of pathophysiology in multifactorial diseases - - what is clinically - relevant crosstalk?", "output": "There is no related enetity." }, { "input": "Recently, genomics and proteomics have been utilized as advanced tools for investigation of cellular signaling pathways and molecular interactions, and elucidated promiscuous networks composed of numerous interactions among pathways.", "output": "There is no related enetity." }, { "input": "However, some of these interactions are considered to be simply contributing to background ' noise ' and others are as ' crosstalk ' biologically - relevant to cellular physiology, leading to synergy effects more than additive responses in an entire organism.", "output": "There is no related enetity." }, { "input": "Effort is now required to determine which interactions truly contribute to final physiological output.", "output": "There is no related enetity." }, { "input": "A receptor is the prime example of connectors among the networks.", "output": "There is no related enetity." }, { "input": "It functions, not simply as a signaling gateway, but also as an active trader by forming inter - receptor dimers.", "output": "There is no related enetity." }, { "input": "Furthermore, various receptors can modulate the function of the other receptors by input to common intracellular signaling pathways, establishing functional crosstalk among networks.", "output": "There is no related enetity." }, { "input": "Our findings by combined analyses of gene polymorphisms of two separate genes present evidences that such is the case with human body in a clinical setting: 1 ) an integrated effect of epidermal growth factor receptor ( EGFR ) and protease activated receptor - 1 ( PAR - 1 ) on susceptibility to airway hyperresponsiveness ( AHR ), and 2 ) a crosstalk effect between muscarinic acetylcholine receptor ( mAChRs ) and beta ( 2 ) adrenoceptor ( beta ( 2 ) AR ) on bronchodilatory response to anticholinergic agents in patients with COPD.", "output": "acetylcholine." }, { "input": "These results indicate that these interactions are unlikely to be ' noise ' but functionally - relevant ' crosstalk ' in a human body.", "output": "There is no related enetity." }, { "input": "This review attempts to highlight the clinically - relevant ' crosstalk ' paradigm in a human body which provides us a novel insight necessary to investigate pathophysiology in common multifactorial diseases and to develop new drugs.", "output": "There is no related enetity." }, { "input": "Mechanism of copper ( I ) / TEMPO - catalyzed aerobic alcohol oxidation.", "output": "copper ( I ), alcohol." }, { "input": "Homogeneous Cu / TEMPO catalyst systems ( TEMPO = 2, 2, 6, 6 - tetramethylpiperidine - N - oxyl ) have emerged as some of the most versatile and practical catalysts for aerobic alcohol oxidation.", "output": "Cu, TEMPO, TEMPO, 2 , 2 , 6 , 6 - tetramethylpiperidine - N - oxyl, alcohol." }, { "input": "Recently, we disclosed a ( bpy ) Cu ( I ) / TEMPO / NMI catalyst system ( NMI = N - methylimidazole ) that exhibits fast rates and high selectivities, even with unactivated aliphatic alcohols.", "output": "Cu ( I ), TEMPO, NMI, NMI, N - methylimidazole, alcohols." }, { "input": "Here, we present a mechanistic investigation of this catalyst system, in which we compare the reactivity of benzylic and aliphatic alcohols.", "output": "benzylic and aliphatic alcohols." }, { "input": "This work includes analysis of catalytic rates by gas - uptake and in situ IR kinetic methods and characterization of the catalyst speciation during the reaction by EPR and UV - visible spectroscopic methods.", "output": "There is no related enetity." }, { "input": "The data support a two - stage catalytic mechanism consisting of ( 1 ) \" catalyst oxidation \" in which Cu ( I ) and TEMPO - H are oxidized by O ( 2 ) via a binuclear Cu ( 2 ) O ( 2 ) intermediate and ( 2 ) \" substrate oxidation \" mediated by Cu ( II ) and the nitroxyl radical of TEMPO via a Cu ( II ) - alkoxide intermediate.", "output": "Cu ( I ), TEMPO, H, O ( 2 ), Cu ( 2 ) O ( 2 ), Cu ( II ), nitroxyl, Cu ( II ), alkoxide." }, { "input": "Catalytic rate laws, kinetic isotope effects, and spectroscopic data show that reactions of benzylic and aliphatic alcohols have different turnover - limiting steps.", "output": "benzylic and aliphatic alcohols." }, { "input": "Catalyst oxidation by O ( 2 ) is turnover limiting with benzylic alcohols, while numerous steps contribute to the turnover rate in the oxidation of aliphatic alcohols.", "output": "O ( 2 ), benzylic alcohols, aliphatic alcohols." }, { "input": "Recent progress in biological activities and synthetic methodologies of pyrroloquinoxalines.", "output": "pyrroloquinoxalines." }, { "input": "Pyrroloquinoxalines have proved to be a very attractive scaffold for medicinal chemist in the recent past.", "output": "Pyrroloquinoxalines." }, { "input": "These compounds were extensively studied as bioactive compounds and many of them are known to be biologically and medicinally useful molecules, such as anti - HIV agents, antimalarial agents, antagonist agents, anticancer agents, and PARP - 1 inhibitors.", "output": "There is no related enetity." }, { "input": "Additionally, pyrroloquinoxalines are also important intermediates for the construction of 5 - HT3 receptor agonists.", "output": "pyrroloquinoxalines." }, { "input": "In this review the developments in biological activities and synthetic methodologies of pyrroloquinoxalines are discussed.", "output": "pyrroloquinoxalines." }, { "input": "Small - molecule inhibitors for the treatment of hepatitis B virus documented in patents.", "output": "There is no related enetity." }, { "input": "Hepatitis B virus ( HBV ) infection is a serious health problem worldwide, and the current treatment methods including vaccines, immunomodulators, interferons and nucleoside analogs are far from satisfactory.", "output": "nucleoside." }, { "input": "For the search of new anti - HBV agents, much investigation has revealed a large number of small - molecule compounds with various skeletons and promising anti - HBV activities.", "output": "There is no related enetity." }, { "input": "Although some reviews on anti - HBV progress have been published, they are mainly concentrated on the results reported in journal articles.", "output": "There is no related enetity." }, { "input": "This review provides an overview of the structural features and anti - HBV properties of the small - molecule anti - HBV inhibitors claimed in recent patents ( from 2001 to 2010 ).", "output": "There is no related enetity." }, { "input": "These small - molecules can be structurally classified as two main types, nucleoside analogs ( cyclic and acyclic nucleosides ) and non - nucleosides ( natural and synthesized compounds ), which are declared with the activity inhibiting the secretion of HBsAg and HBeAg and HBV DNA replication in vitro, as well as anti - DHBV DNA in vivo.", "output": "nucleoside, nucleosides, nucleosides." }, { "input": "Especially, the non - nucleosides with diverse skeletons and novel mechanism offer prolific candidates for anti - HBV drug discovery, which are preferred to be used as adjuvant therapy for HBV infection.", "output": "nucleosides." }, { "input": "This paper will provide valuable information for understanding the current anti - HBV investigation and developing new anti - HBV agents.", "output": "There is no related enetity." }, { "input": "Radiolytic transformation of rotenone with potential anti - adipogenic activity.", "output": "rotenone." }, { "input": "Radiolytic transformation of the isoflavonoid rotenone ( 1 ) with gamma - irradiation afforded two new degraded products, rotenoisins A ( 2 ) and ( 3 ).", "output": "isoflavonoid rotenone, rotenoisins A." }, { "input": "The structures of the two new rotenone derivatives were elucidated on the basis of spectroscopic methods.", "output": "rotenone." }, { "input": "The new products 2 and 3 exhibited significantly enhanced inhibitory activities against pancreatic lipase and adipocyte differentiation in 3T3 - L1 cells when compared to parent rotenone.", "output": "rotenone." }, { "input": "ATP stimulates PGE ( 2 ) / cyclin D1 - dependent VSMCs proliferation via STAT3 activation: role of PKCs - dependent NADPH oxidase / ROS generation.", "output": "ATP, PGE ( 2 ), NADPH." }, { "input": "Vascular smooth muscle cells ( VSMCs ) that function as synthetic units play important roles in cardiovascular diseases.", "output": "There is no related enetity." }, { "input": "Extracellular nucleotides, such as ATP, have been shown to act via activation of P2 purinoceptors implicated in various inflammatory diseases, we hypothesized that extracellular nucleotides contribute to vascular diseases via up - regulation of inflammatory proteins, including cyclooxygenase - 2 ( COX - 2 ) and cytosolic phospholipase A2 ( cPLA2 ) in VSMCs.", "output": "nucleotides, ATP, nucleotides." }, { "input": "However, the mechanisms of ATP - induced cPLA2 and COX - 2 expression and PGE2 synthesis remain largely unclear.", "output": "ATP, PGE2." }, { "input": "We showed that pretreatment with the inhibitors of STAT3 ( CBE ), NADPH oxidase [ diphenyleneiodonium chloride ( DPI ) or apocynin ( APO ) ], ROS [ N - acetyl - l - cysteine ( NAC ) ], and PKC ( Ro - 318220, G o 6983, or Rottlerin ) or transfection with siRNAs of STAT3 and p47 ( phox ) markedly inhibited ATP gamma S - induced cPLA2 and COX - 2 mRNA / protein expression and promoter activity and PGE2 secretion.", "output": "NADPH, diphenyleneiodonium chloride, DPI, apocynin, APO, N - acetyl - l - cysteine, NAC, Ro - 318220, G o 6983, Rottlerin, PGE2." }, { "input": "ATP gamma S further stimulated PKC, p47 ( phox ), and STAT3 translocation.", "output": "There is no related enetity." }, { "input": "Moreover, ATP gamma S - induced STAT3 phosphorylation and translocation was inhibited by pretreatment with the inhibitors of PKC, NADPH oxidase, and ROS.", "output": "NADPH." }, { "input": "ATP gamma S enhanced NADPH oxidase activity and ROS generation in VSMCs, which were reduced by pretreatment with Ro - 318220, G o 6983, or Rottlerin.", "output": "NADPH, Ro - 318220, G o 6983, Rottlerin." }, { "input": "Finally, we found that ATP gamma S significantly induced cyclin D1 expression and VSMCs proliferation, which were inhibited by pretreatment with NAC, APO, DPI, Ro - 318220, G o 6983, Rottlerin, or CBE or transfection with siRNAs of COX - 2 and cyclin D1.", "output": "NAC, APO, DPI, Ro - 318220, G o 6983, Rottlerin." }, { "input": "We also demonstrated that ATP gamma S induced cyclin D1 expression via a PGE2 - dependent pathway.", "output": "PGE2." }, { "input": "These results suggested that ATP gamma S - induced cPLA2 / COX - 2 expression and PGE2 secretion is mediated through a PKC / NADPH oxidase / ROS / STAT3 - dependent pathway in VSMCs.", "output": "PGE2, NADPH." }, { "input": "DMAP1 is an essential regulator of ATM activity and function.", "output": "There is no related enetity." }, { "input": "The hereditary autosomal recessive disease ataxia telangiectasia ( A - T ) is caused by mutation in the DNA damage kinase ATM.", "output": "There is no related enetity." }, { "input": "ATM ' s main function is to orchestrate DNA repair, thereby maintaining genomic stability.", "output": "There is no related enetity." }, { "input": "ATM activity is increased in response to several stimuli, including ionising radiation ( IR ) and hypotonic stress.", "output": "There is no related enetity." }, { "input": "DNMT1 - associated protein 1 ( DMAP1 ) is a member of the TIP60 - p400 histone acetyl transferase ( HAT ) complex, which acetylates histone H4 at lysine 16 ( H4K16 ) to affect chromatin relaxation and modulate ATM activation.", "output": "acetyl, lysine." }, { "input": "Here we demonstrate that DMAP1 is required for both modes of ATM activation.", "output": "There is no related enetity." }, { "input": "Knockdown of DMAP1 impaired IR - induced ATM activation and consequently resulted in radiosensitivity and impaired the G2 / M checkpoint.", "output": "There is no related enetity." }, { "input": "Moreover, DMAP1 was also required for efficient ATM signalling in response to hypotonic stress.", "output": "There is no related enetity." }, { "input": "Overexpression of DMAP1 increased IR - induced ATM substrate phosphorylation, suggesting that DMAP1 function is rate limiting for ATM signalling.", "output": "There is no related enetity." }, { "input": "DMAP1 associated with TIP60 - dependent HAT activity, and depletion of DMAP1 reduced H4K16 acetylation in response to DNA damage.", "output": "There is no related enetity." }, { "input": "Treatment with histone deacetylase inhibitors rescued IR - induced ATM signalling in Dmap1 - depleted cells.", "output": "There is no related enetity." }, { "input": "These results suggest that DMAP1 is a critical regulator of ATM activity and function. Oncogene advance online publication, 14 January 2013; doi: 10. 1038 / onc. 2012. 597.", "output": "There is no related enetity." }, { "input": "Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi Anemia cells.", "output": "There is no related enetity." }, { "input": "Fanconi Anemia ( FA ) is a rare genetic disorder associated with a bone - marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "output": "There is no related enetity." }, { "input": "Majority of the 15 FA genes and encoded proteins characterized so far are integrated into DNA repair pathways, however, other important functions cannot be excluded.", "output": "There is no related enetity." }, { "input": "FA cells are sensitive to oxidants, and accumulation of oxidized proteins has been characterized for several FA subgroups.", "output": "There is no related enetity." }, { "input": "Clinical phenotypes of both FA and other closely related diseases suggest altered functions of mitochondria, organelles responsible for cellular energetic metabolism, and also serving as an important producer and the most susceptible target from reactive oxidative species ( ROS ).", "output": "There is no related enetity." }, { "input": "In this study, we have shown that elevated level of mitochondrial ROS in FA cells is in parallel with the decrease of mitochondrial membrane potential, the decrease of ATP production, impaired oxygen uptake and pathological changes in the morphology of mitochondria.", "output": "oxygen." }, { "input": "This is accompanied by inactivation of enzymes that are essential for the energy production ( F1F0ATPase and cytochrome C oxidase ) and detoxification of ROS ( superoxide dismutase, SOD1 ).", "output": "superoxide." }, { "input": "In turn, overexpression of SOD1 could rescue oxygen consumption rate in FA - deficient cells.", "output": "oxygen." }, { "input": "Importantly, the depletion of mitochondria improved survival rate of mitomycin C treated FA cells suggesting that hypersensitivity of FA cells to chemotherapeutic drugs could be in part due to the mitochondria - mediated oxidative stress.", "output": "There is no related enetity." }, { "input": "On the basis of our results, we propose that deficiency in FA genes lead to disabling mitochondrial ROS - scavenging machinery further affecting mitochondrial functions and suppressing cell respiration. Oncogene advance online publication, 14 January 2013; doi: 10. 1038 / onc. 2012. 583.", "output": "There is no related enetity." }, { "input": "Axl / Gas6 / NF kappa B signalling in schwannoma pathological proliferation, adhesion and survival.", "output": "There is no related enetity." }, { "input": "TAM family receptor tyrosine kinases comprising Tyro3 ( Sky ), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth.", "output": "There is no related enetity." }, { "input": "Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2.", "output": "There is no related enetity." }, { "input": "The benign character of merlin - deficient tumours makes them less responsive to chemotherapy.", "output": "There is no related enetity." }, { "input": "We previously showed that, amongst other growth factor receptors, TAM family receptors ( Tyro3, Axl and Mer ) are significantly overexpressed in schwannoma tissues.", "output": "There is no related enetity." }, { "input": "As Axl is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1, previously shown to be a key regulator in schwannoma growth we hypothesized that Axl is a good target to study in merlin - deficient tumours.", "output": "There is no related enetity." }, { "input": "Moreover, Axl positively regulates the oncogene Yes - associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin - deficient meningioma and mesothelioma.", "output": "There is no related enetity." }, { "input": "Here, we demonstrated strong overexpression and activation of Axl receptor as well as its ligand Gas6 in human schwannoma primary cells compared to normal Schwann cells.", "output": "There is no related enetity." }, { "input": "We show that Gas6 is mitogenic and increases schwannoma cell - matrix adhesion and survival acting via Axl in schwannoma cells.", "output": "There is no related enetity." }, { "input": "Stimulation of the Gas6 / Axl signalling pathway recruits Src, focal adhesion kinase ( FAK ) and NF kappa B.", "output": "There is no related enetity." }, { "input": "We showed that NF kappa B mediates Gas6 / Axl - mediated overexpression of survivin, cyclin D1 and FAK, leading to enhanced survival, cell - matrix adhesion and proliferation of schwannoma.", "output": "There is no related enetity." }, { "input": "We conclude that Axl / FAK / Src / NF kappa B pathway is relevant in merlin - deficient tumours and is a potential therapeutic target for schwannoma and other merlin - deficient tumours. Oncogene advance online publication, 14 January 2013; doi: 10. 1038 / onc. 2012. 587.", "output": "There is no related enetity." }, { "input": "The costimulatory molecule B7 - H4 promote tumor progression and cell proliferation through translocating into nucleus.", "output": "There is no related enetity." }, { "input": "B7 - H4, a member of B7 family, is a transmembrane protein and inhibits T - cells immunity.", "output": "There is no related enetity." }, { "input": "However, in a variety of tumor cells, B7 - H4 was detected predominantly in intracellular compartments with unknown mechanism and functions.", "output": "There is no related enetity." }, { "input": "In this study, we analyzed B7 - H4 expression and subcellular distribution by immunohistochemistry in renal cell carcinoma ( RCC ) tissues.", "output": "There is no related enetity." }, { "input": "B7 - H4 protein was detected on the membrane, in the cytosol and / or in the nucleus in tumor tissues.", "output": "There is no related enetity." }, { "input": "The membrane and nuclear expression of B7 - H4 was significantly correlated with the tumor stages of RCC.", "output": "There is no related enetity." }, { "input": "Moreover, the membrane localization of B7 - H4 was inversely correlated with the intensity of tumor infiltrates lymphocyte ( TILs ), whereas no association was observed between nuclear expression of B7 - H4 and the density of TILs status.", "output": "There is no related enetity." }, { "input": "We further identified that B7 - H4 is a cytoplasmic - nuclear shuttling protein containing a functional nuclear localization sequence ( NLS ) motif.", "output": "There is no related enetity." }, { "input": "A point mutation of B7 - H4 NLS motif blocked the leptomycin B - induced nuclear accumulation of B7 - H4.", "output": "There is no related enetity." }, { "input": "HEK293 cells stably expressing B7 - H4 NLS mutant exhibited more potent inhibition in T - cell proliferation and cytokine production through increasing its surface expression compared with wild - type B7 - H4 transfected cells owing to their increased surface expression.", "output": "There is no related enetity." }, { "input": "Most importantly, overexpression of wild - type B7 - H4 in HEK293 cells enhanced tumor cell proliferation in vitro and tumorigenicity in vivo, promoted G1 / S phase transition.", "output": "There is no related enetity." }, { "input": "The regulation of cell cycle by wild - type B7 - H4 was partialy due to upregulation of Cyclin D 1 and Cyclin E.", "output": "There is no related enetity." }, { "input": "A mutation of B7 - H4 NLS motif abolished the B7 - H4 - mediated cell proliferation and cell cycle regulation.", "output": "There is no related enetity." }, { "input": "Furthermore, B7 - H4 wild - type confers chemoresistance activity to RCC cell lines including Caki - 1 and ACHN.", "output": "There is no related enetity." }, { "input": "Our study provides a new insight into the functional implication of B7 - H4 in its subcellular localization. Oncogene advance online publication, 14 January 2013; doi: 10. 1038 / onc. 2012. 600.", "output": "There is no related enetity." }, { "input": "Papillary thyroid carcinoma arising from a thyroglossal duct cyst: a single institution experience.", "output": "There is no related enetity." }, { "input": "Thyroid cancers arising from a thyroglossal duct cyst ( TGDC ) are rarely reported.", "output": "There is no related enetity." }, { "input": "No clear consensus exists regarding optimal management.", "output": "There is no related enetity." }, { "input": "In this light, TGDC carcinomas recently treated at Asan Medical Center, as well as previously reported cases in the literature, were reviewed.", "output": "There is no related enetity." }, { "input": "There were ten patients who were diagnosed with TGDC carcinoma at our institution.", "output": "There is no related enetity." }, { "input": "All patients underwent pre - operative fine - needle aspiration biopsy ( FNAB ).", "output": "There is no related enetity." }, { "input": "Nine patients were suspected of having papillary carcinoma following cytology.", "output": "There is no related enetity." }, { "input": "The Sistrunk operation ( SO ) was performed in four patients, SO with total thyroidectomy ( SO / TT ) was performed in three patients, and SO / TT with neck dissection was performed in three patients.", "output": "There is no related enetity." }, { "input": "Six patients who received total thyroidectomy underwent radioactive iodine ( RAI ) therapy and T4 suppression.", "output": "iodine." }, { "input": "With a median follow - up period of 28. 5 months, two patients showed recurrence and one of them died of the disease.", "output": "There is no related enetity." }, { "input": "We analyzed 163 cases from 1990 to 2012 with three or more cases TGDC carcinoma, including the present study.", "output": "There is no related enetity." }, { "input": "Among 48 patients who underwent FNAB, 75 % had papillary thyroid carcinoma ( PTC ).", "output": "There is no related enetity." }, { "input": "SO, SO / TT, or SO / TT with neck dissection was performed in 27 %, 41 %, and 32 % of patients, respectively.", "output": "There is no related enetity." }, { "input": "Among 119 patients who received total thyroidectomy, 36 % had concomitant PTC in the thyroid.", "output": "There is no related enetity." }, { "input": "Among 52 patients who received neck dissection, 69 % had cervical nodal involvement.", "output": "There is no related enetity." }, { "input": "The results of our review suggest that when TGDC carcinoma is suspected, ultrasonography and, if necessary, FNAB should be performed.", "output": "There is no related enetity." }, { "input": "If these tests reveal a suspected lesion in the thyroid or lymph node, SO / TT and lymph node dissection should be performed.", "output": "There is no related enetity." }, { "input": "The in vitro and in vivo genotoxicity of isotretinoin assessed by cytokinesis blocked micronucleus assay and comet assay.", "output": "isotretinoin." }, { "input": "Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow - band ultraviolet B ( NBUVB ) irradiation to treat patients with acne and psoriasis vulgaris.", "output": "Isotretinoin, retinoic acid." }, { "input": "As both diseases need frequent and / or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important.", "output": "retinoids." }, { "input": "Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB.", "output": "isotretinoin." }, { "input": "In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin ( 1. 2 - 20 mu M ) ( i. e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations ).", "output": "isotretinoin." }, { "input": "In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy ( 8 or 20mg / day ) or combined with NBUVB ( 20mg isotretinoin / day + NBUVB ).", "output": "isotretinoin, isotretinoin." }, { "input": "The genotoxic effect was evaluated by the cytokinesis - blocked micronucleus and the comet assays.", "output": "There is no related enetity." }, { "input": "Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo.", "output": "isotretinoin." }, { "input": "There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB.", "output": "isotretinoin." }, { "input": "The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses.", "output": "isotretinoin." }, { "input": "Platinum folate nanoparticles toxicity: cancer vs. normal cells.", "output": "Platinum folate." }, { "input": "Almost for two decades metallic nanoparticles are successfully used for cancer detection, imaging and treatment.", "output": "There is no related enetity." }, { "input": "Due to their high electron density they can be easily observed by electron microscopy and used in laser and radiofrequency therapy as energy releasing agents.", "output": "There is no related enetity." }, { "input": "However, the limitation for this practice is an inability to generate tumor - specific heating in a minimally invasive manner to the healthy tissue.", "output": "There is no related enetity." }, { "input": "To overcome this restraint we proposed to use folic acid coated metallic nanoparticles and determine whether they preferentially penetrate cancer cells.", "output": "folic acid." }, { "input": "We developed technique for synthesizing platinum nanoparticles using folic acid as stabilizing agent which produced particles of relatively narrow size distribution, having d = 2. 3 +/- 0. 5 nm.", "output": "platinum, folic acid." }, { "input": "High resolution TEM and zeta potential analysis indicated that the particles produced by this method had a high degree of crystalline order with no amorphous outer shell and a high degree of colloidal stability.", "output": "There is no related enetity." }, { "input": "The keratinocytes and mammary breast cells ( cancer and normal ) were incubated with platinum folate nanoparticles, and the results showed that the IC50 was significantly higher for the normal cells than the cancer cells in both cases, indicating that these nanoparticles preferentially target the cancer cells.", "output": "platinum folate." }, { "input": "TEM images of thin sections taken from the two types of cells indicated that the number of vacuoles and morphology changes after incubation with nanoparticles was also larger for the cancer cells in both types of tissue studied.", "output": "There is no related enetity." }, { "input": "No preferential toxicity was observed when folic acid receptors were saturated with free folic acid prior to exposure to nanoparticles.", "output": "folic acid, folic acid." }, { "input": "These results confirm our hypothesis regarding the preferential penetration of folic acid coated nanoparticles to cancer cells due to receptor mediated endocytosis.", "output": "folic acid." }, { "input": "Identification of benzofuran - 3 - yl ( phenyl ) methanones as novel SIRT1 inhibitors: binding mode, inhibitory mechanism and biological action.", "output": "benzofuran - 3 - yl ( phenyl ) methanones." }, { "input": "SIRT1 is a NAD ( + ) - dependent deacetylase.", "output": "NAD ( + )." }, { "input": "Here we described new SIRT1 inhibitors with the scaffold of benzofuran - 3 - yl ( phenyl ) methanone.", "output": "benzofuran - 3 - yl ( phenyl ) methanone." }, { "input": "The inhibitors were predicted to bind in C - pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347.", "output": "Phe273, Phe312, Ile347." }, { "input": "Introducing hydroxyl to meta position of phenyl may form H - bond with Asn346.", "output": "hydroxyl, phenyl, H, Asn346." }, { "input": "Indeed, ( 2, 5 - dihydroxyphenyl ) ( 5 - hydroxy - 1 - benzofuran - 3 - yl ) methanone ( 16 ), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition.", "output": "( 2 , 5 - dihydroxyphenyl ) ( 5 - hydroxy - 1 - benzofuran - 3 - yl ) methanone, hydroxyls." }, { "input": "The binding mode was validated by structural modifications and kinetic studies.", "output": "There is no related enetity." }, { "input": "Since C - pocket is the site where the nicotinamide moiety of NAD ( + ) binds and the hydrolysis takes place, binding of 16 in C - pocket would block the transformation of NAD ( + ) to productive conformation and hence inhibit the deacetylase activity.", "output": "nicotinamide, NAD ( + ), NAD ( + )." }, { "input": "Consistently, 16 inhibited SIRT1 through up - regulating p53 acetylation on cellular level.", "output": "There is no related enetity." }, { "input": "Comparison of orientation and rotational motion of skeletal muscle cross - bridges containing phosphorylated and dephosphorylated myosin regulatory light chain.", "output": "There is no related enetity." }, { "input": "Calcium binding to thin filaments is a major element controlling active force generation in striated muscles.", "output": "Calcium." }, { "input": "Recent evidence suggests that processes other than Ca ( 2 + ) binding, such as phosphorylation of myosin regulatory light chain ( RLC ) also controls contraction of vertebrate striated muscle ( Cooke, R. ( 2011 ) Biophys. Rev. 3, 33 - 45 ).", "output": "Ca ( 2 + )." }, { "input": "Electron paramagnetic resonance ( EPR ) studies using nucleotide analog spin label probes showed that dephosphorylated myosin heads are highly ordered in the relaxed fibers and have very low ATPase activity.", "output": "nucleotide." }, { "input": "This ordered structure of myosin cross - bridges disappears with the phosphorylation of RLC ( Stewart, M. ( 2010 ) Proc. Natl. Acad. Sci. U. S. A. 107, 430 - 435 ).", "output": "There is no related enetity." }, { "input": "The slower ATPase activity in the dephosporylated moiety has been defined as a new super - relaxed state ( SRX ).", "output": "There is no related enetity." }, { "input": "It can be observed in both skeletal and cardiac muscle fibers ( Hooijman, P., Stewart, M. A., and Cooke, R. ( 2011 ) Biophys. J. 100, 1969 - 1976 ).", "output": "There is no related enetity." }, { "input": "Given the importance of the finding that suggests a novel pathway of regulation of skeletal muscle, we aim to examine the effects of phosphorylation on cross - bridge orientation and rotational motion.", "output": "There is no related enetity." }, { "input": "We find that: ( i ) relaxed cross - bridges, but not active ones, are statistically better ordered in muscle where the RLC is dephosporylated compared with phosphorylated RLC; ( ii ) relaxed phosphorylated and dephosphorylated cross - bridges rotate equally slowly; and ( iii ) active phosphorylated cross - bridges rotate considerably faster than dephosphorylated ones during isometric contraction but the duty cycle remained the same, suggesting that both phosphorylated and dephosphorylated muscles develop the same isometric tension at full Ca ( 2 + ) saturation.", "output": "Ca ( 2 + )." }, { "input": "A simple theory was developed to account for this fact.", "output": "There is no related enetity." }, { "input": "Methylation of histone H3 on lysine 4 by the lysine methyltransferase SET1 protein is needed for normal clock gene expression.", "output": "lysine, lysine." }, { "input": "The circadian oscillator controls time - of - day gene expression by a network of interconnected feedback loops and is reset by light.", "output": "There is no related enetity." }, { "input": "The requisite for chromatin regulation in eukaryotic transcription necessitates temporal regulation of histone - modifying and chromatin - remodeling enzymes for proper clock function.", "output": "There is no related enetity." }, { "input": "CHD1 is known to bind H3K4me3 in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency ( frq ) gene.", "output": "There is no related enetity." }, { "input": "Based on this, we examined a strain lacking SET1 to determine the role of H3K4 methylation in clock - and light - mediated frq regulation.", "output": "There is no related enetity." }, { "input": "Expression of frq was altered in strains lacking set1 under both circadian - and light - regulated gene expression.", "output": "There is no related enetity." }, { "input": "There is a delay in the phasing of H3K4me3 relative to the peak in frq expression.", "output": "There is no related enetity." }, { "input": "White Collar 2 ( WC - 2 ) association with the frq promoter persists longer in Delta set1, suggesting a more permissible chromatin state.", "output": "There is no related enetity." }, { "input": "Surprisingly, SET1 is required for DNA methylation in the frq promoter, indicating a dependence on H3K4me for DNA methylation.", "output": "There is no related enetity." }, { "input": "The data support a model where SET1 is needed for proper regulation by modulating chromatin at frq.", "output": "There is no related enetity." }, { "input": "Inhibitory effect of anthocyanidins on hepatic glutathione S - transferase, UDP - glucuronosyltransferase and carbonyl reductase activities in rat and human.", "output": "anthocyanidins, glutathione, S, UDP, carbonyl." }, { "input": "Abstract 1.", "output": "There is no related enetity." }, { "input": "Anthocyanins and their aglycone anthocyanidins represent the most abundant flavonoids in human diet and popular constituents of various dietary supplements.", "output": "Anthocyanins, anthocyanidins, flavonoids." }, { "input": "The aim of this study was to evaluate inhibitory effect of four anthocyanidins ( delphinidin, cyanidin, malvidin and pelargonidin ) on three families of important drug - metabolizing enzymes: carbonyl reductases ( CBRs ), glutathione S - transferases ( GSTs ) and UDP - glucuronosyltransferases ( UGT ).", "output": "anthocyanidins, delphinidin, cyanidin, malvidin, pelargonidin, carbonyl, glutathione, S, UDP." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "Human or rat hepatic subcellular fractions were incubated with or without pure anthocyanidins ( 100 micro M ) and the activities of CBR, GST and UGT were assayed using menadione, 1 - chloro - 2, 4 - dinitrobenzene and p - nitrophenol as substrates, respectively.", "output": "anthocyanidins, menadione, 1 - chloro - 2 , 4 - dinitrobenzene, p - nitrophenol." }, { "input": "For the most potent inhibitors, half maximal inhibitory concentrations ( IC ( 50 ) ) were determined and the inhibition kinetics study was performed.", "output": "There is no related enetity." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "Anthocyanidins inhibited weakly the activity of GST and moderately the activities of CBR and UGT.", "output": "Anthocyanidins." }, { "input": "Cyanidin was the most potent inhibitor of human UGT with IC ( 50 ) = 69 micro M ( at 200 micro M substrate concentration ) and competitive type of action.", "output": "Cyanidin." }, { "input": "Delphinidin acted as significant non - competitive inhibitor of human CBR with IC ( 50 ) = 16 micro M ( at substrate concentration 500 micro M ).", "output": "Delphinidin." }, { "input": "The inhibitory potency of anthocyanidins differed in rat and human samples significantly.", "output": "anthocyanidins." }, { "input": "4.", "output": "There is no related enetity." }, { "input": "Anthocyanidins are able to inhibit CBR and UGT in vitro.", "output": "Anthocyanidins." }, { "input": "Possible interference of anthocyanidins ( in high - dose dietary supplements ) with simultaneously administered drugs, which are UGT or CBR substrates, should be checked.", "output": "anthocyanidins." }, { "input": "An adhesive bone marrow scaffold and bone morphogenetic - 2 protein carrier for cartilage tissue engineering.", "output": "There is no related enetity." }, { "input": "A chondroitin sulfate - bone marrow ( CS - BM ) adhesive hydrogel was used to localize rhBMP - 2 to enhance articular cartilage tissue formation.", "output": "sulfate." }, { "input": "Chondrocyte pellet culture revealed that 0. 1 and 1 mu g / mL of rhBMP - 2 enhanced sulfated - GAG content.", "output": "There is no related enetity." }, { "input": "rhBMP - 2 localization within the hydrogels was investigated, and it was found that BM, CS - NHS, and rhBMP - 2 levels and time affected rhBMP - 2 retention.", "output": "There is no related enetity." }, { "input": "Retention was modulated from 82 to 99 % over a 3 - week period for the material formulations investigated.", "output": "There is no related enetity." }, { "input": "To evaluate carrier efficacy, rhBMP - 2 and bovine articular chondrocytes were encapsulated within CS - BM, and biochemical evaluation revealed significant increases in total collagen production with rhBMP - 2.", "output": "There is no related enetity." }, { "input": "Histological analysis revealed more robust tissue formation and greater type - II collagen production with encapsulated rhBMP - 2.", "output": "There is no related enetity." }, { "input": "Subsequently, a subcutaneous culture of hydrogels revealed increased total collagen, type - II to type - I collagen ratio, and sulfated GAG in samples carrying rhBMP - 2.", "output": "There is no related enetity." }, { "input": "These findings indicate the development of a multifunctional system capable of localizing rhBMP - 2 to enhance repair tissue quality.", "output": "There is no related enetity." }, { "input": "Novel antiviral activity of l - dideoxy bicyclic nucleoside analogues versus vaccinia and measles viruses in vitro.", "output": "l - dideoxy bicyclic nucleoside." }, { "input": "Dideoxy bicyclic pyrimidine nucleoside analogues ( ddBCNAs ) with d - chirality have previously been described by us to inhibit replication of human cytomegalovirus.", "output": "Dideoxy bicyclic pyrimidine nucleoside, ddBCNAs." }, { "input": "We herein report for the first time that activity against vaccinia virus ( VACV ) was achieved using novel l - analogues.", "output": "There is no related enetity." }, { "input": "A structure - activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n - C ( 9 ) H ( 18 ) - O - n - C ( 5 ) H ( 11 ).", "output": "ether, n - C ( 9 ) H ( 18 ) - O - n - C ( 5 ) H ( 11 )." }, { "input": "This gave an IC ( 50 ) of 190 nM, a 60 - fold enhancement over the FDA - approved antiviral cidofovir.", "output": "cidofovir." }, { "input": "Interestingly, l - ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID ( 50 ) of 7. 5 mu M for the lead compound.", "output": "ddBCNAs." }, { "input": "We propose that l - ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.", "output": "ddBCNAs." }, { "input": "Reversible recruitment and emission of DO3A - derived lanthanide complexes at ligating molecular films on gold.", "output": "lanthanide." }, { "input": "The recruitment of DO3A - derived lanthanide complexes by ligation to isophthalic acid and catechol - modified gold surfaces, and their resulting sensitization, is reported herein.", "output": "lanthanide, isophthalic acid, catechol." }, { "input": "Predictably pH - dependent surface recruitment is associated with the expected fingerprint europium and terbium emission characteristics.", "output": "europium, terbium." }, { "input": "The intensity of the lanthanide luminescence scales exponentially with spacer length, indicating a strong quenching interaction between the lanthanide and the gold surface.", "output": "lanthanide, lanthanide." }, { "input": "The switchable catechol oxidation state provides a means of electrochemically triggering the release of prior ligated complexes.", "output": "catechol." }, { "input": "Determination of very rapid molecular rotation by using the central electron paramagnetic resonance line.", "output": "There is no related enetity." }, { "input": "Picosecond rotational correlation times of perdeuterated tempone ( PDT ) are found in alkane and aromatic liquids by directly using the spectral width of the central electron paramagnetic resonance line.", "output": "perdeuterated tempone, PDT." }, { "input": "This is done by mathematically eliminating the nonsecular spectral density from the spectral parameter equations, thereby removing the need to assume a particular form for it.", "output": "There is no related enetity." }, { "input": "This is preferable to fitting a constant correction factor to the spectral density, because such a factor does not fit well in the low picosecond range.", "output": "There is no related enetity." }, { "input": "The electron - nuclear spin dipolar interaction between the probe and solvent is shown to be negligible for the very rapid rotation of PDT in these liquids at the temperatures of the study.", "output": "PDT." }, { "input": "The rotational correlation times obtained with the proposed method generally agree to within experimental uncertainty with those determined by using the traditional parameters.", "output": "There is no related enetity." }, { "input": "Using the middle line width offers greater precision and smoother trends.", "output": "There is no related enetity." }, { "input": "Previous work with the central line width is discussed, and past discrepancies are explained as possibly resulting from residual inhomogeneous broadening.", "output": "There is no related enetity." }, { "input": "The rotational correlation time almost forms a common curve across all of the solvents when plotted with respect to isothermal compressibility, which shows the high dependence of rotation on liquid free volume.", "output": "There is no related enetity." }, { "input": "Further evidence for the sleep - promoting effects of 5 - HT2A receptor antagonists and demonstration of synergistic effects with the hypnotic, zolpidem in rats.", "output": "zolpidem." }, { "input": "5 - Hydroxytryptamine ( 5 - HT ) 2A antagonists are promising therapeutic agents for the treatment of sleep maintenance insomnias, but unlike hypnotics, they have limited effects on sleep initiation.", "output": "5 - Hydroxytryptamine, 5 - HT." }, { "input": "This study evaluated the effects of several 5 - HT2A antagonists ( eplivanserin, volinanserin and AVE8488 ) alone and / or in combination with the short - acting hypnotic, zolpidem, on the rat sleep profile.", "output": "eplivanserin, volinanserin, AVE8488, zolpidem." }, { "input": "A repeated - measures design was used in which rats were treated with eplivanserin ( 3 and 10 mg / kg, i. p. or p. o. ), volinanserin ( 0. 3 - 3 mg / kg, i. p. ), AVE8488 ( 0. 1 - 3 mg / kg, i. p. ) and zolpidem ( 3 and 10 mg / kg, p. o. ).", "output": "eplivanserin, volinanserin, AVE8488, zolpidem." }, { "input": "In addition, animals received a combination of eplivanserin ( 3 mg / kg, p. o. ) and zolpidem ( 3 mg / kg, p. o. ).", "output": "eplivanserin, zolpidem." }, { "input": "Electroencephalogram was analyzed for 6 h after administration.", "output": "There is no related enetity." }, { "input": "Eplivanserin did not modify wakefulness and non - rapid eye movement sleep ( NREMS ), while zolpidem ( 10 mg / kg po ) induced a marked increase in NREMS duration.", "output": "Eplivanserin, zolpidem." }, { "input": "Volinanserin ( 1 and 3 mg / kg ) and AVE8488 ( 0. 3 mg / kg ) similarly increased NREMS, while reducing wakefulness.", "output": "Volinanserin, AVE8488." }, { "input": "Moreover, the 5 - HT2A antagonists and, to a lesser extent, zolpidem, increased duration of NREMS episodes, while decreasing their frequency.", "output": "zolpidem." }, { "input": "When eplivanserin was co - administered with zolpidem, a synergistic effect was observed as the combination produced an increase in NREMS time and bouts duration.", "output": "eplivanserin, zolpidem." }, { "input": "These findings confirm further that 5 - HT2A antagonists promote the maintenance of sleep, and suggest that combining a 5 - HT2A antagonist with a short - acting hypnotic may be a useful strategy for the treatment of insomnia.", "output": "There is no related enetity." }, { "input": "Assessment of permethylated transition - metal sandwich complexes as internal reference redox systems in ionic liquids.", "output": "permethylated transition - metal." }, { "input": "This work reports the voltammetric behaviour of decamethylcobaltocenium, DmCc ( + ), in different ionic liquids for the first time.", "output": "decamethylcobaltocenium, DmCc ( + )." }, { "input": "Its redox potential was studied relative to that of decamethylferrocene, DmFc, and it is shown that the difference in the mid - point potential between these two permethylated transition - metal sandwich complexes is independent of the ionic liquid composition.", "output": "decamethylferrocene, DmFc, permethylated transition - metal." }, { "input": "A variable difference in mid - point potential, in contrast, was observed for ferrocene and cobaltocenium relative to that of DmFc in similar ionic liquids.", "output": "ferrocene, cobaltocenium, DmFc." }, { "input": "In addition, different limitations in the application of DmFc ( 0 / + ) and DmCc ( + / 0 ) couples as internal reference redox systems in ILs are discussed.", "output": "DmFc ( 0 / + ), DmCc ( + / 0 )." }, { "input": "From these, the observed spontaneous reaction between DmFc and oxygen leads to important implications toward the establishment of particular conditions for DmFc applications.", "output": "DmFc, DmFc." }, { "input": "Carnitine palmitoyltransferase 2 and carnitine / acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.", "output": "Carnitine, carnitine, acylcarnitine, acylcarnitines." }, { "input": "Acylcarnitines are commonly used in the diagnosis of mitochondrial fatty acid beta - oxidation disorders ( mFAODs ).", "output": "Acylcarnitines, fatty acid." }, { "input": "It is generally assumed that this plasma acylcarnitine profile reflects the mitochondrial accumulation of acyl - CoAs.", "output": "acylcarnitine, acyl - CoAs." }, { "input": "The identity of the enzymes and the mitochondrial and plasmalemmal transporters involved in the synthesis and export of these metabolites have remained undefined.", "output": "There is no related enetity." }, { "input": "We used lentiviral shRNA to knock down the expression of medium - chain acyl - CoA dehydrogenase ( MCAD ) in control and carnitine palmitoyltransferase 2 ( CPT2 ) -, carnitine / acylcarnitine translocase ( CACT ) -, and plasmalemmal carnitine transporter ( OCTN2 ) - deficient human fibroblasts.", "output": "acyl - CoA, carnitine, carnitine, acylcarnitine, carnitine." }, { "input": "These cell lines, including mock - transduced controls, were loaded with decanoic acid and carnitine, followed by the measurement of the acylcarnitine profile in the extracellular medium.", "output": "decanoic acid, carnitine, acylcarnitine." }, { "input": "In control fibroblasts, MCAD knockdown markedly increased the production of octanoylcarnitine ( 3 - fold, P < 0. 01 ).", "output": "octanoylcarnitine." }, { "input": "OCTN2 - deficient cell lines also showed extracellular accumulation of octanoylcarnitine ( 2. 8 - fold, P < 0. 01 ), suggesting that the cellular export of acylcarnitines does not depend on OCTN2.", "output": "octanoylcarnitine, acylcarnitines." }, { "input": "In contrast, in CPT2 - and CACT - deficient cells, the accumulation of octanoylcarnitine in the medium did not significantly increase in the MCAD knockdown.", "output": "octanoylcarnitine." }, { "input": "Similar results were obtained using pharmacological inhibition of CPT2 in fibroblasts from MCAD - deficient individuals.", "output": "There is no related enetity." }, { "input": "This shows that CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mFAOD. - Violante, S., IJlst, L., te Brinke, H., Tavares de Almeida, I., Wanders, R.", "output": "acylcarnitine." }, { "input": "J.", "output": "There is no related enetity." }, { "input": "A., Ventura, F.", "output": "There is no related enetity." }, { "input": "V., Houten, S.", "output": "There is no related enetity." }, { "input": "M.", "output": "There is no related enetity." }, { "input": "Carnitine palmitoyltransferase 2 and carnitine / acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.", "output": "Carnitine, carnitine, acylcarnitine, acylcarnitines." }, { "input": "Emerging mechanistic targets in lung injury induced by combustion - generated particles.", "output": "There is no related enetity." }, { "input": "The mechanism for biological effect following exposure to combustion - generated particles is incompletely defined.", "output": "There is no related enetity." }, { "input": "The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures.", "output": "There is no related enetity." }, { "input": "Transient receptor potential ( TRP ) cation channels were identified as \" particle sensors \" in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles.", "output": "There is no related enetity." }, { "input": "TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion - generated particulate matter ( PM ); relative contributions of each depend upon particle composition, dose, and deposition.", "output": "There is no related enetity." }, { "input": "Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca ( + + ) influx, increased RAS expression, mitogen - activated protein kinase signaling, and matrix metalloproteinase - 1 activation.", "output": "Ca ( + + )." }, { "input": "These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions.", "output": "There is no related enetity." }, { "input": "In addition to TRPs and calcium biochemistry, humic - like substances ( HLS ) and cell / tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure.", "output": "calcium, iron." }, { "input": "In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle ( WSP ) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators.", "output": "iron." }, { "input": "Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate.", "output": "There is no related enetity." }, { "input": "Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion - generated PM exposure.", "output": "iron." }, { "input": "Copper tolerance and genetic diversity of Porcellionides sexfasciatus ( ISOPODA ) in a highly contaminated mine habitat.", "output": "Copper." }, { "input": "Organisms inhabiting metal - contaminated areas may develop metal tolerance, with either phenotypic adjustments or genetic changes ( adaptation ) or with both.", "output": "There is no related enetity." }, { "input": "In the present study, three populations of the terrestrial isopod Porcellionides sexfasciatus, collected at an abandoned mine area, were compared to assess the effects of metal contamination on tolerance to lethal and sublethal levels of copper, through comparison of survival, avoidance, and feeding.", "output": "copper." }, { "input": "The effects of metal contamination on genetic diversity were considered using random amplified polymorphic DNA ( RAPD ) markers.", "output": "There is no related enetity." }, { "input": "No evidence of increased metal tolerance of the population inhabiting the contaminated site was found.", "output": "There is no related enetity." }, { "input": "There was no correlation between metal exposure and within - population genetic variance, but the three populations were clearly separated from each other.", "output": "There is no related enetity." }, { "input": "In conclusion, the populations of P. sexfasciatus in the mine landscape live rather isolated from each other and show no differential tolerance to Cu or indications of genetic erosion.", "output": "There is no related enetity." }, { "input": "Their phenotypic plasticity provides a means to survive despite exposure to extremely high metal concentrations in the soil.", "output": "There is no related enetity." }, { "input": "New monoterpene lactones from Actaea cimicifuga.", "output": "monoterpene lactones." }, { "input": "Three new monoterpene lactones, cimicifugolides A - C ( 1 - 3 ), along with a known one ( 4 ), were identified from the dried rhizome of Actaea cimicifuga L. that was used as traditional Chinese medicine for thousands of years with the Chinese common name of shengma.", "output": "monoterpene lactones, cimicifugolides A - C." }, { "input": "The structures of the new isolates were established using spectroscopic methods, including NMR, mass, UV, and IR spectra.", "output": "There is no related enetity." }, { "input": "The inhibition activity of compounds 1, 2, and 4 against pancreatic lipase was evaluated.", "output": "There is no related enetity." }, { "input": "Structure - activity relationships of glucosamine - derived glycerolipids: the role of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity.", "output": "glucosamine, glycero." }, { "input": "The potent antitumor activity of 1 - O - hexadecyl - 2 - O - methyl - 3 - O - ( 2 ' - amino - 2 ' - deoxy - beta - D - glucopyranosyl ) - sn - glycerol ( 1 ) was previously shown to arise through an apoptosis - independent pathway.", "output": "1 - O - hexadecyl - 2 - O - methyl - 3 - O - ( 2 ' - amino - 2 ' - deoxy - beta - D - glucopyranosyl ) - sn - glycerol." }, { "input": "Here, a systematic structure - activity study in which the effects of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity is described.", "output": "There is no related enetity." }, { "input": "Eight analogues of 1 were synthesized, and their antitumor activity against breast ( JIMT1 and BT549 ), pancreas ( MiaPaCa2 ) and prostate ( DU145, PC3 ) cancer was determined.", "output": "There is no related enetity." }, { "input": "1 - O - Hexadecyl - 2 - O - methyl - 3 - O - ( 2 ' - amino - 2 ' - deoxy - alpha - D - glucopyranosyl ) - sn - glycerol ( 2 ) consistently displayed the most potent activity against all five cell lines with CC ( 50 ) values in the range of 6 - 10 mu M.", "output": "1 - O - Hexadecyl - 2 - O - methyl - 3 - O - ( 2 ' - amino - 2 ' - deoxy - alpha - D - glucopyranosyl ) - sn - glycerol." }, { "input": "However, replacement of the O - glycosidic linkage by a thioglycosidic linkage or replacement of the amino group by an azide or guanidino group leads to a threefold or greater decrease in potency.", "output": "O, thioglycosidic, amino, azide, guanidino." }, { "input": "The glycero moiety also contributes to the overall activity of 1 and 2 but its effects are of lesser importance.", "output": "glycero." }, { "input": "Investigation into the mode of action of this class of compounds revealed that, in agreement with previous findings, the cytotoxic effects arise through induction of large acid vacuoles.", "output": "There is no related enetity." }, { "input": "A unique palladium catalyst for efficient and selective alkoxycarbonylation of olefins with formates.", "output": "palladium, olefins, formates." }, { "input": "Forget about CO!", "output": "CO." }, { "input": "Carbonylations are among the most important homogeneously catalyzed reactions in the chemical industry, but typically require carbon monoxide.", "output": "carbon monoxide." }, { "input": "Instead, straightforward and efficient alkoxycarbonylations of olefins can proceed with alkyl formates in the presence of a specific palladium catalyst.", "output": "olefins, alkyl formates, palladium." }, { "input": "Aromatic, terminal aliphatic, and internal olefins are carbonylated to give industrially important linear esters at low catalyst loadings.", "output": "olefins, esters." }, { "input": "Synthesis, characterization, and cure chemistry of renewable bis ( cyanate ) esters derived from 2 - methoxy - 4 - methylphenol.", "output": "bis ( cyanate ) esters, 2 - methoxy - 4 - methylphenol." }, { "input": "A series of renewable bis ( cyanate ) esters have been prepared from bisphenols synthesized by condensation of 2 - methoxy - 4 - methylphenol ( creosol ) with formaldehyde, acetaldehyde, and propionaldehyde.", "output": "bis ( cyanate ) esters, bisphenols, 2 - methoxy - 4 - methylphenol, creosol, formaldehyde, acetaldehyde, propionaldehyde." }, { "input": "The cyanate esters have been fully characterized by infrared spectroscopy, ( 1 ) H and ( 13 ) C NMR spectroscopy, and single crystal X - ray diffraction.", "output": "cyanate esters, ( 1 ) H, ( 13 ) C." }, { "input": "These compounds melt from 88 to 143 degrees C, while cured resins have glass transition temperatures from 219 to 248 degrees C, water uptake ( 96 h, 85 degrees C immersion ) in the range of 2. 05 - 3. 21 %, and wet glass transition temperatures from 174 to 193 degrees C.", "output": "There is no related enetity." }, { "input": "These properties suggest that creosol - derived cyanate esters may be useful for a wide variety of military and commercial applications.", "output": "creosol, cyanate esters." }, { "input": "The cure chemistry of the cyanate esters has been studied with FTIR spectroscopy and differential scanning calorimetry.", "output": "cyanate esters." }, { "input": "The results show that cyanate esters with more sterically demanding bridging groups cure more slowly, but also more completely than those with a bridging methylene group.", "output": "cyanate esters, methylene." }, { "input": "In addition to the structural differences, the purity of the cyanate esters has a significant effect on both the cure chemistry and final Tg of the materials.", "output": "cyanate esters." }, { "input": "In some cases, post - cure of the resins at 350 degrees C resulted in significant decomposition and off - gassing, but cure protocols that terminated at 250 - 300 degrees C generated void - free resin pucks without degradation.", "output": "There is no related enetity." }, { "input": "Thermogravimetric analysis revealed that cured resins were stable up to 400 degrees C and then rapidly degraded.", "output": "There is no related enetity." }, { "input": "TGA / FTIR and mass spectrometry results showed that the resins decomposed to phenols, isocyanic acid, and secondary decomposition products, including CO2.", "output": "phenols, isocyanic acid, CO2." }, { "input": "Char yields of cured resins under N2 ranged from 27 to 35 %, while char yields in air ranged from 8 to 11 %.", "output": "N2." }, { "input": "These data suggest that resins of this type may potentially be recycled to parent phenols, creosol, and other alkylated creosols by pyrolysis in the presence of excess water vapor.", "output": "phenols, creosol, alkylated creosols." }, { "input": "The ability to synthesize these high temperature resins from a phenol ( creosol ) that can be derived from lignin, coupled with the potential to recycle the composites, provides a possible route to the production of sustainable, high - performance, thermosetting resins with reduced environmental impact.", "output": "phenol, creosol." }, { "input": "In situ TEM of two - phase lithiation of amorphous silicon nanospheres.", "output": "silicon." }, { "input": "To utilize high - capacity Si anodes in next - generation Li - ion batteries, the physical and chemical transformations during the Li - Si reaction must be better understood.", "output": "Si, Li, Li - Si." }, { "input": "Here, in situ transmission electron microscopy is used to observe the lithiation / delithiation of amorphous Si nanospheres; amorphous Si is an important anode material that has been less studied than crystalline Si.", "output": "Si, Si, Si." }, { "input": "Unexpectedly, the experiments reveal that the first lithiation occurs via a two - phase mechanism, which is contrary to previous understanding and has important consequences for mechanical stress evolution during lithiation.", "output": "There is no related enetity." }, { "input": "On the basis of kinetics measurements, this behavior is suggested to be due to the rate - limiting effect of Si - Si bond breaking.", "output": "Si - Si." }, { "input": "In addition, the results show that amorphous Si has more favorable kinetics and fracture behavior when reacting with Li than does crystalline Si, making it advantageous to use in battery electrodes.", "output": "Si, Li, Si." }, { "input": "Amorphous spheres up to 870 nm in diameter do not fracture upon lithiation; this is much larger than the 150 nm critical fracture diameter previously identified for crystalline Si spheres.", "output": "Si." }, { "input": "Bioactive carboxylic acids from Lysimachia clethroides.", "output": "carboxylic acids." }, { "input": "Six new carboxylic acids ( 1 - 6 ), together with 11 known ones ( 7 - 17 ), were isolated from the aerial parts of Lysimachia clethroides.", "output": "carboxylic acids." }, { "input": "Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence.", "output": "There is no related enetity." }, { "input": "Five new carboxylic acids ( 1 and 3 - 6 ) were evaluated for their in vitro inhibitory activity against aldose reductase.", "output": "carboxylic acids, aldose." }, { "input": "Chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms.", "output": "There is no related enetity." }, { "input": "Opisthobranchs are slow - moving, brightly colored, and shell - less slug.", "output": "There is no related enetity." }, { "input": "Interestingly, these naked molluscs appear to be free of predation causing great interests to biologists, chemists, and pharmacologists as well.", "output": "There is no related enetity." }, { "input": "It is well documented that their ability to escape predation is realized by utilizing chemical substances as defensive allomones.", "output": "There is no related enetity." }, { "input": "Due to their extraordinary capacity to produce a variety of chemical defensive molecules and in particular, some of which exhibited promising pharmacological activities, opisthobranch molluscs became the hotspot of research subject in the recent years.", "output": "There is no related enetity." }, { "input": "The authors and co - workers have systematically investigated the possible diet relationship between the South China Sea opisthobranch molluscs and their related prey organisms, including sponges, corals, and algae in the last decade.", "output": "There is no related enetity." }, { "input": "A series of interesting results have been obtained concerning the chemistry and chemoecology of the studied marine organisms.", "output": "There is no related enetity." }, { "input": "The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms.", "output": "There is no related enetity." }, { "input": "Some selected representative examples are described in detail.", "output": "There is no related enetity." }, { "input": "Two new stemona alkaloids from Stemona tuberosa Lour.", "output": "There is no related enetity." }, { "input": "Two new pyrrolo [ 1, 2 - alpha ] azepine - type stemona alkaloids, named as tuberostemonoxirine ( 1 ) and 9 alpha - epi - tuberospironine ( 2 ), were isolated from the roots of Stemona tuberosa.", "output": "pyrrolo [ 1 , 2 - alpha ] azepine, tuberostemonoxirine, 9 alpha - epi - tuberospironine." }, { "input": "The structures and relative configurations of new compounds were established on the basis of extensive spectroscopic evidences, especially 1D and 2D NMR and HR - MS experiments.", "output": "There is no related enetity." }, { "input": "Design and application of anthracene derivative with aggregation - induced emission charateristics for visualization and monitoring of erythropoietin unfolding.", "output": "anthracene." }, { "input": "Erythropoietin ( EPO ) is an attractive protein - unfolding / folding model because of its high degree of unfolding and folding reversibility and intermediate size.", "output": "There is no related enetity." }, { "input": "Due to its function for regulating red blood cell production by stimulating late erythroid precursor cells, EPO presents obvious values to biological research.", "output": "There is no related enetity." }, { "input": "A nonemissive anthracene derivative, that is 9, 10 - bis [ 4 - ( 3 - sulfonatopropoxyl ) - styryl ] anthracene sodium salt ( BSPSA ), with aggregation - induced emission ( AIE ) charateristics shows a novel phenomenon of AIE when EPO is added.", "output": "anthracene, 9 , 10 - bis [ 4 - ( 3 - sulfonatopropoxyl ) - styryl ] anthracene sodium salt, BSPSA." }, { "input": "The AIE biosensor for EPO shows the limit of detection is 1 x 10 ( - 9 ) M.", "output": "There is no related enetity." }, { "input": "Utilizing the AIE feature of BSPSA, the unfolding process of EPO using guanidine hydrochloride is monitored, which indicates three steps for the folding structures of EPO to transform to random coil.", "output": "BSPSA, guanidine hydrochloride." }, { "input": "Computational modeling suggests that the BSPSA luminogens prefer docking in the hydrophobic cavity in the EPO folding structures, and the assembly of BSPSA in this cavity makes the AIE available, making the monitoring of unfolding of EPO possible.", "output": "BSPSA, BSPSA." }, { "input": "Heterogeneous cationic liposomes modified with 3 beta - { N - [ ( N ', N ' - dimethylamino ) ethyl ] carbamoyl } cholesterol can induce partial conformational changes in messenger RNA and regulate translation in an Escherichia coli cell - free translation system.", "output": "3 beta - { N - [ ( N ' , N ' - dimethylamino ) ethyl ] carbamoyl } cholesterol." }, { "input": "The effect of cationic liposomes ( CLs ) on messenger RNA ( mRNA ) conformation and translation was studied, focusing on membrane heterogeneity.", "output": "There is no related enetity." }, { "input": "CLs, composed of 1, 2 - dioleoyl - sn - glycerol - 3 - phosphocholine / 1, 2 - dioleoyl - 3 - timethylammonium propane ( DOPC / DOTAP ) and DOPC / 3 beta - { N - [ ( N ', N ' - dimethylamino ) ethyl ] carbamoyl } cholesterol ( DOPC / DC - Ch ), inhibited mRNA translation in an Escherichia coli cell - free translation system.", "output": "1 , 2 - dioleoyl - sn - glycerol - 3 - phosphocholine, 1 , 2 - dioleoyl - 3 - timethylammonium propane, DOPC, DOTAP, DOPC, 3 beta - { N - [ ( N ' , N ' - dimethylamino ) ethyl ] carbamoyl } cholesterol, DOPC, DC - Ch." }, { "input": "Analysis of the membrane fluidity and polarity indicated a heterogeneous DOPC / DC - Ch ( 70 / 30 ) membrane, while other CLs exhibited homogeneous disordered membranes.", "output": "DOPC, DC - Ch." }, { "input": "mRNA adsorbed onto DOPC / DC - Ch liposomes showed translational activity, while DOPC / DOTAP liposomes inhibited mRNA translation in proportion to its adsorption onto membranes.", "output": "DOPC, DC - Ch, DOPC, DOTAP." }, { "input": "Dehydration of DOPC / DOTAP ( 70 / 30 ) and DOPC / DC - Ch ( 70 / 30 ) was observed in the presence of mRNA but not in the case of zwitterionic DOPC liposomes, indicating that mRNA binds in regions between the phosphate [ - PO ( 2 ) ( - ) - ] and carbonyl [ - C = O - ] moieties of lipids.", "output": "DOPC, DOTAP, DOPC, DC - Ch, DOPC, phosphate, PO ( 2 ) ( - ), carbonyl, C = O." }, { "input": "UV resonance Raman spectroscopy suggests that adenine, cytosine, and guanine interact with DOPC / DOTAP ( 70 / 30 ) and DOPC / DC - Ch ( 70 / 30 ) but not with DOPC.", "output": "adenine, cytosine, guanine, DOPC, DOTAP, DOPC, DC - Ch, DOPC." }, { "input": "Circular dichroism indicates that DOPC / DOTAP ( 70 / 30 ) extensively denatured the mRNA.", "output": "DOPC, DOTAP." }, { "input": "In contrast, heterogeneous DOPC / DC - Ch ( 70 / 30 ) induced partial conformational changes but maintained the translational activity of mRNA.", "output": "DOPC, DC - Ch." }, { "input": "Two new diterpenoids from Excoecaria acerifolia.", "output": "diterpenoids." }, { "input": "A new tigliane diterpenoid, acerifolin A ( 1 ), and a new isopimarane diterpenoid, acerifolin B ( 2 ), together with two known compounds, were isolated from Excoecaria acerifolia.", "output": "tigliane, diterpenoid, acerifolin A, isopimarane, diterpenoid, acerifolin B." }, { "input": "Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques.", "output": "There is no related enetity." }, { "input": "All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control.", "output": "cisplantin." }, { "input": "HOW GOOD IS THE LEVOTHYROXINE REPLACEMENT IN PRIMARY HYPOTHYROIDISM PATIENTS IN BRAZIL? - DATA OF A MULTICENTRE STUDY.", "output": "LEVOTHYROXINE." }, { "input": "Background: Studies done in every continent has shown that only around 50 % of the patients subjected to thyroid hormone replacement have TSH in the normal range.", "output": "There is no related enetity." }, { "input": "However, until to date, there are no consistent data about Brazil.", "output": "There is no related enetity." }, { "input": "Objectives: To evaluate levothyroxine ( LT4 ) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil.", "output": "levothyroxine, LT4." }, { "input": "Methods: Patients with primary hypothyroidism followed in referral centers ( University Hospitals from Universidade Federal do Rio de Janeiro - UFRJ, Unicamp, Universidade Federal do Paran a - UFPR and Universidade Federal do Cear a - UFC ) answered a questionnairethat inquired about clinical and biochemical conditions, social - economic status, life quality and clinicians ' orientations as well as their understanding about the information given.", "output": "There is no related enetity." }, { "input": "Serum TSH was checked close to the interview.", "output": "There is no related enetity." }, { "input": "Results: 2292 consecutive patients met the inclusion criteria.", "output": "There is no related enetity." }, { "input": "Mean age 51. 2 years and TSH values between 0. 4 and 4. 0 mUI / l were considered to be within the reference range.", "output": "There is no related enetity." }, { "input": "Among all patients taking thyroid medication, 42. 7 % % had an abnormal serum TSH ( 28. 3 % were undertreated and 14. 4 % were over treated ).", "output": "There is no related enetity." }, { "input": "Approximately all patients ( 99 % ) took LT4 in the morning but less than 30 minutes before breakfast ( 85. 4 % ).", "output": "LT4." }, { "input": "Regarding the clinicians ' orientations: 97. 5 % of the patients were instructed to take the medication daily, and 92. 6 % to take 30 minutes before breakfast ( 92. 6 % ).", "output": "There is no related enetity." }, { "input": "However, only 52. 1 % were told that not to take LT4 along with other medication.", "output": "LT4." }, { "input": "Conclusions: Our study found that there was a significant number of patients taking thyroid hormones were not in the therapeutic range.", "output": "There is no related enetity." }, { "input": "Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.", "output": "LT4." }, { "input": "Improved Postprandial Ghrelin Response by Nateglinide or Acarbose Therapy Contributes to Glucose Stability in Type 2 Diabetic Patients.", "output": "Nateglinide, Acarbose, Glucose." }, { "input": "Background: Recent studies highlight an important role of ghrelin in glucose homeostasis, while the association between ghrelin regulation and glucose fluctuation is unclear.", "output": "glucose, glucose." }, { "input": "Aim: We compared the effects of two postprandial hypoglycemic agents on ghrelin response and determined the contribution of ghrelin response to glucose stability in type 2 diabetic ( T2DM ) patients.", "output": "glucose." }, { "input": "Subjects and Methods: Forty newly - diagnosed T2DM patients were randomly allocated to receive Nateglinide or Acarbose for 4 weeks, with twenty BMI - matched normoglycemic subjects as controls.", "output": "Nateglinide, Acarbose." }, { "input": "Mean glucose values and daily average glucose excursion were assessed using continuous glucose monitoring system.", "output": "glucose, glucose, glucose." }, { "input": "Serum ghrelin levels were determined by ELISA.", "output": "There is no related enetity." }, { "input": "Results: T2DM patients had similar fasting ghrelin levels ( P = 0. 546 ), while their postprandial ghrelin suppressions at 30 min and 120 min were reduced as compared to BMI - matched normoglycemic controls ( P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Both Nateglinide and Acarbose increased postprandial ghrelin suppression at 120 min and reduced ghrelin area under the curve ( AUCGHRL ) ( P < 0. 05 ), while only Nateglinide increased postprandial ghrelin suppression at 30 min ( P < 0. 01 ), which was positively correlated with the increased early - phase insulin secretion by 4 weeks of Nateglinide therapy ( r = 0. 48, P = 0. 05 ).", "output": "Nateglinide, Acarbose, Nateglinide, Nateglinide." }, { "input": "The decrease in AUCGHRL was positively correlated with the decrease in daily average glucose excursion and mean glucose values either by 4 weeks of Nateglinide or Acarbose therapy ( P < 0. 05 ).", "output": "glucose, glucose, Nateglinide, Acarbose." }, { "input": "Conclusions: Both Natelinide and Acarbose increase postprandial ghrelin suppression.", "output": "Natelinide, Acarbose." }, { "input": "Improved ghrelin regulation is most likely to play a role in glucose stability in T2DM patients with Natelinide or Acarbose therapy.", "output": "glucose, Natelinide, Acarbose." }, { "input": "Stable Isolation of Phycocyanin from Spirulina platensis Associated with High - Pressure Extraction Process.", "output": "There is no related enetity." }, { "input": "A method for stably purifying a functional dye, phycocyanin from Spirulina platensis was developed by a hexane extraction process combined with high pressure.", "output": "hexane." }, { "input": "This was necessary because this dye is known to be very unstable during normal extraction processes.", "output": "There is no related enetity." }, { "input": "The purification yield of this method was estimated as 10. 2 %, whose value is 3 % - 5 % higher than is the case from another conventional separation method using phosphate buffer.", "output": "There is no related enetity." }, { "input": "The isolated phycocyanin from this process also showed the highest purity of 0. 909 based on absorbance of 2. 104 at 280 nm and 1. 912 at 620 nm.", "output": "There is no related enetity." }, { "input": "Two subunits of phycocyanin namely alpha - phycocyanin ( 18. 4 kDa ) and beta - phycocyanin ( 21. 3 kDa ) were found to remain from the original mixtures after being extracted, based on SDS - PAGE analysis, clearly demonstrating that this process can stably extract phycocyanin and is not affected by extraction solvent, temperature, etc.", "output": "There is no related enetity." }, { "input": "The stability of the extracted phycocyanin was also confirmed by comparing its DPPH ( alpha, alpha - diphenyl - beta - picrylhydrazyl ) scavenging activity, showing 83 % removal of oxygen free radicals.", "output": "DPPH, alpha , alpha - diphenyl - beta - picrylhydrazyl, oxygen." }, { "input": "This activity was about 15 % higher than that of commercially available standard phycocyanin, which implies that the combined extraction method can yield relatively intact chromoprotein through absence of degradation.", "output": "There is no related enetity." }, { "input": "The results were achieved because the low temperature and high pressure extraction effectively disrupted the cell membrane of Spirulina platensis and degraded less the polypeptide subunits of phycocyanin ( which is a temperature / pH - sensitive chromoprotein ) as well as increasing the extraction yield.", "output": "There is no related enetity." }, { "input": "Synthesis of bisindolylmethanes and their cytotoxicity properties.", "output": "bisindolylmethanes." }, { "input": "Polymer supported dichlorophosphate ( PEG - OPOCl ( 2 ) ) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis ( indolyl ) methanes with short reaction time, at room temperature.", "output": "dichlorophosphate, PEG - OPOCl ( 2 ), indole, aromatic aldehydes, bis ( indolyl ) methanes." }, { "input": "The synthesized compounds and their anti - cancer activity are evaluated.", "output": "There is no related enetity." }, { "input": "Can you enhance executive control without glucose?", "output": "glucose." }, { "input": "The effects of fructose on problem solving.", "output": "fructose." }, { "input": "The consumption of glucose can enhance executive control by increasing blood glucose and providing energy for brain processes.", "output": "glucose, glucose." }, { "input": "However, a glucose mouth rinse also positively affects executive control in the absence of an effect on blood glucose.", "output": "glucose, glucose." }, { "input": "This observation suggests that glucose can enhance executive control via another mechanism, perhaps by increasing cortical activation in motivational reward pathways.", "output": "glucose." }, { "input": "This hypothesis was examined in the current study by having participants consume fructose, glucose or a placebo 10 minutes before solving word anagrams.", "output": "fructose, glucose." }, { "input": "Fructose was used because it does not affect blood glucose levels, inhibits cortical responding, and cannot entrain a taste preference post - ingestion.", "output": "Fructose, glucose." }, { "input": "The latter evidences that fructose differs from glucose in its ability to elicit activation in motivational reward pathways.", "output": "fructose, glucose." }, { "input": "It was observed that consuming fructose and glucose resulted in the resolution of more anagrams than the placebo.", "output": "fructose, glucose." }, { "input": "These results suggest that at least some of the effects of glucose and fructose on problem solving operate through a common peripheral mechanism that is independent of motivational reward pathways.", "output": "glucose, fructose." }, { "input": "Binding site exploration of CCR5 using in silico methodologies: a 3D - QSAR approach.", "output": "There is no related enetity." }, { "input": "Chemokine receptor 5 ( CCR5 ) is an important receptor used by human immunodeficiency virus type 1 ( HIV - 1 ) to gain viral entry into host cell.", "output": "There is no related enetity." }, { "input": "In this study, we used a combined approach of comparative modeling, molecular docking, and three dimensional quantitative structure activity relationship ( 3D - QSAR ) analyses to elucidate detailed interaction of CCR5 with their inhibitors.", "output": "There is no related enetity." }, { "input": "Docking study of the most potent inhibitor from a series of compounds was done to derive the bioactive conformation.", "output": "There is no related enetity." }, { "input": "Parameters such as random selection, rational selection, different charges and grid spacing were utilized in the model development to check their performance on the model predictivity.", "output": "There is no related enetity." }, { "input": "Final comparative molecular field analysis ( CoMFA ) and comparative molecular similarity indices analysis ( CoMSIA ) models were chosen based on the rational selection method, Gasteiger - H u ckel charges and a grid spacing of 0. 5 A.", "output": "There is no related enetity." }, { "input": "Rational model for CoMFA ( q ( 2 ) = 0. 722, r ( 2 ) = 0. 884, Q ( 2 ) = 0. 669 ) and CoMSIA ( q ( 2 ) = 0. 712, r ( 2 ) = 0. 825, Q ( 2 ) = 0. 522 ) was obtained with good statistics.", "output": "There is no related enetity." }, { "input": "Mapping of contour maps onto CCR5 interface led us to better understand of the ligand - protein interaction.", "output": "There is no related enetity." }, { "input": "Docking analysis revealed that the Glu283 is crucial for interaction.", "output": "Glu283." }, { "input": "Two new amino acid residues, Tyr89 and Thr167 were identified as important in ligand - protein interaction.", "output": "amino acid, Tyr89, Thr167." }, { "input": "No site directed mutagenesis studies on these residues have been reported.", "output": "There is no related enetity." }, { "input": "Identification and quantification of the sedative and anticonvulsant flavone glycoside from Chrysanthemum boreale.", "output": "flavone glycoside." }, { "input": "The flowers or leaves of Chrysanthemum boreale ( Compositae ) have been traditionally used as herb tea to reduce anxiety, insomnia, and stress.", "output": "There is no related enetity." }, { "input": "Sedative and anticonvulsant activities were evaluated in mice using pentobarbital - induced sleeping assay and pentylenetetrazole ( PTZ ) - induced convulsion assay.", "output": "pentobarbital, pentylenetetrazole, PTZ." }, { "input": "The flower extract exhibited more potent activities than the extracts of the leaves and stems, and chromatographic isolation yielded the five compounds acacetin, linarin, acacetin 7 - O - beta - D - glucopyranosyl - ( 1 --> 2 ) [ alpha - L - rhamnopyranosyl - ( 1 --> 6 ) ] - beta - D - glucopyranoside, chlorogenic acid, and 3, 5 - di - O - caffeoylquinic acid.", "output": "acacetin, linarin, acacetin 7 - O - beta - D - glucopyranosyl - ( 1 --> 2 ) [ alpha - L - rhamnopyranosyl - ( 1 --> 6 ) ] - beta - D - glucopyranoside, chlorogenic acid, 3 , 5 - di - O - caffeoylquinic acid." }, { "input": "These compounds were simultaneously analyzed by HPLC, and the method was validated.", "output": "There is no related enetity." }, { "input": "The contents of linarin, which were shown to be most abundant in C. boreale, were observed in the order of leaf ( 11. 93 mg / g ) > flower ( 8. 50 mg / g ) > stem ( 5. 60 mg / g ).", "output": "linarin." }, { "input": "Linarin and its aglycone, acacetin, exhibited sedative and anticonvulsant activities in the present in vivo assays.", "output": "Linarin, acacetin." }, { "input": "It can be considered that linarin is one of the active compounds effective against anxiety, insomnia, and stress, with acacetin as its active moiety.", "output": "linarin, acacetin." }, { "input": "Stability of citrate - capped silver nanoparticles in exposure media and their effects on the development of embryonic zebrafish ( Danio rerio ).", "output": "citrate, silver." }, { "input": "The stability of citrate - capped silver nanoparticles ( AgNPs ) and the embryonic developmental toxicity were evaluated in the fish test water.", "output": "citrate, silver." }, { "input": "Serious aggregation of AgNPs was observed in undiluted fish water ( DM - 100 ) in which high concentration of ionic salts exist.", "output": "There is no related enetity." }, { "input": "However, AgNPs were found to be stable for 7 days in DM - 10, prepared by diluting the original fish water ( DM - 100 ) with deionized water to 10 %.", "output": "There is no related enetity." }, { "input": "The normal physiology of zebrafish embryos were evaluated in DM - 10 to see if DM - 10 can be used as a control vehicle for the embryonic fish toxicity test.", "output": "There is no related enetity." }, { "input": "As results, DM - 10 without AgNPs did not induce any significant adverse effects on embryonic development of zebrafish determined by mortality, hatching, malformations and heart rate.", "output": "There is no related enetity." }, { "input": "When embryonic toxicity of AgNPs was tested in both DM - 10 and in DM - 100, AgNPs showed higher toxicity in DM - 10 than in DM - 100.", "output": "There is no related enetity." }, { "input": "This means that the big - sized aggregates of AgNPs were low toxic compared to the nano - sized AgNPs.", "output": "There is no related enetity." }, { "input": "AgNPs induced delayed hatching, decreased heart rate, pericardial edema, and embryo death.", "output": "There is no related enetity." }, { "input": "Accumulation of AgNPs in the embryo bodies was also observed.", "output": "There is no related enetity." }, { "input": "Based on this study, citrate - capped AgNPs are not aggregated in DM - 10 and it can be used as a control vehicle in the toxicity test of fish embryonic development.", "output": "citrate." }, { "input": "Diclofenac: New data on chronic toxicity and bioconcentration in fish.", "output": "Diclofenac." }, { "input": "Diclofenac ( DCF ) is a widely used nonsteroidal anti - inflammatory drug that is regularly detected in surface waters.", "output": "Diclofenac, DCF." }, { "input": "To support a robust aquatic risk assessment, two early life stage ( ELS ) tests, compliant with the Organisation for Economic Co - operation and Development ( OECD ) test guideline 210, were conducted in rainbow trout and in zebrafish.", "output": "There is no related enetity." }, { "input": "Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined.", "output": "There is no related enetity." }, { "input": "The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305.", "output": "DCF." }, { "input": "The bioconcentration factor ( BCF ) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish.", "output": "DCF." }, { "input": "In the rainbow trout ELS test, the no observed effect concentration ( NOEC ) including histopathology was 320 micro g / L.", "output": "There is no related enetity." }, { "input": "The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 micro g / L.", "output": "DCF." }, { "input": "However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 micro g / L not a repeatable, treatment - related effect of DCF.", "output": "DCF." }, { "input": "This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 micro g / L.", "output": "DCF." }, { "input": "This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng / L to low micro g / L.", "output": "DCF." }, { "input": "Caged CO ( 2 ) for the direct observation of CO ( 2 ) - consuming reactions.", "output": "CO ( 2 ), CO ( 2 )." }, { "input": "CO ( 2 ) - consuming reactions, in particular carboxylations, play important roles in technical processes and in nature.", "output": "CO ( 2 )." }, { "input": "Their kinetic behavior and the reaction mechanisms of carboxylating enzymes are difficult to study because CO ( 2 ) is inconvenient to handle as a gas, exists in equilibrium with bicarbonate in aqueous solution, and typically yields products that show no significant spectroscopic differences from the reactants in the UV / Vis range.", "output": "CO ( 2 ), bicarbonate." }, { "input": "Here we demonstrate the utility of 3 - nitrophenylacetic acid and related compounds ( caged CO ( 2 ) ) in conjunction with infrared spectroscopy as widely applicable tools for the investigation of such reactions, permitting convenient measurement of the kinetics of CO ( 2 ) consumption.", "output": "3 - nitrophenylacetic acid, CO ( 2 ), CO ( 2 )." }, { "input": "The use of isotopically labeled caged CO ( 2 ) provides a tool for the assignment of infrared absorption bands, thus aiding insight into reaction intermediates and mechanisms.", "output": "CO ( 2 )." }, { "input": "Isolation and identification of cell - specific microRNAs targeting a messenger RNA using a biotinylated anti - sense oligonucleotide capture affinity technique.", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs ) are small non - coding RNAs that regulate expression by translational repression or messenger RNA ( mRNA ) degradation.", "output": "There is no related enetity." }, { "input": "Although numerous bioinformatic prediction models exist to identify miRNA - mRNA interactions, experimental validation of bona fide interactions can be difficult and laborious.", "output": "There is no related enetity." }, { "input": "Few methods can comprehensively identify miRNAs that target a single mRNA.", "output": "There is no related enetity." }, { "input": "We have developed an experimental approach to search for miRNAs targeting any mRNA using a capture affinity assay involving a biotinylated DNA anti - sense oligonucleotide.", "output": "There is no related enetity." }, { "input": "This method identifies miRNAs targeting the full length of the mRNA.", "output": "There is no related enetity." }, { "input": "The method was tested using three separate mRNA targets: alpha - 1 antitrypsin ( AAT ) mRNA, interleukin - 8 mRNA and secretory leucoprotease inhibitor mRNA.", "output": "There is no related enetity." }, { "input": "AAT mRNA - specific and total miRNAs from three different cell lines ( monocytic THP - 1, bronchial epithelial 16HBE14o - and liver HepG2 cells ) were profiled, and validation studies revealed that AAT mRNA - specific miRNAs functionally target the AAT mRNA in a cell - specific manner, providing the first evidence of innate miRNAs selectively targeting and modulating AAT mRNA expression.", "output": "There is no related enetity." }, { "input": "Interleukin - 8 and secretory leucoprotease inhibitor mRNAs and their cognate miRNAs were also successfully captured using this approach.", "output": "There is no related enetity." }, { "input": "This is a simple and an efficient method to potentially identify miRNAs targeting sequences within the full length of a given mRNA transcript.", "output": "There is no related enetity." }, { "input": "Coumarins from roots of Clausena excavata.", "output": "Coumarins." }, { "input": "Two new coumarins, clauexcavatins A ( 1 ) and B ( 2 ), along with seven known ones ( 3 - 9 ), were isolated from the roots of Clausena excavata Burm.", "output": "coumarins, clauexcavatins A ( 1 ) and B ( 2 )." }, { "input": "f.", "output": "There is no related enetity." }, { "input": "( Rutaceae ).", "output": "There is no related enetity." }, { "input": "Their structures were elucidated on the basis of spectral data.", "output": "There is no related enetity." }, { "input": "Physicochemical characterization of phosphopeptide / titanium dioxide interactions employing the quartz crystal microbalance technique.", "output": "titanium dioxide, quartz." }, { "input": "The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides.", "output": "There is no related enetity." }, { "input": "During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide ( TiO ( 2 ) ) have been developed and tested.", "output": "phosphoryl, titanium dioxide, TiO ( 2 )." }, { "input": "The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used.", "output": "There is no related enetity." }, { "input": "In the present study, the physical chemistry of the phosphopeptide binding to TiO ( 2 ) is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring ( QCM - D ).", "output": "TiO ( 2 ), quartz." }, { "input": "Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions.", "output": "amino acid." }, { "input": "The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO ( 2 ) surface increases in a nonlinear fashion with increasing degree of phosphorylation.", "output": "TiO ( 2 )." }, { "input": "An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied.", "output": "There is no related enetity." }, { "input": "The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides.", "output": "amino acid, amino acids, phosphoryl." }, { "input": "Regardless of the net peptide charge, the TiO ( 2 ) - phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin.", "output": "TiO ( 2 )." }, { "input": "This study highlights and explains some of the most common problems with the TiO ( 2 ) - based enrichment methods used today.", "output": "TiO ( 2 )." }, { "input": "Surfactant - mediated control of colloid pattern assembly and attachment strength in evaporating droplets.", "output": "There is no related enetity." }, { "input": "This study demonstrates that the pattern assembly and attachment strength of colloids in an evaporating sessile droplet resting on a smooth substrate can be controlled by adding nonionic solutes ( surfactant ) to the solution.", "output": "There is no related enetity." }, { "input": "As expected, increasing the surfactant concentration leads to a decrease in initial surface tension of the drop, sigma ( 0 ).", "output": "There is no related enetity." }, { "input": "For the range of initial surface tensions investigated ( 39 - 72 mN m ( - 1 ) ), three distinct deposition patterns were produced: amorphous stains ( sigma ( 0 ) = 63 - 72 mN m ( - 1 ) ), coffee - ring stains ( sigma ( 0 ) = 48 - 53 mN m ( - 1 ) ), and concentric rings ( sigma ( 0 ) = 39 - 45 mN m ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "A flow - displacement system was used to measure the attachment strength of the dried colloids.", "output": "There is no related enetity." }, { "input": "Characteristic drying regimes associated with the three unique pattern formations are attributed to abrupt transitions of contact line dynamics during evaporation.", "output": "There is no related enetity." }, { "input": "The first transition from slipping - to pinned - contact line was found to be a direct result of the competition between mechanical instability of the droplet and the friction generated by pinned colloids at the contact line.", "output": "There is no related enetity." }, { "input": "The second transition from pinned - to recurrent - stick - rip - slip - contact line was caused by repeated liquid film rupturing from evaporation - intensified surfactant concentration.", "output": "There is no related enetity." }, { "input": "Data from flow - displacement tests indicate that attachment strength of dried particles is strongest for amorphous stains ( lowest surfactant concentration ) and weakest for concentric rings ( highest surfactant concentration ).", "output": "There is no related enetity." }, { "input": "The mechanism behind these observations was ascribed to the formation and adsorption of micelles onto colloid and substrate surfaces as the droplet solution evaporates.", "output": "There is no related enetity." }, { "input": "The range of attachment forces observed between the colloids and the solid substrate were well captured by extended - DLVO interactions accounting for van der Waals attraction, electric double layer repulsion, and micelle - protrusion repulsion.", "output": "There is no related enetity." }, { "input": "Both empirical and theoretical results suggest that an increasingly dense layer of adsorbed micellar - protrusions on colloid and substrate surfaces acts as a physical barrier that hinders strong van der Waals attractive interactions at close proximity.", "output": "There is no related enetity." }, { "input": "Thereby, colloid stains dried at higher surfactant concentrations are more easily detached from the substrate when dislodging forces are applied than stains dried at lower surfactant concentrations.", "output": "There is no related enetity." }, { "input": "Anxiogenic - like effects of Uncaria tomentosa ( Willd. ) DC. aqueous extract in an elevated plus maze test in mice: a preliminary study.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to examine the effect of orally administered Uncaria tomentosa aqueous extracts ( UTE ) ( Willd. ex Roem. & Schult. ) DC.", "output": "There is no related enetity." }, { "input": "( Rubiaceae ) during 7, 15, 30 and 90 days of treatment on the expression of anxiety, as expressed in the elevated plus maze test in male Albino Swiss mice.", "output": "There is no related enetity." }, { "input": "UTE revealed an anxiogenic effect in relation to the control group at 15 and 30 days, but it was reversed after 90 days of administration, without affecting the locomotor activity or any deleterious effects on the overall performance of the animal, either for its ambulation, or clinical status, and body weight and organ weight / body weight from liver, lung and kidney were unaffected.", "output": "There is no related enetity." }, { "input": "These biphasic effects are usually indicative of heterogeneity in sites of action due to the presence of many alkaloids ( speciophylline, uncarine F and uncarine E ) and flavanols ( catechin and epigallocatechin ) identified and isolated from UTE.", "output": "speciophylline, uncarine F, uncarine E, flavanols, catechin, epigallocatechin." }, { "input": "Cooperative effects for CYP2E1 differ between styrene and its metabolites.", "output": "styrene." }, { "input": "Abstract 1.", "output": "There is no related enetity." }, { "input": "Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive.", "output": "There is no related enetity." }, { "input": "Previously, we demonstrated that steady - state styrene metabolism by CYP2E1 exhibits positive cooperativity.", "output": "There is no related enetity." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism.", "output": "styrene, styrene." }, { "input": "To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4 - nitrophenol using CYP2E1 Supersomes (R) and human liver microsomes.", "output": "styrene, 4 - nitrophenol." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site ( 67 micro M ) and lower affinity for the cooperative site ( 1100 micro M ), while increasing substrate turnover at high concentrations.", "output": "Styrene." }, { "input": "Styrene oxide and 4 - vinylphenol possessed similar affinity for CYP2E1.", "output": "Styrene oxide, 4 - vinylphenol." }, { "input": "Styrene oxide behaved cooperatively like styrene, but 4 - vinylphenol decreased turnover at high concentrations.", "output": "Styrene oxide, styrene, 4 - vinylphenol." }, { "input": "Styrene glycol was a very poor competitive inhibitor.", "output": "Styrene glycol." }, { "input": "Among all compounds, there was a positive correlation with binding and hydrophobicity.", "output": "There is no related enetity." }, { "input": "4.", "output": "There is no related enetity." }, { "input": "Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds.", "output": "There is no related enetity." }, { "input": "Characterisation of the essential oil from different aerial parts of Lindera chunii Merr.", "output": "There is no related enetity." }, { "input": "( Lauraceae ).", "output": "There is no related enetity." }, { "input": "The essential oils from three organs ( i. e. flowers, leaves and stems ) of wild Lindera chunii Merr. in Dinghu Mountain ( China ) were obtained by microwave - assisted hydrodistillation.", "output": "There is no related enetity." }, { "input": "The essential oils were analysed by gas chromatography with flame ionisation detection and gas chromatography with mass spectrometry.", "output": "There is no related enetity." }, { "input": "The yields of essential oil varied from 0. 06 % to 0. 59 % and showed a remarkable variation among the plant organs.", "output": "There is no related enetity." }, { "input": "A total of 43 compounds accounting for 95. 4 - 96. 3 % of the total essential oil were identified, and the major compounds were germacrene B ( 0. 7 - 43. 2 % ), viridiflorene ( trace to 14. 6 % ), globulol ( 6. 3 - 11. 6 % ), alpha - cadinol ( 1. 7 - 8. 6 % ) and tau - cadinol ( 0. 5 - 7. 3 % ).", "output": "germacrene B, viridiflorene, globulol, alpha - cadinol, tau - cadinol." }, { "input": "This study shows that the chemical compositions of the essential oils from the different organs of L. chunii are very variable.", "output": "There is no related enetity." }, { "input": "Interactions between pectic compounds and procyanidins are influenced by methylation degree and chain length.", "output": "procyanidins." }, { "input": "The interactions between procyanidins and pectic compounds are of importance in food chemistry.", "output": "procyanidins." }, { "input": "Procyanidins with low ( 9 ) and high ( 30 ) average degrees of polymerization ( DP9 and DP30 ) were extracted from two cider apple varieties.", "output": "Procyanidins." }, { "input": "Commercial apple and citrus pectins, as well as three pectin subfractions ( homogalacturonans, partially methylated homogalacturonans with degree of methylation 30 and 70 ) at 30 mM galacturonic acid equivalent, were titrated with the two procyanidin fractions ( at 30 mM ( - ) - epicatechin equivalent ) by isothermal titration calorimetry and UV - vis spectrophotometry.", "output": "galacturonic acid, procyanidin, ( - ) - epicatechin." }, { "input": "Slightly stronger affinities were recorded between commercial apple or citrus pectins and procyanidins of DP30 ( Ka = 1460 and 1225 M ( - 1 ) respectively, expressed per monomer units ) compared to procyanidins of DP9 ( Ka = 1240 and 1085 M ( - 1 ), respectively ), but stoichiometry and absorbance maxima differed between apple and citrus pectins.", "output": "procyanidins, procyanidins." }, { "input": "It was proposed that methylated homogalacturonans interacted with procyanidins DP30 mainly through hydrophobic interactions.", "output": "procyanidins." }, { "input": "The stronger association was obtained with the longer procyanidin molecules interacting with highly methylated pectins.", "output": "procyanidin." }, { "input": "Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity.", "output": "There is no related enetity." }, { "input": "Damage to the heart can result from both traditional chemotherapeutic agents, such as doxorubicin, and newer ' targeted ' therapies, such as trastuzumab.", "output": "doxorubicin." }, { "input": "This chemotherapeutic cardiotoxicity is potentially life - threatening and necessitates limiting or discontinuing an otherwise - effective cancer treatment.", "output": "There is no related enetity." }, { "input": "Clinical strategies focus on surveillance rather than prevention, although there are no specific therapies for this highly morbid adverse effect.", "output": "There is no related enetity." }, { "input": "Current models for prospectively predicting risk of chemotherapeutic cardiotoxicity are limited.", "output": "There is no related enetity." }, { "input": "Cardiotoxicity can occur idiosyncratically in patients without obvious demographic risk factors, suggesting a genetically determined susceptibility, and candidate - gene studies have identified a limited number of variants that increase risk.", "output": "There is no related enetity." }, { "input": "In this commentary we indicate a need for more powerful means to identify risk prospectively, and suggest that broad pharmacogenomic approaches may be fruitful.", "output": "There is no related enetity." }, { "input": "Bioactive abietane and ent - kaurane diterpenoids from Isodon tenuifolius.", "output": "abietane, ent - kaurane, diterpenoids." }, { "input": "Three new abietane diterpenoids, isoabietenins A - C ( 1 - 3 ), and 13 new ent - kauranoids, tenuifolins A - M ( 4 - 16 ), along with four known compounds ( 17 - 20 ), were isolated from the aerial parts of Isodon tenuifolius.", "output": "abietane, diterpenoids, isoabietenins A - C, ent - kauranoids, tenuifolins A - M." }, { "input": "The structures of the new metabolites were established on the basis of detailed spectroscopic analysis.", "output": "There is no related enetity." }, { "input": "The absolute configurations of 1, 15, and 16 were confirmed by single - crystal X - ray diffraction.", "output": "There is no related enetity." }, { "input": "Selected compounds were evaluated for their cytotoxicity against a small panel of human tumor cell lines, and some compounds showed inhibitory effects.", "output": "There is no related enetity." }, { "input": "Furthermore, several isolates exhibited inhibitory activity against nitric oxide production in LPS - activated RAW264. 7 macrophages.", "output": "nitric oxide." }, { "input": "Long - loop G - quadruplexes are misfolded population minorities with fast transition kinetics in human telomeric sequences.", "output": "There is no related enetity." }, { "input": "Single - stranded guanine ( G ) - rich sequences at the 3 ' end of human telomeres provide ample opportunities for physiologically relevant structures, such as G - quadruplexes, to form and interconvert.", "output": "There is no related enetity." }, { "input": "Population equilibrium in this long sequence is expected to be intricate and beyond the resolution of ensemble - average techniques, such as circular dichroism, NMR, or X - ray crystallography.", "output": "There is no related enetity." }, { "input": "By combining a force - jump method at the single - molecular level and a statistical population deconvolution at the sub - nanometer resolution, we reveal a complex population network with unprecedented transition dynamics in human telomeric sequences that contain four to eight TTAGGG repeats.", "output": "There is no related enetity." }, { "input": "Our kinetic data firmly establish that G - triplexes are intermediates to G - quadruplexes while long - loop G - quadruplexes are misfolded population minorities whose formation and disassembly are faster than G - triplexes or regular G - quadruplexes.", "output": "There is no related enetity." }, { "input": "The existence of misfolded DNA supports the emerging view that structural and kinetic complexities of DNA can rival those of RNA or proteins.", "output": "There is no related enetity." }, { "input": "While G - quadruplexes are the most prevalent species in all the sequences studied, the abundance of a misfolded G - quadruplex in a particular telomeric sequence decreases with an increase in the loop length or the number of long - loops in the structure.", "output": "There is no related enetity." }, { "input": "These population patterns support the prediction that in the full - length 3 ' overhang of human telomeres, G - quadruplexes with shortest TTA loops would be the most dominant species, which justifies the modeling role of regular G - quadruplexes in the investigation of telomeric structures.", "output": "There is no related enetity." }, { "input": "Alkaloids from Microcos paniculata with cytotoxic and nicotinic receptor antagonistic activities.", "output": "There is no related enetity." }, { "input": "Microcos paniculata is a large shrub or small tree that grows in several countries in South and Southeast Asia.", "output": "There is no related enetity." }, { "input": "In the present study, three new piperidine alkaloids, microgrewiapines A - C ( 1 - 3 ), as well as three known compounds, inclusive of microcosamine A ( 4 ), 7 ' - ( 3 ', 4 ' - dihydroxyphenyl ) - N - [ 4 - methoxyphenyl ) ethyl ] propenamide ( 5 ), and liriodenine ( 6 ), were isolated from cytotoxic fractions of the separate chloroform - soluble extracts of the stem bark, branches, and leaves of M. paniculata.", "output": "piperidine alkaloids, microgrewiapines A - C, microcosamine A, 7 ' - ( 3 ' , 4 ' - dihydroxyphenyl ) - N - [ 4 - methoxyphenyl ) ethyl ] propenamide, liriodenine, chloroform." }, { "input": "Compounds 1 - 6 and 1a ( microgrewiapine A 3 - acetate ) showed a range of cytotoxicity values against the HT - 29 human colon cancer cell line.", "output": "microgrewiapine A 3 - acetate." }, { "input": "When evaluated for their effects on human alpha 3 beta 4 or alpha 4 beta 2 nicotinic acetylcholine receptors ( nAChRs ), several of these compounds were shown to be active as nAChR antagonists.", "output": "acetylcholine." }, { "input": "As a result of this study, microgrewiapine A ( 1 ) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells and to exhibit nicotinic receptor antagonistic activity for both the h alpha 3 beta 4 and h alpha 4 beta 2 receptor subtypes.", "output": "microgrewiapine A." }, { "input": "Thioredoxin - mimetic peptides ( TXM ) reverse auranofin induced apoptosis and restore insulin secretion in insulinoma cells.", "output": "auranofin." }, { "input": "The thioredoxin reductase / thioredoxin system ( TrxR / Trx1 ) plays a major role in protecting cells from oxidative stress.", "output": "There is no related enetity." }, { "input": "Disruption of the TrxR - Trx1 system keeps Trx1 in the oxidized state leading to cell death through activation of the ASK1 - Trx1 apoptotic pathway.", "output": "There is no related enetity." }, { "input": "The potential mechanism and ability of tri - and tetra - oligopeptides derived from the canonical - CxxC - motif of the Trx1 - active site to mimic and enhance Trx1 cellular activity was examined.", "output": "There is no related enetity." }, { "input": "The Trx mimetics peptides ( TXM ) protected insulinoma INS 832 / 13 cells from oxidative stress induced by selectively inhibiting TrxR with auranofin ( AuF ).", "output": "auranofin, AuF." }, { "input": "TXM reversed the AuF - effects preventing apoptosis, and increasing cell - viability.", "output": "AuF." }, { "input": "The TXM peptides were effective in inhibiting AuF - induced MAPK, JNK and p38 ( MAPK ) phosphorylation, in correlation with preventing caspase - 3 cleavage and thereby PARP - 1 dissociation.", "output": "AuF." }, { "input": "The ability to form a disulfide - bridge - like conformation was estimated from molecular dynamics simulations.", "output": "disulfide." }, { "input": "The TXM peptides restored insulin secretion and displayed Trx1 denitrosylase activity.", "output": "There is no related enetity." }, { "input": "Their potency was 10 - 100 - fold higher than redox reagents like NAC, AD4, or ascorbic acid.", "output": "NAC, AD4, ascorbic acid." }, { "input": "Unable to reverse ERK1 / 2 phosphorylation, TXM - CB3 ( NAc - Cys - Pro - Cys amide ) appeared to function in part, through inhibiting ASK1 - Trx dissociation.", "output": "NAc - Cys - Pro - Cys amide." }, { "input": "These highly effective anti - apoptotic effects of Trx1 mimetic peptides exhibited in INS 832 / 13 cells could become valuable in treating adverse oxidative - stress related disorders such as diabetes.", "output": "There is no related enetity." }, { "input": "Dose - dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.", "output": "vitamin D." }, { "input": "Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality.", "output": "vitamin D." }, { "input": "The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes.", "output": "There is no related enetity." }, { "input": "The current study examined the effect of the active form of vitamin D 3, 1, 25 - dihydroxyvitamin D 3 ( 1, 25 ( OH ) 2 D 3 ), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages.", "output": "vitamin D 3, 1 , 25 - dihydroxyvitamin D 3, 1 , 25 ( OH ) 2 D 3." }, { "input": "Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations ( 0, 10 - (1) (3), 10 - (1) (1), 10 - 9, 10 - 7 or 10 - 5 M ) of 1, 25 ( OH ) 2 D 3 for up to 6 days and markers of muscle and fat development measured.", "output": "1 , 25 ( OH ) 2 D 3." }, { "input": "Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media.", "output": "There is no related enetity." }, { "input": "Relative to controls, low physiological concentrations ( 10 - (1) (3) and 10 - (1) (1) M ) of 1, 25 ( OH ) 2 D3 increased fat droplet accumulation, whereas high physiological ( 10 - 9 M ) and supraphysiological concentrations ( >= 10 - 7 M ) inhibited fat accumulation.", "output": "1 , 25 ( OH ) 2 D3." }, { "input": "This increased accumulation of fat with low physiological concentrations ( 10 - (1) (3) and 10 - (1) (1) M ) was associated with a sequential up - regulation of PPAR gamma 2 ( PPARG ) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations ( >= 10 - 9 M ) reduced all these effects, and the highest concentration ( 10 - 5 M ) appeared to have toxic effects.", "output": "There is no related enetity." }, { "input": "This is the first study to demonstrate dose - dependent effects of 1, 25 ( OH ) 2 D 3 on the transdifferentiation of muscle cells into adipose cells.", "output": "1 , 25 ( OH ) 2 D 3." }, { "input": "Low physiological concentrations ( possibly mimicking a deficient state ) induced adipogenesis, whereas higher ( physiological and supraphysiological ) concentrations attenuated this effect.", "output": "There is no related enetity." }, { "input": "Omega - 3 Fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance.", "output": "Omega - 3 Fatty acids." }, { "input": "Fish oils ( FOs ) have anti - inflammatory effects and lower serum triglycerides.", "output": "There is no related enetity." }, { "input": "This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of omega - 3 fatty acids on adipocytes and macrophages in vitro.", "output": "omega - 3 fatty acids." }, { "input": "Insulin - resistant, nondiabetic subjects were treated with Omega - 3 - Acid Ethyl Esters ( 4 g / day ) or placebo for 12 weeks.", "output": "Omega - 3 - Acid Ethyl Esters." }, { "input": "Plasma macrophage chemoattractant protein 1 ( MCP - 1 ) levels were reduced by FO, but the levels of other cytokines were unchanged.", "output": "There is no related enetity." }, { "input": "The adipose ( but not muscle ) of FO - treated subjects demonstrated a decrease in macrophages, a decrease in MCP - 1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment.", "output": "There is no related enetity." }, { "input": "Adipose and muscle omega - 3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin.", "output": "omega - 3 fatty acid." }, { "input": "In vitro, M1 - polarized macrophages expressed high levels of MCP - 1.", "output": "There is no related enetity." }, { "input": "The addition of omega - 3 fatty acids reduced MCP - 1 expression with no effect on TNF - alpha.", "output": "omega - 3 fatty acids." }, { "input": "In addition, omega - 3 fatty acids suppressed the upregulation of adipocyte MCP - 1 that occurred when adipocytes were cocultured with macrophages.", "output": "omega - 3 fatty acids." }, { "input": "Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP - 1 expression in insulin - resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Allele - Specific Transcriptional Activity at Type 2 Diabetes - Associated Single Nucleotide Polymorphisms in Regions of Pancreatic Islet Open Chromatin at the JAZF1 Locus.", "output": "There is no related enetity." }, { "input": "Translation of noncoding common variant association signals into meaningful molecular and biological mechanisms explaining disease susceptibility remains challenging.", "output": "There is no related enetity." }, { "input": "For the type 2 diabetes association signal in JAZF1 intron 1, we hypothesized that the underlying risk variants have cis - regulatory effects in islets or other type 2 diabetes - relevant cell types.", "output": "There is no related enetity." }, { "input": "We used maps of experimentally predicted open chromatin regions to prioritize variants for functional follow - up studies of transcriptional activity.", "output": "There is no related enetity." }, { "input": "Twelve regions containing type 2 diabetes - associated variants were tested for enhancer activity in 832 / 13 and MIN6 insulinoma cells.", "output": "There is no related enetity." }, { "input": "Three regions exhibited enhancer activity and only rs1635852 displayed allelic differences in enhancer activity; the type 2 diabetes risk allele T showed lower transcriptional activity than the nonrisk allele C.", "output": "There is no related enetity." }, { "input": "This risk allele showed increased binding to protein complexes, suggesting that it functions as part of a transcriptional repressor complex.", "output": "There is no related enetity." }, { "input": "We applied DNA affinity capture to identify factors in the complex and determined that the risk allele preferentially binds the pancreatic master regulator PDX1.", "output": "There is no related enetity." }, { "input": "These data suggest that the rs1635852 region in JAZF1 intron 1 is part of a cis - regulatory complex and that maps of open chromatin are useful to guide identification of variants with allelic differences in regulatory activity at type 2 diabetes loci.", "output": "There is no related enetity." }, { "input": "Benzophenone - 1 stimulated the growth of BG - 1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha - mediated signaling pathway in cellular and xenograft mouse models.", "output": "Benzophenone - 1, estrogen." }, { "input": "2, 4 - Dihydroxybenzophenone ( benzophenone - 1; BP - 1 ) is an UV stabilizer primarily used to prevent polymer degradation and deterioration in quality due to UV irradiation.", "output": "2 , 4 - Dihydroxybenzophenone, benzophenone - 1, BP - 1." }, { "input": "Recently, BP - 1 has been reported to bioaccumulate in human bodies by absorption through the skin and has the potential to induce health problems including endocrine disruption.", "output": "BP - 1." }, { "input": "In the present study, we examined the xenoestrogenic effect of BP - 1 on BG - 1 human ovarian cancer cells expressing estrogen receptors ( ERs ) and relevant xenografted animal models in comparison with 17 - beta estradiol ( E2 ).", "output": "BP - 1, estrogen, 17 - beta estradiol." }, { "input": "In in vitro cell viability assay, BP - 1 ( 10 ( - 8 ) - 10 ( - 5 ) M ) significantly increased BG - 1 cell growth the way E2 did.", "output": "BP - 1." }, { "input": "The mechanism underlying the BG - 1 cell proliferation was proved to be related with the up - regulation of cyclin D1, a cell cycle progressor, by E2 or BP - 1.", "output": "BP - 1." }, { "input": "Both BP - 1 and E2 induced cell growth and up - regulation of cyclin D1 were reversed by co - treatment with ICI 182, 780, an ER antagonist, suggesting that BP - 1 may mediate the cancer cell proliferation via an ER - dependent pathway like E2.", "output": "BP - 1, ICI 182 , 780, BP - 1." }, { "input": "On the other hand, the expression of p21, a regulator of cell cycle progression at G1 phase, was not altered by BP - 1 though it was down - regulated by E2.", "output": "BP - 1." }, { "input": "In xenograft mouse models transplanted with BG - 1 cells, BP - 1 or E2 treatment significantly increased the tumor mass formation compared to a vehicle ( corn oil ) within 8 weeks.", "output": "BP - 1." }, { "input": "In histopathological analysis, the tumor sections of E2 or BP - 1 group displayed extensive cell formations with high density and disordered arrangement, which were supported by the increased number of BrdUrd positive nuclei and the over - expression of cyclin D1 protein.", "output": "BP - 1." }, { "input": "Taken together, these results suggest that BP - 1 is an endocrine disrupting chemical ( EDC ) that exerts xenoestrogenic effects by stimulating the proliferation of BG - 1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2.", "output": "BP - 1." }, { "input": "Effects of dopamine D2 agonist quinpirole on neuronal activity of anterior cingulate cortex and striatum in rats.", "output": "dopamine, quinpirole." }, { "input": "RATIONALE: The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized.", "output": "quinpirole." }, { "input": "However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex ( ACC ) and striatum ( STR ), two crucial regions for cognitive and motor functions, after quinpirole administration.", "output": "quinpirole." }, { "input": "OBJECTIVE: This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration.", "output": "quinpirole." }, { "input": "METHODS: Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane - anesthetized rats after administration of saline or 0. 05 or 0. 5 mg / kg quinpirole.", "output": "urethane, quinpirole." }, { "input": "RESULTS: In contrast to the responses to saline, quinpirole dose - dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR.", "output": "quinpirole." }, { "input": "By examining the ensemble neuronal activities of inhibition - responded neurons, there was no significant activity difference among the \" treatments \" ( saline and low - and high - dose quinpirole ), the \" periods \" ( the duration of 0 - 15 and 16 - 45 min after i. v. injection ), and the interaction between \" treatments \" and \" periods. \" Regarding activation - responded neurons, however, there was a significant \" periods \" difference in both ACC and STR, and the activity of 16 - 45 min was significantly higher than the activity of 0 - 15 min after high - dose quinpirole administration in ACC ( p < 0. 05 ) and STR ( p < 0. 001 ).", "output": "quinpirole, quinpirole." }, { "input": "CONCLUSION: Dose - dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats.", "output": "quinpirole, quinpirole." }, { "input": "The late excitatory effect of high - dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity.", "output": "quinpirole." }, { "input": "Differential sensitivity to pro - oxidant exposure in two populations of killifish ( Fundulus heteroclitus ).", "output": "There is no related enetity." }, { "input": "New Bedford Harbor ( MA, U. S. A.; NBH ) is a Superfund site inhabited by Atlantic killifish ( Fundulus heteroclitus ) with altered aryl hydrocarbon receptor ( Ahr ) signaling, leading to resistance to effects of polychlorinated biphenyls ( PCBs ) and 2, 3, 7, 8 - tetrachlorodibenzo - p - dioxin ( TCDD ).", "output": "aryl hydrocarbon, polychlorinated biphenyls, PCBs, 2 , 3 , 7 , 8 - tetrachlorodibenzo - p - dioxin, TCDD." }, { "input": "The Ahr is a transcription factor that regulates gene expression of many Phase I and II detoxifying enzymes and interacts with Nrf2, a transcription factor that regulates the response to oxidative stress.", "output": "There is no related enetity." }, { "input": "This study tested the hypothesis that PCB - resistant killifish exhibit altered sensitivity to oxidative stress.", "output": "PCB." }, { "input": "Killifish F ( 1 ) embryos from NBH and a clean reference site ( Scorton Creek, MA, U. S. A.; SC ) were exposed to model pro - oxidant and Nrf2 - activator, tert - butylhydroquinone ( tBHQ ).", "output": "tert - butylhydroquinone, tBHQ." }, { "input": "Embryos were exposed at specific embryonic developmental stages ( 5, 7, and 9 days post fertilization ) and toxicity was assessed, using a deformity score, survival, heart rate, and gene expression to compare sensitivity between PCB - resistant and - sensitive ( reference ) populations.", "output": "PCB." }, { "input": "Acute exposure to tBHQ resulted in transient reduction in heart rate in NBH and SC F ( 1 ) embryos.", "output": "tBHQ." }, { "input": "However, embryos from NBH were more sensitive to tBHQ, with more frequent and severe deformities, including pericardial edema, tail deformities, small body size, and reduced pigment and erythrocytes.", "output": "tBHQ." }, { "input": "NBH embryos had lower basal expression of antioxidant genes catalase and glutathione - S - transferase alpha ( gsta ), and upon exposure to tBHQ, exhibited lower levels of expression of catalase, gsta, and superoxide dismutase compared to controls.", "output": "glutathione, S, tBHQ, superoxide." }, { "input": "This result suggests that adaptation to tolerate PCBs has altered the sensitivity of NBH fish to oxidative stress during embryonic development, demonstrating a cost of the PCB resistance adaptation.", "output": "PCBs, PCB." }, { "input": "Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K / Akt and p38MAPK / caspase - 8 pathways.", "output": "There is no related enetity." }, { "input": "Mutations in REarranged during Transfection ( RET ) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma ( MTC ) that responds poorly to conventional chemotherapy.", "output": "tyrosine." }, { "input": "Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients.", "output": "There is no related enetity." }, { "input": "Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: ( i ) stalling PI3K / Akt / Bad pathway that resulted in mitochondrial transmembrane potential ( MTP ) loss, cytochrome - c release and activation of the executioner caspases - 9 and - 3, and ( ii ) upholding p38MAPK / caspase - 8 / caspase - 3 pathway via inhibition of Ras / Raf / ERK.", "output": "theaflavins." }, { "input": "Over - expression of either constitutively active myristoylated - Akt - cDNA ( Myr - Akt - cDNA ) or dominant - negative - caspase - 8 - cDNA ( Dn - caspase - 8 - cDNA ) partially blocked theaflavin - induced apoptosis, while co - transfection of Myr - Akt - cDNA and Dn - caspase - 8 - cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways.", "output": "theaflavins." }, { "input": "A search for the upstream signaling revealed that theaflavin - induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase.", "output": "theaflavin." }, { "input": "In such anti - survival cellular micro - environment, pro - apoptotic signals were triggered to culminate into programmed death of MTC cell.", "output": "There is no related enetity." }, { "input": "These findings not only unveil a hitherto unexplained mechanism underlying theaflavin - induced MTC death, but also validate RET as a promising and potential target for MTC therapy.", "output": "theaflavin." }, { "input": "Operationalizing value - based pricing of medicines: a taxonomy of approaches.", "output": "There is no related enetity." }, { "input": "The UK Government is proposing a novel form of price regulation for branded medicines, which it has dubbed ' value - based pricing ' ( VBP ).", "output": "There is no related enetity." }, { "input": "The specifics of how VBP will work are unclear.", "output": "There is no related enetity." }, { "input": "We provide an account of the possible means by which VBP of medicines might be operationalized, and a taxonomy to describe and categorize the various approaches.", "output": "There is no related enetity." }, { "input": "We begin with a brief discussion of the UK Government ' s proposal for VBP and proceed to define a taxonomy of approaches to VBP.", "output": "There is no related enetity." }, { "input": "The taxonomy has five main dimensions: ( 1 ) what is identified as being of value, ( 2 ) how each element is measured, ( 3 ) how it is valued, ( 4 ) how the different elements of value are aggregated, and ( 5 ) how the result is then used to determine the price of a medicine.", "output": "There is no related enetity." }, { "input": "We take as our starting point that VBP will include a measure of health gain and that, as proposed by the UK Government, this will be built on the QALY.", "output": "There is no related enetity." }, { "input": "Our principal interest is in the way criteria other than QALYs are taken into account, including severity of illness, the extent of unmet need, and wider societal considerations such as impacts on carers.", "output": "There is no related enetity." }, { "input": "We set out to: ( 1 ) identify and describe the full range of alternative means by which ' value ' might be measured and valued, ( 2 ) identify and describe the options available for aggregating the different components of value to establish a maximum price, and ( 3 ) note the challenges and relative advantages associated with these approaches.", "output": "There is no related enetity." }, { "input": "We review the means by which aspects of VBP are currently operationalized in a selection of countries and place these, and proposals for the UK, in the context of our taxonomy.", "output": "There is no related enetity." }, { "input": "Finally, we give an initial assessment of the challenges, pros and cons of each approach.", "output": "There is no related enetity." }, { "input": "We conclude that identifying where VBP should lie on each of the five dimensions entails value judgements: there are no simple ' right or wrong ' solutions.", "output": "There is no related enetity." }, { "input": "If a wider definition of value than incremental QALYs gained is adopted, as is desirable, then a pragmatic way to aggregate the different elements of value, including both QALYs and benefits unrelated to QALYs, is to use a multi - criteria decision analysis ( MCDA ) approach.", "output": "There is no related enetity." }, { "input": "All approaches to VBP ultimately require the conversion of value, however assessed, into a monetary price.", "output": "There is no related enetity." }, { "input": "This requires assessment of the marginal values of all types of benefit, not just of QALYs.", "output": "There is no related enetity." }, { "input": "All stages of the VBP process are subject to uncertainty and margins of error.", "output": "There is no related enetity." }, { "input": "Consequently, the assessment of overall value can provide bounds to a price negotiation but cannot be expected to identify a precise value - based price.", "output": "There is no related enetity." }, { "input": "PXR antagonists and implication in drug metabolism.", "output": "There is no related enetity." }, { "input": "Adopted orphan nuclear receptor ( NR ), pregnane X receptor ( PXR ), plays a central role in the regulation of xeno - and endobiotic metabolism.", "output": "pregnane." }, { "input": "Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology ( e. g., cholestasis, hypercholesterolemia, and inflammation ).", "output": "There is no related enetity." }, { "input": "However, more recently, it is clear that PXR is also an important mediator of adverse xeno - ( e. g., enhances acetaminophen toxicity ) and endobiotic ( e. g., hepatic steatosis ) metabolic phenotypes.", "output": "acetaminophen." }, { "input": "Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue - specific enhancement of the malignant phenotype.", "output": "There is no related enetity." }, { "input": "Thus, in these instances, there may be a role for PXR antagonists.", "output": "There is no related enetity." }, { "input": "However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described.", "output": "There is no related enetity." }, { "input": "The mode of action of these antagonists ( e. g., sulforaphane ) remains less clear.", "output": "sulforaphane." }, { "input": "Our laboratory efforts have focused on this question.", "output": "There is no related enetity." }, { "input": "Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less - toxic PXR antagonists.", "output": "azoles." }, { "input": "In this review, we describe our published and unpublished findings on recent structure - function studies involving the azole chemical scaffold.", "output": "azole." }, { "input": "Further work in the future is needed to fully define potent, more - selective PXR antagonists that may be useful in clinical application.", "output": "There is no related enetity." }, { "input": "A molecular platinum cluster junction: a single - molecule switch.", "output": "platinum." }, { "input": "We present a theoretical study of electron transport through single - molecule junctions incorporating a Pt ( 6 ) metal cluster bound within an organic framework.", "output": "Pt ( 6 )." }, { "input": "The insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nanometallic device with high conductance at the Fermi level and two sequential high on / off switching states.", "output": "There is no related enetity." }, { "input": "The origin of this property can be traced back to the existence of a degenerate HOMO consisting of two asymmetric orbitals with energies close to the Fermi level of the metal leads.", "output": "There is no related enetity." }, { "input": "The degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances that become pinned to the Fermi level and display destructive interference.", "output": "There is no related enetity." }, { "input": "Recent developments in emerging microimmunoassays.", "output": "There is no related enetity." }, { "input": "Creative and novel microimmunoassay approaches continue to proliferate across many platforms originating from several fields of study.", "output": "There is no related enetity." }, { "input": "These efforts are aimed at improving one or more metrics for clinical tests, including improved sensitivity, increased speed, reduced cost, smaller sample size, the ability to analyze multiple antigens in parallel and ease of use.", "output": "There is no related enetity." }, { "input": "Many approaches focus on the production of microarrays that accomplish standard assays in parallel, or mobile solid - support formats to overcome issues of high background noise and long incubation times.", "output": "There is no related enetity." }, { "input": "In this article, innovative developments beyond existing commercial tests in the microimmunoassay arena are reviewed, covering January 2008 to April 2012.", "output": "There is no related enetity." }, { "input": "These developing experimental platforms are discussed in terms of their ability to augment or replace current commercial approaches.", "output": "There is no related enetity." }, { "input": "Polyamine production is downstream and upstream of oncogenic PI3K signalling and contributes to tumour cell growth.", "output": "Polyamine." }, { "input": "PI3K ( phosphoinositide 3 - kinase ) signalling pathways regulate a large array of cell biological functions in normal and cancer cells.", "output": "phosphoinositide." }, { "input": "In the present study we investigated the involvement of PI3K in modulating small molecule metabolism.", "output": "There is no related enetity." }, { "input": "A LC ( liquid chromatography ) - MS screen in colorectal cancer cell lines isogenic for oncogenic PIK3CA mutations revealed an association between PI3K activation and the levels of polyamine pathway metabolites, including 5 - methylthioadenosine, putrescine and spermidine.", "output": "polyamine, 5 - methylthioadenosine, putrescine, spermidine." }, { "input": "Pharmacological inhibition confirmed that the PI3K pathway controls polyamine production.", "output": "polyamine." }, { "input": "Despite inducing a decrease in PKB ( protein kinase B ) / Akt phosphorylation, spermidine promoted cell survival and opposed the anti - proliferative effects of PI3K inhibitors.", "output": "spermidine." }, { "input": "Conversely, polyamine depletion by an ornithine decarboxylase inhibitor enhanced PKB / Akt phosphorylation, but suppressed cell survival.", "output": "polyamine, ornithine." }, { "input": "These results suggest that spermidine mediates cell proliferation and survival downstream of PI3K / Akt and indicate that these two biochemical pathways control each other ' s activities, highlighting a mechanism by which small molecule metabolism feeds back to regulate kinase signalling.", "output": "spermidine." }, { "input": "Consistent with this feedback loop having a functional role in these cell models, pharmacological inhibitors of PI3K and ornithine decarboxylase potentiated each other in inhibiting tumour growth in a xenograft model.", "output": "ornithine." }, { "input": "The results of the present study support the notion that the modulation of spermidine concentrations may be a previously unrecognized mechanism by which PI3K sustains chronic proliferation of cancer cells.", "output": "spermidine." }, { "input": "Facile fabrication of \" dual click \" one - and two - dimensional orthogonal Peptide concentration gradients.", "output": "There is no related enetity." }, { "input": "Peptides, proteins, and extracellular matrix act synergistically to influence cellular function at the biotic - synthetic interface.", "output": "There is no related enetity." }, { "input": "However, identifying the individual and cooperative contributions of the various combinations and concentration regimes is extremely difficult.", "output": "There is no related enetity." }, { "input": "The confined channel deposition method we describe affords highly tunable orthogonal reactive concentration gradients that greatly expand the dynamic range, spatial control, and chemical versatility of the reactive silanes that can be controllably deposited.", "output": "silanes." }, { "input": "Using metal - free \" dual click \" immobilization chemistries, multiple peptides with a variety of functionality can be immobilized efficiently and reproducibly enabling optimal concentration profiling and the assessment of synergistic interactions.", "output": "There is no related enetity." }, { "input": "Hydroxy - terminated conjugated polymer nanoparticles have near - unity bright fraction and reveal cholesterol - dependence of IGF1R nanodomains.", "output": "Hydroxy, cholesterol." }, { "input": "Fluorescent nanoparticles have enabled many discoveries regarding how molecular machines function.", "output": "There is no related enetity." }, { "input": "Quantum dots have been the dominant class of fluorescent nanoparticles but suffer from blinking and from a substantial dark fraction - - particles where the fluorescence is never seen - - complicating any analysis of biological function.", "output": "There is no related enetity." }, { "input": "Nanoparticles composed of conjugated fluorescent polymers ( Pdots ) have recently been shown to have high brightness and no blinking.", "output": "There is no related enetity." }, { "input": "Here we develop a robust and efficient means to measure the dark fraction of Pdots, conjugating Atto dyes to the nanoparticles and testing fluorescence colocalization of dye and Pdot puncta.", "output": "There is no related enetity." }, { "input": "This established that the Pdots we generated had minimal dark fraction: ~ 3 %.", "output": "There is no related enetity." }, { "input": "The application of nanoparticles in biological environments is highly sensitive to surface functionalization.", "output": "There is no related enetity." }, { "input": "For Pdots we found that passivation with uncharged hydroxy - terminated polyethylene glycol caused a dramatic reduction in nonspecific cell binding and aggregation compared to a charged coating.", "output": "hydroxy, polyethylene glycol." }, { "input": "Using carbonyl di - imidazole the hydroxy - Pdots were functionalized efficiently with streptavidin for high stability targeting, allowing specific labeling of mammalian cells.", "output": "carbonyl di - imidazole, hydroxy." }, { "input": "Type I insulin - like growth factor receptor ( IGF1R ) regulates cell survival and development, with roles in aging, heart disease, and cancer.", "output": "There is no related enetity." }, { "input": "We used hydroxy - Pdots to track the dynamics of IGF1R on a breast cancer cell - line, determining the diffusion characteristics and showing cholesterol - containing membrane nanodomains were important for receptor mobility at the plasma membrane.", "output": "hydroxy, cholesterol." }, { "input": "The near - unity bright fraction and low nonspecific binding of hydroxy - Pdots, combined with Pdot photostability and lack of blinking, provides many advantages for investigations at the single molecule level.", "output": "hydroxy." }, { "input": "Acetylcholinesterase immobilized capillary reactors - tandem mass spectrometry: an on - flow tool for ligand screening.", "output": "There is no related enetity." }, { "input": "The use of immobilized capillary enzyme reactors ( ICERs ) for online ligand screening has been adopted as a new technique for high - throughput screening ( HTS ).", "output": "There is no related enetity." }, { "input": "In this work, the selected target was the enzyme acetylcholinesterase ( AChE ), and the AChE - ICERs produced were used in a liquid chromatograph - tandem ion - trap mass spectrometer.", "output": "There is no related enetity." }, { "input": "The activity and kinetic parameters were evaluated by monitoring the choline ' s precursor ion ( M + H ) ( + ) m / z 104. 0 and its ion fragment ( C2H3OH ) - ( M + H ) ( + ) m / z 60. 0.", "output": "choline, H, C2H3OH, H." }, { "input": "The assay method was validated using the reference AChE inhibitors tacrine and galanthamine.", "output": "tacrine, galanthamine." }, { "input": "Two new ligands, out of a library of 17 coumarin derivatives, were identified, and the half - maximal inhibitory concentration ( IC50 ), inhibition constant ( K ( i ) ), and the inhibition mechanism were determined.", "output": "coumarin." }, { "input": "A coumarin derivative with IC50 similar to tacrine was highlighted.", "output": "coumarin, tacrine." }, { "input": "Structure - based design and synthesis of C - 1 - and C - 4 - modified analogs of zanamivir as neuraminidase inhibitors.", "output": "C, C, zanamivir." }, { "input": "In order to exploit the 430 - cavity in the active sites of neuraminidases, 22 zanamivir analogs with C - 1 and C - 4 modification were synthesized, and their inhibitory activities against both group - 1 ( H5N1, H1N1 ) and group - 2 neuraminidases ( H3N2 ) were determined.", "output": "zanamivir, C, C." }, { "input": "Compound 9f exerts the most potency, with IC ( 50 ) value of 0. 013, 0. 001, and 0. 09 mu M against H3N2, H5N1, and H1N1, which is similar to that of zanamivir ( H3N2 IC ( 50 ) = 0. 0014 mu M, H5N1 IC ( 50 ) = 0. 012 mu M, H1N1 IC ( 50 ) = 0. 001 mu M ).", "output": "zanamivir." }, { "input": "Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half - life ( t ( 1 / 2 ) ) than that of zanamivir following administration ( po dose ).", "output": "zanamivir." }, { "input": "Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C - 1 - position being projected toward the 430 - loop region.", "output": "There is no related enetity." }, { "input": "This study may represent a novel starting point for the future development of improved antiflu agents.", "output": "There is no related enetity." }, { "input": "Highly transparent low resistance ZnO / Ag nanowire / ZnO composite electrode for thin film solar cells.", "output": "ZnO, Ag, ZnO." }, { "input": "We present an indium - free transparent conducting composite electrode composed of silver nanowires ( AgNWs ) and ZnO bilayers.", "output": "indium, silver, ZnO." }, { "input": "The AgNWs form a random percolating network embedded between the ZnO layers.", "output": "ZnO." }, { "input": "The unique structural features of our ZnO / AgNW / ZnO multilayered composite allow for a novel transparent conducting electrode with unprecedented excellent thermal stability ( ~ 375 degrees C ), adhesiveness, and flexibility as well as high electrical conductivity ( ~ 8. 0 Omega / sq ) and good optical transparency ( > 91 % at 550 nm ).", "output": "ZnO, ZnO." }, { "input": "Cu ( In, Ga ) ( S, Se ) 2 ( CIGSSe ) thin film solar cells incorporating this composite electrode exhibited a 20 % increase of the power conversion efficiency compared to a conventional sputtered indium tin oxide - based CIGSSe solar cell.", "output": "Cu ( In , Ga ) ( S , Se ) 2, CIGSSe, oxide, CIGSSe." }, { "input": "The ZnO / AgNW / ZnO composite structure enables effective light transmission and current collection as well as a reduced leakage current, all of which lead to better cell performance.", "output": "ZnO, ZnO." }, { "input": "Development of a natural products database from the biodiversity of Brazil.", "output": "There is no related enetity." }, { "input": "We describe herein the design and development of an innovative tool called the NuBBE database ( NuBBEDB ), a new Web - based database, which incorporates several classes of secondary metabolites and derivatives from the biodiversity of Brazil.", "output": "There is no related enetity." }, { "input": "This natural product database incorporates botanical, chemical, pharmacological, and toxicological compound information.", "output": "There is no related enetity." }, { "input": "The NuBBEDB provides specialized information to the worldwide scientific community and can serve as a useful tool for studies on the multidisciplinary interfaces related to chemistry and biology, including virtual screening, dereplication, metabolomics, and medicinal chemistry.", "output": "There is no related enetity." }, { "input": "The NuBBEDB site is at http: / / nubbe. iq. unesp. br / nubbeDB. html.", "output": "There is no related enetity." }, { "input": "Effect of headgroup on the physicochemical properties of phospholipid bilayers in electric fields: size matters.", "output": "There is no related enetity." }, { "input": "The effect of molecular structure on ensemble structure of phospholipid films has been investigated.", "output": "There is no related enetity." }, { "input": "Bilayers of dimyristoyl phosphatidylethanolamine ( DMPE ) were prepared on Au ( 111 ) electrodes using Langmuir - Blodgett and Langmuir - Schaeffer deposition.", "output": "dimyristoyl phosphatidylethanolamine, DMPE, Au ( 111 )." }, { "input": "Capacitance and charge density measurements were used to investigate the adsorption behavior and barrier properties of the lipid bilayers.", "output": "There is no related enetity." }, { "input": "In situ polarization modulation infrared reflection absorption spectroscopy ( PM - IRRAS ) was employed to investigate the organization of the molecules within the bilayer.", "output": "There is no related enetity." }, { "input": "DMPE bilayers exhibit lower capacitance than bilayers formed from the related lipid, dimyristoyl phosphatidylcholine ( DMPC ).", "output": "DMPE, dimyristoyl phosphatidylcholine, DMPC." }, { "input": "The infrared data show that these results can be explained by structural differences between the bilayers formed from each molecule.", "output": "There is no related enetity." }, { "input": "DMPE organizes into bilayers with hydrocarbon chains tilted at a smaller angle to the surface normal, which results in a thicker film.", "output": "DMPE, hydrocarbon." }, { "input": "The hydrocarbon chains contain few conformational defects.", "output": "hydrocarbon." }, { "input": "Spectra in the carbonyl and phosphate stretching mode regions indicate low solvent content of DMPE films.", "output": "carbonyl, phosphate, DMPE." }, { "input": "Both of these effects combine to produce films with lower capacitance and enhanced barrier properties.", "output": "There is no related enetity." }, { "input": "The results are explained in terms of the differences in structure between the constituent molecules.", "output": "There is no related enetity." }, { "input": "On the origin of thermal untwisting of DNA.", "output": "There is no related enetity." }, { "input": "In aqueous solutions, the helical twist of DNA decreases with temperature.", "output": "There is no related enetity." }, { "input": "This phenomenon was noticed and studied experimentally several decades ago, but its physical origin remains elusive.", "output": "There is no related enetity." }, { "input": "The present paper shows that the thermal untwisting can be predicted from the specific properties of the torsional elasticity of the double helix revealed in recent computational studies.", "output": "There is no related enetity." }, { "input": "The temperature coefficient of untwisting estimated using coarse - grained models fitted to all - atom MD data accounts for the experimental results nearly quantitatively.", "output": "There is no related enetity." }, { "input": "The agreement is further improved with the computed torsional rigidity scaled to remove the discrepancy from experiment.", "output": "There is no related enetity." }, { "input": "The results confirm that the torsional rigidity of DNA is strongly anharmonic.", "output": "There is no related enetity." }, { "input": "They indicate that for random DNA, its value grows with small twisting and decreases with untwisting.", "output": "There is no related enetity." }, { "input": "Fragment - based design of novel quinazolinon derivatives as human acrosin inhibitors.", "output": "quinazolinon." }, { "input": "Human acrosin is a promising target for the male contraceptives.", "output": "There is no related enetity." }, { "input": "On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy.", "output": "quinazolinon." }, { "input": "In vitro anti - acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities.", "output": "There is no related enetity." }, { "input": "In particular, compounds 5c and 5g are more active than the known inhibitors.", "output": "There is no related enetity." }, { "input": "Molecular docking studies revealed that the quinazolinon inhibitors interacted with human acrosin mainly through hydrogen bonding and hydrophobic interactions.", "output": "quinazolinon, hydrogen." }, { "input": "The binding mode was also consistent with the structure - activity relationships.", "output": "There is no related enetity." }, { "input": "The quinazolinon derivatives in this study can serve as new lead structure for the development of novel male contraceptives.", "output": "quinazolinon." }, { "input": "4 - Aminoquinoline - Triazine - Based Hybrids with Improved In Vitro Antimalarial Activity Against CQ - Sensitive and CQ - Resistant Strains of Plasmodium falciparum.", "output": "4 - Aminoquinoline - Triazine." }, { "input": "A systematic chemical modification in the triazine moiety covalently attached via suitable linkers to 4 - amino - 7 - chloroquinolines yielded a series of new 7 - chloro - 4 - aminoquinoline - triazine hybrids exhibiting high in vitro activity against W2 ( chloroquine - resistant ) and D6 ( chloroquine - sensitive ) strains of Plasmodium falciparum without any toxicity against mammalian cell lines ( Vero, LLC - PK11, HepG2 ).", "output": "triazine, 4 - amino - 7 - chloroquinolines, 7 - chloro - 4 - aminoquinoline - triazine, chloroquine, chloroquine." }, { "input": "Many of the compounds ( 6, 8, 10, 11, 13, 14, 16, 27, 29 and 33 ) showed excellent potency against chloroquine sensitive and resistant strains.", "output": "chloroquine." }, { "input": "In particular, compounds 6, 8, 14, 16 and 29 were found to be significantly more active than chloroquine against the chloroquine - resistant strains ( W2 clone ) of P. falciparum.", "output": "chloroquine, chloroquine." }, { "input": "Morphological, ecological and genetic aspects associated with endemism in the Fly Orchid group.", "output": "There is no related enetity." }, { "input": "The European genus Ophrys ( Orchidaceae ) is famous for its insect - like floral morphology, an adaptation for a pseudocopulatory pollination strategy involving Hymenoptera males.", "output": "There is no related enetity." }, { "input": "A large number of endemic Ophrys species have recently been described, especially within the Mediterranean Basin, which is one of the major species diversity hotspots.", "output": "There is no related enetity." }, { "input": "Subtle morphological variation and specific pollinator dependence are the two main perceptible criteria for describing numerous endemic taxa.", "output": "There is no related enetity." }, { "input": "However, the degree to which endemics differ genetically remains a challenging question.", "output": "There is no related enetity." }, { "input": "Additionally, knowledge regarding the factors underlying the emergence of such endemic entities is limited.", "output": "There is no related enetity." }, { "input": "To achieve new insights regarding speciation processes in Ophrys, we have investigated species boundaries in the Fly Orchid group ( Ophrys insectifera sensu lato ) by examining morphological, ecological and genetic evidence.", "output": "There is no related enetity." }, { "input": "Classically, authors have recognized one widespread taxon ( O. insectifera ) and two endemics ( O. aymoninii from France and O. subinsectifera from Spain ).", "output": "There is no related enetity." }, { "input": "Our research has identified clear morphological and ecological factors segregating among these taxa; however, genetic differences were more ambiguous.", "output": "There is no related enetity." }, { "input": "Insights from cpDNA sequencing and amplified fragment length polymorphisms genotyping indicated a recent diversification in the three extant Fly Orchid species, which may have been further obscured by active migration and admixture across the European continent.", "output": "There is no related enetity." }, { "input": "Our genetic results still indicate weak but noticeable phylogeographic clustering that partially correlates with the described species.", "output": "There is no related enetity." }, { "input": "Particularly, we report several isolated haplotypes and genetic clusters in central and southeastern Europe.", "output": "There is no related enetity." }, { "input": "With regard to the morphological, ecological and genetic aspects, we discuss the endemism status within the Fly Orchid group from evolutionary, taxonomical and conservation perspectives.", "output": "There is no related enetity." }, { "input": "Food - related impulsivity in obesity and Binge Eating Disorder - a systematic review.", "output": "There is no related enetity." }, { "input": "Impulsivity towards food has been recognized as a potential factor leading to increased food intake in obesity.", "output": "There is no related enetity." }, { "input": "Patients suffering from binge eating disorder ( BED ) form a specific subgroup of obese people that might be characterized by increased impulsivity.", "output": "There is no related enetity." }, { "input": "These assumptions, although, have yet to be verified.", "output": "There is no related enetity." }, { "input": "Therefore, this review evaluates evidence for food - related impulsivity in obese people with and without BED and examines possible differences between both populations.", "output": "There is no related enetity." }, { "input": "More precisely, evidence for the two components of impulsivity is analyzed separately: evidence for reward sensitivity, specifically, the urge for appetitive stimuli and evidence for rash - spontaneous behaviour such as acting disinhibited with no regard for the consequences.", "output": "There is no related enetity." }, { "input": "Our search resulted in 51 articles demonstrating generally increased food - related impulsivity.", "output": "There is no related enetity." }, { "input": "We found particular emphasis on increased reward sensitivity in obese people, which appeared to be more pronounced in people with BED.", "output": "There is no related enetity." }, { "input": "There was little and conflicting evidence, however, concerning increased rash - spontaneous behaviour in obese people without BED, but consistent evidence of an increase in obese people with BED.", "output": "There is no related enetity." }, { "input": "All in all, the evidence supports the view that BED represents a specific phenotype of obesity with increased food - related impulsivity.", "output": "There is no related enetity." }, { "input": "Taking these specific deficits into account can enhance the effectiveness of weight reduction programmes and psychotherapy.", "output": "There is no related enetity." }, { "input": "Therapy of obese patients with cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Obesity has reached epidemic proportions and is a significant public health concern.", "output": "There is no related enetity." }, { "input": "Obesity is associated with increased diabetes, cardiovascular and kidney disease, and associated morbidity and mortality.", "output": "There is no related enetity." }, { "input": "Despite the increasing public health problem of obesity, there is a dearth of effective treatment options.", "output": "There is no related enetity." }, { "input": "Following the FDA mandated withdrawal of sibutramine, the treatment options for obesity were limited to orlistat as the only pharmacological treatment option for long - term management of obesity.", "output": "sibutramine, orlistat." }, { "input": "Recently two new medications ( Belviq and Qsymia ) were approved by FDA for long - term management of obesity.", "output": "Belviq, Qsymia." }, { "input": "Many other antiobesity drugs are under development.", "output": "There is no related enetity." }, { "input": "Bariatric surgery has been shown to be effective in the treatment of obesity and its comorbidities.", "output": "There is no related enetity." }, { "input": "The available data suggest that even modest weight loss improves diabetes and cardiovascular disease ( CVD ) risk factors.", "output": "There is no related enetity." }, { "input": "We summarize the treatment options for obesity and the efficacy of these options in ameliorating cardiovascular risk factors.", "output": "There is no related enetity." }, { "input": "We also focus on the recently approved antiobesity drugs.", "output": "There is no related enetity." }, { "input": "Inactivation of BAD by IKK inhibits TNF alpha - induced apoptosis independently of NF - kappa B activation.", "output": "There is no related enetity." }, { "input": "The I kappa B kinase complex ( IKK ) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis.", "output": "There is no related enetity." }, { "input": "The prosurvival function of IKK centers on activation of the transcription factor NF - kappa B, whose target gene products inhibit caspases and prevent prolonged JNK activation.", "output": "There is no related enetity." }, { "input": "Here, we report that inactivation of the BH3 - only protein BAD by IKK independently of NF - kappa B activation suppresses TNF alpha - induced apoptosis.", "output": "There is no related enetity." }, { "input": "TNF alpha - treated Ikk beta ( - / - ) mouse embryonic fibroblasts ( MEFs ) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK.", "output": "There is no related enetity." }, { "input": "IKK phosphorylates BAD at serine - 26 ( Ser26 ) and primes it for inactivation.", "output": "serine, Ser26." }, { "input": "Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNF alpha - induced apoptosis in cultured cells and increasing mortality in animals.", "output": "Ser26." }, { "input": "Our results reveal that IKK inhibits TNF alpha - induced apoptosis through two distinct but cooperative mechanisms: activation of the survival factor NF - kappa B and inactivation of the proapoptotic BH3 - only BAD protein.", "output": "There is no related enetity." }, { "input": "Green tea catechin leads to global improvement among Alzheimer ' s disease - related phenotypes in NSE / hAPP - C105 Tg mice.", "output": "catechin." }, { "input": "Amyloid beta ( Alpha beta ) has been reported to be responsible for the functional and structural abnormalities of Alzheimer ' s disease ( AD ) through the induction of oxidative stress.", "output": "There is no related enetity." }, { "input": "The aim of this study was to determine whether or not treatment of transgenic ( Tg ) mice with green tea catechin ( GTC ), a radical scavenger, improves AD phenotypes.", "output": "catechin." }, { "input": "To test this, 7 - month - old Tg mice were treated with a low ( 1 mg ) or high ( 10 mg ) dose of GTC for 6 months.", "output": "There is no related enetity." }, { "input": "Surprisingly, GTC - treated Tg mice exhibited significant decreases in behavioral impairment, A beta - 42 production, APP - C99 / 89 expression, gamma - secretase component and Wnt protein levels, gamma - secretase activity and MAPK activation.", "output": "There is no related enetity." }, { "input": "In contrast, the levels of APP - C83 protein and enzyme activities ( alpha - secretase, neprilysin and Pin1 ) were elevated in the GTC - treated groups.", "output": "There is no related enetity." }, { "input": "Moreover, GTC - treated groups showed lower levels of total cholesterol and low - density lipoprotein cholesterol, whereas the level of high - density lipoprotein cholesterol increased.", "output": "cholesterol, cholesterol, cholesterol." }, { "input": "These results provide the first experimental evidence that GTC improves AD phenotypes, thereby suggesting that GTC can be used in the prevention of AD or treatment of AD patients.", "output": "There is no related enetity." }, { "input": "Contribution of single - minded 2 to hyperglycaemia - induced neurotoxicity.", "output": "There is no related enetity." }, { "input": "Diabetes mellitus is associated to central nervous system damage, which results in impairment of brain functions and cognitive deficits and decline in memory.", "output": "There is no related enetity." }, { "input": "However, the mechanisms mediating the actions of glucose on the neurons remained elusive.", "output": "glucose." }, { "input": "Single - minded 2 ( Sim2 ), a basic helix - loop - helix ( bHLH ) - PAS transcriptional repressor, is thought to be involved in some symptoms of Down syndrome.", "output": "There is no related enetity." }, { "input": "We hypothesized that Sim2 mediated hyperglycaemia - induced neuronal injury and impairment of learning and memory.", "output": "There is no related enetity." }, { "input": "It was found that expression of Sim2 protein in cortical neurons was increased in streptozotocin - induced diabetes mellitus rat model.", "output": "streptozotocin." }, { "input": "Drebrin, down - regulated by Sim2, was subsequently decreased as detected by confocal laser scanning microscopy and Western blot analysis.", "output": "There is no related enetity." }, { "input": "The expression pattern of Sim2 and Drebrin correspond to 50mmol / L glucose ( hyperglycaemia ) was also found in primary cultured neurons.", "output": "glucose." }, { "input": "Curcumin, one neuroprotective agent, inhibited hyperglycaemia - induced neurotoxicity.", "output": "Curcumin." }, { "input": "Moreover, curcumin alleviated Sim2 expression, and reversely raised Drebrin expression in neurons treated with hyperglycaemia.", "output": "curcumin." }, { "input": "Finally, we found that silencing Sim2 expression decreased hyperglycaemia - induced neuronal injury.", "output": "There is no related enetity." }, { "input": "In conclusion, Sim2 may mediate neurotoxicity during hyperglycaemia and thereby play a critical role in the development of hyperglycaemia - induced cognitive deficits.", "output": "There is no related enetity." }, { "input": "Genistein protection against acetaminophen - induced liver injury via its potential impact on the activation of UDP - glucuronosyltransferase and antioxidant enzymes.", "output": "Genistein, acetaminophen, UDP." }, { "input": "The purpose of this study was to investigate genistein ' s influence on the relationship between the activation of uridine diphosphate glucuronosyltransferase ( UGTs ) and the protection against acetaminophen - induced liver toxicity.", "output": "genistein, uridine diphosphate, acetaminophen." }, { "input": "Animal experimental results revealed that genistein ( 50, 100 or 200mg / BWkg ) significantly ameliorated the biomarkers alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase and malondialdehyde, as indicators of acute liver damage caused by APAP ( 200mg / BWkg ).", "output": "genistein, alanine, alanine, lactate, malondialdehyde, APAP." }, { "input": "The level of GSH declined sharply after treatment with APAP within 1h in both the liver and blood with and without genistein.", "output": "GSH, APAP, genistein." }, { "input": "However, after 16h, the levels approached or returned to the original level.", "output": "There is no related enetity." }, { "input": "Genistein may accelerate and promote APAP glucuronidation as the results showed that APAP - glucuronide increased by 18. 44 %, 46. 79 %, and 66. 49 % for 4h of treatment with genistein dosages of 50, 100 or 200mg / BWkg, respectively, compared with the APAP - only treatment.", "output": "Genistein, APAP, APAP, glucuronide, genistein, APAP." }, { "input": "The activation of UGTs and glutathione peroxidase and the inhibition of CYP2E1 by genistein were observed, and UGTs mRNA expression level with genistein was measured.", "output": "glutathione, genistein, genistein." }, { "input": "These findings suggest that genistein can prevent and protect against APAP - induced liver toxicity due to the inhibition of APAP biotransformation and the resistance to oxidative stress via the modulation of the activities of metabolism and the antioxidant enzyme.", "output": "genistein, APAP, APAP." }, { "input": "Exposure to 1800 MHz radiofrequency electromagnetic radiation induces oxidative DNA base damage in a mouse spermatocyte - derived cell line.", "output": "There is no related enetity." }, { "input": "Whether exposure to radiofrequency electromagnetic radiation ( RF - EMR ) emitted from mobile phones can induce DNA damage in male germ cells remains unclear.", "output": "There is no related enetity." }, { "input": "In this study, we conducted a 24h intermittent exposure ( 5 min on and 10 min off ) of a mouse spermatocyte - derived GC - 2 cell line to 1800 MHz Global System for Mobile Communication ( GSM ) signals in GSM - Talk mode at specific absorption rates ( SAR ) of 1 W / kg, 2 W / kg or 4 W / kg.", "output": "There is no related enetity." }, { "input": "Subsequently, through the use of formamidopyrimidine DNA glycosylase ( FPG ) in a modified comet assay, we determined that the extent of DNA migration was significantly increased at a SAR of 4 W / kg.", "output": "formamidopyrimidine." }, { "input": "Flow cytometry analysis demonstrated that levels of the DNA adduct 8 - oxoguanine ( 8 - oxoG ) were also increased at a SAR of 4 W / kg.", "output": "8 - oxoguanine, 8 - oxoG." }, { "input": "These increases were concomitant with similar increases in the generation of reactive oxygen species ( ROS ); these phenomena were mitigated by co - treatment with the antioxidant alpha - tocopherol.", "output": "oxygen, alpha - tocopherol." }, { "input": "However, no detectable DNA strand breakage was observed by the alkaline comet assay.", "output": "There is no related enetity." }, { "input": "Taking together, these findings may imply the novel possibility that RF - EMR with insufficient energy for the direct induction of DNA strand breaks may produce genotoxicity through oxidative DNA base damage in male germ cells.", "output": "There is no related enetity." }, { "input": "Effects of methoxychlor and its metabolite 2, 2 - bis ( p - hydroxyphenyl ) - 1, 1, 1 - trichloroethane on 11 beta - hydroxysteroid dehydrogenase activities in vitro.", "output": "methoxychlor, 2 , 2 - bis ( p - hydroxyphenyl ) - 1 , 1 , 1 - trichloroethane, 11 beta - hydroxysteroid." }, { "input": "Methoxychlor ( MXC ) is primarily used as a pesticide and widely present in the environment.", "output": "Methoxychlor, MXC." }, { "input": "The objective of the present study is to investigate the direct effects of MXC and its metabolite 2 - bis ( p - hydroxyphenyl ) - 1, 1, 1 - trichloroethane ( HPTE ) on two isoforms of 11 beta - hydroxysteroid dehydrogenase ( 11 beta - HSD1 and 11 beta - HSD2 ) in vitro.", "output": "MXC, 2 - bis ( p - hydroxyphenyl ) - 1 , 1 , 1 - trichloroethane, HPTE, 11 beta - hydroxysteroid." }, { "input": "Human liver microsome, rat testis microsome and adult Leydig cells were used for the measurement of 11 beta - HSD1 activity.", "output": "There is no related enetity." }, { "input": "Human placental and rat kidney microsomes were used for 11 beta - HSD2 activity.", "output": "There is no related enetity." }, { "input": "The IC ( 50 ) values on human 11 beta - HSD1 by MXC and HPTE were 1. 91 +/- 0. 07 and 8. 88 +/- 0. 08 mu M, respectively.", "output": "MXC, HPTE." }, { "input": "HPTE inhibited rat 11 beta - HSD1 with IC ( 50 ) of 9. 15 +/- 0. 05 mu M, while MXC did not inhibit the enzyme.", "output": "HPTE, MXC." }, { "input": "MXC and HPTE were competitive inhibitors of 11 beta - HSD1.", "output": "MXC, HPTE." }, { "input": "HPTE also inhibited human and rat 11 beta - HSD2 with IC ( 50 ) values of 55. 57 +/- 0. 08 and 12. 96 +/- 0. 11 mu M, respectively, while MXC did not inhibit 11 beta - HSD2.", "output": "HPTE, MXC." }, { "input": "In summary, our results showed that MXC and its metabolite HPTE inhibited both isoforms of 11 beta - HSD in a species - and chemical structure - dependent manner.", "output": "MXC, HPTE." }, { "input": "Viper venom induced inflammation with Montivipera xanthina ( Gray, 1849 ) and the anti - snake venom activities of Artemisia absinthium L. in rat.", "output": "There is no related enetity." }, { "input": "The present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti - snake venom activities of Artemisia absinthium L. in comparison with carrageenan - induced acute inflammation model in rats.", "output": "There is no related enetity." }, { "input": "The LD50 value was estimated as 8. 78 mg / kg within 24 h by different venom doses administrated intraperitoneally in mice.", "output": "There is no related enetity." }, { "input": "The IC50 value was 0. 43 +/- 0. 18 mu g / ml after 48 h treatment while the calculated value was 0. 73 +/- 0. 10 mu g / ml for the culture media totally refreshed after 2 h treatment with venom.", "output": "There is no related enetity." }, { "input": "Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw.", "output": "There is no related enetity." }, { "input": "Intraperitoneal administration of 25 and 50 mg / kg extract was inhibited venom induced paw swelling at 0. 5, 1, 2 and 3 h ( p < 0. 05 ) while 12. 5, 25 and 50 mg / kg extract treatment was inhibited carrageenan - induced paw swelling at 2, 3, 4 and 5 h ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "In conclusion, the in vivo toxicity and inflammatory actions and in vitro cytotoxic actions of crude M. xanthina venom were performed as a first report and inhibition of venom - induced inflammation by methanolic extract of A. absinthium was described.", "output": "There is no related enetity." }, { "input": "A success in Toxinology translational research in Brazil: Bridging the gap.", "output": "There is no related enetity." }, { "input": "Basic research is fundamental for discovering potential diagnostic and therapeutic tools, including drugs, vaccines and new diagnostic techniques.", "output": "There is no related enetity." }, { "input": "On this basis, diagnosis and treatment methods for many diseases have been developed.", "output": "There is no related enetity." }, { "input": "Presently, discovering new candidate molecules and testing them in animals are relatively easy tasks that require modest resources and responsibility.", "output": "There is no related enetity." }, { "input": "However, crossing the animal - to - human barrier is still a great challenge that most researchers tend to avoid.", "output": "There is no related enetity." }, { "input": "Thus, bridging this current gap between clinical and basic research must be encouraged and elucidated in training programmes for health professionals.", "output": "There is no related enetity." }, { "input": "This project clearly shows the challenges faced by a group of Brazilian researchers who, after discovering a new fibrin sealant through 20 years of painstaking basic work, insisted on having the product applied clinically.", "output": "There is no related enetity." }, { "input": "The Brazilian government has recently become aware of this challenge and has accordingly defined the product as strategic to the public health of the country.", "output": "There is no related enetity." }, { "input": "Thus, in addition to financing research and development laboratories, resources were invested in clinical trials and in the development of a virtual platform termed the Virtual System to Support Clinical Research ( SAVPC ); this platform imparts speed, reliability and visibility to advances in product development, fostering interactions among sponsors, physicians, students and, ultimately, the research subjects themselves.", "output": "There is no related enetity." }, { "input": "This pioneering project may become a future model for other public institutions in Brazil, principally in overcoming neglected diseases, which unfortunately continue to afflict this tropical country.", "output": "There is no related enetity." }, { "input": "Antibacterial activity of Veronica montana L. extract and of protocatechuic acid incorporated in a food system.", "output": "protocatechuic acid." }, { "input": "This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid.", "output": "phenolic, protocatechuic acid." }, { "input": "The antibacterial activity was determined by microdilution assay against six strains of Gram - positive and Gram - negative bacteria.", "output": "There is no related enetity." }, { "input": "Listeria monocytogenes was the most sensitive of the tested bacterial species.", "output": "There is no related enetity." }, { "input": "Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant.", "output": "protocatechuic acid." }, { "input": "The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator ( 25 degrees C and 4 degrees C, respectively ), after 3days of inoculation.", "output": "There is no related enetity." }, { "input": "Sensory evaluation was carried out in order to validate the mentioned food system.", "output": "There is no related enetity." }, { "input": "A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane.", "output": "There is no related enetity." }, { "input": "Prediction of pharmacokinetic properties was also performed using computational analyzes.", "output": "There is no related enetity." }, { "input": "The obtained results can serve as an important platform for the development of effective natural preservatives.", "output": "There is no related enetity." }, { "input": "RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF - kappa B activation and down regulating inflammatory cytokines.", "output": "There is no related enetity." }, { "input": "Peptides designed from osteoprotegerin ( OPG ) have previously been shown to inhibit receptor activator of NF - kappa B ligand ( RANKL ) and prevent bone loss without significantly inhibiting inflammation.", "output": "There is no related enetity." }, { "input": "The objective of this study was to develop a novel peptide with dual inhibitory activity against bone loss and inflammation using site - directed mutagenesis.", "output": "There is no related enetity." }, { "input": "Out of the three putative sites ( i. e., Tyr70 - Asp78, Tyr82 - Glu96, and Leu113 - Arg122 ) available on OPG for RANKL binding, Leu113 - Arg122 was used as a template for peptide synthesis.", "output": "Tyr70, Asp78, Tyr82, Glu96, Leu113, Arg122, Leu113, Arg122." }, { "input": "Peptide mutants of the template sequence ( 112YLEIEFCLKHR122 ) were synthesized and initially screened for their inhibitory effect on RANK - RANKL binding by competitive ELISA.", "output": "There is no related enetity." }, { "input": "The most active peptide was further evaluated in vitro for RANKL induced osteoclastogenesis in mouse macrophage cells, and in vivo for Freund ' s complete adjuvant induced arthritis ( AIA ) in Lewis rats.", "output": "There is no related enetity." }, { "input": "The efficacy of the candidate peptide was compared with that of the standard drug celecoxib.", "output": "celecoxib." }, { "input": "The peptide YR - 11 ( YLEIEFSLKHR ), obtained by direct substitution of cysteine with a serine residue in the template sequence, significantly ( p < 0. 05 ) inhibited RANK - RANKL binding, and RANKL induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity.", "output": "YR - 11, cysteine, serine." }, { "input": "Administration of YR - 11 peptide at the dose of 30mg / kg ( i. p. ) ameliorated both bone loss and inflammation in AIA rats.", "output": "YR - 11." }, { "input": "To elucidate the mechanism for inhibition of inflammation in arthritic rats, serum and tissue cytokines ( TNF - alpha, IL - 1 beta, and IL - 6 ) were analyzed by ELISA and RT - PCR methods.", "output": "There is no related enetity." }, { "input": "Results confirmed that YR - 11 peptide inhibited pro - inflammatory cytokines in the sera and hind paw tissues of AIA rats through its suppressive effect on RANKL induced nuclear translocation of NF - kappa B.", "output": "YR - 11." }, { "input": "The results obtained in this study substantiate the therapeutic benefit of this novel peptide in the prevention of bone loss and inflammation in rheumatoid arthritis with reduced side effects.", "output": "There is no related enetity." }, { "input": "Surface functionalization of doxorubicin - loaded liposomes with octa - arginine for enhanced anticancer activity.", "output": "doxorubicin, octa - arginine." }, { "input": "Doxorubicin - loaded PEGylated liposomes ( commercially available as DOXIL (R) or Lipodox (R) ) were surface functionalized with a cell - penetrating peptide, octa - arginine ( R8 ).", "output": "Doxorubicin, DOXIL, Lipodox, octa - arginine." }, { "input": "For this purpose, R8 - peptide was conjugated to the polyethylene glycol - dioleoyl phosphatidylethanolamine ( PEG - DOPE ) amphiphilic co - polymer.", "output": "polyethylene glycol - dioleoyl phosphatidylethanolamine, PEG - DOPE." }, { "input": "The resultant R8 - PEG - PE conjugate was introduced into the lipid bilayer of liposomes at 2mol % of total lipid amount via spontaneous micelle - transfer technique.", "output": "R8 - PEG - PE." }, { "input": "The liposomal modification did not alter the particle size distribution, as measured by Particle Size Analyzer and transmission electron microscopy ( TEM ).", "output": "There is no related enetity." }, { "input": "However, surface - associated cationic peptide increased zeta potential of the modified liposomes.", "output": "There is no related enetity." }, { "input": "R8 - functionalized liposomes ( R8 - Dox - L ) markedly increased the intracellular and intratumoral delivery of doxorubicin as measured by flow cytometry and visualizing by confocal laser scanning microscopy ( CLSM ) compared to unmodified Doxorubicin - loaded PEGylated liposomes ( Dox - L ).", "output": "Dox, doxorubicin, Doxorubicin, Dox." }, { "input": "R8 - Dox - L delivered loaded Doxorubicin to the nucleus, being released from the endosomes at higher efficiency compared to unmodified liposomes, which had marked entrapment in the endosomes at tested time point of 1h.", "output": "Dox, Doxorubicin." }, { "input": "The significantly higher accumulation of loaded drug to its site of action for R8 - Dox - L resulted in improved cytotoxic activity in vitro ( cell viability of 58. 5 +/- 7 % for R8 - Dox - L compared to 90. 6 +/- 2 % for Dox - L at Dox dose of 50 mu g / mL for 4h followed by 24h incubation ) and enhanced suppression of tumor growth ( 348 +/- 53mm ( 3 ) for R8 - Dox - L, compared to 504 +/- 54mm ( 3 ) for Dox - L treatment ) in vivo compared to Dox - L.", "output": "Dox, Dox, Dox, Dox, Dox, Dox, Dox." }, { "input": "R8 - modification has the potential for broadening the therapeutic window of pegylated liposomal doxorubicin treatment, which could lead to lower non - specific toxicity.", "output": "doxorubicin." }, { "input": "Preparation of carbamazepine - Soluplus (R) solid dispersions by hot - melt extrusion, and prediction of drug - polymer miscibility by thermodynamic model fitting.", "output": "carbamazepine, Soluplus." }, { "input": "Hot - melt extrusion ( HME ) is a dust - and solvent - free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic polymers.", "output": "There is no related enetity." }, { "input": "Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation.", "output": "There is no related enetity." }, { "input": "The present study investigates the feasibility of forming solid dispersions of carbamazepine ( CBZ ) into polyethyleneglycol - polyvinyl caprolactam - polyvinyl acetate grafted copolymer ( Soluplus (R) ) by hot - melt extrusion.", "output": "carbamazepine, CBZ, polyethyleneglycol, polyvinyl caprolactam, polyvinyl acetate, Soluplus." }, { "input": "Physicochemical properties of the raw materials, extrudates, co - melted products, and corresponding physical mixtures were characterized by thermo - gravimetric analysis ( TGA ), differential scanning calorimetry ( DSC ), attenuated total reflectance infrared ( ATR - FTIR ) spectroscopy and hot stage microscopy ( HSM ), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory - Huggins theory, Hansen solubility parameters, and solid - liquid equilibrium equation.", "output": "CBZ, Soluplus." }, { "input": "It was found that hot - melt extrusion of carbamazepine and Soluplus (R) is feasible on a single - screw hot - melt extruder without the addition of plasticizers.", "output": "carbamazepine, Soluplus." }, { "input": "DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed ~ 5 % w / w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ.", "output": "CBZ, CBZ, CBZ, CBZ." }, { "input": "Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility / dispersibility of carbamazepine in Soluplus (R) hot - melt extrudates.", "output": "carbamazepine, Soluplus." }, { "input": "The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.", "output": "There is no related enetity." }, { "input": "Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies.", "output": "There is no related enetity." }, { "input": "The effectiveness of Hibiscus sabdariffa L.", "output": "There is no related enetity." }, { "input": "( HS ) in the treatment of risk factors associated with cardiovascular disease is assessed in this review by taking a comprehensive approach to interpreting the randomized clinical trial ( RCT ) results in the context of the available ethnomedical, phytochemical, pharmacological, and safety and toxicity information.", "output": "There is no related enetity." }, { "input": "HS decoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countries worldwide in the treatment of hypertension and hyperlipidemia with no reported adverse events or side effects.", "output": "There is no related enetity." }, { "input": "HS extracts have a low degree of toxicity with a LD50 ranging from 2, 000 to over 5, 000mg / kg / day.", "output": "There is no related enetity." }, { "input": "There is no evidence of hepatic or renal toxicity as the result of HS extract consumption, except for possible adverse hepatic effects at high doses.", "output": "There is no related enetity." }, { "input": "There is evidence that HS acts as a diuretic, however in most cases the extract did not significantly influence electrolyte levels.", "output": "There is no related enetity." }, { "input": "Animal studies have consistently shown that consumption of HS extract reduces blood pressure in a dose dependent manner.", "output": "There is no related enetity." }, { "input": "In RCTs, the daily consumption of a tea or extract produced from HS calyxes significantly lowered systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) in adults with pre to moderate essential hypertension and type 2 diabetes.", "output": "There is no related enetity." }, { "input": "In addition, HS tea was as effective at lowering blood pressure as the commonly used blood pressure medication Captropril, but less effective than Lisinopril.", "output": "Captropril, Lisinopril." }, { "input": "Total cholesterol, low - density lipoprotein cholesterol ( LDL - C ), and triglycerides were lowered in the majority of normolipidemic, hyperlipidemic, and diabetic animal models, whereas high - density lipoprotein cholesterol ( HDL - C ) was generally not affected by the consumption of HS extract.", "output": "cholesterol, cholesterol, triglycerides, cholesterol." }, { "input": "Over half of the RCTs showed that daily consumption of HS tea or extracts had favorable influence on lipid profiles including reduced total cholesterol, LDL - C, triglycerides, as well as increased HDL - C.", "output": "cholesterol, triglycerides." }, { "input": "Anthocyanins found in abundance in HS calyxes are generally considered the phytochemicals responsible for the antihypertensive and hypocholesterolemic effects, however evidence has also been provided for the role of polyphenols and hibiscus acid.", "output": "Anthocyanins, polyphenols, hibiscus acid." }, { "input": "A number of potential mechanisms have been proposed to explain the hypotensive and anticholesterol effects, but the most common explanation is the antioxidant effects of the anthocyanins inhibition of LDL - C oxidation, which impedes atherosclerosis, an important cardiovascular risk factor.", "output": "anthocyanins." }, { "input": "This comprehensive body of evidence suggests that extracts of HS are promising as a treatment of hypertension and hyperlipidemia, however more high quality animal and human studies informed by actual therapeutic practices are needed to provide recommendations for use that have the potential for widespread public health benefit.", "output": "There is no related enetity." }, { "input": "Antidepressant use and glycemic control.", "output": "There is no related enetity." }, { "input": "RATIONALE: Past research on the association of antidepressant medication use with glycemic control abnormalities has produced mixed results.", "output": "There is no related enetity." }, { "input": "OBJECTIVE: To examine the association of antidepressant use with glycemic control abnormalities and screen - positive diabetes in a representative population sample of US adults without a diagnosis of diabetes.", "output": "There is no related enetity." }, { "input": "METHODS: Using data from adult participants of the National Health and Nutrition Examination Survey ( NHANES, 2005 - 2010 ), the association of antidepressant use with continuous measures of HbA1c, fasting blood sugar, 2 - h oral glucose tolerance test, insulin sensitivity and screen - positive diabetes according to HbA1c, fasting blood sugar and 2 - h oral glucose tolerance test were assessed.", "output": "sugar, glucose, glucose." }, { "input": "RESULTS: Antidepressant use was not associated with increased levels of HbA1c, fasting blood sugar, 2 - h oral glucose tolerance test, reduced insulin sensitivity or increased prevalence of screen - positive diabetes.", "output": "sugar, glucose." }, { "input": "Results were mostly consistent across sociodemographic groups and across different lengths of exposure, different classes of antidepressants and levels of body mass index.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: In this representative population sample, antidepressant use was not associated with an increased risk of abnormalities in glycemic control or undetected diabetes.", "output": "There is no related enetity." }, { "input": "Positive findings from past research may be attributable to detection bias, in that individuals prescribed antidepressants may be more likely to be tested and diagnosed with diabetes.", "output": "There is no related enetity." }, { "input": "Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses.", "output": "vitamin B6." }, { "input": "Pyridoxal - 5 ' - phosphate ( PLP ), the bioactive form of vitamin B6, reportedly functions as a prosthetic group for > 4 % of classified enzymatic activities of the cell.", "output": "Pyridoxal - 5 ' - phosphate, PLP, vitamin B6." }, { "input": "It is therefore not surprising that alterations of vitamin B6 metabolism have been associated with multiple human diseases.", "output": "vitamin B6." }, { "input": "As a striking example, mutations in the gene coding for antiquitin, an evolutionary old aldehyde dehydrogenase, result in pyridoxine - dependent seizures, owing to the accumulation of a metabolic intermediate that inactivates PLP.", "output": "aldehyde, pyridoxine, PLP." }, { "input": "In addition, PLP is required for the catabolism of homocysteine by transsulfuration.", "output": "PLP, homocysteine." }, { "input": "Hence, reduced circulating levels of B6 vitamers ( including PLP as well as its major precursor pyridoxine ) are frequently paralleled by hyperhomocysteinemia, a condition that has been associated with an increased risk for multiple cardiovascular diseases.", "output": "B6, PLP, pyridoxine." }, { "input": "During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer.", "output": "vitamin B6." }, { "input": "Thus, high circulating levels of vitamin B6, as such or as they reflected reduced amounts of circulating homocysteine, have been associated with improved disease outcome in patients bearing a wide range of hematological and solid neoplasms.", "output": "vitamin B6, homocysteine." }, { "input": "More recently, the proficiency of vitamin B6 metabolism has been shown to modulate the adaptive response of tumor cells to a plethora of physical and chemical stress conditions.", "output": "vitamin B6." }, { "input": "Moreover, elevated levels of pyridoxal kinase ( PDXK ), the enzyme that converts pyridoxine and other vitamin B6 precursors into PLP, have been shown to constitute a good, therapy - independent prognostic marker in patients affected by non - small cell lung carcinoma ( NSCLC ).", "output": "pyridoxal, pyridoxine, vitamin B6, PLP." }, { "input": "Here, we will discuss the clinical relevance of vitamin B6 metabolism as a prognostic factor in cancer patients. Oncogene advance online publication, 21 January 2013; doi: 10. 1038 / onc. 2012. 623.", "output": "vitamin B6." }, { "input": "Effects of aging on apoptosis gene expression in oral mucosal tissues.", "output": "There is no related enetity." }, { "input": "Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti - inflammatory effects that benefits the mucosa.", "output": "There is no related enetity." }, { "input": "The oral cavity presents a model of host - bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues.", "output": "There is no related enetity." }, { "input": "This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model.", "output": "There is no related enetity." }, { "input": "Macaca mulatta primates from 2 to 23 years of age ( n = 23 ) were used in a cross - sectional study to obtain clinical healthy gingival tissues specimens.", "output": "There is no related enetity." }, { "input": "Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated.", "output": "There is no related enetity." }, { "input": "The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes.", "output": "There is no related enetity." }, { "input": "The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca ( + 2 ) - induced death signaling, cell cycle checkpoints, and potential effects of survival factors.", "output": "Ca ( + 2 )." }, { "input": "Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals.", "output": "There is no related enetity." }, { "input": "The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden.", "output": "There is no related enetity." }, { "input": "Characterization of osteoblastic and osteolytic proteins in prostate cancer bone metastases.", "output": "There is no related enetity." }, { "input": "BACKGROUND: Approximately 90 % of patients who die of Prostate Cancer ( PCa ) have bone metastases, which promote a spectrum of osteoblastic, osteolytic or mixed bone responses.", "output": "There is no related enetity." }, { "input": "Numerous secreted proteins have been reported to promote osteoblastic or osteolytic bone responses.", "output": "There is no related enetity." }, { "input": "We determined whether previously identified and / or novel proteins were associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases.", "output": "There is no related enetity." }, { "input": "METHODS: Gene expression was analyzed on 14 PCa metastases from 11 patients by microarray profiling and qRT - PCR, and protein expression was analyzed on 33 PCa metastases from 30 patients by immunohistochemistry on highly osteoblastic and highly osteolytic bone specimens.", "output": "There is no related enetity." }, { "input": "RESULTS: Transcript and protein levels of BMP - 2, BMP - 7, DKK - 1, ET - 1, and Sclerostin were not significantly different between osteoblastic and osteolytic metastases.", "output": "There is no related enetity." }, { "input": "However, levels of OPG, PGK1, and Substance P proteins were increased in osteoblastic samples.", "output": "There is no related enetity." }, { "input": "In addition, Emu1, MMP - 12, and sFRP - 1 were proteins identified with a novel role of being associated with either the osteoblastic or osteolytic bone response.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: This is the first detailed analysis of bone remodeling proteins in human specimens of PCa bone metastases.", "output": "There is no related enetity." }, { "input": "Three proteins not previously shown to be involved may have a role in the PCa bone response.", "output": "There is no related enetity." }, { "input": "Furthermore, our data suggests that the relative expression of numerous, rather than a single, bone remodeling proteins determine the bone response in PCa bone metastases.", "output": "There is no related enetity." }, { "input": "Prostate (c) 2013 Wiley Periodicals, Inc.", "output": "There is no related enetity." }, { "input": "Mineralization of phenanthrene sorbed on multiwalled carbon nanotubes.", "output": "phenanthrene, carbon." }, { "input": "Carbon nanotubes have attracted attention around the world because of their high sorption capacity for hydrophobic organic compounds ( HOCs ); however, the bioavailability of HOCs sorbed on carbon nanotubes to bacteria is not well known.", "output": "Carbon, carbon." }, { "input": "In the present study, ( 14 ) C - labeled and unlabeled phenanthrene was spiked onto four kinds of multiwalled carbon nanotubes ( MWCNTs ) and aged for 60 d, and the mineralization of phenanthrene sorbed on MWCNTs was studied.", "output": "( 14 ) C, phenanthrene, carbon, phenanthrene." }, { "input": "The mineralization efficiencies of phenanthrene sorbed on the four kinds of MWCNTs were 2. 38, 8. 84, 23. 88, and 31. 47 %, respectively, after incubation for 35 d, which were positively correlated with the sum of fast and slow desorption fractions of phenanthrene ( p < 0. 05 ).", "output": "phenanthrene, phenanthrene." }, { "input": "The authors found that the mineralization efficiencies agreed well with the MWCNT properties; the increasing specific surface area and mesopore and micropore volume of MWCNTs caused a significant decrease in the mineralization efficiency of phenanthrene ( p < 0. 05 ).", "output": "phenanthrene." }, { "input": "After incubation for 35 d, the density of bacteria had a significant positive correlation with both the desorption and the mineralization efficiencies.", "output": "There is no related enetity." }, { "input": "The authors inferred that, although MWCNTs might have toxic effects on the bacteria, the biodegrading ability of bacteria might not decrease significantly under the influence of MWCNTs with low surface area.", "output": "There is no related enetity." }, { "input": "Biotinylated phosphoproteins from kinase - catalyzed biotinylation are stable to phosphatases: implications for phosphoproteomics.", "output": "There is no related enetity." }, { "input": "Kinase - catalyzed protein phosphorylation is involved in a wide variety of cellular events.", "output": "There is no related enetity." }, { "input": "Development of methods to monitor phosphorylation is critical to understand cell biology.", "output": "There is no related enetity." }, { "input": "Our lab recently discovered kinase - catalyzed biotinylation, where ATP - biotin is utilized by kinases to label phosphopeptides or phosphoproteins with a biotin tag.", "output": "ATP, biotin, biotin." }, { "input": "To exploit kinase - catalyzed biotinylation for phosphoprotein purification and identification in a cellular context, the susceptibility of the biotin tag to phosphatases was characterized.", "output": "biotin." }, { "input": "We found that the phosphorylbiotin group on peptide and protein substrates was relatively insensitive to protein phosphatases.", "output": "phosphorylbiotin." }, { "input": "To understand how phosphatase stability would impact phosphoproteomics research applications, kinase - catalyzed biotinylation of cell lysates was performed in the presence of kinase or phosphatase inhibitors.", "output": "There is no related enetity." }, { "input": "We found that biotinylation with ATP - biotin was sensitive to inhibitors, although with variable effects compared to ATP phosphorylation.", "output": "ATP, biotin, ATP." }, { "input": "The results suggest that kinase - catalyzed biotinylation is well suited for phosphoproteomics studies, with particular utility towards monitoring low - abundance phosphoproteins or characterizing the influence of inhibitor drugs on protein phosphorylation.", "output": "There is no related enetity." }, { "input": "Genetic dissection of sesquiterpene biosynthesis by Fusarium fujikuroi.", "output": "sesquiterpene." }, { "input": "A treasure trove of terpenes: The products of two fungal sesquiterpene synthases from the rice pathogen Fusarium fujikuroi were identified by gene - knockout experiments, genetic engineering of the fungus for production optimization, isolation of the sesquiterpenes, and structure elucidation by spectroscopic methods.", "output": "terpenes, sesquiterpene, sesquiterpenes." }, { "input": "Synthesis and characterization of conformationally rigid chiral pyridine - N - heterocyclic carbene - based palladacycles with an unexpected Pd - N bond cleavage.", "output": "pyridine, N - heterocyclic carbene, palladacycles, Pd, N." }, { "input": "The versatility of a previously developed method for the synthesis of chiral carbene - based palladacycles is demonstrated through the synthesis of two new chiral pyridine - functionalized N - heterocyclic carbene palladacycles with different wingtip groups.", "output": "carbene, palladacycles, pyridine, N - heterocyclic carbene, palladacycles." }, { "input": "The efficiency in their resolution with different counter anions and different chiral amino acid salt auxiliaries has been studied.", "output": "amino acid." }, { "input": "The absolute stereochemistries of all the chiral compounds were confirmed by single crystal X - ray crystallography.", "output": "There is no related enetity." }, { "input": "An unexpected Pd - N bond cleavage that resulted in the racemization of the alpha - carbon center in these complexes has also been investigated.", "output": "Pd, N, alpha - carbon." }, { "input": "TGF - beta 1 Conjugated to Gold Nanoparticles Results in Protein Conformational Changes and Attenuates the Biological Function.", "output": "There is no related enetity." }, { "input": "Gold nanoparticles ( AuNPs ) are widely used as carriers or therapeutic agents due to their great biocompatibility and unique physical properties.", "output": "There is no related enetity." }, { "input": "Transforming growth factor - beta 1 ( TGF - beta 1 ), a member of the cysteine - knot structural superfamily, plays a pivotal role in many diseases and is known as an immunosuppressive agent that attenuates immune response resulting in tumor growth.", "output": "cysteine." }, { "input": "The results reported herein reflect strong interactions between TGF - beta 1 and the surface of AuNPs when incubated with serum - containing medium, and demonstrate a time - and dose - dependent pattern.", "output": "There is no related enetity." }, { "input": "Compared with other serum proteins that can also bind to the AuNP surface, AuNP - TGF beta 1 conjugate is a thermodynamically favored compound.", "output": "There is no related enetity." }, { "input": "Epithelial cells undergo epithelial - mesenchymal transition ( EMT ) upon treatment with TGF - beta 1; however, treatment with AuNPs reverses this effect, as detected by cell morphology and expression levels of EMT markers.", "output": "There is no related enetity." }, { "input": "TGF - beta 1 is found to bind to AuNPs through S - Au bonds by X - ray photoelectron spectroscopy.", "output": "S - Au." }, { "input": "Fourier transform infrared spectroscopy is employed to analyze the conformational changes of TGF - beta 1 on the surface of AuNPs.", "output": "There is no related enetity." }, { "input": "The results indicate that TGF - beta 1 undergoes significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, which results in the deactivation of TGF - beta 1 protein.", "output": "There is no related enetity." }, { "input": "An in vivo experiment also shows that addition of AuNPs attenuates the growth of TGF - beta 1 - secreting murine bladder tumor 2 cells in syngeneic C3H / HeN mice, but not in immunocompromised NOD - SCID mice, and this is associated with an increase in the number of tumor - infiltrating CD4 ( + ) and CD8 ( + ) T lymphocytes and a decrease in the number of intrasplenic Foxp3 ( + ) lymphocytes.", "output": "There is no related enetity." }, { "input": "The findings demonstrate that AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF - beta 1 signaling.", "output": "There is no related enetity." }, { "input": "Scaffold effects on osteogenic differentiation of equine mesenchymal stem cells: an in vitro comparative study.", "output": "There is no related enetity." }, { "input": "The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells ( MSCs ) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen - based scaffolds or with fibrin glue.", "output": "There is no related enetity." }, { "input": "The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied.", "output": "There is no related enetity." }, { "input": "Shrinking hydrogel - DNA spots generates 3D microdots arrays.", "output": "There is no related enetity." }, { "input": "This report describes a straightforward approach for the achievement of sub - 100 micrometers size hydrogel dots supporting DNA immobilization.", "output": "There is no related enetity." }, { "input": "Hydrogel - DNA spots are arrayed and UV - crosslinked on PolyShrink, an innovative polymer material having the remarkable property of isotropically shrinking under high temperature.", "output": "There is no related enetity." }, { "input": "Curing the microarray enables then spot miniaturization, resulting in 6 micro m thick and 60 micro m wide hydrogel dots in which oligonucleotides are immobilized in a 3D hydrophilic environment.", "output": "There is no related enetity." }, { "input": "The probe immobilization within the hydrogel network and its capacity to detect targets specifically and quantitatively is demonstrated using chemiluminescent as well as colorimetric detection techniques.", "output": "There is no related enetity." }, { "input": "The hydrogel material improves probe accessibility within the spot, leading to an enhanced sensitivity.", "output": "There is no related enetity." }, { "input": "Mimicking native extracellular matrix with phytic Acid - crosslinked protein nanofibers for cardiac tissue engineering.", "output": "phytic Acid." }, { "input": "A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium.", "output": "There is no related enetity." }, { "input": "Hemoglobin / gelatin / fibrinogen ( Hb / gel / fib ) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity.", "output": "There is no related enetity." }, { "input": "It is hypothesized that ex vivo pretreatment of mesenchymal stem cells ( MSCs ) using 5 - azacytidine and such a functional nanofibrous construct having a high oxygen - carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects.", "output": "5 - azacytidine, oxygen." }, { "input": "The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.", "output": "phytic acid." }, { "input": "Comparison of contact angle hysteresis of different probe liquids on the same solid surface.", "output": "There is no related enetity." }, { "input": "Advancing and receding contact angles of water, formamide and diiodomethane were measured on 1, 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine ( DPPC ) layers deposited on three different solid supports - glass, mica and poly ( methyl methacrylate ).", "output": "formamide, diiodomethane, 1 , 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine, DPPC, poly ( methyl methacrylate )." }, { "input": "Up to five statistical monolayers were deposited on the surfaces by spreading DPPC solution.", "output": "DPPC." }, { "input": "It was found that even on five statistical DPPC monolayers, the hysteresis of a given liquid depends on the kind of solid support.", "output": "DPPC." }, { "input": "Also on the same solid support the contact angle hysteresis is different for each probe liquid used.", "output": "There is no related enetity." }, { "input": "The AFM images show that the heights of roughness of the DPPC films cannot be the primary cause of the observed hysteresis because the heights are too small to cause the observed hystereses.", "output": "DPPC." }, { "input": "It is believed that the hysteresis is due to the liquid film present right behind the three - phase solid surface / liquid drop / gas ( vapour ) contact line and the presence of Derjaguin pressure.", "output": "There is no related enetity." }, { "input": "The value of contact angle hysteresis depends on both the solid surface and liquid properties as well as on intermolecular interactions between them.", "output": "There is no related enetity." }, { "input": "Enhancing macrocyclic diterpenes as multidrug - resistance reversers: structure - activity studies on jolkinol D derivatives.", "output": "diterpenes, jolkinol D." }, { "input": "The phytochemical study of Euphorbia piscatoria yielded jolkinol D ( 1 ) in a large amount, whose derivatization gave rise to 12 ester derivatives ( 2 - 13 ) and hydrolysis to compound 14.", "output": "jolkinol D, ester." }, { "input": "The in vitro modulation of P - gp of compounds 1 - 14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene.", "output": "There is no related enetity." }, { "input": "Apart from jolkinol D, all derivatives ( 2 - 14 ) showed potential as MDR reversal agents.", "output": "jolkinol D." }, { "input": "In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure - activity relationships essential in overcoming multidrug resistance ( MDR ), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol / water partition coefficient were identified that can contribute to the development of new selective P - gp reversal agents.", "output": "lathyrane diterpene, octanol." }, { "input": "Separation and structure elucidation of a new homoflavanol derivative from Pteridium aquilinum ( L. ) Kuhn.", "output": "homoflavanol." }, { "input": "A novel homoflavanol derivative ( 1 ) with an unprecedented skeleton, as well as two known flavonoids kaempferol ( 2 ) and quercetin ( 3 ), was isolated from the plant Pteridium aquilinum ( L. ) Kuhn, and the structure and relative stereochemistry of the new compound ( 1 ) were elucidated on the basis of spectroscopic data.", "output": "homoflavanol, flavonoids, kaempferol, quercetin." }, { "input": "Biomimetic polymer brushes containing tethered acetylcholine analogs for protein and hippocampal neuronal cell patterning.", "output": "acetylcholine." }, { "input": "This paper describes a method to control neuronal cell adhesion and differentiation with both chemical and topographic cues by using a spatially defined polymer brush pattern.", "output": "There is no related enetity." }, { "input": "First, biomimetic methacrylate polymer brushes containing tethered neurotransmitter acetylcholine functionalities in the form of dimethylaminoethyl methacrylate or free hydroxyl - terminated poly ( ethylene glycol ) units were prepared using the \" grown from \" method through surface - initiated atom transfer radical polymerization reactions.", "output": "methacrylate, acetylcholine, dimethylaminoethyl methacrylate, hydroxyl, poly ( ethylene glycol )." }, { "input": "The surface properties of the resulting brushes were thoroughly characterized with various techniques and hippocampal neuronal cell culture on the brush surfaces exhibit cell viability and differentiation comparable to, or even better than, those on commonly used poly - l - lysine coated glass coverslips.", "output": "poly - l - lysine." }, { "input": "The polymer brushes were then patterned via UV photolithography techniques to provide specially designed surface features with different sizes ( varying from 2 to 200 mu m ) and orientations ( horizontal and vertical ).", "output": "There is no related enetity." }, { "input": "Protein absorption experiments and hippocampal neuronal cell culture tests on the brush patterns showed that both protein and neurons can adhere to the patterns and therefore be guided by such patterns.", "output": "There is no related enetity." }, { "input": "These results also demonstrate that, because of their unique chemical composition and well - defined nature, the developed polymer brushes may find many potential applications in cell - material interactions studies and neural tissue engineering.", "output": "There is no related enetity." }, { "input": "Self - Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles.", "output": "There is no related enetity." }, { "input": "The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal - metal interactions and supramolecular assembly.", "output": "There is no related enetity." }, { "input": "Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self - assembly into structures such as nanoparticles, nanosheets and nanofibers.", "output": "There is no related enetity." }, { "input": "In this study, we combined these two concepts by investigating the self - assembly of discrete metal complexes in aqueous solution using block copolypeptides.", "output": "There is no related enetity." }, { "input": "Normally, discrete metal complexes such as [ Au ( CN ) ( 2 ) ] -, when molecularly dispersed in water, cannot interact with one another.", "output": "[ Au ( CN ) ( 2 ) ] -." }, { "input": "Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K ( 183 ) L ( 19 ) to [ Au ( CN ) ( 2 ) ] - solutions induced one - dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal - metal interactions.", "output": "[ Au ( CN ) ( 2 ) ] -." }, { "input": "Transmission electron microscopy ( TEM ) showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji ( traditional Japanese straw sandals ).", "output": "There is no related enetity." }, { "input": "This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water.", "output": "There is no related enetity." }, { "input": "Crowd computing: using competitive dynamics to develop and refine highly predictive models.", "output": "There is no related enetity." }, { "input": "A recent application of a crowd computing platform to develop highly predictive in silico models for use in the drug discovery process is described.", "output": "There is no related enetity." }, { "input": "The platform, Kaggle (TM), exploits a competitive dynamic that results in model optimization as the competition unfolds.", "output": "There is no related enetity." }, { "input": "Here, this dynamic is described in detail and compared with more - conventional modeling strategies.", "output": "There is no related enetity." }, { "input": "The complete and full structure of the underlying dataset is disclosed and some thoughts as to the broader utility of such ' gamification ' approaches to the field of modeling are offered.", "output": "There is no related enetity." }, { "input": "Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP - 2 and MMP - 9 activities by cytotoxin protein NN - 32 purified from Indian spectacled cobra ( Naja naja ) venom.", "output": "There is no related enetity." }, { "input": "A cytotoxin NN - 32 ( 6. 7 kDa ) from Indian cobra ( Naja naja ) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay.", "output": "Trypan blue, MTT." }, { "input": "NN - 32 induced apoptosis of U937 cell and cell cycle arrest of sub - G1 phase were revealed by FACS analysis.", "output": "There is no related enetity." }, { "input": "Increased Bax / Bcl - 2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP - 2 and MMP - 9 activities were observed after NN - 32 treatment of U937 cell.", "output": "There is no related enetity." }, { "input": "Antileukemic activity of NN - 32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.", "output": "There is no related enetity." }, { "input": "Pharmacy benefit managers and their obligations during serious prescription drug shortages.", "output": "There is no related enetity." }, { "input": "Pharmacy benefit managers are connected to some 215 million Americans and to every prescribing physician and retail pharmacy in the United States.", "output": "There is no related enetity." }, { "input": "Many of them have their own large and sophisticated dispensing operations.", "output": "There is no related enetity." }, { "input": "These capabilities could be put to use when drug shortages threaten life.", "output": "There is no related enetity." }, { "input": "Indeed, these capabilities are such that they confer obligations on pharmacy benefit managers to address such shortages - - not only on behalf of their clients but for society in general.", "output": "There is no related enetity." }, { "input": "N - 1, C - 3 substituted indoles as 5 - LOX inhibitors - - in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.", "output": "indoles." }, { "input": "Based upon the structures of some known 5 - LOX inhibitors, a set of five compounds carrying appropriate substituents at N - 1 and C - 3 of indole were synthesized and investigated for 5 - LOX inhibitory activities.", "output": "indole." }, { "input": "Fifty percent inhibitory concn ( IC ( 50 ) ) of these compounds ranges from 0. 6 to 5 mu M and found to be comparable to that of clinically used 5 - LOX inhibitor, zileuton.", "output": "zileuton." }, { "input": "The compounds under present investigations exhibited appreciable interactions with 5 - LOX as apparent from their association constants calculated from the mass spectral data.", "output": "There is no related enetity." }, { "input": "Compound 5a with a tosyl group at N - 1 and pyrolidinyl - 1, 2 - dione substituent at C - 3 of indole, exhibiting IC ( 50 ) 0. 6 mu M and stoichiometry of 1: 7 in the enzyme - compound complex was identified as highly potent 5 - LOX inhibitor and seems to be suitable for further investigations.", "output": "tosyl, pyrolidinyl - 1 , 2 - dione, indole." }, { "input": "9 9 mTc - ( Me ) FGCDEVD, a potential tracer for apoptosis detection.", "output": "9 9 mTc - ( Me ) FGCDEVD." }, { "input": "( Me ) FGC ( Bz ) DEVD was radiolabeled with technetium - 99m in high yield.", "output": "( Me ) FGC ( Bz ) DEVD, technetium - 99m." }, { "input": "This tracer was preferentially accumulated in apoptotic cells in the in vitro studies.", "output": "There is no related enetity." }, { "input": "Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors.", "output": "cisplatin." }, { "input": "Therefore, ( 99m ) Tc - ( Me ) FGCDEVD is a potential tracer for apoptosis detection.", "output": "( 99m ) Tc - ( Me ) FGCDEVD." }, { "input": "sigma, pi aromaticity and anti - aromaticity as retrieved by the linear response kernel.", "output": "There is no related enetity." }, { "input": "The chemical importance of the linear response kernel from conceptual Density Functional Theory ( DFT ) is investigated for some sigma and pi aromatic and anti - aromatic systems.", "output": "There is no related enetity." }, { "input": "The effect of the ring size is studied by looking at some well known aromatic and anti - aromatic molecules of different sizes, showing that the linear response is capable of correctly classifying and quantifying the aromaticity for five - to eight - membered aromatic and anti - aromatic molecules.", "output": "There is no related enetity." }, { "input": "The splitting of the linear response in sigma and pi contributions is introduced and its significance is illustrated using some sigma - aromatic molecules.", "output": "There is no related enetity." }, { "input": "The linear response also correctly predicts the aromatic transition states of the Diels - Alder reaction and the acetylene trimerisation and shows the expected behavior along the reaction coordinate, proving that the method is accurate not only at the minimum of the potential energy surface, but also in non - equilibrium states.", "output": "acetylene." }, { "input": "Finally, the reason for the close correlation between the linear response and the Para Delocalisation Index ( PDI ), found in previous and the present study, is proven mathematically.", "output": "There is no related enetity." }, { "input": "These results show the linear response to be a reliable DFT - index to probe the sigma and pi aromaticity or anti - aromaticity of a broad range of molecules.", "output": "There is no related enetity." }, { "input": "Exciton diffusion in near - infrared absorbing solution - processed organic thin films.", "output": "There is no related enetity." }, { "input": "We report on singlet - singlet annihilation and exciton diffusion in as - prepared p - type and annealed n - type thin films of the low - bandgap quinoidal quaterthiophene [ QQT ( CN ) 4 ] using ultrafast transient absorption measurements.", "output": "quinoidal quaterthiophene, QQT ( CN ) 4." }, { "input": "The decay dynamics of exciton populations are well described by a one - dimensional diffusion - limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction.", "output": "There is no related enetity." }, { "input": "Our results show that the exciton diffusion constants in QQT ( CN ) 4 films do not vary significantly upon thermal annealing.", "output": "QQT ( CN ) 4." }, { "input": "Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as - prepared and annealed QQT ( CN ) 4 films, respectively.", "output": "QQT ( CN ) 4." }, { "input": "We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering.", "output": "There is no related enetity." }, { "input": "Because of the possibility of patterning p - n regions in QQT ( CN ) 4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high - performance p - n nanostructured near infrared light - sensing devices.", "output": "QQT ( CN ) 4, quinoidal oligothiophene." }, { "input": "Highly effective Ir ( x ) Sn ( 1 - x ) O2 electrocatalysts for oxygen evolution reaction in the solid polymer electrolyte water electrolyser.", "output": "Ir, Sn, O2, oxygen." }, { "input": "We developed an advanced surfactant - assistant method for the Ir ( x ) Sn ( 1 - x ) O ( 2 ) ( 0 < x <= 1 ) nanoparticle ( NP ) preparation, and examined the OER performances by a series of half - cell and full - cell tests.", "output": "Ir, Sn, O ( 2 )." }, { "input": "In contrast to the commercial Ir black, the collective data confirmed the outstanding activity and stability of the fabricated Ir ( x ) Sn ( 1 - x ) O ( 2 ) ( x = 1, 0. 67 and 0. 52 ) NPs, which could be ascribed to the amorphous structure, good dispersion, high pore volume, solid - solution state and Ir - rich surface for bi - metal oxides, and relatively large size ( 10 - 11 nm ), while Ir ( 0. 31 ) Sn ( 0. 69 ) exhibited poor electro - catalytic activity because of the separated two phases, a SnO ( 2 ) - rich phase and an IrO ( 2 ) - rich phase.", "output": "Ir, Sn, O ( 2 ), Ir, bi - metal oxides, Ir, Sn, SnO ( 2 ), IrO ( 2 )." }, { "input": "Furthermore, compared with highly active IrO ( 2 ), the improved durability, precious - metal Ir utilization efficiency and correspondingly reduced Ir loading were realized by the addition of Sn component.", "output": "IrO ( 2 ), Ir, Ir, Sn." }, { "input": "When the Ir ( 0. 52 ) Sn ( 0. 48 ) O ( 2 ) cell operated at 80 degrees C using Nafion (R) 115 membrane and less than 0. 8 mg cm ( - 2 ) of the noble - metal Ir loading, the cell voltages we achieved were 1. 631 V at 1000 mA cm ( - 2 ), and 1. 821 V at 2000 mA cm ( - 2 ).", "output": "Ir, Sn, O ( 2 ), Nafion, Ir." }, { "input": "The IR - free voltage at the studied current density was very close to the onset voltage of oxygen evolution.", "output": "oxygen." }, { "input": "The only 50 mu V h ( - 1 ) of voltage increased for the 500 h durability test at 500 mA cm ( - 2 ).", "output": "There is no related enetity." }, { "input": "In fact, these results are exceptional compared to the performances for OER in SPEWE cells known so far.", "output": "There is no related enetity." }, { "input": "This work highlights the potential of using highly active and stable IrO ( 2 ) - SnO ( 2 ) amorphous NPs to enhance the electrolysis efficiency, reduce the noble - metal Ir loading and thus the cost of hydrogen production from the solid polymer electrolyte water electrolysis.", "output": "IrO ( 2 ), SnO ( 2 ), Ir, hydrogen." }, { "input": "Intracameral cefuroxime: prophylaxis of postoperative endophthalmitis after cataract surgery.", "output": "cefuroxime." }, { "input": "Results of the landmark European Society of Cataract and Refractive Surgeons trial and additional prospective and retrospective studies support the use of intracameral cefuroxime in the prophylaxis of endophthalmitis following cataract surgery.", "output": "cefuroxime." }, { "input": "Prophylaxis with intracameral cefuroxime at the recommended dose appears to be well tolerated in patients undergoing cataract surgery.", "output": "cefuroxime." }, { "input": "However, off - label use of intracameral cefuroxime usually requires a two - step dilution process with the potential for dilution errors, and there are also concerns regarding the risk of contamination.", "output": "cefuroxime." }, { "input": "Aprokam (R) ( intracameral cefuroxime ) has been approved in the EU for the prophylaxis of postoperative endophthalmitis after cataract surgery.", "output": "Aprokam, cefuroxime." }, { "input": "After reconstitution of Aprokam (R), no further dilution is required and each vial is only indicated for single - patient use; this has the potential to reduce the risk of both dilution errors and contamination.", "output": "Aprokam." }, { "input": "The Inhibitory Effects of the Standardized Extracts of Ginkgo biloba on Aromatase Activity in JEG - 3 Human Choriocarcinoma Cells.", "output": "There is no related enetity." }, { "input": "Breast cancer is the most common cancer in women worldwide.", "output": "There is no related enetity." }, { "input": "There are many endocrine adjuvant therapies for breast cancer patients that are categorized according to their mechanisms.", "output": "There is no related enetity." }, { "input": "Among them, aromatase inhibitors ( AIs ) that block the synthesis of estrogens have proven superiority compared with tamoxifen and have replaced it as a first - line hormonal therapy.", "output": "estrogens, tamoxifen." }, { "input": "However, AIs also have limitations due to their side effects - increased rate of bone loss and musculoskeletal complaints.", "output": "There is no related enetity." }, { "input": "We therefore need new candidate AIs with fewer side effects.", "output": "There is no related enetity." }, { "input": "The extracts of Ginkgo biloba ( EGb ), which contain phytochemicals from the tree, had biphasic effects for estrogens and osteoporosis - inhibiting activities in our previous experiments.", "output": "estrogens." }, { "input": "In this study, we explored the possibility of EGb as an AI and their mechanisms.", "output": "There is no related enetity." }, { "input": "Aromatase activities were inhibited by EGb both in JEG - 3 cells and in recombinant CYP19 microsomes.", "output": "There is no related enetity." }, { "input": "The results of polymerase chain reaction for aromatase from a coding sequence and specific promoter sequences ( exon I. a, exon I. c ) in JEG - 3 cells as well as the results of reporter gene assays showed that EGb dose - dependently decreased the aromatase gene expression.", "output": "There is no related enetity." }, { "input": "The decreased protein levels were demonstrated by Western blotting.", "output": "There is no related enetity." }, { "input": "From these results, we concluded that EGb could act as an AI at both the enzyme and transcriptional levels.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Dendrimer and cancer: a patent review ( 2006 - present ).", "output": "There is no related enetity." }, { "input": "INTRODUCTION: Dendrimers were widely used in cancer diagnosis and therapy during the past decade.", "output": "There is no related enetity." }, { "input": "The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion.", "output": "There is no related enetity." }, { "input": "In addition, the interior pockets as well as the charged surface of dendrimer can be encapsulated / bound with anti - cancer drugs or therapeutic DNAs / siRNAs.", "output": "There is no related enetity." }, { "input": "AREAS COVERED: The combination of dendrimer chemistry and new cancer therapy techniques such as radiotherapy, photodynamic therapy, neuron capture therapy, and photothermal therapy provides promising strategies in future cancer therapy.", "output": "There is no related enetity." }, { "input": "Here, we focused on recent advances on this topic in the patents ( 2006 - present ) and discussed the advantages of dendrimer technology in these inventions.", "output": "There is no related enetity." }, { "input": "EXPERT OPINION: The challenges and perspectives of dendrimer - based theranostics for cancer diagnosis and therapy are discussed.", "output": "There is no related enetity." }, { "input": "Future efforts in this area should be focused on designing materials to solve problems such as cancer metastasis, multidrug resistance ( MDR ) in cancer cells, and early - stage cancer diagnosis.", "output": "There is no related enetity." }, { "input": "Comparative single - dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch.", "output": "rasagiline." }, { "input": "Abstract 1.", "output": "There is no related enetity." }, { "input": "A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson ' s disease.", "output": "rasagiline." }, { "input": "Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration.", "output": "rasagiline, rasagiline." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "A total of 18 minipigs were randomly divided into three groups ( six animals for each group ).", "output": "There is no related enetity." }, { "input": "A single dose of 1 mg rasagiline tablet was orally administrated to one group.", "output": "rasagiline." }, { "input": "Meanwhile, single dose of 1. 25 and 2. 5 mg ( 2 and 4 cm ( 2 ) ) rasagiline patches were given ( at the postauricular skin ) to the other two groups, respectively.", "output": "rasagiline." }, { "input": "The pharmacokinetic parameters such as plasma half - life ( t ( 1 / 2 ) ), time to peak plasma - concentration ( T ( max ) ), mean residence time ( MRT ), area under the curve ( AUC ( ( 0 - ) ( t ) ( ) ) ) were significantly ( p < 0. 05 ) different between transdermal and oral administrations.", "output": "There is no related enetity." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "The plasma half - life ( t ( 1 / 2 ) ) of rasagiline ( 1. 25 mg patch: 11. 8 +/- 6. 5 h, 2. 5 mg patch: 12. 5 +/- 4. 7 h ) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration ( 1 mg tablet: 4. 7 +/- 2. 5 h ).", "output": "rasagiline." }, { "input": "The dose - normalized relative bioavailability of rasagiline patch in minipig were 178. 5 % and 156. 4 %, respectively, for 1. 25 and 2. 5 mg patches compared with 1 mg rasagiline tablet.", "output": "rasagiline, rasagiline." }, { "input": "The prolonged t ( 1 / 2 ) and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.", "output": "rasagiline." }, { "input": "Chemical reactivity and biological activity of chalcones and other alpha, beta - unsaturated carbonyl compounds.", "output": "chalcones, alpha , beta - unsaturated carbonyl." }, { "input": "Abstract 1.", "output": "There is no related enetity." }, { "input": "Chalcones are structural analogues of benzalacetophenone ( BAP ).", "output": "Chalcones, benzalacetophenone, BAP." }, { "input": "Several derivatives have been identified in plants and anticarcinogenic and anti - inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase - 1 ( HO - 1 ).", "output": "There is no related enetity." }, { "input": "HO - 1 expression is triggered by the Nrf2 - Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael - type reaction.", "output": "chalcones, thiol." }, { "input": "2.", "output": "There is no related enetity." }, { "input": "The present study used a model system estimating the reactivity of different synthetic chalcones and other alpha, beta - unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO - 1 expression in human dermal fibroblasts.", "output": "chalcones, alpha , beta - unsaturated carbonyl, thiols." }, { "input": "3.", "output": "There is no related enetity." }, { "input": "Chemical reactivity with the thiol group of N - acetylcysteine was determined with 5, 5 ' - dithiobis - ( 2 - nitrobenzoic acid ) and followed chemical principles of structure - reactivity relationship.", "output": "thiol, N - acetylcysteine, 5 , 5 ' - dithiobis - ( 2 - nitrobenzoic acid )." }, { "input": "Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ( ( 2E ) - 1 - phenyl - 3 - pyrimidin - 2 - ylprop - 2 - en - 1 - one ) and chalcone 7 ( 1, 3 - diphenylprop - 2 - yn - 1 - one ).", "output": "sulforaphane, dimethylfumarate, chalcone, ( 2E ) - 1 - phenyl - 3 - pyrimidin - 2 - ylprop - 2 - en - 1 - one, chalcone, 1 , 3 - diphenylprop - 2 - yn - 1 - one." }, { "input": "This result demonstrates that alpha, beta - unsaturated carbonyl derivatives react with thiols differently.", "output": "alpha , beta - unsaturated carbonyl, thiols." }, { "input": "All compounds were also biologically active; however, expression of HO - 1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake.", "output": "There is no related enetity." }, { "input": "Most efficient inducers of HO - 1 expression were BAP, 4 - hydroxynonenal and chalcone 1 ( 4 - [ ( 1E ) - 3 - oxo - 3 - phenylprop - 1 - en - 1 - yl ] benzonitrile ), chalcone 5 ( ( 2E ) - 1 - phenyl - 3 - [ 4 - ( trifluoromethyl ) - phenyl ] prop - 2 - en - 1 - one ) and chalcone 7.", "output": "BAP, 4 - hydroxynonenal, chalcone, 4 - [ ( 1E ) - 3 - oxo - 3 - phenylprop - 1 - en - 1 - yl ] benzonitrile, chalcone, ( 2E ) - 1 - phenyl - 3 - [ 4 - ( trifluoromethyl ) - phenyl ] prop - 2 - en - 1 - one, chalcone." }, { "input": "Redox - active pi - conjugated organometallic monolayers: pronounced Coulomb blockade characteristic at room temperature.", "output": "organometallic." }, { "input": "We report the electrical transport characteristics of a series of molecular wires, fc - C = C - C6H4 - SAc ( fc = ferrocenyl; Ac = acetyl ) and AcS - C6H4 - C = C - ( fc ) n - C = C - C6H4 - SAc ( n = 2, 3 ), consisting of multiple redox - active ferrocenyl centers.", "output": "fc - C = C - C6H4 - SAc, ferrocenyl, acetyl, AcS - C6H4 - C = C - ( fc ) n - C = C - C6H4 - SAc, ferrocenyl." }, { "input": "The self - assembled monolayers of these molecular wires on Au surfaces were comprehensively characterized by electrochemistry and conductive atomic force microscopy techniques.", "output": "Au." }, { "input": "Characterization of the wires revealed that electron transport is made extremely efficient by the organometallic redox states.", "output": "organometallic." }, { "input": "There is a strong electronic coupling between ferrocenyl moieties, and superior electron - transport ability exists through these semirigid molecular wires.", "output": "ferrocenyl." }, { "input": "Standard rate constants for the electron transfer between the electrode and the ferrocenyl moieties were measured for the monolayers by a potential - step chronoamperometry technique.", "output": "ferrocenyl." }, { "input": "The electron conduction through the molecular wires was estimated using the monolayers as a bridge from the Au ( 111 ) metal surface to the gold tip of a conductive atomic force microscope ( CAFM ).", "output": "Au ( 111 )." }, { "input": "Using the CAFM, Coulomb blockade behavior arising from the capacitive charging of the multinuclear redox - active molecules was observed at room temperature.", "output": "There is no related enetity." }, { "input": "The conductance switching was mediated by the presence of various ferrocenyl redox states and each current step corresponded to a specific redox state.", "output": "ferrocenyl." }, { "input": "Supramolecular organization and magnetic properties of mesogen - hybridized mixed - valent manganese single molecule magnets [ Mn ( III ) 8Mn ( IV ) 4O12 ( L ( x, y, z - CB ) ) 16 ( H2O ) 4 ].", "output": "manganese, Mn ( III ) 8Mn ( IV ) 4O12 ( L ( x , y , z - CB ) ) 16 ( H2O ) 4." }, { "input": "Single molecule magnets ( SMM ) may be considered for the construction of future integrated nanodevices, provided however that some degree of ordering is imparted to these molecules ( surfaces nanostructuration ).", "output": "There is no related enetity." }, { "input": "Combining such nanoobjects with liquid - crystalline orderings to control their assembly and to potentially address them individually therefore appears as one promising strategy.", "output": "There is no related enetity." }, { "input": "Four mesomorphic, mixed - valent [ Mn ( III ) ( 8 ) Mn ( IV ) ( 4 ) O ( 12 ) ( L ( x, y, z - CB ) ) ( 16 ) ( H ( 2 ) O ) ( 4 ) ] SMM, differing in the number of liquid - crystalline promoters, ( L ( x, y, z - CB ) ), were synthesized, and their self - organizing and magnetic properties were investigated.", "output": "Mn ( III ) ( 8 ) Mn ( IV ) ( 4 ) O ( 12 ) ( L ( x , y , z - CB ) ) ( 16 ) ( H ( 2 ) O ) ( 4 )." }, { "input": "The influence of the peripheral modifications, and precisely how supramolecular ordering and magnetic properties may be affected by the evolution of the proto - mesogenic cyanobiphenyl - based ligands substitution pattern, was explored.", "output": "There is no related enetity." }, { "input": "Small - angle X - ray scattering studies revealed that all of the hybridized clusters self - organize into room - temperature bilayer smectic phases, mandated by the specific mesogenic functionalization and that the polymetallic cores are further organized according to a short - range pseudo - 2D lattice with hexagonal and / or square symmetry.", "output": "There is no related enetity." }, { "input": "All mesomorphous hybridized dodecamanganese complexes still behave as SMM: they exhibit blocking of the magnetization at about 2. 6 K as evidenced by the occurrence of frequency - dependent out - of - phase ac susceptibility signals as well as an opening of the hysteresis cycle with coercive fields varying between 0. 13 and 0. 6 T, depending on the surface ligands topology.", "output": "dodecamanganese." }, { "input": "Comparison of the magnetic properties within this series reveals intricate correlations between the structural features of the mesomorphous molecule magnet ( i. e., symmetry of the ligands substitution patterns, molecular conformation, average intercluster distances, and respective inclination ) with respect to the relative proportion of slow - and fast - relaxing species and the absolute values of the coercive fields.", "output": "There is no related enetity." }, { "input": "Type I collagen self - assembly: the roles of substrate and concentration.", "output": "There is no related enetity." }, { "input": "Collagen molecules, self - assembled into macroscopic hierarchical tissue networks, are the main organic building block of many biological tissues.", "output": "There is no related enetity." }, { "input": "A particularly common and important form of this self - assembly consists of type I collagen fibrils, which exhibit a nanoscopic signature, D - periodic gap / overlap spacing, with a distribution of values centered at approximately 67 nm.", "output": "There is no related enetity." }, { "input": "In order to better understand the relationship between type I collagen self - assembly and D - spacing distribution, we investigated surface - mediated collagen self - assembly as a function of substrate and incubation concentration.", "output": "There is no related enetity." }, { "input": "Collagen fibril assembly on phlogopite and muscovite mica as well as fibrillar gel coextrusion in glass capillary tubes all exhibited D - spacing distributions similar to those commonly observed in biological tissues.", "output": "There is no related enetity." }, { "input": "The observation of D - spacing distribution by self - assembly of type I collagen alone is significant as it eliminates the necessity to invoke other preassembly or postassembly hypotheses, such as variation in the content of collagen types, enzymatic cross - linking, or other post - translational modifications, as mechanistic origins of D - spacing distribution.", "output": "There is no related enetity." }, { "input": "The D - spacing distribution on phlogopite mica is independent of type I collagen concentration, but on muscovite mica D - spacing distributions showed increased negative skewness at 20 mu g / mL and higher concentrations.", "output": "There is no related enetity." }, { "input": "Tilted D - spacing angles were found to correlate with decreased D - spacing measurements, an effect that can be removed with a tilt angle correction, resulting in no concentration dependence of D - spacing distribution on muscovite mica.", "output": "There is no related enetity." }, { "input": "We then demonstrated that tilted D - spacing is uncommon in biological tissues and it does not explain previous observations of low D - spacing values in ovariectomized dermis and bone.", "output": "There is no related enetity." }, { "input": "Impact of ketorolac administration around ovarian stimulation on in vivo and in vitro fertilization and subsequent embryo development.", "output": "ketorolac." }, { "input": "Abstract We performed this study to investigate the effect of ketorolac ( a non - steroidal anti - inflammatory drug ) administration around ovarian stimulation on in vivo and in vitro fertilization process.", "output": "ketorolac." }, { "input": "Sixty - four female mice ( ICR ) were injected with ketorolac ( 0, 7. 5, 15 and 30 micro g / d ) for 3 d starting from the day of eCG treatment.", "output": "ketorolac." }, { "input": "In experiment 1, 41 mice were triggered by hCG and then mated; two - cell embryos were obtained and in vitro development up to blastocyst was observed.", "output": "There is no related enetity." }, { "input": "In experiment 2, 23 mice were triggered by hCG and mature oocytes were collected; in vitro fertilization rate and subsequent embryo development up to blastocyst was recorded.", "output": "There is no related enetity." }, { "input": "In experiment 1, the blastocyst - forming rates per in vivo fertilized two - cell embryo showed an inverse relationship with a dosage of ketorolac ( 97. 6 %, 64. 2 %, 35. 4 % and 25. 9 % ).", "output": "ketorolac." }, { "input": "In experiment 2, degenerated oocytes were frequently observed in a dose - dependent manner ( 4. 3 %, 22. 9 %, 22. 4 % and 75. 0 % ).", "output": "There is no related enetity." }, { "input": "Lower fertilization rates were noted in all the three ketorolac - treating groups; blastocyst - forming rate was significantly lower in 30 - micro g - treating group when compared with the control group.", "output": "ketorolac." }, { "input": "Administration of ketorolac around ovarian stimulation significantly affects the development of in vivo fertilized embryo in a dose - dependent manner.", "output": "ketorolac." }, { "input": "High - dose ketorolac could result in a poor oocyte quality and decreased embryo developmental competence.", "output": "ketorolac." }, { "input": "Ubiquitin - omics reveals novel networks and associations with human disease.", "output": "There is no related enetity." }, { "input": "Human neurodegenerative and infectious diseases and tumorigenesis are associated with alterations in ubiquitin pathways.", "output": "There is no related enetity." }, { "input": "Over 10 % of the genome encode for genes that either bind or manipulate ubiquitin to affect a large proportion of biological processes.", "output": "There is no related enetity." }, { "input": "This has been the basis for the development of approaches allowing the enrichment of ubiquitinated proteins for comparisons using proteomics and mass spectrometry.", "output": "There is no related enetity." }, { "input": "Tools such as tagged tandem ubiquitin binding domains, chemically derivatized ubiquitin or anti - gly - gly - lys antibodies combined with mass spectrometry have contributed to surveys of poly - ubiquitinated proteins, poly - ubiquitin linkage diversity and protein ubiquitination sites and their relation to other posttranslational modifications at a proteome wide level, providing insights in to how dynamic alterations in ubiquitination and deubiquitination steps are associated with normal physiology and pathogenesis.", "output": "gly - gly - lys." }, { "input": "Implications of pH manipulation methods for metal toxicity: not all acidic environments are created equal.", "output": "There is no related enetity." }, { "input": "The toxicity of many metals is impacted by environmental pH, through both competition and complexation by hydroxide and carbonate ions.", "output": "hydroxide, carbonate." }, { "input": "To establish safe environmental regulation it is important to properly define the relationship between pH and metal toxicity, a process that involves manipulating the pH of test water in the lab.", "output": "There is no related enetity." }, { "input": "The current study compares the effects of the three most common pH manipulation methods ( carbon dioxide, acid - base addition, and chemical buffers ) on acute Pb toxicity of a model fish species, Pimephales promelas.", "output": "carbon dioxide, Pb." }, { "input": "Acidification of test water revealed that the Pb and Pb ( 2 + ) LC50 values were impacted by the pH manipulation method, with the following order of effects: HCl < CO2 < MOPS.", "output": "Pb, Pb ( 2 + ), HCl." }, { "input": "Conversely no differences in toxicity were observed when test pH was alkalinized using MOPS or NaOH.", "output": "There is no related enetity." }, { "input": "The different impacts of pH manipulation methods on Pb toxicity are likely due to different physiological stresses resulting from the respective methods; the physiological implications of each method are discussed.", "output": "There is no related enetity." }, { "input": "The results suggest that when studying the impacts of pH on metal toxicity it is important to properly replicate the ambient conditions of interest as artificial buffering using CO2 environments or organic buffers significantly affects the physiology of the test organisms above and beyond what is expected from pH alone.", "output": "There is no related enetity." }, { "input": "Thus, using CO2 and organic buffers overestimates the impact of acid pH on Pb toxicity.", "output": "There is no related enetity." }, { "input": "Individual and combined effects of copper and parasitism on osmoregulation in the European eel Anguilla anguilla.", "output": "copper." }, { "input": "The European eel ( Anguilla anguilla ), a catadromous species, breeds in the sea and migrates to estuarine, lagoon or freshwater habitats for growth and development.", "output": "There is no related enetity." }, { "input": "Yellow eels, exposed to low or fluctuating salinities, are also exposed to multiple other stressors as pollution, over - fishing and parasitism, which contribute to the dramatic decrease of eel populations in several European countries.", "output": "There is no related enetity." }, { "input": "The objective of this study was to evaluate the single and combined effects of waterborne copper and experimental infestation of eels with the nematode Anguillicoloides crassus after a salinity challenge from nearly isotonic ( 18ppt ) to hypo - ( 5ppt ) and hypertonic ( 29ppt ) conditions, in order to investigate the osmoregulatory capacity of eels exposed to these stressors.", "output": "copper." }, { "input": "In a nearly isotonic condition ( 18ppt ), blood osmolality remained constant over the 6 weeks contamination to Cu ( 2 + ) and Anguillicoloides crassus.", "output": "Cu ( 2 + )." }, { "input": "In fish exposed to a salinity challenge of 29ppt for 2 weeks, no significant effect was recorded in blood osmolality, Na ( + ) / K ( + ) - ATPase ( NKA ) activity, Na ( + ) and Cl ( - ) concentrations.", "output": "Na ( + ), K ( + ), Na ( + ), Cl ( - )." }, { "input": "After 2 weeks at 5ppt however, a significant blood osmolality decrease was detected in fish exposed to Anguillicoloides crassus infestation with or without Cu ( 2 + ) addition.", "output": "Cu ( 2 + )." }, { "input": "This decrease may originate from lower Cl ( - ) levels measured in eels exposed to both stressors.", "output": "Cl ( - )." }, { "input": "Blood Na ( + ) levels remained relatively stable in all tested animals, but gill NKA activities were lower in eels exposed to combined stress.", "output": "Na ( + )." }, { "input": "No apparent branchial lesions were detected following the different treatments and immunolocalization of NKA revealed well - differentiated ionocytes.", "output": "There is no related enetity." }, { "input": "Thus, the 5ppt challenge in eels exposed to copper and Anguillicoloides crassus seems to clearly enhance iono / osmoregulatory disturbances.", "output": "copper." }, { "input": "Funded by ANR CES / CIEL 2008 - 12.", "output": "There is no related enetity." }, { "input": "Hepatic transcriptome profiling indicates differential mRNA expression of apoptosis and immune related genes in eelpout ( Zoarces viviparus ) caught at G o teborg harbor, Sweden.", "output": "There is no related enetity." }, { "input": "The physiology and reproductive performance of eelpout ( Zoarces viviparus ) have been monitored along the Swedish coast for more than three decades.", "output": "There is no related enetity." }, { "input": "In this study, transcriptomic profiling was applied for the first time as an exploratory tool to search for new potential candidate biomarkers and to investigate possible stress responses in fish collected from a chronically polluted area.", "output": "There is no related enetity." }, { "input": "An oligonucleotide microarray with more than 15, 000 sequences was used to assess differentially expressed hepatic mRNA levels in female eelpout collected from the contaminated area at G o teborg harbor compared to fish from a national reference site, Fj a llbacka.", "output": "There is no related enetity." }, { "input": "Genes involved in apoptosis and DNA damage ( e. g., SMAC / diablo homolog and DDIT4 / DNA - damage - inducible protein transcript 4 ) had higher mRNA expression levels in eelpout from the harbor compared to the reference site, whereas mRNA expression of genes involved in the innate immune system ( e. g., complement components and hepcidin ) and protein transport / folding ( e. g., signal recognition particle and protein disulfide - isomerase ) were expressed at lower levels.", "output": "disulfide." }, { "input": "Gene Ontology enrichment analysis revealed that genes involved biological processes associated with protein folding, immune responses and complement activation were differentially expressed in the harbor eelpout compared to the reference site.", "output": "There is no related enetity." }, { "input": "The differential mRNA expression of selected genes involved in apoptosis / DNA damage and in the innate immune system was verified by quantitative PCR, using the same fish in addition to eelpout captured four years later.", "output": "There is no related enetity." }, { "input": "Thus, our approach has identified new potential biomarkers of pollutant exposure and has generated hypotheses on disturbed physiological processes in eelpout.", "output": "There is no related enetity." }, { "input": "Despite a higher mRNA expression of genes related to apoptosis ( e. g., diablo homolog ) in eelpout captured in the harbor there were no significant differences in the number of TUNEL - positive apoptotic cells between sites.", "output": "There is no related enetity." }, { "input": "The mRNA level of genes involved in apoptosis / DNA damage and the status of the innate immune system in fish species captured in polluted environments should be studied in more detail to lay the groundwork for future biomonitoring studies.", "output": "There is no related enetity." }, { "input": "A new bioassay for the ecotoxicological testing of VOCs on groundwater invertebrates and the effects of toluene on Niphargus inopinatus.", "output": "There is no related enetity." }, { "input": "A protocol was developed for testing the ecotoxicological effects of volatile organic compounds ( VOCs ) on groundwater invertebrates.", "output": "There is no related enetity." }, { "input": "Test substance volatility was addressed in a \" closed from start to analysis \" - design.", "output": "There is no related enetity." }, { "input": "Since manifestation of toxic effects may be delayed in ' slower metabolizing ' organisms such as groundwater fauna, a time - independent ( TI - ) approach was adopted.", "output": "There is no related enetity." }, { "input": "Toluene was used as a model substance and its toxicity to the groundwater amphipod Niphargus inopinatus was assessed as an example.", "output": "Toluene." }, { "input": "The method evaluation process considered various methodological issues such as partitioning of the toxicant between the water and the gas phase ( Henry equilibrium ), the possible depletion of oxygen in closed test vials, as well as microbial biodegradation of the test substance.", "output": "oxygen." }, { "input": "For N. inopinatus, an LC50, 14 days of 46. 6mgL ( - 1 ) toluene was obtained.", "output": "toluene." }, { "input": "The ultimate LC50 value was estimated at 23. 3mgL ( - 1 ) toluene.", "output": "toluene." }, { "input": "No oxygen depletion occurred in the test vials and Henry equilibrium was found to be established after 6h.", "output": "oxygen." }, { "input": "The new test system proposed now awaits broad practical application.", "output": "There is no related enetity." }, { "input": "A rationally designed dual role anode material for lithium - ion and sodium - ion batteries: case study of eco - friendly Fe3O4.", "output": "lithium, sodium, Fe3O4." }, { "input": "Identifying dual role electrode materials capable of storing both lithium and sodium are thought to be highly relevant, as these materials could find potential applications simultaneously in lithium and sodium ion batteries.", "output": "lithium, sodium, lithium, sodium." }, { "input": "In this regard, the concept of dual alkali storage is demonstrated in Fe ( 3 ) O ( 4 ) anode material undergoing conversion reaction.", "output": "Fe ( 3 ) O ( 4 )." }, { "input": "To enable improved storage, a rational active material and electrode design is proposed.", "output": "There is no related enetity." }, { "input": "Accordingly, the following features were simultaneously incorporated into the design: ( i ) an optimal particle size, ( ii ) a conducting matrix, ( iii ) adequately large active material surface area and ( iv ) strong electrode material - current collector integrity.", "output": "There is no related enetity." }, { "input": "Electrodes incorporating this rational design exhibit excellent high rate performance and impressive cyclability during lithium storage.", "output": "lithium." }, { "input": "For instance, Fe ( 3 ) O ( 4 ) electrodes deliver a charge capacity of 950 mAh g ( - 1 ) at 1. 2 C ( ~ 2. 6 times higher than graphite and 5. 4 times higher than Li ( 4 ) Ti ( 5 ) O ( 12 ) ).", "output": "Fe ( 3 ) O ( 4 ), graphite, Li ( 4 ) Ti ( 5 ) O ( 12 )." }, { "input": "Further, these electrodes show no signs of capacity fade even up to 1100 cycles.", "output": "There is no related enetity." }, { "input": "Impressively, the cells could also be charged - discharged to 65 % of their theoretical capacity in just 5 min or 12 C ( 11. 11 A g ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "The rate performance and cyclability of lithium storage achieved here are amongst the highest reported values in the literature for the conversion reaction in Fe ( 3 ) O ( 4 ).", "output": "lithium, Fe ( 3 ) O ( 4 )." }, { "input": "Besides lithium storage, the dual role of this anode is shown by demonstrating its sodium storage ability by conversion reaction for the first time.", "output": "lithium, sodium." }, { "input": "Bandgap broadly tunable GaZnSeAs alloy nanowires.", "output": "GaZnSeAs." }, { "input": "Composition - tunable semiconductor alloy nanowires are emerging as an important class of materials for the realization of high - performance laterally - arranged multiple bandgap ( LAMB ) solar cells.", "output": "There is no related enetity." }, { "input": "Here we report the first growth of GaZnSeAs quaternary alloy nanowires with composed elements between two different groups using a temperature / space - selective CVD route.", "output": "GaZnSeAs." }, { "input": "Under laser excitation, these special quaternary alloy nanowires exhibit composition - related characteristic emissions, with peak wavelengths gradually tunable from 470 nm ( 2. 64 eV ) to 832 nm ( 1. 49 eV ), covering almost the entire visible spectrum.", "output": "There is no related enetity." }, { "input": "Surface photovoltage measurements further reveal that these alloy nanowires have tunable bandgaps along the length of the substrate, making them promising candidates for developing high - efficiency LAMB solar cells.", "output": "There is no related enetity." }, { "input": "These quaternary alloy nanowires represent a new advancement in material synthesis and would have potential applications in a variety of function - tunable and broadband - response optoelectronic devices.", "output": "There is no related enetity." }, { "input": "Two - dimensional supramolecular electron spin arrays.", "output": "There is no related enetity." }, { "input": "A bottom - up approach is introduced to fabricate two - dimensional self - assembled layers of molecular spin - systems containing Mn and Fe ions arranged in a chessboard lattice.", "output": "Mn, Fe." }, { "input": "We demonstrate that the Mn and Fe spin states can be reversibly operated by their selective response to coordination / decoordination of volatile ligands like ammonia ( NH3 ).", "output": "Mn, Fe, ammonia, NH3." }, { "input": "Effects of acute and sub - chronic nicotine on impulsive choice in rats in a probabilistic delay - discounting task.", "output": "nicotine." }, { "input": "RATIONALE: Cigarette smokers typically display impulsivity by preferring immediate rewards over larger, delayed rewards at shorter delays than do non - smokers.", "output": "There is no related enetity." }, { "input": "Suggesting causality, nicotine injections in rats increase the choice for an immediate reward over a larger, delayed reward.", "output": "nicotine." }, { "input": "OBJECTIVES: To examine the generality of this latter effect, the present study employed a delay - discounting task to determine if acute and sub - chronic nicotine will also increase impulsive choice when subjective reward value is manipulated by changes in the probability, rather than magnitude, of reward.", "output": "nicotine." }, { "input": "MATERIALS AND METHODS: Rats were presented with two levers, one of which delivered an immediate water reward on half of the trials, while the other lever delivered the same reward on every trial, but only after one of five increasing delays.", "output": "There is no related enetity." }, { "input": "RESULTS: Acute injections of 1. 2 mg / kg, but not 0. 8 mg / kg, of nicotine increased the preference for the immediate ( but less certain ) reward lever at intermediate delays.", "output": "nicotine." }, { "input": "Moreover, twice - daily injections of 0. 8 mg / kg of nicotine for 6 days progressively increased the preference for the immediate reward.", "output": "nicotine." }, { "input": "Latency to make the first response on each trial was not affected by nicotine.", "output": "nicotine." }, { "input": "CONCLUSIONS: The similar increases in impulsive choice produced by both acute and sub - chronic nicotine in delay - discounting paradigms whether subjective reward value is manipulated by changes in reward magnitude or probability suggests that nicotine may be increasing what is common to these paradigms, namely delay discounting.", "output": "nicotine, nicotine." }, { "input": "Whatever the mechanism, these data indicate that both acute and sub - chronic nicotine may help develop and maintain an addiction by increasing impulsivity.", "output": "nicotine." }, { "input": "Regional inhibition of cholinesterase in free - ranging western pond turtles ( Emys marmorata ) occupying California mountain streams.", "output": "There is no related enetity." }, { "input": "The present study investigated the potential effects of cholinesterase ( ChE ) - inhibiting pesticides on western pond turtles ( Emys marmorata ) occupying streams in two regions of California, USA.", "output": "There is no related enetity." }, { "input": "The southern region was suspected of having increased exposure to atmospheric deposition of contaminants originating from Central Valley agriculture.", "output": "There is no related enetity." }, { "input": "The northern region represented reference ChE activities because this area was located outside of the prominent wind patterns that deposit pesticides into the southern region.", "output": "There is no related enetity." }, { "input": "Total ChE activity was measured in plasma from a total of 81 turtles from both regions.", "output": "There is no related enetity." }, { "input": "Cholinesterase activity of turtles was significantly depressed by 31 % ( p = 0. 005 ) in the southern region after accounting for additional sources of variation in ChE activity.", "output": "There is no related enetity." }, { "input": "Male turtles had significantly increased ChE activity compared with females ( p = 0. 054 ).", "output": "There is no related enetity." }, { "input": "Cloaca temperature, length, mass, handling time, body condition, and lymph presence were not significant predictors of turtle ChE activity.", "output": "There is no related enetity." }, { "input": "In the southern region, 6. 3 % of the turtles were below the diagnostic threshold of two standard deviations less than the reference site mean ChE activity.", "output": "There is no related enetity." }, { "input": "Another diagnostic threshold determined that 75 % of the turtles from the southern region had ChE activities depressed by 20 % of the reference mean.", "output": "There is no related enetity." }, { "input": "The decrease in ChE activity in the southern region suggests sublethal effects of pesticide exposure, potentially altering neurotransmission, which can result in various deleterious behaviors.", "output": "There is no related enetity." }, { "input": "A refined aquatic ecological risk assessment for a pyrethroid insecticide used for adult mosquito management.", "output": "pyrethroid." }, { "input": "The use of pyrethroid insecticides has increased substantially throughout the world over the past few decades as the use of organophorous, carbamate, and organochlorine insecticides is being phased out.", "output": "pyrethroid, organophorous, carbamate, organochlorine." }, { "input": "Pyrethroids are the most common class of insecticides for ultralow - volume ( ULV ) aerosol applications used to manage high densities of adult mosquitoes.", "output": "Pyrethroids." }, { "input": "Pyrethroids are highly toxic to nontarget organisms such as certain aquatic organisms, and there have been concerns about the effect of applications of ULV insecticides on these organisms.", "output": "Pyrethroids." }, { "input": "To address the uncertainties associated with the risks of ULV applications and the contradictory findings of other ecological risk assessments, the authors performed a probabilistic aquatic ecological risk assessment for permethrin using actual environmental deposition on surfaces to estimate permethrin concentrations in water.", "output": "permethrin, permethrin." }, { "input": "The present study is the first ecological risk assessment for pyrethroids to quantitatively integrate the reduction in bioavailability resulting from the presence of dissolved organic matter.", "output": "pyrethroids." }, { "input": "As part of the risk assessment, the authors incorporated a species sensitivity distribution to take into account the differences in toxicity for different species.", "output": "There is no related enetity." }, { "input": "The 95th percentile estimated concentration would result in less than 0. 0001 % of the potentially affected fraction of species reaching the lethal concentration that kills 50 % of a population.", "output": "There is no related enetity." }, { "input": "The results of the present study are supported by the weight of evidence that pyrethroids applied by ground - based ULV equipment will not result in deleterious effects on aquatic organisms.", "output": "pyrethroids." }, { "input": "Simulations in evolution.", "output": "There is no related enetity." }, { "input": "III.", "output": "There is no related enetity." }, { "input": "Randomness as a generator of opportunities.", "output": "There is no related enetity." }, { "input": "In Neo - Darwinism, variation and natural selection are the two evolutionary mechanisms which propel biological evolution.", "output": "There is no related enetity." }, { "input": "Our previous reports presented a histogram model to simulate the evolution of populations of individuals classified into bins according to an unspecified, quantifiable phenotypic character, and whose number in each bin changed generation after generation under the influence of fitness, while the total population was maintained constant.", "output": "There is no related enetity." }, { "input": "The histogram model also allowed Shannon entropy ( SE ) to be monitored continuously as the information content of the total population decreased or increased.", "output": "There is no related enetity." }, { "input": "Here, a simple Perl ( Practical Extraction and Reporting Language ) application was developed to carry out these computations, with the critical feature of an added random factor in the percent of individuals whose offspring moved to a vicinal bin.", "output": "There is no related enetity." }, { "input": "The results of the simulations demonstrate that the random factor mimicking variation increased considerably the range of values covered by Shannon entropy, especially when the percentage of changed offspring was high.", "output": "There is no related enetity." }, { "input": "This increase in information content is interpreted as facilitated adaptability of the population.", "output": "There is no related enetity." }, { "input": "Silver nanoparticle toxicity effect on growth and cellular viability of the aquatic plant Lemna gibba.", "output": "Silver." }, { "input": "The toxicity effect of silver nanoparticles ( AgNPs ) on growth and cellular viability was investigated on the aquatic plant Lemna gibba exposed over 7 d to 0, 0. 01, 0. 1, 1, and 10 mg / L of AgNPs.", "output": "silver." }, { "input": "Growth inhibition was demonstrated by a significant decrease of frond numbers dependent on AgNP concentration.", "output": "There is no related enetity." }, { "input": "Under these conditions, reduction in plant cellular viability was detected for 0. 1, 1, and 10 mg / L of AgNPs within 7 d of AgNPs treatment.", "output": "There is no related enetity." }, { "input": "This effect was highly correlated with the production of intracellular reactive oxygen species ( ROS ).", "output": "oxygen." }, { "input": "A significant increase of intracellular ROS formation was triggered by 1 and 10 mg / L of AgNP exposure.", "output": "There is no related enetity." }, { "input": "The induced oxidative stress was related to Ag accumulation within L. gibba plant cells and with the increasing concentration of AgNP exposure in the medium.", "output": "Ag." }, { "input": "The authors ' results clearly suggested that AgNP suspension represented a potential source of toxicity for L. gibba plant cells.", "output": "There is no related enetity." }, { "input": "Due to the low release capacity of free soluble Ag from AgNP dissolution in the medium, it is most likely that the intracellular uptake of Ag was directly from AgNPs, triggering cellular oxidative stress that may be due to the release of free Ag inside plant cells.", "output": "Ag, Ag, Ag." }, { "input": "Therefore, the present study demonstrated that AgNP accumulation in an aquatic environment may represent a potential source of toxicity and a risk for the viability of duckweeds.", "output": "There is no related enetity." }, { "input": "Toxic effects of environment - friendly antifoulant nonivamide on Phaeodactylum tricornutum.", "output": "nonivamide." }, { "input": "Nonivamide, a synthetic derivate of natural capsaicin, has an effective antifouling activity.", "output": "Nonivamide, capsaicin." }, { "input": "However, the poor understanding of the toxicity mechanism limits the application of nonivamide in antifouling paints.", "output": "nonivamide." }, { "input": "The present study investigated the inhibitory effects and toxicity mechanism of nonivamide on Phaeodactylum tricornutum.", "output": "nonivamide." }, { "input": "Under a 1. 5 x 10 ( 5 ) cells / ml of initial algal density ( IAD ), the effective concentration causing 50 % inhibition at 4 - d ( 4 d - EC50 ) value of nonivamide was 5. 1 mg / L.", "output": "nonivamide." }, { "input": "Reactive oxygen species ( ROS ) level was significantly increased in nonivamide - treated algae.", "output": "oxygen, nonivamide." }, { "input": "Algal antioxidants, including catalases ( CAT ), peroxidases ( POD ), superoxide dismutases ( SOD ), and glutathione ( GSH ), were all stimulated by the ROS burst.", "output": "superoxide, glutathione, GSH." }, { "input": "The excessive ROS substances led to the loss of algal photosynthetic pigments and also damage to the integrity of the lipid membrane.", "output": "There is no related enetity." }, { "input": "Furthermore, ROS - related genes, including psbA, psbD, psaB, rbcL, nad1, and cob, were found to be suppressed in the chloroplasts and mitochondria of nonivamide - treated algae, and the concentration of cytoplasmic Ca ( 2 + ), an important regulator of chloroplast and mitochondrion, was elevated.", "output": "nonivamide, Ca ( 2 + )." }, { "input": "The present study demonstrates that nonivamide could cause peroxidative damages to P. tricornutum by inducing ROS overproduction, which may be initiated by the suppression of ROS - related genes in algal chloroplasts and mitochondria.", "output": "nonivamide." }, { "input": "Mechanism for different fluorescence response of a coumarin - amide - dipicolylamine linkage to Zn ( II ) and Cd ( II ) in water.", "output": "coumarin, amide, dipicolylamine, Zn ( II ), Cd ( II )." }, { "input": "A coumarin - amide - dipicolylamine linkage ( L ) was synthesized and used as a fluorescent receptor for metal cations in water.", "output": "coumarin, amide, dipicolylamine." }, { "input": "The receptor dissolved in water with neutral pH shows almost no fluorescence due to the photoinduced electron transfer ( PET ) from the amide and amine nitrogens to the excited state coumarin moiety.", "output": "amide and amine nitrogens, coumarin." }, { "input": "Coordination of Zn ( 2 + ) or Cd ( 2 + ) with L creates strong fluorescence at 437 or 386 nm, respectively, due to the suppression of PET.", "output": "Zn ( 2 + ), Cd ( 2 + )." }, { "input": "In contrast, other metal cations scarcely show fluorescence enhancement.", "output": "There is no related enetity." }, { "input": "IR, NMR, and potentiometric analysis revealed that both Zn ( 2 + ) and Cd ( 2 + ) are coordinated with two pyridine N, amine N, and amide O; however, the Zn ( 2 + ) center is also coordinated with a hydroxide anion ( OH ( - ) ).", "output": "Zn ( 2 + ), Cd ( 2 + ), pyridine, N, amine, N, amide, O, Zn ( 2 + ), hydroxide, OH ( - )." }, { "input": "The structure difference for Zn and Cd complexes results in longer - and shorter - wavelength fluorescence.", "output": "Zn, Cd." }, { "input": "Ab initio calculations revealed that pi electrons on the excited state Cd complex are delocalized over the molecules and the Cd complex shows shorter - wavelength emission.", "output": "Cd, Cd." }, { "input": "In contrast, pi electrons of OH ( - ) - coordinated Zn complex are localized on the coumarin moiety.", "output": "OH ( - ), Zn, coumarin." }, { "input": "This increases the electron density of coumarin moiety and shows longer - wavelength fluorescence.", "output": "coumarin." }, { "input": "Size - matching effect on inorganic nanosheets: control of distance, alignment, and orientation of molecular adsorption as a bottom - up methodology for nanomaterials.", "output": "There is no related enetity." }, { "input": "We have been investigating complexes composed of nanolayered materials with anionic charges such as clay nanosheets and dye molecules such as cationic porphyrins.", "output": "porphyrins." }, { "input": "It was found that the structure of dye assembly on the layered materials can be effectively controlled by the use of electrostatic host - guest interaction.", "output": "There is no related enetity." }, { "input": "The intermolecular distance, the molecular orientation angle, the segregation / integration behavior, and the immobilization strength of the dyes can be controlled in the clay - dye complexes.", "output": "There is no related enetity." }, { "input": "The mechanism to control these structural factors has been discussed and was established as a size - matching effect.", "output": "There is no related enetity." }, { "input": "Unique photochemical reactions such as energy transfer through the use of this methodology have been examined.", "output": "There is no related enetity." }, { "input": "Almost 100 % efficiency of the energy - transfer reaction was achieved in the clay - porphyrin complexes as a typical example for an artificial light - harvesting system.", "output": "porphyrin." }, { "input": "Control of the molecular orientation angle is found to be useful in regulating the energy - transfer efficiency and in preparing photofunctional materials exhibiting solvatochromic behavior.", "output": "There is no related enetity." }, { "input": "Through our study, clay minerals turned out to serve as protein - like media to control the molecular position, modify the properties of the molecule, and provide a unique environment for chemical reactions.", "output": "There is no related enetity." }, { "input": "The dynamic nature of the kinome.", "output": "There is no related enetity." }, { "input": "Recent advances in proteomics have facilitated the analysis of the kinome ' en masse '.", "output": "There is no related enetity." }, { "input": "What these studies have revealed is a surprisingly dynamic network of kinase responses to highly selective kinase inhibitors, thereby illustrating the complex biological responses to these small molecules.", "output": "There is no related enetity." }, { "input": "Moreover these studies have identified key transcription factors, such as c - Myc and FOXO ( forkhead box O ), that play pivotal roles in kinome reprogramming in cancer cells.", "output": "There is no related enetity." }, { "input": "Since many kinase inhibitors fail despite a high efficacy of blocking their intended targets, elucidating kinome changes at a more global level will be essential to understanding the mechanisms of kinase inhibitor pharmacology.", "output": "There is no related enetity." }, { "input": "The development of technologies to study the kinome, as well as examples of kinome resilience and reprogramming, will be discussed in the present review.", "output": "There is no related enetity." }, { "input": "Physically - motivated force fields from symmetry - adapted perturbation theory.", "output": "There is no related enetity." }, { "input": "We present a general methodology for generating accurate and transferable ab initio force fields, employing the framework of symmetry adapted perturbation theory ( SAPT ).", "output": "There is no related enetity." }, { "input": "The resulting force fields are \" physically - motivated \" in that they contain separate, explicit terms to account for the various fundamental intermolecular interactions, such as exchange, electrostatics, induction, and dispersion, with each term parametrized to a corresponding term in the SAPT energy decomposition.", "output": "There is no related enetity." }, { "input": "Crucially, the resulting force fields are largely compatible with existing, standard simulation packages, requiring only minimal modifications.", "output": "There is no related enetity." }, { "input": "We present several novel parametrization techniques that yield robust, physically meaningful atomic parameters that are transferable between molecular environments.", "output": "There is no related enetity." }, { "input": "We demonstrate the accuracy and generality of our method by validating against experimental second virial coefficients for a variety of small molecules.", "output": "There is no related enetity." }, { "input": "We then show that the resulting atomic parameters can be combined using physically motivated ansatzes to accurately predict arbitrary heteromolecular interaction energies, with example applications including prediction of gas adsorption in functionalized metal - organic framework materials.", "output": "There is no related enetity." }, { "input": "Ordered nanoscale Archimedean tilings of a templated 3 - miktoarm star terpolymer.", "output": "There is no related enetity." }, { "input": "The directed self - assembly of 3 - miktoarm star terpolymer chains ( polyisoprene - arm - polystyrene - arm - polyferrocenylethylmethylsilane ( 3 mu - ISF ) ) into 2D Archimedean tilings is described.", "output": "polyisoprene, polystyrene, polyferrocenylethylmethylsilane, 3 mu - ISF." }, { "input": "A morphological change from ( 4. 8 ( 2 ) ) to ( 6 ( 3 ) ) tiling is reported in the 3 mu - ISF thin film blended with PS homopolymer when a greater swelling of PI is achieved during the solvent annealing process.", "output": "3 mu - ISF." }, { "input": "Highly oriented ( 4. 8 ( 2 ) ) tilings were produced by templating the self - assembled three colored structures in blended thin films.", "output": "There is no related enetity." }, { "input": "The use of ( 4. 8 ( 2 ) ) and ( 6 ( 3 ) ) tilings as nanolithographic masks to transfer square and triangular hole arrays into the substrate is also demonstrated.", "output": "There is no related enetity." }, { "input": "Effective optical Faraday rotations of semiconductor EuS nanocrystals with paramagnetic transition - metal ions.", "output": "EuS, transition - metal." }, { "input": "Novel EuS nanocrystals containing paramagnetic Mn ( II ), Co ( II ), or Fe ( II ) ions have been reported as advanced semiconductor materials with effective optical rotation under a magnetic field, Faraday rotation.", "output": "EuS, Mn ( II ), Co ( II ), Fe ( II )." }, { "input": "EuS nanocrystals with transition - metal ions, EuS: M nanocrystals, were prepared by the reduction of the Eu ( III ) dithiocarbamate complex tetraphenylphosphonium tetrakis ( diethyldithiocarbamate ) europium ( III ) with transition - metal complexes at 300 degrees C.", "output": "EuS, EuS, Eu ( III ), dithiocarbamate, tetraphenylphosphonium tetrakis ( diethyldithiocarbamate ) europium ( III ), transition - metal." }, { "input": "The EuS: M nanocrystals thus prepared were characterized using X - ray diffraction ( XRD ), transmission electron microscopy ( TEM ), inductively coupled plasma atomic emission spectroanalysis ( ICP - AES ), and a superconducting quantum interference device ( SQUID ) magnetometer.", "output": "EuS." }, { "input": "Enhanced Faraday rotations of the EuS: M nanocrystals were observed around 550 nm, and their enhanced spin polarization was estimated using electron paramagnetic resonance ( EPR ) measurements.", "output": "EuS." }, { "input": "In this report, the magneto - optical relationship between the Faraday rotation efficiency and spin polarization is discussed.", "output": "There is no related enetity." }, { "input": "Chemisorbed monolayers of corannulene penta - thioethers on gold.", "output": "corannulene penta - thioethers." }, { "input": "Penta ( tert - butylthio ) corannulene and penta ( 4 - dimethylaminophenylthio ) corannulene form highly stable monolayers on gold surfaces, as indicated by X - ray photoelectron spectroscopy ( XPS ).", "output": "Penta ( tert - butylthio ) corannulene, penta ( 4 - dimethylaminophenylthio ) corannulene." }, { "input": "Formation of these homogeneous monolayers involves multivalent coordination of the five sulfur atoms to gold with the peripheral alkyl or aryl substituents pointing away from the surface.", "output": "sulfur." }, { "input": "No dissociation of C - S bonds upon binding could be observed at room temperature.", "output": "C - S." }, { "input": "Yet, the XPS experiments reveal strong chemical bonding between the thioether groups and gold.", "output": "thioether." }, { "input": "Temperature - dependent XPS study shows that the thermal stability of the monolayers is higher than the typical stability of self - assembled monolayers ( SAMs ) of thiolates on gold.", "output": "thiolates." }, { "input": "Weight change by baseline BMI from three - year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database.", "output": "There is no related enetity." }, { "input": "The aim was to explore weight and body mass index ( BMI ) changes by baseline BMI in patients completing three years of monotherapy with various first - and second - generation antipsychotics in a large cohort in a post hoc analysis of three - year observational data.", "output": "There is no related enetity." }, { "input": "Data were analyzed by antipsychotic and three baseline BMI bands: underweight / normal weight ( BMI < 25 kg / m ( 2 ) ), overweight ( 25 - 30 kg / m ( 2 ) ) and obese ( > 30 kg / m ( 2 ) ).", "output": "There is no related enetity." }, { "input": "Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given.", "output": "There is no related enetity." }, { "input": "Specifically, a smaller proportion of patients gained >= 7 % baseline bodyweight, and a greater proportion of patients lost >= 7 % baseline bodyweight with increasing baseline BMI.", "output": "There is no related enetity." }, { "input": "For olanzapine ( the antipsychotic associated with highest mean weight gain in the total drug cohort ), the percentage of patients gaining >= 7 % baseline weight was 45 % ( 95 % CI: 43 - 48 ) in the underweight / normal weight BMI cohort and 20 % ( 95 % CI: 15 - 27 ) in the obese BMI cohort; 7 % ( 95 % CI: 6 - 8 ) of the underweight / normal cohort and 19 % ( 95 % CI: 13 - 27 ) of the obese cohort lost >= 7 % baseline weight.", "output": "olanzapine." }, { "input": "BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.", "output": "There is no related enetity." }, { "input": "Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes.", "output": "There is no related enetity." }, { "input": "Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology.", "output": "There is no related enetity." }, { "input": "Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts.", "output": "There is no related enetity." }, { "input": "To address this, we show that incorporation of a d ( 6 ) - piano stool complex within a host protein affords an artificial transfer hydrogenase ( ATHase ) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis.", "output": "There is no related enetity." }, { "input": "To illustrate the generality of the approach, the ATHase was combined with various NADH -, FAD - and haem - dependent enzymes, resulting in orthogonal redox cascades.", "output": "NADH, FAD, haem." }, { "input": "Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving ( i ) a double stereoselective amine deracemization, ( ii ) a horseradish peroxidase - coupled readout of the transfer hydrogenase activity towards its genetic optimization, ( iii ) the formation of L - pipecolic acid from L - lysine and ( iv ) regeneration of NADH to promote a monooxygenase - catalysed oxyfunctionalization reaction.", "output": "amine, L - pipecolic acid, L - lysine, NADH." }, { "input": "Biochemical modulation of cell energy by 2 - deoxyglucose and malonate in 7, 12 - dimethylbenz ( a ) anthracene - induced carcinogenesis in rats.", "output": "2 - deoxyglucose, malonate, 7 , 12 - dimethylbenz ( a ) anthracene." }, { "input": "The goal of this study was to explore the impact of 2 - deoxglucose or malonate individually or in combination on the level of cell energy ( adenosine - 5 ' - triphosphate ) and oxidative stress in 7, 12 - dimethylbenz ( a ) anthracene ( DMBA ) - induced mammary proliferation in rats.", "output": "2 - deoxglucose, malonate, adenosine - 5 ' - triphosphate, 7 , 12 - dimethylbenz ( a ) anthracene, DMBA." }, { "input": "A total of 60 adult female Sprague Dawley rats were randomly divided into five groups ( 12 rats each ): group I serves as the control group.", "output": "There is no related enetity." }, { "input": "Rats in groups ( II - V ) were administrated intragastrically a single dose of 50 mg / kg body weight ( bw ) of DMBA.", "output": "DMBA." }, { "input": "A day after DMBA administration, rats in group III were injected intraperitoneally ( ip ) with 100 mg 2 - deoxyglucose ( 2 - DG ) / kg bw daily.", "output": "DMBA, 2 - deoxyglucose, 2 - DG." }, { "input": "Rats in group IV were injected ip with 10 mg sodium malonate / kg bw daily.", "output": "sodium malonate." }, { "input": "Rats in group V were injected ip with 100 mg 2 - DG / kg bw and 10 mg sodium malonate / kg bw ( treatment for 90 days ).", "output": "sodium malonate." }, { "input": "The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase ( GRase ) and superoxide dismutase ( SOD ), glutathione peroxidase ( GPx ) and elevating the levels of malondialdehyde ( MDA ) and nitric oxide ( NO ) in mammary tissues when compared with control.", "output": "DMBA, glutathione, superoxide, glutathione, malondialdehyde, MDA, nitric oxide." }, { "input": "The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment.", "output": "MDA, NO." }, { "input": "Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA - injected rats was positively significantly correlated with the elevation of the level of NO.", "output": "DMBA, NO." }, { "input": "These data explained the possible additive effect of 2 - DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.", "output": "2 - DG, malonate." }, { "input": "Phytotoxicity evaluation and phytochemical analysis of three medicinally important plants from Pakistan.", "output": "There is no related enetity." }, { "input": "This work examines the crude methanolic extracts of three medicinally important plants native to Pakistan for potent phytotoxic activities and important phytochemicals.", "output": "There is no related enetity." }, { "input": "These plants include Euphorbia wallichii, Bergenia ciliata and Phytolacca latbenia.", "output": "There is no related enetity." }, { "input": "The phytotoxic effects were checked at 10, 000, 1000, and 100 micro g / ml against two economically important standard target species, Triticum aestivum ( monocot representative ) and Brassica napus ( dicot representative ).", "output": "There is no related enetity." }, { "input": "The phytotoxicity effects on seed germination, seedling growth and seedling weight were checked.", "output": "There is no related enetity." }, { "input": "A simple, cost - effective in vitro phytotoxicity assay ( that uses petri plates ) was used to evaluate the allelopathic properties of crude extracts.", "output": "There is no related enetity." }, { "input": "At highest concentration, extracts from all the three plants showed phytotoxic activities such that P. latbenia > E. wallichii > B. ciliata.", "output": "There is no related enetity." }, { "input": "In seedling growth, root length was affected more than shoot length, whereas among the target species B. napus was found to be more sensitive towards extracts when compared with T. aestivum.", "output": "There is no related enetity." }, { "input": "Phytochemical analysis showed that P. latbenia is rich in saponins and terpenoids, while E. wallichii and B. ciliata are rich in tannins, terpenoids and cardiac glycoside.", "output": "saponins, terpenoids, tannins, terpenoids." }, { "input": "P. latbenia also carries a moderate amount of cardiac glycosides.", "output": "There is no related enetity." }, { "input": "Heavy metals accumulation in crab and shrimps from Pulicat lake, north Chennai coastal region, southeast coast of India.", "output": "There is no related enetity." }, { "input": "The accumulation of heavy metals such as lead ( Pb ), iron ( Fe ), zinc ( Zn ), cadmium ( Cd ), and chromium ( Cr ) was examined in crab ( Scylla serrata ) and shrimps ( Penaeus semisulcatus, Penaeus indicus, and Penaeus monodon ) collected from Pulicat lake that receives effluents from industries located in north Chennai, southeast coast of India.", "output": "Pb, iron, Fe, zinc, Zn, cadmium, Cd, chromium, Cr." }, { "input": "The results showed limited difference between crab and prawns as well as significant variations between the organs.", "output": "There is no related enetity." }, { "input": "Pb is the highly accumulated metal in both crab and shrimps, except P. monodon.", "output": "Pb." }, { "input": "The highest metal concentration was mostly found in the liver followed by other organs.", "output": "There is no related enetity." }, { "input": "The concentration of metals in edible parts ( muscle ) was within the permissible level and safe for consumption.", "output": "There is no related enetity." }, { "input": "However, the results of the study clearly indicate the biomagnification of metals in Pulicat lake.", "output": "There is no related enetity." }, { "input": "Differential gene expression and bioinformatics analysis of copper resistance gene afe _ 1073 in Acidithiobacillus ferrooxidans.", "output": "copper." }, { "input": "Copper resistance of acidophilic bacteria is very significant in bioleaching of copper ore since high concentration of copper are harmful to the growth of organisms.", "output": "Copper, copper, copper." }, { "input": "Copper resistance gene afe _ 1073 was putatively considered to be involved in copper homeostasis in Acidithiobacillus ferrooxidans ATCC23270.", "output": "Copper, copper." }, { "input": "In the present study, differential expression of afe _ 1073 in A. ferrooxidans strain DY26 and DC was assessed with quantitative reverse transcription polymerase chain reaction.", "output": "There is no related enetity." }, { "input": "The results showed the expression of afe _ 1073 in two strains increased with the increment of copper concentrations.", "output": "copper." }, { "input": "The expression of DY26 was lower than that of DC at the same copper concentration although A. ferrooxidans strain DY26 possessed higher copper resistance than strain DC.", "output": "copper, copper." }, { "input": "In addition, bioinformatics analysis showed AFE _ 1073 was a typical transmembrane protein P1b1 - ATPase, which could reduce the harm of Cu ( + ) by pumping it out from the cell.", "output": "Cu ( + )." }, { "input": "There were two mutation sites in AFE _ 1073 between DY26 and DC and one may change the hydrophobicity of AFE _ 1073, which could enhance the ability of DY26 to pump out Cu ( + ).", "output": "Cu ( + )." }, { "input": "Therefore, DY26 needed less gene expression of afe _ 1073 for resisting copper toxicity than that of DC at the same copper stress.", "output": "copper, copper." }, { "input": "Our study will be beneficial to understanding the copper resistance mechanism of A. ferrooxidans.", "output": "copper." }, { "input": "Conjugated oligoelectrolytes increase power generation in E. coli microbial fuel cells.", "output": "There is no related enetity." }, { "input": "A series of conjugated oligoelectrolytes with structural variations is used to stain E. coli.", "output": "There is no related enetity." }, { "input": "By taking advantage of a high - throughput screening platform that incorporates gold anodes, it is found that MFCs with COE - modified E. coli generate significantly higher power densities, relative to unmodified E. coli.", "output": "There is no related enetity." }, { "input": "These findings highlight the potential of using water - soluble molecules inspired by the work on organic semiconductors to improve electrode / microbe interfaces.", "output": "There is no related enetity." }, { "input": "Androgen synthesis in patients with congenital adrenal hyperplasia due to 21 - hydroxylase deficiency.", "output": "Androgen." }, { "input": "A hallmark of severe congenital adrenal hyperplasia due to 21 - hydroxylase deficiency is pre - and postnatal virilization.", "output": "There is no related enetity." }, { "input": "The most characteristic biochemical abnormality is the elevation of 17 alpha - hydroxyprogesterone, which is metabolized to the most potent androgen receptor agonist dihydrotestosterone.", "output": "17 alpha - hydroxyprogesterone, androgen, dihydrotestosterone." }, { "input": "17 alpha - Hydroxyprogesterone can be metabolized to dihydrotestosterone via 4 - androstenedione through the classical Delta 4 - pathway or via 17 alpha - hydroxypregnenolone and dehydroepiandrosterone through the classical Delta 5 - pathway, as well as through an alternative route, called the ' backdoor pathway ', that bypasses dehydroepiandrosterone, 4 - androstenedione, and testosterone as intermediates.", "output": "17 alpha - Hydroxyprogesterone, dihydrotestosterone, 4 - androstenedione, 17 alpha - hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone, 4 - androstenedione, testosterone." }, { "input": "This review article will summarize recent advances in the understanding of the activities of androgen synthesis pathways in patients with 21 - hydroxylase deficiency obtained by urinary steroid metabolomics based on gas chromatography - mass spectrometry.", "output": "androgen, steroid." }, { "input": "Compared with healthy controls, the relative activities of the backdoor and Delta 4 - pathways increase in patients with congenital adrenal hyperplasia during neonatal age and infancy, whereas the activity of the Delta 5 - pathway remains unchanged.", "output": "There is no related enetity." }, { "input": "Thereafter, the activity of the Delta 5 - pathway dominates, whereas a decreasing 5 alpha - reductase activity leads to a diminished role of the backdoor pathway for androgenic steroid production.", "output": "steroid." }, { "input": "Beside the backdoor pathway, the Delta 4 - pathway seems to be responsible for increased androgen generation in patients with 21 - hydroxylase deficiency before the onset of adrenarche, whereas the Delta 5 - pathway might contribute to the increased androgen formation in those patients only after the onset of adrenarche.", "output": "androgen, androgen." }, { "input": "Adjustment of Born - Oppenheimer electronic wave functions to simplify close coupling calculations.", "output": "There is no related enetity." }, { "input": "Technical problems connected with use of the Born - Oppenheimer clamped - nuclei approximation to generate electronic wave functions, potential energy surfaces ( PES ), and associated properties are discussed.", "output": "There is no related enetity." }, { "input": "A computational procedure for adjusting the phases of the wave functions, as well as their order when potential crossings occur, is presented which is based on the calculation of overlaps between sets of molecular orbitals and configuration interaction eigenfunctions obtained at neighboring nuclear conformations.", "output": "There is no related enetity." }, { "input": "This approach has significant advantages for theoretical treatments describing atomic collisions and photo - dissociation processes by means of ab initio PES, electronic transition moments, and nonadiabatic radial and rotational coupling matrix elements.", "output": "There is no related enetity." }, { "input": "It ensures that the electronic wave functions are continuous over the entire range of nuclear conformations considered, thereby greatly simplifying the process of obtaining the above quantities from the results of single - point Born - Oppenheimer calculations.", "output": "There is no related enetity." }, { "input": "The overlap results are also used to define a diabatic transformation of the wave functions obtained for conical intersections that greatly simplifies the computation of off - diagonal matrix elements by eliminating the need for complex phase factors.", "output": "There is no related enetity." }, { "input": "Giant Ising - type magnetic anisotropy in trigonal bipyramidal Ni ( II ) complexes: experiment and theory.", "output": "trigonal bipyramidal Ni ( II )." }, { "input": "This paper reports the experimental and theoretical investigations of two trigonal bipyramidal Ni ( II ) complexes, [ Ni ( Me ( 6 ) tren ) Cl ] ( ClO ( 4 ) ) ( 1 ) and [ Ni ( Me ( 6 ) tren ) Br ] ( Br ) ( 2 ).", "output": "trigonal bipyramidal Ni ( II ), [ Ni ( Me ( 6 ) tren ) Cl ] ( ClO ( 4 ) ), [ Ni ( Me ( 6 ) tren ) Br ] ( Br )." }, { "input": "High - field, high - frequency electron paramagnetic resonance spectroscopy performed on a single crystal of 1 shows a giant uniaxial magnetic anisotropy with an experimental D ( expt ) value ( energy difference between the M ( s ) = +/- 1 and M ( s ) = 0 components of the ground spin state S = 1 ) estimated to be between - 120 and - 180 cm ( - 1 ).", "output": "There is no related enetity." }, { "input": "The theoretical study shows that, for an ideally trigonal Ni ( II ) complex, the orbital degeneracy leads to a first - order spin - orbit coupling that results in a splitting of the M ( s ) = +/- 1 and M ( s ) = 0 components of approximately - 600 cm ( - 1 ).", "output": "Ni ( II )." }, { "input": "Despite the Jahn - Teller distortion that removes the ground term degeneracy and reduces the effects of the first - order spin - orbit interaction, the D value remains very large.", "output": "There is no related enetity." }, { "input": "A good agreement between theoretical and experimental results ( theoretical D ( theor ) between - 100 and - 200 cm ( - 1 ) ) is obtained.", "output": "There is no related enetity." }, { "input": "Self - healing mussel - inspired multi - pH - responsive hydrogels.", "output": "There is no related enetity." }, { "input": "Self - healing hydrogels can be made using either reversible covalent cross - links or coordination chemistry bonds.", "output": "There is no related enetity." }, { "input": "Here we present a multi - pH - responsive system inspired by the chemistry of blue mussel adhesive proteins.", "output": "There is no related enetity." }, { "input": "By attaching DOPA to an amine - functionalized polymer, a multiresponsive system is formed upon reaction with iron.", "output": "DOPA, amine, iron." }, { "input": "The degree of polymer cross - linking is pH controlled through the pH - dependent DOPA / iron coordination chemistry.", "output": "DOPA, iron." }, { "input": "This leads to the formation of rapidly self - healing high - strength hydrogels when pH is raised from acidic toward basic values.", "output": "There is no related enetity." }, { "input": "Close to the pK ( a ) value, or more precisely the pI value, of the polymer, the gel collapses due to reduced repulsion between polymer chains.", "output": "There is no related enetity." }, { "input": "Thereby a bistable gel - system is obtained.", "output": "There is no related enetity." }, { "input": "The present polymer system more closely resembles mussel adhesive proteins than those previously reported and thus also serves as a model system for mussel adhesive chemistry.", "output": "There is no related enetity." }, { "input": "Effects of hydrogen bonding on internal conversion of GFP - like chromophores.", "output": "hydrogen." }, { "input": "I.", "output": "There is no related enetity." }, { "input": "The para - amino systems.", "output": "para - amino." }, { "input": "To understand the effects of solvent - solute hydrogen bonding ( SSHB ) on the excited - state dynamics of two GFP - like chromophores, p - ABDI and p - CFABDI, we have determined the quantum yields for fluorescence ( Phi f ) and the isomerization Z --> E ( Phi ZE ) and the femtosecond fluorescence and transient infrared absorption in selected solvents.", "output": "hydrogen." }, { "input": "The behavior that Phi ZE =~ 0. 50 in aprotic solvents, such as CH3CN, indicates that the E - Z photoisomerization adopts a one - bond - flip mechanism through the torsion of the exocyclic C = C bond ( the tau torsion ) to form a perpendicular species ( tau ~ 90 degrees ) in the singlet excited state followed by internal conversion ( IC ) to the ground state and partition to form the E and Z isomers with equal probabilities.", "output": "CH3CN, C = C." }, { "input": "The observed Phi ZE decreased from 0. 50 to 0. 15 - 0. 28 when CH3CN was replaced with the protic solvents CH3OH and CF3CH2OH.", "output": "CH3CN, CH3OH, CF3CH2OH." }, { "input": "In conjunction with the solvent - independent rapid ( < 1 ps ) kinetics for the fluorescence decay and the solvent - dependent slow ( 7 - 20 ps ) kinetics for the ground - state recovery, we conclude that the SSHB modifies the potential energy surface for the tau torsion in a way that the IC occurs also for the twisted intermediates with a tau - torsion angle smaller than 90 degrees, which favors the formation of the Z isomers.", "output": "There is no related enetity." }, { "input": "The possibility of IC induced by torsion of the exocyclic C - C bond ( the phi torsion ) is also considered but excluded.", "output": "C - C." }, { "input": "Surface functionalization of a polymeric lipid bilayer for coupling a model biological membrane with molecules, cells, and microstructures.", "output": "There is no related enetity." }, { "input": "We describe a stable and functional model biological membrane based on a polymerized lipid bilayer with a chemically modified surface.", "output": "There is no related enetity." }, { "input": "A polymerized lipid bilayer was formed from a mixture of two diacetylene - containing phospholipids, 1, 2 - bis ( 10, 12 - tricosadiynoyl ) - sn - glycero - 3 - phosphocholine ( DiynePC ) and 1, 2 - bis ( 10, 12 - tricosadiynoyl ) - sn - glycero - 3 - phosphoethanolamine ( DiynePE ).", "output": "diacetylene, 1 , 2 - bis ( 10 , 12 - tricosadiynoyl ) - sn - glycero - 3 - phosphocholine, DiynePC, 1 , 2 - bis ( 10 , 12 - tricosadiynoyl ) - sn - glycero - 3 - phosphoethanolamine, DiynePE." }, { "input": "DiynePC formed a stable bilayer structure, whereas the ethanolamine headgroup of DiynePE enabled functional molecules to be grafted onto the membrane surface.", "output": "DiynePC, ethanolamine, DiynePE." }, { "input": "Copolymerization of DiynePC and DiynePE resulted in a robust bilayer.", "output": "DiynePC, DiynePE." }, { "input": "Functionalization of the polymeric bilayer provided a route to a robust and biomimetic surface that can be linked with biomolecules, cells, and three - dimensional ( 3D ) microstructures.", "output": "There is no related enetity." }, { "input": "Biotin and peptides were grafted onto the polymeric bilayer for attaching streptavidin and cultured mammalian cells by molecular recognition, respectively.", "output": "There is no related enetity." }, { "input": "Nonspecific adsorption of proteins and cells on polymeric bilayers was minimum.", "output": "There is no related enetity." }, { "input": "DiynePE was also used to attach a microstructure made of an elastomer ( polydimethylsiloxan: PDMS ) onto the membrane, forming a confined aqueous solution between the two surfaces.", "output": "DiynePE, polydimethylsiloxan, PDMS." }, { "input": "The microcompartment enabled us to assay the activity of a membrane - bound enzyme ( cyochrome P450 ).", "output": "There is no related enetity." }, { "input": "Natural ( fluid ) lipid bilayers were incorporated together with membrane - bound proteins by lithographically polymerizing DiynePC / DiynePE bilayers.", "output": "DiynePC, DiynePE." }, { "input": "The hybrid membrane of functionalized polymeric bilayers and fluid bilayers offers a novel platform for a wide range of biomedical applications including biosensor, bioassay, cell culture, and cell - based assay.", "output": "There is no related enetity." }, { "input": "Quercetin - loaded microcapsules ameliorate experimental colitis in mice by anti - inflammatory and antioxidant mechanisms.", "output": "Quercetin." }, { "input": "Quercetin ( 1 ) is an anti - inflammatory and antioxidant flavonoid.", "output": "Quercetin, flavonoid." }, { "input": "However, the oral administration of 1 did not lead to beneficial effects in experimental animal colitis models, which involve cytokines and oxidative stress.", "output": "There is no related enetity." }, { "input": "A possible explanation is that the absorption profile of 1 prevents its activity.", "output": "There is no related enetity." }, { "input": "Therefore, it was reasoned that the controlled release of 1 would improve its therapeutic effect.", "output": "There is no related enetity." }, { "input": "Thus, the therapeutic effect and mechanisms of 1 - loaded microcapsules in acetic acid - induced colitis in mice were evaluated.", "output": "acetic acid." }, { "input": "Microcapsules were prepared using pectin / casein polymer and 1.", "output": "There is no related enetity." }, { "input": "The oral administration of 1 - loaded microcapsules decreased neutrophil recruitment, attenuated histological alterations, and reduced macroscopical damage, edema, and IL - 1 beta and IL - 33 production in the colon samples.", "output": "There is no related enetity." }, { "input": "Microcapsules loaded with 1 also prevented the reduction of anti - inflammatory cytokine IL - 10 and the antioxidant capacity of the colon.", "output": "There is no related enetity." }, { "input": "These preclinical data indicate that pectin / casein polymer microcapsules loaded with 1 improved the anti - inflammatory and antioxidant effects of 1 compared to the nonencapsulated drug.", "output": "There is no related enetity." }, { "input": "Therefore, quercetin seems to be a promising active molecule in inflammatory bowel disease if provided with adequate controlled release.", "output": "quercetin." }, { "input": "5 ' C - rich telomeric overhangs are an outcome of rapid telomere truncation events.", "output": "There is no related enetity." }, { "input": "A subset of human tumors ensures indefinite telomere length maintenance by activating a telomerase - independent mechanism known as Alternative Lengthening of Telomeres ( ALT ).", "output": "There is no related enetity." }, { "input": "Most tumor cells of ALT origin share a constellation of unique characteristics, which include large stores of extra - chromosomal telomeric material, chronic telomere dysfunction and a peculiar enrichment in chromosome ends with 5 ' C - rich overhangs.", "output": "There is no related enetity." }, { "input": "Here we demonstrate that acute telomere de - protection and the subsequent DNA damage signal are not sufficient to facilitate formation of 5 ' C - overhangs at the chromosome end.", "output": "There is no related enetity." }, { "input": "Rather chromosome ends bearing 5 ' C - overhangs are a by - product of rapid cleavage events, processing of which occurs independently of the DNA damage response and is partly mediated through the XRCC3 endonuclease.", "output": "There is no related enetity." }, { "input": "A novel class of 3 - ( phenoxy - phenyl - methyl ) - pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure - activity relationships.", "output": "3 - ( phenoxy - phenyl - methyl ) - pyrrolidines, norepinephrine, serotonin." }, { "input": "A series of 3 - ( phenoxy - phenyl - methyl ) - pyrrolidine analogues were discovered to be potent and balanced norepinephrine ( NE ) and serotonin ( 5 - hydroxytryptamine, 5 - HT ) reuptake inhibitors.", "output": "3 - ( phenoxy - phenyl - methyl ) - pyrrolidine, norepinephrine, serotonin, 5 - hydroxytryptamine, 5 - HT." }, { "input": "Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS - targeted drug.", "output": "There is no related enetity." }, { "input": "Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor ( NSRI ) with minimal off - target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior.", "output": "There is no related enetity." }, { "input": "Synthesis of 2 - aminomethyl - 4 - phenyl - 1 - azabicyclo [ 2. 2. 1 ] heptanes via LiAlH 4 - induced reductive cyclization of 2 - ( 4 - chloro - 2 - cyano - 2 - phenylbutyl ) aziridines and evaluation of their antimalarial activity.", "output": "2 - aminomethyl - 4 - phenyl - 1 - azabicyclo [ 2 . 2 . 1 ] heptanes, LiAlH 4, 2 - ( 4 - chloro - 2 - cyano - 2 - phenylbutyl ) aziridines." }, { "input": "2 - ( 4 - Chloro - 2 - cyano - 2 - phenylbutyl ) aziridines were employed for the one - step stereoselective construction of both endo - and exo - 2 - aminomethyl - 4 - phenyl - 1 - azabicyclo [ 2. 2. 1 ] heptanes as new azaheterobicyclic scaffolds via a double LiAlH ( 4 ) - induced reductive cyclization protocol.", "output": "2 - ( 4 - Chloro - 2 - cyano - 2 - phenylbutyl ) aziridines, endo - and exo - 2 - aminomethyl - 4 - phenyl - 1 - azabicyclo [ 2 . 2 . 1 ] heptanes, azaheterobicyclic, LiAlH ( 4 )." }, { "input": "Antiplasmodial assessment of these 1 - azabicyclo [ 2. 2. 1 ] heptanes revealed moderate to good activities in the micromolar range, with the exo - isomers being the most promising structures.", "output": "1 - azabicyclo [ 2 . 2 . 1 ] heptanes." }, { "input": "Furthermore, the proposed mode of action was supported by ligand docking studies, pointing to a strong binding interaction with the enzyme plasmepsin II.", "output": "There is no related enetity." }, { "input": "Acute effects of hexabromocyclododecane on Leydig cell cyclic nucleotide signaling and steroidogenesis in vitro.", "output": "hexabromocyclododecane, nucleotide." }, { "input": "Hexabromocyclododecane ( HBCDD ), an additive brominated flame retardant routinely added to various consumer products, was reported to have toxic effects upon biota, including endocrine disruption.", "output": "Hexabromocyclododecane, HBCDD." }, { "input": "In this study, the potential toxicity of HBCDD was tested in peripubertal rat Leydig cells in vitro during 6h exposure.", "output": "HBCDD." }, { "input": "HBCDD inhibited human chorionic gonadotropin - and forskolin - supported cAMP accumulation and steroidogenesis.", "output": "HBCDD, forskolin, cAMP." }, { "input": "It also inhibited basal cAMP production, but elevated basal steroidogenesis.", "output": "cAMP." }, { "input": "The expression of several cAMP - dependent genes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3 beta - hydroxysteroid dehydrogenase, was also inhibited by HBCDD treatment.", "output": "cAMP, cholesterol, 3 beta - hydroxysteroid, HBCDD." }, { "input": "Nevertheless, this was not accompanied by a decrease in steroidogenic acute regulatory protein expression, as documented by western blot analysis, and activity of steroidogenic enzymes, as documented by unaffected steroidogenesis in the presence of permeable 22 ( R ) - hydroxycholesterol.", "output": "22 ( R ) - hydroxycholesterol." }, { "input": "However, HBCDD caused significant decrease in mitochondrial membrane potential in untreated and human chorionic gonadotropin - treated cells.", "output": "HBCDD." }, { "input": "This indicates that HBCDD acute toxicity in Leydig cells reflects changes in mitochondrial membrane potential - dependent cAMP production and basal and cAMP - regulated cholesterol transport.", "output": "HBCDD, cAMP, cAMP, cholesterol." }, { "input": "This in turn facilitates basal but inhibits cAMP - dependent steroidogenesis.", "output": "cAMP." }, { "input": "Acute effects of HBCDD treatment on transcription are also indicative of its sustained effects on Leydig cell function.", "output": "HBCDD." }, { "input": "Olfactory evolution: mice rethink stink.", "output": "There is no related enetity." }, { "input": "Animals use a vast array of chemicals to communicate with others.", "output": "There is no related enetity." }, { "input": "How such signals originate is poorly known.", "output": "There is no related enetity." }, { "input": "Now a study traces the emergence of a signal from a metabolic product and the evolution of its behavioural significance.", "output": "There is no related enetity." }, { "input": "Disubstituted diaryl diselenides as potential atheroprotective compounds: Involvement of TrxR and GPx - like systems.", "output": "diaryl diselenides." }, { "input": "Oxidative modifications of low - density lipoproteins ( LDLs ) have a determinant role in atherogenesis and the study of agents that can modulate LDL oxidation is of pharmacological and therapeutic significance.", "output": "There is no related enetity." }, { "input": "Therefore, the aim of this study was to evaluate the antioxidant effect of the disubstituted diaryl diselenides, p - methoxyl - diphenyl diselenide ( p - CH ( 3 ) O - C ( 6 ) H ( 4 ) Se ) ( 2 ) ( DM ) and p - chloro - diphenyl diselenide ( p - Cl - C ( 6 ) H ( 4 ) Se ) ( 2 ) ( DC ), on Cu ( 2 + ) - induced LDL oxidation.", "output": "diaryl diselenides, p - methoxyl - diphenyl diselenide, ( p - CH ( 3 ) O - C ( 6 ) H ( 4 ) Se ) ( 2 ), p - chloro - diphenyl diselenide, ( p - Cl - C ( 6 ) H ( 4 ) Se ) ( 2 ), Cu ( 2 + )." }, { "input": "Both compounds caused a dose - dependent inhibition of human serum and isolated LDL oxidation evidenced by the increasing of the lag phase of lipid peroxidation and decreased the lipid oxidation rate ( V ( max ) ).", "output": "There is no related enetity." }, { "input": "The protein moieties from isolated LDL were also protected from Cu ( 2 + ) - induced oxidation.", "output": "Cu ( 2 + )." }, { "input": "Moreover, the disubstituted diaryl diselenides efficiently decreased the oxidized LDL ( ox - LDL ) induced foam cell formation in J774A. 1 macrophage cells.", "output": "diaryl diselenides." }, { "input": "Mechanistically, we have demonstrated that the antioxidant and antiatherogenic effects of DM and DC are related to formation of their selenol intermediates ( RSeH ) either by a direct reaction with endogenous thiols ( GPx - like activity ) or via their reduction by TrxR ( using NADPH as electron donor ).", "output": "selenol, RSeH, thiols, NADPH." }, { "input": "Considering the powerful effect of DM and DC against LDL - induced toxicity, they could be considered for developing of new therapeutic approaches to preventing and treating atherosclerosis and cardiovascular diseases.", "output": "There is no related enetity." }, { "input": "Genotoxicity of dried Hoodia parviflora aerial parts.", "output": "There is no related enetity." }, { "input": "Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products.", "output": "There is no related enetity." }, { "input": "Its effects are ascribed to a number of glycosides that have been shown to be present in plant extracts from several Hoodia species, the best known of which is H. gordonii.", "output": "There is no related enetity." }, { "input": "H. parviflora has been identified as an alternative to H. gordonii, and, as part of the process to develop H. parviflora, in vitro genotoxicity tests, as recommended by recent European Food Safety Authority guidance, were conducted on a dried powder preparation of H. parviflora aerial parts.", "output": "There is no related enetity." }, { "input": "The preparation was tested for reverse mutation at doses up to 5, 000 mu g / plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and in Escherichia coli WP2 uvrA TA, both in the presence and in the absence of an exogenous source of metabolic activation ( rat liver S9 ).", "output": "There is no related enetity." }, { "input": "In addition, the dried powder was evaluated in an in vitro cytotoxicity chromosome aberration assay using human lymphocytes.", "output": "There is no related enetity." }, { "input": "Test conditions included both a 4 ( up to 2500 mu g / mg ) and 44 - h exposure period ( up to 1000 mu g / mg ) and the incorporation of an exogenous source of metabolic activation ( 4 - h exposure only ).", "output": "There is no related enetity." }, { "input": "H. parviflora dried powder was non - genotoxic in both in vitro assays.", "output": "There is no related enetity." }, { "input": "Differential activation and modulation of the glucagon - like peptide - 1 receptor by small molecule ligands.", "output": "There is no related enetity." }, { "input": "The glucagon - like peptide - 1 receptor ( GLP - 1R ) is a major therapeutic target for the treatment of type 2 diabetes due to its role in glucose homeostasis.", "output": "glucose." }, { "input": "Despite the availability of peptide - based GLP - 1R drugs for treatment of this disease, there is great interest in developing small molecules that can be administered orally.", "output": "There is no related enetity." }, { "input": "The GLP - 1R system is complex, with multiple endogenous and clinically used peptide ligands that exhibit different signaling biases at this receptor.", "output": "There is no related enetity." }, { "input": "This study revealed that small molecule ligands acting at this receptor are differentially biased to peptide ligands and also from each other with respect to the signaling pathways that they activate.", "output": "There is no related enetity." }, { "input": "Furthermore, allosteric small molecule ligands were also able to induce bias in signaling mediated by orthosteric ligands.", "output": "There is no related enetity." }, { "input": "This was dependent on both the orthosteric and allosteric ligand as no two allosteric - orthosteric ligand pairs could induce the same signaling profile.", "output": "There is no related enetity." }, { "input": "We highlight the need to profile compounds across multiple signaling pathways and in combination with multiple orthosteric ligands in systems such as the GLP - 1R where more than one endogenous ligand exists.", "output": "There is no related enetity." }, { "input": "In the context of pleiotropical coupling of receptors and the interplay of multiple pathways leading to physiologic responses, profiling of small molecules in this manner may lead to a better understanding of the physiologic consequences of biased signaling at this receptor.", "output": "There is no related enetity." }, { "input": "This could enable the design and development of improved therapeutics that have the ability to fine - tune receptor signaling, leading to beneficial therapeutic outcomes while reducing side effect profiles.", "output": "There is no related enetity." }, { "input": "Formation, reactivity, and antiplatelet activity of mixed disulfide conjugates of clopidogrel.", "output": "disulfide, clopidogrel." }, { "input": "In this work, we investigated the formation, reactivity, and antiplatelet activity of various mixed disulfide conjugates of clopidogrel.", "output": "disulfide, clopidogrel." }, { "input": "Our results showed that the production of the active metabolite ( AM ) from 2 - oxoclopidogrel by human liver microsomes ( HLMs ) is greatly affected by the thiol reductants used.", "output": "2 - oxoclopidogrel, thiol." }, { "input": "Among the 10 thiol compounds tested, glutathione ( GSH ) is most efficient in producing the AM at a rate of 167 pmoles AM / min / mg HLM.", "output": "thiol, glutathione, GSH." }, { "input": "Interestingly, no AM but only the mixed disulfide conjugates were formed in the presence of 6 - chloropyridazine - 3 - thiol ( CPT ), 2, 5 - dimethylfuran - 3 - thiol, and 3 - nitropyridine - 2 - thiol ( NPT ).", "output": "disulfide, 6 - chloropyridazine - 3 - thiol, CPT, 2 , 5 - dimethylfuran - 3 - thiol, 3 - nitropyridine - 2 - thiol, NPT." }, { "input": "The mass spectrometry ( MS ) and MS ( 2 ) spectra of the conjugates of these thiol compounds confirmed the presence of a mixed disulfide bond linkage between the AM and the thiol reductants.", "output": "disulfide, thiol." }, { "input": "Kinetic studies revealed that the mixed disulfide conjugates were capable of exchanging thiols with GSH to release the AM with second order rate constants ranging from 1. 2 to 28 M ( - 1 ) s ( - 1 ).", "output": "disulfide, thiols, GSH." }, { "input": "The mixed disulfide conjugates of CPT and NPT showed potent inhibition of platelet aggregation after pretreatment with 1 mM GSH, confirming that the AM is responsible for the antiplatelet activity of clopidogrel.", "output": "disulfide, CPT, NPT, GSH, clopidogrel." }, { "input": "Collectively, our results provide strong support for a cytochrome P450 ( P450 ) - mediated bioactivation mechanism involving the initial formation of a glutathionyl conjugate, followed by thiol - disulfide exchange with another GSH molecule to release the AM.", "output": "thiol, disulfide, GSH." }, { "input": "Furthermore, the stable mixed disulfide conjugates identified in this study provide a platform to quantitatively generate the therapeutic AM without the need for P450 - mediated bioactivation.", "output": "disulfide." }, { "input": "This property can be further explored to overcome the interindividual variability in clopidogrel therapy.", "output": "clopidogrel." }, { "input": "Effects of metformin on burn - induced hepatic endoplasmic reticulum stress in male rats.", "output": "metformin." }, { "input": "Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum ( ER ) stress.", "output": "There is no related enetity." }, { "input": "We have recently shown that insulin reduces ER stress and improves liver function and morphology; however, it is not clear whether these changes are directly insulin mediated or are due to glucose alterations.", "output": "glucose." }, { "input": "Metformin is an antidiabetic agent that decreases hyperglycemia by different pathways than insulin; therefore, we asked whether metformin affects postburn ER stress and hepatic metabolism.", "output": "Metformin, metformin." }, { "input": "The aim of the present study is to determine the effects of metformin on postburn hepatic ER stress and metabolic markers.", "output": "metformin." }, { "input": "Male rats were randomized to sham, burn injury and burn injury plus metformin and were sacrificed at various time points.", "output": "metformin." }, { "input": "Outcomes measured were hepatic damage, function, metabolism and ER stress.", "output": "There is no related enetity." }, { "input": "Burn - induced decrease in albumin mRNA and increase in alanine transaminase ( p < 0. 01 versus sham ) were not normalized by metformin treatment.", "output": "alanine, metformin." }, { "input": "In addition, ER stress markers were similarly increased in burn injury with or without metformin compared with sham ( p < 0. 05 ).", "output": "metformin." }, { "input": "We also found that gluconeogenesis and fatty acid metabolism gene expressions were upregulated with or without metformin compared with sham ( p < 0. 05 ).", "output": "fatty acid, metformin." }, { "input": "Our results indicate that, whereas thermal injury results in hepatic ER stress, metformin does not ameliorate postburn stress responses by correcting hepatic ER stress.", "output": "metformin." }, { "input": "A brief history of oxytocin and its role in modulating psychostimulant effects.", "output": "oxytocin." }, { "input": "Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let - down reflex.", "output": "oxytocin." }, { "input": "Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia.", "output": "Oxytocin." }, { "input": "In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity.", "output": "oxytocin." }, { "input": "We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes.", "output": "oxytocin." }, { "input": "Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects.", "output": "oxytocin." }, { "input": "Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents.", "output": "oxytocin, cocaine, methamphetamine." }, { "input": "Evidence also outlines a role for oxytocin in the prosocial effects of 3, 4 - methylenedioxymethamphetamine ( MDMA, Ecstasy ) in both rodents and humans.", "output": "oxytocin, 3 , 4 - methylenedioxymethamphetamine, MDMA, Ecstasy." }, { "input": "Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.", "output": "oxytocin, MDMA." }, { "input": "Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione - Treated Diabetic Humans.", "output": "Thiazolidinedione." }, { "input": "Obesity is associated with increased adipose tissue macrophage ( ATM ) infiltration, and rodent studies suggest that inflammatory factors produced by ATMs contribute to insulin resistance and type 2 diabetes.", "output": "There is no related enetity." }, { "input": "However, a relationship between ATM content and insulin resistance has not been clearly established in humans.", "output": "There is no related enetity." }, { "input": "Since thiazolidinediones attenuate adipose tissue inflammation and improve insulin sensitivity, we examined the temporal relationship of the effects of pioglitazone on these two parameters.", "output": "thiazolidinediones, pioglitazone." }, { "input": "The effect of 10 and 21 days of pioglitazone treatment on insulin sensitivity in 26 diabetic subjects was assessed by hyperinsulinemic - euglycemic clamp studies.", "output": "pioglitazone." }, { "input": "Because chemoattractant factors, cytokines, and immune cells have been implicated in regulating the recruitment of ATMs, we studied their temporal relationship to changes in ATM content.", "output": "There is no related enetity." }, { "input": "Improved hepatic and peripheral insulin sensitivity was seen after 21 days of pioglitazone.", "output": "pioglitazone." }, { "input": "We found early reductions in macrophage chemoattractant factors after only 10 days of pioglitazone, followed by a 69 % reduction in ATM content at 21 days and reduced ATM activation at both time points.", "output": "pioglitazone." }, { "input": "Although markers for dendritic cells and neutrophils were reduced at both time points, there were no significant changes in regulatory T cells.", "output": "There is no related enetity." }, { "input": "These results are consistent with an association between adipose macrophage content and systemic insulin resistance in humans.", "output": "There is no related enetity." }, { "input": "Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Patients with type 2 diabetes often show slowing of information processing.", "output": "There is no related enetity." }, { "input": "Disruptions in the brain white matter network, possibly secondary to vascular damage, may underlie these cognitive disturbances.", "output": "There is no related enetity." }, { "input": "The present study reconstructed the white matter network of 55 nondemented individuals with type 2 diabetes ( mean age 71 +/- 4y ) and 50 age -, sex - and education - matched controls using diffusion MRI based fiber tractography.", "output": "There is no related enetity." }, { "input": "Graph theoretical analysis was then applied to quantify the efficiency of these networks.", "output": "There is no related enetity." }, { "input": "Patients with type 2 diabetes showed alterations in local and global network properties compared to controls ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "These structural network abnormalities were related to slowing of information processing speed in patients.", "output": "There is no related enetity." }, { "input": "This relation was partly independent of cerebrovascular lesion load.", "output": "There is no related enetity." }, { "input": "This study shows that the approach of characterizing the brain as a network using diffusion MRI and graph theory can provide new insights into how abnormalities in the white matter affect cognitive function in patients with diabetes.", "output": "There is no related enetity." }, { "input": "A link between GIP and osteopontin in adipose tissue and insulin resistance.", "output": "There is no related enetity." }, { "input": "Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance.", "output": "There is no related enetity." }, { "input": "Since GIP ( glucose - dependent insulinotropic polypeptide ) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin ( OPN ) expression in adipose tissue and thereby induce insulin resistance.", "output": "glucose." }, { "input": "GIP stimulated OPN protein expression in a dose - dependent fashion in rat primary adipocytes.", "output": "There is no related enetity." }, { "input": "The level of OPN mRNA was higher in adipose tissue of obese individuals ( 0. 13 +/- } 0. 04 vs 0. 04 +/- } 0. 01, P < 0. 05 ) and correlated inversely with measures of insulin sensitivity ( r = - 0. 24, P = 0. 001 ).", "output": "There is no related enetity." }, { "input": "A common variant of the GIP receptor ( GIPR ) ( rs10423928 ) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity.", "output": "There is no related enetity." }, { "input": "Carriers of the A - allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue.", "output": "There is no related enetity." }, { "input": "Carriers of GIPR rs10423928 A - allele showed protective properties via reduced GIP effects.", "output": "There is no related enetity." }, { "input": "Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.", "output": "There is no related enetity." }, { "input": "beta - Cell - Specific Protein Kinase A Activation Enhances the Efficiency of Glucose Control by Increasing Acute - Phase Insulin Secretion.", "output": "Glucose." }, { "input": "Acute insulin secretion determines the efficiency of glucose clearance.", "output": "glucose." }, { "input": "Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state.", "output": "glucose." }, { "input": "Incretin hormones, which increase beta - cell cAMP, restore acute - phase insulin secretion and improve glucose control.", "output": "cAMP, glucose." }, { "input": "To determine the physiological role of the cAMP - dependent protein kinase ( PKA ), a mouse model was developed to increase PKA activity specifically in the pancreatic beta - cells.", "output": "cAMP." }, { "input": "In response to sustained hyperglycemia, PKA activity potentiated both acute and sustained insulin release.", "output": "There is no related enetity." }, { "input": "In contrast, a glucose bolus enhanced acute - phase insulin secretion alone.", "output": "glucose." }, { "input": "Acute - phase insulin secretion was increased 3. 5 - fold, reducing circulating glucose to 58 % of levels in controls.", "output": "glucose." }, { "input": "Exendin - 4 increased acute - phase insulin release to a similar degree as PKA activation.", "output": "There is no related enetity." }, { "input": "However, incretins did not augment the effects of PKA on acute - phase insulin secretion, consistent with incretins acting primarily via PKA to potentiate acute - phase insulin secretion.", "output": "There is no related enetity." }, { "input": "Intracellular calcium signaling was unaffected by PKA activation, suggesting that the effects of PKA on acute - phase insulin secretion are mediated by the phosphorylation of proteins involved in beta - cell exocytosis.", "output": "calcium." }, { "input": "Thus, beta - cell PKA activity transduces the cAMP signal to dramatically increase acute - phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose.", "output": "glucose." }, { "input": "Impaired local production of pro - resolving lipid mediators in obesity and 17 - HDHA as a potential treatment for obesity - associated inflammation.", "output": "17 - HDHA." }, { "input": "Obesity - induced chronic low - grade inflammation originates from adipose tissue and is crucial for obesity - driven metabolic deterioration including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation, and could result from a lack of local specialized pro - resolving lipid mediators ( SPM ) such as resolvins and protectins, which derive from the n - 3 polyunsaturated fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ).", "output": "resolvins, polyunsaturated fatty acids, eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA." }, { "input": "We assessed obesity - induced changes of n - 3 - derived SPM in adipose tissue and effects of dietary EPA / DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated effects on inflammation and metabolic dysregulation.", "output": "EPA, DHA." }, { "input": "Obesity significantly decreased DHA - derived 17 - hydroxydocosahexaenoic acid ( 17 - HDHA, resolvin D1 precursor ) and protectin D1 levels in murine adipose tissue.", "output": "DHA, 17 - hydroxydocosahexaenoic acid, 17 - HDHA, resolvin D1, protectin D1." }, { "input": "Dietary EPA / DHA treatment restored endogenous biosynthesis of n - 3 derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity.", "output": "EPA, DHA." }, { "input": "Notably, 17 - HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression and improved glucose tolerance parallel to insulin sensitivity in obese mice.", "output": "17 - HDHA, glucose." }, { "input": "These findings indicate that impaired biosynthesis of certain SPM and SPM precursors including 17 - HDHA and protectin D1 contributes to adipose tissue inflammation in obesity and suggest 17 - HDHA as a novel treatment option for obesity - associated complications.", "output": "17 - HDHA, protectin D1, 17 - HDHA." }, { "input": "Leptin levels and adipose tissue percentage in adolescents with polycystic ovary syndrome.", "output": "There is no related enetity." }, { "input": "The main purpose of the research is to compare serum leptin ( Lep ) levels and adipose tissue percentage in adolescents diagnosed with polycystic ovary syndrome ( PCOS ) and those in healthy subjects.", "output": "There is no related enetity." }, { "input": "The results showed a greater percentage of patients with increased adipose tissue and significantly higher serum Lep levels in the PCOS group compared to the healthy controls.", "output": "There is no related enetity." }, { "input": "It was proved that there is a correlation between Lep and body mass index, body adipose tissue, waist circumference and HOMA index.", "output": "There is no related enetity." }, { "input": "PCOS in adolescents is a condition related to highly predominant overweight and obesity with exceeding level of body adipose tissue and higher serum Lep levels compared to healthy age - matched controls.", "output": "There is no related enetity." }, { "input": "Parathyroid and calcium metabolism disorders during pregnancy.", "output": "calcium." }, { "input": "Abstract Parathyroid disorders are not common among pregnant women, but harbor a significant morbidity and mortality potential if they remain unrecognized and untreated.", "output": "There is no related enetity." }, { "input": "The symptoms caused by abnormally low or high blood free calcium level are mostly non - specific in the initial stages, thus when recognized might pose a real danger.", "output": "calcium." }, { "input": "Here we will survey the alterations in calcium metabolism induced by pregnancy, and describe the clinical manifestations, diagnosis and treatment of parathyroid and other calcium metabolism disorders during pregnancy.", "output": "calcium, calcium." }, { "input": "The current literature on the impact of calcium and vitamin D deficiency during pregnancy will also be reviewed.", "output": "calcium, vitamin D." }, { "input": "7 - Chloro - 4 - quinolinyl Hydrazones: A Promising and Potent Class of Antileishmanial Compounds.", "output": "7 - Chloro - 4 - quinolinyl Hydrazones." }, { "input": "In this work, we report the antileishmanial evaluation of twenty 7 - chloro - 4 - quinolinyl hydrazone derivatives ( 1 - 20 ).", "output": "7 - chloro - 4 - quinolinyl hydrazone." }, { "input": "Firstly, the compounds were tested against promastigotes of four different Leishmania species.", "output": "There is no related enetity." }, { "input": "After that, all derivatives were assayed against L. braziliensis amastigotes and murine macrophages.", "output": "There is no related enetity." }, { "input": "Furthermore, it was investigated whether the antiamastigote L. braziliensis effect of the compounds could be associated with nitric oxide production.", "output": "nitric oxide." }, { "input": "Compounds 6 and 7 showed a strong leishmanicidal activity against intracellular parasite with IC50 in nanogram levels ( 30 and 20 ng / mL, respectively ).", "output": "There is no related enetity." }, { "input": "Appreciable activity of three compounds tested can be considered an important finding for the rational design of new leads for antileishmanial compounds.", "output": "There is no related enetity." }, { "input": "Investigation of the interaction of gamma - Al2O3 with aqueous solutions of dimethyl methylphosphonate using infrared multiple internal reflection spectroscopy.", "output": "Al2O3, dimethyl methylphosphonate." }, { "input": "The interaction of dilute solutions of dimethyl methylphosphonate ( DMMP ) in H ( 2 ) O with thin porous layers of gamma - Al ( 2 ) O ( 3 ) has been studied under steady - state conditions using infrared multiple - internal - reflection spectroscopy.", "output": "dimethyl methylphosphonate, DMMP, H ( 2 ) O, Al ( 2 ) O ( 3 )." }, { "input": "Upon the initial introduction of the DMMP solution to a previously H ( 2 ) O - saturated surface, DMMP diffuses into the porous layer and displaces weakly hydrogen - bonded H ( 2 ) O molecules.", "output": "DMMP, H ( 2 ) O, DMMP, hydrogen, H ( 2 ) O." }, { "input": "This is accompanied by hydrolysis of the gamma - Al ( 2 ) O ( 3 ) to form Al ( OH ) ( 3 ) and / or AlO ( OH ).", "output": "Al ( 2 ) O ( 3 ), Al ( OH ) ( 3 ), AlO ( OH )." }, { "input": "The P = O group of DMMP interacts predominantly with H ( 2 ) O and gives no clear indication of bonding to the oxide surface itself, from which it is inferred that the displacement of weakly adsorbed H ( 2 ) O results from the interaction of acidic Al - OH sites with the methoxy O atoms of DMMP.", "output": "P = O, DMMP, H ( 2 ) O, oxide, H ( 2 ) O, Al - OH, methoxy, O, DMMP." }, { "input": "No hydrolysis of the DMMP, either in solution or in contact with the oxide, was detectable under the present conditions.", "output": "DMMP, oxide." }, { "input": "The results have practical implications in the decontamination of materials following exposure to toxic reagents related to DMMP.", "output": "DMMP." }, { "input": "Laboratory adapted Escherichia coli K - 12 becomes a pathogen of Caenorhabditis elegans upon restoration of O antigen biosynthesis.", "output": "There is no related enetity." }, { "input": "Escherichia coli has been the leading model organism for many decades.", "output": "There is no related enetity." }, { "input": "It is a fundamental player in modern biology, facilitating the molecular biology revolution of the last century.", "output": "There is no related enetity." }, { "input": "The acceptance of E. coli as model organism is predicated primarily on the study of one E. coli lineage; E. coli K - 12.", "output": "There is no related enetity." }, { "input": "However, the antecedents of today ' s laboratory strains have undergone extensive mutagenesis to create genetically tractable offspring but which resulted in loss of several genetic traits such as O antigen expression.", "output": "There is no related enetity." }, { "input": "Here we have repaired the wbbL locus, restoring the ability of E. coli K - 12 strain MG1655 to express the O antigen.", "output": "There is no related enetity." }, { "input": "We demonstrate that O antigen production results in drastic alterations of many phenotypes and the density of the O antigen is critical for the observed phenotypes.", "output": "There is no related enetity." }, { "input": "Importantly, O antigen production enables laboratory strains of E. coli to enter the gut of the Caenorhabditis elegans worm and to kill C. elegans at rates similar to pathogenic bacterial species.", "output": "There is no related enetity." }, { "input": "We demonstrate C. elegans killing is a feature of other commensal E. coli.", "output": "There is no related enetity." }, { "input": "We show killing is associated with bacterial resistance to mechanical shear and persistence in the C. elegans gut.", "output": "There is no related enetity." }, { "input": "These results suggest C. elegans is not an effective model of human - pathogenic E. coli infectious disease.", "output": "There is no related enetity." }, { "input": "How do metabolites differ from their parent molecules and how are they excreted?", "output": "There is no related enetity." }, { "input": "Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance.", "output": "There is no related enetity." }, { "input": "In this study we have analyzed molecules from three distinct chemical spaces ( i ) approved drugs, ( ii ) human metabolites, and ( iii ) traditional Chinese medicine ( TCM ) to investigate four aspects determining the disposition of small organic molecules.", "output": "There is no related enetity." }, { "input": "First, we examined the physicochemical properties of these three classes of molecules and identified characteristic features resulting from their distinctive biological functions.", "output": "There is no related enetity." }, { "input": "For example, human metabolites and TCM molecules can be larger and more hydrophobic than drugs, which makes them less likely to cross membranes.", "output": "There is no related enetity." }, { "input": "We then quantified the shifts in physicochemical property space induced by metabolism from a holistic perspective by analyzing a data set of several thousand experimentally observed metabolic trees.", "output": "There is no related enetity." }, { "input": "Results show how the metabolic system aims to retain nutrients / micronutrients while facilitating a rapid elimination of xenobiotics.", "output": "There is no related enetity." }, { "input": "In the third part we compared these global shifts with the contributions made by individual metabolic reactions.", "output": "There is no related enetity." }, { "input": "For better resolution, all reactions were classified into phase I and phase II biotransformations.", "output": "There is no related enetity." }, { "input": "Interestingly, not all metabolic reactions lead to more hydrophilic molecules.", "output": "There is no related enetity." }, { "input": "We were able to identify biotransformations leading to an increase of logP by more than one log unit, which could be used for the design of drugs with enhanced efficacy.", "output": "There is no related enetity." }, { "input": "The study closes with the analysis of the physicochemical properties of metabolites found in the bile, faeces, and urine.", "output": "There is no related enetity." }, { "input": "Metabolites in the bile can be large and are often negatively charged.", "output": "There is no related enetity." }, { "input": "Molecules with molecular weight > 500 Da are rarely found in the urine, and most of these large molecules are charged phase II conjugates.", "output": "There is no related enetity." }, { "input": "Contribution of lipids in honeybee ( Apis mellifera ) royal jelly to health.", "output": "There is no related enetity." }, { "input": "Honeybee ( Apis mellifera ) royal jelly ( RJ ) has a long history in human medicine because of its health - protecting properties.", "output": "There is no related enetity." }, { "input": "To develop a fundamental and comprehensive understanding of lipids in RJ, this article reviews the available literature on lipid compounds identified from RJ extracts and in vitro pharmacological effects of 10 - hydroxy - 2 - decenoic acid in RJ and other closely related compounds, some of which are also identified as lipid compounds in RJ.", "output": "10 - hydroxy - 2 - decenoic acid." }, { "input": "Overall, the lipids in RJ are composed of mostly ( aliphatic ) fatty acids, almost all of which are present as free fatty acids and scarcely any as esters.", "output": "fatty acids, fatty acids, esters." }, { "input": "Most fatty acids in RJ are medium - chain fatty acids, whether hydroxylated in terminal and / or internal positions, terminated with mono - or dicarboxylic acid groups, and saturated or monounsaturated at the 2 - position.", "output": "fatty acids, medium - chain fatty acids, mono - or dicarboxylic acid." }, { "input": "Besides these fatty acids, lipids in RJ contain sterols in minor amounts.", "output": "fatty acids." }, { "input": "Lipids in RJ are useful as preventive and supportive medicines with functionalities that include potential inhibitors of cancer growth, immune system modulators, alternative therapies for menopause, skin - aging protectors, neurogenesis inducers, and more.", "output": "There is no related enetity." }, { "input": "Taken together, the evidence suggests that health - protecting properties of RJ can be, in part, ascribed to actions of lipids in RJ.", "output": "There is no related enetity." }, { "input": "Stimuli - Responsive Magnetic Nanomicelles as Multifunctional Heat and Cargo Delivery Vehicles.", "output": "There is no related enetity." }, { "input": "Hybrid nanoarchitectures are among the most promising nanotechnology - enabled materials for biomedical applications.", "output": "There is no related enetity." }, { "input": "Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality.", "output": "There is no related enetity." }, { "input": "Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies.", "output": "iron oxide." }, { "input": "Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules.", "output": "There is no related enetity." }, { "input": "Stimuli - responsive polymers are especially attractive since their properties can be modulated in a controlled manner.", "output": "There is no related enetity." }, { "input": "Here we report on multifunctional thermo - responsive poly ( N - isopropylacrylamide - co - acrylamide ) - block - poly ( epsilon - caprolactone ) random block copolymer micelles as magnetic hyperthermia - mediated payload release and imaging agents.", "output": "poly ( N - isopropylacrylamide - co - acrylamide ) - block - poly ( epsilon - caprolactone )." }, { "input": "The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically - relevant temperatures.", "output": "doxorubicin." }, { "input": "A surface functionalization of the micelles with the integrin beta 4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over - express the A9 antigen resulted in concentration of the micelles on the surface of cells.", "output": "There is no related enetity." }, { "input": "No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application.", "output": "There is no related enetity." }, { "input": "Furthermore, SPION - loaded micelles demonstrate significant MRI contrast enhancement abilities.", "output": "There is no related enetity." }, { "input": "Drug - induced nanocarrier assembly as a strategy for the cellular delivery of nucleotides and nucleotide analogues.", "output": "nucleotides, nucleotide." }, { "input": "The natural nucleotide adenosine triphosphate ( ATP ) and nucleotide analogues such as azidothymidine triphosphate ( AZT - TP ) display important pharmacological activities for the treatment of ischemia and HIV infections, respectively.", "output": "adenosine triphosphate, ATP, nucleotide, azidothymidine triphosphate, AZT - TP." }, { "input": "Their clinical use is, however, limited mostly due to their hydrophilicity, which highly restricts their diffusion into the target cells.", "output": "There is no related enetity." }, { "input": "Few nanocarriers have been proposed to address the challenge of ATP / AZT - TP cellular delivery, but the loading efficiency, preparation complexity, and efficient cellular delivery remain important barriers to their development.", "output": "ATP, AZT - TP." }, { "input": "In this study, we propose an original, straightforward and versatile design of nucleotide and nucleotide analogue nanocarriers based on the natural polysaccharide chitosan ( CS ).", "output": "nucleotide, nucleotide." }, { "input": "We show that the drugs ATP and AZT - TP can induce ionotropic gelation of CS, leading to CS / ATP and CS / AZT - TP nanoparticles with high drug entrapment efficiency and loading rate - up to 44 %.", "output": "ATP, AZT - TP, ATP, AZT - TP." }, { "input": "Such nanocarriers release ATP and AZT - TP in physiological media and allow an efficient in vitro cellular delivery of these molecules down to the cell cytoplasm.", "output": "ATP, AZT - TP." }, { "input": "Inhibitory effects of curcumin on gastric cancer cells: A proteomic study of molecular targets.", "output": "curcumin." }, { "input": "Curcumin, a natural anticancer agent, has been shown to inhibit cell growth in a number of tumor cell lines and animal models.", "output": "Curcumin." }, { "input": "We examined the inhibition of curcumin on cell viability and its induction of apoptosis using different gastric cancer cell lines ( BGC - 823, MKN - 45 and SCG - 7901 ).", "output": "curcumin." }, { "input": "3 - ( 4, 5 - dimethyl - thiazol - 2 - yl ) - 2 - 5 - diphenyltetrazolium - bromide ( MTT ) assay showed that curcumin inhibited cell growth in a dose - ( 1, 5, 10 and 30 mu M ) and time - ( 24, 48, 72 and 96h ) dependent manner; analysis of Annexin V binding showed that curcumin induced apoptosis at the dose of 10 and 30 mu M when the cells were treated for 24 and 48h.", "output": "3 - ( 4 , 5 - dimethyl - thiazol - 2 - yl ) - 2 - 5 - diphenyltetrazolium - bromide, MTT, curcumin, curcumin." }, { "input": "As cancers are caused by dysregulation of various proteins, we investigated target proteins associated with curcumin by two - dimensional gel electrophoresis ( 2 - DE ) and MALDI - TOF - TOF mass spectrometer.", "output": "curcumin." }, { "input": "BGC - 823cells were treated with 30 mu M curcumin for 24h and total protein was extracted for the 2 - DE.", "output": "curcumin." }, { "input": "In the first dimension of the 2 - DE, protein samples ( 800 mu g ) were applied to immobilized pH gradient ( IPG ) strips ( 24cm, pH 3 - 10, NL ) and the isoelectric focusing ( IEF ) was performed using a step - wise voltage ramp; the second dimension was performed using 12. 5 % SDS - PAGE gel at 1W constant power per gel.", "output": "SDS." }, { "input": "In total, 75 proteins showed significant changes over 1. 5 - fold in curcumin - treated cells compared to control cells ( Student ' s t - test, p < 0. 05 ).", "output": "curcumin." }, { "input": "Among them, 33 proteins were upregulated and 42 proteins downregulated by curcumin as determined by spot densitometry.", "output": "curcumin." }, { "input": "52 proteins with significant mascot scores were identified and implicated in cancer development and progression.", "output": "There is no related enetity." }, { "input": "Their biological function included cell proliferation, cycle and apoptosis ( 20 % ), metabolism ( 16 % ), nucleic acid processing ( 15 % ), cytoskeleton organization and movement ( 11 % ), signal transduction ( 11 % ), protein folding, proteolysis and translation ( 20 % ), and immune response ( 2 % ).", "output": "There is no related enetity." }, { "input": "Furthermore, protein - protein interacting analysis demonstrated the interaction networks affected by curcumin in gastric cancer cells.", "output": "curcumin." }, { "input": "These data provide some clues for explaining the anticancer mechanisms of curcumin and explore more potent molecular targets of the drug expected to be helpful for the development of new drugs.", "output": "curcumin." }, { "input": "A bacterial source for mollusk pyrone polyketides.", "output": "pyrone polyketides." }, { "input": "In the oceans, secondary metabolites often protect otherwise poorly defended invertebrates, such as shell - less mollusks, from predation.", "output": "There is no related enetity." }, { "input": "The origins of these metabolites are largely unknown, but many of them are thought to be made by symbiotic bacteria.", "output": "There is no related enetity." }, { "input": "In contrast, mollusks with thick shells and toxic venoms are thought to lack these secondary metabolites because of reduced defensive needs.", "output": "There is no related enetity." }, { "input": "Here, we show that heavily defended cone snails also occasionally contain abundant secondary metabolites, gamma - pyrones known as nocapyrones, which are synthesized by symbiotic bacteria.", "output": "gamma - pyrones, nocapyrones." }, { "input": "The bacteria, Nocardiopsis alba CR167, are related to widespread actinomycetes that we propose to be casual symbionts of invertebrates on land and in the sea.", "output": "There is no related enetity." }, { "input": "The natural roles of nocapyrones are unknown, but they are active in neurological assays, revealing that mollusks with external shells are an overlooked source of secondary metabolite diversity.", "output": "nocapyrones." }, { "input": "Identification of early replicating fragile sites that contribute to genome instability.", "output": "There is no related enetity." }, { "input": "DNA double - strand breaks ( DSBs ) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation - induced cytidine deaminase ( AID ).", "output": "cytidine." }, { "input": "Here we identify recurrent, early replicating, and AID - independent DNA lesions, termed early replication fragile sites ( ERFSs ), by genome - wide localization of DNA repair proteins in B cells subjected to replication stress.", "output": "There is no related enetity." }, { "input": "ERFSs colocalize with highly expressed gene clusters and are enriched for repetitive elements and CpG dinucleotides.", "output": "CpG, dinucleotides." }, { "input": "Although distinct from late - replicating common fragile sites ( CFS ), the stability of ERFSs and CFSs is similarly dependent on the replication - stress response kinase ATR.", "output": "There is no related enetity." }, { "input": "ERFSs break spontaneously during replication, but their fragility is increased by hydroxyurea, ATR inhibition, or deregulated c - Myc expression.", "output": "hydroxyurea." }, { "input": "Moreover, greater than 50 % of recurrent amplifications / deletions in human diffuse large B cell lymphoma map to ERFSs.", "output": "There is no related enetity." }, { "input": "In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites.", "output": "There is no related enetity." }, { "input": "Point - to - point ligand - receptor interactions across the subunit interface modulate the induction and stabilization of conformational states of alpha7 nAChR by benzylidene anabaseines.", "output": "benzylidene anabaseines." }, { "input": "The homomeric alpha 7 nicotinic acetylcholine receptor is a well - studied therapeutic target, though its characteristically rapid desensitization complicates the development of drugs with specific agonist effects.", "output": "acetylcholine." }, { "input": "Moreover, some experimental compounds such as GTS - 21 ( 2, 4diMeOBA ), a derivative of the alpha 7 - selective partial agonist benzylidene anabaseine ( BA ), produce a prolonged residual desensitization ( RD ) in which the receptor remains non - activatable long after the drug has been removed from extracellular solution.", "output": "GTS - 21, 2 , 4diMeOBA, benzylidene anabaseine." }, { "input": "In contrast, the desensitization caused by GTS - 21 ' s dihydroxy metabolite ( 2, 4diOHBA ) is relatively short - lived.", "output": "GTS - 21, dihydroxy, 2 , 4diOHBA." }, { "input": "RD is hypothetically due to stable binding of the ligand to the receptor in its desensitized state.", "output": "There is no related enetity." }, { "input": "We can attribute the reduction in RD to a single BA hydroxyl group on the 4 ' benzylidene position.", "output": "hydroxyl, benzylidene." }, { "input": "Computational prediction derived from homology modeling showed the serine36 ( S36 ) residue of alpha 7 as a reasonable candidate for point - to - point interaction between BA compounds and the receptor.", "output": "serine36." }, { "input": "Through evaluating the activity of BA and simple derivatives on wild - type and mutant alpha 7 receptors, it was observed that the drug - receptor pairs which were capable of hydrogen bonding at residue 36 exhibited significantly less stable desensitization.", "output": "hydrogen." }, { "input": "Further experiments involving the type II positive allosteric modulator ( PAM ) PNU - 120596 showed that the various BA compounds ' preference to induce either a PAM - sensitive ( D ( s ) ) or PAM - insensitive ( D ( i ) ) desensitized state is concentration dependent and suggested that both states are destabilized by S36 H - bonding.", "output": "PNU - 120596, H." }, { "input": "These results indicate that the fine - tuning of agonists for specific interaction with S36 can facilitate the development of therapeutics with targeted effects on ion channel desensitization properties and conformational state stability.", "output": "There is no related enetity." }, { "input": "Rhododendron tomentosum ( Ledum palustre ).", "output": "There is no related enetity." }, { "input": "A review of traditional use based on current research.", "output": "There is no related enetity." }, { "input": "Rhododendron tomentosum Harmaja ( previously: Ledum palustre ) is a fragrant evergreen shrub found in peaty soils in northern Europe, Asia and North America, commonly referred to as wild rosemary, marsh tea, marsh rosemary or northern Labrador tea.", "output": "There is no related enetity." }, { "input": "At least since the eighteenth century it has been used in ethnomedicine for the treatment of various ailments, such as rheumatism, cough, cold and insect bites, as well as a repellent.", "output": "There is no related enetity." }, { "input": "The essential oil of wild rosemary with the rich polyphenolic fraction possesses analgesic, anti - inflammatory, antimicrobial, antiviral, antifungal and insecticidal potential, demonstrated by in vivo and in vitro studies.", "output": "There is no related enetity." }, { "input": "In addition, recent scientific research reported the promising antidiabetic, antioxidant and anticancer properties.", "output": "There is no related enetity." }, { "input": "This review summarizes the information concerning taxonomy, botany, ecology, chemical composition, biological activities, toxicology and traditional and contemporary application of Rhododendron tomentosum plants.", "output": "There is no related enetity." }, { "input": "Cell penetrating peptide tethered bi - ligand liposomes for delivery to brain in vivo: Biodistribution and transfection.", "output": "There is no related enetity." }, { "input": "Targeted nano - particulate systems hold extraordinary potential for delivery of therapeutics across blood brain barrier ( BBB ).", "output": "There is no related enetity." }, { "input": "In this work, we investigated the potential of novel bi - ligand ( transferrin - poly - l - arginine ) liposomal vector for delivery of desired gene to brain, in vivo.", "output": "poly - l - arginine." }, { "input": "The in vivo evaluation of the delivery vectors is essential for clinical translation.", "output": "There is no related enetity." }, { "input": "We followed an innovative approach of combining transferrin receptor targeting with enhanced cell penetration to design liposomal vectors for improving the transport of molecules into brain.", "output": "There is no related enetity." }, { "input": "The biodistribution profile of 1, 1 ' - dioctadecyl - 3, 3, 3 ', 3 ' - tetramethyl - indocarbocyanine iodide ( DiR ) - labeled liposomes was evaluated in adult rats after single intravenous injection at dose of 15. 2 mu moles of phospholipids / kg body weight.", "output": "1 , 1 ' - dioctadecyl - 3 , 3 , 3 ' , 3 ' - tetramethyl - indocarbocyanine iodide, DiR." }, { "input": "We demonstrated that bi - ligand liposomes accumulated in rat brain at significantly ( p < 0. 05 ) higher concentrations as compared to the single - ligand ( transferrin ) or plain liposomes.", "output": "There is no related enetity." }, { "input": "In addition, the bi - ligand liposomes resulted in increased expression of beta - galactosidase ( beta - gal ) plasmid in rat brain tissue in comparison to the single - ligand liposomes.", "output": "There is no related enetity." }, { "input": "Histological examination of the transfected tissues did not show any signs of tissue necrosis or inflammation.", "output": "There is no related enetity." }, { "input": "Hemolysis assay further authenticated the biocompatibility of bi - ligand liposomes in blood up to 600 nmoles of phospholipids / 1. 4 x 10 ( 7 ) erythrocytes.", "output": "There is no related enetity." }, { "input": "The findings of this study provide important and detailed information regarding the distribution of bi - ligand liposomes in vivo and accentuate their ability to demonstrate improved brain penetration and transfection potential over single - ligand liposomes.", "output": "There is no related enetity." }, { "input": "Suppressive effects of Indigofera suffruticosa Mill extracts on lipopolysaccharide - induced inflammatory responses in murine RAW 264. 7 macrophages.", "output": "There is no related enetity." }, { "input": "Indigofera suffruticosa Mill is used as an herbal medicine for the treatment of inflammation.", "output": "There is no related enetity." }, { "input": "The aim of this study is to assess the anti - inflammatory potency of I. suffruticosa and its likely molecular mechanisms of action in lipopolysaccharide ( LPS ) - induced RAW 264. 7 macrophages.", "output": "There is no related enetity." }, { "input": "Both water and ethanolic extracts of I. suffruticosa significantly decreased LPS - induced nitric oxide ( NO ) as well as the expression of inducible nitric oxide synthase ( iNOS ), tumor necrosis factor - alpha, and pro - interleukin - 1 beta.", "output": "nitric oxide, NO, nitric oxide." }, { "input": "Moreover, LPS - induced inhibitory factor - kappa B - alpha phosphorylation, nuclear factor - kappa B ( NF - kappa B ) nuclear protein - DNA binding affinity, and NF - kappa B reporter gene activity were dramatically inhibited by I. suffruticosa extracts.", "output": "There is no related enetity." }, { "input": "Exogenous addition of I. suffruticosa significantly induced heme oxygenase - 1 ( HO - 1 ) expression, and the presence of HO - 1 small interfering RNA partly reversed the inhibitory effects of I. suffruticosa on LPS - induced NO production and iNOS expression.", "output": "NO." }, { "input": "Furthermore, I. suffruticosa induced HO - 1 expression may be through activation of the ERK / nuclear factor E2 - related factor 2 pathway.", "output": "There is no related enetity." }, { "input": "Eight phenolic compounds were found in the I. suffruticosa extracts, but salicylic acid was the only one detected in the plasma of mice fed with I. suffruticosa extracts.", "output": "phenolic, salicylic acid." }, { "input": "In summary, I. suffruticosa have a strong anti - inflammatory property that diminishes pro - inflammatory mediator expressions by lessening LPS - induced NF - kappa B activation and inducing HO - 1 expression in macrophages.", "output": "There is no related enetity." }, { "input": "Oxidative stress involvement in manganese - induced alpha - synuclein oligomerization in organotypic brain slice cultures.", "output": "manganese." }, { "input": "Overexposure to manganese ( Mn ) has been known to induce neuronal damage.", "output": "manganese, Mn." }, { "input": "However, little is known of the role that reactive oxygen species ( ROS ) play in protein aggregation resulting from Mn exposure.", "output": "oxygen, Mn." }, { "input": "The current study investigated whether oxidative stress is involved in manganese - induced alpha - synuclein oligomerization in organotypic brain slices.", "output": "manganese." }, { "input": "After application of Mn ( 0 - 400 mu M ) for 24h, there was a dose - dependent increase in average percentage of propidium iodide positive ( PI ( + ) ) nuclei in slices and levels of lactate dehydrogenase ( LDH ) in the culture medium.", "output": "Mn, propidium iodide, lactate." }, { "input": "Moreover, the treatment with Mn resulted in a dose - dependent increase in neurocyte apoptosis, ROS level, and decrease in superoxide dismutase ( SOD ) activity.", "output": "Mn, superoxide." }, { "input": "Mn also caused oxidative damage in cell lipid and protein.", "output": "Mn." }, { "input": "At the same time, the exposure of Mn leaded to significantly increase in the expression of alpha - synuclein mRNA and protein.", "output": "Mn." }, { "input": "Alpha - synuclein oligomerization occurred in Mn - treated slices, especially on membrane - bound form.", "output": "Mn." }, { "input": "It indicated that alpha - synuclein oligomers were more likely to combination cell membranes and resulting in membrane damage.", "output": "There is no related enetity." }, { "input": "Mn - induced neurocyte damage and alpha - synuclein oligomerization were also partially alleviated by the pretreatment with GSH and aggravated by H2O2 pretreatment.", "output": "Mn, GSH, H2O2." }, { "input": "The findings revealed Mn might exert its neurotoxic effects by oxidative stress - mediated alpha - synuclein oligomerization in organotypic brain slices.", "output": "Mn." }, { "input": "In vitro toxicological characterisation of the S - containing arsenic metabolites thio - dimethylarsinic acid and dimethylarsinic glutathione.", "output": "S, arsenic, thio - dimethylarsinic acid, dimethylarsinic glutathione." }, { "input": "Inorganic arsenic is a well - documented, exposure relevant human carcinogen.", "output": "arsenic." }, { "input": "A promising starting point to further understand the mechanisms behind inorganic arsenic carcinogenicity might be a formation of reactive, highly toxic metabolites during human arsenic metabolism.", "output": "arsenic, arsenic." }, { "input": "This study characterises the toxicity of recently identified S - containing arsenic metabolites in cultured human A549 lung adenocarcinoma epithelium cells.", "output": "S, arsenic." }, { "input": "In direct comparison to arsenite, thio - dimethylarsinic acid ( thio - DMA ( V ) ) and dimethylarsinic glutathione ( DMAG ) exerted a 5 - to 20 - fold stronger cytotoxicity and showed a 2 - to 20 - fold higher cellular bioavailability, respectively.", "output": "arsenite, thio - dimethylarsinic acid, thio - DMA, dimethylarsinic glutathione, DMAG." }, { "input": "All three arsenicals disturbed cell cycle progression at cytotoxic concentrations, but failed to increase the level of reactive oxygen and nitrogen species ( RONS ) in healthy A549 cells.", "output": "oxygen, nitrogen." }, { "input": "However, a strong disturbance of the oxidative defense system was observed after incubation with absolutely sub - cytotoxic, pico - to nanomolar concentrations of arsenite and thio - DMA ( V ), respectively.", "output": "arsenite, thio - DMA." }, { "input": "Thus, both GSH and GSSG levels were significantly decreased by up to 40 %.", "output": "GSH, GSSG." }, { "input": "Accordingly, RONS levels of oxidatively ( H2O2 ) stressed cells were strongly increased by the arsenicals.", "output": "H2O2." }, { "input": "Since in vivo RONS are permanently endogenously and exogenously produced, this boost of the existing oxidative stress by arsenite and thio - DMA ( V ) might contribute to the process of inorganic arsenic induced carcinogenicity.", "output": "arsenite, thio - DMA, arsenic." }, { "input": "Occurrence of copper acclimation in the least killifish Heterandria formosa, and associated biochemical and physiological mechanisms.", "output": "copper." }, { "input": "We investigated the occurrence of copper acclimation in the least killifish, Heterandria formosa using both lethal and sublethal endpoints.", "output": "copper." }, { "input": "We also investigated potential mechanisms underlying the observed acclimation.", "output": "There is no related enetity." }, { "input": "To assess the occurrence of acclimation, fish were exposed to either a background Cu level or to 15 mu g / L Cu for seven days and subsequently exposed to a lethal Cu level ( 150 mu g / L Cu ).", "output": "Cu, Cu, Cu, Cu." }, { "input": "During the latter exposure, fish were monitored for survival till all fish had died, and ( during the first 8h of this exposure ) for changes in whole - body Na levels and lipid peroxidation ( LPO ).", "output": "Na." }, { "input": "During the high - level Cu exposure, fish pre - exposed to copper had a significantly longer time - to - death than did the control fish.", "output": "Cu, copper." }, { "input": "Similarly, neither whole - body Na nor LPO changed in the Cu - pre - exposed fish during the 8h of the exposure to 150 mu g / L Cu - while both decreased significantly in the control fish.", "output": "Na, Cu, Cu." }, { "input": "Thus, acclimation was evident for both time - to - death and the sublethal endpoints.", "output": "There is no related enetity." }, { "input": "These results also indicate that Cu toxicity may involve both Na loss and LPO, and that Cu - acclimation may be brought about by prevention of these effects.", "output": "Cu, Na, Cu." }, { "input": "Our follow - up study on potential mechanisms underlying this copper acclimation used a similar pre - exposure / exposure design.", "output": "copper." }, { "input": "Fish were subsampled at the end of the 7 - day acclimation period - just before the commencement of high - level Cu exposure ( T ), after 4h of this Cu exposure ( T ), and again after 8h of this Cu exposure ( T ).", "output": "Cu, Cu, Cu." }, { "input": "Whole - body Cu accumulation, Na / K - ATPase activity, metallothionein levels, and catalase activity were quantified for these time points.", "output": "Cu, Na, K." }, { "input": "While Cu levels were higher in the Cu - pre - exposed fish than in the control fish at T, net Cu accumulation was faster in the control fish than in the Cu - pre - exposed fish during the subsequent high - level Cu exposure.", "output": "Cu, Cu, Cu, Cu, Cu." }, { "input": "Consequently, changes in Cu accumulation dynamics may play a role in the resistance.", "output": "Cu." }, { "input": "Metallothionein induction may also play a role in the observed acclimation, as Cu - acclimated fish had a significantly higher metallothionein concentration compared to the control fish.", "output": "Cu." }, { "input": "There was no evidence of involvement of Na / K - ATPase in the acclimation, as the activity of this enzyme remained lower in the pre - exposed fish than in the control fish throughout both Cu exposure periods.", "output": "Na, K, Cu." }, { "input": "There was limited evidence that a reduced loss of catalase activity plays a role in the acclimation; catalase activity did not differ after the pre - exposure period but was significantly higher in Cu - acclimated fish than in the control fish at T.", "output": "Cu." }, { "input": "MRI - detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted - cell viability.", "output": "There is no related enetity." }, { "input": "Biocompatible nanomaterials and hydrogels have become an important tool for improving cell - based therapies by promoting cell survival and protecting cell transplants from immune rejection.", "output": "There is no related enetity." }, { "input": "Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene.", "output": "There is no related enetity." }, { "input": "Here, we report a pH - nanosensor - based magnetic resonance imaging ( MRI ) technique that can monitor cell death in vivo non - invasively.", "output": "There is no related enetity." }, { "input": "We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance.", "output": "There is no related enetity." }, { "input": "Moreover, the readout from this pH - sensitive nanosensor can be directly co - registered with high - resolution anatomical images.", "output": "There is no related enetity." }, { "input": "All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.", "output": "There is no related enetity." }, { "input": "In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae.", "output": "imperatorin, isoimperatorin, cnidilin." }, { "input": "Coumarins are important constituents of Radix Angelicae Dahuricae, a well - known traditional Chinese medicine possess several known bioactivities with potentials in the treatment of central nervous system diseases.", "output": "Coumarins." }, { "input": "By using an HPLC - MS / MS method, we analyzed the in vivo plasma and brain pharmacokinetics of three ingredients of coumarins, including imperatorin, isoimperatorin and cnidilin in mice after oral administration of Dahuricae extract at doses of 800mg / kg.", "output": "coumarins, imperatorin, isoimperatorin, cnidilin." }, { "input": "The biosamples were prepared using acetonitrile precipitation and the separation was achieved on an XDB - C18 column by gradient elution.", "output": "acetonitrile." }, { "input": "The BBB permeability and P - gp - mediated efflux were further examined in Madin Canine kidney cells transfected with full length cDNA for human multidrug resistance gene1 ( MDCKII - MDR1 ).", "output": "There is no related enetity." }, { "input": "Our results demonstrate that the method has excellent and satisfactory selectivity, sensitivity, linearity, precision, and accuracy for simultaneous determination of imperatorin, isoimperatorin and cnidilin.", "output": "imperatorin, isoimperatorin, cnidilin." }, { "input": "The pharmacokinetics parameters were determined by using noncompartmental analyses, including the AUC ( 0 - t ) in plasma ( 1695. 22, 1326. 45 and 636. 98mg * h / L ), the AUC ( 0 - t ) in brain ( 1812. 35, 2125. 17 and 1145. 83ng * h / g ) as well as the T1 / 2 in plasma ( 0. 66, 0. 82, 0. 97h ) and brain ( 0. 96, 1. 1, 0. 99h ) for imperatorin, isoimperatorin and cnidilin, respectively, suggesting that the three coumarins could easily pass through the BBB in vivo.", "output": "imperatorin, isoimperatorin, cnidilin, coumarins." }, { "input": "In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the P - gp - mediated efflux ratios of 0. 53 and 0. 06, as well as medium permeability of cnidilin with 0. 82.", "output": "imperatorin, isoimperatorin, cnidilin." }, { "input": "All data suggest that these three coumarins have high BBB permeability and have pharmacokinetic potentials for the treatment of central nervous system diseases.", "output": "coumarins." }, { "input": "Phenolic glycosides from Curculigo orchioides Gaertn.", "output": "Phenolic glycosides." }, { "input": "Five new chlorophenolic glucosides, curculigine E ( 1 ), curculigine F ( 2 ), curculigine G ( 3 ), curculigine H ( 5 ), curculigine I ( 6 ) and one new phenolic glycoside, orcinoside H ( 4 ), together with eight known phenolic glycosides ( 7 - 14 ) were isolated from the Curculigo orchioides Gaertn.", "output": "chlorophenolic glucosides, curculigine E, curculigine F, curculigine G, curculigine H, curculigine I, phenolic glycoside, orcinoside H, phenolic glycosides." }, { "input": "Their structures were established by spectroscopic techniques ( IR, UV, MS, 1D and 2D NMR ).", "output": "There is no related enetity." }, { "input": "The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3 - E1 cell line using MTT assays.", "output": "phenolic glycosides, MTT." }, { "input": "Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10. 1 - 14. 1 %.", "output": "There is no related enetity." }, { "input": "ABT - 737 resistance in B - cells isolated from chronic lymphocytic leukemia patients and leukemia cell lines is overcome by the pleiotropic kinase inhibitor quercetin through Mcl - 1 down - regulation.", "output": "ABT - 737, quercetin." }, { "input": "Chronic lymphocytic leukemia ( CLL ) is the most frequent form of leukemia in adult population and despite numerous studies, it is considered an incurable disease.", "output": "There is no related enetity." }, { "input": "Since CLL is characterized by overexpression of pro - survival Bcl - 2 family members, treatments with their antagonists, such as ABT - 737, represent a promising new therapeutic strategy.", "output": "ABT - 737." }, { "input": "ABT - 737 is a BH3 mimetic agent which binds Bcl - 2, Bcl - XL and Bcl - w with high affinity, while weakly interacts with Mcl - 1 and Bfl - 1.", "output": "ABT - 737." }, { "input": "Previous studies demonstrated that quercetin, a flavonoid naturally present in food and beverages, was able to sensitize B - cells isolated from CLL patients to apoptosis when associated with death ligands or fludarabine, through a mechanism involving Mcl - 1 down - regulation.", "output": "quercetin, flavonoid." }, { "input": "Here, we report that the association between ABT - 737 and quercetin synergistically induces apoptosis in B - cells and in five leukemic cell lines ( Combination Index < 1 ).", "output": "ABT - 737, quercetin." }, { "input": "Peripheral blood mononuclear cell from healthy donors were not affected by quercetin treatment.", "output": "quercetin." }, { "input": "The molecular pathways triggered by quercetin have been investigated in HPB - ALL cells, characterized by the highest resistance to both ABT - 737 and quercetin when applied as single molecules, but highly sensitivity to the co - treatment.", "output": "quercetin, ABT - 737, quercetin." }, { "input": "In this cell line, quercetin down - regulated Mcl - 1 through the inhibition of PI3K / Akt signaling pathway, leading to Mcl - 1 instability.", "output": "quercetin." }, { "input": "The same mechanism was confirmed in B - cells.", "output": "There is no related enetity." }, { "input": "These results may open new clinical perspectives based on a translational approach in CLL therapy.", "output": "There is no related enetity." }, { "input": "c - Src - dependent MAPKs / AP - 1 activation is involved in TNF - alpha - induced matrix metalloproteinase - 9 expression in rat heart - derived H9c2 cells.", "output": "There is no related enetity." }, { "input": "TNF - alpha plays a critical mediator in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances.", "output": "There is no related enetity." }, { "input": "The implication of TNF - alpha in inflammatory responses has been shown to be mediated through up - regulation of inflammatory genes, including matrix metalloproteinase - 9 ( MMP - 9 ).", "output": "There is no related enetity." }, { "input": "However, the detailed mechanisms of TNF - alpha - induced MMP - 9 expression are largely unclear in the heart cells.", "output": "There is no related enetity." }, { "input": "Here, we demonstrated that in rat embryonic - heart derived H9c2 cells, TNF - alpha could induce MMP - 9 mRNA expression associated with an increase in the secretion of MMP - 9, determined by real - time PCR, zymography, and promoter activity assays.", "output": "There is no related enetity." }, { "input": "TNF - alpha - mediated responses were attenuated by pretreatment with the inhibitor of c - Src ( PP1 ), EGFR ( AG1478 ), PDGFR ( AG1296 ), PI3K ( LY294002 ), Akt ( SH - 5 ), MEK1 / 2 ( U0126 ), p38 MAPK ( SB202190 ), JNK1 / 2 ( SP600125 ), or AP - 1 ( Tanshinone IIA ) and transfection with siRNA of c - Src, EGFR, PDGFR, p110, Akt, or c - Jun.", "output": "PP1, AG1478, AG1296, LY294002, SH - 5, U0126, SB202190, SP600125, Tanshinone IIA." }, { "input": "TNF - alpha stimulated c - Src, PDGFR, and EGFR phosphorylation, which were reduced by PP1.", "output": "PP1." }, { "input": "In addition, TNF - alpha - stimulated Akt phosphorylation was inhibited by PP1, AG1478, AG1296, or LY294002.", "output": "PP1, AG1478, AG1296, LY294002." }, { "input": "We further demonstrated that TNF - alpha markedly stimulated p38 MAPK, p42 / p44 MAPK, and JNK1 / 2 phosphorylation via a c - Src / EGFR, PDGFR / PI3K / Akt pathway.", "output": "There is no related enetity." }, { "input": "Finally, we showed that, in H9c2 cells, TNF - alpha - stimulated AP - 1 promoter activity, c - Jun mRNA expression, and c - Jun phosphorylation were attenuated by PP1, AG1478, AG1296, LY294002, SB202190, SP600125, or U0126.", "output": "PP1, AG1478, AG1296, LY294002, SB202190, SP600125, U0126." }, { "input": "These results suggested that TNF - alpha - induced MMP - 9 expression is mediated through a c - Src / EGFR, PDGFR / PI3K / Akt / MAPKs / AP - 1 cascade in H9c2 cells.", "output": "There is no related enetity." }, { "input": "Consequently, MMP - 9 induction may contribute to cell migration and cardiovascular inflammation.", "output": "There is no related enetity." }, { "input": "A flexible approach to 1, 4 - di - substituted 2 - aminoimidazoles that inhibit and disperse biofilms and potentiate the effects of beta - lactams against multi - drug resistant bacteria.", "output": "1 , 4 - di - substituted 2 - aminoimidazoles, beta - lactams." }, { "input": "The pyrrole - imidazole alkaloids are a 2 - aminoimidazoles containing family of natural products that possess anti - biofilm activity.", "output": "pyrrole - imidazole alkaloids, 2 - aminoimidazoles." }, { "input": "A library of 1, 4 - di - substituted 2 - aminoimidazole / triazoles ( 2 - AITs ) was synthesized, and its anti - biofilm activity as well as oxacillin resensitization efficacy toward methicillin resistant Staphylococcus aureus ( MRSA ) was investigated.", "output": "1 , 4 - di - substituted 2 - aminoimidazole, triazoles, 2 - AITs." }, { "input": "These 2 - AITs were found to inhibit biofilm formation by MRSA with low micromolar IC50 values.", "output": "2 - AITs." }, { "input": "Additionally, the most active compound acted synergistically with oxacillin against MRSA lowering the minimum inhibitory concentration ( MIC ) 4 - fold.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of some novel resveratrol amide derivatives as potential anti - tumor agents.", "output": "resveratrol amide." }, { "input": "Three series of novel resveratrol amide derivatives ( 1a - q, 2a - h, 3a - l ) were synthesized and evaluated for their biological activities.", "output": "resveratrol amide." }, { "input": "All compounds were characterized by ( 1 ) H NMR, ( 13 ) C NMR, MS and elemental analysis.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "Furthermore, compound 3e was also characterized by X - ray crystallography.", "output": "There is no related enetity." }, { "input": "All the compounds were evaluated for their anti - tumor activity against MCF - 7, A549 and B16 - F10 tumor cell lines as well as cyclooxygenase - 2 ( COX - 2 ) - derived prostaglandin E2 ( PGE2 ) inhibitory activity of murine macrophage RAW 264. 7 cell line.", "output": "prostaglandin E2, PGE2." }, { "input": "Among them, compounds 1c, 1g and 3e displayed the most potent COX - 2 inhibitory activity with the IC50 values of 1. 02, 1. 27 and 1. 98 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Molecular docking studies were performed to position compounds 1c and 3e into the active site of COX - 2 to determine the probable binding modes.", "output": "There is no related enetity." }, { "input": "Design and synthesis of novel 1, 2, 3 - triazole - dithiocarbamate hybrids as potential anticancer agents.", "output": "1 , 2 , 3 - triazole - dithiocarbamate." }, { "input": "A series of novel 1, 2, 3 - triazole - dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines ( MGC - 803, MCF - 7, PC - 3, EC - 109 ).", "output": "1 , 2 , 3 - triazole - dithiocarbamate." }, { "input": "Majority of the synthesized compounds exhibited moderate to potent activity against MGC - 803 and MCF - 7.", "output": "There is no related enetity." }, { "input": "Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0. 73 to 11. 61 mu M and 0. 49 - 12. 45 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Particularly, compound 3a was more potent than 5 - fluorouracil against all tested human cancer cell lines.", "output": "5 - fluorouracil." }, { "input": "Flow cytometry analysis demonstrated that treatment of MGC - 803 with 3c led to cell cycle arrest at G2 / M phase accompanied by an increase in apoptotic cell death after 12 h.", "output": "There is no related enetity." }, { "input": "Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation.", "output": "Cd." }, { "input": "Upregulation of Zip14 contributes to hepatic zinc ( Zn ) and non - transferrin - bound iron ( Fe ) uptake during infection and inflammation.", "output": "zinc, Zn, iron, Fe." }, { "input": "We investigated whether this essential metal transporter is also involved in hepatic cadmium ( Cd ) uptake under these conditions.", "output": "cadmium, Cd." }, { "input": "An injection of lipopolysaccharide ( LPS ), turpentine oil ( Tur ) and n - hexane ( Hex ) resulted in an decrease in plasma Zn and Fe concentrations to 25 - 50 % and an increase in hepatic concentrations of both metals to 150 - 200 % of control mice.", "output": "n - hexane, Hex, Zn, Fe." }, { "input": "LPS significantly increased plasma interleukin ( IL ) - 6 levels more rapidly than Tur or Hex.", "output": "Hex." }, { "input": "Tur or Hex significantly increased hepatic Zip14 mRNA expression and decreased ferroportin 1 mRNA expression following continuous increase of IL - 6 level.", "output": "Hex." }, { "input": "Hepatic Cd and Zn concentrations increased significantly after repeated injections of Cd in Tur - or Hex - treated mice fed a control diet.", "output": "Cd, Zn, Cd, Hex." }, { "input": "Treatment with Tur or Hex additionally increased hepatic Cd accumulation in Zn - deficient mice, unlike in Fe - deficient mice.", "output": "Hex, Cd, Zn, Fe." }, { "input": "These results suggest that Zn transporters, such as Zip14, may be involved in hepatic Cd uptake during inflammation.", "output": "Zn, Cd." }, { "input": "Differential toxicity and gene expression in Caco - 2 cells exposed to arsenic species.", "output": "arsenic." }, { "input": "Inorganic arsenic [ As ( V ) + As ( III ) ] and its metabolites, especially the trivalent forms [ monomethylarsonous acid, MMA ( III ), and dimethylarsinous acid, DMA ( III ) ], are considered the forms of arsenic with the highest degree of toxicity, linked to certain types of cancer and other pathologies.", "output": "arsenic, As ( V ), As ( III ), monomethylarsonous acid, MMA ( III ), dimethylarsinous acid, DMA ( III ), arsenic." }, { "input": "The gastrointestinal mucosa is exposed to these forms of arsenic, but it is not known what toxic effect these species may have on it.", "output": "arsenic." }, { "input": "The aim of the present work was to evaluate the toxicity and some mechanisms of action of inorganic arsenic and its metabolites [ monomethylarsonic acid, MMA ( V ), dimethylarsinic acid, DMA ( V ), MMA ( III ) and DMA ( III ) ] in intestinal epithelial cells, using the Caco - 2 human cell line as a model.", "output": "monomethylarsonic acid, MMA ( V ), dimethylarsinic acid, DMA ( V ), MMA ( III ), DMA ( III )." }, { "input": "The results show that the pentavalent forms do not produce toxic effects on the intestinal monolayer, but the trivalent species have a different degree of toxicity.", "output": "There is no related enetity." }, { "input": "As ( III ) induces death mainly by necrosis, whereas only apoptotic cells are detected after exposure to MMA ( III ), and for DMA ( III ) the percentages of apoptosis and necrosis are similar.", "output": "As ( III ), MMA ( III ), DMA ( III )." }, { "input": "The three forms produce reactive oxygen species, accompanied by a reduction in intracellular GSH and lipid peroxidation, the latter being especially notable in the dimethylated form.", "output": "oxygen, GSH." }, { "input": "They also alter the enzyme activity of glutathione peroxidase and catalase and induce expression of stress proteins and metallothioneins.", "output": "glutathione." }, { "input": "The results indicate that the trivalent forms of arsenic can affect cell viability of intestinal cells by mechanisms related to the induction of oxidative stress.", "output": "arsenic." }, { "input": "Further studies are needed to evaluate how the effects observed in this study affect the structure and functionality of the intestinal epithelium.", "output": "There is no related enetity." }, { "input": "Evidence for a new binding mode to GSK - 3: allosteric regulation by the marine compound palinurin.", "output": "palinurin." }, { "input": "Glycogen synthase kinase 3 beta ( GSK - 3 beta ) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer ' s disease, mood disorders, diabetes and cancer.", "output": "There is no related enetity." }, { "input": "Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies.", "output": "There is no related enetity." }, { "input": "We describe here the isolation and biochemical characterization of the marine natural sesquiterpene palinurin as a GSK - 3 beta inhibitor.", "output": "sesquiterpene, palinurin." }, { "input": "Experimental studies performed for characterizing the inhibitory mechanism indicate that GSK - 3 beta inhibition by palinurin cannot be competed out by ATP nor peptide substrate.", "output": "palinurin, ATP." }, { "input": "Molecular modelling techniques have enabled us to propose an unconventional binding mode to GSK - 3 beta.", "output": "There is no related enetity." }, { "input": "Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of palinurin leads to GSK - 3 beta inhibition.", "output": "palinurin." }, { "input": "The inhibitory activities determined for a series of structurally related analogues support the proposed binding mode of palinurin, which is the first compound described to target this allosteric site.", "output": "palinurin." }, { "input": "The results offer new opportunities for designing and developing selective inhibitors with novel mechanisms of action.", "output": "There is no related enetity." }, { "input": "Isolation and identification of beta - hematin inhibitors from Flacourtia indica as promising antiplasmodial agents.", "output": "beta - hematin." }, { "input": "An ethanolic extract ( A001 ) of the leaves and twigs of Flacourtia indica ( Burm. f. ) Merr., was purified to give a new phenolic glycoside, 2 - ( 2 - benzoyl - beta - D - glucopyranosyloxy ) - 7 - ( 1 alpha, 2 alpha, 6 alpha - trihydroxy - 3 - oxocyclohex - 4 - enoyl ) - 5 - hydroxybenzyl alcohol ( 1 ) together with poliothrysoside ( 2 ), catechin - [ 5, 6 - e ] - 4 beta - ( 3, 4 - dihydroxyphenyl ) dihydro - 2 ( 3H ) - pyranone ( 3 ), 2 - ( 6 - benzoyl - beta - D - glucopyranosyloxy ) - 7 - ( 1 alpha, 2 alpha, 6 alpha - trihydroxy - 3 - oxocyclohex - 4 - enoyl ) - 5 - hydroxybenzyl alcohol ( 4 ), chrysoeriol - 7 - O - beta - D - glucopyranoside ( 5 ), and mururin A ( 6 ).", "output": "phenolic glycoside, 2 - ( 2 - benzoyl - beta - D - glucopyranosyloxy ) - 7 - ( 1 alpha , 2 alpha , 6 alpha - trihydroxy - 3 - oxocyclohex - 4 - enoyl ) - 5 - hydroxybenzyl alcohol, poliothrysoside, catechin - [ 5 , 6 - e ] - 4 beta - ( 3 , 4 - dihydroxyphenyl ) dihydro - 2 ( 3H ) - pyranone, 2 - ( 6 - benzoyl - beta - D - glucopyranosyloxy ) - 7 - ( 1 alpha , 2 alpha , 6 alpha - trihydroxy - 3 - oxocyclohex - 4 - enoyl ) - 5 - hydroxybenzyl alcohol, chrysoeriol - 7 - O - beta - D - glucopyranoside, mururin A." }, { "input": "Compound 6 significantly inhibited the in vitro growth of both a chloroquine - sensitive ( 3D7 ) and a chloroquine - resistant ( K1 ) strain of Plasmodium falciparum.", "output": "chloroquine, chloroquine." }, { "input": "It forms a complex with hematin and inhibits beta - hematin formation, suggesting that this compound act on a heme polymerization target.", "output": "hematin, beta - hematin, heme." }, { "input": "Safety evaluation of daidzein in laying hens: part II.", "output": "daidzein." }, { "input": "Effects on calcium - related metabolism.", "output": "calcium." }, { "input": "Daidzein, an estrogen - like product, has become increasingly popular as a dietary supplement, particularly for postpeak - estrus animals seeking a safe natural alternative to play a role of estrogen.", "output": "Daidzein, estrogen, estrogen." }, { "input": "However, there is little available safety data of it for raisers and consumers.", "output": "There is no related enetity." }, { "input": "A subchronic laying hensafety study has been conducted to examine if the high - dose daidzein could affect calcium - related metabolism ( eggshell quality and bone mineralization ).", "output": "daidzein, calcium." }, { "input": "Seven hundred and sixty - eight 56 - week - old Hyline Brown were randomly assigned to 4 groups with 8 replicates of 24 birds each ( 192 laying hensper group ) and 3weeks later fed diets supplemented with 0 ( control ), 10, 50 and 100mg of daidzein / kg for 12week.", "output": "daidzein." }, { "input": "Eggshell thickness, eggshell percentage, eggshell strength, eggshell Ca concentration was increased linearly with increasing dietary daidzein supplementation ( P = 0. 001, P = 0. 007, P = 0. 002 and P = 0. 000, respectively ).", "output": "Ca, daidzein." }, { "input": "Serum Ca increased linearly with increasing dietarydaidzein supplementation ( P = 0. 042 ), and serum P showed a significant quadratic response to dietarydaidzein supplementation ( P = 0. 036 ).", "output": "Ca, dietarydaidzein, dietarydaidzein." }, { "input": "Bone ash and bone Ca were significantly influenced by dietarydaidzein supplementation ( P < 0. 05 ).", "output": "Ca, dietarydaidzein." }, { "input": "These findings indicate that daidzein hold no observed adverse effect on calcium metabolism, but also a safe and effective food additive for calcium metabolism in animals and humans.", "output": "daidzein, calcium, calcium." }, { "input": "Osteoporosis in men: recent progress.", "output": "There is no related enetity." }, { "input": "As osteoporosis in men has been recognized as an important clinical problem, new information is being accumulated on its scope, pathophysiology, evaluation, and treatment.", "output": "There is no related enetity." }, { "input": "Fracture risk calculators, such as FRAX, identify a large proportion of the older male population to be at heightened risk for fracture.", "output": "There is no related enetity." }, { "input": "The classification of osteoporosis into primary and secondary forms, while still useful, is affected by the fact that many men have multiple contributing factors to their fracture risk.", "output": "There is no related enetity." }, { "input": "The role of sex steroids is being better defined as other risk factors for fracture are delineated.", "output": "steroids." }, { "input": "As longevity continues to increase in men and until osteoporotic fracture is truly recognized as a potentially fatal disorder, many men will be undiagnosed and untreated.", "output": "There is no related enetity." }, { "input": "Two recent studies provide more evidence that treatments which decrease fracture risk in women do the same in men.", "output": "There is no related enetity." }, { "input": "With the publication of guidelines and increasing strength of evidence for treatment efficacy, it is hoped that more men will be evaluated and treated for this often neglected disorder.", "output": "There is no related enetity." }, { "input": "Impact assessment of dredging to remove coal fly ash at the Tennessee Valley Authority Kingston Fossil plant using fathead minnow elutriate exposures.", "output": "coal." }, { "input": "On December 22, 2008, failure of an earthen containment structure resulted in the release of approximately 4. 1 million m ( 3 ) of coal fly ash into the Emory River and the surrounding area from the Tennessee Valley Authority Kingston Fossil Plant near Kingston, Tennessee, USA.", "output": "coal." }, { "input": "The purpose of the present study was to assess the potential of dredging activities performed to remove the fly ash from the river to result in increased risk to pelagic fish, with special consideration of mobilization of metals.", "output": "There is no related enetity." }, { "input": "Elutriates were created using two sources of fly ash by bubbling with air over 10 d.", "output": "There is no related enetity." }, { "input": "This elutriate preparation method was designed to represent worst - case conditions for oxidation, metal release, and dissolution.", "output": "There is no related enetity." }, { "input": "Larval and juvenile Pimephales promelas underwent 10 - d exposures to these elutriates.", "output": "There is no related enetity." }, { "input": "Larval end points included survival and biomass, and juvenile end points included survival, length, biomass, liver somatic index, and bioaccumulation.", "output": "There is no related enetity." }, { "input": "No significant toxicity was observed.", "output": "There is no related enetity." }, { "input": "Bioaccumulation of metals in juveniles was found to be primarily attributable to metals associated with particles in the gut.", "output": "There is no related enetity." }, { "input": "Results suggest little potential for toxicity to related fish species due to fly ash removal dredging activities given the extreme conditions represented by the elutriates in the present study.", "output": "There is no related enetity." }, { "input": "Electrospun TiO2 nanorods with carbon nanotubes for efficient electron collection in dye - sensitized solar cells.", "output": "TiO2, carbon." }, { "input": "A high power conversion efficiency of 10. 24 % can be obtained in a dye - sensitized solar cell by incorporating multiwall carbon nanotubes inside a TiO2 nanorod photoanode.", "output": "carbon, TiO2." }, { "input": "The multiwall carbon nanotubes in the nanorod can effectively collect and transport photogenerated electrons reducing the recombination as well as improving efficiency of the device.", "output": "There is no related enetity." }, { "input": "Role of fat body lipogenesis in protection against the effects of caloric overload in Drosophila.", "output": "There is no related enetity." }, { "input": "The Drosophila fat body is a liver - and adipose - like tissue that stores fat and serves as a detoxifying and immune responsive organ.", "output": "There is no related enetity." }, { "input": "We have previously shown that a high sugar diet leads to elevated hemolymph glucose and systemic insulin resistance in developing larvae and adults.", "output": "sugar, glucose." }, { "input": "Here, we used stable isotope tracer feeding to demonstrate that rearing larvae on high sugar diets impaired the synthesis of esterified fatty acids from dietary glucose.", "output": "sugar, fatty acids, glucose." }, { "input": "Fat body lipid profiling revealed changes in both carbon chain length and degree of unsaturation of fatty acid substituents, particularly in stored triglycerides.", "output": "carbon, fatty acid, triglycerides." }, { "input": "We tested the role of the fat body in larval tolerance of caloric excess.", "output": "There is no related enetity." }, { "input": "Our experiments demonstrated that lipogenesis was necessary for animals to tolerate high sugar feeding as tissue - specific loss of orthologs of carbohydrate response element - binding protein or stearoyl - CoA desaturase 1 resulted in lethality on high sugar diets.", "output": "sugar, carbohydrate, stearoyl - CoA, sugar." }, { "input": "By contrast, increasing the fat content of the fat body by knockdown of king - tubby was associated with reduced hyperglycemia and improved growth and tolerance of high sugar diets.", "output": "sugar." }, { "input": "Our work supports a critical role for the fat body and the Drosophila carbohydrate response element - binding protein ortholog in metabolic homeostasis in Drosophila.", "output": "carbohydrate." }, { "input": "Polycyclic peptide therapeutics.", "output": "There is no related enetity." }, { "input": "Owing to their excellent binding properties, high stability, and low off - target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics.", "output": "There is no related enetity." }, { "input": "Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide.", "output": "vancomycin, actinomycin D, romidepsin." }, { "input": "All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish - hunting coil snail in the case of ziconotide.", "output": "vancomycin, actinomycin D, romidepsin." }, { "input": "Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets.", "output": "There is no related enetity." }, { "input": "For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches.", "output": "cystine." }, { "input": "More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display.", "output": "There is no related enetity." }, { "input": "In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures.", "output": "There is no related enetity." }, { "input": "Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed.", "output": "There is no related enetity." }, { "input": "Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.", "output": "There is no related enetity." }, { "input": "Ataxia telangiectasia mutated ( ATM ) is dispensable for endonuclease I - SceI - induced homologous recombination in mouse embryonic stem cells.", "output": "There is no related enetity." }, { "input": "Ataxia telangiectasia mutated ( ATM ) is activated upon DNA double strand breaks ( DSBs ) and phosphorylates numerous DSB response proteins, including histone H2AX on serine 139 ( Ser - 139 ) to form gamma - H2AX.", "output": "serine, Ser." }, { "input": "Through interaction with MDC1, gamma - H2AX promotes DSB repair by homologous recombination ( HR ).", "output": "There is no related enetity." }, { "input": "H2AX Ser - 139 can also be phosphorylated by DNA - dependent protein kinase catalytic subunit and ataxia telangiectasia - and Rad3 - related kinase.", "output": "Ser." }, { "input": "Thus, we tested whether ATM functions in HR, particularly that controlled by gamma - H2AX, by comparing HR occurring at the euchromatic ROSA26 locus between mouse embryonic stem cells lacking either ATM, H2AX, or both.", "output": "There is no related enetity." }, { "input": "We show here that loss of ATM does not impair HR, including H2AX - dependent HR, but confers sensitivity to inhibition of poly ( ADP - ribose ) polymerases.", "output": "poly ( ADP - ribose )." }, { "input": "Loss of ATM or H2AX has independent contributions to cellular sensitivity to ionizing radiation.", "output": "There is no related enetity." }, { "input": "The ATM - independent HR function of H2AX requires both Ser - 139 phosphorylation and gamma - H2AX / MDC1 interaction.", "output": "Ser." }, { "input": "Our data suggest that ATM is dispensable for HR, including that controlled by H2AX, in the context of euchromatin, excluding the implication of such an HR function in genomic instability, hypersensitivity to DNA damage, and poly ( ADP - ribose ) polymerase inhibition associated with ATM deficiency.", "output": "poly ( ADP - ribose )." }, { "input": "Occupational exposure to anaesthetic gases and high - frequency audiometry.", "output": "There is no related enetity." }, { "input": "Objectives: Occupational exposure to anaestethic gases has been suggested to induce auditory damages.", "output": "There is no related enetity." }, { "input": "The aim of this study is to investigate high - frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system.", "output": "There is no related enetity." }, { "input": "METHODS: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care.", "output": "There is no related enetity." }, { "input": "We have used tonal audiometry as well as high - frequency one.", "output": "There is no related enetity." }, { "input": "We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases.", "output": "There is no related enetity." }, { "input": "Results were compared statistically.", "output": "There is no related enetity." }, { "input": "Results: Results show a strong correlation ( p = 0. 000 ) between left and right ear responses to all the audiometric tests.", "output": "There is no related enetity." }, { "input": "The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies ( 2000 HZ p = 0. 009 and 4000 Hz p = 0. 04 ); in high - frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way ( 10, 000 Hz p = 0. 025, 12, 000 Hz p = 0. 008, 14, 000 Hz p = 0. 026, 16, 000 Hz p = 0. 08 ).", "output": "There is no related enetity." }, { "input": "The highest values are the ones related to exposed subjects both in standard ( 2000 Hz p = 0. 01, 4000 Hz p = 0. 02 ) and in high - frequency audiometry ( 10, 000 Hz p = 0. 011, 12, 000 Hz p = 0. 004, 14, 000 Hz p = 0. 012, 16, 000 Hz p = 0. 004 ).", "output": "There is no related enetity." }, { "input": "Conclusion: Results, even if preliminary and referred to a low - range sample, show an involvement of the anatomic structure responsible for the perception of high - frequency audiometric responses in subjects exposed to anaesthetic gases.", "output": "There is no related enetity." }, { "input": "Effects of DNA methylation on nucleosome stability.", "output": "There is no related enetity." }, { "input": "Methylation of DNA at CpG dinucleotides represents one of the most important epigenetic mechanisms involved in the control of gene expression in vertebrate cells.", "output": "CpG, dinucleotides." }, { "input": "In this report, we conducted nucleosome reconstitution experiments in conjunction with high - throughput sequencing on 572 KB of human DNA and 668 KB of mouse DNA that was unmethylated or methylated in order to investigate the effects of this epigenetic modification on the positioning and stability of nucleosomes.", "output": "There is no related enetity." }, { "input": "The results demonstrated that a subset of nucleosomes positioned by nucleotide sequence was sensitive to methylation where the modification increased the affinity of these sequences for the histone octamer.", "output": "nucleotide." }, { "input": "The features that distinguished these nucleosomes from the bulk of the methylation - insensitive nucleosomes were an increase in the frequency of CpG dinucleotides and a unique rotational orientation of CpGs such that their minor grooves tended to face toward the histones in the nucleosome rather than away.", "output": "CpG, dinucleotides, CpGs." }, { "input": "These methylation - sensitive nucleosomes were preferentially associated with exons as compared to introns while unmethylated CpG islands near transcription start sites became enriched in nucleosomes upon methylation.", "output": "CpG." }, { "input": "The results of this study suggest that the effects of DNA methylation on nucleosome stability in vitro can recapitulate what has been observed in the cell and provide a direct link between DNA methylation and the structure and function of chromatin.", "output": "There is no related enetity." }, { "input": "Quantitative purity - activity relationships of natural products: the case of anti - tuberculosis active triterpenes from Oplopanax horridus.", "output": "triterpenes." }, { "input": "The present study provides an extension of the previously developed concept of purity - activity relationships ( PARs ) and enables the quantitative evaluation of the effects of multiple minor components on the bioactivity of residually complex natural products.", "output": "There is no related enetity." }, { "input": "The anti - tuberculosis active triterpenes from the Alaskan ethnobotanical Oplopanax horridus were selected as a case for the development of the quantitative PAR ( QPAR ) concept.", "output": "There is no related enetity." }, { "input": "The residual complexity of the purified triterpenes was initially evaluated by 1D - and 2D - NMR and identified as a combination of structurally related and unrelated impurities.", "output": "triterpenes." }, { "input": "Using a biochemometric approach, the qHNMR purity and anti - TB activity of successive chromatographic fractions of O. horridus triterpenes were correlated by linear regression analysis to generate a mathematical QPAR model.", "output": "triterpenes." }, { "input": "The results demonstrate that impurities, such as widely occurring monoglycerides, can have a profound impact on the observed antimycobacterial activity of triterpene - enriched fractions.", "output": "monoglycerides, triterpene." }, { "input": "The QPAR concept is shown to be capable of providing a quantitative assessment in situations where residually complex constitution contributes toward the biological activity of natural products.", "output": "There is no related enetity." }, { "input": "A comparison of the signalling properties of two tyramine receptors from Drosophila.", "output": "tyramine." }, { "input": "In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates.", "output": "phenolamines, tyramine, octopamine, catecholamines, noradrenaline, adrenaline." }, { "input": "The alpha - and beta - adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine.", "output": "octopamine, octopamine, tyramine." }, { "input": "Similarly, the Tyramine 1 subgroup of receptors ( or Octopamine / Tyramine receptors ) are better activated by tyramine than octopamine.", "output": "Tyramine, Octopamine, Tyramine, tyramine, octopamine." }, { "input": "However, recently, a new Tyramine 2 subgroup of receptors was identified, which appears to be activated highly preferentially by tyramine.", "output": "Tyramine, tyramine." }, { "input": "We examined immunocytochemically the ability of CG7431, the founding member of this subgroup from Drosophila melanogaster, to be internalized in transfected Chinese hamster ovary ( CHO ) cells by different agonists.", "output": "There is no related enetity." }, { "input": "It was only internalized after activation by tyramine.", "output": "tyramine." }, { "input": "Conversely, the structurally related receptor, CG16766, was internalized by a number of biogenic amines, including octopamine, dopamine, noradrenaline, adrenaline, which also were able to elevate cyclic AMP levels.", "output": "amines, octopamine, dopamine, noradrenaline, adrenaline, cyclic AMP." }, { "input": "Studies with synthetic agonists and antagonists confirm that CG16766 has a different pharmacological profile to that of CG7431.", "output": "There is no related enetity." }, { "input": "Species orthologues of CG16766 were only found in Drosophila species, whereas orthologues of CG7431 could be identified in the genomes of a number of insect species.", "output": "There is no related enetity." }, { "input": "We propose that CG16766 represents a new group of tyramine receptors, which we have designated the Tyramine 3 receptors.", "output": "tyramine, Tyramine." }, { "input": "Formaldehyde metabolism and formaldehyde - induced stimulation of lactate production and glutathione export in cultured neurons.", "output": "Formaldehyde, formaldehyde, lactate, glutathione." }, { "input": "Formaldehyde is endogenously produced in the human body and brain levels of this compound are elevated in neurodegenerative conditions.", "output": "Formaldehyde." }, { "input": "Although the toxic potential of an excess of formaldehyde has been studied, little is known on the molecular mechanisms underlying its neurotoxicity as well as on the ability of neurons to metabolize formaldehyde.", "output": "formaldehyde, formaldehyde." }, { "input": "To address these topics, we have used cerebellar granule neuron cultures as model system.", "output": "There is no related enetity." }, { "input": "These cultures express mRNAs of various enzymes that are involved in formaldehyde metabolism and were remarkably resistant toward acute formaldehyde toxicity.", "output": "formaldehyde, formaldehyde." }, { "input": "Cerebellar granule neurons metabolized formaldehyde with a rate of around 200 nmol / ( h x mg ) which was accompanied by significant increases in the cellular and extracellular concentrations of formate.", "output": "formaldehyde, formate." }, { "input": "In addition, formaldehyde application significantly increased glucose consumption, almost doubled the rate of lactate release from viable neurons and strongly accelerated the export of the antioxidant glutathione.", "output": "formaldehyde, glucose, lactate, glutathione." }, { "input": "The latter process was completely prevented by inhibition of the known glutathione exporter multidrug resistance protein 1.", "output": "glutathione." }, { "input": "These data indicate that cerebellar granule neurons are capable of metabolizing formaldehyde and that the neuronal glycolysis and glutathione export are severely affected by the presence of formaldehyde.", "output": "formaldehyde, glutathione, formaldehyde." }, { "input": "Formulation and characterization of Brucea javanica oil microemulsion for improving safety.", "output": "There is no related enetity." }, { "input": "Abstract Objective: This study engaged in investigation of optimal formulation, characteristics analysis of Brucea javanica oil microemulsion ( BJOM ) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo.", "output": "There is no related enetity." }, { "input": "Methods: Pseudo - ternary phase diagram techniques were used to determine the appropriate ratio of surfactant, cosurfactant and oil phases.", "output": "There is no related enetity." }, { "input": "Subsequent stability testing of BJOM was performed by dilution, centrifugation and accelerated stability testing.", "output": "There is no related enetity." }, { "input": "The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material.", "output": "There is no related enetity." }, { "input": "These results were utilized to evaluate the safety of BJOM by haemolytic, irritative and allergic testing in vitro.", "output": "There is no related enetity." }, { "input": "In addition, the cytotoxicity of BJOM was examined using the tetrazolium salt 3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 - diphenyltetrazolium bromide ( MTT ), with particular emphasis given to potential uses in cancer treatment.", "output": "tetrazolium, 3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyltetrazolium bromide, MTT." }, { "input": "Results: The most suitable method of preparation for BJOM was found to be a one to one ratio ( K ( m ) 1: 1 ) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio.", "output": "There is no related enetity." }, { "input": "The microemulsion droplets of BJOM possessed a spherical shape, uniform size and average diameter of 23. 8 nm.", "output": "There is no related enetity." }, { "input": "The expiration date of BJOM was found to be 568 d.", "output": "There is no related enetity." }, { "input": "The safety study demonstrated no hemolysis activity at the experimental BJOM concentrations; however, mild hemolysis was observed at higher concentrations of Brucea javanica oil emulsion ( BJOE ), a common commercially available product.", "output": "There is no related enetity." }, { "input": "Irritation observed upon BJOM treatment can be primarily attributed to Brucea javanica oil ( BJO ) with little influence of BJOM excipients.", "output": "There is no related enetity." }, { "input": "In addition, BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs.", "output": "There is no related enetity." }, { "input": "The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells, with BJOM demonstrating significantly more dramatic anticancer activity.", "output": "There is no related enetity." }, { "input": "Conclusion: An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.", "output": "There is no related enetity." }, { "input": "Solution structure, dynamics and binding studies of a family 11 carbohydrate - binding module from Clostridium thermocellum ( CtCBM11 ).", "output": "carbohydrate." }, { "input": "Non - catalytic cellulosomal CBMs ( carbohydrate - binding modules ) are responsible for increasing the catalytic efficiency of cellulosic enzymes by selectively putting the substrate ( a wide range of poly - and oligo - saccharides ) and enzyme into close contact.", "output": "carbohydrate." }, { "input": "In the present study we carried out an atomistic rationalization of the molecular determinants of ligand specificity for a family 11 CBM from thermophilic Clostridium thermocellum [ CtCBM11 ( C. thermocellum CBM11 ) ], based on a NMR and molecular modelling approach.", "output": "There is no related enetity." }, { "input": "We have determined the NMR solution structure of CtCBM11 at 25 degrees C and 50 degrees C and derived information on the residues of the protein that are involved in ligand recognition and on the influence of the length of the saccharide chain on binding.", "output": "saccharide." }, { "input": "We obtained models of the CtCBM11 - cellohexaose and CtCBM11 - cellotetraose complexes by docking in accordance with the NMR experimental data.", "output": "cellohexaose, cellotetraose." }, { "input": "Specific ligand - protein CH - pi and Van der Waals interactions were found to be determinant for the stability of the complexes and for defining specificity.", "output": "There is no related enetity." }, { "input": "Using the order parameters derived from backbone dynamics analysis in the presence and absence of ligand and at 25 degrees C and 50 degrees C, we determined that the protein ' s backbone conformational entropy is slightly positive.", "output": "There is no related enetity." }, { "input": "This data in combination with the negative binding entropy calculated from ITC ( isothermal titration calorimetry ) studies supports a selection mechanism where a rigid protein selects a defined oligosaccharide conformation.", "output": "There is no related enetity." }, { "input": "Phthalocyanine - Peptide Conjugates: Receptor - Targeting Bifunctional Agents for Imaging and Photodynamic Therapy.", "output": "Phthalocyanine." }, { "input": "The synthesis of a series of new zinc phthalocyanine - peptide conjugates targeting the gastrin - releasing peptide ( GRP ) and integrin receptors is reported.", "output": "zinc phthalocyanine." }, { "input": "Two alternative synthetic methods based on Sonogashira cross - coupling of an iodinated zinc phthalocyanine with acetylenic bombesin or arginine - glycine - aspartic acid ( RGD ) derivatives, either in solution or on solid phase, are presented.", "output": "zinc phthalocyanine, acetylenic bombesin, arginine, glycine, aspartic acid." }, { "input": "The water - soluble conjugates were screened for their photodynamic efficacy against several cancer cell lines expressing different levels of GRP and integrin receptors, and their intracellular localization was evaluated via confocal fluorescence microscopy.", "output": "There is no related enetity." }, { "input": "Variations in photocytotoxicity between the conjugates correlate to differences in hydrophobicity as well as receptor - mediated cell uptake.", "output": "There is no related enetity." }, { "input": "In the case of the phthalocyanine - bombesin conjugate, competition experiments confirm the involvement of the GRP receptor in both the phototherapeutic activity as well as intracellular localization.", "output": "phthalocyanine, bombesin." }, { "input": "These findings warrant further in vivo studies to evaluate the potential of this conjugate as photosensitizer for photodynamic therapy ( PDT ) of cancers overexpressing the GRP receptor.", "output": "There is no related enetity." }, { "input": "Chemical synthesis and characterization of epicatechin glucuronides and sulfates: bioanalytical standards for epicatechin metabolite identification.", "output": "epicatechin glucuronides and sulfates." }, { "input": "The monoglucuronides and sulfates of epicatechin, 3 ' - O - methylepicatechin, and 4 ' - O - methylepicatechin, respectively, were synthesized as authentic bioanalytical standards.", "output": "monoglucuronides, sulfates, 3 ' - O - methylepicatechin, 4 ' - O - methylepicatechin." }, { "input": "Reversed - phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed.", "output": "glucuronides, sulfates." }, { "input": "Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated.", "output": "epicatechin glucuronides and sulfates." }, { "input": "These results should prove invaluable to the research community as analytical standards as well as in future studies of the biological and pharmacological effects of epicatechin in humans.", "output": "epicatechin." }, { "input": "Flavone tetraglycosides and benzyl alcohol glycosides from the Mongolian medicinal plant Dracocephalum ruyschiana.", "output": "Flavone tetraglycosides, benzyl alcohol glycosides." }, { "input": "From an extract of the aerial parts of Dracocephalum ruyschiana, five new flavone tetraglycosides, five new benzyl alcohol glycosides, and 19 known compounds were isolated.", "output": "flavone tetraglycosides, benzyl alcohol glycosides." }, { "input": "The tetraglycosides contain a 7 - O - beta - d - glucopyranosyl - ( 1 --> 2 ) - beta - d - glucopyranosyl - ( 1 --> 2 ) - [ alpha - l - rhamnopyranosyl - ( 1 --> 6 ) ] - beta - d - glucopyranosyl moiety.", "output": "7 - O - beta - d - glucopyranosyl - ( 1 --> 2 ) - beta - d - glucopyranosyl - ( 1 --> 2 ) - [ alpha - l - rhamnopyranosyl - ( 1 --> 6 ) ] - beta - d - glucopyranosyl." }, { "input": "The benzyl alcohol glycosides had acyl groups on their glycosyl or aglycone moieties.", "output": "benzyl alcohol glycosides, acyl, glycosyl." }, { "input": "The compounds were tested for antioxidant activity using DPPH.", "output": "DPPH." }, { "input": "Although the new compounds were not active, phenylpropanoylquinic acid derivatives were revealed as radical scavengers in D. ruyschiana.", "output": "phenylpropanoylquinic acid." }, { "input": "Inactivation of Lrp5 in osteocytes reduces young ' s modulus and responsiveness to the mechanical loading.", "output": "There is no related enetity." }, { "input": "Low - density - lipoprotein receptor - related protein 5 ( Lrp5 ) is a co - receptor in Wnt signaling, which plays a critical role in development and maintenance of bone.", "output": "There is no related enetity." }, { "input": "Osteoporosis - pseudoglioma syndrome, for instance, arises from loss - of - function mutations in Lrp5, and global deletion of Lrp5 in mice results in significantly lower bone mineral density.", "output": "There is no related enetity." }, { "input": "Since osteocytes are proposed to act as a mechanosensor in the bone, we addressed a question whether a conditional loss - of - function mutation of Lrp5 selective to osteocytes ( Dmp1 - Cre; Lrp5 ( f / f ) ) would alter responses to ulna loading.", "output": "There is no related enetity." }, { "input": "Loading was applied to the right ulna for 3 min ( 360 cycles at 2Hz ) at a peak force of 2. 65 N for 3 consecutive days, and the contralateral ulna was used as a non - loaded control.", "output": "There is no related enetity." }, { "input": "Young ' s modulus was determined using a midshaft section of the femur.", "output": "There is no related enetity." }, { "input": "The results showed that compared to age - matched littermate controls, mice lacking Lrp5 in osteocytes exhibited smaller skeletal size with reduced bone mineral density and content.", "output": "There is no related enetity." }, { "input": "Compared to controls, Lrp5 deletion in osteocytes also led to a 4. 6 - fold reduction in Young ' s modulus.", "output": "There is no related enetity." }, { "input": "In response to ulna loading, mineralizing surface, mineral apposition rate, and bone formation rate were diminished in mice lacking Lrp5 in osteocytes by 52 %, 85 %, and 69 %, respectively.", "output": "There is no related enetity." }, { "input": "Collectively, the results support the notion that the loss - of - function mutation of Lrp5 in osteocytes causes suppression of mechanoresponsiveness and reduces bone mass and Young ' s modulus.", "output": "There is no related enetity." }, { "input": "In summary, Lrp5 - mediated Wnt signaling significantly contributes to maintenance of mechanical properties and bone mass.", "output": "There is no related enetity." }, { "input": "Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight.", "output": "There is no related enetity." }, { "input": "Experiments to investigate bone ' s physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result.", "output": "There is no related enetity." }, { "input": "It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading.", "output": "There is no related enetity." }, { "input": "It is generally assumed that this normal loading is similar between experimental groups.", "output": "There is no related enetity." }, { "input": "In the study reported here we found that this was not always the case.", "output": "There is no related enetity." }, { "input": "Male and female 17 - week - old C57BL / 6 mice were housed in groups of six, and a single episode ( 40 cycles ) of non - invasive axial loading, engendering 2, 200 mu epsilon on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks.", "output": "There is no related enetity." }, { "input": "This engendered an adaptive increase in bone mass in females, but not males.", "output": "There is no related enetity." }, { "input": "Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1. 3 times per hour, whereas the females never fought.", "output": "There is no related enetity." }, { "input": "We therefore housed all mice individually.", "output": "There is no related enetity." }, { "input": "In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice.", "output": "There is no related enetity." }, { "input": "In contrast, in males, adaptive increases in the loaded compared with non - loaded control bones was only apparent in animals housed individually.", "output": "There is no related enetity." }, { "input": "Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading.", "output": "There is no related enetity." }, { "input": "This indicates the importance of ensuring that physical activity is consistent between groups.", "output": "There is no related enetity." }, { "input": "Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads.", "output": "There is no related enetity." }, { "input": "Synthesis of some new 2 - ( 3 - pyridyl ) - 4, 5 - disubstituted thiazoles as potent antimicrobial agents.", "output": "2 - ( 3 - pyridyl ) - 4 , 5 - disubstituted thiazoles." }, { "input": "As a part of ongoing studies in developing new potent antimicrobial agents, a series of novel 2 - ( 3 - pyridyl ) - 4, 5 - disubstituted thiazoles was efficiently synthesized and characterized by spectral and elemental analyses.", "output": "2 - ( 3 - pyridyl ) - 4 , 5 - disubstituted thiazoles." }, { "input": "The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against ten bacterial and five fungal human pathogenic strains using the disc diffusion assay.", "output": "There is no related enetity." }, { "input": "Among the synthesized compounds, 5 - acetyl - 4 - methyl - 2 - ( 3 - pyridyl ) thiazole ( 5 ) exhibited twofold antibacterial activity of ampicillin in inhibiting the growth of Staphylococcus epidermidis ( MIC 0. 24 mu g / mL ) and also showed equipotent antifungal activity with amphotricin B against Geotricum candidum ( MIC 0. 48 mu g / mL ).", "output": "5 - acetyl - 4 - methyl - 2 - ( 3 - pyridyl ) thiazole, ampicillin, amphotricin B." }, { "input": "From structure - activity relationship ( SAR ) point of view, increasing the size of the substitutions either at position 4 or 5 on the thiazole nucleus decreased the antimicrobial activity.", "output": "thiazole." }, { "input": "Introducing new dimensions in MIA - QSAR: A case for chemokine receptor inhibitors.", "output": "There is no related enetity." }, { "input": "Multivariate image analysis applied to quantitative structure - activity relationships ( MIA - QSAR ) is a very simple correlative method that uses pixels ( binaries ) of chemical structures built from 2D viewer programs as descriptors; structural changes correspond to different pixel coordinates, which explain the variance in the bioactivities block.", "output": "There is no related enetity." }, { "input": "The MIA - QSAR method has shown to be predictive and capable of encoding some chemical information, but introduction of more descriptive information, such as atom size and colors to differentiate atom types, would improve predictability and interpretability.", "output": "There is no related enetity." }, { "input": "The bioactivities of a series of chemokine receptor ( CCR2 ) inhibitors have been modeled using both conventional and atom color / size - dependent MIA - QSAR ( namely aug - MIA - QSAR ); the latter showed to be better.", "output": "There is no related enetity." }, { "input": "Moreover, the results were comparable to those obtained by 3D methodologies, indicating that 2D shape and substituent size are more significant descriptors than the conformational profiles required by field fit techniques.", "output": "There is no related enetity." }, { "input": "Paeonol suppresses oxidized low - density lipoprotein induced endothelial cell apoptosis via activation of LOX - 1 / p38MAPK / NF - kappa B pathway.", "output": "Paeonol." }, { "input": "Paeonol is an active compound isolated from traditional Chinese medicine, and has been shown to have anti - atherosclerosis, anti - inflammatory, antioxidant effects.", "output": "Paeonol." }, { "input": "The present investigation was undertaken to determine the suppression effects of paeonol on oxidized low - density lipoprotein ( ox - LDL ) induced endothelial cell line HUVEC apoptosis and to uncover some of the underlying mechanisms of these effects.", "output": "paeonol." }, { "input": "Cell viability and lactate dehydrogenase ( LDH ) were measured to evaluate the cell injuries.", "output": "lactate." }, { "input": "Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry.", "output": "Hoechst 33342." }, { "input": "Intracellular reactive oxygen species ( ROS ) generation was detected by 2 ', 7 ' - dichlorofluorescein diacetate ( DCFH - DA ).", "output": "oxygen, 2 ' , 7 ' - dichlorofluorescein diacetate, DCFH - DA." }, { "input": "Real - time PCR was used to confirm the expression of LOX - 1 mRNA.", "output": "There is no related enetity." }, { "input": "Western blotting was used to evaluate the protein expression of LOX - 1 and Bcl - 2, as well as caspase - 3 cleavage, p38 - mitogen - activated protein kinase ( p38MAPK ) phosphorylation.", "output": "There is no related enetity." }, { "input": "NF - kappa B nuclear translocation was detected by Western blotting and immunofluorescence.", "output": "There is no related enetity." }, { "input": "Caspase - 3 activity was measured using a colorimetric protease assay kit.", "output": "There is no related enetity." }, { "input": "The results showed that ox - LDL significantly decreased cell viability and increased the LDH release, as well as the apoptotic rate ( P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Pre - treatment of paeonol resulted in remarkable increase of cell viability, decrease of LDH release and cell apoptosis in a concentration - dependent manner.", "output": "paeonol." }, { "input": "Besides, ox - LDL caused the up - regulation of LOX - 1, the down - regulation of Bcl - 2, the phosphorylation of p38MAPK, the translocation of NF - kappa B and the activation of caspase - 3.", "output": "There is no related enetity." }, { "input": "Paeonol pre - treatment reversed these effects introduced by ox - LDL.", "output": "Paeonol." }, { "input": "Moreover, paeonol also showed its inhibition effects on ox - LDL induced ROS overproduction.", "output": "paeonol." }, { "input": "These results indicate the preventive effects of paeonol on ox - LDL induced endothelial cell apoptosis.", "output": "paeonol." }, { "input": "The effects might, at least partly, be obtained via inhibition of LOX - 1 - ROS - p38MAPK - NF - kappa B signaling pathway.", "output": "There is no related enetity." }, { "input": "Testing of Perilla frutescens extract and Vicenin 2 for their antispasmodic effect.", "output": "Vicenin 2." }, { "input": "Gastrointestinal discomfort is frequently observed.", "output": "There is no related enetity." }, { "input": "The effects of Perilla frutescens extract and Vicenin 2 ( a compound in this extract ) were assayed in rat ileum with or without stimulation with acetylcholine or Ba ( 2 + ).", "output": "Vicenin 2, acetylcholine, Ba ( 2 + )." }, { "input": "Both had no direct spasmolytic effect, but both decreased acetylcholine - or Ba ( 2 + ) - induced contraction of rat ileum indicating an antispasmodic effect.", "output": "acetylcholine, Ba ( 2 + )." }, { "input": "This is valuable because effects were only observed when spasms were induced and may disturb the patient.", "output": "There is no related enetity." }, { "input": "The extract and the compound may be used to maintain and improve gut health.", "output": "There is no related enetity." }, { "input": "Genetic risk factors for glucocorticoid - induced osteonecrosis: a meta - analysis.", "output": "There is no related enetity." }, { "input": "Glucocorticoid - induced osteonecrosis is a common and severe adverse event.", "output": "There is no related enetity." }, { "input": "We conducted a meta - analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid - induced osteonecrosis.", "output": "There is no related enetity." }, { "input": "Published literature from PubMed and EMBASE were searched for eligible publications.", "output": "There is no related enetity." }, { "input": "Pooled odds ratio ( OR ) and 95 % confidence interval ( CI ) were calculated using a fixed - or random - effects model.", "output": "There is no related enetity." }, { "input": "There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid - induced osteonecrosis.", "output": "There is no related enetity." }, { "input": "Meta - analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes ( PAI - 1, MTHFR, ABCB1 ).", "output": "There is no related enetity." }, { "input": "The meta - analysis revealed that the PAI - 1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele ( combined studies: OR = 1. 932, 95 % CI = 1. 145 - 3. 261 ).", "output": "There is no related enetity." }, { "input": "The OR for the 4G / 4G vs. 5G / 5G genotype of PAI - 1 was 3. 217 ( 95 % CI 1. 667 - 6. 209 with combined studies ), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G / 5G and 4G / 4G genotype vs. 5G allele, with odds ratios of 2. 304 ( 95 % CI = 1. 235 - 4. 299 ) and 2. 307 ( 95 % CI = 1. 527 - 3. 485 ) in combined studies, respectively.", "output": "There is no related enetity." }, { "input": "The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele ( OR 1. 668, 95 % CI = 1. 214 - 2. 293 ) and TT genotype ( OR 2. 946, 95 % CI = 1. 422 - 6. 101 ).", "output": "There is no related enetity." }, { "input": "There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T / A polymorphisms and risk of osteonecrosis.", "output": "There is no related enetity." }, { "input": "Results of this meta - analysis indicate that the PAI - 1 4G / 5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.", "output": "There is no related enetity." }, { "input": "Protective effect of silymarin against ethanol - induced gastritis in rats: role of sulfhydryls, nitric oxide and gastric sensory afferents.", "output": "silymarin, ethanol, sulfhydryls, nitric oxide." }, { "input": "Silymarin has been known to exert antioxidant, anti - carcinogenic and anti - inflammatory effects.", "output": "Silymarin." }, { "input": "In this study, we examined the effect of silymarin on gastritis in rats.", "output": "silymarin." }, { "input": "Oral administration of silymarin dose - dependently decreased gastric lesions in ethanol - induced gastritis model.", "output": "silymarin, ethanol." }, { "input": "Silymarin also significantly suppressed the development of gastric lesions in aspirin - or water immersion - restraint stress - induced gastritis models.", "output": "Silymarin, aspirin." }, { "input": "Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide ( NO ) synthase inhibitor l - NAME, SH blocker N - ethylmaleimide or TRPV1 antagonist capsazepine in ethanol - induced gastritis model.", "output": "silymarin, nitric oxide, NO, l - NAME, SH, N - ethylmaleimide, capsazepine, ethanol." }, { "input": "In addition, ex vivo analysis revealed that ethanol - induced decrease in gastric mucus and non - protein sulfhydryl ( NPSH ) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol - induced gastritis model.", "output": "ethanol, sulfhydryl, silymarin, silymarin, ethanol." }, { "input": "Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP - SH and the modulation of capsaicin - sensitive gastric sensory afferents.", "output": "silymarin, silymarin, NO, SH, capsaicin." }, { "input": "Apoptosis - inducing activity of the actin - depolymerizing agent aplyronine A and its side - chain derivatives.", "output": "aplyronine A." }, { "input": "Aplyronine A ( 1 ) and mycalolide B ( 2 ), which are cytotoxic actin - depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S ( 3 ) cells.", "output": "Aplyronine A, mycalolide B." }, { "input": "Based on these results, actin - depolymerizing compounds were expected to exhibit apoptosis - inducing activity in cancer cells.", "output": "There is no related enetity." }, { "input": "Compounds 3 - 6, which were synthesized based on the side - chain structure of aplyronine A, were evaluated for their actin - depolymerizing activities in vitro and cytotoxicities against HL60 cells.", "output": "aplyronine A." }, { "input": "The growth - inhibitory activities of 3 - 6 were well correlated with their actin - depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells.", "output": "There is no related enetity." }, { "input": "These results suggested that actin - depolymerizing agents 1, 2, and 6 - induced apoptosis in HL60 cells may have been due to their actin - depolymerizing activity.", "output": "There is no related enetity." }, { "input": "Phosphonic analogues of glutamic acid as irreversible inhibitors of Staphylococcus aureus endoproteinase GluC: an efficient synthesis and inhibition of the human IgG degradation.", "output": "Phosphonic, glutamic acid." }, { "input": "Endoproteinase GluC ( V8 protease ) is one of many virulence factors released by the Staphylococcus aureus species in vivo.", "output": "There is no related enetity." }, { "input": "The V8 protease is able to hydrolyze some serpins and all classes of mammalian immunoglobulins.", "output": "There is no related enetity." }, { "input": "The application of specific and potent inhibitors of V8 protease may lead to the development of new antibacterial agents.", "output": "There is no related enetity." }, { "input": "Herein, we present the synthesis and the inhibitory properties of novel peptidyl derivatives of a phosphonic glutamic acid analogue.", "output": "phosphonic glutamic acid." }, { "input": "One of the compounds Boc - Phe - Leu - Glu ( P ) ( OC ( 6 ) H ( 4 ) ) ( 2 ) displayed an apparent second - order inhibition rate value of 8540 M ( - 1 ) s ( - 1 ).", "output": "Boc - Phe - Leu - Glu ( P ) ( OC ( 6 ) H ( 4 ) ) ( 2 )." }, { "input": "The Boc - Phe - Leu - Glu ( P ) ( OC ( 6 ) H ( 4 ) ) ( 2 ) compound with the highest inhibitory potency showed the ability to prevent V8 - mediated human IgG proteolysis in vitro.", "output": "Boc - Phe - Leu - Glu ( P ) ( OC ( 6 ) H ( 4 ) ) ( 2 )." }, { "input": "Design and synthesis of dimethylaminomethyl - substituted curcumin derivatives / analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.", "output": "dimethylaminomethyl - substituted curcumin, curcumin." }, { "input": "A series of dimethylaminomethyl - substituted curcumin derivatives / analogues were designed and synthesized.", "output": "dimethylaminomethyl - substituted curcumin." }, { "input": "All compounds effectively inhibited HepG2, SGC - 7901, A549 and HCT - 116 tumor cell lines proliferation in MTT assay.", "output": "MTT." }, { "input": "Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines.", "output": "curcumin." }, { "input": "Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals.", "output": "DPPH, galvinoxyl." }, { "input": "Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin.", "output": "curcumin." }, { "input": "Design, synthesis, characterization and anti - inflammatory evaluation of novel pyrazole amalgamated flavones.", "output": "pyrazole, flavones." }, { "input": "A series of novel pyrazole amalgamated flavones has been designed and synthesized from 1 - methyl - 5 - ( 2, 4, 6 - trimethoxy - phenyl ) - 1H - pyrazole 6.", "output": "pyrazole, flavones, 1 - methyl - 5 - ( 2 , 4 , 6 - trimethoxy - phenyl ) - 1H - pyrazole." }, { "input": "The structures of regioisomers 6 and 7 were resolved by 2D ( 1 ) H - ( 1 ) H COSY, ( 1 ) H - ( 13 ) C HSQC and ( 1 ) H - ( 13 ) C HMBC experiments.", "output": "( 1 ) H, ( 1 ) H, ( 1 ) H, ( 13 ) C, ( 1 ) H, ( 13 ) C." }, { "input": "The newly synthesized compounds were tested for their in vitro COX inhibition and in vivo carrageenan induced hind paw edema in rats and acetic acid induced vascular permeability in mice.", "output": "acetic acid." }, { "input": "Although the compounds have inhibitory profile against both COX - 1 and COX - 2, some of the compounds are found to be selective against COX - 2, supported by inhibition of paw edema and vascular permeability.", "output": "There is no related enetity." }, { "input": "Docking studies were also carried out to determine the structural features which sway the anti - inflammatory activity of the tested compounds.", "output": "There is no related enetity." }, { "input": "The keto and phenolic - OH are major factors that are prominently involved in interaction with COX - 2 active site.", "output": "keto, phenolic, OH." }, { "input": "Antimycobacterial activity evaluation, time - kill kinetic and 3D - QSAR study of C - ( 3 - aminomethyl - cyclohexyl ) - methylamine derivatives.", "output": "C - ( 3 - aminomethyl - cyclohexyl ) - methylamine." }, { "input": "A series of C - ( 3 - aminomethyl - cyclohexyl ) - methylamine derivatives were synthesized and evaluated for their antitubercular activity.", "output": "C - ( 3 - aminomethyl - cyclohexyl ) - methylamine." }, { "input": "Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv.", "output": "There is no related enetity." }, { "input": "One of the compound having t - butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1. 1 +/- 0. 2 mu M.", "output": "t - butyl, benzene, ethambutol." }, { "input": "The time - kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days.", "output": "There is no related enetity." }, { "input": "Additionally atom - based quantitative structure - activity relationship ( QSAR ) model was developed that gave a statistically satisfying result ( R ( 2 ) ) = 0. 92, Q ( 2 ) = 0. 75, Pearson - R = 0. 96 and effectively predicts the anti - tuberculosis activity of training and test set compounds.", "output": "There is no related enetity." }, { "input": "Longer HSD11B2 CA - repeat in impaired glucose tolerance and type 2 diabetes.", "output": "glucose." }, { "input": "Type 2 11 beta - hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids.", "output": "11 beta - hydroxysteroid, cortisol, cortisone, glucose." }, { "input": "We investigated the association of HSD11B2 variant with glucose homeostasis.", "output": "glucose." }, { "input": "Subjects with normal glucose tolerance ( n = 585 ), impaired glucose tolerance ( n = 202 ) and type 2 diabetes ( n = 355 ) were genotyped for a highly polymorphic CA - repeat polymorphism in the first intron of HSD11B2.", "output": "glucose, glucose." }, { "input": "Allele and genotype frequencies differed between normal and impaired glucose tolerance ( P = 0. 0014 and 0. 0407, respectively; 4DF ) or type 2 diabetes ( P = 0. 0053 and 0. 0078 ), with significant linear trends between the repeat length and the phenotype fraction.", "output": "glucose." }, { "input": "In normal subjects, total CA - repeat length was negatively correlated with fasting insulin and HOMA - beta.", "output": "There is no related enetity." }, { "input": "Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.", "output": "glucose." }, { "input": "Crosslinking using rapid thermal processing for the fabrication of efficient solution - processed phosphorescent organic light - emitting diodes.", "output": "There is no related enetity." }, { "input": "Copolymers with a triscarbazole hole - transport group and an oxetane or benzocyclobutene crosslinkable group can be readily thermally crosslinked on timescales of 30 min or less, with rapid thermal processing ( RTP ) being highly effective for this purpose.", "output": "triscarbazole, oxetane, benzocyclobutene." }, { "input": "Devices with RTP - crosslinked hole - transport layers and spin - coated emissive layers exhibit high external quantum efficiencies of up to 15 %.", "output": "There is no related enetity." }, { "input": "Pycnogenol (R) Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome.", "output": "There is no related enetity." }, { "input": "This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol (R) maritime pine bark extract on health risk factors in subjects with metabolic syndrome.", "output": "There is no related enetity." }, { "input": "Pycnogenol (R) was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides ( TG ), low HDL cholesterol, high blood pressure and fasting blood glucose.", "output": "triglycerides, cholesterol, glucose." }, { "input": "Sixty - four subjects ( range 45 - 55 years ) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol (R) was administered for 6 months.", "output": "There is no related enetity." }, { "input": "A group of 66 equivalent subjects were followed up as controls.", "output": "There is no related enetity." }, { "input": "In the 6 - month study Pycnogenol (R) supplementation 150 mg / day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects.", "output": "cholesterol." }, { "input": "Pycnogenol lowered fasting glucose from baseline 123 +/- 8. 6 mg / dl to 106. 4 +/- 5. 3 after 3 months and to 105. 3 +/- 2. 5 at the end of the study ( p < 0. 05 vs controls ).", "output": "glucose." }, { "input": "Men ' s waist circumference decreased with Pycnogenol from 106. 2 +/- 2. 2 cm to 98. 8 +/- 2. 3 cm and to 98. 3 +/- 2. 1 after 3 and 6 months.", "output": "There is no related enetity." }, { "input": "Women ' s waist decreased from 90. 9 +/- 1. 6 cm to 84. 6 +/- 2. 1 cm and to 83. 6 +/- 2. 2 cm after 3 and 6 months.", "output": "There is no related enetity." }, { "input": "Both genders waist circumference reduction was significant as compared to controls at both time points.", "output": "There is no related enetity." }, { "input": "In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group ( - 34. 6 %; p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "In conclusion, this study indicates a role for Pycnogenol (R) for improving health risk factors in subjects with metabolic syndrome.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Tailor - Made Micro - Object Optical Sensor Based on Mesoporous Pellets for Visual Monitoring and Removal of Toxic Metal Ions from Aqueous Media.", "output": "There is no related enetity." }, { "input": "Methods for the continuous monitoring and removal of ultra - trace levels of toxic inorganic species ( e. g., mercury, copper, and cadmium ions ) from aqueous media such as drinking water and biological fluids are essential.", "output": "mercury, copper, cadmium." }, { "input": "In this paper, the design and engineering of a simple, pH - dependent, micro - object optical sensor is described based on mesoporous aluminosilica pellets with an adsorbed dressing receptor ( a porphyrinic chelating ligand ).", "output": "aluminosilica." }, { "input": "This tailor - made optical sensor permits ultra - fast ( <= 60 s ), specific, pH - dependent visualization and removal of Cu ( 2 + ), Cd ( 2 + ), and Hg ( 2 + ) at sub - picomolar concentrations ( ~ 10 ( - 11 ) mol dm ( - 3 ) ) from aqueous media, including drinking water and a suspension of red blood cells.", "output": "Cu ( 2 + ), Cd ( 2 + ), Hg ( 2 + )." }, { "input": "The acidic active acid sites of the pellets consist of heteroatoms arranged around uniformly shaped pores in 3D nanoscale gyroidal mesostructures densely coated with the chelating ligand.", "output": "There is no related enetity." }, { "input": "The sensor can be used in batch mode, as well as in a flow - through system in which sampling, target ion recognition and removal, and analysis are integrated in a highly automated and efficient manner.", "output": "There is no related enetity." }, { "input": "Because the pellets exhibit long - term stability, reproducibility, and versatility over a number of analysis / regeneration cycles, they can be expected to be useful for the fabrication of inexpensive sensor devices for naked - eye detection of toxic pollutants.", "output": "There is no related enetity." }, { "input": "Electrochemical Synthesis of Transparent, Amorphous, C ( 60 ) - Rich, Photoactive, and Low - Doped Film with an Interconnected Structure.", "output": "C ( 60 )." }, { "input": "An electrochemical synthesis is developed through quantitative electrochemical reaction of N - alkylcarbazole leading to a novel class of structurally interconnected high - C ( 60 ) content ( 60 wt % ) polymer films with negligible doping and intrinsic physicochemical properties of pure C ( 60 ).", "output": "N - alkylcarbazole, C ( 60 ), C ( 60 )." }, { "input": "This strategy allows preparation of previously unavailable low - doped fullerene - containing non - conjugated polymers and broadens the potential applications of electrochemical synthesis for controlled polymer film structures.", "output": "fullerene." }, { "input": "In vivo biological responses to silk proteins functionalized with bone sialoprotein.", "output": "There is no related enetity." }, { "input": "Recombinant 6mer + BSP protein, combining six repeats of the consensus sequence for Nephila clavipes dragline ( 6mer ) and bone sialoprotein sequence ( BSP ), shows good support for cell viability and induces the nucleation of hydroxyapatite and tricalcium phosphate during osteoblast in vitro culture.", "output": "hydroxyapatite, tricalcium phosphate." }, { "input": "The present study is conducted to characterize this bioengineered protein - based biomaterial further for in vivo behavior related to biocompatibility.", "output": "There is no related enetity." }, { "input": "6mer + BSP protein films are implanted in subcutaneous pouches in the back of mice and responses are evaluated by flow cytometry and histology.", "output": "There is no related enetity." }, { "input": "The results show no major differences between the inflammatory responses induced by 6mer + BSP films and the responses observed for the controls.", "output": "There is no related enetity." }, { "input": "Thus, this new chimeric protein could represent an alternative for bone regeneration applications.", "output": "There is no related enetity." }, { "input": "CO and CO - releasing molecules in medicinal chemistry.", "output": "CO, CO." }, { "input": "Since the discovery that CO acts as a cytoprotective and homeostatic molecule, increasing research efforts have been devoted to the exploitation of its therapeutic effects.", "output": "CO." }, { "input": "Both endogenous and exogenous CO improves experimental lung, vascular and cardiac injuries and protects against several inflammatory states.", "output": "CO." }, { "input": "The technology is now in place to bring CO to clinical applications, but the use of the gaseous molecule poses several problems.", "output": "CO." }, { "input": "The challenges associated with the clinical implementation of the gas have in part been answered by the development of CO - releasing molecules ( CO - RMs ).", "output": "CO, CO." }, { "input": "As stable solid forms of CO, these molecules represent an alternative to the administration of carbon monoxide ( orally or by injection ).", "output": "CO, carbon monoxide." }, { "input": "In this article, we present insights into the biochemical action of CO and discuss the efficacy of CO and CO - RMs in preclinical disease models.", "output": "CO, CO, CO." }, { "input": "Recent advances in the CO - RMs field are critically addressed.", "output": "CO." }, { "input": "Combined effects of Ag nanoparticles and oxygen plasma treatment on PLGA morphological, chemical, and antibacterial properties.", "output": "Ag, oxygen." }, { "input": "The purpose of this study is to investigate the combined effects of oxygen plasma treatments and silver nanoparticles ( Ag ) on PLGA in order to modulate the surface antimicrobial properties through tunable bacteria adhesion mechanisms.", "output": "oxygen, silver, Ag, PLGA." }, { "input": "PLGA nanocomposite films, produced by solvent casting with 1 wt % and 7 wt % of Ag nanoparticles were investigated.", "output": "PLGA, Ag." }, { "input": "The PLGA and PLGA / Ag nanocomposite surfaces were treated with oxygen plasma.", "output": "PLGA, PLGA, Ag, oxygen." }, { "input": "Surface properties of PLGA were investigated by field emission scanning electron microscopy ( FESEM ), atomic force microscopy ( AFM ), static contact angle ( CA ), and high resolution X - ray photoelectron spectroscopy ( XPS ).", "output": "PLGA." }, { "input": "Antibacterial tests were performed using an Escherichia coli RB ( a Gram negative ) and Staphylococcus aureus 8325 - 4 ( a Gram positive ).", "output": "There is no related enetity." }, { "input": "The PLGA surface becomes hydrophilic after the oxygen treatment and its roughness increases with the treatment time.", "output": "PLGA, oxygen." }, { "input": "The surface treatment and the Ag nanoparticle introduction have a dominant influence on the bacteria adhesion and growth.", "output": "Ag." }, { "input": "Oxygen - treated PLGA / Ag systems promote higher reduction of the bacteria viability in comparison to the untreated samples and neat PLGA.", "output": "Oxygen, PLGA, Ag, PLGA." }, { "input": "The combination of Ag nanoparticles with the oxygen plasma treatment opens new perspectives for the studied biodegradable systems in biomedical applications.", "output": "Ag, oxygen." }, { "input": "Surface - enhanced Raman scattering dye - labeled Au nanoparticles for triplexed detection of leukemia and lymphoma cells and SERS flow cytometry.", "output": "Au." }, { "input": "The labeling of cell surface receptors by fluorescent markers is an established method for the identification of cell phenotype in both research and clinical settings.", "output": "There is no related enetity." }, { "input": "Fluorescence dye labeling has inherent constraints, most notably the upper limit of labels per cell that may be probed using a single excitation source, in addition to a physical limit to the number of broad emission spectra that can be distinctly collected within the visible wavelength region.", "output": "There is no related enetity." }, { "input": "SERS labeling has the potential to mitigate these shortfalls.", "output": "There is no related enetity." }, { "input": "Herein, antibody - targeted, PEG - coated surface - enhanced Raman scattering ( SERS ) Au nanoparticles are used simultaneously to label three cell surface markers of interest on malignant B cells from the LY10 lymphoma cell line.", "output": "PEG, Au." }, { "input": "The SERS probes were characterized by multiple methods to confirm their monodispersity and functionalization with both PEG and monoclonal antibodies.", "output": "PEG." }, { "input": "The specificity of the particles ' cell labeling was demonstrated on both primary chronic lymphocytic leukemia and LY10 cells using SERS from cell suspensions and confocal Raman mapping, respectively.", "output": "There is no related enetity." }, { "input": "Fluorescence flow cytometry was employed to confirm the binding of SERS probes to LY10 over large cell populations, and the particles ' SERS was collected directly from labeled cells using a commercial flow cytometer.", "output": "There is no related enetity." }, { "input": "To the best of our knowledge, this is the first demonstration of SERS flow cytometry from cells tagged with targeted SERS probes.", "output": "There is no related enetity." }, { "input": "Surface - modified HK: siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition.", "output": "There is no related enetity." }, { "input": "We characterized in this study the pharmacokinetics and antitumor efficacy of histidine - lysine ( HK ): siRNA nanoplexes modified with PEG and a cyclic RGD ( cRGD ) ligand targeting alpha v beta 3 and alpha v beta 5 integrins.", "output": "histidine, lysine, PEG." }, { "input": "With noninvasive imaging, systemically administered surface - modified HK: siRNA nanoplexes showed nearly 4 - fold greater blood levels, 40 % higher accumulation in tumor tissue, and 60 % lower luciferase activity than unmodified HK: siRNA nanoplexes.", "output": "There is no related enetity." }, { "input": "We then determined whether the surface - modified HK: siRNA nanoplex carrier was more effective in reducing MDA - MB - 435 tumor growth with an siRNA targeting Raf - 1.", "output": "There is no related enetity." }, { "input": "Repeated systemic administration of the selected surface modified HK: siRNA nanoplexes targeting Raf - 1 showed 35 % greater inhibition of tumor growth than unmodified HK: siRNA nanoplexes and 60 % greater inhibition of tumor growth than untreated mice.", "output": "There is no related enetity." }, { "input": "The improved blood pharmacokinetic results and tumor localization observed with the integrin - targeting surface modification of HK: siRNA nanoplexes correlated with greater tumor growth inhibition.", "output": "There is no related enetity." }, { "input": "This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases.", "output": "PEG." }, { "input": "Vesicles composed of fatty acid and N - [ 3 - ( dimethylamino ) propyl ] - octadecanamide: effect of fatty acid chain length on physicochemical properties of vesicles.", "output": "fatty acid, N - [ 3 - ( dimethylamino ) propyl ] - octadecanamide, fatty acid." }, { "input": "Abstract Background and objectives: Vesicles, recently claimed as drug delivery carriers, were prepared by taking advantage of an electrostatic interaction between the carboxylic groups of fatty acids ( FAs ) and the amino groups of N - [ 3 - ( Dimethylamino ) propyl ] - Octadecanamide ( DMAPODA ).", "output": "carboxylic, fatty acids, amino, N - [ 3 - ( Dimethylamino ) propyl ] - Octadecanamide, DMAPODA." }, { "input": "The study is to find out the effect of FAs ' chain length on physicochemical properties of vesicles.", "output": "There is no related enetity." }, { "input": "Methods: Decanoic acid ( DA ), myristic acid ( MA ), stearic acid ( SA ) and behenic acid ( BA ) were used as FAs.", "output": "Decanoic acid, myristic acid, stearic acid, behenic acid." }, { "input": "Vesicles composed of them and DMAPODA were studied about formation on microscope, calorimetric analysis, size and zeta potential.", "output": "DMAPODA." }, { "input": "Results: On microphotographs, all of FAs could form vesicles when mixed with DMAPODA in an equi - molar ratio.", "output": "DMAPODA." }, { "input": "However, DA / DMAPODA vesicles were disintegrated during the homogenization.", "output": "DMAPODA." }, { "input": "Due to the asymmetry of DA / DMAPODA associate, it seems to hardly form a stable and well - packed bilayer.", "output": "DMAPODA." }, { "input": "On thermograms, the vesicles exhibited one strong peak, indicating that FAs can be homogeneously mixed with the cationic amphiphile.", "output": "There is no related enetity." }, { "input": "The sizes of the four kinds of vesicles suspended in an aqueous solution ( final pH 7. 5 ) were in the same order ( hundreds of nanometer ) on microphotographs.", "output": "There is no related enetity." }, { "input": "But, on a light scattering machine, the mean size of MA / DMAPODA vesicle was measured to be much greater than those of the other vesicles, possibly because of the low absolute value of the zeta potential.", "output": "DMAPODA." }, { "input": "In addition, the medium pH value had a significant effect on the size of BA / DMAPODA vesicle possibly because the zeta potential was strongly dependent on the pH value.", "output": "DMAPODA." }, { "input": "Conclusion: FAs ' chain length would affect the physicochemical properties of vesicles composed of them and DMAPODA.", "output": "DMAPODA." }, { "input": "Elucidation of the Molecular Interaction between Cisplatin and Flavonol ( s ) and their Effect on DNA Binding.", "output": "Cisplatin, Flavonol." }, { "input": "Combination therapy of cisplatin with flavonols is a promising treatment for increasing the efficacy of cisplatin when combating cancer.", "output": "cisplatin, flavonols, cisplatin." }, { "input": "However, little is known about the molecular interactions between cisplatin and flavonols.", "output": "cisplatin, flavonols." }, { "input": "The data herein helps to elucidate this interaction.", "output": "There is no related enetity." }, { "input": "Spectrophotometric data in the UV - visible range indicates that hydroxyl groups on the B - ring of flavonols are essential for reactivity with cisplatin.", "output": "hydroxyl, flavonols, cisplatin." }, { "input": "The use of a quartz crystal microbalance with dissipation monitoring approach clearly supports the critical role played by B - ring hydroxyls in their interactions with a cisplatin - bound double - stranded DNA surface; an increase in the number of hydroxyl groups on the B - ring of flavonols parallels the increase in their reaction rates with cisplatin and correlates well with their reported effects on leukemia cell apoptosis efficacy.", "output": "quartz, hydroxyls, cisplatin, hydroxyl, flavonols, cisplatin." }, { "input": "This study underscores the importance of B - ring hydroxyls in cisplatin ' s toxicity and may be used to better understand and improve combination therapies of flavonols with cisplatin.", "output": "hydroxyls, cisplatin, flavonols, cisplatin." }, { "input": "Bioactivation of the nasal toxicant 2, 6 - dichlorobenzonitrile: an assessment of metabolic activity in human nasal mucosa and identification of indicators of exposure and potential toxicity.", "output": "2 , 6 - dichlorobenzonitrile." }, { "input": "The herbicide 2, 6 - dichlorobenzonitrile ( DCBN ) is a potent nasal toxicant in rodents; however, it is not known whether DCBN causes similar nasal toxicity in humans.", "output": "2 , 6 - dichlorobenzonitrile, DCBN, DCBN." }, { "input": "The tissue - selective toxicity of DCBN in mouse nasal mucosa is largely dependent on target tissue bioactivation by CYP2A5.", "output": "DCBN." }, { "input": "The human orthologues of CYP2A5, CYP2A6 and CYP2A13, are both expressed in nasal mucosa and are capable of activating DCBN.", "output": "DCBN." }, { "input": "In this study, we directly determined the ability of human nasal mucosa to bioactivate DCBN.", "output": "DCBN." }, { "input": "We also tested the suitability of a glutathione conjugate of DCBN ( GS - DCBN ) or its derivatives as biomarkers of DCBN exposure and nasal toxicity in mouse models.", "output": "glutathione, DCBN, DCBN, DCBN." }, { "input": "We found that human fetal nasal mucosa microsomes catalyze the formation of GS - DCBN, with a Km value comparable to that of adult mouse nasal mucosa microsomes.", "output": "DCBN." }, { "input": "The activity of the human nasal mucosa microsomes was inhibited by 8 - methoxypsoralen, a known CYP2A inhibitor.", "output": "8 - methoxypsoralen." }, { "input": "GS - DCBN and its metabolites were detected in the nasal mucosa and nasal - wash fluid obtained from DCBN - treated mice, in amounts that increased with escalations in DCBN dose, and they were all still detectable at 24 h after a DCBN treatment ( at 10 mg / kg ).", "output": "DCBN, DCBN, DCBN, DCBN." }, { "input": "Further studies in Cyp2a5 - null mice indicated that GS - DCBN and its metabolites in nasal - wash fluid were generated in the nasal mucosa, rather than in other organs.", "output": "DCBN." }, { "input": "Thus, our data indicate for the first time that the human nasal mucosa is capable of bioactivating DCBN and that GS - DCBN and its metabolites in nasal - wash fluid may collectively serve as indicators of DCBN exposure and potential nasal toxicity in humans.", "output": "DCBN, DCBN, DCBN." }, { "input": "Toward large - scale energy harvesting by a nanoparticle - enhanced triboelectric nanogenerator.", "output": "There is no related enetity." }, { "input": "This article describes a simple, cost - effective, and scalable approach to fabricate a triboelectric nanogenerator ( NG ) with ultrahigh electric output.", "output": "There is no related enetity." }, { "input": "Triggered by commonly available ambient mechanical energy such as human footfalls, a NG with size smaller than a human palm can generate maximum short - circuit current of 2 mA, delivering instantaneous power output of 1. 2 W to external load.", "output": "There is no related enetity." }, { "input": "The power output corresponds to an area power density of 313 W / m ( 2 ) and a volume power density of 54, 268 W / m ( 3 ) at an open - circuit voltage of ~ 1200 V.", "output": "There is no related enetity." }, { "input": "An energy conversion efficiency of 14. 9 % has been achieved.", "output": "There is no related enetity." }, { "input": "The power was capable of instantaneously lighting up as many as 600 multicolor commercial LED bulbs.", "output": "There is no related enetity." }, { "input": "The record high power output for the NG is attributed to optimized structure, proper materials selection and nanoscale surface modification.", "output": "There is no related enetity." }, { "input": "This work demonstrated the practicability of using NG to harvest large - scale mechanical energy, such as footsteps, rolling wheels, wind power, and ocean waves.", "output": "There is no related enetity." }, { "input": "The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro.", "output": "There is no related enetity." }, { "input": "Alternative splicing ( AS ) is one of the most significant components of the functional complexity of human UDP - glucuronosyltransferase enzymes ( UGTs ), particularly for the UGT1A gene, which represents one of the best examples of a drug - metabolizing gene regulated by AS.", "output": "UDP." }, { "input": "Shorter UGT1A isoforms [ isoform 2 ( i2 ) ] are deficient in glucuronic acid transferase activity but function as negative regulators of enzyme activity through protein - protein interaction.", "output": "glucuronic acid." }, { "input": "Their abundance, relative to active UGT1A enzymes, is expected to be a determinant of the global transferase activity of cells and tissues.", "output": "There is no related enetity." }, { "input": "Here we tested whether i2 - mediated inhibition increases with greater abundance of the i2 protein relative to the isoform 1 ( i1 ) enzyme, using the extrahepatic UGT1A7 as a model and a series of 23 human embryonic kidney 293 clonal cell lines expressing variable contents of i1 and i2 proteins.", "output": "There is no related enetity." }, { "input": "Upon normalization for i1, a significant reduction of 7 - ethyl - 10 - hydroxycamptothecin glucuronide formation was observed for i1 + i2 clones ( mean of 53 % ) compared with the reference i1 cell line.", "output": "7 - ethyl - 10 - hydroxycamptothecin glucuronide." }, { "input": "In these clones, the i2 protein content varied greatly ( 38 - 263 % relative to i1 ) and revealed two groups: 17 clones with i2 < i1 ( 60 % +/- 3 % ) and 6 clones with i2 >= i1 ( 153 % +/- 24 % ).", "output": "There is no related enetity." }, { "input": "The inhibition induced by i2 was more substantial for clones displaying i2 >= i1 ( 74. 5 %; P = 0. 001 ) compared with those with i2 < i1 ( 45. 5 % ).", "output": "There is no related enetity." }, { "input": "Coimmunoprecipitation supports a more substantial i1 - i2 complex formation when i2 exceeds i1.", "output": "There is no related enetity." }, { "input": "We conclude that the relative abundance of regulatory i2 proteins has the potential to drastically alter the local drug metabolism in the cells, particularly when i2 surpasses the protein content of i1.", "output": "There is no related enetity." }, { "input": "Understanding photosynthetic light - harvesting: a bottom up theoretical approach.", "output": "There is no related enetity." }, { "input": "We discuss a bottom up approach for modeling photosynthetic light - harvesting.", "output": "There is no related enetity." }, { "input": "Methods are reviewed for a full structure - based parameterization of the Hamiltonian of pigment - protein complexes ( PPCs ).", "output": "There is no related enetity." }, { "input": "These parameters comprise ( i ) the local transition energies of the pigments in their binding sites in the protein, the site energies; ( ii ) the couplings between optical transitions of the pigments, the excitonic couplings; and ( iii ) the spectral density characterizing the dynamic modulation of pigment transition energies and excitonic couplings by protein vibrations.", "output": "There is no related enetity." }, { "input": "Starting with quantum mechanics perturbation theory, we provide a microscopic foundation for the standard PPC Hamiltonian and relate the expressions obtained for its matrix elements to quantities that can be calculated with classical molecular mechanics / electrostatics approaches including the whole PPC in atomic detail and using charge and transition densities obtained with quantum chemical calculations on the isolated building blocks of the PPC.", "output": "There is no related enetity." }, { "input": "In the second part of this perspective, the Hamiltonian is utilized to describe the quantum dynamics of excitons.", "output": "There is no related enetity." }, { "input": "Situations are discussed that differ in the relative strength of excitonic and exciton - vibrational coupling.", "output": "There is no related enetity." }, { "input": "The predictive power of the approaches is demonstrated in application to different PPCs, and challenges for future work are outlined.", "output": "There is no related enetity." }, { "input": "Multiple dosing of ephedra - free dietary supplements: hemodynamic, electrocardiographic, and bacterial contamination effects.", "output": "There is no related enetity." }, { "input": "Four popular ephedra - free dietary supplements were evaluated for their effects on heart rate ( HR ), blood pressure ( BP ), and electrocardiographic ( ECG ) parameters.", "output": "There is no related enetity." }, { "input": "Twelve healthy men participated in a study randomized for product sequence, with a 21 - day washout period between supplement - administration phases.", "output": "There is no related enetity." }, { "input": "Throughout the study, Holter monitors were used to assess ECG and HR activity.", "output": "There is no related enetity." }, { "input": "BP was assessed automatically on multiple occasions.", "output": "There is no related enetity." }, { "input": "The supplements were ingested three times daily for 3 days.", "output": "There is no related enetity." }, { "input": "Caffeine content, microbial load, and serum caffeine concentrations were determined.", "output": "Caffeine, caffeine." }, { "input": "Mean systolic ( SBP ) and diastolic BP ( DBP ) readings showed significant increases relative to baseline ( 10. 8 +/- 2. 5 and 5. 3 +/- 3. 1 mm Hg, respectively; P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "All supplements significantly increased HR and decreased bradycardia runs; abnormal atrial / ventricular events were frequently noted.", "output": "There is no related enetity." }, { "input": "Gastrointestinal and sympathomimetic symptoms were also common.", "output": "There is no related enetity." }, { "input": "Two supplements were heavily contaminated with Bacillus species.", "output": "There is no related enetity." }, { "input": "In light of these findings, the use of ephedra - free dietary supplements should be discouraged in individuals with hypertension, diabetes, or other cardiovascular diseases.", "output": "There is no related enetity." }, { "input": "Role of diuretics and lipid formulations in the prevention of amphotericin B - induced nephrotoxicity.", "output": "amphotericin B." }, { "input": "PURPOSE: To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B ( AmB ) - induced nephrotoxicity ( AIN ) in human populations.", "output": "amphotericin B, AmB." }, { "input": "METHOD: A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.", "output": "There is no related enetity." }, { "input": "RESULTS AND CONCLUSION: Co - administration of mannitol failed to show any clinically significant benefit in preventing AIN.", "output": "mannitol." }, { "input": "Potassium - sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral / parenteral potassium supplements in preventing hypokalemia due to AmB.", "output": "Potassium, amiloride, spironolactone, potassium, AmB." }, { "input": "Lipid - based formulations of AmB are clinically effective and safe in preventing AIN.", "output": "AmB." }, { "input": "However, due to their high cost and limited accessibility, these formulations are generally used as second - line antifungal therapy in cases of conventional AmB refractoriness and / or intolerance or pre - existing renal dysfunction.", "output": "AmB." }, { "input": "The potential effects of other nephroprotective agents, such as N - acetylcysteine, AIN merit further considerations and investigations.", "output": "N - acetylcysteine." }, { "input": "Structural and up - conversion properties of Er3 + and Yb3 + co - doped Y2Ti2O7 phosphors.", "output": "Er3 +, Yb3 +, Y2Ti2O7." }, { "input": "Y ( 2 ) Ti ( 2 ) O ( 7 ) ( YTO ) and Er ( 3 + ) / Yb ( 3 + ) co - doped Y ( 2 ) Ti ( 2 ) O ( 7 ) ( EYYTO ) phosphors have been prepared by solid - state reaction method.", "output": "Y ( 2 ) Ti ( 2 ) O ( 7 ), YTO, Er ( 3 + ), Yb ( 3 + ), Y ( 2 ) Ti ( 2 ) O ( 7 ), EYYTO." }, { "input": "Structures of YTO and EYYTO phosphors are identified as face centered cubic pyrochlores.", "output": "YTO, EYYTO." }, { "input": "Up - conversion emission spectra of EYYTO under 976 nm excitation is studied, which revealed three prominent emission lines at ~ 524, 548 and 661 nm originating from ( 2 ) H ( 11 / 2 ) --> ( 4 ) I ( 15 / 2 ), ( 4 ) S ( 3 / 2 ) --> ( 4 ) I ( 15 / 2 ) and ( 4 ) F ( 9 / 2 ) --> ( 4 ) I ( 15 / 2 ) electronic transitions of Er ( 3 + ) ion, respectively in green and red regions.", "output": "EYYTO, Er ( 3 + )." }, { "input": "The power dependence study suggests that these bands arise due to two photon absorption.", "output": "There is no related enetity." }, { "input": "The monodispersed laser ablated colloidal solution of EYYTO shows strong red and green emissions on excitation with 976 nm laser.", "output": "EYYTO." }, { "input": "The variation of luminescence intensity at different laser excitation powers is observed and thus a color can be tuned.", "output": "There is no related enetity." }, { "input": "The photoluminescence lifetime of green band at 548 nm ( ( 4 ) S ( 3 / 2 ) level ) has been found to be ~ 446 mu s.", "output": "There is no related enetity." }, { "input": "Anti - aging molecule, Sirt1: a novel therapeutic target for diabetic nephropathy.", "output": "There is no related enetity." }, { "input": "Caloric restriction prolongs the lifespan of many species.", "output": "There is no related enetity." }, { "input": "Therefore, investigators have researched the usefulness of caloric restriction for healthy lifespan extension.", "output": "There is no related enetity." }, { "input": "Sirt1, an NAD ( + ) - dependent deacetylase, was identified as a molecule necessary for caloric restriction - related anti - aging strategies.", "output": "NAD ( + )." }, { "input": "Sirt1 functions as an intracellular energy sensor to detect the concentration of NAD ( + ), and controls in vivo metabolic changes under caloric restriction and starvation through its deacetylase activity to many targets including histones, nuclear transcriptional factors, and enzymes.", "output": "NAD ( + )." }, { "input": "During the past decade, investigators have reported the relationship between disturbance of Sirt1 activation and the onset of aging - and obesity - associated diseases such as diabetes, cardiovascular disease and neurodegenerative disorders.", "output": "There is no related enetity." }, { "input": "Consequently, a calorie restriction - mimetic action of Sirt1 is now expected as a new therapy for these diseases.", "output": "There is no related enetity." }, { "input": "In addition, recent studies have gradually clarified the role of Sirt1 in the onset of kidney disease.", "output": "There is no related enetity." }, { "input": "Its activation may also become a new target of treatment in the patients with chronic kidney disease including diabetic nephropathy.", "output": "There is no related enetity." }, { "input": "In this article, we would like to review the role of Sirt1 in the onset of kidney disease based on previous studies, and discuss its possibility as the target of treatment in diabetic nephropathy.", "output": "There is no related enetity." }, { "input": "[ ( 3 ) H ] UR - PLN196: a selective nonpeptide radioligand and insurmountable antagonist for the neuropeptide Y Y ( 2 ) receptor.", "output": "[ ( 3 ) H ] UR - PLN196." }, { "input": "Radioing in on NPY: Attachment of a [ 2, 3 - ( 3 ) H ] propionyl group through an appropriate linker to the guanidine group of an ( S ) - argininamide - type neuropeptide Y ( NPY ) Y ( 2 ) receptor antagonist resulted in a subtype - selective radioligand.", "output": "[ 2 , 3 - ( 3 ) H ] propionyl, guanidine, ( S ) - argininamide." }, { "input": "Glycan sequence - dependent Nod2 activation investigated by using a chemically synthesized bacterial peptidoglycan fragment library.", "output": "There is no related enetity." }, { "input": "Nucleotide oligomerization domain - containing protein 2 ( Nod2 ), an innate immune receptor, recognizes bacterial cell - wall peptidoglycan ( PGN ), the minimum ligand of which is muramyl dipeptide ( MDP ).", "output": "Nucleotide, muramyl dipeptide, MDP." }, { "input": "Enzymatic digestion of PGN appears to be important for Nod2 recognition.", "output": "There is no related enetity." }, { "input": "PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAc beta ( 1 --> 4 ) MurNAc or MurNAc beta ( 1 --> 4 ) GlcNAc.", "output": "GlcNAc beta ( 1 --> 4 ) MurNAc, MurNAc beta ( 1 --> 4 ) GlcNAc." }, { "input": "In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 ( hNod2 ) were investigated.", "output": "disaccharide, tetrasaccharide." }, { "input": "The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties.", "output": "There is no related enetity." }, { "input": "( MurNAc beta ( 1 --> 4 ) GlcNAc ) ( 2 ) - containing structures exhibited stronger activity than those containing ( GlcNAc beta ( 1 --> 4 ) MurNAc ) ( 2 ).", "output": "MurNAc beta ( 1 --> 4 ) GlcNAc, GlcNAc beta ( 1 --> 4 ) MurNAc." }, { "input": "The results suggest that differences in the enzymatic degradation process affect the host ' s immunomodulation process.", "output": "There is no related enetity." }, { "input": "Ca (2) + - dependent phosphorylation of Ca (2) + cycling proteins generates robust rhythmic local Ca (2) + releases in cardiac pacemaker cells.", "output": "Ca (2) +, Ca (2) +, Ca (2) +." }, { "input": "The spontaneous beating of the heart is governed by spontaneous firing of sinoatrial node cells, which generate action potentials due to spontaneous depolarization of the membrane potential, or diastolic depolarization.", "output": "There is no related enetity." }, { "input": "The spontaneous diastolic depolarization rate is determined by spontaneous local submembrane Ca (2) + releases through ryanodine receptors ( RyRs ).", "output": "Ca (2) +, ryanodine." }, { "input": "We sought to identify specific mechanisms of intrinsic Ca (2) + cycling by which sinoatrial node cells, but not ventricular myocytes, generate robust, rhythmic local Ca (2) + releases.", "output": "Ca (2) +, Ca (2) +." }, { "input": "At similar physiological intracellular Ca (2) + concentrations, local Ca (2) + releases were large and rhythmic in permeabilized sinoatrial node cells but small and random in permeabilized ventricular myocytes.", "output": "Ca (2) +, Ca (2) +." }, { "input": "Furthermore, sinoatrial node cells spontaneously released more Ca (2) + from the sarcoplasmic reticulum than did ventricular myocytes, despite comparable sarcoplasmic reticulum Ca (2) + content in both cell types.", "output": "Ca (2) +, Ca (2) +." }, { "input": "This ability of sinoatrial node cells to generate larger and rhythmic local Ca (2) + releases was associated with increased abundance of sarcoplasmic reticulum Ca (2) + - ATPase ( SERCA ), reduced abundance of the SERCA inhibitor phospholamban, and increased Ca (2) + - dependent phosphorylation of phospholamban and RyR.", "output": "Ca (2) +, Ca (2) +, Ca (2) +." }, { "input": "The increased phosphorylation of RyR in sinoatrial node cells may facilitate Ca (2) + release from the sarcoplasmic reticulum, whereas Ca (2) + - dependent increase in phosphorylation of phospholamban relieves its inhibition of SERCA, augmenting the pumping rate of Ca (2) + required to support robust, rhythmic local Ca (2) + releases.", "output": "Ca (2) +, Ca (2) +, Ca (2) +, Ca (2) +." }, { "input": "The differences in Ca (2) + cycling between sinoatrial node cells and ventricular myocytes provide insights into the regulation of intracellular Ca (2) + cycling that drives the automaticity of sinoatrial node cells.", "output": "Ca (2) +, Ca (2) +." }, { "input": "Physical interaction between MYCN oncogene and polycomb repressive complex 2 ( PRC2 ) in neuroblastoma: functional and therapeutic implications.", "output": "There is no related enetity." }, { "input": "CLU ( clusterin ) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto - oncogene, but the mechanism of repression was unclear.", "output": "There is no related enetity." }, { "input": "Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non - canonical E box sequence CACGCG in the 5 ' - flanking region.", "output": "There is no related enetity." }, { "input": "Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members.", "output": "There is no related enetity." }, { "input": "MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU.", "output": "There is no related enetity." }, { "input": "Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects.", "output": "There is no related enetity." }, { "input": "The expression of CLU can be restored in MYCN - amplified cells by epigenetic drugs with therapeutic results.", "output": "There is no related enetity." }, { "input": "Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference.", "output": "There is no related enetity." }, { "input": "Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU.", "output": "There is no related enetity." }, { "input": "Biselectivity of isoDGR Peptides for Fibronectin Binding Integrin Subtypes alpha 5 beta 1 and alpha v beta 6: Conformational Control through Flanking Amino Acids.", "output": "Amino Acids." }, { "input": "Integrins are the major class of cell adhesion proteins.", "output": "There is no related enetity." }, { "input": "Their interaction with different ligands of the extracellular matrix is diverse.", "output": "There is no related enetity." }, { "input": "To get more insight into these interactions, artificial ligands endowed with a well - defined activity / selectivity profile are necessary.", "output": "There is no related enetity." }, { "input": "Herein, we present a library of cyclic pentapeptides, based on our previously reported peptide motif c ( - phg - isoDGR - X - ), in which high activity toward fibronectin binding integrins alpha 5 beta 1 and alpha v beta 6 and not on vitronectin binding integrins alpha v beta 3 and alpha v beta 5 has been achieved by changing the flanking amino acids.", "output": "cyclic pentapeptides, amino acids." }, { "input": "The structure of the most promising candidates has been determined using a combined approach of NMR, distance geometry, and molecular dynamics simulations, and docking studies have been further used to elucidate the peptide - integrin interactions at the molecular level.", "output": "There is no related enetity." }, { "input": "The peptides ' binding affinity has been characterized by enzyme linked immunosorbent assay experiments, and the results have been verified by cell adhesion experiments on specifically functionalized surfaces.", "output": "There is no related enetity." }, { "input": "Chiral selective transmembrane transport of amino acids through artificial channels.", "output": "amino acids." }, { "input": "Peptide - appended pillar [ n ] arene ( n = 5, 6 ) derivatives have been synthesized.", "output": "pillar [ n ] arene ( n = 5 , 6 )." }, { "input": "( 1 ) H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes.", "output": "( 1 ) H." }, { "input": "Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel - to - lipid ratio ( EC ( 50 ) = 0. 002 mol % ).", "output": "amino acids." }, { "input": "In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.", "output": "amino acid, amino acid." }, { "input": "DNA origami nanopillars as standards for three - dimensional superresolution microscopy.", "output": "There is no related enetity." }, { "input": "Nanopillars are promising nanostructures composed of various materials that bring new functionalities for applications ranging from photovoltaics to analytics.", "output": "There is no related enetity." }, { "input": "We developed DNA nanopillars with a height of 220 nm and a diameter of ~ 14 nm using the DNA origami technique.", "output": "There is no related enetity." }, { "input": "Modifying the base of the nanopillars with biotins allowed selective, upright, and rigid immobilization on solid substrates.", "output": "biotins." }, { "input": "With the help of site - selective dye labels, we visualized the structure and determined the orientation of the nanopillars by three - dimensional fluorescence superresolution microscopy.", "output": "There is no related enetity." }, { "input": "Because of their rigidity and nanometer - precise addressability, DNA origami nanopillars qualify as scaffold for the assembly of plasmonic devices as well as for three - dimensional superresolution standards.", "output": "There is no related enetity." }, { "input": "Homopolar dihydrogen bonding in alkali metal amidoboranes: crystal engineering of low - dimensional molecular materials.", "output": "dihydrogen, alkali metal amidoboranes." }, { "input": "Hydrogen bonding is a predominant interaction in supramolecular chemistry.", "output": "Hydrogen." }, { "input": "The absence of a conventional hydrogen bond donor in LiNMe ( 2 ) BH ( 3 ) and KNMe ( 2 ) BH ( 3 ) results in the formation of elaborate M... H - B polymeric arrays supported by heteropolar and homopolar H... H bonding, in a unique synergistic combination of unconventional intermolecular interactions.", "output": "hydrogen, LiNMe ( 2 ) BH ( 3 ), KNMe ( 2 ) BH ( 3 ), H - B, H, H." }, { "input": "Base - flipping propensities of unmethylated, hemimethylated, and fully methylated CpG sites.", "output": "CpG." }, { "input": "Methylation of C5 of cytosines at CpG dinucleotide sites of the DNA is one of the most important factors regulating the expression of genes.", "output": "cytosines, CpG dinucleotide." }, { "input": "The interactions of these CpG sites with proteins are essential for recognition and catalysis and in many cases are characterized by the flipping of either of the cytosine bases out of the DNA helix.", "output": "CpG, cytosine." }, { "input": "In this paper, we present results from molecular dynamics simulations indicating that methylation of CpG sites suppresses spontaneous extra - helical conformations of either of the two cytosines.", "output": "CpG, cytosines." }, { "input": "Thus, cytosines in unmethylated sites flip out easier than in hemimethylated sites and the latter flip out easier than in fully methylated sites.", "output": "cytosines." }, { "input": "The different propensities for base flipping is observed not only between the cytosines that differ in their methylation states but also between the cytosines on the complementary strand.", "output": "cytosines, cytosines." }, { "input": "From alchemical mutation calculations, we find that methylation of one of the cytosines increases the free energy of the extra - helical conformation by 10. 3 - 16. 5 kJ / mol and this increase is additive with respect to the second methylation.", "output": "cytosines." }, { "input": "Potential of mean force calculations confirm these results and reveal that cytosines in unmethylated sites favor flipping via the major - groove pathway.", "output": "cytosines." }, { "input": "We perform several analyses to correlate this behavior with structural changes induced by the different methylation states of the CpG site.", "output": "CpG." }, { "input": "However, we demonstrate that the driving force for these propensities is the change in the electronic distribution around the pyrimidine ring upon methylation.", "output": "pyrimidine." }, { "input": "In particular, unmethylated cytosine interacts more favorably ( primarily via electrostatic forces ) with solvent water molecules than methylated cytosine.", "output": "cytosine, cytosine." }, { "input": "This is observed for, both, extra - helical cytosines and intra - helical cytosines in which the cytosine on the complementary strand flips out and water molecules enter the DNA double - helix and substitute the hydrogen bonds with the orphan guanine.", "output": "cytosines, cytosines, cytosine, hydrogen, guanine." }, { "input": "On the basis of these results of spontaneous base flipping, we conjecture that the mechanism for base flipping observed in complexes between hemimethylated DNAs and proteins is not likely to be passive.", "output": "There is no related enetity." }, { "input": "Highly luminescent and photostable quantum dot - silica monolith and its application to light - emitting diodes.", "output": "silica." }, { "input": "A highly luminescent and photostable quantum dot - silica monolith ( QD - SM ) substance was prepared by preliminary surface exchange of the QDs and base - catalyzed sol - gel condensation of silica.", "output": "silica." }, { "input": "The SM was heavily doped with 6 - mercaptohexanol exchanged QDs up to 12 vol % ( 26 wt % ) without particle aggregation.", "output": "6 - mercaptohexanol." }, { "input": "Propylamine catalyst was important in maintaining the original luminescence of the QDs in the SM during sol - gel condensation.", "output": "There is no related enetity." }, { "input": "The silica layer was a good barrier against oxygen and moisture, so that the QD - SM maintained its initial luminescence after high - power UV radiation ( ~ 1 W ) for 200 h and through the 150 degrees C LED encapsulant curing process.", "output": "silica, oxygen." }, { "input": "Green and red light - emitting QD - SMs were applied as color - converting layers on blue LEDs, and the external quantum efficiency reached up to 89 % for the green QD - SM and 63 % for the red one.", "output": "There is no related enetity." }, { "input": "A white LED made with a mixture of green and red QDs in the SM, in which the color coordinate was adjusted at ( 0. 23, 0. 21 ) in CIE1931 color space for a backlight application, showed an efficacy of 47 lm / W, the highest value yet reported.", "output": "There is no related enetity." }, { "input": "Silica precipitation by synthetic minicollagens.", "output": "Silica." }, { "input": "Oligomeric Pro - Hyp - Gly - ( POG - ) peptides, wherein the collagenous triple helix is supported by C - terminal capping, exhibit silica precipitation properties ( O, Hyp = ( 2S, 4R ) hydroxyproline ).", "output": "Pro - Hyp - Gly, C, silica, Hyp, ( 2S , 4R ) hydroxyproline." }, { "input": "As quantified by a molybdate assay, the length of the covalently tethered triple helix ( number of POG units ) determines the amount of amorphous silica obtained from silicic acid solution.", "output": "silica, silicic acid." }, { "input": "Although lacking charged side chains, the synthetic collagens precipitate large quantities of silicic acid resulting in micrometer - sized spheres of varying surface morphologies as analyzed by scanning electron microscopy.", "output": "silicic acid." }, { "input": "Similar precipitation efficiencies on a fast time scale of less than 10 min were previously described only for biogenic diatom proteins and sponge collagen, respectively, which have a considerably higher structural complexity and limited accessibility.", "output": "There is no related enetity." }, { "input": "The minicollagens described here provide an unexpected alternative to the widely used precipitation conditions, which generally depend on ( poly - ) amines in phosphate buffer.", "output": "( poly - ) amines, phosphate." }, { "input": "Collagen can form intimate connections with inorganic matter.", "output": "There is no related enetity." }, { "input": "Hence, silica - enclosed collagens have promising perspectives as composite materials.", "output": "silica." }, { "input": "Purification and characterization of glucose 6 - phosphate dehydrogenase enzyme from rainbow trout ( Oncorhynchus mykiss ) liver and investigation of the effects of some metal ions on enzyme activity.", "output": "glucose 6 - phosphate." }, { "input": "Glucose 6 - phosphate dehydrogenase ( < sc > d < / sc > - glucose 6 - phosphate: NADP ( + ) oxidoreductase, EC 1. 1. 1. 49; G6PD ) is a key enzyme that is localized in all mammal tissues, especially in cytoplasmic sections and that catalyzes the first step of pentose phosphate metabolic pathway.", "output": "Glucose 6 - phosphate, < sc > d < / sc > - glucose 6 - phosphate, NADP ( + ), pentose phosphate." }, { "input": "In this study, G6PD enzyme was purified 1444 - fold with a yield of 77 % from rainbow trout liver using 2 ', 5 ' - ADP - sepharose - 4B affinity chromatography.", "output": "2 ' , 5 ' - ADP - sepharose - 4B." }, { "input": "Moreover, a purity check of the enzyme was performed with sodium dodecyl sulfate - polyacrylamide gel electrophoresis.", "output": "sodium dodecyl sulfate, polyacrylamide." }, { "input": "Some characteristic features like optimal pH, stable pH, optimal temperature and optimal ionic strength were determined for the purified enzyme.", "output": "There is no related enetity." }, { "input": "In addition to this, in vitro effects of ions like silver nitrate ( Ag ( + ) ), thallium sulphate ( TI ( + ) ), cobalt ( II ) nitrate ( Co ( 2 + ) ) and arsenic ( V ) oxide ( As ( 5 + ) ) on enzyme activity were researched.", "output": "silver nitrate, Ag ( + ), thallium sulphate, TI ( + ), cobalt ( II ) nitrate, Co ( 2 + ), arsenic ( V ) oxide, As ( 5 + )." }, { "input": "Half - maximal inhibitory concentration ( IC ( 50 ) ) values of Ag ( + ), Co ( 2 + ) and As ( 5 + ) metal ions, which showed an inhibitory effect, were found to be 0. 0044, 0. 084 and 4. 058 mM, respectively; and their inhibition constants ( K ( i ) ) were found to be 0. 0052 +/- 0. 00042, 0. 087 +/- 0. 015700 and 4. 833 +/- 1. 753207 mM, respectively.", "output": "Ag ( + ), Co ( 2 + ), As ( 5 + )." }, { "input": "Tl ( + ) not exhibited inhibitory effect on the enzyme activity.", "output": "Tl ( + )." }, { "input": "Hepatoprotective effect of carob against acute ethanol - induced oxidative stress in rat.", "output": "ethanol." }, { "input": "The present study was undertaken to determine whether subacute treatment with aqueous extract of carob ( Ceratonia siliqua L. ) pods ( AECPs ) protects against ethanol ( EtOH ) - induced oxidative stress in rat liver.", "output": "ethanol, EtOH." }, { "input": "Animals were divided into four groups: control, carob, EtOH and EtOH + carob.", "output": "EtOH, EtOH." }, { "input": "Wistar rats were intraperitoneally pretreated with AECP ( 600 mg / kg body weight ( bw ) ) during 7 days and intoxicated for 6 h by acute oral administration of EtOH ( 6 g / kg bw ) 24 h after the last injection.", "output": "EtOH." }, { "input": "We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury.", "output": "EtOH, aspartate, alanine." }, { "input": "EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase.", "output": "EtOH, malondialdehyde, superoxide, glutathione." }, { "input": "Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal.", "output": "EtOH." }, { "input": "Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels.", "output": "hydrogen peroxide." }, { "input": "The carob pretreatment reversed EtOH effects to near control levels.", "output": "EtOH." }, { "input": "These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue - free iron accumulation.", "output": "EtOH." }, { "input": "Indeed, carob can be offered as a food additive to protect against EtOH - induced oxidative damage.", "output": "EtOH." }, { "input": "Responses of Portulaca oleracea Linn. to selenium exposure.", "output": "There is no related enetity." }, { "input": "The present study was investigated to evaluate the uptake and accumulation of selenium ( Se ) by the stem cuttings of Portulaca oleracea L. grown in alfisol amended with various concentrations of Se.", "output": "selenium, Se." }, { "input": "P. oleracea accumulated a maximum of 63. 4 micro g g ( - 1 ) dry weight in a short growth period of 42 days.", "output": "There is no related enetity." }, { "input": "The order of accumulation of Se among the plant parts was leaves ( 31. 5 mu g g ( - 1 ) ) > stems ( 16. 4 mu g g ( - 1 ) ) > roots ( 15. 5 mu g g ( - 1 ) ).", "output": "Se." }, { "input": "The accumulation potential was fourfold higher than the plant available concentration of 15. 2 mu g g ( - 1 ) of Se g ( - 1 ) of soil ( diethylenetriaminepentaacetic acid extracted ).", "output": "Se, diethylenetriaminepentaacetic acid." }, { "input": "Although the plant was able to accumulate Se in their tissues, increase in Se concentrations in soil caused a concentration - dependent decrease in the growth rate of plants ( regeneration of leaves, number of leaves, number of roots, root length, stem length and biomass ).", "output": "Se, Se." }, { "input": "Green approach & # 8212; multicomponent production of boron & # 8212; containing hantzsch and biginelli esters.", "output": "boron." }, { "input": "Multicomponent reactions are excellent methods that meet the requirements of green chemistry, by reducing the number of steps, and consequently reducing purification requirements.", "output": "There is no related enetity." }, { "input": "Accordingly, in this work, 11 novel hybrid - boron - containing molecules, namely eight 1, 4 - dihydropyridines and three 3, 4 - dihydropyrimidinones, derived from formylphenylboronic acids ( ortho, meta and para ), were obtained using a green approach, involving H - 4CR and B - 3CR practices, in the presence of ethanol, which is a green solvent, and using three comparatively different modes of activation ( mantle heating, yield 3 % - 7 % in 24 h, Infrared Radiation ( IR ) irradiation, yield 12 % - 17 % in 12 h, and microwave irradiation, yield 18 % - 80 %, requiring very low reaction times of 0. 25 - 0. 33 h ).", "output": "boron, 1 , 4 - dihydropyridines, 3 , 4 - dihydropyrimidinones, formylphenylboronic acids, ethanol." }, { "input": "In addition, as a green - approach is offered, a convenient analysis, of the 12 green chemistry principles for the overall procedure was performed.", "output": "There is no related enetity." }, { "input": "Finally, since all the products are new, characterizations were carried out using common analytic procedures ( 1H, 11B, and 13C NMR, FAB + MS, HRMS, and IR ).", "output": "1H, 11B, 13C." }, { "input": "The accurate mass data of unexpected ions related to interactions between thioglycerol and the expected products, in the FAB + - mode, enabled unequivocal characterization of the target molecules.", "output": "thioglycerol." }, { "input": "Adsorption and Self - Assembly of Large Polycyclic Molecules on the Surfaces of TiO2 Single Crystals.", "output": "TiO2." }, { "input": "Titanium dioxide is one of the most frequently studied metal oxides, and its ( 110 ) rutile surface serves as a prototypical model for the surface science of such materials.", "output": "Titanium dioxide, metal oxides." }, { "input": "Recent studies have also shown that the ( 011 ) surface is relatively easy for preparation in ultra - high vacuum ( UHV ) and that both the ( 110 ) and ( 011 ) surfaces could be precisely characterized using scanning tunneling microscopy ( STM ).", "output": "There is no related enetity." }, { "input": "The supramolecular self - assembly of organic molecules on the surfaces of titanium dioxide plays an important role in nanofabrication, and it can control the formation and properties of nanostructures, leading to wide range of applications covering the fields of catalysis, coatings and fabrication of sensors and extends to the optoelectronic industry and medical usage.", "output": "titanium dioxide." }, { "input": "Although the majority of experiments and theoretical calculations are focused on the adsorption of relatively small organic species, in recent years, there has been increasing interest in the properties of larger molecules that have several aromatic rings in which functional units could also be observed.", "output": "There is no related enetity." }, { "input": "The purpose of this review is to summarize the achievements in the study of single polycyclic molecules and thin layers adsorbed onto the surfaces of single crystalline titanium dioxide over the past decade.", "output": "titanium dioxide." }, { "input": "Anti - inflammatory activity of Bromelia hieronymi: comparison with bromelain.", "output": "There is no related enetity." }, { "input": "Some plant proteases ( e. g., papain, bromelain, ficin ) have been used as anti - inflammatory agents for some years, and especially bromelain is still being used as alternative and / or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators.", "output": "There is no related enetity." }, { "input": "Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus.", "output": "cysteine." }, { "input": "In this study the anti - inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented.", "output": "cysteine." }, { "input": "Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan - induced and serotonine - induced rat paw edema, as well as in cotton pellet granuloma model.", "output": "serotonine." }, { "input": "Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti - inflammatory responses.", "output": "There is no related enetity." }, { "input": "Treatment of the partially purified extract and bromelain with E - 64 provoked loss of anti - inflammatory activity on carrageenan - induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti - inflammatory action.", "output": "E - 64." }, { "input": "Primary hepatocyte cultures as prominent in vitro tools to study hepatic drug transporters.", "output": "There is no related enetity." }, { "input": "Abstract Before any drug can be placed on the market, drug efficacy and safety must be ensured through rigorous testing.", "output": "There is no related enetity." }, { "input": "Animal models are used for this purpose, though currently increasing attention goes to the use of alternative in vitro systems.", "output": "There is no related enetity." }, { "input": "In particular, liver - based testing platforms that allow the prediction of pharmacokinetic ( PK ) and pharmacotoxicological properties during the early phase of drug development are of interest.", "output": "There is no related enetity." }, { "input": "They also enable the screening of potential effects on hepatic drug transporters.", "output": "There is no related enetity." }, { "input": "The latter are known to affect drug metabolism and disposition, thereby possibly underlying drug - drug interactions, which, in turn, may result in liver toxicity.", "output": "There is no related enetity." }, { "input": "Clearly, stable in vivo - like functional expression of drug transporters in hepatic in vitro settings is a prerequisite to be applicable in routine PK and pharmacotoxicological testing.", "output": "There is no related enetity." }, { "input": "In the first part of the article, an updated overview of hepatic drug transporters is provided, followed by a state - of - the - art review of drug - transporter production and activity in primary hepatocyte cultures ( PHCs ), being the gold - standard in vitro system.", "output": "There is no related enetity." }, { "input": "Specific focus is hereby put on strategies to maintain long - term functional expression, in casu of drug transporters, in these systems.", "output": "There is no related enetity." }, { "input": "In the second part, the use of PHCs to assess hepatobiliary transport and transporter - mediated interactions is outlined.", "output": "There is no related enetity." }, { "input": "Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin.", "output": "metformin." }, { "input": "AIM: Assess the pharmacodynamics of lixisenatide once daily ( QD ) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin.", "output": "metformin." }, { "input": "METHODS: In this 28 - day, randomized, open - label, parallel - group, multicentre study ( NCT01175473 ), patients ( mean HbA1c 7. 3 % ) received subcutaneous lixisenatide QD ( 10 micro g weeks 1 - 2, then 20 micro g; n = 77 ) or liraglutide QD ( 0. 6 mg week 1, 1. 2 mg week 2, then 1. 8 mg; n = 71 ) 30 min before breakfast.", "output": "There is no related enetity." }, { "input": "Primary endpoint was change in postprandial plasma glucose ( PPG ) exposure from baseline to day 28 during a breakfast test meal.", "output": "glucose." }, { "input": "RESULTS: Lixisenatide reduced PPG significantly more than liraglutide [ mean change in AUC ( 0 ) (: 30 - 4: 30h ): - 12. 6 vs. - 4. 0 h / mmol / l, respectively; p < 0. 0001 ( 0: 30 h = start of meal ) ].", "output": "There is no related enetity." }, { "input": "Change in maximum PPG excursion was - 3. 9 mmol / l vs. - 1. 4 mmol / l, respectively ( p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "More lixisenatide - treated patients achieved 2 - h PPG < 7. 8 mmol / l ( 69 % vs. 29 % ).", "output": "There is no related enetity." }, { "input": "Changes in fasting plasma glucose were greater with liraglutide ( - 0. 3 vs. - 1. 3 mmol / l, p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Lixisenatide provided greater decreases in postprandial glucagon ( p < 0. 05 ), insulin ( p < 0. 0001 ) and C - peptide ( p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Mean HbA1c decreased in both treatment groups ( from 7. 2 % to 6. 9 % with lixisenatide vs. 7. 4 % to 6. 9 % with liraglutide ) as did body weight ( - 1. 6 kg vs. - 2. 4 kg, respectively ).", "output": "There is no related enetity." }, { "input": "Overall incidence of adverse events was lower with lixisenatide ( 55 % ) versus liraglutide ( 65 % ), with no serious events or hypoglycaemia reported.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG ( AUC ) during a morning test meal versus prebreakfast liraglutide.", "output": "There is no related enetity." }, { "input": "Lixisenatide provided significant decreases in postprandial insulin, C - peptide ( vs. an increase with liraglutide ) and glucagon, and better gastrointestinal tolerability than liraglutide.", "output": "There is no related enetity." }, { "input": "Anti - M u llerian hormone trend after laparoscopic surgery in women with ovarian endometrioma.", "output": "There is no related enetity." }, { "input": "Abstract Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts.", "output": "There is no related enetity." }, { "input": "Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate the extent of the ovarian reserve damage after stripping technique of unilateral endometriomas, by dosing the Anti - M u llerian Hormone ( AMH ).", "output": "There is no related enetity." }, { "input": "This prospective study was conducted at the Center of Minimally Invasive Pelvic Surgery of the Department of Health of Woman and Child, University of Padua, from October 2010 to June 2012.", "output": "There is no related enetity." }, { "input": "Twenty - five women underwent excision of monolateral endometriosis ovarian cyst by stripping without accessing a bipolar coagulation and performing an intracortical suture.", "output": "There is no related enetity." }, { "input": "The AMH serum levels were estimated in the early proliferative phase of the cycle, before surgery ( time 0 ), 24 h after surgery ( time 1 ), the first menstrual cycle after surgery ( time 2 ) and the third menstrual cycle after surgery ( time 3 ).", "output": "There is no related enetity." }, { "input": "We found a nonstatistically significant decreases in serum AMH levels after surgical excision of the cysts.", "output": "There is no related enetity." }, { "input": "Our results suggest that an appropriate surgical technique, without the use of the bipolar coagulation of ovarian border, does not determine a significant reduction of ovarian reserve.", "output": "There is no related enetity." }, { "input": "Eukaryotic initiation factor 5A dephosphorylation is required for translational arrest in stationary phase cells.", "output": "There is no related enetity." }, { "input": "The protein known as eIF5A ( eukaryotic initiation factor 5A ) has an elusive role in translation.", "output": "There is no related enetity." }, { "input": "It has a unique and essential hypusine modification at a conserved lysine residue in most eukaryotes.", "output": "lysine." }, { "input": "In addition, this protein is modified by phosphorylation with unknown functions.", "output": "There is no related enetity." }, { "input": "In the present study we show that a phosphorylated state of eIF5A predominates in exponentially growing Trypanosoma cruzi cells, and extensive dephosphorylation occurs in cells in stationary phase.", "output": "There is no related enetity." }, { "input": "Phosphorylation occurs mainly at Ser ( 2 ), as shown in yeast eIF5A.", "output": "Ser." }, { "input": "In addition, a novel phosphorylation site was identified at Tyr ( 21 ).", "output": "Tyr." }, { "input": "In exponential cells, T. cruzi eIF5A is partially associated with polysomes, compatible with a proposed function as an elongation factor, and becomes relatively enriched in polysomal fractions in stationary phase.", "output": "There is no related enetity." }, { "input": "Overexpression of the wild - type eIF5A, or eIF5A with Ser ( 2 ) replaced by an aspartate residue, but not by alanine, increases the rate of cell proliferation and protein synthesis.", "output": "Ser, aspartate, alanine." }, { "input": "However, the presence of an aspartate residue instead of Ser ( 2 ) is toxic for cells reaching the stationary phase, which show a less - pronounced protein synthesis arrest and a decreased amount of eIF5A in dense fractions of sucrose gradients.", "output": "aspartate, Ser, sucrose." }, { "input": "We conclude that eIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions.", "output": "There is no related enetity." }, { "input": "Potent and Selective Inhibition of Histone Deacetylase 6 ( HDAC6 ) Does Not Require a Surface - Binding Motif.", "output": "There is no related enetity." }, { "input": "Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 ( HDAC6 ).", "output": "Hydroxamic acids." }, { "input": "Several inhibitors, including compound 14 ( BRD9757 ), exhibited excellent potency and selectivity despite the absence of a surface - binding motif.", "output": "BRD9757." }, { "input": "The binding of these highly efficient ligands for HDAC6 is rationalized via structure - activity relationships.", "output": "There is no related enetity." }, { "input": "These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.", "output": "There is no related enetity." }, { "input": "Left, right, or both?", "output": "There is no related enetity." }, { "input": "On the configuration of the phenanthroindolizidine alkaloid tylophorine from Tylophora indica.", "output": "phenanthroindolizidine alkaloid." }, { "input": "The alkaloid ( - ) - tylophorine was isolated from a sample of Tylophora indica, and the crude extract was analyzed by HPLC / MS ( n ) and chiral HPLC / MS.", "output": "( - ) - tylophorine." }, { "input": "While the literature states that the naturally occurring form of this alkaloid is the R - enantiomer and that its S - antipode is usually not found in nature, we confirmed the hypothesis of Govindachari and Nagarajan that natural levorotatory tylophorine is indeed a nearly racemic mixture with a slight excess of the R - enantiomer.", "output": "levorotatory tylophorine." }, { "input": "Evaluation of in vivo anti - hyperglycemic and antioxidant potentials of alpha - santalol and sandalwood oil.", "output": "alpha - santalol." }, { "input": "Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide.", "output": "There is no related enetity." }, { "input": "The objective of this study was to evaluate the in vivo anti - hyperglycemic and antioxidant potential of sandalwood oil and its major constituent alpha - santalol.", "output": "alpha - santalol." }, { "input": "The in vivo anti - hyperglycemic experiment was conducted in alloxan - induced diabetic male Swiss albino mice models.", "output": "alloxan." }, { "input": "The in vivo antioxidant experiment was performed in d - galactose mediated oxidative stress induced male Swiss albino mice models.", "output": "d - galactose." }, { "input": "Intraperitoneal administration of alpha - santalol ( 100mg / kg BW ) and sandalwood oil ( 1g / kg BW ) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan - induced diabetic mice.", "output": "alpha - santalol, glucose, bilirubin, peroxides, alloxan." }, { "input": "Similarly, intraperitoneal administration of alpha - santalol ( 100mg / kg BW ) and sandalwood oil ( 1g / kg BW ) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d - galactose mediated oxidative stress induced mice.", "output": "alpha - santalol, bilirubin, superoxide, sulfhydryl, carbonyl, nitric oxide, peroxide, d - galactose." }, { "input": "Besides, it was observed that the beneficial effects of alpha - santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource.", "output": "alpha - santalol." }, { "input": "Endothelium - dependent vasodilatation effects of the essential oil from Fructus alpiniae zerumbet ( EOFAZ ) on rat thoracic aortic rings in vitro.", "output": "There is no related enetity." }, { "input": "Fructus Alpiniae Zerumbet ( FAZ ) is an herb widely used to treat vascular disorders in Guizhou province, China, the essential oil has been identified as one of it vasodilation effect active components, and especial, the composition was significantly difference from the leaves.", "output": "There is no related enetity." }, { "input": "Vasodilation effects and mechanism of essential oil from FAZ ( EOFAZ ) were investigated.", "output": "There is no related enetity." }, { "input": "The EOFAZ showed significant vasodilation effect on endothelium - with rat thoracic aortic rings preincubated with norepinephrine ( NE, 1. 0 mu M ) or KCl ( 60mM ) in a concentration - dependent manner ( 1. 14 - 72. 96 mu g / ml ).", "output": "There is no related enetity." }, { "input": "The non - selective nitric oxide synthase inhibitor l - NAME, as well as the soluble guanylate cyclase inhibitor MB, attenuated the relaxation of EOFAZ in endothelium - intact rat thoracic aortic rings.", "output": "nitric oxide, l - NAME, guanylate." }, { "input": "However, there were not significantly affected the vasodilation effects pretreated with cyclooxygenase inhibition by indomethacin ( Indo ) or beta - noradrenergic inhibition by propranolol ( Prop ).", "output": "indomethacin, Indo, propranolol, Prop." }, { "input": "The present results first demonstrated that vasodilation effect of EOFAZ depending upon the endothelium and concentration, and the mechanism involvement of NOS - cGMP system.", "output": "cGMP." }, { "input": "In contrast, prostacyclin and beta - adrenoceptor may not be associated with EOFAZ - induced vasorelaxation.", "output": "prostacyclin." }, { "input": "Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents.", "output": "chalcones." }, { "input": "Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv strain.", "output": "There is no related enetity." }, { "input": "Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3. 5 and 7. 5 mu g - mL ( - 1 ).", "output": "There is no related enetity." }, { "input": "In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non - cancerous human epithelial kidney cell line ( HEK - 293 ) showed that most active compound 25a was approximately 2. 85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective.", "output": "There is no related enetity." }, { "input": "Transformation of paralytic shellfish poisoning toxins in UK surf clams ( Spisula solida ) for targeted production of reference materials.", "output": "There is no related enetity." }, { "input": "The periodic occurrence of Paralytic Shellfish Poisoning ( PSP ) toxins in UK surf clams and the recent move away from biological assays for PSP testing resulted in the need to determine method performance characteristics for the replacement analytical method in this species.", "output": "There is no related enetity." }, { "input": "With the requirement for laboratory reference materials to aid this validation together with known issues relating to toxin transformation in live clams and homogenised tissue, there was the need to assess the toxin transformation characteristics of PSP toxins in surf clam tissue.", "output": "There is no related enetity." }, { "input": "Initial work examined the rates of toxin transformation in UK surf clam tissue incubated with toxin standards, showing rapid transformation of N - sulfocarbamoyl toxins with slower transformation of carbamate toxins.", "output": "N - sulfocarbamoyl, carbamate." }, { "input": "Full transformational pathways were determined using a combination of three different analytical methods and confirmed the major expected transformations involving decarbamoylation, with some evidence for additional reaction pathways.", "output": "There is no related enetity." }, { "input": "Results obtained from the analysis of surf clam and oyster tissues incubated with varying concentrations of toxic Alexandrium algae highlighted expected transformation reactions, although significant differences were observed in the extent of the transformations amongst the range of toxins studied, with less efficient transformation of N - hydroxylated toxins as compared with other carbamate and N - sulfocarbamoyl toxins.", "output": "N, carbamate and N - sulfocarbamoyl." }, { "input": "Analysis of PSP - toxic incurred oyster, scallop and mussel tissues incubated with variable proportions of surf clam tissue showed large differences in the extent of the transformations.", "output": "There is no related enetity." }, { "input": "Total conversion of N - sulfocarbamoyl toxins was confirmed at low relative proportions of surf clam tissue in all three species, whereas transformation of carbamate toxins was found to occur only in the presence of higher proportions of surf clam tissue in oysters and mussels in comparison with scallops.", "output": "N, carbamate." }, { "input": "Results enabled the production of three laboratory reference materials prepared following incubation of incurred homogenates with optimum proportions of surf clam tissue, resulting in materials containing a large number of PSP toxins.", "output": "There is no related enetity." }, { "input": "Stability experiments provided good preliminary evidence for the stability of these targeted materials under storage conditions.", "output": "There is no related enetity." }, { "input": "The work therefore provides both additional information relating to the transformational activity in UK surf clams and highlights a good potential method for the targeted production of reference materials which include a wider range of toxins than normally present in naturally incurred shellfish.", "output": "There is no related enetity." }, { "input": "Mercuric chloride - induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E.", "output": "Mercuric chloride, sodium selenite, vitamin E." }, { "input": "Mercury has been recognized as an environmental pollutant that adversely affects male reproductive systems of animals.", "output": "Mercury." }, { "input": "This study examined the effects of mercuric chloride on the antioxidant system and histopathological changes and also evaluated the ameliorating effects of sodium selenite and / or vitamin E in the rat testis tissues.", "output": "mercuric chloride, sodium selenite, vitamin E." }, { "input": "Sexually mature male Wistar rats ( weighing 300 - 320g and each group six animals ) were given mercuric chloride ( 1mg / kg bw ) and / or sodium selenite ( 0. 25mg / kg bw ) + vitamin E ( 100mg / kg ) daily via gavage for 4weeks.", "output": "mercuric chloride, sodium selenite, vitamin E." }, { "input": "In the present study, mercuric chloride exposure resulted in an increase in the TBARS level and a decrease in the SOD, CAT, GPx activities, with respect to the control.", "output": "mercuric chloride." }, { "input": "Further, light microscopic investigation revealed that mercury exposure induced histopathological alterations in the testis tissues.", "output": "mercury." }, { "input": "Supplementation of sodium selenite and / or vitamin E to mercury - induced groups declined lipid peroxidation, increased SOD, CAT, GPx activities.", "output": "sodium selenite, vitamin E, mercury." }, { "input": "While some histopathological changes were detected in mercuric chloride treated group, milder histopathological changes were observed in animal co - treated with sodium selenite and / or vitamin E supplementation to mercuric chloride - treated rats.", "output": "mercuric chloride, sodium selenite, vitamin E, mercuric chloride." }, { "input": "As a result, mercuric chloride induced testicular toxicity is reduced by sodium selenite and / or vitamin E, but not ameliorate completely.", "output": "mercuric chloride, sodium selenite, vitamin E." }, { "input": "Biomonitoring a human population inhabiting nearby a deactivated uranium mine.", "output": "uranium." }, { "input": "Environmental exposure to uranium and its daughter radionuclides, has been linked to several negative effects such as those related with important physiological processes, like hematopoiesis, and may also be associated with genotoxicity effects.", "output": "uranium." }, { "input": "Herein, genotoxic effects, immunotoxicity, trace elements and C reactive protein ( CRP ) analyses, were performed in peripheral blood samples collected from individuals of a population living near a deactivated uranium mine.", "output": "uranium." }, { "input": "C reactive protein analysis was performed to exclude candidates with active inflammatory processes from further evaluations.", "output": "There is no related enetity." }, { "input": "DNA damage and immunotoxicity ( immunophenotyping and immune cell counts ) were evaluated by comet assay and flow cytometry, respectively.", "output": "There is no related enetity." }, { "input": "Significant DNA damage was observed in the peripheral blood samples from volunteers living in the Cunha Baixa village.", "output": "There is no related enetity." }, { "input": "A significant decrease of NK and T lymphocytes counts were observed in the individuals from the Cunha Baixa village, when compared with individuals from the reference site.", "output": "There is no related enetity." }, { "input": "Uranium and manganese levels were significantly higher in the Cunha Baixa village inhabitants.", "output": "Uranium, manganese." }, { "input": "On the other hand, zinc levels were significantly lower in those individuals when compared with the volunteers from the control village.", "output": "zinc." }, { "input": "Results suggest that inhabitants from Cunha Baixa have a higher risk of suffering from serious diseases such as cancer, since high DNA damages were observed in peripheral blood leukocytes and also decreased levels of NK and T cells, which play an essential role in the defense against tumor growth.", "output": "There is no related enetity." }, { "input": "Nonhuman primate models of polycystic ovary syndrome.", "output": "There is no related enetity." }, { "input": "With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome ( PCOS ), suggesting early life targeting for prevention.", "output": "There is no related enetity." }, { "input": "Fetal exposure to testosterone ( T ), of all nonhuman primate emulations, provides the closest PCOS - like phenotypes, with early - to - mid gestation T - exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co - pathologies of PCOS.", "output": "testosterone." }, { "input": "Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment.", "output": "There is no related enetity." }, { "input": "Fetal exposures to dihydrotestosterone ( DHT ) or diethylstilbestrol ( DES ) suggest androgenic and estrogenic aspects of fetal programming.", "output": "dihydrotestosterone, DHT, diethylstilbestrol, DES." }, { "input": "Neonatal exposure to T produces no PCOS - like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche ( high T ), or high LH and weight gain ( moderate T ).", "output": "There is no related enetity." }, { "input": "Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.", "output": "There is no related enetity." }, { "input": "Eight New Diterpenoids and Two New Nor - Diterpenoids from the Stems of Croton cascarilloides.", "output": "Diterpenoids, Nor - Diterpenoids." }, { "input": "From the stems of Croton cascarilloides, eight new diterpenoids, named crotocascarins A - H ( 1 - 8 ), having a crotofolane skeleton were isolated along with two new nor - diterpenoids ( 9 and 10 ), named crotocascarins alpha and beta, derived through rearrangement of the crotofolane skeleton.", "output": "diterpenoids, crotocascarins A - H, crotofolane, nor - diterpenoids, crotofolane." }, { "input": "The structures of these compounds were elucidated by means of extensive one - and two - dimensional NMR spectroscopic analyses.", "output": "There is no related enetity." }, { "input": "The absolute structures of the diterpene moiety were determined by application of the circular dichroism ( CD ) rule for the gamma - lactone ring.", "output": "diterpene, gamma - lactone." }, { "input": "The relative structures of the two crotofolanes ( 1 and 2 ) and one rearranged compound ( 9 ) were confirmed by X - ray crystallographic analyses.", "output": "crotofolanes." }, { "input": "Compounds 1, 2 and 9 possessed 2 - methylbutyric acid in their molecules, the absolute configuration of which was found to be 2S by comparison of its HPLC behavior with that of an authentic sample.", "output": "2 - methylbutyric acid." }, { "input": "Therefore, the absolute structures of these crotocascarins ( 1, 2 and 9 ) were unambiguously determined.", "output": "crotocascarins." }, { "input": "The absolute structures of crotofolanes are reported for the first time in this paper.", "output": "crotofolanes." }, { "input": "Silencing of RB1 but not of RB2 / P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells.", "output": "There is no related enetity." }, { "input": "Stem cell senescence is considered deleterious because it may impair tissue renewal and function.", "output": "There is no related enetity." }, { "input": "On the other hand, senescence may arrest the uncontrolled growth of transformed stem cells and protect organisms from cancer.", "output": "There is no related enetity." }, { "input": "This double function of senescence is strictly linked to the activity of genes that the control cell cycle such as the retinoblastoma proteins RB1, RB2 / P130, and P107.", "output": "There is no related enetity." }, { "input": "We took advantage of the RNA interference technique to analyze the role of these proteins in the biology of mesenchymal stem cells ( MSC ).", "output": "There is no related enetity." }, { "input": "Cells lacking RB1 were prone to DNA damage.", "output": "There is no related enetity." }, { "input": "They showed elevated levels of p53 and p21 ( cip1 ) and increased regulation of RB2 / P130 and P107 expression.", "output": "There is no related enetity." }, { "input": "These cells gradually adopted a senescent phenotype with impairment of self - renewal properties.", "output": "There is no related enetity." }, { "input": "No significant modification of cell growth was observed as it occurs in other cell types or systems.", "output": "There is no related enetity." }, { "input": "In cells with silenced RB2 / P130, we detected a reduction of DNA damage along with a higher proliferation rate, an increase in clonogenic ability, and the diminution of apoptosis and senescence.", "output": "There is no related enetity." }, { "input": "Cells with silenced RB2 / P130 were cultivated for extended periods of time without adopting a transformed phenotype.", "output": "There is no related enetity." }, { "input": "Of note, acute lowering of P107 did not induce relevant changes in the in vitro behavior of MSC.", "output": "There is no related enetity." }, { "input": "We also analyzed cell commitment and the osteo - chondro - adipogenic differentiation process of clones derived by MSC cultures.", "output": "There is no related enetity." }, { "input": "In all clones obtained from cells with silenced retinoblastoma genes, we observed a reduction in the ability to differentiate compared with the control clones.", "output": "There is no related enetity." }, { "input": "In summary, our data show evidence that the silencing of the expression of RB1 or RB2 / P130 is not compensated by other gene family members, and this profoundly affects MSC functions.", "output": "There is no related enetity." }, { "input": "Parallel buprenorphine phMRI responses in conscious rodents and healthy human subjects.", "output": "buprenorphine." }, { "input": "Pharmacological magnetic resonance imaging ( phMRI ) is one method by which a drug ' s pharmacodynamic effects in the brain can be assessed.", "output": "There is no related enetity." }, { "input": "Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined.", "output": "There is no related enetity." }, { "input": "In the current investigation, we aimed to build on recent clinical work in which the functional response to 0. 1 and 0. 2 mg / 70 kg i. v. buprenorphine ( partial micro - opioid receptor agonist ) was measured in healthy humans.", "output": "buprenorphine." }, { "input": "Here, we measured the phMRI response to 0. 04 and 0. 1 mg / kg i. v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species.", "output": "buprenorphine, buprenorphine." }, { "input": "PhMRI of 0. 04 and 0. 1 mg / kg i. v. buprenorphine yielded dose - dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum.", "output": "buprenorphine." }, { "input": "Similar dose - dependent phMRI activation was observed in the human phMRI studies.", "output": "There is no related enetity." }, { "input": "These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia.", "output": "buprenorphine." }, { "input": "This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.", "output": "There is no related enetity." }, { "input": "Resistance to conventional insecticides in Pakistani populations of Musca domestica L.", "output": "There is no related enetity." }, { "input": "( Diptera: Muscidae ): a potential ectoparasite of dairy animals.", "output": "There is no related enetity." }, { "input": "The house fly, Musca domestica L., is an important hygienic pest of humans and dairy animals with the potential to develop resistance to most chemical classes of insecticides.", "output": "There is no related enetity." }, { "input": "Six adult house fly strains from dairy farms in Punjab, Pakistan were evaluated for resistance to selected insecticides from organochlorine, organophosphate, carbamate and pyrethroid classes.", "output": "organochlorine, organophosphate, carbamate, pyrethroid." }, { "input": "For a chlorocyclodiene and two organophosphates tested, the resistance ratios ( RR ) at LC50 were in the range of 5. 60 - 22. 02 fold for endosulfan, 7. 66 - 23. 24 fold for profenofos and 2. 47 - 7. 44 fold for chlorpyrifos.", "output": "chlorocyclodiene, organophosphates, endosulfan, chlorpyrifos." }, { "input": "For two pyrethroids and one carbamate, the RR values at LC50 were 30. 22 - 70. 02 for cypermethrin, 5. 73 - 18. 31 for deltamethrin, and 4. 39 - 15. 50 for methomyl.", "output": "pyrethroids, carbamate, cypermethrin, deltamethrin, methomyl." }, { "input": "This is the first report of resistance to different classes of insecticides in Pakistani dairy populations of house flies.", "output": "There is no related enetity." }, { "input": "Regular insecticide resistance monitoring programs on dairy farms are needed to prevent field control failures.", "output": "There is no related enetity." }, { "input": "Moreover, integrated approaches including the judicious use of insecticides are needed to delay the development of insecticide resistance in house flies.", "output": "There is no related enetity." }, { "input": "In obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight.", "output": "There is no related enetity." }, { "input": "The OFELY study.", "output": "There is no related enetity." }, { "input": "Obesity is associated with higher areal bone density ( aBMD ) but its protective effect on the risk of fracture is controversial.", "output": "There is no related enetity." }, { "input": "We aimed to analyse bone microarchitecture and biomechanical properties in obese ( OB ) postmenopausal French women compared with normal weight ( NW ) women.", "output": "There is no related enetity." }, { "input": "A matched case - control study from the OFELY cohort was conducted in 63 OB women ( BMI > 30, mean age69 +/- 8 years ) age - matched with 126 NW women ( 19 < BMI < 25 ).", "output": "There is no related enetity." }, { "input": "Bone architecture was measured with high - resolution pQCT at the distal radius and tibia and bone strength was assessed by micro - finite element analysis ( micro FEA ).", "output": "There is no related enetity." }, { "input": "aBMD, total body fat ( FM ) and lean ( LM ) masses were measured by DXA.", "output": "There is no related enetity." }, { "input": "aBMD was 15 % higher at the total hip in OB compared with NW.", "output": "There is no related enetity." }, { "input": "At the radius, OB had 13 and 14 % higher volumetric total and trabecular bone densities, 11 % higher cortical thickness, 13 % greater trabecular number, and 22 % lower distribution of trabecular separation compared with NW ( p adjusted for height, physical activity and medication use < 0. 01 for all ).", "output": "There is no related enetity." }, { "input": "Differences of a similar magnitude were found at the distal tibia.", "output": "There is no related enetity." }, { "input": "At both sites, micro FEA showed significant higher values of bone strength in OB compared to controls.", "output": "There is no related enetity." }, { "input": "After normalizing values for individual body weight, we observed that all the parameters were relatively lower in OB compared to NW women.", "output": "There is no related enetity." }, { "input": "The increase of FM was four fold greater than the increase of LM in OB.", "output": "There is no related enetity." }, { "input": "The effect of FM on bone parameters was more pronounced at the tibia than compared to the non - weight bearing site.", "output": "There is no related enetity." }, { "input": "Nevertheless, the coefficients of correlation were about half of those of LM for the biomechanical parameters.", "output": "There is no related enetity." }, { "input": "We conclude that higher absolute values of bone densities, cortical and trabecular architecture and strength indices were not in proportion to the excess of BMI and particularly of FM in obese postmenopausal French women.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Ceftazidime - avibactam: a novel cephalosporin / beta - lactamase inhibitor combination.", "output": "Ceftazidime, avibactam, cephalosporin." }, { "input": "Avibactam ( formerly NXL104, AVE1330A ) is a synthetic non - beta - lactam, beta - lactamase inhibitor that inhibits the activities of Ambler class A and C beta - lactamases and some Ambler class D enzymes.", "output": "Avibactam, NXL104, AVE1330A, beta - lactam." }, { "input": "This review summarizes the existing data published for ceftazidime - avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials.", "output": "ceftazidime, avibactam." }, { "input": "Although not a beta - lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to beta - lactamases.", "output": "beta - lactam, avibactam, cephem, avibactam." }, { "input": "Very little is known about the potential for avibactam to select for resistance.", "output": "avibactam." }, { "input": "The addition of avibactam greatly ( 4 - 1024 - fold minimum inhibitory concentration [ MIC ] reduction ) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of beta - lactamase enzyme ( s ).", "output": "avibactam, ceftazidime." }, { "input": "Against Pseudomonas aeruginosa, the addition of avibactam also improves the activity of ceftazidime ( ~ fourfold MIC reduction ).", "output": "avibactam, ceftazidime." }, { "input": "Limited data suggest that the addition of avibactam does not improve the activity of ceftazidime versus Acinetobacter species or most anaerobic bacteria ( exceptions: Bacteroides fragilis, Clostridium perfringens, Prevotella spp. and Porphyromonas spp. ).", "output": "avibactam, ceftazidime." }, { "input": "The pharmacokinetics of avibactam follow a two - compartment model and do not appear to be altered by the co - administration of ceftazidime.", "output": "avibactam, ceftazidime." }, { "input": "The maximum plasma drug concentration ( C ( max ) ) and area under the plasma concentration - time curve ( AUC ) of avibactam increase linearly with doses ranging from 50 mg to 2, 000 mg.", "output": "avibactam." }, { "input": "The mean volume of distribution and half - life of 22 L ( ~ 0. 3 L / kg ) and ~ 2 hours, respectively, are similar to ceftazidime.", "output": "ceftazidime." }, { "input": "Like ceftazidime, avibactam is primarily renally excreted, and clearance correlates with creatinine clearance.", "output": "ceftazidime, avibactam, creatinine." }, { "input": "Pharmacodynamic data suggest that ceftazidime - avibactam is rapidly bactericidal versus beta - lactamase - producing Gram - negative bacilli that are not inhibited by ceftazidime alone. Clinical trials to date have reported that ceftazidime - avibactam is as effective as standard carbapenem therapy in complicated intra - abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin - resistant Gram - negative isolates.", "output": "ceftazidime, avibactam, ceftazidime, ceftazidime, avibactam, carbapenem, cephalosporin." }, { "input": "The safety and tolerability of ceftazidime - avibactam has been reported in three phase I pharmacokinetic studies and two phase II clinical studies.", "output": "ceftazidime, avibactam." }, { "input": "Ceftazidime - avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug - related treatment - emergent adverse events reported to date. In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus beta - lactamase - producing Gram - negative bacilli.", "output": "Ceftazidime, avibactam, avibactam, ceftazidime." }, { "input": "The exact roles for ceftazidime - avibactam will be defined by efficacy and safety data from further clinical trials.", "output": "ceftazidime, avibactam." }, { "input": "Potential future roles for ceftazidime - avibactam include the treatment of suspected or documented infections caused by resistant Gram - negative - bacilli producing extended - spectrum beta - lactamase ( ESBL ), Klebsiella pneumoniae carbapenemases ( KPCs ) and / or AmpC beta - lactamases.", "output": "ceftazidime, avibactam." }, { "input": "In addition, ceftazidime - avibactam may be used in combination ( with metronidazole ) for suspected polymicrobial infections.", "output": "ceftazidime, avibactam, metronidazole." }, { "input": "Finally, the increased activity of ceftazidime - avibactam versus P. aeruginosa may be of clinical benefit in patients with suspected or documented P. aeruginosa infections.", "output": "ceftazidime, avibactam." }, { "input": "Increased human dermal microvascular endothelial cell survival induced by cysteamine.", "output": "cysteamine." }, { "input": "BACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine.", "output": "cysteamine." }, { "input": "Recently, new adverse effects of cysteamine were reported.", "output": "cysteamine." }, { "input": "Skin biopsies showed microvascular proliferation ( angioendotheliomatosis ).", "output": "There is no related enetity." }, { "input": "To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells ( HDMVEC ).", "output": "cysteamine, cysteamine." }, { "input": "METHODS: After cysteamine exposure ( range 0 - 3. 0 mM ) during 24 h, cell viability was measured using water soluble tetrazolium salt - 1 ( WST - 1 ) in both control HDMVEC and fibroblasts.", "output": "cysteamine, tetrazolium salt - 1." }, { "input": "Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine ( BrdU ) incorporation and caspase 3 and caspase 7 activity, respectively.", "output": "bromodeoxyuridine, BrdU." }, { "input": "Intracellular glutathione ( GSH ) was measured in HDMVEC after cysteamine exposure of 0, 0. 1 or 1. 0 mM.", "output": "glutathione, GSH, cysteamine." }, { "input": "Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation.", "output": "cysteamine." }, { "input": "Next, cell viability in HDMVEC was measured after 24 h of GSH exposure ( range 0 - 10. 0 mM ).", "output": "GSH." }, { "input": "RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0. 03 - 3. 0 mM ( p < 0. 01 ) and 0. 03 - 1. 0 mM ( p = 0. 01 ) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine.", "output": "cysteamine, cysteamine." }, { "input": "Apoptosis remained unaffected by incubation with 0 - 1. 0 mM cysteamine, 3. 0 mM caused increased apoptosis.", "output": "cysteamine." }, { "input": "Intracellular GSH was significantly increased after incubation with cysteamine 0. 1 mM ( p = 0. 02 ) and 1. 0 mM ( p < 0. 01 ).", "output": "GSH, cysteamine." }, { "input": "HDMVEC viability increased after exposure to GSH 1. 0 - 5. 0 mM ( p < 0. 01 ).", "output": "GSH." }, { "input": "CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content.", "output": "Cysteamine, GSH." }, { "input": "We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine.", "output": "cysteamine." }, { "input": "Effect of wheel - running during abstinence on subsequent nicotine - seeking in rats.", "output": "nicotine." }, { "input": "RATIONALE: Exercise appears to be a promising non - pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population.", "output": "nicotine." }, { "input": "OBJECTIVES: The aim of this study is to determine if wheel - running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine - seeking in rats that had extended access to nicotine self - administration during adolescence.", "output": "nicotine." }, { "input": "METHODS: Male adolescent rats ( n = 55 ) were trained to self - administer saline or nicotine infusions ( 5 or 10 mu g / kg ) under a fixed ratio 1 schedule with a maximum of 20 infusions / day beginning on postnatal day 30.", "output": "nicotine." }, { "input": "After 5 days, access was extended to 23 h / day with unlimited infusions for a total of 10 days.", "output": "There is no related enetity." }, { "input": "After the last self - administration session, rats were moved to polycarbonate cages for a 10 - day abstinence period where they either had access to a locked or unlocked running wheel for 2 h / day.", "output": "polycarbonate." }, { "input": "Nicotine - seeking was examined following the 10th day of abstinence under a within - session extinction / cue - induced reinstatement paradigm.", "output": "Nicotine." }, { "input": "RESULTS: Intake was higher at the 10 mu g / kg dose as compared to the 5 mu g / kg dose; however, intake did not differ within doses prior to wheel assignment.", "output": "There is no related enetity." }, { "input": "Compared to saline controls, rats that self - administered nicotine at either dose showed a significant increase in drug - seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect.", "output": "nicotine." }, { "input": "Nicotine led to modest but significant levels of cue - induced reinstatement; however, in this adolescent - onset model, levels were variable and not affected by exercise.", "output": "Nicotine." }, { "input": "CONCLUSIONS: Exercise may effectively reduce relapse vulnerability for adolescent - onset nicotine addiction.", "output": "nicotine." }, { "input": "Mephedrone and methylenedioxypyrovalerone ( MDPV ), major constituents of \" bath salts, \" produce opposite effects at the human dopamine transporter.", "output": "Mephedrone, methylenedioxypyrovalerone, MDPV, dopamine." }, { "input": "RATIONALE: Psychoactive \" bath salts \" represent a relatively new drug of abuse combination that was placed in Schedule I in October 2011.", "output": "There is no related enetity." }, { "input": "Two common ingredients of bath salts include the cathinone analogs: mephedrone and methylenedioxypyrovalerone ( MDPV ).", "output": "cathinone, mephedrone, methylenedioxypyrovalerone, MDPV." }, { "input": "The mechanism of action of these synthetic cathinone analogs has not been well investigated.", "output": "cathinone." }, { "input": "MATERIALS AND METHODS: Because cathinone and methcathinone are known to act as releasing agents at the human dopamine transporter ( hDAT ), mephedrone and MDPV were investigated at hDAT expressed in Xenopus oocytes.", "output": "cathinone, methcathinone, dopamine, mephedrone, MDPV." }, { "input": "RESULTS: Whereas mephedrone was found to have the signature of a dopamine - releasing agent similar to methamphetamine or methcathinone, MDPV behaved as a cocaine - like reuptake inhibitor of dopamine.", "output": "mephedrone, dopamine, methamphetamine, methcathinone, MDPV, cocaine, dopamine." }, { "input": "CONCLUSIONS: Mephedrone and MDPV produce opposite electrophysiological signatures through hDAT expressed in oocytes.", "output": "Mephedrone, MDPV." }, { "input": "Implications are that the combination ( as found in bath salts ) might produce effects similar to a combination of methamphetamine and cocaine.", "output": "methamphetamine, cocaine." }, { "input": "Resin acid conversion with CYP105A1: an enzyme with potential for the production of pharmaceutically relevant diterpenoids.", "output": "Resin acid, diterpenoids." }, { "input": "Cytochrome P450s are very versatile enzymes with great potential for biotechnological applications because of their ability to oxidize unactivated C H bonds.", "output": "C H." }, { "input": "CYP105A1 from Streptomyces griseolus was first described as a herbicide - inducible sulfonylurea hydroxylase, but it is also able to convert other substrates such as vitamin D ( 3 ).", "output": "sulfonylurea, vitamin D ( 3 )." }, { "input": "To extend the substrate pool of this interesting enzyme further, we screened a small diterpenoid compound library and were able to show the conversion of several resin acids.", "output": "diterpenoid, resin acids." }, { "input": "Binding of abietic acid, dehydroabietic acid, and isopimaric acid to the active site was assayed, and V ( max ) and K ( m ) values were calculated.", "output": "abietic acid, dehydroabietic acid, isopimaric acid." }, { "input": "The products were analyzed by NMR spectroscopy and identified as 15 - hydroxyabietic acid, 15 - hydroxydehydroabietic acid, and 15, 16 - epoxyisopimaric acid.", "output": "15 - hydroxyabietic acid, 15 - hydroxydehydroabietic acid, 15 , 16 - epoxyisopimaric acid." }, { "input": "As the observed products are difficult to obtain by chemical synthesis, CYP105A1 has proved to be a promising candidate for biotechnological applications that combine bioconversion and chemical synthesis to obtain functionalized resin acids.", "output": "resin acids." }, { "input": "Anisotropically Luminescent Hydrogels Containing Magnetically - Aligned MWCNTs - Eu ( III ) Hybrids.", "output": "Eu ( III )." }, { "input": "The anisotropic emission properties of an Eu ( III ) - MWCNTs - based nanocomposite PNIPAAm hydrogel is induced upon application of a 10 T magnetic field, the latter dictating the alignment of the carbon nanotubes.", "output": "Eu ( III ), carbon." }, { "input": "This structuration creates directional highways for light to be preferentially absorbed, giving rise to orientation - dependent light emission intensity.", "output": "There is no related enetity." }, { "input": "Thermal control of the transparency of the aqueous matrix also allowed a stimulus - induced switching of the materials ' emission properties.", "output": "There is no related enetity." }, { "input": "The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation.", "output": "phenethyl isothiocyanate." }, { "input": "Phenethylisothiocyanate ( PEITC ), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 ( P450 ) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens.", "output": "Phenethylisothiocyanate, PEITC, isothiocyanate." }, { "input": "PEITC has been reported to be a mechanism - based inactivator of some P450s.", "output": "PEITC." }, { "input": "We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC.", "output": "PEITC, PEITC." }, { "input": "PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione ( GSH ) and not fully recovered by dialysis.", "output": "PEITC, glutathione, GSH." }, { "input": "The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation.", "output": "PEITC." }, { "input": "GSH - adducts of phenethyl isocyanate ( PIC ) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450 - catalyzed desulfurization of PEITC.", "output": "GSH, phenethyl isocyanate, PIC, phenethylamine, PIC, PEITC." }, { "input": "Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme.", "output": "PIC." }, { "input": "Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo - protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1.", "output": "sulfur, PEITC." }, { "input": "Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur - containing compounds, such as parathion.", "output": "PEITC, sulfur, parathion." }, { "input": "Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC.", "output": "Cys, PIC." }, { "input": "Metal - enzyme frameworks: role of metal ions in promoting enzyme self - assembly on alpha - zirconium ( IV ) phosphate nanoplates.", "output": "alpha - zirconium ( IV ) phosphate." }, { "input": "Previously, an ion - coupled protein binding ( ICPB ) model was proposed to explain the thermodynamics of protein binding to negatively charged alpha - Zr ( IV ) phosphate ( alpha - ZrP ).", "output": "alpha - Zr ( IV ) phosphate, alpha - ZrP." }, { "input": "This model is tested here using glucose oxidase ( GO ) and met - hemoglobin ( Hb ) and several cations ( Zr ( IV ), Cr ( III ), Au ( III ), Al ( III ), Ca ( II ), Mg ( II ), Zn ( II ), Ni ( II ), Na ( I ), and H ( I ) ).", "output": "glucose, Zr ( IV ), Cr ( III ), Au ( III ), Al ( III ), Ca ( II ), Mg ( II ), Zn ( II ), Ni ( II ), Na ( I ), H ( I )." }, { "input": "The binding constant of GO with alpha - ZrP was increased ~ 380 - fold by the addition of either 1 mM Zr ( IV ) or 1 mM Ca ( II ), and affinities followed the trend Zr ( IV ) ~ Ca ( II ) > Cr ( III ) > Mg ( II ) >> H ( I ) > Na ( I ).", "output": "alpha - ZrP, Zr ( IV ), Ca ( II ), Zr ( IV ), Ca ( II ), Cr ( III ), Mg ( II ), H ( I ), Na ( I )." }, { "input": "Binding studies could not be conducted with Au ( III ), Al ( III ), Zn ( II ), Cu ( II ), and Ni ( II ), as these precipitated both proteins.", "output": "Au ( III ), Al ( III ), Zn ( II ), Cu ( II ), Ni ( II )." }, { "input": "Zr ( IV ) increased Hb binding constant to alpha - ZrP by 43 - fold, and affinity enhancements followed the trend Zr ( IV ) > H ( I ) > Mg ( II ) > Na ( I ) > Ca ( II ) > Cr ( III ).", "output": "Zr ( IV ), alpha - ZrP, Zr ( IV ), H ( I ), Mg ( II ), Na ( I ), Ca ( II ), Cr ( III )." }, { "input": "Zeta potential studies clearly showed metal ion binding to alpha - ZrP and affinities followed the trend, Zr ( IV ) >> Cr ( III ) > Zn ( II ) > Ni ( II ) > Mg ( II ) > Ca ( II ) > Au ( III ) > Na ( I ) > H ( I ).", "output": "alpha - ZrP, Zr ( IV ), Cr ( III ), Zn ( II ), Ni ( II ), Mg ( II ), Ca ( II ), Au ( III ), Na ( I ), H ( I )." }, { "input": "Electron microscopy showed highly ordered structures of protein / metal / alpha - ZrP intercalates on micrometer length scales, and protein intercalation was also confirmed by powder X - ray diffraction.", "output": "alpha - ZrP." }, { "input": "Specific activities of GO / Zr ( IV ) / alpha - ZrP and Hb / Zr ( IV ) / alpha - ZrP ternary complexes were 2. 0 x 10 ( - 3 ) and 6. 5 x 10 ( - 4 ) M ( - 1 ) s ( - 1 ), respectively.", "output": "Zr ( IV ), alpha - ZrP, Zr ( IV ), alpha - ZrP." }, { "input": "While activities of all GO / cation / alpha - ZrP samples were comparable, those of Hb / cation / alpha - ZrP followed the trend Mg ( II ) > Na ( I ) > H ( I ) > Cr ( III ) > Ca ( II ) ~ Zr ( IV ).", "output": "alpha - ZrP, alpha - ZrP, Mg ( II ), Na ( I ), H ( I ), Cr ( III ), Ca ( II ), Zr ( IV )." }, { "input": "Metal ions enhanced protein binding by orders of magnitude, as predicted by the ICPB model, and binding enhancements depended on charge as well as the phosphophilicity / oxophilicity of the cation.", "output": "There is no related enetity." }, { "input": "Reaction - diffusion framework: the mechanism of the polymorphic transition of alpha - to beta - cobalt hydroxide.", "output": "alpha - to beta - cobalt hydroxide." }, { "input": "A new and simple method is proposed to explore the mechanism of the intercalation / deintercalation of a variety of anions throughout the formation of alpha - Co ( OH ) 2 crystals and their polymorphic conversion to beta - Co ( OH ) 2.", "output": "alpha - Co ( OH ) 2, beta - Co ( OH ) 2." }, { "input": "This method is based on the reaction - diffusion of hydroxide ions in a gel matrix containing the cobalt salt.", "output": "hydroxide, cobalt." }, { "input": "The spatiotemporal evolution of each polymorph and their interaction is revealed by tracking the location of the two sharp interfaces between the two polymorphs ( conversion zone ) and between the gel and alpha - Co ( OH ) 2 ( formation zone ) and by measuring the weight composition of each zone.", "output": "alpha - Co ( OH ) 2." }, { "input": "We thereby find that the dynamics of the transformation reaction are correctly described by the two - dimensional Avrami - Erofe ' ev equation at different temperatures.", "output": "There is no related enetity." }, { "input": "The data suggest that the structural redistribution of the atoms inside the alpha - Co ( OH ) 2 particles plays the fundamental role in establishing the overall rate of the reaction.", "output": "alpha - Co ( OH ) 2." }, { "input": "On the other hand, we notice that other factors such as the nature of the intercalated anions and the concentration of the polymer matrix alter considerably the final rate of the transition reaction through increasing the stability of the alpha phase.", "output": "There is no related enetity." }, { "input": "Investigation of the conformational changes of a conducting polymer in gas sensor active layers by means of polarization - modulation infrared reflection absorption spectroscopy ( PM - IRRAS ).", "output": "There is no related enetity." }, { "input": "Polarization - Modulation Infrared Reflection Absorption Spectroscopy ( PM - IRRAS ) was employed to observe the changes in the molecular conformation of poly ( 2 - phenyl - 1, 4 - xylylene ) ( PPPX ) films that occurred after exposure to organic solvent vapors.", "output": "poly ( 2 - phenyl - 1 , 4 - xylylene ), PPPX." }, { "input": "The PPPX films were supported on solid matrixes by casting, spin - coating, and Langmuir - Blodgett ( LB ) techniques.", "output": "PPPX." }, { "input": "The results show that the polymer is sensitive to the solvent vapors, which affect some of the vibration dipole moments, as detected by PM - IRRAS.", "output": "There is no related enetity." }, { "input": "The sensitivity depends on the method employed to immobilize the polymer, with more significant changes in films formed using techniques that result in a less systematically organized conformation.", "output": "There is no related enetity." }, { "input": "This feature enables the use of surface vibration spectroscopy to detect organic solvent vapors and may be applied in an artificial nose.", "output": "There is no related enetity." }, { "input": "Schisandra lignans - loaded enteric nanoparticles: preparation, characterization, and in vitro - in vivo evaluation.", "output": "lignans." }, { "input": "Schisandrae lignans ( SL ) have been well proven to possess hepatoprotective effect against the hepatic dysfunction induced by various chemical hepatotoxins.", "output": "lignans." }, { "input": "Deoxyschisandrin ( DA ) and schisantherin A ( SA ) are both considered as the major active components in SL.", "output": "Deoxyschisandrin, schisantherin A." }, { "input": "The objective of the study was to prepare and evaluate Schisandra lignans ( composed of DA and SA ) - loaded enteric nanoparticles produced by a novel toxic solvent - free modified spontaneous emulsification solvent diffusion ( SESD ) method.", "output": "lignans." }, { "input": "An organic Schisandra lignans / Eudragit ( (R) ) S100 solution was injected into an aqueous poloxamer 188 solution under a agitation.", "output": "lignans, Eudragit, poloxamer 188." }, { "input": "The nanoparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency ( EE ) and physical stability of the drug, wettability, in vitro release and in vivo bioavailability.", "output": "There is no related enetity." }, { "input": "Nanoparticles with a smooth surface and dense structure were obtained with high EE ( EE ( DA ) > 90 %; EE ( SA ) > 85 % ).", "output": "There is no related enetity." }, { "input": "The drug was in a noncrystalline state in the matrix and physically stable for 120 days at room temperature.", "output": "There is no related enetity." }, { "input": "In vitro drug release study, the drug dissolution rate from the nanoparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the nanoparticles was stable after 120 days.", "output": "There is no related enetity." }, { "input": "The appropriate size of nanoparticles ( ~ 93 nm ), the solubilization of the surfactant, the noncrystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the nanoparticles when compared to pure drug suspension.", "output": "There is no related enetity." }, { "input": "Stabilization of iron oxide nanoparticles in high sodium and calcium brine at high temperatures with adsorbed sulfonated copolymers.", "output": "iron oxide, sodium, calcium." }, { "input": "A series of sulfonated random and block copolymers were adsorbed on the surface of ~ 100 nm iron oxide ( IO ) nanoparticles ( NPs ) to provide colloidal stability in extremely concentrated brine composed of 8 % wt NaCl + 2 % wt CaCl2 ( API brine; 1. 4 M NaCl + 0. 2 M CaCl2 ) at 90 degrees C.", "output": "iron oxide, NaCl, CaCl2, NaCl, CaCl2." }, { "input": "A combinatorial materials chemistry approach, which employed Ca ( 2 + ) - mediated adsorption of anionic acrylic acid - containing sulfonated polymers to preformed citrate - stabilized IO nanoclusters, enabled the investigation of a large number of polymer coatings.", "output": "Ca ( 2 + ), acrylic acid, citrate." }, { "input": "Initially a series of poly ( 2 - methyl - 2 - acrylamidopropanesulfonate - co - acrylic acid ) ( poly ( AMPS - co - AA ) ) ( 1: 8 to 1: 1 mol: mol ), poly ( styrenesulfonate - block - acrylic acid ) ( 2. 4: 1 mol: mol ), and poly ( styrenesulfonate - alt - maleic acid ) ( 3: 1 mol: mol ) copolymers were screened for solubility in API brine at 90 degrees C.", "output": "poly ( 2 - methyl - 2 - acrylamidopropanesulfonate - co - acrylic acid ), poly ( AMPS - co - AA ), poly ( styrenesulfonate - block - acrylic acid ), poly ( styrenesulfonate - alt - maleic acid )." }, { "input": "The ratio of AMPS to AA groups was varied to balance the requirement of colloid dispersibility at high salinity ( provided by AMPS ) against the need for anchoring of the polymers to the iron oxide surface ( via the AA ).", "output": "AMPS, AMPS, iron oxide." }, { "input": "Steric stabilization of IO NPs coated with poly ( AMPS - co - AA ) ( 1: 1 mol: mol ) provided colloidal stability in API brine at room temperature and 90 degrees C for up to 1 month.", "output": "poly ( AMPS - co - AA )." }, { "input": "The particles were characterized before and after coating at ambient and elevated temperatures by a variety of techniques including colloidal stability experiments, dynamic light scattering, zeta potential, and thermogravimetric analysis.", "output": "There is no related enetity." }, { "input": "Pulsed magnetic field improves the transport of iron oxide nanoparticles through cell barriers.", "output": "iron oxide." }, { "input": "Understanding how a magnetic field affects the interaction of magnetic nanoparticles ( MNPs ) with cells is fundamental to any potential downstream applications of MNPs as gene and drug delivery vehicles.", "output": "There is no related enetity." }, { "input": "Here, we present a quantitative analysis of how a pulsed magnetic field influences the manner in which MNPs interact with and penetrate across a cell monolayer.", "output": "There is no related enetity." }, { "input": "Relative to a constant magnetic field, the rate of MNP uptake and transport across cell monolayers was enhanced by a pulsed magnetic field.", "output": "There is no related enetity." }, { "input": "MNP transport across cells was significantly inhibited at low temperature under both constant and pulsed magnetic field conditions, consistent with an active mechanism ( i. e., endocytosis ) mediating MNP transport.", "output": "There is no related enetity." }, { "input": "Microscopic observations and biochemical analysis indicated that, in a constant magnetic field, transport of MNPs across the cells was inhibited due to the formation of large ( > 2 mu m ) magnetically induced MNP aggregates, which exceeded the size of endocytic vesicles.", "output": "There is no related enetity." }, { "input": "Thus, a pulsed magnetic field enhances the cellular uptake and transport of MNPs across cell barriers relative to a constant magnetic field by promoting accumulation while minimizing magnetically induced MNP aggregation at the cell surface.", "output": "There is no related enetity." }, { "input": "Recent advancements in small molecule inhibitors of insulin - like growth factor - 1 receptor ( IGF - 1R ) tyrosine kinase as anticancer agents.", "output": "tyrosine." }, { "input": "Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer inhuman, have driven the current cancer chemotherapy to intently focus on development of target - based approaches rather than conventional approaches.", "output": "There is no related enetity." }, { "input": "From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases ( PTKs ) have been exploited the most.", "output": "tyrosine." }, { "input": "Insulin receptors ( IRs ), insulin like growth factor receptors ( IGF - 1R ) and their hybrid receptors belong to tyrosine kinase receptor ( TKR ) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF - 1 or IGF - 2.", "output": "tyrosine." }, { "input": "The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells.", "output": "steroidal hormones." }, { "input": "Various strategies such as anti - IGF - 1R antibodies, IGF - 1 mimetic peptides, antisense strategies, IGF - 1R specific peptide aptamers, targeted degradation of IGF - 1R and expression of dominant negative IGF - 1R mutants have been explored to inhibit the IGF - 1R signaling.", "output": "There is no related enetity." }, { "input": "However, targeting IGF - 1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption, distribution, metabolism, excretion and toxicity ( ADMET ) parameters, oral route of administration, lesser side effects and cost effectiveness.", "output": "There is no related enetity." }, { "input": "The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF - 1R active or allosteric sites reported till date.", "output": "There is no related enetity." }, { "input": "Enhancing the efficacy of Ara - C through conjugation with PAMAM dendrimer and linear PEG: a comparative study.", "output": "Ara - C, PAMAM, PEG." }, { "input": "1 beta - d - Arabinofuranosylcytosine ( Cytarabine, Ara - C ) is a key drug in the treatment of acute myeloid leukemia.", "output": "1 beta - d - Arabinofuranosylcytosine, Cytarabine, Ara - C." }, { "input": "Ara - C has a number of limitations such as a rapid deactivation by cytidine deaminase leading to the formation of a biologically inactive metabolite, Ara - U ( 1 beta - d - arabinofuranosyluracil ), a low lipophilicity, and fast clearance from the body.", "output": "Ara - C, cytidine, Ara - U, 1 beta - d - arabinofuranosyluracil." }, { "input": "To address these problems, we developed a conjugate in which hydroxyl - terminated PAMAM dendrimer, G4 - OH [ \" D \" ] and PEG were used as carriers for the drug ( Ara - C ).", "output": "hydroxyl, PAMAM, OH, PEG, Ara - C." }, { "input": "The conjugates were synthesized using an efficient multistep protection / deprotection method resulting in the formation of a covalent bond between the primary hydroxyl group of Ara - C and dendrimer / PEG.", "output": "hydroxyl, Ara - C, PEG." }, { "input": "The structure, physicochemical properties, and drug release kinetics were characterized extensively.", "output": "There is no related enetity." }, { "input": "( 1 ) H NMR and MALDI - TOF mass spectrometry suggested covalent attachment of 10 Ara - C molecules to the dendrimer.", "output": "( 1 ) H, Ara - C." }, { "input": "The release profile of Ara - C in human plasma and in PBS buffer ( pH 7. 4 ) showed that the conjugates released the drug over 14 days in PBS, with the release sped up in plasma.", "output": "Ara - C." }, { "input": "In PBS, while most of the drug is released from PEG - Ara - C, the dendrimer continues to release the drug in a sustained fashion.", "output": "PEG, Ara - C." }, { "input": "The results also suggested that the formation of the inactive form of Ara - C ( Ara - U ) was delayed upon conjugation of Ara - C to the polymers.", "output": "Ara - C, Ara - U, Ara - C." }, { "input": "The inhibition of cancer growth by the dendrimer - Ara - C and PEG - Ara - C conjugates was evaluated in A549 human adenocarcinoma epithelial cells.", "output": "Ara - C, PEG, Ara - C." }, { "input": "Both dendrimer - and PEG - Ara - C conjugates were 4 - fold more effective in inhibition of A549 cells compared to free Ara - C after 72 h of treatment.", "output": "PEG, Ara - C, Ara - C." }, { "input": "Catalytic hydrotrifluoromethylation of unactivated alkenes.", "output": "alkenes." }, { "input": "A visible - light - mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF ( 3 ) source and MeOH as the reductant is disclosed.", "output": "alkenes, CF ( 3 ), MeOH." }, { "input": "This effective transformation operates at room temperature in the presence of 5 mol % Ru ( bpy ) ( 3 ) Cl ( 2 ); the process is characterized by its operational simplicity and functional group tolerance.", "output": "Ru ( bpy ) ( 3 ) Cl ( 2 )." }, { "input": "Discovery of a potential anti - inflammatory agent: 3 - oxo - 29 - noroleana - 1, 9 ( 11 ), 12 - trien - 2, 20 - dicarbonitrile.", "output": "3 - oxo - 29 - noroleana - 1 , 9 ( 11 ) , 12 - trien - 2 , 20 - dicarbonitrile." }, { "input": "Fifteen novel derivatives of glycyrrhetinic acid ( GA ) were synthesized and evaluated for anti - inflammatory activities.", "output": "glycyrrhetinic acid." }, { "input": "It was found that the introduction of 1 - en - 3 - one and 9 ( 11 ), 12 - diene and 2, 20 - dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS - induced NO production.", "output": "1 - en - 3 - one, 9 ( 11 ) , 12 - diene, 2 , 20 - dinitrile, NO." }, { "input": "Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase ( iNOS ) and the mRNA expression of TNF - alpha, IL - 6, and IL - 1 beta in LPS - stimulated RAW 264. 7 macrophages.", "output": "NO." }, { "input": "Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of I kappa B - alpha, as well as the ratio of nuclear / cytosolic content of p65.", "output": "There is no related enetity." }, { "input": "Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS - induced sepsis shock.", "output": "There is no related enetity." }, { "input": "It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor.", "output": "NO." }, { "input": "Synthesis and micellar mimic properties of bile acid trimers.", "output": "bile acid." }, { "input": "Two fan - shaped bile acid trimers have been synthesized via Cu ( I ) - catalyzed azide - alkyne cycloaddition ( CuAAC ) ' click chemistry ', and their extraction experiments of cresol red sodium ( CR ) and pyrene were investigated in the polar and non - polar solvents, respectively.", "output": "bile acid, Cu ( I ), azide - alkyne, cresol red sodium, pyrene." }, { "input": "The transmission electron microscopy ( TEM ) results showed that the homogenous hollow capsules formed with the diameter size range of 40 - 70 nm in a solution of water and acetone.", "output": "acetone." }, { "input": "Thus the amphiphilicity of fan - shaped bile acid trimers might be used as the promising candidate in biological and drug delivery applications.", "output": "bile acid." }, { "input": "1 - ( 4 - Phenylpiperazin - 1 - yl ) - 2 - ( 1H - pyrazol - 1 - yl ) ethanones as novel CCR1 antagonists.", "output": "1 - ( 4 - Phenylpiperazin - 1 - yl ) - 2 - ( 1H - pyrazol - 1 - yl ) ethanones." }, { "input": "A novel series of CCR1 antagonists based on the 1 - ( 4 - phenylpiperazin - 1 - yl ) - 2 - ( 1H - pyrazol - 1 - yl ) ethanone scaffold was identified by screening a compound library utilizing CCR1 - expressing human THP - 1 cells.", "output": "1 - ( 4 - phenylpiperazin - 1 - yl ) - 2 - ( 1H - pyrazol - 1 - yl ) ethanone." }, { "input": "SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 ( CCR1 binding IC ( 50 ) = 4 nM using [ ( 125 ) I ] - CCL3 as the chemokine ligand ).", "output": "[ ( 125 ) I ] - CCL3." }, { "input": "Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species.", "output": "There is no related enetity." }, { "input": "Inhibition of monoamine oxidase by phthalide analogues.", "output": "monoamine, phthalide." }, { "input": "Based on recent reports that the small molecules, isatin and phthalimide, are suitable scaffolds for the design of high potency monoamine oxidase ( MAO ) inhibitors, the present study examines the MAO inhibitory properties of a series of phthalide [ 2 - benzofuran - 1 ( 3H ) - one ] analogues.", "output": "isatin, phthalimide, monoamine, phthalide, 2 - benzofuran - 1 ( 3H ) - one." }, { "input": "Phthalide is structurally related to isatin and phthalimide and it is demonstrated here that substitution at C6 of the phthalide moiety yields compounds endowed with high binding affinities to both human MAO isoforms.", "output": "Phthalide, isatin, phthalimide, phthalide." }, { "input": "Among the nineteen homologues evaluated, the lowest IC ( 50 ) values recorded for the inhibition of MAO - A and - B were 0. 096 and 0. 0014 mu M, respectively.", "output": "There is no related enetity." }, { "input": "In most instances, C6 - substituted phthalides exhibit MAO - B specific inhibition.", "output": "phthalides." }, { "input": "Among a series of 6 - benzyloxyphthalides bearing substituents on the para position of the phenyl ring the general order of potency was CF ( 3 ) > I > Br > Cl > F > CH ( 3 ) > H.", "output": "6 - benzyloxyphthalides, phenyl, CF ( 3 ), I, Br, Cl, F, CH ( 3 ), H." }, { "input": "The results also show that the binding modes of representative phthalides are reversible and competitive at both MAO isoforms.", "output": "phthalides." }, { "input": "Based on these data, C6 - substituted phthalides may serve as leads for the development of therapies for neurodegenerative disorders such as Parkinson ' s disease.", "output": "C6, phthalides." }, { "input": "Synthesis, crystal structure and antibacterial activity of new highly functionalized ionic compounds based on the imidazole nucleus.", "output": "imidazole." }, { "input": "Several new highly functionalized imidazolium derivatives were synthesized, via appropriate synthetic routes, using imidazole, 1 - methylimidazole and 2 - phenyl - 1 - methylimidazole as key intermediates.", "output": "imidazolium, imidazole, 1 - methylimidazole, 2 - phenyl - 1 - methylimidazole." }, { "input": "The antibacterial activity of the prepared compounds was evaluated against: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella thipymurium using disk - diffusion and MIC methods.", "output": "There is no related enetity." }, { "input": "Crystal X - ray structures are reported for six compounds.", "output": "There is no related enetity." }, { "input": "Potent and selective tariquidar bioisosters as potential PET radiotracers for imaging P - gp.", "output": "tariquidar." }, { "input": "Compounds 8a - d have been designed as bioisosters of tariquidar for imaging P - gp expression and density by PET.", "output": "tariquidar." }, { "input": "The results displayed that compounds 8b and 8d could be considered potential P - gp / BCRP ligands suitable as ( 11 ) C and ( 18 ) F radiotracers, respectively.", "output": "( 11 ) C, ( 18 ) F." }, { "input": "Chemometrics - Based Approach to Feature Selection of Chromatographic Profiles and its Application to Search Active Fraction of Herbal Medicine.", "output": "There is no related enetity." }, { "input": "In our previous report ( J Pharmaceut Biomed 56 ( 2011 ) 443 - 447 ), a support vector machine ( SVM ) - based pharmacodynamic model was established for predicting active fractions of herbal medicines ( HMs ), where information contents embedded in the chromatograms of the fractions were represented with the peak areas.", "output": "There is no related enetity." }, { "input": "However, in this representation the global characteristics of the chromatograms were completely missed, which is definitely contrary to the global and holistic views in theories of HMs and undoubtedly reduce the success rate of this model.", "output": "There is no related enetity." }, { "input": "To deal with the challenge, two chemometrics methods, that is, minimum redundancy maximum relevance ( mRMR ) and particle swarm optimizer ( PSO ), were applied in this article for feature selection of the whole chromatograms, and the PSO was also used to tune the SVM parameters.", "output": "There is no related enetity." }, { "input": "As a case, a sample HM, that is, Xiangdan injection, was investigated.", "output": "There is no related enetity." }, { "input": "The predictive accuracy was fully evaluated and compared with those by other popular and reported methods.", "output": "There is no related enetity." }, { "input": "Furthermore, the confirmation on the independent predicting set exhibited that the predicted bioactivities were well consistent with the experimental values.", "output": "There is no related enetity." }, { "input": "The important potential application of the present model is to be extended to help search active fractions of other HMs.", "output": "There is no related enetity." }, { "input": "Activity cliffs: facts or artifacts?", "output": "There is no related enetity." }, { "input": "The fact that similar compounds may have very different properties has a large impact in several areas of chemistry.", "output": "There is no related enetity." }, { "input": "In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large ' jumps ' in activity due to small changes in structure, that is, activity cliffs.", "output": "There is no related enetity." }, { "input": "A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure - activity relationships ( SAR ) in compound data sets.", "output": "There is no related enetity." }, { "input": "Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution because one may identify ' false positive cliffs '.", "output": "There is no related enetity." }, { "input": "In addition to apparent cliffs due to inaccurate determinations of activity, computationally identified cliffs can be artifacts attributed to the molecular representation and quantitative definition of ' high ' structural similarity.", "output": "There is no related enetity." }, { "input": "This paper brings together and discusses, in a brief and integrated manner, some of the major aspects that raise the question whether all the activity cliffs detected in compound data sets are facts or artifacts.", "output": "There is no related enetity." }, { "input": "Structural basis for autoinhibition of the guanine nucleotide exchange factor FARP2.", "output": "guanine nucleotide." }, { "input": "FARP2 is a Dbl - family guanine nucleotide exchange factor ( GEF ) that contains a 4. 1, ezrin, radixin and moesin ( FERM ) domain, a Dbl - homology ( DH ) domain and two pleckstrin homology ( PH ) domains.", "output": "guanine nucleotide." }, { "input": "FARP2 activates Rac1 or Cdc42 in response to upstream signals, thereby regulating processes such as neuronal axon guidance and bone homeostasis.", "output": "There is no related enetity." }, { "input": "How the GEF activity of FARP2 is regulated remained poorly understood.", "output": "There is no related enetity." }, { "input": "We have determined the crystal structures of the catalytic DH domain and the DH - PH - PH domains of FARP2.", "output": "There is no related enetity." }, { "input": "The structures reveal an auto - inhibited conformation in which the GEF substrate - binding site is blocked collectively by the last helix in the DH domain and the two PH domains.", "output": "There is no related enetity." }, { "input": "This conformation is stabilized by multiple interactions among the domains and two well - structured inter - domain linkers.", "output": "There is no related enetity." }, { "input": "Our cell - based activity assays confirm the suppression of the FARP2 GEF activity by these auto - inhibitory elements.", "output": "There is no related enetity." }, { "input": "Chronic, low concentration exposure to pharmaceuticals impacts multiple organ systems in zebrafish.", "output": "There is no related enetity." }, { "input": "Pharmaceuticals are found in both receiving and drinking water due to their persistent release in waste - water effluents, raising concerns for environmental and human health.", "output": "There is no related enetity." }, { "input": "Chronic, aqueous exposure of zebrafish ( Danio rerio ) to environmentally relevant concentrations of acetaminophen ( ACE ), venlafaxaine ( VEN ) ( 10 mu gL ( - 1 ) ), carbamazepine ( CBZ ) and gemfibrozil ( GEM ) ( 0. 5 and 10 mu gL ( - 1 ) ) decreased reproductive output.", "output": "acetaminophen, ACE, venlafaxaine, VEN, carbamazepine, CBZ, gemfibrozil, GEM." }, { "input": "Atretic oocytes and altered ovarian histology were seen in female zebrafish exposed to CBZ and GEM, suggesting a direct effect on oocyte development that may account for the reduced fecundity.", "output": "CBZ, GEM." }, { "input": "Apoptosis within the theca and granulosa cells was identified in exposed female zebrafish with atretic oocytes by TUNEL positive staining.", "output": "There is no related enetity." }, { "input": "The incidence of follicular apoptosis was nearly 2 - fold higher in exposed females than the controls.", "output": "There is no related enetity." }, { "input": "All compounds significantly altered kidney proximal tubule morphology but there was no difference in the incidence of apoptotic cells within the kidney between control and exposed in either males or females.", "output": "There is no related enetity." }, { "input": "Liver histology was altered by ACE and GEM exposure.", "output": "ACE, GEM." }, { "input": "Parental exposure to pharmaceuticals did not increase developmental abnormalities, hatching success, or mortality in embryos.", "output": "There is no related enetity." }, { "input": "Yet, direct exposure of embryos to ACE increased developmental abnormalities and mortality; exposure to 0. 5 mu gL ( - 1 ) of all pharmaceuticals increased mortality.", "output": "ACE." }, { "input": "CBZ decreased plasma 11 - ketotestosterone concentrations in males and females.", "output": "CBZ, 11 - ketotestosterone." }, { "input": "Overall, these data suggest that low concentration, chronic exposure of fish to pharmaceuticals impacts fish development as well as multiple organ systems in adult fish, leading to effects on reproduction and histology of liver and kidney.", "output": "There is no related enetity." }, { "input": "These results are significant in understanding the consequences of chronic, low concentration pharmaceutical exposure to fish and suggest that exposed populations are at risk of negative impacts to reproduction and health.", "output": "There is no related enetity." }, { "input": "Exposure to an organochlorine pesticide ( chlordecone ) and development of 18 - month - old infants.", "output": "organochlorine, chlordecone." }, { "input": "Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control.", "output": "Chlordecone, organochlorine." }, { "input": "Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food.", "output": "There is no related enetity." }, { "input": "Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development.", "output": "chlordecone." }, { "input": "This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth - cohort of Guadeloupean children.", "output": "chlordecone." }, { "input": "In a prospective longitudinal study conducted in Guadeloupe ( Timoun mother - child cohort study ), exposure to chlordecone was measured at birth from an umbilical cord blood sample ( n = 141 ) and from a breast milk sample collected at 3 months postpartum ( n = 75 ).", "output": "chlordecone." }, { "input": "Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire.", "output": "There is no related enetity." }, { "input": "Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores.", "output": "chlordecone." }, { "input": "When analyses were conducted separately for boys and girls, this effect was only observed among boys.", "output": "There is no related enetity." }, { "input": "These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.", "output": "chlordecone, organochlorine." }, { "input": "Synthesis of novel 16 - spiro steroids: Spiro - 7 ' - ( aryl ) tetrahydro - 1H - pyrrolo [ 1, 2 - c ] [ 1, 3 ] thiazolo - trans - androsterone hybrid heterocycles.", "output": "16 - spiro steroids, Spiro - 7 ' - ( aryl ) tetrahydro - 1H - pyrrolo [ 1 , 2 - c ] [ 1 , 3 ] thiazolo - trans - androsterone." }, { "input": "The 1, 3 - dipolar cycloaddition of azomethine ylide derived in situ from the reaction of acenaphthylene - 1, 2 - dione and 1, 3 - thiazolane - 4 - carboxylic acid to various exocyclic dipolarophiles synthesized from trans - androsterone and trans - dehydroandrosterone afforded a library of novel spiro [ 5 '. 2 '' ] acenaphthylene - 1 '' - one - spiro [ 16. 6 ' ] - ( 7 ' - aryl ) - tetrahydro - 1H - pyrrolo [ 1, 2 - c ] [ 1, 3 ] thiazolo - trans - androsterone / dehydroandrosterone hybrid heterocycles respectively.", "output": "azomethine, acenaphthylene - 1 , 2 - dione, 1 , 3 - thiazolane - 4 - carboxylic acid, trans - androsterone, trans - dehydroandrosterone, spiro [ 5 ' . 2 '' ] acenaphthylene - 1 '' - one - spiro [ 16 . 6 ' ] - ( 7 ' - aryl ) - tetrahydro - 1H - pyrrolo [ 1 , 2 - c ] [ 1 , 3 ] thiazolo - trans - androsterone, dehydroandrosterone." }, { "input": "These reactions proceeded stereo - specifically affording a single isomer of the 16 - spiro steroids in excellent yields.", "output": "16 - spiro steroids." }, { "input": "p63 involvement in poly ( ADP - ribose ) polymerase 1 signaling of topoisomerase I - dependent DNA damage in carcinoma cells.", "output": "poly ( ADP - ribose )." }, { "input": "Poly ( ADP - ribose ) polymerase 1 ( PARP - 1 ) inhibitors are thought as breakthrough for cancer treatment in solid tumors such as breast cancer through their effects on PARP ' s enzymatic activity.", "output": "Poly ( ADP - ribose )." }, { "input": "Our previous findings showed that the hydrophilic PARP inhibitor PJ34 enhances the sensitivity of p53 proficient MCF7 breast carcinoma cells to topotecan, a DNA Topoisomerase I ( TOP 1 ) inhibitor.", "output": "There is no related enetity." }, { "input": "In the present study, we combine the classical TOP 1 poison camptothecin or its water - soluble derivative topotecan with PJ34 to investigate the potentiation of chemotherapeutic efficiency in MCF7 ( p53 ( WT ) ), MDA - MB231 ( p53 ( mut ) ) breast carcinoma cells and SCC022 ( p53 ( null ) ) squamous carcinoma cells.", "output": "camptothecin, topotecan, PJ34." }, { "input": "We show that, following TPT - PJ34 combined treatment, MCF7 cells exhibit apoptotic death while MDA - MB231 and SCC022 cells are more resistant to these agents.", "output": "TPT, PJ34." }, { "input": "Specifically, in MCF7, ( i ) PJ34 in combination with TPT causes a G2 / M cell cycle arrest followed by massive apoptosis; ( ii ) PJ34 addition reverts TPT - dependent PARP - 1 automodification and triggers caspase - dependent PARP - 1 proteolysis; ( iii ) TPT, used as a single agent, stimulates p53 expression while in combination with PJ34 increases p53, TAp63 alpha and TAp63 gamma protein levels with a concomitant reduction of MDM2 protein.", "output": "PJ34, TPT, PJ34, TPT, TPT, PJ34." }, { "input": "The identification of p63 proteins as new players involved in the cancer cell response to TPT - PJ34 is relevant for a better understanding of the PARP1 - dependent signaling of DNA damage.", "output": "TPT, PJ34." }, { "input": "Furthermore, our data indicate that, in response to TPT - PJ34 combined chemotherapy, a functional cooperation between p53 and TAp63 proteins may occur and be essential to trigger apoptotic cell death.", "output": "TPT, PJ34." }, { "input": "Sesquiterpenes from the rhizomes of Alpinia japonica and their inhibitory effects on nitric oxide production.", "output": "Sesquiterpenes, nitric oxide." }, { "input": "A novel norsesquiterpene ( 1 ), three new bisabolenes sesquiterpenes ( 2 - 4 ), along with 7 known compounds ( 5 - 11 ), were isolated from the rhizomes of Alpinia japonica.", "output": "bisabolenes, sesquiterpenes." }, { "input": "The structures of the new compounds were elucidated by analysis of spectroscopic data.", "output": "There is no related enetity." }, { "input": "The absolute configuration of C - 1 in 3 was deduced via the circular dichroism data of the in situ formed [ Rh2 ( OCOCF3 ) 4 ] complexes.", "output": "[ Rh2 ( OCOCF3 ) 4 ]." }, { "input": "Inhibitory effects of the isolates on nitric oxide production in lipopolysaccaride - activated RAW264. 7 macrophages were evaluated.", "output": "nitric oxide." }, { "input": "Compound 6 showed significant inhibitory activity with IC50 value of 5. 3 mu Mu, and compounds 1, 3, 5 and 7 - 10 exhibited moderate inhibitory activities with IC50 values between 24. 5 and 46. 3 mu M.", "output": "There is no related enetity." }, { "input": "Liposomes modified with P - aminophenyl - alpha - d - mannopyranoside: A carrier for targeting cerebral functional regions in mice.", "output": "P - aminophenyl - alpha - d - mannopyranoside." }, { "input": "Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood - brain barrier ( BBB ) and by poor accumulation in these regions.", "output": "There is no related enetity." }, { "input": "To overcome these hurdles, liposomes modified with P - aminophenyl - alpha - d - mannopyranoside ( MAN ) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes ( LIP ) modified with MAN ( MAN - LIP ) to target various functional regions of the brain.", "output": "P - aminophenyl - alpha - d - mannopyranoside, MAN, MAN, MAN." }, { "input": "An in vitro BBB model was established to evaluate the transendothelial ability of MAN - LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging.", "output": "MAN." }, { "input": "Liposome targeting was evaluated using in vivo and ex vivo imaging.", "output": "There is no related enetity." }, { "input": "After MAN - LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased.", "output": "MAN." }, { "input": "MAN - LIP concentrated in the cortex at 4h, shifting distribution to the cerebellum and brainstem at 12h.", "output": "MAN." }, { "input": "The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12h.", "output": "There is no related enetity." }, { "input": "The results demonstrate that MAN - LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio - temporal pattern.", "output": "MAN." }, { "input": "Inhibition of protein tyrosine phosphatases in spinal dorsal horn attenuated inflammatory pain by repressing Src signaling.", "output": "tyrosine." }, { "input": "Tyrosine phosphorylation of N - methyl - d - aspartate ( NMDA ) subtype glutamate receptors by Src - family protein tyrosine kinases ( SFKs ) plays a critical role in spinal sensitization.", "output": "Tyrosine, N - methyl - d - aspartate, NMDA, glutamate, tyrosine." }, { "input": "Besides SFKs, the tyrosine phosphorylation levels of proteins are also determined by protein tyrosine phosphatases ( PTPs ).", "output": "tyrosine, tyrosine." }, { "input": "However, whether PTPs are involved in spinal nociceptive processing is largely unknown.", "output": "There is no related enetity." }, { "input": "The present study found that intrathecal application of broad - spectrum PTPs inhibitors orthovanadate or Bpv ( phen ) generated little effects on the paw withdrawal thresholds of intact rats to Von Frey filament stimuli.", "output": "orthovanadate, Bpv ( phen )." }, { "input": "Although the basal nociceptive responses didn ' t require the involvement of PTPs, the mechanical allodynia evoked by intrathecal injection of NMDA was greatly attenuated by orthovanadate and Bpv ( phen ), suggesting that PTPs activity, once stimulated by NMDA receptors, became essential for spinal sensitization.", "output": "NMDA, orthovanadate, Bpv ( phen ), NMDA." }, { "input": "Biochemical analysis demonstrated that PTPs functioned to activate SFKs member Src and promote Src interaction with NR2B subunit - containing NMDA receptors ( NR2B receptors ).", "output": "NMDA." }, { "input": "As a result, PTPs inhibition largely suppressed Src - mediated NR2B phosphorylation at Tyr1472 and reduced the synaptic concentration of NR2B receptors in spinal dorsal horn of NMDA - treated rats.", "output": "Tyr1472, NMDA." }, { "input": "Importantly, intraplantar injection of Complete Freund ' s Adjuvant ( CFA ) naturally activated spinal PTPs to initiate Src signaling, because PTPs inhibition significantly repressed Src activity, reduced Src phosphorylation of NR2B, decreased NR2B synaptic accumulation and eventually ameliorated inflammatory pain.", "output": "There is no related enetity." }, { "input": "These data indicated an important role played by spinal PTPs in inducing Src - dependent NR2B receptor hyperfunction and suggested that PTPs inhibition might represent an effective strategy for the treatment of inflammatory pain.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of 1, 3, 4 - thiadiazole analogues as novel AChE and BuChE inhibitors.", "output": "1 , 3 , 4 - thiadiazole." }, { "input": "In this paper a series of new 1, 3, 4 - thiadiazole derivatives has been designed, synthesized and evaluated as the acetyl - and butyrylcholinesterase inhibitors.", "output": "1 , 3 , 4 - thiadiazole, acetyl." }, { "input": "Some analogues showed promising inhibition of both enzymes in vitro in the nM range.", "output": "There is no related enetity." }, { "input": "Generally, inhibitory potency of compounds was stronger against AChE than BuChE, and one of them was 1154 - fold more active inhibiting AChE ( IC50 = 0. 17 mu M ) than BuChE.", "output": "There is no related enetity." }, { "input": "The kinetic studies showed that one of the most active analogues 8 ( IC50 = 0. 09 mu M, AChE ) acted as a non - competitive AChE inhibitor and was characterized by the high selectivity index ( 300 ).", "output": "There is no related enetity." }, { "input": "The other derivative ( 1 ) exhibited a mixed - type of AChE inhibition.", "output": "There is no related enetity." }, { "input": "Docking simulations enabled the detection of key binding interactions of the compounds with AChE and revealed that they occupied mainly the catalytic active site.", "output": "There is no related enetity." }, { "input": "The scoring function for the novel compounds was similar or higher than for the reference inhibitor.", "output": "There is no related enetity." }, { "input": "Additionally, based on Lipinski and other filters, the drug - likeness of compounds was assessed.", "output": "There is no related enetity." }, { "input": "They revealed that the compounds possess properties which can suggest the favourable pharmacokinetics in the human body after oral admission.", "output": "There is no related enetity." }, { "input": "cRGD - functionalized polymeric magnetic nanoparticles as a dual - drug delivery system for safe targeted cancer therapy.", "output": "There is no related enetity." }, { "input": "In this paper we give a method of integrated treatment for cancer and drug - induced complications in the process of cancer therapy through dual - drug delivery system ( DDDS ).", "output": "There is no related enetity." }, { "input": "Two hydrophilic drugs, doxorubicin ( an antitumor drug ) and verapamil ( an antiangiocardiopathy drug ) combined preliminarily with chitosan shell coated on magnetic nanoparticles ( MNPs ), followed by entrapping into the PLGA nanoparticles.", "output": "doxorubicin, verapamil, PLGA." }, { "input": "Further modification was conducted by conjugating tumor - targeting ligand, cyclo ( Arg - Gly - Asp - D - Phe - Lys ) ( c ( RGDfK ) ) peptide, onto the end carboxyl groups on the PLGA - NPs.", "output": "cyclo ( Arg - Gly - Asp - D - Phe - Lys ), carboxyl, PLGA." }, { "input": "The size of the resulting cRGD - DOX / VER - MNP - PLGA NPs was approximately 144nm under simulate physiological environment.", "output": "DOX, VER, PLGA." }, { "input": "Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74. 8 and 53. 2wt % for cRGD - DOX / VER - MNP - PLGA NPs.", "output": "DOX, VER, DOX, VER, PLGA." }, { "input": "This paper contains interesting pilot data such as NIR - triggered drug release, in vivo drug distribution studies and whole - mouse optical imaging.", "output": "There is no related enetity." }, { "input": "Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy.", "output": "There is no related enetity." }, { "input": "Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches.", "output": "There is no related enetity." }, { "input": "Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells ( VSMCs ).", "output": "There is no related enetity." }, { "input": "The dynamic interplay of Ca ( 2 + ) and K ( + ) channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles.", "output": "Ca ( 2 + ), K ( + )." }, { "input": "The abnormally - elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca ( 2 + ) and K ( + ) channels in the VSMCs.", "output": "Ca ( 2 + ), K ( + )." }, { "input": "In this short review, we focus on the three well - studied ion channels in VSMCs, namely the L - type Ca ( 2 + ) ( CaV1. 2 ) channels, the voltage - gated K ( + ) ( KV ) channels, and the large - conductance Ca ( 2 + ) - activated K ( + ) ( BK ) channels.", "output": "Ca ( 2 + ), K ( + ), Ca ( 2 + ), K ( + )." }, { "input": "First, we provide a brief overview on the physiological role of vascular CaV1. 2, KV and BK channels in regulating arterial tone.", "output": "There is no related enetity." }, { "input": "Second, we discuss the current understanding of the expression changes and regulation of CaV1. 2, KV and BK channels in the vasculature during hypertension.", "output": "There is no related enetity." }, { "input": "Third, based on available proof - of - concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels.", "output": "There is no related enetity." }, { "input": "Developing advanced X - ray scattering methods combined with crystallography and computation.", "output": "There is no related enetity." }, { "input": "The extensive use of small angle X - ray scattering ( SAXS ) over the last few years is rapidly providing new insights into protein interactions, complex formation and conformational states in solution.", "output": "There is no related enetity." }, { "input": "This SAXS methodology allows for detailed biophysical quantification of samples of interest.", "output": "There is no related enetity." }, { "input": "Initial analyses provide a judgment of sample quality, revealing the potential presence of aggregation, the overall extent of folding or disorder, the radius of gyration, maximum particle dimensions and oligomerization state.", "output": "There is no related enetity." }, { "input": "Structural characterizations include ab initio approaches from SAXS data alone, and when combined with previously determined crystal / NMR, atomistic modeling can further enhance structural solutions and assess validity.", "output": "There is no related enetity." }, { "input": "This combination can provide definitions of architectures, spatial organizations of protein domains within a complex, including those not determined by crystallography or NMR, as well as defining key conformational states of a protein interaction.", "output": "There is no related enetity." }, { "input": "SAXS is not generally constrained by macromolecule size, and the rapid collection of data in a 96 - well plate format provides methods to screen sample conditions.", "output": "There is no related enetity." }, { "input": "This includes screening for co - factors, substrates, differing protein or nucleotide partners or small molecule inhibitors, to more fully characterize the variations within assembly states and key conformational changes.", "output": "There is no related enetity." }, { "input": "Such analyses may be useful for screening constructs and conditions to determine those most likely to promote crystal growth of a complex under study.", "output": "There is no related enetity." }, { "input": "Moreover, these high throughput structural determinations can be leveraged to define how polymorphisms affect assembly formations and activities.", "output": "There is no related enetity." }, { "input": "This is in addition to potentially providing architectural characterizations of complexes and interactions for systems biology - based research, and distinctions in assemblies and interactions in comparative genomics.", "output": "There is no related enetity." }, { "input": "Thus, SAXS combined with crystallography / NMR and computation provides a unique set of tools that should be considered as being part of one ' s repertoire of biophysical analyses, when conducting characterizations of protein and other macromolecular interactions.", "output": "There is no related enetity." }, { "input": "A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.", "output": "indole alkaloids." }, { "input": "Uncaria rhynchophylla ( Miq. ) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou - teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases.", "output": "There is no related enetity." }, { "input": "The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids.", "output": "indole alkaloids." }, { "input": "In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla.", "output": "indole alkaloids." }, { "input": "This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species.", "output": "There is no related enetity." }, { "input": "In vitro biokinetics of chlorpromazine and the influence of different dose metrics on effect concentrations for cytotoxicity in Balb / c 3T3, Caco - 2 and HepaRG cell cultures.", "output": "chlorpromazine." }, { "input": "The extrapolation of in vitro to in vivo toxicity data is a challenge.", "output": "There is no related enetity." }, { "input": "Differences in sensitivity between cell systems may be due to intrinsic properties of the cell but also because of differences in exposure.", "output": "There is no related enetity." }, { "input": "In this study, the cytotoxicity and biokinetics of the antipsychotic chlorpromazine ( CPZ ) were studied in in vitro assays using different cell types and exposure conditions.", "output": "chlorpromazine, CPZ." }, { "input": "Different dose metrics were assessed to express the sensitivity to CPZ.", "output": "CPZ." }, { "input": "The biokinetics of CPZ were measured in cell cultures of Balb / c 3T3, Caco - 2 and HepaRG cells.", "output": "CPZ." }, { "input": "Cytotoxicity was measured by Alamar Blue and expressed using different dose metrics, including the nominal, measured total and measured free CPZ medium concentrations.", "output": "CPZ." }, { "input": "CPZ was taken up by the cells; the highest amounts in the cell compartments were found in the Caco - 2 and HepaRG cells.", "output": "CPZ." }, { "input": "CPZ was highly protein - bound in the Caco - 2 cell medium containing 10 % fetal bovine serum, resulting in lower bioavailable exposure concentrations.", "output": "CPZ." }, { "input": "Moreover, also uptake into the cells strongly influenced the concentration in the medium.", "output": "There is no related enetity." }, { "input": "The Balb / c 3T3 cells were the most sensitive to the toxic effect of CPZ.", "output": "CPZ." }, { "input": "The use of different dose metrics influenced the cytotoxicity results found in the three cell types.", "output": "There is no related enetity." }, { "input": "The data show that in comparing the sensitivity of the tested cell systems, the freely dissolved concentration is a more appropriate dose metric than total concentration in the medium.", "output": "There is no related enetity." }, { "input": "The ranking in sensitivity of the three cell types for CPZ was dependent on the dose metric used.", "output": "CPZ." }, { "input": "Aspiration toxicology of hydrocarbons and lamp oils studied by in vitro technology.", "output": "hydrocarbons." }, { "input": "Medical literature regularly reports on accidental poisoning in children after aspiration of combustibles such as lamp oils which usually contain hydrocarbons or rape methyl esters ( RMEs ).", "output": "hydrocarbons, methyl esters." }, { "input": "We aimed to analyze the toxic potential of alkanes and different combustible classes in vitro with regard to biologic responses and mechanisms mediating toxicity.", "output": "alkanes." }, { "input": "Two different in vitro models were used, i. e. ( i ) a captive bubble surfactometer ( CBS ) to assess direct influence of combustibles on biophysical properties of surfactant film and ( ii ) cell cultures ( BEAS - 2B and R3 / 1 cells, primary macrophages, re - differentiated epithelia ) closely mimicking the inner lung surface.", "output": "There is no related enetity." }, { "input": "Biological endpoints included cell viability, cytotoxicity and inflammatory mediator release.", "output": "There is no related enetity." }, { "input": "CBS measurements demonstrate that combustibles affect film dynamics, i. e. the surface tension / area characteristics during compression and expansion, in a dose and molecular chain length dependent manner.", "output": "There is no related enetity." }, { "input": "Cell culture results confirm the dose dependent toxicity.", "output": "There is no related enetity." }, { "input": "Generally, cytotoxicity and cytokine release are higher in short - chained alkanes and hydrocarbon - based combustibles than in long - chained substances, e. g. highest inducible cytotoxicity in BEAS - 2B was for hexane 84. 6 %, decane 74 % and hexadecane 30. 8 %.", "output": "alkanes, hydrocarbon, hexane, decane, hexadecane." }, { "input": "Effects of RME - based combustibles differed between the cell models.", "output": "There is no related enetity." }, { "input": "Our results confirm data from animal experiments and give new insights into the mechanisms underlying the adverse health effects observed.", "output": "There is no related enetity." }, { "input": "Nonylphenol, an environmental estrogen, affects voltage - gated K + currents and L - type Ca (2) + currents in a non - monotonic manner in GH 3 pituitary cells.", "output": "Nonylphenol, estrogen, K +, Ca (2) +." }, { "input": "We have investigated the characteristics of voltage - gated K ( + ) channels and L - type Ca ( 2 + ) channels in GH3 rat pituitary cells and the effects of the xenoestrogen ( XEs ) nonylphenol ( NP ) on these ion channel currents.", "output": "K ( + ), Ca ( 2 + ), xenoestrogen, nonylphenol." }, { "input": "Our results have shown that the lower concentrations ( 10 ( - 15 ) - 10 ( - 14 ) M ) of NP decreased the amplitudes of voltage - gated K ( + ) currents ( IKv ) and activated L - type Ca ( 2 + ) currents ( ICa - L ) by reducing half - activation membrane potentials of activation kinetics curves.", "output": "K ( + ), Ca ( 2 + )." }, { "input": "However, the higher concentrations ( 10 ( - 10 ) - 10 ( - 9 ) M ) of NP increased the amplitudes of IKv and inhibited ICa - L by reducing the peak values of ICa - L.", "output": "There is no related enetity." }, { "input": "Thus, NP affects IKv and ICa - L in an opposite and non - monotonic manner.", "output": "There is no related enetity." }, { "input": "Apigenin induces c - Myc - mediated apoptosis in FRO anaplastic thyroid carcinoma cells.", "output": "Apigenin." }, { "input": "Apigenin promotes apoptosis in cancer cells.", "output": "Apigenin." }, { "input": "We studied the effect of apigenin on cell survival and c - Myc expression in FRO anaplastic thyroid carcinoma ( ATC ) cells.", "output": "apigenin." }, { "input": "Apigenin caused apoptosis via the elevation of c - Myc levels in conjunction with the phosphorylation of p38 and p53.", "output": "Apigenin." }, { "input": "In the c - Myc siRNA - transfected and apigenin - treated cells, compared with the apigenin - treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated.", "output": "apigenin, apigenin." }, { "input": "In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c - Myc levels.", "output": "apigenin, apigenin." }, { "input": "In conclusion, our results indicate that apigenin induces apoptosis mediated via c - Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells.", "output": "apigenin." }, { "input": "These findings suggest that augmented c - Myc acts as a core regulator and is necessary for apigenin - induced apoptosis in FRO ATC cells.", "output": "apigenin." }, { "input": "Tissue distributions of fluoride and its toxicity in the gills of a freshwater teleost, Cyprinus carpio.", "output": "fluoride." }, { "input": "Fish take up fluoride directly from water and are susceptible to fluoride contamination of their environment.", "output": "fluoride." }, { "input": "In this study, we examined the tissue distributions of fluoride and its toxicity in the gills of the common carp ( Cyprinus carpio ) chronically exposed to fluoride.", "output": "fluoride, fluoride." }, { "input": "Carp were exposed to a range of aqueous fluoride ( 35 - 124 mg / L ) and sampled at 30, 60 and 90 days.", "output": "fluoride." }, { "input": "The accumulation of fluoride in the tissues increased with the level and duration of exposure.", "output": "fluoride." }, { "input": "Steady state was not achieved under the experimental conditions.", "output": "There is no related enetity." }, { "input": "The gills accumulated the highest levels of fluoride followed by the liver > brain > kidney > muscle > intestine.", "output": "fluoride." }, { "input": "A dose - dependent inhibition was observed for the enzyme activities of Na ( + ) - K ( + ) - ATPase and Ca ( 2 + ) - ATPase in the gills after the fish were exposed for 90 days.", "output": "Na ( + ), K ( + ), Ca ( 2 + )." }, { "input": "Also, accumulation of fluoride was associated with the inhibition of superoxide dismutase ( SOD ) activities and a dose - dependent stimulation of malondialdehyde ( MDA ) levels in the gill tissues, suggesting that fluoride promoted oxidative stress in the fish.", "output": "fluoride, superoxide, malondialdehyde, MDA, fluoride." }, { "input": "Microscopic examinations revealed injuries to gill tissues and chloride cells, with the severity of injury increasing with exposure concentration.", "output": "chloride." }, { "input": "These results suggest that chronic exposure to elevated concentrations of fluoride may induce toxicity in the common carp.", "output": "fluoride." }, { "input": "Developmental abnormalities and changes in cholinesterase activity in sea urchin embryos and larvae from sperm exposed to engineered nanoparticles.", "output": "There is no related enetity." }, { "input": "The objective of this study is to examine the toxicity of engineered nanoparticles ( NPs ) that are dispersed in sea water by using an in vivo model.", "output": "There is no related enetity." }, { "input": "Because many products of nanotechnology contain NPs and are commonly used and well - established in the market, the accidental release of NPs into the air and water is quite possible.", "output": "There is no related enetity." }, { "input": "Indeed, at the end of their life cycle, some NPs are inevitably released into waste water and can reach marine ecosystem and affect the organisms there.", "output": "There is no related enetity." }, { "input": "Although there are few data on the presence of NPs in the marine environment, our awareness of their potential impact on environmental and organismal health is growing.", "output": "There is no related enetity." }, { "input": "Shallow - water benthonic organisms such as sea urchins provide planktonic larvae as a trophic base for finfish juveniles and are exposed to water from estuaries and precipitation.", "output": "There is no related enetity." }, { "input": "Such organisms can therefore be directly affected by NPs that are dispersed into those media.", "output": "There is no related enetity." }, { "input": "We evaluated the effects of exposure to different concentrations of nanosilver, titanium oxide and cobalt NPs on the sperm of the sea urchin Paracentrotus lividus by analyzing the functionality and the morphology and biochemistry of the first developmental stages of the sea urchin.", "output": "titanium oxide, cobalt." }, { "input": "Sperm were exposed to sea water containing suspensions of NPs ranging from 0. 0001 mg / L to 1 mg / L.", "output": "There is no related enetity." }, { "input": "Fertilization ability was not affected, but developmental anomalies were identified in embryos from the gastrula to pluteus stages, including morphological alterations of the skeletal rods.", "output": "There is no related enetity." }, { "input": "In addition, the enzymatic activity ( cholinesterase, ChE ) of the larvae was measured.", "output": "There is no related enetity." }, { "input": "Acetylcholinesterase ( AChE ) and propionylcholinesterase activity ( PrChE ) was affected in all of the exposed samples.", "output": "There is no related enetity." }, { "input": "The results did not vary consistently with the concentration of NP, but controls were significantly different from exposed samples.", "output": "There is no related enetity." }, { "input": "Exposure of sea urchin to these NPs may cause neurotoxic damage, and the altered ChE activity may be involved in skeletogenic aberrations.", "output": "There is no related enetity." }, { "input": "In conclusion, the sea urchin represents a suitable and sensitive model for testing the toxicity and effects of engineered NPs that are dispersed in sea water.", "output": "There is no related enetity." }, { "input": "Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety - like behavior, learning, and memory in mice.", "output": "BHF177, baclofen." }, { "input": "gamma - Aminobutyric acid B ( GABAB ) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression.", "output": "gamma - Aminobutyric acid." }, { "input": "However, full agonists of this receptor induce side - effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption.", "output": "There is no related enetity." }, { "input": "Positive allosteric modulators ( PAMs ) of the GABAB receptor may have similar therapeutic effects as agonists with superior side - effect profiles.", "output": "There is no related enetity." }, { "input": "The present study behaviorally characterized N - ( [ 1R, 2R, 4S ] - bicyclo [ 2. 2. 1 ] hept - 2 - yl ) - 2 - methyl - 5 - ( 4 - [ trifluoromethyl ] phenyl ) - 4 - pyrimidinamine ( BHF177 ), a GABAB receptor PAM, in mouse models of anxiety - like behavior, learning and memory.", "output": "N - ( [ 1R , 2R , 4S ] - bicyclo [ 2 . 2 . 1 ] hept - 2 - yl ) - 2 - methyl - 5 - ( 4 - [ trifluoromethyl ] phenyl ) - 4 - pyrimidinamine, BHF177." }, { "input": "In addition, the effects of BHF177 were compared with the agonist baclofen.", "output": "BHF177, baclofen." }, { "input": "Unlike the anxiolytic chlordiazepoxide, baclofen ( 0. 5, 1. 5, and 2. 5 mg / kg, intraperitoneally ) and BHF177 ( 10, 20, and 40 mg / kg, orally ) had no effect on anxiety - like behavior in the elevated plus maze, light / dark box, or Vogel conflict test.", "output": "chlordiazepoxide, baclofen, BHF177." }, { "input": "Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen.", "output": "Baclofen, baclofen." }, { "input": "At the highest dose tested ( 2. 5 mg / kg ), baclofen - treated mice exhibited sedation - like effects ( i. e., reduced locomotor activity ) across many of the tests, whereas BHF177 - treated mice exhibited no sedation - like effects.", "output": "baclofen, BHF177." }, { "input": "BHF177 exhibited pro - convulsion properties only in mice, but not in rats, indicating that this effect may be species - specific.", "output": "BHF177." }, { "input": "At doses that were not sedative or pro - convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze.", "output": "baclofen, BHF177." }, { "input": "These data suggest that BHF177 has little sedative activity, no anxiolytic - like profile, and minimal impairment of learning and memory in mice.", "output": "BHF177." }, { "input": "Consumer and farmer safety evaluation of application of botanical pesticides in black pepper crop protection.", "output": "There is no related enetity." }, { "input": "This study presents a consumer and farmer safety evaluation on the use of four botanical pesticides in pepper berry crop protection.", "output": "There is no related enetity." }, { "input": "The pesticides evaluated include preparations from clove, tuba root, sweet flag and pyrethrum.", "output": "There is no related enetity." }, { "input": "Their safety evaluation was based on their active ingredients being eugenol, rotenone, beta - asarone and pyrethrins, respectively.", "output": "eugenol, rotenone, beta - asarone, pyrethrins." }, { "input": "Botanical pesticides from Acorus calamus are of possible concern because of the genotoxic and carcinogenic ingredient beta - asarone although estimated margins of exposure ( MOE ) for consumers indicate a low priority for risk management.", "output": "beta - asarone." }, { "input": "For the other three botanical pesticides the margin of safety ( MOS ) between established acute reference doses and / or acceptable daily intake values and intake estimates for the consumer, resulting from their use as a botanical pesticide are not of safety concern, with the exception for levels of rotenone upon use of tuba root extracts on stored berries.", "output": "rotenone." }, { "input": "Used levels of clove and pyrethrum as botanical pesticides in pepper berry crop production is not of safety concern for consumers or farmers, whereas for use of tuba root and sweet flag some risk factors were defined requiring further evaluation and / or risk management.", "output": "There is no related enetity." }, { "input": "It seems prudent to look for alternatives for use of sweet flag extracts containing beta - asarone.", "output": "beta - asarone." }, { "input": "Effect of dietary treatment with dimethylarsinous acid ( DMA ( III ) ) on the urinary bladder epithelium of arsenic ( + 3 oxidation state ) methyltransferase ( As3mt ) knockout and C57BL / 6 wild type female mice.", "output": "dimethylarsinous acid, DMA ( III ), arsenic." }, { "input": "Chronic exposure to inorganic arsenic ( iAs ) is carcinogenic to the human urinary bladder.", "output": "arsenic." }, { "input": "It produces urothelial cytotoxicity and proliferation in rats and mice.", "output": "There is no related enetity." }, { "input": "DMA ( V ), a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the mouse urothelium.", "output": "DMA ( V )." }, { "input": "DMA ( III ) was shown to be the likely urinary metabolite of DMA ( V ) inducing urothelial changes and is also postulated to be one of the active metabolites of iAs.", "output": "DMA ( III ), DMA ( V )." }, { "input": "To evaluate potential DMA ( III ) - induced urothelial effects, it was administered to As3mt knockout mice which cannot methylate arsenicals.", "output": "DMA ( III ), methylate arsenicals." }, { "input": "Female C57BL / 6 wild type and As3mt knockout mice ( 10 / group ) were administered DMA ( III ), 77. 3ppm in water for four weeks.", "output": "DMA ( III )." }, { "input": "Urothelial effects were evaluated by light and scanning electron microscopy ( EM ) and immunohistochemical detection of bromodeoxyuridine ( BrdU ) incorporation.", "output": "bromodeoxyuridine, BrdU." }, { "input": "EM findings were rated 1 - 5, with higher rating indicating greater extent of cytotoxicity visualized.", "output": "There is no related enetity." }, { "input": "DMA ( III ) significantly increased the BrdU labeling index, a ratio of BrdU labeled cells to non - labeled cells, in the treated knockout group compared to control and wild type treated groups.", "output": "DMA ( III ), BrdU, BrdU." }, { "input": "DMA ( III ) induced simple hyperplasia in more knockout mice ( 4 / 10 ) compared to wild type mice ( 2 / 10 ).", "output": "DMA ( III )." }, { "input": "All treated knockout mice had more and larger intracytoplasmic granules compared to the treated wild type mice.", "output": "There is no related enetity." }, { "input": "Changes in EM classification were not significant.", "output": "There is no related enetity." }, { "input": "In conclusion, DMA ( III ) induces urothelial toxicity and regenerative hyperplasia in mice and most likely plays a role in inorganic arsenic - induced urothelial changes.", "output": "DMA ( III ), arsenic." }, { "input": "However, DMA ( V ) does not induce hyperplasia in mice, suggesting that urinary concentrations of DMA ( III ) do not reach cytotoxic levels in DMA ( V ) - treated mice.", "output": "DMA ( V ), DMA ( III ), DMA ( V )." }, { "input": "Arylsulfonamide inhibitors of aggrecanases as potential therapeutic agents for osteoarthritis: Synthesis and biological evaluation.", "output": "Arylsulfonamide." }, { "input": "Aggrecanases, in particular aggrecanase - 2 ( ADAMTS - 5 ), are considered the principal proteases responsible for aggrecan degradation in osteoarthritis.", "output": "There is no related enetity." }, { "input": "For this reason, considerable effort has been put on the discovery and development of aggrecanase inhibitors able to slow down or halt the progression of osteoarthritis.", "output": "There is no related enetity." }, { "input": "We report herein the synthesis and biological evaluation of a series of arylsulfonamido - based hydroxamates as aggrecanase inhibitors.", "output": "arylsulfonamido, hydroxamates." }, { "input": "Compound 18 was found to have a nanomolar activity for ADAMTS - 5, ADAMTS - 4 and MMP - 13 and high selectivity over MMP - 1 and MMP - 14.", "output": "There is no related enetity." }, { "input": "Furthermore, this compound proved to be effective in blocking ex vivo cartilage degradation without having effect on cell cytotoxicity.", "output": "There is no related enetity." }, { "input": "Chemically differentiating ascorbate - mediated dissolution of quantum dots in cell culture media.", "output": "ascorbate." }, { "input": "To investigate the dynamic dissolution of quantum dots ( QDs ) in cell culture media, in this study we constructed an online automatic analytical system comprising a sequential in - tube solid phase extraction ( SPE ) device and an inductively coupled plasma ( ICP ) mass spectrometer.", "output": "There is no related enetity." }, { "input": "By means of selectively extracting QDs and cadmium ions ( Cd ( 2 + ) ) onto the interior surface of the polytetrafluoroethylene ( PTFE ) tube, this novel SPE device could be used to determine the degree of QD dissolution through a simple adjustment of sample acidity.", "output": "cadmium, Cd ( 2 + ), polytetrafluoroethylene, PTFE." }, { "input": "To the best of our knowledge, this study is the first to exploit PTFE tubing as a selective SPE adsorbent for the online chemical differentiation of QDs and Cd ( 2 + ) ions with the goal of monitoring the phenomenon of QD dissolution in complicated biological matrices.", "output": "PTFE, Cd ( 2 + )." }, { "input": "We confirmed the analytical reliability of this system through comparison of the measured Cd - to - QD ratios to the expected values.", "output": "Cd." }, { "input": "When analyzing QDs and Cd ( 2 + ) ions at picomolar levels, a temporal resolution of 8 min was required to load sufficient amounts of the analytes to meet the sensitivity requirements of the ICP mass spectrometer.", "output": "Cd ( 2 + )." }, { "input": "To demonstrate the practicability of this developed method, we measured the dynamic variations in the Cd - to - QD705 ratio in the presence of ascorbate as a physiological stimulant to generate reactive oxygen species in cell culture media and trigger the dissolution of QDs; our results suggest that the ascorbate - induced QD dissolution was dependent on the time, treatment concentration, and nature of the biomolecule.", "output": "Cd, ascorbate, oxygen, ascorbate." }, { "input": "Evaluation of genotoxic effects of five flavour enhancers ( glutamates ) on the root meristem cells of Allium cepa.", "output": "glutamates." }, { "input": "The effects of different treatments with flavour enhancers monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, and magnesium diglutamate on the cytology, DNA content, and interphase nuclear volume ( INV ) of A. cepa were investigated.", "output": "monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, magnesium diglutamate." }, { "input": "Three concentrations of these additives - 20, 40, and 60 ppm - were applied for 6, 12, and 24 h.", "output": "There is no related enetity." }, { "input": "All the concentrations of these chemicals showed an inhibitory effect on cell division in root tips of A. cepa and caused a decrease in mitotic index values.", "output": "There is no related enetity." }, { "input": "Additionally, all the treatments changed the frequency of mitotic phases when compared with the control groups.", "output": "There is no related enetity." }, { "input": "These compounds increased chromosome abnormalities, among them are micronuclei, c - mitosis, anaphase bridges, stickiness, binucleus, laggards, and breaks.", "output": "There is no related enetity." }, { "input": "The nuclear DNA content and INV decreased when compared with control groups.", "output": "There is no related enetity." }, { "input": "Preparation of novel monoclonal antibodies against chelated cadmium ions.", "output": "cadmium." }, { "input": "The detection of cadmium ions using enzyme - linked immunosorbent assays ( ELISA ) has been reported by several research groups.", "output": "cadmium." }, { "input": "Because cadmium ions are too small to stimulate the immune system, high molecular weight immunogens of cadmium are constructed using bifunctional chelators.", "output": "cadmium, cadmium." }, { "input": "At present, the most commonly used bifunctional chelator for the preparation of antigens for heavy metal ions is 1 - ( 4 - isothiocyanobenzyl ) ethylenediamine N, N, N ', N ' - tetraacetic acid ( ITCBE ).", "output": "1 - ( 4 - isothiocyanobenzyl ) ethylenediamine N , N , N ' , N ' - tetraacetic acid, ITCBE." }, { "input": "However, the price of ITCBE is high.", "output": "ITCBE." }, { "input": "So we are interested in a cheaper bifunctional chelator, 1 - ( 4 - aminobenzyl ) ethylenediamine N, N, N ', N ' - tetraacetic acid ( aminobenzyl - EDTA ).", "output": "1 - ( 4 - aminobenzyl ) ethylenediamine N , N , N ' , N ' - tetraacetic acid, aminobenzyl - EDTA." }, { "input": "Here, cadmium ions were conjugated to carrier proteins using aminobenzyl - EDTA to make artificial antigens.", "output": "cadmium, aminobenzyl - EDTA." }, { "input": "Then, several mice were immunized with the antigen.", "output": "There is no related enetity." }, { "input": "And monoclonal antibodies ( MAbs ) against cadmium were produced.", "output": "cadmium." }, { "input": "Spleen cells of immunized mice were fused with myeloma cells.", "output": "There is no related enetity." }, { "input": "The resulting hybridomas were screened using protein conjugates which were covalently bound to metal - free EDTA or cadmium.", "output": "EDTA, cadmium." }, { "input": "Three hybridoma cell lines ( A3, E4 and B5 ) that produced MAbs with high selectivity and sensitivity were expanded for further study.", "output": "There is no related enetity." }, { "input": "Cross - reactivities with other metals were below 1 %.", "output": "There is no related enetity." }, { "input": "These antibodies were used to construct competitive ELISAs.", "output": "There is no related enetity." }, { "input": "The IC50 for A3 was 8. 4 mu g / l.", "output": "There is no related enetity." }, { "input": "The detection range and the lowest detection limit using the antibody A3 was 0. 394 - 64. 39 and 0. 051 mu g / l, respectively.", "output": "There is no related enetity." }, { "input": "Spike - recovery studies in tap water showed that the antibody A3 could be used for cadmium detection in drinking water.", "output": "cadmium." }, { "input": "Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain.", "output": "zinc, glutathione." }, { "input": "A deficit in zinc ( Zn ) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant - sensitive signals in neuronal cells.", "output": "zinc, Zn." }, { "input": "This work tested the hypothesis that a decreased Zn availability can affect glutathione ( GSH ) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR - 32 cells to upregulate GSH when challenged with dopamine ( DA ).", "output": "Zn, glutathione, GSH, GSH, dopamine." }, { "input": "GSH levels were low in the brain of gestation day 19 ( GD19 ) fetuses from dams fed marginal Zn diets throughout gestation and in Zn - deficient IMR - 32 cells.", "output": "GSH, Zn, Zn." }, { "input": "gamma - Glutamylcysteine synthetase ( GCL ), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency ( ZD ).", "output": "gamma - Glutamylcysteine, GSH, Zn." }, { "input": "The protein and mRNA levels of the GCL modifier ( GCLM ) and catalytic ( GCLC ) subunits were lower in the Zn - deficient GD19 fetal brain and in IMR - 32 cells compared with controls.", "output": "Zn." }, { "input": "The nuclear translocation of transcription factor nuclear factor ( erythroid - derived 2 ) - like 2, which controls GCL transcription, was impaired by ZD.", "output": "There is no related enetity." }, { "input": "Posttranslationally, the caspase - 3 - dependent GCLC cleavage was high in Zn - deficient IMR - 32 cells.", "output": "Zn." }, { "input": "Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration.", "output": "GSH." }, { "input": "Although Zn - deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low.", "output": "Zn, GSH." }, { "input": "In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels.", "output": "Zn, GSH." }, { "input": "This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn - deficient neurons to pro - oxidative stressors.", "output": "GSH, Zn." }, { "input": "Effects of baicalin on airway remodeling in asthmatic mice.", "output": "baicalin." }, { "input": "Airway remodeling is an important characteristic of asthma, linking inflammation with airway hyperresponsiveness.", "output": "There is no related enetity." }, { "input": "Baicalin, a major active component, was isolated from Radix Scutellariae.", "output": "Baicalin." }, { "input": "Many studies show that baicalin has anti - inflammatory, anti - bacterial, and anti - allergic effects.", "output": "baicalin." }, { "input": "Here we investigate the influence of baicalin on asthmatic airway remodeling and the mechanism underlining the anti - remodeling effect in vivo. Asthmatic airway remodeling mice model was established by ovalbumin exposure.", "output": "baicalin." }, { "input": "Seventy female BALB / c mice were randomly assigned to seven experimental groups: blank, ovalbumin, hexadecadrol, control, and baicalin ( 25 mg / kg, 50 mg / kg, 100 mg / kg ) groups.", "output": "baicalin." }, { "input": "Pulmonary function was measured using a whole - body plethysmograph in conscious and unrestrained mice.", "output": "There is no related enetity." }, { "input": "The lung pathology was observed and measured.", "output": "There is no related enetity." }, { "input": "The production of cytokines in bronchoalveolar lavage fluid and serum was measured using enzyme - labeled immunosorbent assay kits, and the expression levels of transforming growth factor - beta 1 and vascular endothelial growth factor were detected by immunohistochemistry.", "output": "There is no related enetity." }, { "input": "The protein expression levels of transforming growth factor - beta 1, vascular endothelial growth factor, extracellular signal - regulated kinase, and p21ras were measured using Western blot.", "output": "There is no related enetity." }, { "input": "The results show that ovalbumin exposure significantly increased the expression of interleukin - 13 in BALF and serum, and transforming growth factor - beta 1, vascular endothelial growth factor, extracellular signal - regulated kinase and p21ras expressions in the lungs.", "output": "There is no related enetity." }, { "input": "Baicalin attenuated the effects of ovalbumin significantly. It can be concluded that baicalin has significant anti - remodeling effect on ovalbumin - induced asthmatic airway remodeling mice model by decreasing expression of transforming growth factor - beta 1, interleukin - 13, and vascular endothelial growth factor and inhibiting the activation of the extracellular signal - regulated kinase pathway.", "output": "Baicalin, baicalin." }, { "input": "Apelin inhibits diet - induced obesity by enhancing lymphatic and blood vessel integrity.", "output": "There is no related enetity." }, { "input": "Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels.", "output": "There is no related enetity." }, { "input": "Therefore, induction of vessel abnormality by adipokines has been well studied, whereas how altered vascular function promotes obesity is relatively unexplored.", "output": "There is no related enetity." }, { "input": "Also, surviving Prox1 heterozygous mice showed abnormal lymphatic patterning and adult - onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function.", "output": "There is no related enetity." }, { "input": "Here we propose a new anti - obesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin.", "output": "There is no related enetity." }, { "input": "Apelin - knockout mice given a high - fat diet showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement.", "output": "There is no related enetity." }, { "input": "Fatty acids present in the high - fat diet induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization.", "output": "Fatty acids." }, { "input": "Moreover, treatment of high - fat - diet - fed apelin - knockout mice with a selective cyclooxygenase - 2 inhibitor, celecoxib, improved vascular function, and also attenuated obesity.", "output": "celecoxib." }, { "input": "Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue owing to inhibition of high - fat - diet - induced hyperpermeability of vessels.", "output": "There is no related enetity." }, { "input": "These results indicate that apelin inhibits high - fat - diet - induced obesity by enhancing vessel integrity.", "output": "There is no related enetity." }, { "input": "Apelin could serve as a therapeutic target for treating obesity and related diseases.", "output": "There is no related enetity." }, { "input": "Absorption, elimination, and metabolism of CS - 1036, a novel alpha - amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.", "output": "CS - 1036, glucose." }, { "input": "The absorption, metabolism, and excretion of ( 2R, 3R, 4R ) - 4 - hydroxy - 2 - ( hydroxymethyl ) pyrrolidin - 3 - yl 4 - O - ( 6 - deoxy - beta - d - glucopyranosyl ) - alpha - d - glucopyranoside ( CS - 1036 ), a novel and potent pancreatic and salivary alpha - amylase inhibitor, were evaluated in F344 / DuCrlCrlj rats and cynomolgus monkeys.", "output": "( 2R , 3R , 4R ) - 4 - hydroxy - 2 - ( hydroxymethyl ) pyrrolidin - 3 - yl 4 - O - ( 6 - deoxy - beta - d - glucopyranosyl ) - alpha - d - glucopyranoside, CS - 1036." }, { "input": "The total body clearance and volume of distribution of CS - 1036 were low ( 2. 67 - 3. 44 ml / min / kg and 0. 218 - 0. 237 l / kg for rats and 2. 25 - 2. 84 ml / min / kg and 0. 217 - 0. 271 l / kg for monkeys ).", "output": "CS - 1036." }, { "input": "After intravenous administration of [ ( 14 ) C ] CS - 1036 to rats and monkeys, radioactivity was mainly excreted into urine ( 77. 2 % for rats and 81. 1 % for monkeys ).", "output": "[ ( 14 ) C ] CS - 1036." }, { "input": "After oral administration, most of the radioactivity was recovered from feces ( 80. 28 % for rats and 88. 13 % for monkeys ) with a low oral bioavailability ( 1. 73 - 2. 44 % for rats and 0. 983 - 1. 20 % for monkeys ).", "output": "There is no related enetity." }, { "input": "In rats, intestinal secretion is suggested to be involved in the fecal excretion as a minor component because fecal excretion after intravenous administration was observed ( 15. 66 % ) and biliary excretion was almost negligible.", "output": "There is no related enetity." }, { "input": "Although intestinal flora was involved in CS - 1036 metabolism, CS - 1036 was the main component in feces ( 70. 3 % for rats and 48. 7 % for monkeys ) and in the intestinal contents ( 33 - 68 % for rats up to 2 hours after the dose ) after oral administration.", "output": "CS - 1036, CS - 1036." }, { "input": "In Zucker diabetic fatty rats, CS - 1036 showed a suppressive effect on plasma glucose elevation after starch loading with a 50 % effective dose at 0. 015 mg / kg.", "output": "CS - 1036, glucose." }, { "input": "In summary, CS - 1036 showed optimal pharmacokinetic profiles: low oral absorption and favorable stability in gastrointestinal lumen, resulting in suppression of postprandial hyperglycemia by alpha - amylase inhibition.", "output": "CS - 1036." }, { "input": "Identification and characterization of novel alternative splice variants of human constitutive androstane receptor in liver samples of Koreans and Caucasians.", "output": "androstane." }, { "input": "Human constitutive androstane receptor ( hCAR, NR1I3 ) is a member of the orphan nuclear receptor family and regulates the transcription of many drug - metabolizing enzymes and drug transporters.", "output": "androstane." }, { "input": "Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants ( SVs ) in non - Asian ethnicities.", "output": "There is no related enetity." }, { "input": "In the present study, we identified 18 hCAR SVs ( SV1 - SV18 ), including four novel SVs in Korean human livers.", "output": "There is no related enetity." }, { "input": "Among the four novel SVs, SV2 showed enhanced transactivation activity when cotransfected with CYP2B6 reporter gene, whereas other SVs were nonfunctional.", "output": "There is no related enetity." }, { "input": "When profiles of major hCAR SVs were compared among 30 livers from Korean patients and 20 livers from Caucasian patients, the relative composition of each SV showed interethnic variation as well as interindividual variation.", "output": "There is no related enetity." }, { "input": "The most predominant form of hCAR SV was not wild type, but either SV4 or SV7.", "output": "There is no related enetity." }, { "input": "The summed relative amounts of SV4 and SV7 ranged from 34. 5 to 57. 6 % in the 30 Korean livers and from 47. 2 to 82. 6 % in the 20 Caucasian livers, suggesting large interindividual variation.", "output": "There is no related enetity." }, { "input": "The mean relative amount of nonfunctional SV9 was significantly higher in Koreans ( 29. 8 % ) than in Caucasians ( 12. 8 % ).", "output": "There is no related enetity." }, { "input": "The mean relative amount of novel SV2 was 9. 7 % in Korean livers and 3. 5 % in Caucasian livers.", "output": "There is no related enetity." }, { "input": "Expression profiling of hCAR proteins in human livers also supported large interindividual variation in the expressional ratio of wild - type and SVs.", "output": "There is no related enetity." }, { "input": "Our results describe for the first time the direct comparison of hCAR SV profiles between Koreans and Caucasians.", "output": "There is no related enetity." }, { "input": "The functional relevance of these interindividual and interethnic variations of hCAR mRNA expression needs to be further characterized.", "output": "There is no related enetity." }, { "input": "Electrochemical Removal Of Selenate From Aqueous Solutions.", "output": "Selenate." }, { "input": "Removal of selenate from solution is investigated in batch electrochemical systems using reactive iron anodes and copper plate cathode in a bicarbonate medium.", "output": "selenate, iron, bicarbonate." }, { "input": "Iron anodes produce ferrous hydroxide, which is a major factor in the removal of selenate from solution.", "output": "Iron, ferrous hydroxide, selenate." }, { "input": "Iron anodes also generate a significant decrease in the oxidation - reduction potential ( ORP ) of the solution because it prevents generation of oxygen gas at the anode by electrolysis.", "output": "Iron, oxygen." }, { "input": "The removal rates varied from 45. 1 to 97. 4 %, depending on current density and selenate concentration.", "output": "selenate." }, { "input": "The transformation of selenate by the process is modeled based on a heterogeneous reaction coupled with electrochemical generation of ferrous and hydroxide.", "output": "selenate, ferrous, hydroxide." }, { "input": "The rates are optimized at lower initial concentrations, higher electrical currents, and the presence of anions.", "output": "There is no related enetity." }, { "input": "Presence of dissolved oxygen does not cause any significant effects the removal of selenate.", "output": "oxygen, selenate." }, { "input": "Introduction of Target Cliffs as a Concept To Identify and Describe Complex Molecular Selectivity Patterns.", "output": "There is no related enetity." }, { "input": "The study of target specificity or selectivity of small molecules is an important task in drug design.", "output": "There is no related enetity." }, { "input": "In an ideal situation, a compound would exclusively interact with an individual target and hence be target specific.", "output": "There is no related enetity." }, { "input": "However, such exclusive binding events are likely to be rare, as increasing evidence suggests.", "output": "There is no related enetity." }, { "input": "Because many compounds are active against more than one target, apparent selectivity often results from potency differences, i. e., a compound that is highly potent against a given target and weakly potent against one or more others displays target selectivity.", "output": "There is no related enetity." }, { "input": "In a simple case, a compound might have known activity against a pair of targets and be selective for one over the other.", "output": "There is no related enetity." }, { "input": "Then, selectivity is straightforward to rationalize.", "output": "There is no related enetity." }, { "input": "However, there are many more complex selectivity relationships associated with multi - target activities of compounds that are difficult to analyze and compare in a consistent manner.", "output": "There is no related enetity." }, { "input": "For this purpose, we introduce herein target cliffs as a concept to describe complex selectivity patterns.", "output": "There is no related enetity." }, { "input": "A target cliff is defined as a pair of targets against which at least one compound displays a large difference in potency.", "output": "There is no related enetity." }, { "input": "As such, target cliffs are distinct from activity cliffs.", "output": "There is no related enetity." }, { "input": "However, qualifying target pairs ( target cliffs ) and compound pairs ( activity cliffs ) can be systematically extracted from the same data structure termed target - compound matrices.", "output": "There is no related enetity." }, { "input": "Furthermore, these two types of cliffs can be compared to identify and prioritize compounds that are selective and reveal structure - activity relationship ( SAR ) information.", "output": "There is no related enetity." }, { "input": "Impairment of regulatory T cell function in autoimmune thyroid disease.", "output": "There is no related enetity." }, { "input": "Background: Autoimmune thyroid disease ( AITD ) pathogenesis may result from a loss of immune tolerance to thyroid antigens.", "output": "There is no related enetity." }, { "input": "Regulatory T cells ( Tregs ) control immune responses, prevent excessive inflammation, and may be dysfunctional in AITD.", "output": "There is no related enetity." }, { "input": "We investigated the role of Tregs in Hashimoto ' s thyroiditis ( HT ) and Graves ' disease ( GD ).", "output": "There is no related enetity." }, { "input": "Our goal was to identify differences in CD4 + CD25hi Treg function or number in patients with GD and HT, compared to healthy controls ( HC ).", "output": "There is no related enetity." }, { "input": "Methods: Treg number was assessed by flow cytometric analysis in samples from twenty AITD patients ( 7 GD, 13 HT ), 9 HC, and 7 individuals with Down syndrome ( DS ), a genetic disorder associated with multiple autoimmune disorders including AITD.", "output": "There is no related enetity." }, { "input": "Treg function was assessed by the inhibition of proliferation ( radioactive thymidine incorporation into DNA ) of blood - derived T effector cells ( Teff ) by Tregs in a co - culture.", "output": "There is no related enetity." }, { "input": "Various methods of stimulation were contrasted.", "output": "There is no related enetity." }, { "input": "Cytokine levels were determined in conditioned media from the co - cultures.", "output": "There is no related enetity." }, { "input": "Results: No differences were found in the frequency of Tregs as a percentage of CD4 + cells between AITD and HC.", "output": "There is no related enetity." }, { "input": "AITD Tregs were less capable of inhibiting the proliferation of Teff cells when compared to HC, however, the impairment was dependent on the type of stimulation used.", "output": "There is no related enetity." }, { "input": "DS patients without AITD exhibited normal Treg function.", "output": "There is no related enetity." }, { "input": "We observed few differences in cytokine production between HC and AITD patients.", "output": "There is no related enetity." }, { "input": "Conclusions: Tregs from AITD patients are partly dysfunctional, possibly explaining their autoimmunity.", "output": "There is no related enetity." }, { "input": "Future work will elucidate the diagnostic potential and pathophysiology of Tregs in AITD.", "output": "There is no related enetity." }, { "input": "Petroacetylene, a new polyacetylene from the marine sponge Petrosia solida that inhibits blastulation of starfish embryos.", "output": "Petroacetylene, polyacetylene." }, { "input": "A new C ( 30 ) linear polyacetylene compound designated petroacetylene ( 1 ) has been isolated from the marine sponge Petrosia solida Hoshino 1981, collected off the coast of Amami - Oshima, Kagoshima Prefecture, Japan.", "output": "polyacetylene, petroacetylene." }, { "input": "The structure was elucidated on the basis of spectroscopic data and chemical means.", "output": "There is no related enetity." }, { "input": "Petroacetylene ( 1 ) inhibited blastulation of starfish embryos at a concentration of 3. 1 mu g mL ( - 1 ) or greater.", "output": "Petroacetylene." }, { "input": "Synthesis, microwave spectrum, and conformational properties of 2 - fluoroethyl azide ( FCH2CH2N3 ).", "output": "2 - fluoroethyl azide, FCH2CH2N3." }, { "input": "A novel synthesis producing neat 2 - fluoroethyl azide ( FCH2CH2N3 ) is described.", "output": "2 - fluoroethyl azide, FCH2CH2N3." }, { "input": "A conformational analysis using microwave spectroscopy augmented by quantum chemical calculations at the CCSD ( T ) / cc - pVTZ, B3LYP / aug - cc - pVTZ, and B3LYP / cc - pVTZ levels of theory has been performed for this compound.", "output": "There is no related enetity." }, { "input": "The spectra of the ground vibrational state and two vibrationally excited states of one rotameric form were assigned.", "output": "There is no related enetity." }, { "input": "A large number of transitions was assigned, and very accurate values were obtained for the rotational and quartic centrifugal distortion constants.", "output": "There is no related enetity." }, { "input": "The identified conformer has synclinal orientations for the F - C - C - N and C - C - N - N chains of atoms bringing the fluorine atom and the azido group into close proximity.", "output": "F - C - C - N, C - C - N - N, fluorine, azido." }, { "input": "It is concluded from consideration of absolute intensities that this conformer is indeed the preferred form of the molecule in accord with the theoretical calculations.", "output": "There is no related enetity." }, { "input": "The experimental and CCSD ( T ) rotational constants are in very good agreement, whereas much larger discrepancies were seen for the experimental and B3LYP quartic centrifugal distortion constants.", "output": "There is no related enetity." }, { "input": "Self - aggregation properties of ionic liquid 1, 3 - didecyl - 2 - methylimidazolium chloride in aqueous solution: from spheres to cylinders to bilayers.", "output": "1 , 3 - didecyl - 2 - methylimidazolium chloride." }, { "input": "The self - aggregation behavior of the double - chained ionic liquid ( IL ) 1, 3 - didecyl - 2 - methylimidazolium chloride ( [ C10C10mim ] Cl ) in aqueous solution has been investigated with a number of different experimental techniques.", "output": "1 , 3 - didecyl - 2 - methylimidazolium chloride, [ C10C10mim ] Cl." }, { "input": "Two cmc values ( cmc1 and cmc2 ) are obtained from conductivity measurements.", "output": "There is no related enetity." }, { "input": "The fraction of neutralized charge on the micellar surface suggests that cmc1 corresponds to the formation of spherical micelles and cmc2 to the transition from spherical to cylindrical micelles.", "output": "There is no related enetity." }, { "input": "Data obtained from fluorescence spectroscopy ( using pyrene and Nile red as chemical probes ), fluorescence anisotropy ( using rhodamine B as probe ), and chemical shift ( 1 ) H NMR ( in D2O ) provide a picture that is also consistent with a sphere - to - cylinder transition.", "output": "pyrene, Nile red, rhodamine B, ( 1 ) H, D2O." }, { "input": "This structural change is further confirmed by diffusion - ordered NMR spectroscopy ( DOSY ), from the self - diffusion coefficients for surfactant unimer and aggregates.", "output": "There is no related enetity." }, { "input": "Furthermore, a third evolution from cylindrical micelles to bilayer aggregates is proposed from the analysis of diffusion coefficients at high surfactant concentration ( [ IL ] > 0. 2 M ).", "output": "There is no related enetity." }, { "input": "Phase scanning experiments performed with polarized light microscopy clearly demonstrate the presence of a lamellar liquid crystalline phase at very high IL concentration, thus confirming the coexistence of bilayer structures with elongated micelles, found at lower concentration.", "output": "There is no related enetity." }, { "input": "Additionally, [ C10C10mim ] Cl micelles are proposed as novel reaction media, as evidenced by the solvolysis reaction of 4 - methoxybenzenesulfonyl chloride ( MBSC ).", "output": "[ C10C10mim ] Cl, 4 - methoxybenzenesulfonyl chloride, MBSC." }, { "input": "Spiropyran polymeric microcapillary coatings for photodetection of solvent polarity.", "output": "Spiropyran." }, { "input": "Fused silica microcapillaries were functionalized with spiropyran - polymer brushes using surface - initiated ring - opening metathesis polymerization.", "output": "silica, spiropyran." }, { "input": "Based on the inherited spiropyran properties, the functionalized capillaries were successfully used to photoidentify solvents of different polarity when passing through the microcapillary in continuous flow.", "output": "spiropyran." }, { "input": "In the present study, six different solvents ( toluene, tetrahydrofuran, acetone, acetonitrile, ethanol, and methanol ) can be easily detected while passing through the modified microcapillary by simply irradiating a portion of it with UV light ( 365 nm ).", "output": "toluene, tetrahydrofuran, acetone, acetonitrile, ethanol, methanol." }, { "input": "This converts the closed spiropyran moiety to the open merocyanine form, and as a consequence, the microcapillary gains a distinct color and spectral response depending on the polarity of the solvent.", "output": "spiropyran, merocyanine." }, { "input": "The rate of ring - opening of the spiropyran - polymer brushes coatings has been determined in situ in the presence of different solvents, showing that the coloration rate is also influenced by the solvent polarity and therefore can be used as an additional parameter for solvent sensing.", "output": "spiropyran." }, { "input": "( Quasi - ) 2D aggregation of polystyrene - b - dextran at the air - water interface.", "output": "polystyrene." }, { "input": "Polystyrene - b - dextran ( PS - b - Dextran ) copolymers can be used to prepare dextran brushes at solid surfaces, applying Langmuir - Blodgett deposition.", "output": "Polystyrene." }, { "input": "When recording the interfacial pressure versus area isotherms of a PS - b - Dextran monolayer, time - dependent hysteresis was observed upon compression and expansion.", "output": "There is no related enetity." }, { "input": "We argue that this is due to ( quasi - ) 2D aggregation of the copolymer at the air - water surface, with three contributions.", "output": "There is no related enetity." }, { "input": "First, at large area per molecule, a zero surface pressure is measured; we ascribe this to self - assembly of block copolymers into surface micelles.", "output": "There is no related enetity." }, { "input": "At intermediate area we identify a second regime ( \" desorption regime \" ) where aggregation into large patches occurs due to van der Waals attraction between PS blocks.", "output": "There is no related enetity." }, { "input": "At high surface pressure ( \" brush regime \" ) we observe hysteretic behavior attributed to H - bonding between dextran chains.", "output": "H." }, { "input": "When compared to hysteresis of other amphiphilic diblock copolymers ( also containing PS, e. g., polystyrene - b - poly ( ethylene oxide ) ) a general criterion can be formulated concerning the extent of hysteresis: when the hydrophobic ( PS ) block is of equal size as ( or bigger than ) the hydrophilic block, the hysteresis is maximal.", "output": "polystyrene, poly ( ethylene oxide )." }, { "input": "The ( quasi - ) 2D aggregation of PS - b - Dextran has significant implications for the preparation of dextran brushes at solid surfaces using Langmuir - Blodgett deposition.", "output": "There is no related enetity." }, { "input": "For each grafting density the monolayer needs to relax, up to several hours, prior to transfer.", "output": "There is no related enetity." }, { "input": "High - yield dispersions of large - diameter semiconducting single - walled carbon nanotubes with tunable narrow chirality distributions.", "output": "carbon." }, { "input": "Here, we report a thorough study on the ability of fluorene - based semiconducting polymers to disperse large - diameter ( average diameter < d > =~ 1. 3 nm ) laser vaporization ( LV ) single - walled carbon nanotubes ( SWCNTs ).", "output": "fluorene, carbon." }, { "input": "We demonstrate the ability to select purely semiconducting species using poly [ ( 9, 9 - dioctylfluorenyl - 2, 7 - diyl ) - alt - co - ( 6, 6 ' - { 2, 2 ' - bipyridine } ) ] ( PFO - BPy ) and poly [ ( 9, 9 - dihexylfluorenyl - 2, 7 - diyl ) - co - ( 9, 10 - anthracene ) ] ( PFH - A ), producing samples with narrow and bright excitonic emission relative to comparable aqueous dispersions.", "output": "poly [ ( 9 , 9 - dioctylfluorenyl - 2 , 7 - diyl ) - alt - co - ( 6 , 6 ' - { 2 , 2 ' - bipyridine } ) ], PFO - BPy, poly [ ( 9 , 9 - dihexylfluorenyl - 2 , 7 - diyl ) - co - ( 9 , 10 - anthracene ) ], PFH - A." }, { "input": "Rapid processing and high yields offer the ability to easily incorporate these semiconducting SWCNTs into commercially scalable applications, as demonstrated by large - area thin films prepared by ultrasonic spraying.", "output": "There is no related enetity." }, { "input": "By modifying the growth temperature of the LV synthesis, we demonstrate the ability to tune the range of diameters and chiralities within dispersions by exerting synthetic control over the composition of the starting material.", "output": "There is no related enetity." }, { "input": "This synthetic control allows us to show that PFH - A preferentially disperses near - armchair semiconducting SWCNTs over a large range of diameters ( 0. 8 nm < d < 1. 4 nm ) and induces unique solvatochromic shifts for the excitonic transitions of nanotubes with particular chiral indices.", "output": "PFH - A." }, { "input": "Use of the Combination Index to determine interactions between plant - derived phenolic acids on hepatotoxicity endpoints in human and rat hepatoma cells.", "output": "phenolic acids." }, { "input": "The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived.", "output": "There is no related enetity." }, { "input": "This disparity could be due to interactions between the various phytochemicals present in the whole plant.", "output": "There is no related enetity." }, { "input": "The phenolic acids, rosmarinic acid ( RA ), caffeic acid ( CA ) and ferulic acid ( FA ) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects.", "output": "phenolic acids, rosmarinic acid, caffeic acid, ferulic acid." }, { "input": "However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically.", "output": "phenolic acids." }, { "input": "In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations.", "output": "phenolic acids." }, { "input": "A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human ( HepG2 / C3A ) and rat ( MH1C1 ) hepatocyte cell line.", "output": "There is no related enetity." }, { "input": "The Combination Index ( CI ) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures.", "output": "There is no related enetity." }, { "input": "Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents.", "output": "There is no related enetity." }, { "input": "Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types.", "output": "There is no related enetity." }, { "input": "There was only a 53 % concordance between the rat and human cells which may be suggestive of species differences.", "output": "There is no related enetity." }, { "input": "The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components.", "output": "There is no related enetity." }, { "input": "Epigenetics and pesticides.", "output": "There is no related enetity." }, { "input": "Pesticides, a wide class of environmental contaminants, may cause both acute and delayed health effects in exposed subjects.", "output": "There is no related enetity." }, { "input": "These effects can range from simple irritation of the skin and eyes to more severe effects such as affecting the nervous system, the reproductive system and cancer.", "output": "There is no related enetity." }, { "input": "The molecular mechanisms underlying such effects are still under investigation.", "output": "There is no related enetity." }, { "input": "Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence.", "output": "There is no related enetity." }, { "input": "Several epigenetic mechanisms, including DNA methylation, histone modifications and microRNA expression, can be triggered by environmental factors.", "output": "There is no related enetity." }, { "input": "We review current evidences indicating that epigenetic modifications may mediate pesticide effects on human health.", "output": "There is no related enetity." }, { "input": "In vitro, animal, and human investigations have identified several classes of pesticides that modify epigenetic marks, including endocrine disruptors, persistent organic pollutants, arsenic, several herbicides and insecticides.", "output": "arsenic." }, { "input": "Several investigations have examined the effects of environmental exposures and epigenetic markers, and identified toxicants that modify epigenetic states.", "output": "There is no related enetity." }, { "input": "These modifications are similar to the ones found in pathological tissue samples.", "output": "There is no related enetity." }, { "input": "In spite of the current limitations, available evidence supports the concept that epigenetics holds substantial potential for furthering our understanding of the molecular mechanisms of pesticides health effects, as well as for predicting health - related risks due to conditions of environmental exposure and individual susceptibility.", "output": "There is no related enetity." }, { "input": "Selective brain region activation by histamine H3 receptor antagonist / inverse agonist ABT - 239 enhances acetylcholine and histamine release and increases c - Fos expression.", "output": "histamine, ABT - 239, acetylcholine, histamine." }, { "input": "Histamine axons originate solely from the tuberomamillary nucleus ( TMN ) to innervate almost all brain regions.", "output": "Histamine." }, { "input": "This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleep - wake cycle.", "output": "histamine." }, { "input": "An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations.", "output": "There is no related enetity." }, { "input": "Here we report that systemic administration of the non - imidazole histamine H3 receptor antagonist 4 - ( 2 - { 2 - [ ( 2R ) - 2 - methylpyrrolidinyl ] ethyl } - benzofuran - 5 - yl ) benzonitrile ( ABT - 239, 3 mg / kg ) increased c - Fos expression dose - dependently in rat cortex and nucleus basalis magnocellularis ( NBM ) but not in the nucleus accumbens ( NAcc ) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex.", "output": "histamine, 4 - ( 2 - { 2 - [ ( 2R ) - 2 - methylpyrrolidinyl ] ethyl } - benzofuran - 5 - yl ) benzonitrile, ABT - 239, acetylcholine, histamine." }, { "input": "To further understand functional histaminergic pathways in the brain, dual - probe microdialysis was used to pharmacologically block H3 receptors in the TMN.", "output": "There is no related enetity." }, { "input": "Perfusion of the TMN with ABT - 239 ( 10 mu M ) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc.", "output": "ABT - 239, histamine." }, { "input": "When administered locally, ABT - 239 increased histamine release from the NBM, but not from the NAcc.", "output": "ABT - 239, histamine." }, { "input": "Systemic as well as intra - TMN administration of ABT - 239 increased c - Fos expression in the NBM, and cortex, but not in the striatum or NAcc.", "output": "ABT - 239." }, { "input": "Thus, as defined by their sensitivity to ABT - 239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region - specific manner.", "output": "ABT - 239." }, { "input": "This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.", "output": "histamine, histamine." }, { "input": "Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis.", "output": "There is no related enetity." }, { "input": "PRM - 151, recombinant human Pentraxin - 2 ( PTX - 2 ) also referred to as serum amyloid P ( SAP ), is under development for treatment of fibrosis.", "output": "There is no related enetity." }, { "input": "A First - in - Human ( FIH ) trial was performed to assess the safety, tolerability, and pharmacokinetics of single ascending intravenous doses of PRM - 151 administered to healthy subjects, using a randomized, blinded, placebo controlled study design.", "output": "There is no related enetity." }, { "input": "Each cohort included three healthy subjects ( PRM - 151: placebo; 2: 1 ).", "output": "There is no related enetity." }, { "input": "SAP levels were assessed using a validated ELISA method, non - discriminating between endogenous and exogenous SAP.", "output": "There is no related enetity." }, { "input": "At a dose level of 10 mg / kg, at which a physiologic plasma level of SAP was reached, two additional healthy volunteers and three pulmonary fibrosis ( PF ) patients were enrolled enabling comparison of the pharmacokinetic SAP profile between healthy volunteers and PF patients.", "output": "There is no related enetity." }, { "input": "In addition, the percentage of fibrocytes ( CD45 + / Procollagen - 1 + cells ) in whole blood samples was assessed to demonstrate biological activity of PRM - 151 in the target population.", "output": "There is no related enetity." }, { "input": "PRM - 151 administration was generally well tolerated.", "output": "There is no related enetity." }, { "input": "In two pulmonary fibrosis patients non - specific, transient skin reactions ( urticaria and erythema ) were observed.", "output": "There is no related enetity." }, { "input": "PRM - 151 administration resulted in a 6 - to 13 - fold increase in mean baseline plasma SAP levels at dose levels of 5, 10, and 20 mg / kg.", "output": "There is no related enetity." }, { "input": "The estimated t1 / 2 of PRM - 151 in healthy volunteers was 30 h.", "output": "There is no related enetity." }, { "input": "Pharmacokinetic profiles were comparable between healthy volunteers and PF patients.", "output": "There is no related enetity." }, { "input": "PRM - 151 administration resulted in a 30 - 50 % decrease in fibrocyte numbers 24 h post - dose.", "output": "There is no related enetity." }, { "input": "This suggests that administration of PRM - 151 may be associated with a reduction of fibrocytes in PF patients, a population for which current pharmacotherapeutic options are limited.", "output": "There is no related enetity." }, { "input": "The pharmacological action of PRM - 151 should be confirmed in future research.", "output": "There is no related enetity." }, { "input": "Autophagy takes place in mutated p53 neuroblastoma cells in response to hypoxia mimetic CoCl ( 2 ).", "output": "CoCl ( 2 )." }, { "input": "Solid tumors like neuroblastoma exhibit hypoxic areas, which can lead both to cell death or aggressiveness increase.", "output": "There is no related enetity." }, { "input": "Hypoxia is a known stress able to induce stabilization of p53, implicated in cell fate regulation.", "output": "There is no related enetity." }, { "input": "Recently, p53 appeared to be involved in autophagy in an opposite manner, depending on its location: when nuclear, it enhanced transcription of pro - autophagic genes whereas when cytoplasmic, it inhibited the autophagic process.", "output": "There is no related enetity." }, { "input": "Today, we used cobalt chloride, a hypoxia mimetic that inhibits proteasomal HIF - 1 degradation and generates reactive oxygen species ( ROS ).", "output": "cobalt chloride, oxygen." }, { "input": "We focused on CoCl2 - induced cell death in a DNA - binding mutated p53 neuroblastoma cell line ( SKNBE ( 2c ) ).", "output": "CoCl2." }, { "input": "An autophagic signaling was evidenced by an increase of Beclin - 1, ATG 5 - 12, and LC3 - II expression whereas the p53 ( mut ) presence decreased with CoCl2 time exposure.", "output": "CoCl2." }, { "input": "Activation of the pathway seemed to protect cells from ROS production and, at least in part, from death.", "output": "There is no related enetity." }, { "input": "The autophagic inhibitors activated the apoptotic signaling and the death was enhanced.", "output": "There is no related enetity." }, { "input": "To delineate the eventual implication of the p53 ( mut ) in the autophagic process in response to hypoxia, we monitored signaling in p53 ( WT ) SHSY5Y cells, after either shRNA - p53 down - regulation or transcriptional activity inhibition by pifithrin alpha.", "output": "There is no related enetity." }, { "input": "We did not detect autophagy neither with p53 ( wt ) nor when p53 was lacking whereas such a response was effective with a mutated or inactivated p53.", "output": "There is no related enetity." }, { "input": "To conclude, mutated p53 in neuroblastoma cells could be linked with the switch between apoptotic response and cell death by autophagy in response to hypoxic mimetic stress.", "output": "There is no related enetity." }, { "input": "Early steps of double - strand break repair in Bacillus subtilis.", "output": "There is no related enetity." }, { "input": "All organisms rely on integrated networks to repair DNA double - strand breaks ( DSBs ) in order to preserve the integrity of the genetic information, to re - establish replication, and to ensure proper chromosomal segregation.", "output": "There is no related enetity." }, { "input": "Genetic, cytological, biochemical and structural approaches have been used to analyze how Bacillus subtilis senses DNA damage and responds to DSBs.", "output": "There is no related enetity." }, { "input": "RecN, which is among the first responders to DNA DSBs, promotes the ordered recruitment of repair proteins to the site of a lesion.", "output": "There is no related enetity." }, { "input": "Cells have evolved different mechanisms for efficient end processing to create a 3 ' - tailed duplex DNA, the substrate for RecA binding, in the repair of one - and two - ended DSBs.", "output": "There is no related enetity." }, { "input": "Strand continuity is re - established via homologous recombination ( HR ), utilizing an intact homologous DNA molecule as a template.", "output": "There is no related enetity." }, { "input": "In the absence of transient diploidy or of HR, however, two - ended DSBs can be directly re - ligated via error - prone non - homologous end - joining.", "output": "There is no related enetity." }, { "input": "Here we review recent findings that shed light on the early stages of DSB repair in Firmicutes.", "output": "There is no related enetity." }, { "input": "Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin - 1.", "output": "phencyclidine." }, { "input": "RATIONALE: Perinatal phencyclidine ( PCP ) administration in rat blocks the N - methyl D - aspartate receptor ( NMDAR ) and causes symptoms reminiscent of schizophrenia in human.", "output": "phencyclidine, PCP, N - methyl D - aspartate." }, { "input": "A growing body of evidence suggests that alterations in gamma - aminobutyric acid ( GABA ) interneuron neurotransmission may be associated with schizophrenia.", "output": "gamma - aminobutyric acid, GABA." }, { "input": "Neuregulin - 1 ( NRG - 1 ) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits.", "output": "GABA." }, { "input": "OBJECTIVES: The aim of this study was to determine the long - term effects of perinatal PCP administration on the projection and local circuit neurons and NRG - 1 expression in the cortex and hippocampus.", "output": "PCP." }, { "input": "METHODS: Rats were treated on postnatal day 2 ( P2 ), P6, P9, and P12 with either PCP ( 10 mg / kg ) or saline.", "output": "PCP." }, { "input": "Morphological studies and determination of NRG - 1 expression were performed at P70.", "output": "There is no related enetity." }, { "input": "RESULTS: We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus ( DG ) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP - treated rats compared with controls.", "output": "PCP." }, { "input": "For the first time, we show the reduced density of reelin - and somatostatin - positive cells in the cortex and hippocampus of animals perinatally treated with PCP.", "output": "PCP." }, { "input": "Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG.", "output": "There is no related enetity." }, { "input": "We also show that perinatal PCP administration leads to an increased NRG - 1 expression in the cortex and hippocampus.", "output": "PCP." }, { "input": "CONCLUSION: Taken together, our findings demonstrate that perinatal PCP administration increases NRG - 1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.", "output": "PCP." }, { "input": "Effects of supplementary selenium source on the blood parameters in beef cows and their nursing calves.", "output": "selenium." }, { "input": "Over 2 years, 32 beef cows nursing calves in southwest Arkansas were randomly selected from a herd of 120 that were managed in six groups and were assigned to six 5. 1 - ha bermudagrass ( Cynodon dactylon [ L. ] Pers. ) pastures.", "output": "There is no related enetity." }, { "input": "Treatments were assigned to pastures ( two pastures / treatment ) and cows had ad libitum access to one of three free - choice minerals: ( 1 ) no supplemental selenium ( Se ), ( 2 ) 26 mg of supplemental Se from sodium selenite per kilogram, and ( 3 ) 26 mg of supplemental Se from seleno - yeast per kilogram ( designed mineral intake = 113 g / cow daily ).", "output": "selenium, Se, Se, sodium selenite, Se, seleno." }, { "input": "Data were analyzed using a mixed model; year and pasture were the random effects and treatment was the fixed effect.", "output": "There is no related enetity." }, { "input": "At the beginning of the calving and breeding seasons, cows supplemented with Se had greater ( P < 0. 01 ) whole blood Se concentration ( WBSe ) and glutathione peroxidase activities ( GSH - Px ) than cows receiving no supplemental Se; cows fed seleno - yeast had greater ( P <= 0. 05 ) WBSe than cows fed sodium selenite, but GSH - Px did not differ ( P >= 0. 25 ) between the two sources.", "output": "Se, Se, glutathione, GSH, Se, seleno, sodium selenite, GSH." }, { "input": "At birth and near peak lactation ( late May ), calves from cows supplemented with Se had greater ( P < 0. 01 ) WBSe than calves from cows fed no Se and calves from cows fed seleno - yeast had greater ( P <= 0. 01 ) WBSe and GSH - Px than calves from cows fed sodium selenite.", "output": "Se, Se, seleno, GSH, sodium selenite." }, { "input": "Thyroxine ( T4 ), triiodothyronine ( T3 ), and the T4: T3 ratio in calves did not differ among treatments ( P >= 0. 35 ).", "output": "Thyroxine, triiodothyronine." }, { "input": "At birth, insulin - like growth factor 1 ( IGF - 1 ) was greater ( P = 0. 02 ) in calves nursing cows with no supplemental Se than in ones with supplemental Se; in calves nursing cows with supplemental sodium selenite, IGF - 1 did not differ ( P = 0. 96 ) from ones offered supplemental seleno - yeast.", "output": "Se, Se, sodium selenite, seleno." }, { "input": "Selenium supplementation of gestating beef cows benefited cows and calves by increasing WBSe and GSH - Px.", "output": "Selenium, GSH." }, { "input": "The use of seleno - yeast as a Se supplement compared to sodium selenite increased the WBSe of both cows and their calves without affecting the T4 to T3 conversion or IGF - 1 concentrations.", "output": "seleno, Se, sodium selenite." }, { "input": "Mechanisms of Pharmacokinetic Enhancement Between Ritonavir and Saquinavir; Micro / Small Dosing Tests Using Midazolam ( CYP3A4 ), Fexofenadine ( p - Glycoprotein ), and Pravastatin ( OATP1B1 ) as Probe Drugs.", "output": "Ritonavir, Saquinavir, Midazolam, Fexofenadine, Pravastatin." }, { "input": "We investigated the mechanisms of ritonavir - mediated enhancement effect on the pharmacokinetics of saquinavir using in vivo probes for CYP3A4 ( midazolam ), p - glycoprotein ( fexofenadine ), and OATP1B1 ( pravastatin ) following oral micro / small dosing.", "output": "ritonavir, saquinavir, midazolam, fexofenadine, pravastatin." }, { "input": "A cocktail of the drugs ( 2 mg of saquinavir, 100 micro g of each probe ) was administered to eight healthy volunteers ( phase 1 ), and then coadministered with 20 mg ( phase 2 ) and 100 mg ( phase 3 ) of ritonavir.", "output": "saquinavir, ritonavir." }, { "input": "Plasma concentrations of the drugs were measured by validated LC - MS / MS methods.", "output": "There is no related enetity." }, { "input": "The mean plasma AUC ( 0 - 24 ) ( pg hour / mL ) of saquinavir at phases 1, 2, and 3 was 101, 2 540, and 23 900 ( P <. 01 ), respectively.", "output": "saquinavir." }, { "input": "The relative area under the plasma concentration - time curve ( AUC ) ( 0 - 24 ) ratios of midazolam and fexofenadine at phases 1, 2, and 3 were 1: 5. 9: 14. 7 ( P <. 01 ), and 1: 1. 4: 2. 2 ( P <. 01 -. 05 ), respectively.", "output": "midazolam, fexofenadine." }, { "input": "In contrast, there was no difference in the pharmacokinetics of pravastatin.", "output": "pravastatin." }, { "input": "Inhibition of intestinal and hepatic CYP3A - mediated metabolism, and intestinal p - glycoprotein - mediated efflux of saquinavir, but not OATP1B1, is involved in the enhancement mechanism.", "output": "saquinavir." }, { "input": "Micro / small dosing is useful for examining the mechanism of drug interactions without safety concern.", "output": "There is no related enetity." }, { "input": "Pharmacogenetics of Allopurinol - Making an Old Drug Safer.", "output": "Allopurinol." }, { "input": "Allopurinol is a drug that has been used for decades to lower serum urate levels in patients with gout or chronic renal failure and in cancer patients undergoing chemotherapy at risk of tumor lysis syndrome.", "output": "Allopurinol." }, { "input": "Patients may develop cutaneous hypersensitivity reactions, ranging from mild rashes to potentially fatal severe cutaneous adverse reactions ( SCARs ) namely drug hypersensitivity syndrome, Stevens - Johnson syndrome ( SJS ), and toxic epidermal necrolysis ( TEN ).", "output": "There is no related enetity." }, { "input": "Recent studies have demonstrated the association between human leukocyte antigen ( HLA ) B * 58: 01 allele and allopurinol - induced SCARs, which might explain ethnic differences in their incidences.", "output": "allopurinol." }, { "input": "Genotyping is now required before starting abacavir and carbamazepine so as to identify individuals susceptible to SJS.", "output": "abacavir, carbamazepine." }, { "input": "However, no genetic screening is advocated before commencement of allopurinol.", "output": "allopurinol." }, { "input": "The lack of availability of a rapid and inexpensive screening test for the HLA - B * 58: 01 allele is one of the obstacles to such screening.", "output": "There is no related enetity." }, { "input": "Development of a test that is quick, accurate, and cost - effective is warranted.", "output": "There is no related enetity." }, { "input": "Graded doping for enhanced colloidal quantum dot photovoltaics.", "output": "There is no related enetity." }, { "input": "A novel approach to improving all - inorganic colloidal quantum dot ( CQD ) homojunction solar cells by engineering the doping spatial profile to produce a doping gradient within the n - type absorber is presented.", "output": "There is no related enetity." }, { "input": "The doping gradient greatly improves carrier collection and enhances the voltages attainable by the device, leading to a 1 power point power conversion efficiency ( PCE ) improvement over previous inorganic CQD solar cells.", "output": "There is no related enetity." }, { "input": "Using conditional inference trees and random forests to predict the bioaccumulation potential of organic chemicals.", "output": "There is no related enetity." }, { "input": "The present study presents a data - oriented, tiered approach to assessing the bioaccumulation potential of chemicals according to the European chemicals regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals ( REACH ).", "output": "There is no related enetity." }, { "input": "The authors compiled data for eight physicochemical descriptors ( partition coefficients, degradation half - lives, polarity, and so forth ) for a set of 713 organic chemicals for which experimental values of the bioconcentration factor ( BCF ) are available.", "output": "There is no related enetity." }, { "input": "The authors employed supervised machine learning methods ( conditional inference trees and random forests ) to derive relationships between the physicochemical descriptors and the BCF values.", "output": "There is no related enetity." }, { "input": "In a first tier, the authors established rules for classifying a chemical as bioaccumulative ( B ) or nonbioaccumulative ( non - B ).", "output": "There is no related enetity." }, { "input": "In a second tier, the authors developed a new tool for estimating numerical BCF values.", "output": "There is no related enetity." }, { "input": "For both cases the optimal set of relevant descriptors was determined; these are biotransformation half - life and octanol - water distribution coefficient ( log D ) for the classification rules and log D, biotransformation half - life, and topological polar surface area for the BCF estimation tool.", "output": "octanol." }, { "input": "The uncertainty of the BCF estimates obtained with the new estimation tool was quantified by comparing the estimated and experimental BCF values of the 713 chemicals.", "output": "There is no related enetity." }, { "input": "Comparison with existing BCF estimation methods indicates that the performance of this new BCF estimation tool is at least as high as that of existing methods.", "output": "There is no related enetity." }, { "input": "The authors recommend the present study ' s classification rules and BCF estimation tool for a consensus application in combination with existing BCF estimation methods.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1187 - 1195.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Population pharmacokinetics and dose optimization of mycophenolic acid in HCT recipients receiving oral mycophenolate mofetil.", "output": "mycophenolic acid, mycophenolate mofetil." }, { "input": "We sought to create a population pharmacokinetic model for total mycophenolic acid ( MPA ), to study the effects of different covariates on MPA pharmacokinetics, to create a limited sampling schedule ( LSS ) to characterize MPA exposure ( i. e., area under the curve or AUC ) with maximum a posteriori Bayesian estimation, and to simulate an optimized dosing scheme for allogeneic hematopoietic cell transplantation ( HCT ) recipients.", "output": "mycophenolic acid, MPA, MPA, MPA." }, { "input": "Four thousand four hundred ninety - six MPA concentration - time points from 408 HCT recipients were analyzed retrospectively using a nonlinear mixed effects modeling approach.", "output": "MPA." }, { "input": "MPA pharmacokinetics was characterized with a two - compartment model with first - order elimination and a time - lagged first - order absorption process.", "output": "MPA." }, { "input": "Concomitant cyclosporine and serum albumin were significant covariates.", "output": "cyclosporine." }, { "input": "The median MPA clearance ( CL ) and volume of the central compartment were 24. 2 L / hour and 36. 4 L, respectively, for a 70 kg patient receiving tacrolimus with a serum albumin of 3. 4 g / dL.", "output": "MPA, tacrolimus." }, { "input": "Dosing simulations indicated that higher oral MMF doses are needed with concomitant cyclosporine, which increases MPA CL by 33. 8 %.", "output": "MMF, cyclosporine, MPA." }, { "input": "The optimal LSS was immediately before and at 0. 25 hours, 1. 25 hours, 2 hours, and 4 hours after oral mycophenolate mofetil administration.", "output": "mycophenolate mofetil." }, { "input": "MPA AUC in an individual HCT recipient can be accurately estimated using a five - sample LSS and maximum a posteriori Bayesian estimation.", "output": "MPA." }, { "input": "Reconstitution of homomeric GluA2 ( flop ) receptors in supported lipid membranes: functional and structural properties.", "output": "There is no related enetity." }, { "input": "AMPA receptors ( AMPARs ) are glutamate - gated ion channels ubiquitous in the vertebrate central nervous system, where they mediate fast excitatory neurotransmission and act as molecular determinants of memory formation and learning.", "output": "AMPA, glutamate." }, { "input": "Together with detailed analyses of individual AMPAR domains, structural studies of full - length AMPARs by electron microscopy and x - ray crystallography have provided important insights into channel assembly and function.", "output": "There is no related enetity." }, { "input": "However, the correlation between the structure and functional states of the channel remains ambiguous particularly because these functional states can be assessed only with the receptor bound within an intact lipid bilayer.", "output": "There is no related enetity." }, { "input": "To provide a basis for investigating AMPAR structure in a membrane environment, we developed an optimized reconstitution protocol using a receptor whose structure has previously been characterized by electron microscopy.", "output": "There is no related enetity." }, { "input": "Single - channel recordings of reconstituted homomeric GluA2 ( flop ) receptors recapitulate key electrophysiological parameters of the channels expressed in native cellular membranes.", "output": "There is no related enetity." }, { "input": "Atomic force microscopy studies of the reconstituted samples provide high - resolution images of membrane - embedded full - length AMPARs at densities comparable to those in postsynaptic membranes.", "output": "There is no related enetity." }, { "input": "The data demonstrate the effect of protein density on conformational flexibility and dimensions of the receptors and provide the first structural characterization of functional membrane - embedded AMPARs, thus laying the foundation for correlated structure - function analyses of the predominant mediators of excitatory synaptic signals in the brain.", "output": "There is no related enetity." }, { "input": "Dicer1 is required to repress neuronal fate during endocrine cell maturation.", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs ) are important regulators of gene expression programs in the pancreas; however, little is known about the role of miRNA pathways during endocrine cell specification and maturation during neonatal life.", "output": "There is no related enetity." }, { "input": "In this study, we deleted Dicer1, an essential RNase for active miRNAs biogenesis, specifically from NGN3 + endocrine progenitor cells.", "output": "There is no related enetity." }, { "input": "We found that deletion of Dicer1 in endocrine progenitors did not affect the specification of hormone - expressing endocrine cells.", "output": "There is no related enetity." }, { "input": "However, the islets in the mutant mice in the neonatal period exhibited morphological defects in organization and loss of hormone expression, and the mutant mice subsequently developed diabetes.", "output": "There is no related enetity." }, { "input": "Dicer1 - deficient beta - cells lost insulin expression while maintaining the expression of beta - cell transcription factors such as Pdx1 and Nkx6. 1 early in the postnatal period.", "output": "There is no related enetity." }, { "input": "Surprisingly, transcriptional profiling showed that that the Dicer1 - deficient endocrine cells expressed neuronal genes before the onset of diabetes.", "output": "There is no related enetity." }, { "input": "The derepression of neuronal genes was associated with a loss in binding of the neuronal transcriptional repressor RE - 1 - silencing transcription factor to its targets in Dicer1 - deficient beta - cells.", "output": "There is no related enetity." }, { "input": "These studies suggest that miRNAs play a critical role in suppressing neuronal genes during the maturation of endocrine cells.", "output": "There is no related enetity." }, { "input": "International Union of Pharmacology.", "output": "There is no related enetity." }, { "input": "LXXXVII.", "output": "There is no related enetity." }, { "input": "Complement peptide C5a, C4a, and C3a receptors.", "output": "There is no related enetity." }, { "input": "The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small ( 74 - 77 amino acid ) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types.", "output": "amino acid." }, { "input": "These fragments, C5a, C4a, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration.", "output": "There is no related enetity." }, { "input": "Their primary function, however, is in inflammation, so they are important targets for the development of antiinflammatory therapies.", "output": "There is no related enetity." }, { "input": "Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation.", "output": "There is no related enetity." }, { "input": "In humans, there is a single receptor for C3a ( C3a receptor ), no known receptor for C4a, and two receptors for C5a ( C5a 1 receptor and C5a 2 receptor ).", "output": "There is no related enetity." }, { "input": "The most recently characterized receptor, the C5a 2 receptor ( previously known as C5L2 or GPR77 ), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this.", "output": "There is no related enetity." }, { "input": "Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology.", "output": "There is no related enetity." }, { "input": "An adsorbent performance indicator as a first step evaluation of novel sorbents for gas separations: application to metal - organic frameworks.", "output": "There is no related enetity." }, { "input": "An adsorbent performance indicator ( API ) is proposed in an effort to initially highlight porous materials of potential interest for PSA separation processes.", "output": "There is no related enetity." }, { "input": "This expression takes into account working capacities, selectivities, and adsorption energies and additionally uses weighting factors to reflect the specific requirements of a given process.", "output": "There is no related enetity." }, { "input": "To demonstrate the applicability of the API, we have performed the adsorption of carbon dioxide and methane at room temperature on a number of metal - organic frameworks, a zeolite and a molecular sieve carbon.", "output": "carbon dioxide, methane, zeolite, carbon." }, { "input": "The API is calculated for two different CO2 / CH4 separation case scenarios: \" bulk separation \" and \" natural gas purification \".", "output": "CO2, CH4." }, { "input": "This comparison highlights how the API can be more versatile than previously proposed comparison factors for an initial indication of potential adsorbent performance.", "output": "There is no related enetity." }, { "input": "Conjugation with betaine: a facile and effective approach to significant improvement of gene delivery properties of PEI.", "output": "There is no related enetity." }, { "input": "Herein, we developed a new gene delivery vector by grafting a betaine monomer ( N, N - dimethyl ( acrylamidopropyl ) ammonium propane sulfonate, DMAAPS ) onto 25 KDa polyethylenimine ( PEI 25K ) via the Michael addition reaction.", "output": "N , N - dimethyl ( acrylamidopropyl ) ammonium propane sulfonate, DMAAPS, polyethylenimine, PEI." }, { "input": "The graft ratio for betaine on PEI polymer could be readily controlled, and in this study three PEI - betaine conjugates PEI - DMAAPS23 %, PEI - DMAAPS55 %, and PEI - DMAAPS95 % were prepared with their graft ratios of 23, 55, and 95 %, respectively.", "output": "PEI, PEI, DMAAPS23, PEI, DMAAPS55, PEI, DMAAPS95." }, { "input": "The PEI - betaine conjugates exhibited much lower protein adsorption and cytotoxicities compared with PEI 25K, and they also showed little or no hemolytic effect.", "output": "PEI, PEI." }, { "input": "Moreover, the PEI - betaine conjugates display satisfactory DNA condensation capability; and in the absence and presence of serum, PEI - DMAAPS23 % / pEGFP and PEI - DMAAPS55 % / pEGFP complexes exhibited remarkable gene transfection efficiencies determined by flow cytometry, which are in general several times higher than that of PEI 25K.", "output": "PEI, PEI, DMAAPS23, PEI, DMAAPS55, PEI." }, { "input": "With these favorable properties, the PEI - betaine conjugates hold great potential for use as efficient gene delivery vectors.", "output": "PEI." }, { "input": "This study suggests that the betaine monomer may serve as a biocompatible modifying agent and this facile strategy may provide a facile and effective way for constructing some other biocompatible materials.", "output": "There is no related enetity." }, { "input": "Interactions between Pluronics ( F127 and F68 ) and bile salts ( NaTDC ) in the aqueous phase and the interface of oil - in - water emulsions.", "output": "Pluronics ( F127 and F68 ), bile salts, NaTDC." }, { "input": "Pluronics are being introduced in food research in order to delay lipid digestion, with the length of hydrophilic and hydrophobic chains playing an important role in the rate of such a process.", "output": "Pluronics." }, { "input": "Since bile salts play a crucial role in the lipid digestion process, the aim of this work is to analyze the interactions between Pluronic F127 or F68 and the bile salt NaTDC when the latter is added at physiological concentrations.", "output": "bile salts, Pluronic F127 or F68, bile salt, NaTDC." }, { "input": "These interactions are studied at the Pluronic - covered oil - water interface and in the aqueous phase of Pluronic - stabilized emulsions.", "output": "Pluronic, Pluronic." }, { "input": "This work has been carried out with techniques such as differential scanning calorimetry, interfacial tension, dilatational rheology, and scanning electron microscopy.", "output": "There is no related enetity." }, { "input": "As a result, Pluronic F127 was shown to be more resistant to displacement by bile salt than F68 at the oil - water interface due to the larger steric hindrance and interfacial coverage provided.", "output": "Pluronic F127, bile salt, F68." }, { "input": "In addition, Pluronics have the ability to compete for the oil - water interface and interact in the bulk with the bile salt.", "output": "Pluronics, bile salt." }, { "input": "Concretely, Pluronic F127 seems to interact with more molecules of bile salt in the bulk, thus hindering their adsorption onto the oil - water interface.", "output": "Pluronic F127, bile salt." }, { "input": "As a conclusion, Pluronic F127 affects to a larger extent the ability of bile salt to promote the further cascade of lipolysis in the presence of lipase owing to a combination of interfacial and bulk events.", "output": "Pluronic F127, bile salt." }, { "input": "Fluorescence ( fluidity / hydration ) and calorimetric studies of interactions of bile acid - drug conjugates with model membranes.", "output": "bile acid." }, { "input": "We have studied the interactions of three bile acid - tamoxifen conjugates, lithocholic acid - tamoxifen ( LA - Tam ( 1 ) - Am ), deoxycholic acid - tamoxifen ( DCA - Tam ( 2 ) - Am ), and cholic acid - tamoxifen ( CA - Tam ( 3 ) - Am ), possessing 1 - 3 tamoxifen molecules having an amine headgroup with model DPPC membranes and compared with N - desmethylated tamoxifen ( TamNHMe ) using DPH based fluorescence anisotropy, Prodan based hydration, and differential scanning calorimetry studies.", "output": "bile acid, tamoxifen, lithocholic acid, tamoxifen, LA - Tam, deoxycholic acid, tamoxifen, DCA - Tam, cholic acid, tamoxifen, CA - Tam, tamoxifen, amine, DPPC, N - desmethylated tamoxifen, TamNHMe, DPH, Prodan." }, { "input": "DPH based anisotropy studies showed that bile acid - tamoxifen conjugates increase membrane fluidity, which strongly depends on the number of tamoxifen molecules conjugated to bile acid and the percentage of doping of bile acid - tamoxifen conjugates in the DPPC membranes.", "output": "DPH, bile acid, tamoxifen, tamoxifen, bile acid, bile acid, tamoxifen, DPPC." }, { "input": "The order of membrane fluidity of the coliposomes from bile acid - tamoxifen conjugates and DPPC lipids in gel phase was found to be CA - Tam ( 3 ) - Am > DCA - Tam ( 2 ) - Am > LA - Tam ( 1 ) - Am > TamNHMe.", "output": "bile acid, tamoxifen, DPPC, CA - Tam, DCA - Tam, LA - Tam, TamNHMe." }, { "input": "Incorporation of bile acid - tamoxifen conjugates showed an unusual complex behavior of membrane hydration, as evident from Prodan based hydration studies.", "output": "bile acid, tamoxifen, Prodan." }, { "input": "Temperature dependent study showed incorporation of LA - Tam ( 1 ) - Am and DCA - Tam ( 2 ) - Am conjugates decreases membrane hydration with an increase in temperature up to the phase transition temperature ( T ( m ) ).", "output": "LA - Tam, DCA - Tam." }, { "input": "Differential scanning calorimetry studies showed a decrease in phase transition temperature ( T ( m ) ) upon an increase in the percentage of doping of TamNHMe and CA - Tam ( 3 ) - Am, whereas LA - Tam ( 1 ) - Am and DCA - Tam ( 2 ) - Am do not cause a major change in the phase transition temperature ( T ( m ) ) of DPPC liposomes.", "output": "TamNHMe, CA - Tam, LA - Tam, DCA - Tam, DPPC." }, { "input": "These studies showed the differential behavior of bile acid - tamoxifen conjugates regulating the membrane fluidity, hydration, and phase transition of model membranes depending upon the percentage of doping and tamoxifen conjugation to bile acids.", "output": "bile acid, tamoxifen, tamoxifen, bile acids." }, { "input": "Understanding and Controlling Morphology Formation in Langmuir - Blodgett Block Copolymer Films Using PS - P4VP and PS - P4VP / PDP.", "output": "PS - P4VP, PS - P4VP, PDP." }, { "input": "This contribution offers a comprehensive understanding of the factors that govern the morphologies of Langmuir - Blodgett ( LB ) monolayers of amphiphilic diblock copolymers ( BCs ).", "output": "There is no related enetity." }, { "input": "This is achieved by a detailed investigation of a wide range of polystyrene - poly ( 4 - vinyl pyridine ) ( PS - P4VP ) block copolymers, in contrast to much more limited ranges in previous studies.", "output": "polystyrene - poly ( 4 - vinyl pyridine ), PS - P4VP." }, { "input": "Parameters that are varied include the block ratios ( mainly for similar total molecular weights, occasionally other total molecular weights ), the presence or not of 3 - n - pentadecylphenol ( PDP, usually equimolar with VP, with which it hydrogen bonds ), the spreading solution concentration ( \" low \" and \" high \" ), and the LB technique ( standard vs \" solvent - assisted \" ).", "output": "3 - n - pentadecylphenol, PDP, hydrogen." }, { "input": "Our observations are compared with previously published results on other amphiphilic diblock copolymers, which had given rise to contradictory interpretations of morphology formation.", "output": "There is no related enetity." }, { "input": "Based on the accumulated results, we re - establish early literature conclusions that three main categories of LB block copolymer morphologies are obtained depending on the block ratio, termed planar, strand, and dot regimes.", "output": "There is no related enetity." }, { "input": "The block composition boundaries in terms of mol % block content are shown to be similar for all BCs having alkyl chain substituents on the hydrophilic block ( such as PS - P4VP / PDP ) and are shifted to higher values for BCs with no alkyl chain substituents ( such as PS - P4VP ).", "output": "PS - P4VP, PDP, PS - P4VP." }, { "input": "This is attributed to the higher surface area per repeat unit of the hydrophilic block monolayer on the water surface for the former, as supported by the onset and limiting areas of the Langmuir isotherms for the BCs in the dot regime.", "output": "There is no related enetity." }, { "input": "2D phase diagrams are discussed in terms of relative effective surface areas of the two blocks.", "output": "There is no related enetity." }, { "input": "We identify and discuss how kinetic effects on morphology formation, which have been highlighted in more recent literature, are superposed on the compositional effects.", "output": "There is no related enetity." }, { "input": "The kinetic effects are shown to depend on the morphology regime, most strongly influencing the strand and, especially, planar regimes, where they give rise to a diversity of specific structures.", "output": "There is no related enetity." }, { "input": "Besides film dewetting mechanisms, which are different when occurring in structured versus unstructured films ( the latter previously discussed in the literature ), kinetic influences are discussed in terms of chain association dynamics leading to depletion effects that impact on growing aggregates.", "output": "There is no related enetity." }, { "input": "These depletion effects particularly manifest themselves in more dilute spreading solutions, with higher molecular weight polymers, and in composition regimes characterized by equilibrium degrees of aggregation that are effectively infinite.", "output": "There is no related enetity." }, { "input": "It is by understanding these various kinetic influences that the diversity of structures can be classified by the three main composition - dependent regimes.", "output": "There is no related enetity." }, { "input": "Robust array - based coregulator binding assay predicting ER alpha - agonist potency and generating binding profiles reflecting ligand structure.", "output": "There is no related enetity." }, { "input": "Testing chemicals for their endocrine - disrupting potential, including interference with estrogen receptor ( ER ) signaling, is an important aspect of chemical safety testing.", "output": "estrogen." }, { "input": "Because of the practical drawbacks of animal testing, the development of in vitro alternatives for the uterotrophic assay and other in vivo ( anti ) estrogenicity tests has high priority.", "output": "There is no related enetity." }, { "input": "It was previously demonstrated that an in vitro assay that profiles ligand - induced binding of ER alpha to a microarray of coregulator - derived peptides might be a valuable candidate for a panel of in vitro assays aiming at an ultimate replacement of the uterotrophic assay.", "output": "There is no related enetity." }, { "input": "In the present study, the reproducibility and robustness of this coregulator binding assay was determined by measuring the binding profiles of 14 model compounds that are recommended by the Office of Prevention, Pesticides and Toxic Substances for testing laboratory proficiency in estrogen receptor transactivation assays.", "output": "estrogen." }, { "input": "With a median coefficient of variation of 5. 0 % and excellent correlation ( R ( 2 ) = 0. 993 ) between duplicate measurements, the reproducibility of the ER alpha - coregulator binding assay was better than the reproducibility of other commonly used in vitro ER functional assays.", "output": "There is no related enetity." }, { "input": "In addition, the coregulator binding assay is correctly predicting the estrogenicity for 13 out of 14 compounds tested.", "output": "There is no related enetity." }, { "input": "When the potency of the ER - agonists to induce ER alpha - coregulator binding was compared to their ER binding affinity, their ranking was similar, and the correlation between the EC50 values was excellent ( R ( 2 ) = 0. 96 ), as was the correlation with their potency in a transactivation assay ( R ( 2 ) = 0. 94 ).", "output": "There is no related enetity." }, { "input": "Moreover, when the ER alpha - coregulator binding profiles were hierarchically clustered using Euclidian cluster distance, the structurally related compounds were found to cluster together, whereas the steroid test compounds having an aromatic A - ring were separated from those with a cyclohexene A - ring.", "output": "steroid, cyclohexene." }, { "input": "We concluded that this assay is capable of distinguishing ER alpha agonists and antagonists and that it even reflects the structural similarity of ER alpha agonists, indicating a potential to achieve identification and classification of ER alpha endocrine disruptors with high fidelity.", "output": "There is no related enetity." }, { "input": "Two - photon circular - linear dichroism of perylene in solution: a theoretical - experimental study.", "output": "perylene." }, { "input": "Herein, we report on the theoretical - experimental analysis of the two - photon absorption ( TPA ) and two - photon circular - linear dichroism ( TPCLD ) spectra of a highly conjugated, rigid, and centrosymmetric molecule in solution, that is, perylene / CH2Cl2.", "output": "perylene, CH2Cl2." }, { "input": "We show how a three - energy - level diagram, under the sum - over - essential states approach, assists in the determination of the magnitude of transition electric dipole moments and the angle between them for the main TPA transitions.", "output": "There is no related enetity." }, { "input": "We demonstrate the potential of TPCLD to reveal the symmetry of excited states and the angles between their transition electric dipole moments and that of the ground state.", "output": "There is no related enetity." }, { "input": "By means of TPCLD, we explain how the overwhelming contribution of certain TPA transitions can mask important spectral features in regions where the transition electric dipole moments are perpendicular.", "output": "There is no related enetity." }, { "input": "TPCLD is expected to enhance the understanding of the photophysical properties of materials that are not accessible using conventional linear and two - photon spectroscopy.", "output": "There is no related enetity." }, { "input": "TPA and TPCLD measurements were performed employing the open - aperture Z - scan technique using an amplified femtosecond system.", "output": "There is no related enetity." }, { "input": "Time - dependent density functional theory ( TD - DFT ) calculations were carried out using response theory at the B3LYP level with the aug - cc - pVDZ basis set.", "output": "There is no related enetity." }, { "input": "Solvent effects were included through the polarizable continuum model ( PCM ).", "output": "There is no related enetity." }, { "input": "Molecular imaging by optically detected electron spin resonance of nitrogen - vacancies in nanodiamonds.", "output": "nitrogen." }, { "input": "We propose a novel biomedical imaging technique, called nanodiamond imaging, that noninvasively records the three - dimensional distribution of biologically tagged nanodiamonds in vivo.", "output": "There is no related enetity." }, { "input": "Our technique performs optically detected electron spin resonance of nitrogen - vacancy centers in nanodiamonds, a nontoxic nanomaterial that is easily biologically functionalized.", "output": "nitrogen." }, { "input": "We demonstrate the feasibility of the technique by imaging multiple nanodiamond targets within pieces of chicken breast; it is the first demonstration of imaging within scattering tissue by optically detected magnetic resonance.", "output": "There is no related enetity." }, { "input": "We achieve a sensitivity equivalent to 740 pg of nanodiamond in 100 s of measurement time and a spatial resolution of 800 mu m over a 1 cm ( 2 ) field of view, and we show how the technique has the potential to yield images with combined high sensitivity ( ~ 100 fg nanodiamond ) AND high spatial resolution ( ~ 100 mu m ) over organism - scale fields of view, features which are mutually exclusive in existing imaging modalities except at the shallowest imaging depths.", "output": "There is no related enetity." }, { "input": "Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro - opiomelanocortin ( POMC ) and / or decreased neuropeptide Y ( NPY ).", "output": "acylethanolamide." }, { "input": "Newly synthesized acylethanolamide derivatives oleoyl - L - valinolamide ( 1 ), oleoyl - D - valinolamide ( 2 ), elaidoyl - L - valinolamide ( 3 ), elaidoyl - D - valinolamide ( 4 ) stearoyl - L - valinolamide ( 5 ), and palmitoyl - L - valinolamide ( 6 ) were investigated in mice as antiobesity compounds.", "output": "acylethanolamide, oleoyl - L - valinolamide, oleoyl - D - valinolamide, elaidoyl - L - valinolamide, elaidoyl - D - valinolamide, stearoyl - L - valinolamide, palmitoyl - L - valinolamide." }, { "input": "Compounds 1, 2, 5, 6 significantly decreased body weight by 6. 57 % following eight injections of 1 mg / kg i. p. during 39 days, while 3 and 4 showed no such activity.", "output": "There is no related enetity." }, { "input": "Receptor binding indicated that no compound activated CB1, CB2, PPAR alpha, or TRPV1 receptors.", "output": "There is no related enetity." }, { "input": "Hypothalamic RT - PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up - regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down - regulated by the respective compounds 1, 5, 6 and 1, 2, 5.", "output": "There is no related enetity." }, { "input": "Oleoyl - L - valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition.", "output": "Oleoyl - L - valinolamide, glucose." }, { "input": "Effects of oleoyl - L - valinolamide on weight were dose - dependent, and it could be given orally.", "output": "oleoyl - L - valinolamide." }, { "input": "1, 2, 4, 5 down - regulated FAAH mRNA expression.", "output": "There is no related enetity." }, { "input": "The effect of inorganic arsenic on endothelium - dependent relaxation: Role of NADPH oxidase and hydrogen peroxide.", "output": "arsenic, NADPH, hydrogen peroxide." }, { "input": "Chronic arsenic ingestion predisposes to vascular disease, but underlying mechanisms are poorly understood.", "output": "arsenic." }, { "input": "In the present study we have analyzed the effects of short - term arsenite exposure on vascular function and endothelium - dependent relaxation.", "output": "arsenite." }, { "input": "Endothelium - dependent relaxations, nitric oxide ( NO ) and endothelium derived hyperpolarizing factor ( EDHF ) - type, were studied in rabbit iliac artery and aortic rings using the G protein - coupled receptor agonist acetylcholine ( ACh ) and by cyclopiazonic acid ( CPA ), which promotes store - operated Ca ( 2 + ) entry by inhibiting the endothelial SERCA pump.", "output": "nitric oxide, NO, acetylcholine, ACh, cyclopiazonic acid, CPA, Ca ( 2 + )." }, { "input": "Production of reactive oxygen species ( ROS ) in the endothelium of rabbit aortic valve leaflets and endothelium - denuded RIA and aortic rings was assessed by imaging of dihydroethidium.", "output": "oxygen, dihydroethidium." }, { "input": "In the iliac artery, exposure to 100 mu M arsenite for 30min potentiated EDHF - type relaxations evoked by both CPA and ACh.", "output": "arsenite, CPA, ACh." }, { "input": "Potentiation was prevented by catalase, the catalase / superoxide dismutase mimetic manganese porphyrin and the NADPH oxidase inhibitor apocynin.", "output": "superoxide, manganese porphyrin, NADPH, apocynin." }, { "input": "By contrast in aortic rings, that exhibited negligible EDHF - type responses, endothelium - dependent NO - mediated relaxations evoked by CPA and ACh were unaffected by arsenite.", "output": "NO, CPA, ACh, arsenite." }, { "input": "Arsenite induced apocynin - sensitive increases in ROS production in the aortic valve endothelium, but not in the media and adventitia of the iliac artery and aorta.", "output": "Arsenite, apocynin." }, { "input": "Our results suggest that arsenite can potentiate EDHF - type relaxations via a mechanism that is dependent on hydrogen peroxide, thus demonstrating that dismutation of the superoxide anion generated by NADPH oxidase can potentially offset loss of NO bioavailability under conditions of reduced eNOS activity.", "output": "arsenite, hydrogen peroxide, superoxide, NADPH, NO." }, { "input": "By contrast, selective increases in endothelial ROS production following exposure to arsenite failed to modify relaxations mediated by endogenous NO.", "output": "arsenite, NO." }, { "input": "Comparative analysis of human CYP3A4 and rat CYP3A1 induction and relevant gene expression by bisphenol A and diethylstilbestrol: implications for toxicity testing paradigms.", "output": "bisphenol A, diethylstilbestrol." }, { "input": "Bisphenol A ( BPA ) and diethylstilbestrol ( DES ) are endocrine - disrupting chemicals that interact with the human pregnane X receptor ( PXR ).", "output": "Bisphenol A, BPA, diethylstilbestrol, DES." }, { "input": "CYP3A4 enzyme is essential in the hydroxylation of steroid hormones and is regulated by PXR.", "output": "steroid." }, { "input": "In the present study, human and rat hepatoma cell lines were exposed to BPA and DES.", "output": "There is no related enetity." }, { "input": "Both BPA and DES ( 10 - 50 mu M ) caused a significant activation of the CYP3A4 promoter via the PXR in the DPX2 human hepatoma cell line.", "output": "BPA, DES." }, { "input": "No activation of rat PXR was seen.", "output": "There is no related enetity." }, { "input": "BPA and DES treated DPX2 cells demonstrated increased expression of CYP3A4 mRNA, and increased enzyme activity.", "output": "BPA, DES." }, { "input": "In summary, BPA, in concentrations relevant to current safety levels of human exposure, activates the human PXR and demonstrates an increase in CYP3A4 mRNA expression and enzyme activity.", "output": "BPA." }, { "input": "BPA actions in this model system occur to a greater extent than DES.", "output": "BPA, DES." }, { "input": "This study raises concerns regarding our current toxicity testing paradigms and species utilization.", "output": "There is no related enetity." }, { "input": "Regulation of amino acid metabolism as a defensive strategy in the brain of three freshwater teleosts in response to high environmental ammonia exposure.", "output": "amino acid, ammonia." }, { "input": "Many teleosts have evolved mechanisms to cope with ammonia toxicity in the brain when confronted with high environmental ammonia ( HEA ).", "output": "ammonia, ammonia." }, { "input": "In the present study, the possible role of conversion of accumulated ammonia to glutamine and other free amino acids in the brain of three freshwater teleosts differing in their sensitivities to ammonia was investigated.", "output": "ammonia, glutamine, amino acids, ammonia." }, { "input": "The detoxification mode of ammonia in brain is suggested to be through amination of glutamate to glutamine by the coupled activities of glutamate dehydrogenase ( GDH ), transaminase ( aspartate aminotransaminase ' AST ' and alanine aminotransaminase ' ALT ' ) and glutamine synthetase ( GSase ).", "output": "ammonia, glutamate, glutamine, glutamate, aspartate, alanine, glutamine." }, { "input": "We investigated the metabolic response of amino acids in the brain of highly sensitive salmonid Oncorhynchus mykiss ( rainbow trout ), the less sensitive cyprinid Cyprinus carpio ( common carp ) and the highly resistant cyprinid Carassius auratus ( goldfish ) when exposed to 1mM ammonia ( as NH4HCO3; pH 7. 9 ) for 0 h ( control ), 3 h, 12 h, 24 h, 48 h, 84 h and 180 h.", "output": "amino acids, ammonia, NH4HCO3." }, { "input": "Results show that HEA exposure increased ammonia accumulation significantly in the brain of all the three species from 12h onwards.", "output": "ammonia." }, { "input": "Unlike in trout, ammonia accumulation in carp and goldfish was restored to control levels ( 48 - 84h ); which was accompanied with a significant increase in glutamine content as well as GSase activity.", "output": "ammonia, glutamine." }, { "input": "In trout, glutamine levels also increased ( 84 - 180 h ) but GSase was not activated.", "output": "glutamine." }, { "input": "The elevated glutamine level in trout was accompanied by a significant depletion of the glutamate pool in contrast to the stable glutamate levels seen in carp and goldfish.", "output": "glutamine, glutamate, glutamate." }, { "input": "This suggests a simultaneous increase in the rate of glutamate formation to match with the demand of glutamine formation in cyprinids.", "output": "glutamate, glutamine." }, { "input": "The activity of GDH was elevated significantly in carp and goldfish but remained unaltered in trout.", "output": "There is no related enetity." }, { "input": "Also, the transaminase enzymes ( AST and ALT ) were elevated significantly in exposed carp and goldfish while only ALT was up - regulated in trout.", "output": "There is no related enetity." }, { "input": "Consequently, in carp and goldfish both aspartate and alanine were utilized under HEA, whereas only alanine was consumed in trout.", "output": "aspartate, alanine, alanine." }, { "input": "With ammonia treatment, significant changes in concentrations of other amino acids also occurred.", "output": "ammonia, amino acids." }, { "input": "None of the species could detoxify brain ammonia into urea.", "output": "ammonia." }, { "input": "This study suggests that protective strategies to combat ammonia toxicity in brain are more pronounced in carp and goldfish than in trout.", "output": "ammonia." }, { "input": "Basic N - interlinked imipramines show apoptotic activity against malignant cells including Burkitt ' s lymphoma.", "output": "N, imipramines." }, { "input": "We here report the synthesis of ethylene glycol N - interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride.", "output": "ethylene glycol, N, imipramine, desipramine, lithium aluminium hydride." }, { "input": "The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt ' s lymphoma cell line.", "output": "There is no related enetity." }, { "input": "Basic amine analogues were found to be important for increased potency.", "output": "amine." }, { "input": "Imipramine and desipramine were also tested for apoptotic activity and were found to be much less active than the novel dimeric compounds.", "output": "Imipramine, desipramine." }, { "input": "Imipramine dimers were only found to be moderate inhibitors of the human serotonin transporter ( hSERT ) having IC ( 50 ) values in the micromolar region whilst the induction of cell death occurred independently of hSERT expression.", "output": "Imipramine, serotonin." }, { "input": "These results demonstrate the potential of newly designed and synthesised imipramines derivatives for use against malignant cells, including those resistant to standard chemotherapy.", "output": "imipramines." }, { "input": "Water ice nanoparticles: size and temperature effects on the mid - infrared spectrum.", "output": "There is no related enetity." }, { "input": "Mid - infrared spectra have been measured for cubic ice ( I ( c ) ) nanoparticles ( 3 - 150 nm diameter ) formed by rapid collisional cooling over a wide range of temperatures ( 5 - 209 K ).", "output": "There is no related enetity." }, { "input": "Spectral diagnostics, such as the ratio of surface related dangling OH to interior H - bonded OH stretch bands, reveal the manner in which particle size depends on bath gas temperature and density, and on water molecule concentration.", "output": "OH, H, OH." }, { "input": "For particles smaller than 5 nm strained intermolecular bonds on the surface and subsurface cause the predominant OH stretch peak position to be dramatically blue shifted by up to 40 cm ( - 1 ).", "output": "OH." }, { "input": "In the size regime of 8 - 200 nm the position of the OH stretch absorption band maximum is relatively unaffected by particle size and it is possible to measure the temperature dependence of the peak location without influences from the surface or scattering.", "output": "OH." }, { "input": "The band maximum shifts in a linear fashion from 3218 cm ( - 1 ) at 30 K to 3253 cm ( - 1 ) at 209 K, which may assist with temperature profiling of ice particles in atmospheric clouds and extraterrestrial systems.", "output": "There is no related enetity." }, { "input": "Over the same temperature range the librational mode band shifts very little, from 870 to 860 cm ( - 1 ).", "output": "There is no related enetity." }, { "input": "In the water stretching and bending regions discrete spectral features associated with the surface or sub - surface layers have been detected in particles as large as 80 nm.", "output": "There is no related enetity." }, { "input": "Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.", "output": "There is no related enetity." }, { "input": "Mitochondrial DNA ( mtDNA ) depletion syndromes ( MDS ) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs.", "output": "There is no related enetity." }, { "input": "MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis ( TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP ) or mtDNA replication ( POLG and C10orf2 ).", "output": "There is no related enetity." }, { "input": "MDS are phenotypically heterogeneous and usually classified as myopathic, encephalomyopathic, hepatocerebral or neurogastrointestinal.", "output": "There is no related enetity." }, { "input": "Myopathic MDS, caused by mutations in TK2, usually present before the age of 2 years with hypotonia and muscle weakness.", "output": "There is no related enetity." }, { "input": "Encephalomyopathic MDS, caused by mutations in SUCLA2, SUCLG1, or RRM2B, typically present during infancy with hypotonia and pronounced neurological features.", "output": "There is no related enetity." }, { "input": "Hepatocerebral MDS, caused by mutations in DGUOK, MPV17, POLG, or C10orf2, commonly have an early - onset liver dysfunction and neurological involvement.", "output": "There is no related enetity." }, { "input": "Finally, TYMP mutations have been associated with mitochondrial neurogastrointestinal encephalopathy ( MNGIE ) disease that typically presents before the age of 20 years with progressive gastrointestinal dysmotility and peripheral neuropathy.", "output": "There is no related enetity." }, { "input": "Overall, MDS are severe disorders with poor prognosis in the majority of affected individuals.", "output": "There is no related enetity." }, { "input": "No efficacious therapy is available for any of these disorders.", "output": "There is no related enetity." }, { "input": "Affected individuals should have a comprehensive evaluation to assess the degree of involvement of different systems.", "output": "There is no related enetity." }, { "input": "Treatment is directed mainly toward providing symptomatic management.", "output": "There is no related enetity." }, { "input": "Nutritional modulation and cofactor supplementation may be beneficial.", "output": "There is no related enetity." }, { "input": "Liver transplantation remains controversial.", "output": "There is no related enetity." }, { "input": "Finally, stem cell transplantation in MNGIE disease shows promising results.", "output": "There is no related enetity." }, { "input": "Vascular endothelial growth factor induces growth of uterine cervix and immune cell recruitment in mice.", "output": "There is no related enetity." }, { "input": "Knowledge of uterine cervical epithelial biology and factors that influence its events may be critical in understanding the process of cervical remodeling ( CR ).", "output": "There is no related enetity." }, { "input": "Here, we examine the impact of exogenous vascular endothelial growth factor ( VEGF ) on uterine cervical epithelial growth in mice ( nonpregnant and pregnant ) treated with VEGF agents ( recombinant and inhibitor ) using a variety of morphological and molecular techniques.", "output": "There is no related enetity." }, { "input": "Exogenous VEGF altered various uterine cervical epithelial cellular events, including marked induction of growth, edema, increase in inter - epithelial paracellular space, and recruitment of immune cells to the outer surface of epithelial cells ( cervical lumen ).", "output": "There is no related enetity." }, { "input": "We conclude that VEGF induces multiple alterations in the uterine cervical epithelial tissues that may play a role in local immune surveillance and uterine cervical growth during CR.", "output": "There is no related enetity." }, { "input": "Upregulation of nuclear factor of activated T - cells by nerve injury contributes to development of neuropathic pain.", "output": "There is no related enetity." }, { "input": "Nerve injury induces long - term changes in gene expression in the nociceptive circuitry and can lead to chronic neuropathic pain.", "output": "There is no related enetity." }, { "input": "However, the transcriptional mechanism involved in neuropathic pain is poorly understood.", "output": "There is no related enetity." }, { "input": "Nuclear factor of activated T - cells ( NFATc ) is a transcriptional factor regulated by the Ca ( 2 + ) - dependent protein phosphatase calcineurin.", "output": "Ca ( 2 + )." }, { "input": "In this study, we determined nerve injury - induced changes in the expression of NFATc1 - c4 in the dorsal root ganglia ( DRG ) and spinal cords and their role in the development of neuropathic pain.", "output": "There is no related enetity." }, { "input": "The mRNA of NFATc1 - c4 was detected in the rat DRG and dorsal spinal cord.", "output": "There is no related enetity." }, { "input": "Nerve injury transiently elevated NFATc1 - c3 mRNA levels and persistently increased NFATc4 and C - C chemokine receptor type 2 ( CCR2 ) mRNA levels in the DRG.", "output": "There is no related enetity." }, { "input": "However, NFATc1 - c4 mRNA levels in the spinal cord were not altered significantly by nerve injury.", "output": "There is no related enetity." }, { "input": "Nerve injury also significantly increased the protein level of dephosphorylated NFATc4 in the DRG.", "output": "There is no related enetity." }, { "input": "Intrathecal injection of the specific NFATc inhibitor 11R - VIVIT or the calcineurin inhibitor FK - 506 ( tacrolimus ) early after nerve injury significantly attenuated the development of tactile allodynia.", "output": "FK - 506, tacrolimus." }, { "input": "In addition, treatment with FK - 506 or 11R - VIVIT significantly reduced the mRNA levels of NFATc4 and CCR2 but not large - conductance Ca ( 2 + ) - activated K ( + ) channels, in the DRG after nerve injury.", "output": "FK - 506, Ca ( 2 + ), K ( + )." }, { "input": "Our findings suggest that peripheral nerve injury causes a time - dependent change in NFATc1 - c4 expression in the DRG.", "output": "There is no related enetity." }, { "input": "Calcineurin - NFATc - mediated expression of pronociceptive cytokines contributes to the transition from acute to chronic pain after nerve injury.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of purine 2 ' - fluoro - 2 ' - deoxyriboside ProTides as anti - influenza virus agents.", "output": "purine 2 ' - fluoro - 2 ' - deoxyriboside." }, { "input": "2 ' - Fluoro - 2 ' - deoxyguanosine has been reported to have potent anti - influenza virus activity in vitro and in vivo.", "output": "2 ' - Fluoro - 2 ' - deoxyguanosine." }, { "input": "Herein we describe the synthesis and biological evaluation of 6 - modified 2 ' - fluoro - 2 ' - deoxyguanosine analogues and their corresponding phosphoramidate ProTides as potential anti - influenza virus agents.", "output": "2 ' - fluoro - 2 ' - deoxyguanosine, phosphoramidate." }, { "input": "Whereas the parent nucleosides were devoid of antiviral activity in two different cellular assays, the 5 ' - O - naphthyl ( methoxy - L - alaninyl ) ProTide derivatives of 6 - O - methyl - 2 ' - fluoro - 2 ' - deoxyguanosine, 6 - O - ethyl - 2 ' - fluoro - 2 ' - deoxyguanosine, and 2 ' - deoxy - 2 ' - fluoro - 6 - chloroguanosine, and the 5 ' - O - naphthyl ( ethoxy - L - alaninyl ) ProTide of 6 - O - ethyl - 2 ' - fluoro - 2 ' - deoxyguanosine displayed antiviral EC ( 99 ) values of ~ 12 mu M.", "output": "nucleosides, 5 ' - O - naphthyl ( methoxy - L - alaninyl ), 6 - O - methyl - 2 ' - fluoro - 2 ' - deoxyguanosine, 6 - O - ethyl - 2 ' - fluoro - 2 ' - deoxyguanosine, 2 ' - deoxy - 2 ' - fluoro - 6 - chloroguanosine, 5 ' - O - naphthyl ( ethoxy - L - alaninyl ), 6 - O - ethyl - 2 ' - fluoro - 2 ' - deoxyguanosine." }, { "input": "The antiviral results are supported by metabolism studies.", "output": "There is no related enetity." }, { "input": "Rapid conversion into the L - alaninyl metabolite and then 6 - modified 2 ' - fluoro - 2 ' - deoxyguanosine 5 ' - monophosphate was observed in enzymatic assays with yeast carboxypeptidase Y or crude cell lysate.", "output": "L - alaninyl, 2 ' - fluoro - 2 ' - deoxyguanosine 5 ' - monophosphate." }, { "input": "Evidence for efficient removal of the 6 - substituent on the guanine part was provided by enzymatic studies with adenosine deaminase, and by molecular modeling of the nucleoside 5 ' - monophosphates in the catalytic site of a model of ADAL1, thus indicating the utility of the double prodrug concept.", "output": "guanine, adenosine, nucleoside 5 ' - monophosphates." }, { "input": "Ezogabine: a novel antiepileptic for adjunctive treatment of partial - onset seizures.", "output": "Ezogabine." }, { "input": "Epilepsy is defined as a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults.", "output": "There is no related enetity." }, { "input": "It is a disruption of the electrical conductivity or activity in the brain, resulting in a seizure.", "output": "There is no related enetity." }, { "input": "In the United States, approximately 120 of every 100, 000 people seek medical attention due to new seizure activity.", "output": "There is no related enetity." }, { "input": "Ezogabine, known as retigabine in Europe, is an ethyl N - ( 2 - amino - 4 - [ { fluorophenyl } methlamino ] phenylcarbamate ).", "output": "Ezogabine, retigabine, ethyl N - ( 2 - amino - 4 - [ { fluorophenyl } methlamino ] phenylcarbamate )." }, { "input": "The drug has been approved by the United States Food and Drug Administration ( FDA ) and European Medicines Agency for adjunctive treatment of partial - onset seizures in adults.", "output": "There is no related enetity." }, { "input": "Ezogabine exerts its therapeutic effect by enhancing transmembrane potassium channels ( KCNQ ion channels ), which is a novel mechanism in comparison with other antiepileptics.", "output": "Ezogabine, potassium." }, { "input": "There are no specific documented contraindications to ezogabine.", "output": "ezogabine." }, { "input": "Warnings target patients that have benign prostatic hyperplasia or are receiving concomitant anticholinergic drugs due to a risk of urinary retention ( 2 % ).", "output": "There is no related enetity." }, { "input": "The FDA has required that ezogabine be part of a risk evaluation and mitigation strategy program in order to inform health care professionals of the risk of urinary retention.", "output": "ezogabine." }, { "input": "Prescribers should inform patients that ezogabine can cause urinary retention, including urinary hesitation, and instruct them to seek immediate medical attention if these symptoms occur.", "output": "ezogabine." }, { "input": "A medication guide has been developed for distribution to patients.", "output": "There is no related enetity." }, { "input": "The role of human carboxylesterases in drug metabolism: have we overlooked their importance?", "output": "There is no related enetity." }, { "input": "Carboxylesterases are a multigene family of mammalian enzymes widely distributed throughout the body that catalyze the hydrolysis of esters, amides, thioesters, and carbamates.", "output": "esters, amides, thioesters, carbamates." }, { "input": "In humans, two carboxylesterases, hCE1 and hCE2, are important mediators of drug metabolism.", "output": "There is no related enetity." }, { "input": "Both are expressed in the liver, but hCE1 greatly exceeds hCE2.", "output": "There is no related enetity." }, { "input": "In the intestine, only hCE2 is present and highly expressed.", "output": "There is no related enetity." }, { "input": "The most common drug substrates of these enzymes are ester prodrugs specifically designed to enhance oral bioavailability by hydrolysis to the active carboxylic acid after absorption from the gastrointestinal tract.", "output": "ester, carboxylic acid." }, { "input": "Carboxylesterases also play an important role in the hydrolysis of some drugs to inactive metabolites.", "output": "There is no related enetity." }, { "input": "It has been widely believed that drugs undergoing hydrolysis by hCE1 and hCE2 are not subject to clinically significant alterations in their disposition, but evidence exists that genetic polymorphisms, drug - drug interactions, drug - disease interactions and other factors are important determinants of the variability in the therapeutic response to carboxylesterase - substrate drugs.", "output": "There is no related enetity." }, { "input": "The implications for drug therapy are far - reaching, as substrate drugs include numerous examples from widely prescribed therapeutic classes.", "output": "There is no related enetity." }, { "input": "Representative drugs include angiotensin - converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet drugs, statins, antivirals, and central nervous system agents.", "output": "statins." }, { "input": "As research interest increases in the carboxylesterases, evidence is accumulating of their important role in drug metabolism and, therefore, the outcomes of pharmacotherapy.", "output": "There is no related enetity." }, { "input": "Recommendations for meeting the pediatric patient ' s need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.", "output": "There is no related enetity." }, { "input": "Children warrant access to care from clinical pharmacists trained in pediatrics.", "output": "There is no related enetity." }, { "input": "The American College of Clinical Pharmacy Pediatrics Practice and Research Network ( ACCP Pediatrics PRN ) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships.", "output": "There is no related enetity." }, { "input": "Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients.", "output": "There is no related enetity." }, { "input": "The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists.", "output": "There is no related enetity." }, { "input": "These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.", "output": "There is no related enetity." }, { "input": "Toll - like receptor 2 mediates peripheral nerve injury - induced NADPH oxidase 2 expression in spinal cord microglia.", "output": "NADPH." }, { "input": "We have previously reported that NADPH oxidase 2 ( Nox2 ) is up - regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity.", "output": "NADPH." }, { "input": "However, the mechanisms and molecules involved in Nox2 induction have not been elucidated.", "output": "There is no related enetity." }, { "input": "Previous studies have shown that Toll - like receptors ( TLRs ) are involved in nerve injury - induced spinal cord microglia activation.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury.", "output": "There is no related enetity." }, { "input": "Studies using TLR knock - out mice have shown that nerve injury - induced microglial Nox2 up - regulation is abrogated in TLR2 but not in TLR3 or - 4 knock - out mice.", "output": "There is no related enetity." }, { "input": "Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels.", "output": "There is no related enetity." }, { "input": "Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro.", "output": "oxygen." }, { "input": "Studies on intracellular signaling pathways indicate that NF - kappa B and p38 MAP kinase activation is required for TLR2 - induced Nox2 expression in glial cells.", "output": "There is no related enetity." }, { "input": "Conclusively, our data show that TLR2 mediates nerve injury - induced Nox2 gene expression in spinal cord microglia via NF - kappa B and p38 activation and thereby may contribute to spinal cord microglia activation.", "output": "There is no related enetity." }, { "input": "Serum levels of 25 - hydroxyvitamin D and the CYP3A biomarker 4 beta - hydroxycholesterol in a high - dose vitamin D supplementation study.", "output": "25 - hydroxyvitamin D, 4 beta - hydroxycholesterol, vitamin D." }, { "input": "The primary aim was to study the relationship between individual serum levels of 25 - hydroxyvitamin D and 4 beta - hydroxycholesterol, which is an endogenous biomarker of the drug - metabolizing CYP3A enzymes.", "output": "25 - hydroxyvitamin D, 4 beta - hydroxycholesterol." }, { "input": "In addition, the relationship between this biomarker and inflammation, measured as C - reactive protein ( CRP ), was investigated.", "output": "There is no related enetity." }, { "input": "Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high - dose ( 4000 IU / day ) vitamin D for 12 months.", "output": "vitamin D." }, { "input": "One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed.", "output": "There is no related enetity." }, { "input": "At this time point, 25 - hydroxyvitamin D levels were found to range between 10 and 284 nM.", "output": "25 - hydroxyvitamin D." }, { "input": "Individual levels of 25 - hydroxyvitamin D as well as CRP were compared with 4 beta - hydroxycholesterol levels.", "output": "25 - hydroxyvitamin D, 4 beta - hydroxycholesterol." }, { "input": "In addition, all participants were genotyped for two polymorphisms ( Taq1 and Foq1 ) in the vitamin D receptor gene.", "output": "vitamin D." }, { "input": "There was no significant correlation between individual serum levels of 25 - hydroxyvitamin D and 4 beta - hydroxycholesterol.", "output": "25 - hydroxyvitamin D, 4 beta - hydroxycholesterol." }, { "input": "However, a moderate, but statistically significant, negative correlation between CRP and 4 beta - hydroxycholesterol levels was observed.", "output": "4 beta - hydroxycholesterol." }, { "input": "This study in patients with highly variable serum levels of 25 - hydroxyvitamin D could not reveal any relationship between vitamin D and 4 beta - hydroxycholesterol, an endogenous biomarker of CYP3A activity.", "output": "25 - hydroxyvitamin D, vitamin D, 4 beta - hydroxycholesterol." }, { "input": "However, the negative correlation between CRP and 4 beta - hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.", "output": "4 beta - hydroxycholesterol." }, { "input": "Apoptotic cell death in rat epididymis following epichlorohydrin treatment.", "output": "epichlorohydrin." }, { "input": "Epichlorohydrin ( ECH ) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility.", "output": "Epichlorohydrin, ECH." }, { "input": "This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment.", "output": "There is no related enetity." }, { "input": "Rats were administrated with a single oral dose of ECH ( 50 mg / kg ).", "output": "ECH." }, { "input": "ECH - induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay.", "output": "ECH, dUTP." }, { "input": "The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively.", "output": "There is no related enetity." }, { "input": "The Western blot analysis demonstrated no significant changes in proapoptotic Bcl - 2 - associated X ( Bax ) and anti - apoptotic Bcl - 2 expression during the time course of the study.", "output": "There is no related enetity." }, { "input": "However, phospho - p38 mitogen - activated protein kinase ( p - p38 MAPK ) and phospho - c - Jun amino - terminal kinase ( p - JNK ) expression increased at 8 - 24 h.", "output": "amino." }, { "input": "Caspase - 3 and caspase - 8 activities also increased at 8 - 48 h and 12 - 48 h, respectively, in the same manner as p - p38 MAPK and p - JNK expression.", "output": "There is no related enetity." }, { "input": "These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway.", "output": "There is no related enetity." }, { "input": "Isolation and characterization of unusual hydrazides from Streptomyces sp. impact of the cultivation support and extraction procedure.", "output": "hydrazides." }, { "input": "Three novel hydrazides, geralcins C - E ( 1 - 3 ), were isolated from Streptomyces sp.", "output": "hydrazides, geralcins C - E." }, { "input": "LMA - 545, together with MH - 031 and geralcins A and B.", "output": "geralcins A and B." }, { "input": "This unusual family of compounds was isolated from liquid - state and agar - supported fermentation using Amberlite XAD - 16 solid - phase extraction during the cultivation step.", "output": "Amberlite XAD - 16." }, { "input": "The use of such neutral resin during the cultivation step allowed the specific adsorption of microbial secondary metabolites, avoiding any contamination of the crude extracts by the constituents of the culture medium.", "output": "There is no related enetity." }, { "input": "The trapped compounds were eluted from the resin with methanol, and their structures elucidated using ( 1 ) H, ( 13 ) C, and ( 15 ) N NMR spectroscopic analysis and high - resolution mass spectrometry.", "output": "methanol, ( 1 ) H, ( 13 ) C, ( 15 ) N." }, { "input": "Molecular modeling calculations were applied in order to support structural attributions.", "output": "There is no related enetity." }, { "input": "No antimicrobial, cytotoxic, or DnaG - inhibition activities were detected for geralcins D and E.", "output": "geralcins D and E." }, { "input": "Geralcin C has no antimicrobial activity but exhibited an IC ( 50 ) of 0. 8 mu M against KB and HCT116 cancer cell lines.", "output": "Geralcin C." }, { "input": "Furthermore, geralcin C inhibited the E. coli DnaG primase, a Gram - negative antimicrobial target, with an IC ( 50 ) of 0. 7 mM.", "output": "geralcin C." }, { "input": "Sigma receptor modulators: a patent review.", "output": "There is no related enetity." }, { "input": "Introduction: Sigma receptors are involved in several central nervous system ( CNS ) disorders, including mood disorders ( depression and anxiety ), psychosis, schizophrenia, movement disorders ( i. e., Parkinson ' s disease ) and memory deficits ( i. e., Alzheimer ' s disease ).", "output": "There is no related enetity." }, { "input": "Recently, the involvement of sigma receptors in neuropathic pain and cancer has also been observed.", "output": "There is no related enetity." }, { "input": "Areas covered: This review aims at highlighting the research advancements published in the patent literature between 1986 and 2012, dividing patents according to both their time frame and applicants.", "output": "There is no related enetity." }, { "input": "The review especially focuses on the development of sigma receptor modulators and their application over the years with respect to CNS diseases, neuropathic pain and neurodegenerative pathologies.", "output": "There is no related enetity." }, { "input": "The literature was sought through Espacenet, Orbit, ISI Web and PubMed databases.", "output": "There is no related enetity." }, { "input": "Expert opinion: In recent years, considerable progress in the knowledge of the biology and pharmacology of sigma receptors has encouraged research on the potential benefits of sigma modulators in a wide range of pathologies.", "output": "There is no related enetity." }, { "input": "So far, only few potent agonists and antagonists of sigma receptors are in clinical trial for acute and chronic neurodegenerative diseases ( SA4503 and ANAVEX 2 - 73 ) or neuropathic pain ( E - 52862 ).", "output": "SA4503, ANAVEX 2 - 73, E - 52862." }, { "input": "NMR solution structure study of the representative component hydroxysafflor yellow A and other quinochalcone C - glycosides from Carthamus tinctorius.", "output": "hydroxysafflor yellow A, quinochalcone C - glycosides." }, { "input": "Hydroxysafflor yellow A ( HSYA ), a representative component of Carthamus tinctorius, has attracted much attention because of its remarkable cardiovascular activities.", "output": "Hydroxysafflor yellow A, HSYA." }, { "input": "Its structure was originally reported in 1993 and has been widely cited to date.", "output": "There is no related enetity." }, { "input": "In our experiments, its solution structure was studied using NMR techniques in different solvents, including DMSO - d ( 6 ), pyridine - d ( 5 ), and CD ( 3 ) OH.", "output": "DMSO - d ( 6 ), pyridine - d ( 5 ), CD ( 3 ) OH." }, { "input": "The results indicate that the structure of HSYA is different than the previously described 1b, with 3 - enol - 1, 7 - diketo form.", "output": "HSYA, 3 - enol - 1 , 7 - diketo." }, { "input": "The structure has two keto - enol tautomers ( 2a and 2b ), and 2a, with the 1 - enol - 3, 7 - diketo form, is the preferred tautomer.", "output": "keto - enol, 1 - enol - 3 , 7 - diketo." }, { "input": "On the basis of this finding, other published quinochalcone C - glycoside structures were revised.", "output": "quinochalcone C - glycoside." }, { "input": "Furthermore, a trend in the ( 13 ) C NMR data of the ( E ) - olefinic carbons of quinochalcone C - glycosides is summarized, and a hypothesis is proposed for the relationship between the features of the molecular structure and the preferred keto - enol tautomer.", "output": "( 13 ) C, ( E ) - olefinic carbons, quinochalcone C - glycosides, keto - enol." }, { "input": "Tubulin inhibitors from an endophytic fungus isolated from Cedrus deodara.", "output": "There is no related enetity." }, { "input": "From an endophytic fungus, a close relative of Talaromyces sp., found in association with Cedrus deodara, four compounds including two new ones ( 2 and 4 ) were isolated and characterized.", "output": "There is no related enetity." }, { "input": "The structures of two compounds ( 1 and 4 ) were confirmed by X - ray crystallography.", "output": "There is no related enetity." }, { "input": "The compounds displayed a range of cytotoxicities against human cancer cell lines ( HCT - 116, A - 549, HEP - 1, THP - 1, and PC - 3 ).", "output": "There is no related enetity." }, { "input": "All the compounds were found to induce apoptosis in HL - 60 cells, as evidenced by fluorescence and scanning electron microscopy studies.", "output": "There is no related enetity." }, { "input": "Also, the compounds caused significant microtubule inhibition in HL - 60 cells.", "output": "There is no related enetity." }, { "input": "Differential mRNA expression levels of human histone - modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia.", "output": "There is no related enetity." }, { "input": "Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors.", "output": "There is no related enetity." }, { "input": "We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia ( ALL ).", "output": "There is no related enetity." }, { "input": "A real - time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls.", "output": "There is no related enetity." }, { "input": "The expression profile of histone - modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls.", "output": "There is no related enetity." }, { "input": "Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300.", "output": "There is no related enetity." }, { "input": "Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL.", "output": "There is no related enetity." }, { "input": "Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules ( significance score = 35 ).", "output": "There is no related enetity." }, { "input": "Ingenuity Pathway Analysis also indicated that curcumin and miR - 34 are upstream regulators of histone - modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR - 34 in leukemia.", "output": "curcumin, curcumin." }, { "input": "This study provides new clues into the molecular mechanisms of pediatric ALL.", "output": "There is no related enetity." }, { "input": "Self - assembly of pyridine - modified lipoic Acid derivatives on gold and their interaction with thyroxine ( t4 ).", "output": "pyridine, lipoic Acid, thyroxine ( t4 )." }, { "input": "Pyridyl derivatives of lipoic acid were prepared as ligands for the study of the interaction with thyroxine ( T4 ).", "output": "Pyridyl, thyroxine ( T4 )." }, { "input": "Thin self - assembled films of the ligands were prepared in 70 % ethanol on gold and their interaction with T4 was studied by titration experiments in an aqueous buffer solution using Surface Plasmon Resonance ( SPR ).", "output": "ethanol." }, { "input": "The thickness and refractive index of the ligand layers were calculated from SPR spectra recorded in two media, also allowing for surface coverage and the density of the layers to be estimated.", "output": "There is no related enetity." }, { "input": "Two ligands, a 4 - pyridyl and a bis ( 2 - hydroxyethyl ) derivative of lipoic acid, were selected to investigate the feasibility for producing molecularly imprinted self - assembled layers on gold for T4.", "output": "4 - pyridyl, bis ( 2 - hydroxyethyl ), lipoic acid." }, { "input": "The methodology was to co - assemble T4 and the ligand onto the gold surface, elute the T4 from the layer under alkaline conditions, and study the rebinding of T4 to the layer.", "output": "There is no related enetity." }, { "input": "Multiple elution / rebinding cycles were conducted in different buffer solutions, and rebinding of T4 could be observed, with a moderate binding affinity that depended greatly on the solvent used.", "output": "There is no related enetity." }, { "input": "More optimal binding was observed in HBS buffer, and the affinity of the interaction could be slightly increased when the 4 - pyridyl and bis ( 2 - hydroxy - ethyl ) derivatives of lipoic acid were combined in the imprinted layer.", "output": "4 - pyridyl, bis ( 2 - hydroxy - ethyl ), lipoic acid." }, { "input": "Carbon - coated LiFePO4 - porous carbon composites as cathode materials for lithium ion batteries.", "output": "Carbon, LiFePO4, carbon, lithium." }, { "input": "This work introduces a facile strategy for the synthesis of carbon - coated LiFePO ( 4 ) - porous carbon ( C - LiFePO ( 4 ) - PC ) composites as a cathode material for lithium ion batteries.", "output": "carbon, LiFePO ( 4 ), carbon, C, LiFePO ( 4 ), lithium." }, { "input": "The LiFePO ( 4 ) particles obtained are about 200 nm in size and homogeneously dispersed in porous carbon matrix.", "output": "LiFePO ( 4 ), carbon." }, { "input": "These particles are further coated with the carbon layers pyrolyzed from sucrose.", "output": "carbon, sucrose." }, { "input": "The C - LiFePO ( 4 ) - PC composites display a high initial discharge capacity of 152. 3 mA h g ( - 1 ) at 0. 1 C, good cycling stability, as well as excellent rate capability ( 112 mA h g ( - 1 ) at 5 C ).", "output": "C, LiFePO ( 4 )." }, { "input": "The likely contributing factors to the excellent electrochemical performance of the C - LiFePO ( 4 ) - PC composites could be related to the combined effects of enhancement of conductivity by the porous carbon matrix and the carbon coating layers.", "output": "C, LiFePO ( 4 ), carbon, carbon." }, { "input": "It is believed that further carbon coating is a facile and effective way to improve the electrochemical performance of LiFePO ( 4 ) - PC.", "output": "carbon, LiFePO ( 4 )." }, { "input": "Hepatotumorigenicity of ethyl tertiary - butyl ether with 2 - year inhalation exposure in F344 rats.", "output": "ethyl tertiary - butyl ether." }, { "input": "Carcinogenicity of ethyl tertiary - butyl ether ( ETBE ) was examined with inhalation exposure using F344 / DuCrlCrlj rats.", "output": "ethyl tertiary - butyl ether, ETBE." }, { "input": "Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1, 500 or 5, 000 ppm ( v / v ) in whole - body inhalation chambers for 6 h / day, 5 days / week for 104 weeks.", "output": "ETBE." }, { "input": "A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5, 000 ppm, but not in females at any concentration.", "output": "There is no related enetity." }, { "input": "In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5, 000 ppm.", "output": "There is no related enetity." }, { "input": "Regarding non - neoplastic lesions, rat - specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5, 000 ppm.", "output": "There is no related enetity." }, { "input": "Increased incidences of urothelial hyperplasia of the pelvis were observed at 1, 500 ppm and above, and mineral deposition was apparent in the renal papilla at 5, 000 ppm in males.", "output": "There is no related enetity." }, { "input": "There were no treatment - related histopathological changes observed in any other organs or tissues in either sex.", "output": "There is no related enetity." }, { "input": "The present 2 - year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.", "output": "ETBE." }, { "input": "Glucocorticoid programming of the fetal male hippocampal epigenome.", "output": "There is no related enetity." }, { "input": "The late - gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems.", "output": "cortisol." }, { "input": "As a result, synthetic glucocorticoids ( sGCs ) are administered to pregnant women at risk of delivering preterm.", "output": "There is no related enetity." }, { "input": "However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring.", "output": "sGC." }, { "input": "Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter - specific epigenetic changes in the hippocampus.", "output": "cortisol." }, { "input": "Fetal guinea pig hippocampi were collected before ( gestational day [ GD52 ] ) and after ( GD65 ) the fetal plasma cortisol surge ( Term ~ GD67 ) and 24 hours after ( GD52 ) and 14 days after ( GD65 ) two repeat courses of maternal sGC ( betamethasone ) treatment ( n = 3 - 4 / gp ).", "output": "cortisol, betamethasone." }, { "input": "We identified extensive genome - wide alterations in promoter methylation in late fetal development ( coincident with the fetal cortisol surge ), whereby the majority of the affected promoters exhibited hypomethylation.", "output": "cortisol." }, { "input": "Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 ( H3K9 ) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated.", "output": "There is no related enetity." }, { "input": "However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated.", "output": "There is no related enetity." }, { "input": "These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome - wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation.", "output": "There is no related enetity." }, { "input": "This is important given the widespread use of sGC in the management of women in preterm labor.", "output": "There is no related enetity." }, { "input": "Impaired Postural Balance in Turner Syndrome.", "output": "There is no related enetity." }, { "input": "An impaired body balance has been found in Turner syndrome ( TS ) in clinical tests like Rombergs ' s test and walking on a balance beam.", "output": "There is no related enetity." }, { "input": "The aim of the study was to assess postural balance in TS subjects with specific balance testing using dynamic posturography and relate to body composition.", "output": "There is no related enetity." }, { "input": "Nineteen TS subjects ( 20 - 57 years ) were included.", "output": "There is no related enetity." }, { "input": "Balance was measured with dynamic posturography ( Equitest ) and compared with 19 sex and age - matched controls ( 22 - 59 years ).", "output": "There is no related enetity." }, { "input": "Equitest, visual, vestibular, and somatosensory systems were provoked with increasing difficulty ( 6 tests, SO1 - SO6 ) and body sway was measured with a dual forceplate.", "output": "There is no related enetity." }, { "input": "Body composition was measured with DXA.", "output": "There is no related enetity." }, { "input": "No difference was found between the TS subjects and the controls on fixed platform with open eyes ( SO1 ), with closed eyes ( SO2 ), with stable platform and visual disorientation ( SO3 ), or on unstable platform with open eyes ( SO4 ).", "output": "There is no related enetity." }, { "input": "In the difficult tests on unstable platform the TS subjects did worse compared with controls both in the test with eyes closed ( SO5 ), p < 0. 01, and in the test with visual disorientation ( SO6 ), p < 0. 05.", "output": "There is no related enetity." }, { "input": "Composite ( a merge of all six recordings ) was significantly lower in the TS - group, p < 0. 05.", "output": "There is no related enetity." }, { "input": "In the TS group high total body weight was related to worse outcome on tests SO5, SO6, and composite, while total bone mass, age, height, or waist showed no significant association with balance scores.", "output": "There is no related enetity." }, { "input": "Our findings indicate that TS could have an increased risk for falling due to impaired ability to manage complex coordination tasks.", "output": "There is no related enetity." }, { "input": "Paclitaxel - conjugated PAMAM dendrimers adversely affect microtubule structure through two independent modes of action.", "output": "Paclitaxel, PAMAM." }, { "input": "Paclitaxel ( Taxol ) is an anticancer drug that induces mitotic arrest via microtubule hyperstabilization but causes side effects due to its hydrophobicity and cellular promiscuity.", "output": "Paclitaxel, Taxol." }, { "input": "The targeted cytotoxicity of hydrophilic paclitaxel - conjugated polyamidoamine ( PAMAM ) dendrimers has been demonstrated in cultured cancer cells.", "output": "paclitaxel, polyamidoamine, PAMAM." }, { "input": "Mechanisms of action responsible for this cytotoxicity are unknown, that is, whether the cytotoxicity is due to paclitaxel stabilization of microtubules, as is whether paclitaxel is released intracellularly from the dendrimer.", "output": "paclitaxel, paclitaxel." }, { "input": "To determine whether the conjugated paclitaxel can bind microtubules, we used a combination of ensemble and single microtubule imaging techniques in vitro.", "output": "paclitaxel." }, { "input": "We demonstrate that these conjugates adversely affect microtubules by ( 1 ) promoting the polymerization and stabilization of microtubules in a paclitaxel - dependent manner, and ( 2 ) bundling preformed microtubules in a paclitaxel - independent manner, potentially due to protonation of tertiary amines in the dendrimer interior.", "output": "paclitaxel, paclitaxel, tertiary amines." }, { "input": "Our results provide mechanistic insights into the cytotoxicity of paclitaxel - conjugated PAMAM dendrimers and uncover unexpected risks of using such conjugates therapeutically.", "output": "paclitaxel, PAMAM." }, { "input": "Hydrolytic activities of crystalline cellulose nanofibers.", "output": "There is no related enetity." }, { "input": "Cellulose is commonly believed to be inactive to organic substances; this inertness is an essential requirement for raw materials in industrial products.", "output": "There is no related enetity." }, { "input": "Here we demonstrate the contradictory but promising properties, which are the hydrolytic activities of crystalline cellulose nanofibers for the ester, monophosphate, and even amide bonds of small organic substrates under extremely mild conditions ( neutral pH, moderate temperature, and atmospheric pressure ).", "output": "ester, monophosphate, amide." }, { "input": "The hydrolytic activities were significantly extended to decompose the coat proteins of model viruses, followed by a drastic decrease in their infection capabilities to the host cells.", "output": "There is no related enetity." }, { "input": "Structure - Relaxivity Relationships of Serum Albumin Targeted MRI Probes Based on a Single Amino Acid Gd Complex.", "output": "Amino Acid, Gd." }, { "input": "The Gd ( III ) complex of DO3A - N - alpha - aminopropionate, Gd ( DOTAla ), was used to generate a small library of putative MRI probes targeted to human serum albumin ( HSA ).", "output": "Gd ( III ), DO3A - N - alpha - aminopropionate, Gd ( DOTAla )." }, { "input": "Ten compounds were synthesized via multistep organic synthesis, and the corresponding Gd complexes were investigated for their affinity to HSA, lipophilicity, and relaxivity in the absence and presence of HSA.", "output": "Gd." }, { "input": "Negative charge and moderate lipophilicity correlate with increased HSA affinity and relaxivity.", "output": "There is no related enetity." }, { "input": "Controllable adhesive superhydrophobic surfaces based on PDMS microwell arrays.", "output": "There is no related enetity." }, { "input": "This paper presents a one - step method to fabricate superhydrophobic surfaces with extremely controllable adhesion based on PDMS microwell arrays.", "output": "There is no related enetity." }, { "input": "The microwell array structures are rapidly produced on PDMS films by a point - by - point femtosecond laser scanning process.", "output": "There is no related enetity." }, { "input": "The as - prepared superhydrophobic surfaces show water controllable adhesion that ranges from ultrahigh to ultralow by adjusting the extent of overlap of the adjacent microwells, on which the sliding angle can be controlled from 180 degrees ( a water droplet can not slide down even when the as - prepared surface is turned upside down ) to 3 degrees.", "output": "There is no related enetity." }, { "input": "A \" micro - airbag effect \" is introduced to explain the adhesion transition phenomenon of the microwell array structures.", "output": "There is no related enetity." }, { "input": "This work provides a facile and promising strategy to fabricate superhydrophobic surfaces with controllable adhesion.", "output": "There is no related enetity." }, { "input": "A continuous network of lipid nanotubes fabricated from the gliding motility of kinesin powered microtubule filaments.", "output": "There is no related enetity." }, { "input": "Synthetic interconnected lipid nanotube networks were fabricated on the millimeter scale based on the simple, cooperative interaction between phospholipid vesicles and kinesin - microtubule ( MT ) transport systems.", "output": "There is no related enetity." }, { "input": "More specifically, taxol - stabilized MTs, in constant 2D motion via surface absorbed kinesin, extracted and extended lipid nanotube networks from large L alpha phase multilamellar liposomes ( 5 - 25 mu m ).", "output": "taxol." }, { "input": "Based on the properties of the inverted motility geometry, the total size of these nanofluidic networks was limited by MT surface density, molecular motor energy source ( ATP ), and total amount and physical properties of lipid source material.", "output": "ATP." }, { "input": "Interactions between MTs and extended lipid nanotubes resulted in bifurcation of the nanotubes and ultimately the generation of highly branched networks of fluidically connected nanotubes.", "output": "There is no related enetity." }, { "input": "The network bifurcation was easily tuned by changing the density of microtubules on the surface to increase or decrease the frequency of branching.", "output": "There is no related enetity." }, { "input": "The ability of these networks to capture nanomaterials at the membrane surface with high fidelity was subsequently demonstrated using quantum dots as a model system.", "output": "There is no related enetity." }, { "input": "The diffusive transport of quantum dots was also characterized with respect to using these nanotube networks for mass transport applications.", "output": "There is no related enetity." }, { "input": "Horizontal gene transfer: linking sex and cell fate.", "output": "There is no related enetity." }, { "input": "Integrative conjugative elements ( ICEs ) enable horizontal gene transfer among bacteria.", "output": "There is no related enetity." }, { "input": "In Pseudomonas, only a phenotypically distinct subpopulation of ICE - bearing cells can mobilize ICE DNA to new hosts.", "output": "There is no related enetity." }, { "input": "Transfer competence is a terminal state; division is limited, and many cells lyse.", "output": "There is no related enetity." }, { "input": "Ultrasound - aided microbubbles facilitate the delivery of drugs to the inner ear via the round window membrane.", "output": "There is no related enetity." }, { "input": "The round window membrane ( RWM ) acts as a barrier between the middle ear and cochlea and can serve as a crucial route for therapeutic medications entering the inner ear via middle ear applications.", "output": "There is no related enetity." }, { "input": "In this study, we targeted the practical application of microbubbles ( MBs ) ultrasound on increasing the RWM permeability for facilitating drug or medication delivery to the inner ear.", "output": "There is no related enetity." }, { "input": "Using biotin - fluorescein isothiocyanate conjugates ( biotin - FITC ) as delivery agents and guinea pig animal models, we showed that MB ultrasound exposure can improve the inner ear system use of biotin - FITC delivery via the RWM by approximately 3. 5 to 38 times that of solely soaking biotin - FITC around the RWM for spontaneous diffusion.", "output": "biotin - fluorescein isothiocyanate, biotin, FITC, biotin, FITC, biotin, FITC." }, { "input": "We also showed that there was significant enhancement of hair cell uptake of gentamicin in animals whose tympanic bullas were soaked with MB - mixed gentamicin - Texas Red or gentamicin and exposed to ultrasound.", "output": "gentamicin, gentamicin, Texas Red, gentamicin." }, { "input": "Furthermore, increased permeability of the RWM from acoustic cavitation of MBs could also be visualized immediately following ultrasound exposure by using Alexa Fluor 488 - conjugated phalloidin as a tracer.", "output": "Alexa Fluor 488, phalloidin." }, { "input": "Most importantly, such applications had no resulting damage to the integrity of the RWM or deterioration of the hearing thresholds assessed by auditory brainstem responses.", "output": "There is no related enetity." }, { "input": "We herein provide a basis for MB ultrasound - mediated techniques with therapeutic medication delivery to the inner ear for future application in humans.", "output": "There is no related enetity." }, { "input": "Protective effects of protein transduction domain - metallothionein fusion proteins against hypoxia - and oxidative stress - induced apoptosis in an ischemia / reperfusion rat model.", "output": "There is no related enetity." }, { "input": "Ischemic heart diseases caused by insufficient oxygen supply to the cardiac muscle require pharmaceutical agents for the prevention of the progress and recurrence.", "output": "oxygen." }, { "input": "Metallothionein ( MT ) has a potential as a protein therapeutic for the treatment of this disease due to its anti - oxidative effects under stressful conditions.", "output": "There is no related enetity." }, { "input": "In spite of its therapeutic potential, efficient delivery systems need to be developed to overcome limitations such as low transduction efficiency, instability and short half - life in the body.", "output": "There is no related enetity." }, { "input": "To enhance intra - cellular transduction efficiency, Tat sequence as a protein transduction domain ( PTD ) was fused with MT in a recombinant method.", "output": "There is no related enetity." }, { "input": "Anti - apoptotic and anti - oxidative effects of Tat - MT fusion protein were evaluated under hyperglycemia and hypoxia stress conditions in cultured H9c2 cells.", "output": "There is no related enetity." }, { "input": "Recovery of cardiac functions by anti - apoptotic and anti - fibrotic effects of Tat - MT was confirmed in an ischemia / reperfusion ( I / R ) rat myocardial infarction model.", "output": "There is no related enetity." }, { "input": "Tat - MT fusion protein effectively protected H9c2 cells under stressful conditions by reducing intracellular ROS production and inhibiting caspase - 3 activation.", "output": "There is no related enetity." }, { "input": "Tat - MT fusion protein inhibited apoptosis, reduced fibrosis area and enhanced cardiac functions in I / R.", "output": "There is no related enetity." }, { "input": "Tat - MT fusion protein could be a promising therapeutic for the treatment of ischemic heart diseases.", "output": "There is no related enetity." }, { "input": "An intra - articular salmon calcitonin - based nanocomplex reduces experimental inflammatory arthritis.", "output": "There is no related enetity." }, { "input": "Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis ( RA ) and to aspects of osteoarthritis ( OA ).", "output": "There is no related enetity." }, { "input": "The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target.", "output": "There is no related enetity." }, { "input": "Both salmon calcitonin ( sCT ) and hyaluronic acid ( HA ) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases ( MMPs ) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP - 1 monocytes.", "output": "There is no related enetity." }, { "input": "Ad - mixtures of sCT and HA further down - regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes ( NPs ) using chitosan.", "output": "There is no related enetity." }, { "input": "The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors.", "output": "cAMP." }, { "input": "When NP were injected by the intra - articular ( I. A. ) route to the mouse knee during on - going inflammatory arthritis of the K / BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved.", "output": "There is no related enetity." }, { "input": "These data highlight remarkable anti - inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro.", "output": "There is no related enetity." }, { "input": "Combining them in NP elicits anti - arthritic effects in vivo following I. A. delivery.", "output": "There is no related enetity." }, { "input": "In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths.", "output": "perfluorinated carboxylic acids, carbon." }, { "input": "Perfluorooctanoic acid ( PFOA ) is in use for the production of fluoropolymers ( PFT ).", "output": "Perfluorooctanoic acid, PFOA, fluoropolymers, PFT." }, { "input": "Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far.", "output": "carbon, PFOA, PFOA." }, { "input": "In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids ( PFCA ) with a carbon chain length ranging from four to twelve carbon atoms.", "output": "perfluorinated carboxylic acids, PFCA, carbon, carbon." }, { "input": "By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity.", "output": "carbon, PFCA." }, { "input": "There was, however, no indication of an apoptotic mechanism for cytotoxicity.", "output": "There is no related enetity." }, { "input": "All PFCA under investigation were negative in two independent genotoxicity assays.", "output": "PFCA." }, { "input": "As PFOA, being a well - known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator - activated receptor alpha ( PPAR alpha ) with PFOA having the highest potential of PPAR alpha activation.", "output": "PFOA, PFCA, PFOA." }, { "input": "Moreover, the compounds showed weak potential to activate PPAR gamma and hardly activated PPAR delta.", "output": "There is no related enetity." }, { "input": "Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA.", "output": "PFCA, carbon, PFOA." }, { "input": "Effect of low dose Bisphenol A on the early differentiation of human embryonic stem cells into mammary epithelial cells.", "output": "Bisphenol A." }, { "input": "It has been previously reported that Bisphenol A ( BPA ) can disturb the development of mammary structure and increase the risk of breast cancer in experimental animals.", "output": "Bisphenol A, BPA." }, { "input": "In this study, an in vitro model of human embryonic stem cell ( hESC ) differentiation into mammary epithelial cells was applied to investigate the effect of low dose BPA on the early stages of mammogenesis.", "output": "BPA." }, { "input": "A newly established hESC line was directionally differentiated into mammary epithelial cells by a well - established three - dimensional ( 3D ) culture system.", "output": "There is no related enetity." }, { "input": "The differentiated mammary epithelial cells were characterized by immunofluorescence and western blotting assay, and were called induced differentiated mammary epithelial cells ( iDMECs ) based on these data.", "output": "There is no related enetity." }, { "input": "The hESCs were treated with low doses of BPA range 10 ( - 9 ) - 10 ( - 6 ) M during the differentiation process, with DMSO as the solvent control and 17 - beta - estrodiol ( E2 ) as the estrogen - positive control.", "output": "BPA, DMSO, 17 - beta - estrodiol." }, { "input": "Our results showed that low dose BPA and E2 could influence the mammosphere area of iDMECs and upregulate the expression level of Oct4 and Nanog proteins, while only BPA could downregulate the expression of E - cadherin protein.", "output": "BPA, BPA." }, { "input": "Taken together, this study provides some insights into the effects of low dose BPA on the early differentiation stage of mammary epithelial cells and suggests an easier canceration status of iDMECs under the effect of low dose BPA during its early differentiation stage.", "output": "BPA, BPA." }, { "input": "Essential trace and toxic element concentrations in organic and conventional milk in NW Spain.", "output": "There is no related enetity." }, { "input": "Dietary composition and husbandry practices largely determine essential trace element status and toxic element exposure of livestock, and consequently their concentrations in animal products.", "output": "There is no related enetity." }, { "input": "This study evaluates the main essential trace ( Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se and Zn ) and toxic ( As, Cd, Hg and Pb ) element concentrations in milk from organic and conventional farms in NW Spain ( n = 50 ).", "output": "Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se, Zn, As, Cd, Hg, Pb." }, { "input": "Milk samples were acid digested and analyzed by ICP - MS.", "output": "There is no related enetity." }, { "input": "Essential trace element concentrations in organic milk were significantly lower compared to conventional milk, this was especially evident for elements that are routinely supplemented at high concentrations in the conventional concentrate feed: Cu ( 41. 0 and 68. 9 mu g / L in organic and conventional milk, respectively ), Zn ( 3326 and 3933 mu g / L ), I ( 78 and 265 mu g / L ) and Se ( 9. 4 and 19. 2 mu g / L ).", "output": "Cu, Zn, I, Se." }, { "input": "Toxic metal concentrations in milk were in general very low and no statistically significant differences were observed between organic and conventional milk.", "output": "There is no related enetity." }, { "input": "In addition, the mineral content of organic milk showed a seasonal pattern, the significantly higher As ( 65 % ) and Fe ( 13 % ) concentrations found in the winter sampling possibly being related to a higher consumption of concentration feed and soil ingestion when grazing.", "output": "As, Fe." }, { "input": "The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model.", "output": "aryl hydrocarbon." }, { "input": "Lead ( Pb ( 2 + ) ) is a naturally occurring systemic toxicant heavy metal that affects several organs in the body including the kidneys, liver, and central nervous system.", "output": "Pb ( 2 + )." }, { "input": "However, Pb ( 2 + ) - induced cardiotoxicity has never been investigated yet and the exact mechanism of Pb ( 2 + ) associated cardiotoxicity has not been studied.", "output": "Pb ( 2 + ), Pb ( 2 + )." }, { "input": "The current study was designed to investigate the potential effect of Pb ( 2 + ) to induce cardiotoxicity in vivo and in vitro rat model and to explore the molecular mechanisms and the role of aryl hydrocarbon receptor ( AhR ) and regulated gene, cytochrome P4501A1 ( CYP1A1 ), in Pb ( 2 + ) - mediated cardiotoxicity.", "output": "Pb ( 2 + ), aryl hydrocarbon, Pb ( 2 + )." }, { "input": "For these purposes, Wistar albino rats were treated with Pb ( 2 + ) ( 25, 50 and 100mg / kg, i. p. ) for three days and the effects on physiological and histopathological parameters of cardiotoxicity were determined.", "output": "Pb ( 2 + )." }, { "input": "At the in vitro level, rat cardiomyocyte H9c2 cell lines were incubated with increasing concentration of Pb ( 2 + ) ( 25, 50, and 100 mu M ) and the expression of hypertrophic genes, alpha - and beta - myosin heavy chain ( alpha - MHC and beta - MHC ), brain Natriuretic Peptide ( BNP ), and CYP1A1 were determined at the mRNA and protein levels using real - time PCR and Western blot analysis, respectively.", "output": "Pb ( 2 + )." }, { "input": "The results showed that Pb ( 2 + ) significantly induced cardiotoxicity and heart failure as evidenced by increase cardiac enzymes, lactate dehydrogenase and creatine kinase and changes in histopathology in vivo.", "output": "Pb ( 2 + ), lactate, creatine." }, { "input": "In addition, Pb ( 2 + ) treatment induced beta - MHC and BNP whereas inhibited alpha - MHC mRNA and protein levels in vivo in a dose - dependent manner.", "output": "Pb ( 2 + )." }, { "input": "In contrast, at the in vitro level, Pb ( 2 + ) treatment induced both beta - MHC and alpha - MHC mRNA levels in time - and dose - dependent manner.", "output": "Pb ( 2 + )." }, { "input": "Importantly, these changes were accompanied with a proportional increase in the expression of CYP1A1 mRNA and protein expression levels, suggesting a role for the CYP1A1 in cardiotoxicity.", "output": "There is no related enetity." }, { "input": "The direct evidence for the involvement of CYP1A1 in the induction of cardiotoxicity by Pb ( 2 + ) was evidenced by the ability of AhR antagonist, resveratrol, to significantly inhibit the Pb ( 2 + ) - modulated effect on beta - MHC and alpha - MHC mRNAs.", "output": "Pb ( 2 + ), resveratrol, Pb ( 2 + )." }, { "input": "It was concluded that acute lead exposure induced cardiotoxicity through AhR / CYP1A1 - mediated mechanism.", "output": "There is no related enetity." }, { "input": "The increased number of Leydig cells by di ( 2 - ethylhexyl ) phthalate comes from the differentiation of stem cells into Leydig cell lineage in the adult rat testis.", "output": "di ( 2 - ethylhexyl ) phthalate." }, { "input": "The objective of the present study is to determine whether di ( 2 - ethylhexyl ) phthalate ( DEHP ) exposure at adulthood increases rat Leydig cell number and to investigate the possible mechanism.", "output": "di ( 2 - ethylhexyl ) phthalate, DEHP." }, { "input": "90 - day - old Long - Evans rats were randomly divided into 3 groups, and were gavaged with the corn oil ( control ) or 10 or 750mg / kg DEHP daily for 7 days, and then received an intraperitoneal injection of 75mg / kg ethane dimethanesulfonate ( EDS ) to eliminate Leydig cells.", "output": "DEHP, ethane dimethanesulfonate, EDS." }, { "input": "Serum testosterone concentrations were assessed by RIA, and the mRNA levels of Leydig cell genes were measured by qPCR.", "output": "testosterone." }, { "input": "EDS eliminated all Leydig cells in the control testis on day 4 post - EDS, as judged by undetectable serum testosterone level and no 3 beta - hydroxysteroid dehydrogenase positive ( 3 beta - HSD ( pos ) ) cells in the interstitium.", "output": "EDS, EDS, testosterone, 3 beta - hydroxysteroid." }, { "input": "However, in DEHP - treated groups, there were detectable serum testosterone concentrations and some oval - shaped 3 beta - HSD ( pos ) cells in the interstitium.", "output": "DEHP, testosterone." }, { "input": "These 3 beta - HSD ( pos ) cells were not stained by the antibody against 11 beta - hydroxysteroid dehydrogenase 1 ( 11 beta - HSD1 ), a marker for Leydig cells at a more advanced stage.", "output": "11 beta - hydroxysteroid." }, { "input": "The disappearance of mRNAs of Leydig cell biomarkers including Lhcgr, Cyp11a1, Cyp17a1, Insl3 and Hsd11b1 in the control testis was observed on day 4 post - EDS.", "output": "EDS." }, { "input": "However, there were detectable concentrations of Lhcgr, Cyp11a1 and Cyp17a1 mRNAs but undetectable concentrations of Insl3, Hsd17b3 and Hsd11b1 in the DEHP - treated testes, indicating that these 3 beta - HSD ( pos ) cells were newly formed progenitor Leydig cells.", "output": "DEHP." }, { "input": "The mRNA level for nestin ( Nes, biomarker for stem Leydig cells ) was significantly increased in the control testis on day 4 post - EDS, but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP - treated testes.", "output": "EDS, DEHP, DEHP." }, { "input": "The present study suggests that DEHP increases the differentiation of stem cells into progenitor Leydig cells.", "output": "DEHP." }, { "input": "The venom of the fishing spider Dolomedes sulfurous contains various neurotoxins acting on voltage - activated ion channels in rat dorsal root ganglion neurons.", "output": "There is no related enetity." }, { "input": "Dolomedes sulfurous is a venomous spider distributed in the south of China and characterized with feeding on fish.", "output": "There is no related enetity." }, { "input": "The venom exhibits great diversity and contains hundreds of peptides as revealed by off - line RP - HPLC / MALDI - TOF - MS analysis.", "output": "There is no related enetity." }, { "input": "The venom peptides followed a triple - modal distribution, with 40. 7 % of peptides falling in the mass range of 1000 - 3000 Da, 25. 6 % peptides in the 7000 - 9000 Da range and 23. 5 % peptides in the 3000 - 5000 Da range.", "output": "There is no related enetity." }, { "input": "This distribution modal is rather different from these of peptides from other spider venoms analyzed.", "output": "There is no related enetity." }, { "input": "The venom could inhibit voltage - activated Na ( + ), K ( + ) and Ca ( 2 + ) channels in rat DRG neurons as revealed by voltage - clamp analysis.", "output": "Na ( + ), K ( + ), Ca ( 2 + )." }, { "input": "Significantly, the venom exhibited inhibitory effects on TTX - R Na ( + ) and T - type Ca ( 2 + ) currents, suggesting that there exist both channel antagonists which might be valuable tools for investigation of both channels and drug development.", "output": "Na ( + ), Ca ( 2 + )." }, { "input": "Additionally, intrathoracically injection of venom could cause serve neurotoxic effects on zebrafish and death at higher concentrations.", "output": "There is no related enetity." }, { "input": "The LD50 value was calculated to be 28. 8 mu g / g body weight.", "output": "There is no related enetity." }, { "input": "Our results indicated that the venom of D. sulfurous contain diverse neurotoxins which serve to capture prey.", "output": "There is no related enetity." }, { "input": "Intensive studies will be necessary to investigate the structures and functions of specific peptides of the venom in the future.", "output": "There is no related enetity." }, { "input": "Maternal exposure to mercury chloride during pregnancy and lactation affects the immunity and social behavior of offspring.", "output": "mercury chloride." }, { "input": "Developmental HgCl2 exposures of F1 offspring ( H - 2 ( q / s ) ) from unsociable SJL / J ( H - 2 ( s ) ) dams with high susceptibility to Hg - induced autoimmunity ( SFvF1 ) and from highly sociable FVB / NJ ( FVB; H - 2 ( q ) ) dams with lower susceptibility to Hg - induced autoimmunity ( FvSF1 ) were investigated.", "output": "HgCl2, Hg, Hg." }, { "input": "Hg exposure increased the serum IgG levels of all offspring at postnatal day 21 ( pnd21 ) and of SJL / J dams but not of FVB dams.", "output": "Hg." }, { "input": "Serum IgG anti - brain antibody ( Ab ) levels of pnd21 SFvF1 offspring and SJL dams were higher than those of the FvSF1 offspring and FVB dams, but Hg only increased the titers of the FVB dams and their offspring.", "output": "Hg." }, { "input": "Hg significantly elevated the presence of IgG in all brain regions of the pnd21 SFvF1 offspring, and the SFvF1 offspring had greater amounts of IgG in the brain than the FvSF1 offspring, which had Hg - induced increases in only two brain regions.", "output": "Hg, Hg." }, { "input": "Cytokine levels were elevated in the brain regions of Hg - treated pnd21 SFvF1 but not of FvSF1 offspring, and SFvF1 females had more brain regions expressing cytokines than the males.", "output": "Hg." }, { "input": "At pnd70, the serum IgG, serum antibrain Abs, amounts of brain IgG, and brain cytokine levels of all of the Hg - treated offspring were equivalent to those of their appropriate controls, suggesting that developmental Hg exposure did not induce chronic immunological effects.", "output": "Hg, Hg." }, { "input": "However, the social behaviors of Hg - exposed SFvF1 offspring at pnd70 were significantly impaired, and SFvF1 females displayed greater decline in social behaviors than males, suggesting that the higher neuroinflammation of SFvF1 females earlier in life is associated with the altered behavior.", "output": "Hg." }, { "input": "Thus, developmental Hg exposure induces long - lasting effects on social behavior of offspring, which is dependent on sex and genetics and the induction of neuroinflammation.", "output": "Hg." }, { "input": "Large - scale and highly efficient synthesis of micro - and nano - fibers with controlled fiber morphology by centrifugal jet spinning for tissue regeneration.", "output": "There is no related enetity." }, { "input": "PLLA fibrous tissue scaffolds with controlled fiber nanoscale surface roughness are fabricated with a novel centrifugal jet spinning process.", "output": "There is no related enetity." }, { "input": "The centrifugal jet spinning technique is a highly efficient synthesis method for micron - to nano - sized fibers with a production rate up to 0. 5 g min ( - 1 ).", "output": "There is no related enetity." }, { "input": "During the centrifugal jet spinning process, a polymer solution jet is stretched by the centrifugal force of a rotating chamber.", "output": "There is no related enetity." }, { "input": "By engineering the rheological properties of the polymer solution, solvent evaporation rate and centrifugal force that are applied on the solution jet, polyvinylpyrrolidone ( PVP ) and poly ( l - lactic acid ) ( PLLA ) composite fibers with various diameters are fabricated.", "output": "polyvinylpyrrolidone, PVP, poly ( l - lactic acid ), PLLA." }, { "input": "Viscosity measurements of polymer solutions allowed us to determine critical polymer chain entanglement limits that allow the generation of continuous fiber as opposed to beads or beaded fibers.", "output": "There is no related enetity." }, { "input": "Above a critical concentration at which polymer chains are partially or fully entangled, lower polymer concentrations and higher centrifugal forces resulted in thinner fibers.", "output": "There is no related enetity." }, { "input": "Etching of PVP from the PLLA - PVP composite fibers doped with increasing PVP concentrations yielded PLLA fibers with increasing nano - scale surface roughness and porosity, which increased the fiber hydrophilicity dramatically.", "output": "PVP, PLLA, PVP, PVP, PLLA." }, { "input": "Scanning electron micrographs of the etched composite fibers suggest that PVP and PLLA were co - contiguously phase separated within the composite fibers during spinning and nano - scale roughness features were created after the partial etching of PVP.", "output": "PVP, PLLA, PVP." }, { "input": "To study the tissue regeneration efficacy of the engineered PLLA fiber matrix, human dermal fibroblasts are used to simulate partial skin graft.", "output": "PLLA." }, { "input": "Fibers with increased PLLA surface roughness and porosity demonstrated a trend towards higher cell attachment and proliferation.", "output": "PLLA." }, { "input": "Vesnarinone Suppresses TNF alpha mRNA Expression by Inhibiting Valosin - Containing Protein.", "output": "Vesnarinone." }, { "input": "Vesnarinone is a synthetic quinolinone derivative used in the treatment of cardiac failure and cancer.", "output": "Vesnarinone, quinolinone." }, { "input": "It is also known to cause agranulocytosis as a side effect, which restricts its use, although the mechanism underlying agranulocytosis is not well understood.", "output": "There is no related enetity." }, { "input": "Here, we show that vesnarinone binds to valosin - containing protein ( VCP ), which interacts with polyubiquitinated proteins and is essential for the degradation of I kappa B alpha to activate nuclear factor ( NF ) kappa B.", "output": "vesnarinone." }, { "input": "We show that vesnarinone impairs the degradation of I kappa B alpha, and that the impairment of the degradation of I kappa B alpha is the result of the inhibition of the interaction between VCP and the 26S proteasome by vesnarinone.", "output": "vesnarinone, vesnarinone." }, { "input": "These results suggest that vesnarinone suppresses NF kappa B activation by inhibiting the VCP - dependent degradation of polyubiquitinated I kappa B alpha, resulting in the suppression of tumor necrosis factor - alpha mRNA expression.", "output": "vesnarinone." }, { "input": "Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes ( MiG ) Study.", "output": "Triglycerides, Metformin." }, { "input": "OBJECTIVEFactors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism.", "output": "triglyceride, glucose." }, { "input": "In a subgroup of women in the Metformin in Gestational Diabetes ( MiG ) trial, maternal plasma triglycerides increased more between enrollment ( 30 weeks ) and 36 weeks in those treated with metformin compared with insulin.", "output": "Metformin, triglycerides, metformin." }, { "input": "The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women. RESEARCH DESIGN AND METHODSOf the 733 women randomized to metformin or insulin in the MiG trial, 432 ( 219 metformin and 213 insulin ) had fasting plasma triglycerides measured at enrollment and at 36 weeks.", "output": "triglycerides, metformin, metformin, triglycerides." }, { "input": "Factors associated with maternal triglycerides were assessed using general linear modeling. RESULTSMean plasma triglyceride concentrations were 2. 43 ( 95 % CI 2. 35 - 2. 51 ) mmol / L at enrollment.", "output": "triglycerides, triglyceride." }, { "input": "Triglycerides were higher at 36 weeks in women randomized to metformin ( 2. 94 [ 2. 80 - 3. 08 ] mmol / L; + 23. 13 % [ 18. 72 - 27. 53 % ] ) than insulin ( 2. 65 [ 2. 54 - 2. 77 ] mmol / L, P = 0. 002; + 14. 36 % [ 10. 91 - 17. 82 % ], P = 0. 002 ).", "output": "Triglycerides, metformin." }, { "input": "At 36 weeks, triglycerides were associated with HbA1c ( P = 0. 03 ), ethnicity ( P = 0. 001 ), and treatment allocation ( P = 0. 005 ).", "output": "triglycerides." }, { "input": "In insulin - treated women, 36 - week triglycerides were associated with 36 - week HbA1c ( P = 0. 02 ), and in metformin - treated women, they were related to ethnicity. CONCLUSIONSAt 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin.", "output": "triglycerides, metformin, triglycerides, glucose, metformin." }, { "input": "Whether there are ethnicity - related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study.", "output": "metformin, glucose, triglycerides." }, { "input": "Decreased serum concentrations of 25 - hydroxycholecalciferol are associated with increased risk of progression to impaired fasting glucose and diabetes.", "output": "25 - hydroxycholecalciferol, glucose." }, { "input": "OBJECTIVE To study the association between vitamin D status and the risk of incident impaired fasting glucose ( IFG ) and diabetes in a population - based cohort of diabetes - free subjects.", "output": "vitamin D, glucose." }, { "input": "RESEARCH DESIGN AND METHODS In a historical prospective cohort study of subjects from the Clalit Health Services database, which includes information on nearly 4 million people, diabetes - free subjects aged 40 - 70 years with serum 25 - hydroxycholecalciferol ( 25 - OHD ) measurements available were followed for 2 years to assess the development of IFG and diabetes in five 25 - OHD subgroups: >= 25, 25. 1 - 37. 5, 37. 6 - 50, 50. 1 - 75, and > 75 nmol / L.", "output": "25 - hydroxycholecalciferol, 25 - OHD, 25 - OHD." }, { "input": "RESULTS The baseline cohort included 117, 960 adults: 83, 526 normoglycemic subjects and 34, 434 subjects with IFG.", "output": "There is no related enetity." }, { "input": "During follow - up, 8, 629 subjects ( 10. 3 % of the normoglycemic group ) developed IFG, and 2, 162 subjects ( 1. 8 % of the total cohort ) progressed to diabetes.", "output": "There is no related enetity." }, { "input": "A multivariable model adjusted for age, sex, population group, immigrant status, BMI, season of vitamin D measurement, LDL and HDL cholesterol, triglycerides, estimated glomerular filtration rate, history of hypertension or cardiovascular disease, Charlson comorbidity index, smoking, and socioeconomic status revealed an inverse association between 25 - OHD and the risk of progression to IFG and diabetes.", "output": "vitamin D, cholesterol, triglycerides, 25 - OHD." }, { "input": "The odds of transitioning from normoglycemia to IFG, from normoglycemia to diabetes, and from IFG to diabetes in subjects with a 25 - OHD level <= 25 nmol / L were greater than those of subjects with a 25 - OHD level > 75 nmol / L [ odds ratio 1. 13 ( 95 % CI 1. 03 - 1. 24 ), 1. 77 ( 1. 11 - 2. 83 ), and 1. 43 ( 1. 16 - 1. 76 ), respectively ].", "output": "25 - OHD, 25 - OHD." }, { "input": "CONCLUSIONS Vitamin D deficiency appears to be an independent risk factor for the development of IFG and diabetes.", "output": "Vitamin D." }, { "input": "Nurse - Community Health Worker Team Improves Diabetes Care in American Samoa: Results of a randomized controlled trial.", "output": "There is no related enetity." }, { "input": "OBJECTIVETo evaluate the effectiveness of a culturally adapted, primary care - based nurse - community health worker ( CHW ) team intervention to support diabetes self - management on diabetes control and other biologic measures. RESEARCH DESIGN AND METHODSTwo hundred sixty - eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were randomly assigned by village clusters to the nurse - CHW team intervention or to a wait - list control group that received usual care. RESULTSParticipants had a mean age of 55 years, 62 % were female, mean years of education were 12. 5 years, 41 % were employed, and mean HbA ( 1c ) was 9. 8 % at baseline.", "output": "There is no related enetity." }, { "input": "At 12 months, mean HbA ( 1c ) was significantly lower among CHW participants, compared with usual care, after adjusting for confounders ( b = - 0. 53; SE = 0. 21; P = 0. 03 ).", "output": "There is no related enetity." }, { "input": "The odds of making a clinically significant improvement in HbA ( 1c ) of at least 0. 5 % in the CHW group was twice the odds in the usual care group after controlling for confounders ( P = 0. 05 ).", "output": "There is no related enetity." }, { "input": "There were no significant differences in blood pressure, weight, or waist circumference at 12 months between groups. CONCLUSIONSA culturally adapted nurse - CHW team intervention was able to significantly improve diabetes control in the U. S.", "output": "There is no related enetity." }, { "input": "Territory of American Samoa.", "output": "There is no related enetity." }, { "input": "This represents an important translation of an evidence - based model to a high - risk population and a resource - poor setting.", "output": "There is no related enetity." }, { "input": "Quantitative Prediction of Repaglinide - Rifampicin Complex Drug Interactions Using Dynamic and Static Mechanistic Models: Delineating Differential CYP3A4 Induction and OATP1B1 Inhibition Potential of Rifampicin.", "output": "Repaglinide, Rifampicin, Rifampicin." }, { "input": "Repaglinide is mainly metabolized by cytochrome P450 enzymes CYP2C8 and CYP3A4, and it is also a substrate to a hepatic uptake transporter, organic anion transporting polypeptide ( OATP ) 1B1.", "output": "Repaglinide." }, { "input": "The purpose of this study is to predict the dosing time - dependent pharmacokinetic interactions of repaglinide with rifampicin, using mechanistic models.", "output": "repaglinide, rifampicin." }, { "input": "In vitro hepatic transport of repaglinide, characterized using sandwich - cultured human hepatocytes, and intrinsic metabolic parameters were used to build a dynamic whole - body physiologically - based pharmacokinetic ( PBPK ) model.", "output": "repaglinide." }, { "input": "The PBPK model adequately described repaglinide plasma concentration - time profiles and successfully predicted area under the plasma concentration - time curve ratios of repaglinide ( within +/- 25 % error ), dosed ( staggered 0 - 24 hours ) after rifampicin treatment when primarily considering induction of CYP3A4 and reversible inhibition of OATP1B1 by rifampicin.", "output": "repaglinide, repaglinide, rifampicin, rifampicin." }, { "input": "Further, a static mechanistic \" extended net - effect \" model incorporating transport and metabolic disposition parameters of repaglinide and interaction potency of rifampicin was devised.", "output": "repaglinide, rifampicin." }, { "input": "Predictions based on the static model are similar to those observed in the clinic ( average error ~ 19 % ) and to those based on the PBPK model.", "output": "There is no related enetity." }, { "input": "Both the models suggested that the combined effect of increased gut extraction and decreased hepatic uptake caused minimal repaglinide systemic exposure change when repaglinide is dosed simultaneously or 1 hour after the rifampicin dose.", "output": "repaglinide, repaglinide, rifampicin." }, { "input": "On the other hand, isolated induction effect as a result of temporal separation of the two drugs translated to an approximate 5 - fold reduction in repaglinide systemic exposure.", "output": "repaglinide." }, { "input": "In conclusion, both dynamic and static mechanistic models are instrumental in delineating the quantitative contribution of transport and metabolism in the dosing time - dependent repaglinide - rifampicin interactions.", "output": "repaglinide, rifampicin." }, { "input": "Discovery of 4 - amino - N - [ ( 1S ) - 1 - ( 4 - chlorophenyl ) - 3 - hydroxypropyl ] - 1 - ( 7H - pyrrolo [ 2, 3 - d ] pyrimidin - 4 - yl ) piperidine - 4 - carboxamide ( AZD5363 ), an orally bioavailable, potent inhibitor of Akt kinases.", "output": "4 - amino - N - [ ( 1S ) - 1 - ( 4 - chlorophenyl ) - 3 - hydroxypropyl ] - 1 - ( 7H - pyrrolo [ 2 , 3 - d ] pyrimidin - 4 - yl ) piperidine - 4 - carboxamide, AZD5363." }, { "input": "Wide - ranging exploration of analogues of an ATP - competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK.", "output": "AZD5363." }, { "input": "This compound demonstrated good preclinical drug metabolism and pharmacokinetics ( DMPK ) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.", "output": "There is no related enetity." }, { "input": "Resolving stable axial trapping points of nanowires in an optical tweezers using photoluminescence mapping.", "output": "There is no related enetity." }, { "input": "Axially resolved microphotoluminescence mapping of semiconductor nanowires held in an optical tweezers reveals important new experimental information regarding equilibrium trapping points and trapping stability of high aspect ratio nanostructures.", "output": "There is no related enetity." }, { "input": "In this study, holographic optical tweezers are used to scan trapped InP nanowires along the beam direction with respect to a fixed excitation source and the luminescent properties are recorded.", "output": "There is no related enetity." }, { "input": "It is observed that nanowires with lengths on the range of 3 - 15 mu m are stably trapped near the tip of the wire with the long segment positioned below the focus in an inverted trapping configuration.", "output": "There is no related enetity." }, { "input": "Through the use of trap multiplexing we investigate the possibility of improving the axial stability of the trapped nanowires.", "output": "There is no related enetity." }, { "input": "Our results have important implication for applications of optically assisted nanowire assembly and optical tweezers based scanning probes microscopy.", "output": "There is no related enetity." }, { "input": "Parameterization of Reactive Force Field: Dynamics of the [ Nb6O19Hx ] ( ( 8 - x ) - ) Lindqvist Polyoxoanion in Bulk Water.", "output": "[ Nb6O19Hx ] ( ( 8 - x ) - )." }, { "input": "We present results on parameterization of reactive force field [ van Duin, A. C. T.; Dasgupta, S.; Lorant, F.; Goddard, W. A. ReaxFF: A Reactive Force Field for Hydrocarbons. J. Phys. Chem. A2001, 105, 9396 - 9409 ] for investigating the properties of the [ Nb6O19Hx ] ( ( 8 - x ) - ) Lindqvist polyoxoanion, x = 0 - 8, in water.", "output": "Hydrocarbons, [ Nb6O19Hx ] ( ( 8 - x ) - )." }, { "input": "Force - field parameters were fitted to an extensive data set consisting of structures and energetics obtained at the Perdew - Burke - Ernzerhof density functional level of theory.", "output": "There is no related enetity." }, { "input": "These parameters can reasonably describe pure water structure as well as water with an excess of H ( + ) and OH ( - ) ions.", "output": "H ( + ), OH ( - )." }, { "input": "Molecular dynamics simulations were performed on [ Nb6O19Hx ] ( ( 8 - x ) - ), x = 0 - 8, submerged in bulk water at 298 K.", "output": "[ Nb6O19Hx ] ( ( 8 - x ) - )." }, { "input": "Analysis of the MD trajectories showed facile H atom transfer between the protonated polyoxoanion core and bulk water.", "output": "H." }, { "input": "The number of oxygen sites labeled with an H atom was found to vary depending on the pH of the solution.", "output": "oxygen, H." }, { "input": "Detailed analysis shows that the total number of protons at bridging ( terminal ), eta - O ( mu 2 - O ), sites ranges from 3 ( 1 ) at pH 7, to 2 ( 0 ) at pH 11, to 1 ( 0 ) at pH 15.", "output": "O, O." }, { "input": "These findings closely reflect available experimental measurements.", "output": "There is no related enetity." }, { "input": "Antidepressant abietane diterpenoids from Chinese eaglewood.", "output": "abietane, diterpenoids." }, { "input": "Ten new abietane diterpenoids, aquilarabietic acids A - J ( 1 - 10 ), and a new podocarpane diterpenoid, aquilarabietic acid K ( 11 ), were isolated from the petroleum ether and ethanol extracts of Chinese eaglewood.", "output": "abietane, diterpenoids, aquilarabietic acids A - J, podocarpane, diterpenoid, aquilarabietic acid K, petroleum ether, ethanol." }, { "input": "Among them, 3, 9, and 10 are artifacts.", "output": "There is no related enetity." }, { "input": "Their structures were established on the basis of data from extensive spectroscopic and X - ray diffraction analyses.", "output": "There is no related enetity." }, { "input": "Bioassay results indicated that 1 at 10 mu M demonstrated remarkable antidepressant activity in vitro by inhibiting norepinephrine reuptake in rat brain synaptosomes by 81. 4 % and with an IC ( 50 ) value of 9. 1 x 10 ( - 7 ) M.", "output": "norepinephrine." }, { "input": "Institutional profile: Institute of Pharmacogenetics at the University Hospital Essen.", "output": "There is no related enetity." }, { "input": "Established in 2005, the Institute of Pharmacogenetics at the University Hospital Essen ( Essen, Germany ), headed by Winfried Siffert, is devoted to the discovery and validation of genetic variants that may impact upon drug responses especially in the field of cardiovascular disorders and cancer.", "output": "There is no related enetity." }, { "input": "Moreover, the institute provides pharmacogenetic testing for those drugs for which pharmacogenetic testing is recommended in order to prevent adverse drug reactions.", "output": "There is no related enetity." }, { "input": "Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy.", "output": "There is no related enetity." }, { "input": "In the past decade, advances in pharmacogenetics and pharmacogenomics ( PGx ) have gradually unveiled the genetic basis of interindividual differences in drug responses.", "output": "There is no related enetity." }, { "input": "A large portion of these advances have been made in the field of anticancer therapy.", "output": "There is no related enetity." }, { "input": "Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information.", "output": "There is no related enetity." }, { "input": "Given the complexity of this genetic information ( e. g., tumor mutation and gene overexpression, chromosomal translocation and germline variations ), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs.", "output": "There is no related enetity." }, { "input": "In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects.", "output": "There is no related enetity." }, { "input": "Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets.", "output": "There is no related enetity." }, { "input": "Uncertain prognosis for high - quality diagnostics: clinical challenges, economic barriers and needed reforms.", "output": "There is no related enetity." }, { "input": "Quality healthcare, as measured by outcomes and costs, needs high - quality diagnostics whose use governs the evidence - based flow of patients from screening to treatment to outcomes monitoring.", "output": "There is no related enetity." }, { "input": "The current patent, regulatory and reimbursement environment may be inadequate to spur their development, thereby placing in jeopardy the goals of healthcare reform and the aspirations of personalized medicine.", "output": "There is no related enetity." }, { "input": "Policy actions to ensure consistent quality standards and to increase development incentives through research support, reimbursement reform, increased intellectual property protection and market - making activities may be required to obtain the well - characterized, clinically proven diagnostics that US healthcare requires.", "output": "There is no related enetity." }, { "input": "Tailoring the lasing modes in semiconductor nanowire cavities using intrinsic self - absorption.", "output": "There is no related enetity." }, { "input": "Understanding the optical gain and mode - selection mechanisms in semiconductor nanowire ( NW ) lasers is key to the development of high - performance nanoscale oscillators, amplified semiconductor / plasmon lasers and single photon emitters, and so forth.", "output": "There is no related enetity." }, { "input": "Modification of semiconductor band structure / bandgap through electric field modulation, elemental doping, or alloying semiconductors has so far gained limited success in achieving output mode tunability of the NW laser.", "output": "There is no related enetity." }, { "input": "One stifling issue is the considerable optical losses induced in the NW cavities by these extrinsic methods that limit their applicability.", "output": "There is no related enetity." }, { "input": "Herein we demonstrate a new optical self - feedback mechanism based on the intrinsic self - absorption of the gain media to achieve low - loss, room - temperature NW lasing with a high degree of mode selectivity ( over 30 nm ).", "output": "There is no related enetity." }, { "input": "The cadmium sulfide ( CdS ) NW lasing wavelength is continuously tunable from 489 to 520 nm as the length of the NWs increases from 4 to 25 mu m.", "output": "cadmium sulfide, CdS." }, { "input": "Our straightforward approach is widely applicable in most semiconductor or semiconductor / plasmonic NW cavities.", "output": "There is no related enetity." }, { "input": "Free energy of adsorption for a peptide at a liquid / solid interface via nonequilibrium molecular dynamics.", "output": "There is no related enetity." }, { "input": "Protein adsorption is of wide interest including in many technological applications such as tissue engineering, nanotechnology, biosensors, drug delivery, and vaccine production among others.", "output": "There is no related enetity." }, { "input": "Understanding the fundamentals of such technologies and their design would be greatly aided by an ability to efficiently predict the conformation of an adsorbed protein and its free energy of adsorption.", "output": "There is no related enetity." }, { "input": "In the study reported here, we show that this is possible when data obtained from nonequilibrium thermodynamic integration ( NETI ) combined with steered molecular dynamics ( SMD ) is subject to bootstrapping.", "output": "There is no related enetity." }, { "input": "For the met - enkephalin pentapeptide at a water - graphite interface, we were able to obtain accurate predictions for the location of the adsorbed peptide and its free energy of adsorption from around 50 and 80 SMD simulations, respectively.", "output": "met - enkephalin, pentapeptide, graphite." }, { "input": "It was also shown that adsorption in this system is both energetically and entropically driven.", "output": "There is no related enetity." }, { "input": "The free energy of adsorption was also decomposed into that associated with formation of the cavity in the water near the graphite surface sufficient to accommodate the adsorbed peptide and that associated with insertion of the peptide into this cavity.", "output": "graphite." }, { "input": "This decomposition reveals that the former is modestly energetically and entropically unfavorable, whereas the latter is the opposite in both regards to a much greater extent.", "output": "There is no related enetity." }, { "input": "Gate - modulated thermoelectric power factor of hole gas in Ge - Si core - shell nanowires.", "output": "Ge, Si." }, { "input": "We experimentally studied the thermoelectric power factor of hole gas in individual Ge - Si core - shell nanowires with Ge core diameters ranging from 11 to 25 nm.", "output": "Ge, Si, Ge." }, { "input": "The Ge cores are dopant - free, but the Fermi level in the cores is pinned by surface and defect states in the epitaxial Si shell thereby doping the cores into the degenerate regime.", "output": "Ge, Si." }, { "input": "This doping mechanism avoids the high concentration of dopants usually encountered in bulk thermoelectric materials and provides a unique opportunity to enhance the carrier mobility with suppressed ionized impurity scattering.", "output": "There is no related enetity." }, { "input": "Moreover, the carrier concentration in small diameter nanowires has also been effectively modulated by field effect, allowing one to probe the electrical conductivity and thermopower within a wide range of carrier concentrations, which is crucial to understand the thermoelectric transport behavior.", "output": "There is no related enetity." }, { "input": "We found that the thermopower of nanowires with Ge core diameters down to 11 nm still follows the behavior of bulk Ge.", "output": "Ge, Ge." }, { "input": "As a result, the power factor is found to be closely correlated with the carrier mobility, which is higher than that of bulk Ge in one of the core - shell nanowires studied here.", "output": "Ge." }, { "input": "Interfacing quantum dots and graphitic surfaces with chlorine atomic ligands.", "output": "chlorine." }, { "input": "The performance of devices based on semiconductor nanocrystals ( NCs ) improves both with stronger interface interactions among NCs and between NCs and solid electrode surfaces.", "output": "There is no related enetity." }, { "input": "The combination of X - ray photoelectron spectroscopy ( XPS ) and solid ( 31 ) P CP / MAS NMR ( cross - polarization / magic angle spinning nuclear magnetic resonance ) shows that the selective substitution of long organic chains by chlorine atomic ligands during the colloidal synthesis by the hot injection method promotes the adsorption of CdSe NCs to carbon sp ( 2 ) surfaces, leading to the formation of well - ordered NC monolayers on graphitic materials.", "output": "( 31 ) P, chlorine, CdSe, carbon." }, { "input": "Sustained PU. 1 levels balance cell - cycle regulators to prevent exhaustion of adult hematopoietic stem cells.", "output": "There is no related enetity." }, { "input": "To provide a lifelong supply of blood cells, hematopoietic stem cells ( HSCs ) need to carefully balance both self - renewing cell divisions and quiescence.", "output": "There is no related enetity." }, { "input": "Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU. 1 acts upstream of these regulators.", "output": "There is no related enetity." }, { "input": "So far, attempts to uncover PU. 1 ' s role in HSC biology have failed because of the technical limitations of complete loss - of - function models.", "output": "There is no related enetity." }, { "input": "With the use of hypomorphic mice with decreased PU. 1 levels specifically in phenotypic HSCs, we found reduced HSC long - term repopulation potential that could be rescued completely by restoring PU. 1 levels.", "output": "There is no related enetity." }, { "input": "PU. 1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell - cycle regulators.", "output": "There is no related enetity." }, { "input": "Levels of PU. 1 were sustained through autoregulatory PU. 1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs.", "output": "There is no related enetity." }, { "input": "These results establish that PU. 1 mediates chromosome looping and functions as a master regulator of HSC proliferation.", "output": "There is no related enetity." }, { "input": "The Hunger Games: p53 regulates metabolism upon serine starvation.", "output": "serine." }, { "input": "Cancer cells reprogram their metabolism to support a high proliferative rate.", "output": "There is no related enetity." }, { "input": "A new study shows that, upon serine starvation, the tumor suppressor p53 activates p21 to shift metabolic flux from purine biosynthesis to glutathione production, which enhances cellular proliferation and viability by combating ROS ( Maddocks et al., 2013 ).", "output": "serine, purine, glutathione." }, { "input": "Structural analogs of huperzine A improve survival in guinea pigs exposed to soman.", "output": "huperzine A." }, { "input": "Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase ( AChE ) and subsequently glutamatergic function, leading to uncontrolled seizures.", "output": "There is no related enetity." }, { "input": "The natural alkaloid ( - ) - huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose.", "output": "( - ) - huperzine A." }, { "input": "It is hypothesized that analogs of both ( + ) - and ( - ) - huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents.", "output": "( + ) - and ( - ) - huperzine A, NMDA." }, { "input": "In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1. 2 or 2 x LD ( 50 ).", "output": "huperzine A." }, { "input": "Synthesis and biological evaluation of new cytotoxic indazolo [ 4, 3 - gh ] isoquinolinone derivatives.", "output": "indazolo [ 4 , 3 - gh ] isoquinolinone." }, { "input": "A series of indazolo [ 4, 3 - gh ] isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone.", "output": "indazolo [ 4 , 3 - gh ] isoquinolinones, Mitoxantrone." }, { "input": "The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC ( non - small - cell lung cancer ) and colon carcinoma.", "output": "There is no related enetity." }, { "input": "In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested.", "output": "There is no related enetity." }, { "input": "Lactose substituted zinc phthalocyanine: a near infrared fluorescence imaging probe for liver cancer targeting.", "output": "Lactose, zinc phthalocyanine." }, { "input": "A near infrared fluorescence probe, lactose substituted zinc phthalocyanine, [ 2, 9 ( 10 ), 16 ( 17 ), 23 ( 24 ) - tetrakis ( ( 1 - ( beta - d - lactose - 2 - yl ) - 1H - 1, 2, 3 - triazol - 4 - yl ) methoxyl ) phthalocyaninato ] zinc ( II ), was synthesized via click reaction.", "output": "lactose, zinc phthalocyanine, [ 2 , 9 ( 10 ) , 16 ( 17 ) , 23 ( 24 ) - tetrakis ( ( 1 - ( beta - d - lactose - 2 - yl ) - 1H - 1 , 2 , 3 - triazol - 4 - yl ) methoxyl ) phthalocyaninato ] zinc ( II )." }, { "input": "Structural characterization and optical experiment demonstrated its excellent biocompatibility and fluorescence imaging ability.", "output": "There is no related enetity." }, { "input": "Near infrared fluorescence imaging in vivo for liver cancer, lung cancer and melanoma cancer with tumor bearing nude mice as models demonstrated that lactose substituted zinc phthalocyanine has specifically targeting ability to liver cancer while no targeting to lung cancer or melanoma, which implied its potential in liver cancer diagnosis as a near infrared optical probe.", "output": "lactose, zinc phthalocyanine." }, { "input": "Facile one - pot synthesis of novel dispirooxindole - pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.", "output": "dispirooxindole - pyrrolidine." }, { "input": "Novel dispirooxindole - pyrrolidine derivatives have been synthesized through 1, 3 - dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3 - ( 1H - indol - 3 - yl ) - 3 - oxo - 2 - ( 2 - oxoindolin - 3 - ylidene ) propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition.", "output": "dispirooxindole - pyrrolidine, azomethine, isatin, sarcosine, 3 - ( 1H - indol - 3 - yl ) - 3 - oxo - 2 - ( 2 - oxoindolin - 3 - ylidene ) propanenitrile, acenaphthenequinone." }, { "input": "Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity.", "output": "There is no related enetity." }, { "input": "Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines.", "output": "There is no related enetity." }, { "input": "Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62. 96 %, 62. 03 %, 67. 67 % and 60. 22 %, respectively, at the dose of 200 mu g / mL and compound 7i shows IC50 value in 50 mu g / mL.", "output": "There is no related enetity." }, { "input": "Manganese - loaded lipid - micellar theranostics for simultaneous drug and gene delivery to lungs.", "output": "Manganese." }, { "input": "Gadolinium ( Gd ) contrast agents are predominantly used for T ( 1 ) MR imaging.", "output": "Gadolinium, Gd." }, { "input": "However, the high toxicity of Gd ( 3 + ) and potential side effects including nephrogenic systemic fibrosis have led to the search for alternative T ( 1 ) contrast agents.", "output": "Gd ( 3 + )." }, { "input": "Since manganese ( Mn ) has paramagnetic properties with five unpaired electrons that permit high spin number, long electronic relaxation times, and labile water exchange, we evaluated Mn as a T ( 1 ) magnetic resonance imaging ( MRI ) contrast agent for lung imaging.", "output": "manganese, Mn, Mn." }, { "input": "Here we report on the design and synthesis of multifunctional lipid - micellar nanoparticles ( LMNs ) containing Mn oxide ( M - LMNs ) for MRI that can also be used for DNA and drug delivery.", "output": "Mn oxide." }, { "input": "Oleic acid - coated MnO nanoparticles were encapsulated in micelles composed of polyethylene glycol ( PEG - 2000 ), phosphatidylethanolamine ( PE ), DC - cholesterol, and dioleoyl - phosphatidylethanolamine ( DOPE ).", "output": "Oleic acid, MnO, polyethylene glycol, PEG - 2000, phosphatidylethanolamine, cholesterol, dioleoyl - phosphatidylethanolamine, DOPE." }, { "input": "The particles are taken up in vitro by human embryonic kidney ( HEK293 ), Lewis lung carcinoma ( LLC1 ), and A549 cells and are devoid of cytotoxicity.", "output": "There is no related enetity." }, { "input": "When administered to mice intranasally, they preferentially accumulate in the lungs.", "output": "There is no related enetity." }, { "input": "In vitro phantom and ex vivo lung MRI results confirmed that M - LMNs are able to enhance T ( 1 ) MRI contrast.", "output": "There is no related enetity." }, { "input": "M - LMNs loaded with plasmid DNA and / or doxorubicin are efficiently taken up by HEK293 cells in vitro and by target cells in vivo.", "output": "doxorubicin." }, { "input": "Taken together, these results demonstrate that M - LMNs are capable of simultaneously providing MRI contrast and DNA and / or drug delivery to target cells in the lung and therefore may prove useful as a lung theranostic, especially for lung cancers.", "output": "There is no related enetity." }, { "input": "Xestospongin C induces monocytic differentiation of HL60 cells through activation of the ERK pathway.", "output": "Xestospongin C." }, { "input": "Xestospongin C ( XC ), which is a group of macrocyclic bis - 1 - oxaquinolizidines, is a potent inhibitor of sarcoendoplasmic reticulum calcium transport ATPase and IP3 receptor.", "output": "Xestospongin C, bis - 1 - oxaquinolizidines." }, { "input": "Nevertheless, very less information is available regarding whether XC induces AML differentiation.", "output": "There is no related enetity." }, { "input": "We investigated the potential role of XC in the differentiation of human leukemia HL60 cells and mechanisms underlying XC actin.", "output": "There is no related enetity." }, { "input": "XC treatment inhibited proliferation by inducing G1 - phase cell cycle arrest in the HL60 cells.", "output": "There is no related enetity." }, { "input": "In addition, XC induced differentiation of HL60 cells into the CD14 ( + ) monocytic lineage, which was indicated by morphological changes, nitroblue tetrazolium reduction assay, and expressions of CD11b and CD14 surface antigens.", "output": "nitroblue tetrazolium." }, { "input": "Our results also showed that XC promotes phagocytic activity and granularity in HL60 cells, suggesting that the cells are functionally activated.", "output": "There is no related enetity." }, { "input": "Furthermore, XC enhanced tumor necrosis factor ( TNF ) - alpha - mediated cytotoxic effect by increasing the numbers of TNF receptors.", "output": "There is no related enetity." }, { "input": "Moreover, we showed that XC activates extracellular signal - regulated kinase ( ERK ) pathway in the differentiation stages.", "output": "There is no related enetity." }, { "input": "Inhibition of ERK activation using PD98059 significantly decreased NBT + HL60 cells induced by XC treatment.", "output": "PD98059." }, { "input": "Taken together, the results show that XC promotes monocytic differentiation of HL60 cells via ERK pathway activation, suggesting that XC could be a candidate for use as a differentiation - inducing agent for AML treatment.", "output": "There is no related enetity." }, { "input": "Identification of polyphenols and their metabolites in human urine after cranberry - syrup consumption.", "output": "polyphenols." }, { "input": "As the beneficial effects of American cranberry ( Vaccinium macrocarpon ) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial.", "output": "phenolic." }, { "input": "A rapid and sensitive method by ultra - performance liquid chromatography coupled to quadrupole - time - of - flight mass spectrometry ( UPLC - Q - TOF - MS ) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup.", "output": "phenolic." }, { "input": "Prior to the analysis, metabolites were extracted using an optimised solid - phase extraction procedure.", "output": "There is no related enetity." }, { "input": "All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns.", "output": "There is no related enetity." }, { "input": "Free coumaroyl hexose ( isomer 1 and 2 ), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4 - O - beta - d - glucuronide, methoxyquercetin 3 - O - galactoside, scopoletin, myricetin and quercetin, together with other 23 phase - I and phase - II metabolites, including various isomers, could be tentatively identified in the urine.", "output": "coumaroyl hexose, dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4 - O - beta - d - glucuronide, methoxyquercetin 3 - O - galactoside, scopoletin, myricetin, quercetin." }, { "input": "Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis ( TM ) software.", "output": "There is no related enetity." }, { "input": "gamma - Oryzanol protects against acute cadmium - induced oxidative damage in mice testes.", "output": "gamma - Oryzanol, cadmium." }, { "input": "Cadmium is a non - essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke.", "output": "Cadmium." }, { "input": "The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of gamma - oryzanol ( ORY ).", "output": "cadmium, gamma - oryzanol, ORY." }, { "input": "Mice were administrated with a single dose of 2. 5mg / kg of CdCl2, and then treated with ORY ( 50mM in canola oil, 5mL / kg ).", "output": "CdCl2, ORY." }, { "input": "Testes were removed after 24h and tested for lipid peroxidation ( TBARS ), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non - proteic thiols contents, and for the activities of superoxide dismutase ( SOD ), catalase ( CAT ), glutathione peroxidase ( GPx ), glutathione S - transferase ( GST ) and delta - aminolevulic acid dehydratase ( delta - ALA - D ).", "output": "ascorbic acid, cadmium, thiols, superoxide, glutathione, glutathione, S, delta - aminolevulic acid, delta - ALA." }, { "input": "Cadmium presented a significant alteration in all parameters, except GPx and CAT activities.", "output": "Cadmium." }, { "input": "Therapy reduced in a slight degree cadmium concentration in testes ( around 23 % ).", "output": "cadmium." }, { "input": "ORY restored SOD and GST activities as well as TBARS production to the control levels.", "output": "ORY." }, { "input": "Furthermore, ORY partially recovered delta - ALA - D activity inhibited by cadmium.", "output": "ORY, delta - ALA, cadmium." }, { "input": "This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium - induced testicular toxicity.", "output": "ORY, cadmium." }, { "input": "Support vector machine: Classifying and predicting mutagenicity of complex mixtures based on pollution profiles.", "output": "There is no related enetity." }, { "input": "Powerful, robust in silico approaches offer great promise for classifying and predicting biological effects of complex mixtures and for identifying the constituents of greatest concern.", "output": "There is no related enetity." }, { "input": "Support vector machine ( SVM ) methods can deal with high dimensional data and small sample size and examine multiple interrelationships among samples.", "output": "There is no related enetity." }, { "input": "In this work, we applied SVM methods to examine pollution profiles and mutagenicity of 60 water samples obtained from 6 cities in China during 2006 - 2011.", "output": "There is no related enetity." }, { "input": "Pollutant profiles were characterized in water extracts by gas chromatography - mass spectrometry ( GC / MS ) and mutagenicity examined by Ames assays.", "output": "There is no related enetity." }, { "input": "We encoded feature vectors of GS - MS peaks in the mixtures and used 48 samples as the training set, reserving 12 samples as the test set.", "output": "There is no related enetity." }, { "input": "The SVM model and regression were constructed from whole pollution profiles that ranked compounds in relation to their correlation to the mutagenicity.", "output": "There is no related enetity." }, { "input": "Both classification and prediction performance were evaluated.", "output": "There is no related enetity." }, { "input": "The SVM model based on whole pollution profiles showed lower performance ( sensitivity, specificity, accuracy and correlation coefficient were 69. 5 - 70. 7 %, 70. 6 - 73. 2 %, 69. 9 - 72. 1 %, and 0. 55 - 0. 59 %, respectively ) than one based on compounds with highest association with mutagenicity.", "output": "There is no related enetity." }, { "input": "A SVM model with the top 10 compounds had the highest performance ( sensitivity, specificity, accuracy, and correlation coefficient were 89. 8 - 90. 3 %, 90. 1 - 92. 1 %, 90. 1 - 91. 3 %, and 0. 80 - 0. 82 %, respectively ), with negligible decreases in performance between the test and training set.", "output": "There is no related enetity." }, { "input": "SVM can be a powerful, robust classifier of the relationship of pollutants and mutagenicity in complex real - world mixtures.", "output": "There is no related enetity." }, { "input": "The top 14 compounds have the greatest contribution to mutagenicity and deserve further studies to identify these constituents.", "output": "There is no related enetity." }, { "input": "Site dependent intestinal absorption of darunavir and its interaction with ketoconazole.", "output": "darunavir, ketoconazole." }, { "input": "The expression of P - gp increases from proximal to distal parts of the small intestine, whereas for P450 enzymes the expression is reported to be highest in duodenum and jejunum, decreasing to more distal sites.", "output": "There is no related enetity." }, { "input": "To evaluate to what extent the regional differences in expression of P - gp and P450 enzymes affect the absorption of a dual substrate, we investigated the transport of darunavir across different small intestinal segments ( duodenum, proximal jejunum and ileum ).", "output": "darunavir." }, { "input": "Moreover, the effect of ketoconazole on the intestinal absorption of darunavir was explored, since these drugs are commonly co - administered.", "output": "ketoconazole, darunavir." }, { "input": "Performing the rat in situ intestinal perfusion technique with mesenteric blood sampling, we found no significant differences in the transport of darunavir at the different intestinal segments.", "output": "darunavir." }, { "input": "The involvement of P - gp in the absorption of darunavir was clearly shown by coperfusion of darunavir with the P - gp inhibitor zosuquidar.", "output": "darunavir, darunavir, zosuquidar." }, { "input": "In presence of zosuquidar, a 2. 2 -, 4. 2 - and 5. 7 - fold increase in Papp values were measured for duodenum, proximal jejunum and ileum, respectively.", "output": "zosuquidar." }, { "input": "Involvement of P450 mediated metabolism in the absorption of darunavir could not be demonstrated in this rat model.", "output": "darunavir." }, { "input": "Upon studying the drug - drug interaction of darunavir with ketoconazole, data were indicative for an inhibitory effect of ketoconazole on P - gp as the main mechanism for the increased transport of darunavir across the small intestine.", "output": "darunavir, ketoconazole, ketoconazole, darunavir." }, { "input": "Cellular Mechanisms of Nociceptin / Orphanin FQ ( N / OFQ ) Peptide ( NOP ) Receptor Regulation and Heterologous Regulation by N / OFQ.", "output": "There is no related enetity." }, { "input": "The nociceptin / orphanin FQ ( N / OFQ ) peptide ( NOP ) receptor is the fourth and most recently discovered member of the opioid receptor superfamily that also includes mu, delta, and kappa opioid receptor subtypes ( MOR, DOR, and KOR, respectively ).", "output": "There is no related enetity." }, { "input": "The widespread anatomic distribution of the NOP receptor enables the modulation of several physiologic processes by its endogenous agonist, N / OFQ.", "output": "There is no related enetity." }, { "input": "Accordingly, the NOP receptor has gained a lot of attention as a potential target for the development of ligands with therapeutic use in several pathophysiological states.", "output": "There is no related enetity." }, { "input": "NOP receptor activation frequently results in effects opposing classic opioid receptor action; therefore, regulation of the NOP receptor and conditions affecting its modulatory tone are important to understand.", "output": "There is no related enetity." }, { "input": "Mounting evidence reveals a heterologous interaction of the NOP receptor with other G protein - coupled receptors, including MOR, DOR, and KOR, which may subsequently influence their function.", "output": "There is no related enetity." }, { "input": "Our focus in this review is to summarize and discuss the findings that delineate the cellular mechanisms of NOP receptor signaling and regulation and the regulation of other receptors by N / OFQ and the NOP receptor.", "output": "There is no related enetity." }, { "input": "Dissolved azaspiracids are absorbed and metabolized by blue mussels ( Mytilus edulis ).", "output": "azaspiracids." }, { "input": "The relationship between azaspiracid shellfish poisoning and a small dinoflagellate, Azadinium spinosum, has been shown recently.", "output": "azaspiracid." }, { "input": "The organism produces AZA1 and - 2, while AZA3 and other analogues are metabolic products formed in shellfish.", "output": "AZA1 and - 2, AZA3." }, { "input": "We evaluated whether mussels were capable of accumulating dissolved AZA1 and - 2, and compared the toxin profiles of these mussels at 24 h with profiles of those exposed to live or lysed A. spinosum.", "output": "AZA1 and - 2." }, { "input": "We also assessed the possibility of preparative production of AZA metabolites by exposing mussels to semi - purified AZA1.", "output": "AZA, AZA1." }, { "input": "We exposed mussels to similar concentration of AZAs: dissolved AZA1 + 2 ( crude extract ) at 7. 5 and 0. 75 mu g L ( - 1 ), dissolved AZA1 + 2 ( 7. 5 mu g L ( - 1 ) ) in combination with Isochrysis affinis galbana, and lysed and live A. spinosum cells at 1 x 10 ( 5 ) and 1 x 10 ( 4 ) cell mL ( - 1 ) ( containing equivalent amounts of AZA1 + 2 ).", "output": "AZAs, AZA1 + 2, AZA1 + 2, AZA1 + 2." }, { "input": "Subsequently, we dissected and analysed digestive glands, gills and remaining flesh.", "output": "There is no related enetity." }, { "input": "Mussels ( whole flesh ) accumulated AZAs to levels above the regulatory limit, except at the lower levels of dissolved AZAs.", "output": "AZAs, AZAs." }, { "input": "The toxin profile of the mussels varied significantly with treatment.", "output": "There is no related enetity." }, { "input": "The gills contained 42 - 46 % and the digestive glands 23 - 24 % of the total toxin load using dissolved AZAs, compared to 3 - 12 % and 75 - 90 %, respectively, in mussels exposed to live A. spinosum.", "output": "AZAs." }, { "input": "Exposure of mussels to semi - purified AZA1 produced the metabolites AZA17 ( 16. 5 % ) and AZA3 ( 1. 7 % ) after 4 days of exposure, but the conversion efficiency was too low to justify using this procedure for preparative isolation.", "output": "AZA1, AZA17, AZA3." }, { "input": "Polycationic nanoparticles synthesized using ARGET ATRP for drug delivery.", "output": "There is no related enetity." }, { "input": "This work provides a systemic comparison for ARGET ATRP and UV - initiated polycationic nanoparticles for drug delivery and a guide to deciding which type of polycationic nanoparticles have the best properties for specific applications.", "output": "There is no related enetity." }, { "input": "Polycationic nanoparticles were synthesized using a previously developed UV - initiated photoemulsion polymerization or a newly developed ARGET ATRP synthesis technique.", "output": "There is no related enetity." }, { "input": "The effect of the ratio of hydrophobic monomer in the feed was evaluated.", "output": "There is no related enetity." }, { "input": "Increasing the feed ratio of hydrophobic monomer was necessary to maintain biocompatibility and pH - responsive membrane disruptive characteristics when switching from the UV - initiated polymerization to ARGET ATRP.", "output": "There is no related enetity." }, { "input": "The resulting polycationic nanoparticles have utility as drug delivery carriers for hydrophobic drugs and / or nucleic acids.", "output": "There is no related enetity." }, { "input": "Change in the transfer profile of orally administered tetrodotoxin to non - toxic cultured pufferfish Takifugu rubripes depending of its development stage.", "output": "tetrodotoxin." }, { "input": "To investigate the effects of growth ( organ development ) on tetrodotoxin ( TTX ) dynamics in the pufferfish body, TTX - containing feed homogenate was administered to 6 - and 15 - month old non - toxic cultured specimens of the pufferfish Takifugu rubripes at a dose of 40 mouse units ( MU ) ( 8. 8 mu g ) / 20 g body weight by oral gavage.", "output": "tetrodotoxin, TTX, TTX." }, { "input": "After 24 h, the specimens were killed and the skin tissues ( dorsal and ventral ), muscle, liver, digestive tract, and gonads were separated.", "output": "There is no related enetity." }, { "input": "TTX content ( mu g / g ) in each tissue, determined by liquid chromatography / mass spectrometry, revealed that the TTX distribution profile, particularly the TTX content of the liver, greatly differed between the two ages; the TTX score of 15 - month old fish ( 3. 3 mu g / g ) was nearly 5 - fold that of 6 - month old fish ( 0. 68 mu g / g ).", "output": "TTX, TTX, TTX, TTX." }, { "input": "The total remaining TTX amount per individual ( relative amount to the given dose ) was 31 % in 6 - month old fish, of which 71 % was in the skin, and 84 % in 15 - month old fish, of which 83 % was in the liver.", "output": "TTX." }, { "input": "The gonadosomatic index ( GSI ) and hepatosomatic index ( HSI ) scores, and histologic observations of the gonads and liver suggest that although there is little difference in maturation stage between these two ages, there are clear distinctions in the developmental stage of the liver.", "output": "There is no related enetity." }, { "input": "The results suggest that the TTX dynamics in T. rubripes are linked to the development of the liver, i. e., the TTX taken up into the pufferfish body via food organisms is eliminated or transferred mainly to the skin in young fish with an undeveloped liver, but as the fish grow and the liver continues to develop, most of the TTX is transferred to and accumulated in the liver.", "output": "TTX, TTX, TTX." }, { "input": "Protein carbonylation in human endothelial cells exposed to cigarette smoke extract.", "output": "There is no related enetity." }, { "input": "Cigarette smoke is a significant independent risk factor for vascular diseases and is a leading cause of structural and functional alterations of the vascular endothelium.", "output": "There is no related enetity." }, { "input": "In this study, we show protein carbonylation in the human umbilical vein endothelial cell line ( ECV - 304 ) exposed to whole - phase cigarette smoke extract.", "output": "There is no related enetity." }, { "input": "The main carbonylated proteins, including cytoskeletal proteins, glycolytic enzymes, xenobiotic metabolizing and antioxidant enzymes, and endoplasmic reticulum proteins, were identified by means of two - dimensional electrophoresis and Matrix - Assisted Laser Desorption / Ionization - Time of Flight ( MALDI - TOF ) mass spectrometry ( redox proteomics ).", "output": "There is no related enetity." }, { "input": "Morphological analyses by fluorescence microscopy evidenced alterations in the microtubule cytoskeleton, especially at longer exposure time to cigarette smoke extract.", "output": "There is no related enetity." }, { "input": "Morphological analyses by transmission electron microscopy showed vacuolisation of the cytoplasm, alteration of mitochondria ultrastructure, and some enlargement of the perinuclear space.", "output": "There is no related enetity." }, { "input": "The possible role played by protein carbonylation caused by reactive species contained in cigarette smoke in the cigarette smoke - induced endothelial injury is discussed.", "output": "There is no related enetity." }, { "input": "Control of human adenovirus type 5 gene expression by cellular Daxx / ATRX chromatin - associated complexes.", "output": "There is no related enetity." }, { "input": "Death domain - associated protein ( Daxx ) cooperates with X - linked alpha - thalassaemia retardation syndrome protein ( ATRX ), a putative member of the sucrose non - fermentable 2 family of ATP - dependent chromatin - remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3. 3 deposition and transcriptional repression of cellular promoters.", "output": "sucrose, ATP." }, { "input": "Despite recent findings on the fundamental importance of chromatin modification in host - cell gene regulation, it remains unclear whether adenovirus type 5 ( Ad5 ) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression.", "output": "There is no related enetity." }, { "input": "Here, we focus on the repressive role of the Daxx / ATRX complex during Ad5 replication, which depends on intact protein - protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX.", "output": "There is no related enetity." }, { "input": "To ensure efficient viral replication, Ad5 E1B - 55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin - dependent E3 - ubiquitin ligase.", "output": "There is no related enetity." }, { "input": "Our studies illustrate the importance and diversity of viral factors antagonizing Daxx / ATRX - mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5.", "output": "There is no related enetity." }, { "input": "We show for the first time that cellular Daxx / ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling.", "output": "There is no related enetity." }, { "input": "Structural and mechanical properties of individual human telomeric G - quadruplexes in molecularly crowded solutions.", "output": "There is no related enetity." }, { "input": "Recent experiments provided controversial observations that either parallel or non - parallel G - quadruplex exists in molecularly crowded buffers that mimic cellular environment.", "output": "There is no related enetity." }, { "input": "Here, we used laser tweezers to mechanically unfold structures in a human telomeric DNA fragment, 5 ' - ( TTAGGG ) 4TTA, along three different trajectories.", "output": "There is no related enetity." }, { "input": "After the end - to - end distance of each unfolding geometry was measured, it was compared with PDB structures to identify the best - matching G - quadruplex conformation.", "output": "There is no related enetity." }, { "input": "This method is well - suited to identify biomolecular structures in complex settings not amenable to conventional approaches, such as in a solution with mixed species or at physiologically significant concentrations.", "output": "There is no related enetity." }, { "input": "With this approach, we found that parallel G - quadruplex coexists with non - parallel species ( 1: 1 ratio ) in crowded buffers with dehydrating cosolutes [ 40 % w / v dimethyl sulfoxide ( DMSO ) or acetonitrile ( ACN ) ].", "output": "dimethyl sulfoxide, DMSO, acetonitrile, ACN." }, { "input": "In crowded solutions with steric cosolutes [ 40 % w / v bovine serum albumin ( BSA ) ], the parallel G - quadruplex constitutes only 10 % of the population.", "output": "There is no related enetity." }, { "input": "This difference unequivocally supports the notion that dehydration promotes the formation of parallel G - quadruplexes.", "output": "There is no related enetity." }, { "input": "Compared with DNA hairpins that have decreased unfolding forces in crowded ( 9 pN ) versus diluted ( 15 pN ) buffers, those of G - quadruplexes remain the same ( 20 pN ).", "output": "There is no related enetity." }, { "input": "Such a result implies that in a cellular environment, DNA G - quadruplexes, instead of hairpins, can stop DNA / RNA polymerases with stall forces often < 20 pN.", "output": "There is no related enetity." }, { "input": "Parathyroid hormone ( 1 - 34 ) counteracts the suppression of interleukin - 11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess.", "output": "There is no related enetity." }, { "input": "Glucocorticoid ( GC ) excess causes a rapid loss of bone with a reduction in bone formation.", "output": "There is no related enetity." }, { "input": "Intermittent PTH ( 1 - 34 ) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess.", "output": "There is no related enetity." }, { "input": "We have previously demonstrated that mechanical strain enhances interleukin ( IL ) - 11 gene transcription by a rapid induction of Delta FosB expression and protein kinase C ( PKC ) - delta - mediated phosphorylation of phosphorylated mothers against decapentaplegic ( Smad ) - 1.", "output": "There is no related enetity." }, { "input": "Because IL - 11 suppresses the expression of dickkopf - 1 and - 2 and stimulates Wnt signaling, IL - 11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation.", "output": "There is no related enetity." }, { "input": "The present study was undertaken to examine the effect of PTH ( 1 - 34 ) and GCs on IL - 11 expression in murine primary osteoblasts ( mPOBs ).", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) treatment of mPOBs enhanced IL - 11 expression in a time - and dose - dependent manner.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) also stimulated Delta FosB expression and Smad1 phosphorylation, which cooperatively stimulated IL - 11 gene transcription.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) - induced Smad1 phosphorylation was mediated via PKC delta and was abrogated in mPOBs from PKC delta knockout mice.", "output": "There is no related enetity." }, { "input": "Dexamethasone suppressed IL - 11 gene transcription enhanced by PTH ( 1 - 34 ) without affecting Delta FosB expression or Smad1 phosphorylation, and dexamethasone - GC receptor complex was bound to JunD, which forms heterodimers with Delta FosB.", "output": "Dexamethasone, dexamethasone." }, { "input": "High doses of PTH ( 1 - 34 ) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti - IL - 11 antibody or IL - 11 small interfering RNA.", "output": "dexamethasone." }, { "input": "These results demonstrate that PTH ( 1 - 34 ) and GCs interact to regulate IL - 11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH ( 1 - 34 ) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL - 11 expression.", "output": "dexamethasone." }, { "input": "A prospective open - label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents.", "output": "paliperidone." }, { "input": "RATIONALE: Treatment studies for the management of pediatric bipolar disorder are limited.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders.", "output": "paliperidone." }, { "input": "METHODS: An 8 - week, prospective, open - label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders ( depression, psychosis, attention - deficit / hyperactivity disorder [ ADHD ] ).", "output": "paliperidone." }, { "input": "Assessments included the Young Mania Rating Scale ( YMRS ), Clinical Global Impression scale ( CGI ), Children ' s Depression Rating Scale - Revised ( CDRS - R ), and Brief Psychiatric Rating Scale ( BPRS ).", "output": "There is no related enetity." }, { "input": "Adverse events were assessed through spontaneous self - reports, vital signs, weight monitoring, and laboratory analysis.", "output": "There is no related enetity." }, { "input": "RESULTS: Fifteen youth with bipolar spectrum disorders ( YMRS at entry: 32. 8 +/- 6. 1 ) were enrolled in the study and 11 ( 73 % ) completed the 8 - week trial.", "output": "There is no related enetity." }, { "input": "The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects.", "output": "paliperidone." }, { "input": "Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores ( - 18. 7 +/- 13. 9, p < 0. 001 ) at endpoint.", "output": "paliperidone." }, { "input": "Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms.", "output": "Paliperidone." }, { "input": "Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight ( 4. 1 +/- 5. 5 lb ) were substantial.", "output": "paliperidone." }, { "input": "CONCLUSIONS: Open - label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth.", "output": "paliperidone." }, { "input": "Future placebo - controlled studies are warranted to confirm these findings.", "output": "There is no related enetity." }, { "input": "White light from a single - emitter light - emitting electrochemical cell.", "output": "There is no related enetity." }, { "input": "We report a novel and generic approach for attaining white light from a single - emitter light - emitting electrochemical cell ( LEC ).", "output": "There is no related enetity." }, { "input": "With an active - layer comprising a multifluorophoric conjugated copolymer ( MCP ) and an electrolyte designed to inhibit MCP energy - transfer interactions during LEC operation, we are able to demonstrate LECs that emit broad - band white light with a color rendering index of 82, a correlated - color temperature of 4000 K, and a current conversion efficacy of 3. 8 cd / A.", "output": "There is no related enetity." }, { "input": "It is notable that this single - emitter LEC configuration eliminates color - drift problems stemming from phase separation, which are commonly observed in conventional blended multiemitter devices.", "output": "There is no related enetity." }, { "input": "Moreover, the key role of the electrolyte in limiting undesired energy - transfer reactions is highlighted by the observation that an electrolyte - free organic light - emitting diode comprising the same MCP emits red light.", "output": "There is no related enetity." }, { "input": "Retinoids and glucocorticoids target common genes in hippocampal HT22 cells.", "output": "Retinoids." }, { "input": "Vitamin A metabolite retinoic acid ( RA ) plays a major role in the aging adult brain plasticity.", "output": "Vitamin A, retinoic acid." }, { "input": "Conversely, chronic excess of glucocorticoids ( GC ) elicits some deleterious effects in the hippocampus.", "output": "There is no related enetity." }, { "input": "We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons.", "output": "There is no related enetity." }, { "input": "We investigated proteins involved either in the signaling pathways [ RA receptor beta ( RAR beta ) and glucocorticoid receptor ( GR ) ] or in neuron differentiation and plasticity [ tissue transglutaminase 2 ( tTG ) and brain - derived neurotrophic factor ( BDNF ) ] in a hippocampal cell line, HT22.", "output": "There is no related enetity." }, { "input": "We applied RA and / or dexamethasone ( Dex ) as activators of the pathways and investigated mRNA and protein expression of their receptors and of tTG and BDNF as well as tTG activity and BDNF secretion.", "output": "dexamethasone, Dex." }, { "input": "Our results confirm the involvement of RA - and GC - dependent pathways and their interaction in our neuronal cell model.", "output": "There is no related enetity." }, { "input": "First, both pathways regulate the transcription and expression of own and reciprocal receptors: RA and Dex increased RAR beta and decreased GR expressions.", "output": "There is no related enetity." }, { "input": "Second, Dex reduces the expression of tTG when associated with RA despite stimulating its expression when used alone.", "output": "Dex." }, { "input": "Importantly, when they are combined, RA counteracts the deleterious effect of glucocorticoids on BDNF regulation and thus may improve neuronal plasticity under stress conditions.", "output": "There is no related enetity." }, { "input": "In conclusion, GC and RA both interact through regulations of the two receptors, RAR beta and GR.", "output": "There is no related enetity." }, { "input": "Furthermore, they both act, synergistically or oppositely, on other target proteins critical for neuronal plasticity, tTG and BDNF.", "output": "There is no related enetity." }, { "input": "Inhibition of ghrelin O - acyltransferase attenuates food deprivation - induced increases in ingestive behavior.", "output": "O." }, { "input": "Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a ' hunger signal '.", "output": "There is no related enetity." }, { "input": "The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O - acyltransferase ( GOAT ) catalyzation.", "output": "O." }, { "input": "The GOAT inhibitor, GO - CoA - Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice.", "output": "There is no related enetity." }, { "input": "Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation.", "output": "There is no related enetity." }, { "input": "In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48 - 56h food deprivation.", "output": "There is no related enetity." }, { "input": "Therefore, we tested the necessity of increased ghrelin in food - deprived Siberian hamsters to stimulate ingestive behaviors.", "output": "There is no related enetity." }, { "input": "To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food.", "output": "There is no related enetity." }, { "input": "Animals were given an injection of GO - CoA - Tat ( i. p., 11 mu mol / kg ) every 6h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48h food deprivation.", "output": "There is no related enetity." }, { "input": "We found that GO - CoA - Tat attenuated food foraging ( 0 - 1h ), food intake ( 0 - 1 and 2 - 4h ), and food hoarding ( 0 - 1h and 2 and 3days ) post - refeeding compared with saline treated animals.", "output": "There is no related enetity." }, { "input": "This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation - induced increases in ingestive behavior.", "output": "There is no related enetity." }, { "input": "Therefore, ghrelin is a critical aspect of the multi - faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans.", "output": "There is no related enetity." }, { "input": "Chemically diverse microtubule stabilizing agents initiate distinct mitotic defects and dysregulated expression of key mitotic kinases.", "output": "There is no related enetity." }, { "input": "Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined.", "output": "There is no related enetity." }, { "input": "The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide / fijianolide B and paclitaxel were studied.", "output": "taccalonolide AJ, laulimalide, fijianolide B, paclitaxel." }, { "input": "These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling.", "output": "There is no related enetity." }, { "input": "Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins.", "output": "There is no related enetity." }, { "input": "Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent than paclitaxel or laulimalide, which is consistent with the distinct defects in expression and activation of Plk1 and Eg5 caused by each stabilizer.", "output": "Taccalonolide AJ, paclitaxel, laulimalide." }, { "input": "Localization studies revealed that TPX2 and Aurora A are associated with each spindle aster formed by each stabilizer.", "output": "There is no related enetity." }, { "input": "This suggests a common mechanism of aster formation.", "output": "There is no related enetity." }, { "input": "However, taccalonolide AJ also causes pericentrin accumulation on every spindle aster.", "output": "taccalonolide AJ." }, { "input": "The presence of pericentrin at every spindle aster initiated by taccalonolide AJ might facilitate the maintenance and stability of the highly focused asters formed by this stabilizer.", "output": "taccalonolide AJ." }, { "input": "Laulimalide and paclitaxel cause completely different patterns of expression and activation of these proteins, as well as phenotypically different spindle phenotypes.", "output": "Laulimalide, paclitaxel." }, { "input": "Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds.", "output": "There is no related enetity." }, { "input": "Creation and screening of a multi - family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR - 104A.", "output": "CB1954, PR - 104A." }, { "input": "Two potentially complementary approaches to improve the anti - cancer strategy gene - directed enzyme prodrug therapy ( GDEPT ) are discovery of more efficient prodrug - activating enzymes, and development of more effective prodrugs.", "output": "There is no related enetity." }, { "input": "Here we demonstrate the utility of a flexible screening system based on the Escherichia coli SOS response to evaluate novel nitroreductase enzymes and prodrugs in concert.", "output": "There is no related enetity." }, { "input": "To achieve this, a library of 47 candidate genes representing 11 different oxidoreductase families was created and screened to identify the most efficient activators of two different nitroaromatic prodrugs, CB1954 and PR - 104A.", "output": "CB1954, PR - 104A." }, { "input": "The most catalytically efficient nitroreductases were found in the NfsA and NfsB enzyme families, with NfsA homologues generally more active than NfsB.", "output": "There is no related enetity." }, { "input": "Some members of the AzoR, NemA and MdaB families also exhibited low - level activity with one or both prodrugs.", "output": "There is no related enetity." }, { "input": "The results of SOS screening in our optimised E. coli reporter strain SOS - R2 were generally predictive of the ability of nitroreductase candidates to sensitise E. coli to CB1954, and of the kcat / Km for each prodrug substrate at a purified protein level.", "output": "CB1954." }, { "input": "However, we also found that not all nitroreductases express stably in human ( HCT - 116 colon carcinoma ) cells, and that activity at a purified protein level did not necessarily predict activity in stably transfected HCT - 116.", "output": "There is no related enetity." }, { "input": "These results highlight a need for all enzyme - prodrug partners for GDEPT to be assessed in the specific context of the vector and cell line that they are intended to target.", "output": "There is no related enetity." }, { "input": "Nonetheless, our oxidoreductase library and optimised screens provide valuable tools to identify preferred nitroreductase - prodrug combinations to advance to preclinical evaluation.", "output": "There is no related enetity." }, { "input": "The fundamental chemical equation of aromaticity.", "output": "There is no related enetity." }, { "input": "In the search for the chemical measure of molecular aromaticity, namely the energetic gain of a cyclic delocalized structure for just being cyclic, the numerous definitions of generic aromatic stabilisation energies proposed hitherto stand as approximates of the conceptual limit devised within the framework of spectral graph theory, i. e. the topological resonance energy ( TRE ).", "output": "There is no related enetity." }, { "input": "After a 36 year challenge, the TRE acyclic reference of any pi - cyclic molecule, originally merely defined by an abstract matching polynomial, is now given a real chemical structure: the M o bius - twisted head - to - tail metathesis cyclo - dimer of the parent ring.", "output": "There is no related enetity." }, { "input": "The original treatment at the H u ckel molecular orbital level of theory can now be extended to DFT or ab initio levels.", "output": "There is no related enetity." }, { "input": "The corresponding ring opening - closing - twisting chemical transformation provides the observable basis for the measure of aromaticity under either vertical or adiabatic conditions.", "output": "There is no related enetity." }, { "input": "The importance of the TiO2 / quantum dots interface in the recombination processes of quantum dot sensitized solar cells.", "output": "TiO2." }, { "input": "Quantum dot sensitized solar cells ( QDSSCs ) present a promising technology for next generation photovoltaic cells, having exhibited a considerable leap in performance over the last few years.", "output": "There is no related enetity." }, { "input": "However, recombination processes occurring in parallel at the TiO ( 2 ) - QDs - electrolyte triple junction constitute one of the major limitations for further improvement of QDSSCs.", "output": "TiO ( 2 )." }, { "input": "Reaching higher conversion efficiencies necessitates gaining a better understanding of the mechanisms of charge recombination in these kinds of cells; this will essentially lead to the development of new solutions for inhibiting the described losses.", "output": "There is no related enetity." }, { "input": "In this study we have systematically examined the contribution of each interface formed at the triple junction to the recombination of the solar cell.", "output": "There is no related enetity." }, { "input": "We show that the recombination of electrons at the TiO ( 2 ) / QDs interface is as important as the recombination from TiO ( 2 ) and QDs to the electrolyte.", "output": "TiO ( 2 ), TiO ( 2 )." }, { "input": "By applying conformal MgO coating both above and below the QD surface, recombination rates were significantly reduced, and an improvement of more than 20 % in cell efficiency was recorded.", "output": "MgO." }, { "input": "Self - templating synthesis of hollow mesoporous silica and their applications in catalysis and drug delivery.", "output": "silica." }, { "input": "Hollow mesoporous silica materials have been intensively pursued because of their unique properties for various applications.", "output": "silica." }, { "input": "Yolk / shell structured hollow mesoporous silica with functional cores inside their hollow interior can further broaden the applications of hollow mesoporous silica.", "output": "silica, silica." }, { "input": "The self - templating strategy has been developed as one of the most important strategies to effectively fabricate hollow mesoporous silicas and their yolk / shell counterparts.", "output": "There is no related enetity." }, { "input": "In this feature article, we provide an overview of advances in the self - templating synthesis of hollow mesoporous silica based on the following three strategies: surface - protected etching, structural difference - based selective etching, and cationic surfactant assisted self - templating.", "output": "silica." }, { "input": "We then discuss some important applications of these self - templating strategy - derived hollow mesoporous silicas, such as nanoreactors for confined catalysis and multifunctional platforms for combined therapy.", "output": "silicas." }, { "input": "Finally, some perspectives for the future development of this active research field are provided.", "output": "There is no related enetity." }, { "input": "An algorithm to detect adverse drug reactions in the neonatal intensive care unit.", "output": "There is no related enetity." }, { "input": "Critically ill newborns in neonatal intensive care units ( NICUs ) are at greater risk of developing adverse drug reactions ( ADRs ).", "output": "There is no related enetity." }, { "input": "Differentiation of ADRs from reactions associated with organ dysfunction / immaturity is difficult.", "output": "There is no related enetity." }, { "input": "Current ADR algorithm scoring was established arbitrarily without validation in infants.", "output": "There is no related enetity." }, { "input": "The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU.", "output": "There is no related enetity." }, { "input": "Algorithm development began with a 24 - item questionnaire for data collection on 100 previously suspected ADRs.", "output": "There is no related enetity." }, { "input": "Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs.", "output": "There is no related enetity." }, { "input": "Consensus \" gold standard \" was reached via teleconference.", "output": "There is no related enetity." }, { "input": "Logistic regression and iterative C programs were used to derive the scoring system.", "output": "There is no related enetity." }, { "input": "For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm.", "output": "There is no related enetity." }, { "input": "Weighted kappa and intraclass correlation coefficient ( ICC ) were used to compare validity and reliability of algorithms.", "output": "There is no related enetity." }, { "input": "The new algorithm consists of 13 items.", "output": "There is no related enetity." }, { "input": "Kappa and ICC of the new algorithm were 0. 76 and 0. 62 versus 0. 31 and 0. 43 for the Naranjo algorithm.", "output": "There is no related enetity." }, { "input": "The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population.", "output": "There is no related enetity." }, { "input": "Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.", "output": "There is no related enetity." }, { "input": "F1 - ATPase of Escherichia coli: the epsilon - inhibited state forms after ATP hydrolysis, is distinct from the ADP - inhibited state, and responds dynamically to catalytic site ligands.", "output": "ATP, ADP." }, { "input": "F1 - ATPase is the catalytic complex of rotary nanomotor ATP synthases.", "output": "ATP." }, { "input": "Bacterial ATP synthases can be autoinhibited by the C - terminal domain of subunit epsilon, which partially inserts into the enzyme ' s central rotor cavity to block functional subunit rotation.", "output": "ATP, C." }, { "input": "Using a kinetic, optical assay of F1. epsilon binding and dissociation, we show that formation of the extended, inhibitory conformation of epsilon ( epsilon X ) initiates after ATP hydrolysis at the catalytic dwell step.", "output": "ATP." }, { "input": "Prehydrolysis conditions prevent formation of the epsilon X state, and post - hydrolysis conditions stabilize it.", "output": "There is no related enetity." }, { "input": "We also show that epsilon inhibition and ADP inhibition are distinct, competing processes that can follow the catalytic dwell.", "output": "ADP." }, { "input": "We show that the N - terminal domain of epsilon is responsible for initial binding to F1 and provides most of the binding energy.", "output": "N." }, { "input": "Without the C - terminal domain, partial inhibition by the epsilon N - terminal domain is due to enhanced ADP inhibition.", "output": "C, N, ADP." }, { "input": "The rapid effects of catalytic site ligands on conformational changes of F1 - bound epsilon suggest dynamic conformational and rotational mobility in F1 that is paused near the catalytic dwell position.", "output": "There is no related enetity." }, { "input": "Imposex effects on the veined rapa whelk ( Rapana venosa ) in Bohai Bay, China.", "output": "There is no related enetity." }, { "input": "Environmentally relevant concentrations of organotin compounds ( OTs ) may trigger sex changes in marine invertebrates and pose a threat to the marine ecosystem.", "output": "organotin." }, { "input": "In this study, we investigated organotin levels and the biological responses of wild veined rapa whelk ( Rapana venosa ) from L u juhe district ( LJH ), Dashentang district ( DST ), and Nanpaihe district ( NPH ) in Bohai Bay, China.", "output": "organotin." }, { "input": "We found that 11. 11 and 22. 95 % of the veined rapa whelks from DST and NPH exhibited imposex characteristics with a relative penis size index ( RPSI ) of 12. 50 and 12. 31, respectively.", "output": "There is no related enetity." }, { "input": "The RNA / DNA ratio was significantly lower in females from DST than those from LJH ( p < 0. 05 ), and a slight increase in DNA damage was observed in females and imposex individuals compared to males.", "output": "There is no related enetity." }, { "input": "Moreover, less genetic distance occurred between LJH and NPH ( 0. 016 ) than between LJH and DST ( 0. 028 ), although they belonged to the same regional population.", "output": "There is no related enetity." }, { "input": "OTs analysis showed that triphenyltin chloride concentrations ( 41. 45 ng / g dried weight ) were significantly higher than tributyltin concentrations ( 9. 51 ng / g dried weight ) in tissues ( p < 0. 05 ), but no significant differences were observed in sediments ( p > 0. 05 ).", "output": "triphenyltin chloride, tributyltin." }, { "input": "In conclusion, the occurrence of imposex individuals and biological responses of the wild veined rapa whelk from Bohai Bay suggest that the marine ecosystem might be at risk.", "output": "There is no related enetity." }, { "input": "The accumulation of metal ( Co, Cr, Cu, Mn and Zn ) in freshwater Ulva ( Chlorophyta ) and its habitat.", "output": "Co, Cr, Cu, Mn, Zn." }, { "input": "The possibility of using freshwater Ulva ( Chlorophyta ) as a bioaccumulator of metals ( Co, Cr, Cu, Mn and Zn ) in lake and river water was examined weekly in the summer of 2010 in three types of samples: the water, the sediment and the thalli of Ulva.", "output": "Co, Cr, Cu, Mn, Zn." }, { "input": "Samples of freshwater Ulva were collected from two aqueous ecosystems lie 250 km away from the basin of the Baltic Sea and 53 km from each other.", "output": "There is no related enetity." }, { "input": "A flow lake located in the centre of the big city was the first water reservoir ( ten sites ) and second, the suburban river ( six sites ).", "output": "There is no related enetity." }, { "input": "The mean metal concentrations in the Ulva tissue from the river and the lake decreased in the following order: Mn > Zn > Cr > Cu > Co and Mn > Cr > Zn > Cu > Co, respectively.", "output": "Mn, Zn, Cr, Cu, Co, Mn, Cr, Zn, Cu, Co." }, { "input": "Moreover, a negative and statistically significant correlation between Mn concentrations in the Ulva thalli and the river water was observed.", "output": "Mn." }, { "input": "Additionally, numerous correlations were noted between the different concentrations of metals within the Ulva thalli, in the water and in the sediment.", "output": "There is no related enetity." }, { "input": "The great concentrations of Mn and Zn and the smallest of Co were found in thalli of Ulva, irrespective of the type of the ecosystem from which samples of algal thalli originated.", "output": "Mn, Zn, Co." }, { "input": "Freshwater Ulva populations examined in this study were clearly characterized a dozen or so times by the higher Mn and Cr accumulation than taxa from that genera coming from sea ecosystems.", "output": "Mn, Cr." }, { "input": "The calculated bioconcentration factor confirm the high potential for freshwater Ulva to be a bioaccumulator of trace metals in freshwater ecosystems.", "output": "There is no related enetity." }, { "input": "Abo -, inco -, ona -, and rima - botulinum toxins in clinical therapy: a primer.", "output": "There is no related enetity." }, { "input": "Botulinum neurotoxin ( BoNT ) is an acetylcholine release inhibitor and a neuromuscular - blocking agent used for the treatment of a variety of medical and cosmetic indications.", "output": "acetylcholine." }, { "input": "Currently, in the United States, there are four BoNT formulations licensed for use: abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, and rimabotulinumtoxinB.", "output": "There is no related enetity." }, { "input": "These revised name designations were established to reinforce the understanding that each BoNT product has an individual potency and is not interchangeable with any other BoNT product.", "output": "There is no related enetity." }, { "input": "The therapeutic use of BoNTs is expanding and new formulations are on the horizon.", "output": "There is no related enetity." }, { "input": "This article is a primer that describes distinctions among currently available, licensed BoNT formulations.", "output": "There is no related enetity." }, { "input": "Toxin pharmacology, product characteristics, storage, handling, preparation, and dosages will be reviewed.", "output": "There is no related enetity." }, { "input": "In addition, issues related to dose equivalency ratios, immunogenicity, potency, and toxin spread will be discussed.", "output": "There is no related enetity." }, { "input": "Therapeutic indications and safety are discussed briefly.", "output": "There is no related enetity." }, { "input": "Knowledge of the available and licensed BoNT formulations and the ability to make distinctions in toxin pharmacology, product characteristics, and indications are vital for product selection, preparation, drug information, avoidance of drug errors, quality assurance, and patient safety.", "output": "There is no related enetity." }, { "input": "Bioaccumulation and biomagnification of mercury and selenium in the sarasota bay ecosystem.", "output": "mercury, selenium." }, { "input": "The bioaccumulation and biomagnification of Hg and Se were investigated in Sarasota Bay, Florida, USA, to characterize the Hg exposure risks to wild bottlenose dolphins in the bay.", "output": "Hg, Se, Hg." }, { "input": "Concentrations of total mercury ( THg ), monomethylmercury ( MMHg ), and total selenium ( TSe ) were monitored in the bay, the latter of which might reduce Hg toxicity.", "output": "mercury, monomethylmercury, MMHg, selenium, Hg." }, { "input": "The food web structure and dolphins ' trophic level - specific consumption rates were evaluated using stable isotope ratios of carbon ( delta ( 13 ) C ) and nitrogen ( delta ( 15 ) N ).", "output": "carbon, ( 13 ) C, nitrogen, ( 15 ) N." }, { "input": "Regressions developed for Hg biomagnification in the food chain were log10 CTHg ( nanograms per gram ) = 0. 27 x delta ( 15 ) N ( /1000 ) - 0. 42, R ( 2 ) = 0. 87, for THg and log10 CMMHg = 0. 33 x delta ( 15 ) N ( /1000 ) - 1. 0, R ( 2 ) = 0. 93, for MMHg.", "output": "Hg, ( 15 ) N, ( 15 ) N, MMHg." }, { "input": "Unlike Hg, nearly constant TSe concentrations were observed at 248 +/- 179 ng g ( - 1 ) in the food web, and the TSe - to - THg molar ratio was predicted by log10 ( CTSe / CTHg ) = - 0. 10 x delta ( 15 ) N ( /1000 ) + 2. 8, R ( 2 ) = 0. 60.", "output": "Hg, ( 15 ) N." }, { "input": "The THg - uptake rates of Sarasota bottlenose dolphins are estimated to vary between 2. 1 and 4. 9 micro g kg ( - 1 ) d ( - 1 ); however, the estimated TSe - uptake rates ( 15. 1 micro g kg ( - 1 ) d ( - 1 ) ) were higher than those for THg, and the Hg - exposure risks of the Sarasota Bay resident bottlenose dolphins are considered to be low.", "output": "Hg." }, { "input": "Approaches employed in the present study can be extended to other environments to characterize Hg contamination in aquatic systems and Hg exposure risks in top predators.", "output": "Hg, Hg." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1143 - 1152.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Neurogenetic disorders and treatment of associated seizures.", "output": "There is no related enetity." }, { "input": "Seizures are a frequent complication associated with several neurogenetic disorders.", "output": "There is no related enetity." }, { "input": "Antiepileptic medications remain the mainstay of treatment in these patients.", "output": "There is no related enetity." }, { "input": "We summarized the available data associated with various antiepileptic therapies used to treat patients with neurogenetic disorders who experienced recurrent seizures.", "output": "There is no related enetity." }, { "input": "A MEDLINE search was conducted to identify articles and abstracts describing the use of antiepileptic therapy for the treatment of various neurogenetic syndromes.", "output": "There is no related enetity." }, { "input": "Of all the neurogenetic syndromes, only autism spectrum disorders, Angelman syndrome, Rett syndrome, Dravet syndrome, and tuberous sclerosis complex were identified as having sufficient published information to evaluate therapy.", "output": "There is no related enetity." }, { "input": "Some efficacy trends were identified, including frequent successes with valproic acid with clonazepam for epilepsy with Angelman syndrome; valproic acid, stiripentol, and clobazam ( triple combination therapy ) for epilepsy with Dravet syndrome; and vigabatrin for infantile spasms associated with tuberous sclerosis complex.", "output": "valproic acid, clonazepam, valproic acid, stiripentol, clobazam, vigabatrin." }, { "input": "Due to a paucity of information regarding the mechanisms by which seizures are generated in the various disorders, approach to seizure control is primarily based on clinical experience and a limited amount of study data exploring patient outcomes.", "output": "There is no related enetity." }, { "input": "Although exposure of the developing brain to antiepileptic medications is of some concern, the control of epileptic activity is an important undertaking in these individuals, as the severity of eventual developmental delay often appears to correlate with the severity of seizures.", "output": "There is no related enetity." }, { "input": "As such, early aggressive therapy is warranted.", "output": "There is no related enetity." }, { "input": "Guidelines for Resident Teaching Experiences.", "output": "There is no related enetity." }, { "input": "Postgraduate year one ( PGY1 ) and postgraduate year two ( PGY2 ) residencies serve to develop pharmacists into skillful clinicians who provide advanced patient - centered care in various general and specialized areas of pharmacy practice.", "output": "There is no related enetity." }, { "input": "Pharmacy residencies are a minimum requirement for many clinical pharmacy positions, as well as for positions in academia.", "output": "There is no related enetity." }, { "input": "The role of clinical pharmacists typically includes teaching, regardless of whether they pursue an academic appointment.", "output": "There is no related enetity." }, { "input": "Common teaching duties of pharmacist - clinicians include giving continuing education or other invited presentations, providing education to colleagues regarding clinical initiatives, precepting pharmacy students ( early and advanced experiences ) and residents, and educating other health care professionals.", "output": "There is no related enetity." }, { "input": "Although ASHP provides accreditation standards for PGY1 and PGY2 residencies, the standards pertaining to teaching or education training are vague.", "output": "There is no related enetity." }, { "input": "Through the years, teaching certificate programs that develop residents ' teaching skills and better prepare residents for a diverse pharmacy job market have increased in popularity; moreover, teaching certificate programs serve as an attractive recruitment tool.", "output": "There is no related enetity." }, { "input": "However, the consistency of requirements for teaching certificate programs is lacking, and standardization is needed.", "output": "There is no related enetity." }, { "input": "The Task Force on Residencies developed two sets of guidelines to define teaching experiences within residencies.", "output": "There is no related enetity." }, { "input": "The first guideline defines the minimum standards for teaching experiences in any residency - training program.", "output": "There is no related enetity." }, { "input": "The second guideline is for programs offering a teaching certificate program to provide standardization, ensuring similar outcomes and quality on program completion.", "output": "There is no related enetity." }, { "input": "One of the main differences between the guidelines is the recommendation that residency programs offering a teaching certificate program be affiliated with an academic institution to provide the pedagogy and variety of teaching experiences for the resident.", "output": "There is no related enetity." }, { "input": "Residency program directors should consider adopting these guidelines to offer consistent teaching experiences.", "output": "There is no related enetity." }, { "input": "In addition, residents should inquire about the elements of teaching in a program as an aid to selecting the training best suited to their needs.", "output": "There is no related enetity." }, { "input": "Genetic loci that control the loss and regain of trabecular bone during unloading and reambulation.", "output": "There is no related enetity." }, { "input": "Changes in trabecular morphology during un - and re - loading are marked by large variations between individuals, implicating a strong genetic influence on the magnitude of the response.", "output": "There is no related enetity." }, { "input": "Here, we subjected more than 350 second - generation ( BALBxC3H ) 4mo old adult female mice to 3wk of hindlimb unloading followed by 3wk of reambulation to identify the quantitative trait loci ( QTLs ) that define an individual ' s propensity to either lose trabecular bone when weightbearing is removed or to gain trabecular bone when weightbearing is reintroduced.", "output": "There is no related enetity." }, { "input": "Longitudinal in vivo micro CT scans demonstrated that individual mice lost between 15 % and 71 % in trabecular BV / TV in the distal femur during unloading ( average: - 43 % ).", "output": "There is no related enetity." }, { "input": "Changes in trabecular BV / TV during the 3wk reambulation period ranged from a continuation of bone loss ( - 18 % ) to large additions ( 56 % ) of tissue ( average: + 10 % ).", "output": "There is no related enetity." }, { "input": "During unloading, six QTLs accounted for 21 % of the total variability in changes in BV / TV while one QTL accounted for 6 % of the variability in changes in BV / TV during reambulation.", "output": "There is no related enetity." }, { "input": "QTLs were also identified for changes in trabecular architecture.", "output": "There is no related enetity." }, { "input": "Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weightbearing.", "output": "There is no related enetity." }, { "input": "The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading.", "output": "There is no related enetity." }, { "input": "The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone ' s sensitivity to weightbearing and may help to identify individuals that are most susceptible to unloading induced bone loss and / or the least capable of recovering.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Desired professional development pathways for clinical pharmacists.", "output": "There is no related enetity." }, { "input": "The 2012 American College of Clinical Pharmacy ( ACCP ) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists.", "output": "There is no related enetity." }, { "input": "This document summarizes recommendations for postgraduate education and training for graduates of U. S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists.", "output": "There is no related enetity." }, { "input": "After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes.", "output": "There is no related enetity." }, { "input": "An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists.", "output": "There is no related enetity." }, { "input": "Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education.", "output": "There is no related enetity." }, { "input": "Initial certification by the Board of Pharmacy Specialties ( BPS ) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting.", "output": "There is no related enetity." }, { "input": "Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification.", "output": "There is no related enetity." }, { "input": "Traineeships, practice - based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth.", "output": "There is no related enetity." }, { "input": "Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies.", "output": "There is no related enetity." }, { "input": "Modeling environmental and human health risks of veterinary medicinal products applied in pond aquaculture.", "output": "There is no related enetity." }, { "input": "A model called ERA - AQUA was developed to assess the risks posed by the use of veterinary medicinal products ( VMPs ) applied in aquaculture ponds for the targeted produce, surrounding aquatic ecosystems, consumers, and trade of the aquaculture produce.", "output": "There is no related enetity." }, { "input": "The model calculates risks by following a risk quotient approach, calculating predicted exposure concentrations ( exposure assessment ) and predicted no - effect concentrations ( effect assessment ) for the endpoint under study.", "output": "There is no related enetity." }, { "input": "The exposure assessment is performed by combining information on the environmental characteristics of the aquaculture pond, characteristics of the cultured species, aquaculture management practices, and physicochemical properties of the compound under study.", "output": "There is no related enetity." }, { "input": "The model predicts concentrations of VMPs in the pond water, pond sediment, cultured species, and watercourse receiving pond effluent discharges by mass balance equations.", "output": "There is no related enetity." }, { "input": "The effect assessment is performed by combining ( eco ) toxicological information and food safety threshold concentrations for the studied compound.", "output": "There is no related enetity." }, { "input": "In the present study, the scientific background, strengths, and limitations of the ERA - AQUA model are presented together with a sensitivity analysis and an example showing its potential applications.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1196 - 1207.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Toxicity and toxicokinetics of binary combinations of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.", "output": "petroleum hydrocarbon." }, { "input": "Petroleum hydrocarbons ( PHCs ) act via narcosis and are expected to have additive toxicity.", "output": "Petroleum hydrocarbons, PHCs." }, { "input": "However, previous work has demonstrated less - than - additive toxicity with PHC distillates and earthworms.", "output": "PHC." }, { "input": "A study was initiated to investigate this through toxicity and toxicokinetic studies with the earthworm Eisenia andrei.", "output": "There is no related enetity." }, { "input": "Three petroleum distillate fractions, F2 ( > C10 - C16 ), F3a ( > C16 - C23 ), and F3b ( > C23 - C34 ), were used in two binary combinations, F2F3a and F3aF3b.", "output": "C10 - C16, C16 - C23, C23 - C34." }, { "input": "In the toxicity study, clean soil was spiked with equitoxic combinations of the two distillates ranging from 0. 5 to 2. 5 toxic units.", "output": "There is no related enetity." }, { "input": "In the toxicokinetic study, a binary combination consisting of one concentration of each distillate was used.", "output": "There is no related enetity." }, { "input": "On a soil concentration basis, the toxicity of the binary combinations of distillates was less than additive.", "output": "There is no related enetity." }, { "input": "Accumulation of the individual distillates, however, was generally reduced when a second distillate was present, resulting in lower body burden.", "output": "There is no related enetity." }, { "input": "This is thought to be due to the presence of a nonaqueous - phase liquid at the soil concentrations used.", "output": "There is no related enetity." }, { "input": "On a tissue concentration basis, toxicity was closer to additive.", "output": "There is no related enetity." }, { "input": "The results demonstrate that tissue concentrations are the preferred metric for toxicity for earthworms.", "output": "There is no related enetity." }, { "input": "They also demonstrate that the Canada - wide soil standards based on individual distillates are likely protective.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1016 - 1026.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Inter - and intraspecific variation in mercury bioaccumulation by snakes inhabiting a contaminated river floodplain.", "output": "mercury." }, { "input": "Although mercury ( Hg ) is a well - studied contaminant, knowledge about Hg accumulation in snakes is limited.", "output": "mercury, Hg, Hg." }, { "input": "The authors evaluated Hg bioaccumulation within and among four snake species ( northern watersnakes, Nerodia sipedon; queen snakes, Regina septemvittata; common garter snakes, Thamnophis sirtalis; and rat snakes, Elaphe obsoleta [ Pantherophis alleghaniensis ] ) from a contaminated site on the South River ( Waynesboro, VA, USA ) and two nearby reference sites.", "output": "Hg." }, { "input": "Total Hg ( THg ) concentrations in northern watersnake tail tissue at the contaminated site ranged from 2. 25 to 13. 84 mg / kg dry weight ( mean: 4. 85 +/- 0. 29 ), or 11 to 19 times higher than reference sites.", "output": "Hg." }, { "input": "Blood THg concentrations ( 0. 03 - 7. 04 mg / kg wet wt; mean: 2. 24 +/- 0. 42 ) were strongly correlated with tail concentrations and were the highest yet reported in a snake species.", "output": "There is no related enetity." }, { "input": "Within watersnakes, nitrogen stable isotope values indicated ontogenetic trophic shifts that correlated with THg bioaccumulation, suggesting that diet plays a substantial role in Hg exposure.", "output": "nitrogen, Hg." }, { "input": "Female watersnakes had higher mean THg concentrations ( 5. 67 +/- 0. 46 mg / kg ) than males ( 4. 93 +/- 0. 49 mg / kg ), but no significant differences between sexes were observed after correcting for body size.", "output": "There is no related enetity." }, { "input": "Interspecific comparisons identified differences in THg concentrations among snake species, with more aquatic species ( watersnakes and queen snakes ) accumulating higher mean concentrations ( 5. 60 +/- 0. 40 and 4. 59 +/- 0. 38 mg / kg in tail tissue, respectively ) than the more terrestrial species, garter snakes and rat snakes ( 1. 28 +/- 0. 32 and 0. 26 +/- 0. 09 mg / kg, respectively ).", "output": "There is no related enetity." }, { "input": "The results of the present study warrant further investigation of potential adverse effects and will aid in prioritizing conservation efforts.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1178 - 1186.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Mild oxidation of thiofunctional polymers to cytocompatible and stimuli - sensitive hydrogels and nanogels.", "output": "There is no related enetity." }, { "input": "Nanogels consist of three dimensionally cross - linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli - sensitive materials.", "output": "There is no related enetity." }, { "input": "For drug transport and intracellular release, redox - sensitive systems are especially of interest, as the intracellular space is reductive.", "output": "There is no related enetity." }, { "input": "In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified.", "output": "There is no related enetity." }, { "input": "Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels.", "output": "alloxan." }, { "input": "This broadens the range of possible payloads to more - sensitive molecules.", "output": "There is no related enetity." }, { "input": "Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg. mL ( - 1 ) are demonstrated.", "output": "There is no related enetity." }, { "input": "EFFECT OF C60 FULLERENES ON THE ACCUMULATION OF WEATHERED p, p ' - DDE BY PLANT AND EARTHWORM SPECIES UNDER SINGLE AND MULTISPECIES CONDITIONS.", "output": "C60, FULLERENES, p , p ' - DDE." }, { "input": "The use of engineered nanomaterials has increased dramatically in recent years, but an understanding of nanomaterial fate and effects in the environment is lacking.", "output": "There is no related enetity." }, { "input": "In particular, the interaction of nanomaterials with coexisting organic contaminants and the subsequent implications for sensitive biota is almost completely unknown.", "output": "There is no related enetity." }, { "input": "Here, the effect of C60 fullerenes on the accumulation of weathered dichlorodiphenyldichloroethylene ( p, p ' - DDE; DDT metabolite ) by Cucurbita pepo ( pumpkin ) and Eisenia fetida ( earthworm ) was determined under single and multispecies conditions.", "output": "C60, fullerenes, dichlorodiphenyldichloroethylene, p , p ' - DDE, DDT." }, { "input": "The plants, in the presence or absence of earthworms, were grown in soil containing weathered DDE ( 200 ng / g ) and 0 or 1, 670 mg / kg C60 fullerenes.", "output": "DDE, C60, fullerenes." }, { "input": "Plants and earthworms were added either simultaneously or sequentially ( earthworms after plants ).", "output": "There is no related enetity." }, { "input": "Neither DDE nor C60 had an impact on survival or biomass of plants and earthworms, although fullerenes significantly decreased ( 29. 6 - 39. 0 % ) the relative root mass.", "output": "DDE, C60, fullerenes." }, { "input": "Under single or multispecies conditions, C60 had little impact on DDE bioaccumulation by either species.", "output": "C60, DDE." }, { "input": "The DDE concentrations in non - fullerene - exposed shoots, roots, and earthworms were 181, 7, 400, and 8, 230 ng / g, respectively.", "output": "DDE, fullerene." }, { "input": "On fullerene exposure, the DDE content was nonsignificantly lower at 163, 7280, and 7540 ng / g, respectively.", "output": "fullerene, DDE." }, { "input": "In the presence of the earthworms, C60 significantly decreased the shoot DDE content ( 28. 6 % ), but no impact on root concentrations was observed.", "output": "C60, DDE." }, { "input": "Root DDE content was unaffected by the presence of fullerenes and decreased by 21. 6 to 37. 5 % during coexposure with earthworms.", "output": "DDE, fullerenes." }, { "input": "Earthworm DDE content was decreased by plant presence.", "output": "DDE." }, { "input": "Earthworms added to soils after plant harvest accumulated more DDE but were unaffected by the C60 exposure.", "output": "DDE, C60." }, { "input": "Additional work is necessary, but these findings suggest that fullerenes may have minimal impact on the bioaccumulation of weathered cocontaminants in soil.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1117 - 1123.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Effects of Lepidium sativum, Nigella sativa and Trigonella foenum - graceum on Phenytoin Pharmacokinetics in Beagle Dogs.", "output": "Phenytoin." }, { "input": "The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress ( Lepidium sativum ), black seed ( Nigella sativa ) and fenugreek ( Trigonella foenum - graceum ) on the disposition of phenytoin after oral administration in a dog model.", "output": "phenytoin." }, { "input": "Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug ' s pharmacokinetic parameters.", "output": "Phenytoin." }, { "input": "After a suitable washout period, animals were commenced on a specific herb treatment for one week.", "output": "There is no related enetity." }, { "input": "Garden cress treatment caused a modest increase in maximum observed concentration ( C ( max ) ) and terminal half - life ( T ( 1 / 2 lambda ) ) of phenytoin with a reduction in clearance by 33 %.", "output": "phenytoin." }, { "input": "The effect of black seed therapy was more drastic on drug elimination and to a lesser extent on its volume of distribution at steady state ( V ( ss ) ) with a consequent reduction in systemic exposure measured by area under the curve ( AUC ( 0 - infinity ) ) by about 87 %.", "output": "There is no related enetity." }, { "input": "The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC ( 0 - infinity ) by ~ 72 %.", "output": "There is no related enetity." }, { "input": "In addition, there was a 73 % increase in V ( ss ).", "output": "There is no related enetity." }, { "input": "Our findings suggest that the phenytoin disposition can be significantly altered by the concurrent consumption of tested herbal products.", "output": "phenytoin." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Soluble metal pool as affected by soil addition with organic inputs.", "output": "There is no related enetity." }, { "input": "The potential impact of diverse inputs of organic matter ( hay, maize straw, and peat ) on the mobility and bioavailability of Cd, Cu, Pb, and Zn was examined at laboratory scale for three soils with contrasting properties and for two moisture regimes: field capacity and saturated conditions.", "output": "Cd, Cu, Pb, Zn." }, { "input": "Soil solution was characterized for total soluble metals, dissolved soil organic carbon, and ultraviolet absorbance at 254 nm.", "output": "carbon." }, { "input": "Speciation analyses were performed with WHAM VI.", "output": "There is no related enetity." }, { "input": "For field capacity conditions, metal mobility increased ( Pb > Cu > Zn > Cd ) for all soils and treatments compared with controls and was significantly correlated ( p < 0. 05 ) with dissolved organic matter ( r = 0. 540 ).", "output": "Pb, Cu, Zn, Cd." }, { "input": "Solubilization of organic matter was mostly driven by Al mobilization ( r = 0. 580, p < 0. 05 ) and variations in solution pH.", "output": "Al." }, { "input": "The bioavailable pool of metals, estimated as free ion activities, decreased with the increasing occurrence of metal - organic matter complexes, which was accompanied by an increase in solution of highly aromatic organic matter.", "output": "There is no related enetity." }, { "input": "Soil saturation generally decreased metal mobility and the ratio of metal - organo matter complexes in solution.", "output": "There is no related enetity." }, { "input": "Consistently, such effects were accompanied by a decrease in the solubilization of organic matter and lower mobilization of Al, Fe, and Mn.", "output": "Al, Fe, Mn." }, { "input": "Environ Toxicol Chem 2013; 32: 1027 - 1032.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Novel Schiff - base - derived FabH inhibitors with dioxygenated rings as antibiotic agents.", "output": "Schiff - base." }, { "input": "Fatty acid biosynthesis plays a vital role in bacterial survival and several key enzymes involved in this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents.", "output": "Fatty acid." }, { "input": "Of these promising targets, beta - ketoacyl - acyl carrier protein ( ACP ) synthase III ( FabH ) is the most attractive target that could trigger the initiation of fatty acid biosynthesis and is highly conserved among Gram - positive and - negative bacteria.", "output": "beta - ketoacyl, acyl, fatty acid." }, { "input": "Designing small molecules with FabH inhibitory activity displays great significance for developing antibiotic agents, which should be highly selective, nontoxic and broad - spectrum.", "output": "There is no related enetity." }, { "input": "In this manuscript, a series of novel Schiff base compounds were designed and synthesized, and their biological activities were evaluated as potential inhibitors.", "output": "Schiff base." }, { "input": "Among these 21 new compounds, ( E ) - N - ( ( 3, 4 - dihydro - 2H - benzo [ b ] [ 1, 4 ] dioxepin - 7 - yl ) methylene ) hexadecan - 1 - amine ( 10 ) showed the most potent antibacterial activity with a MIC value of 3. 89 - 7. 81 mu M ( - 1 ) against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with an IC ( 50 ) value of 1. 6 mu M.", "output": "( E ) - N - ( ( 3 , 4 - dihydro - 2H - benzo [ b ] [ 1 , 4 ] dioxepin - 7 - yl ) methylene ) hexadecan - 1 - amine." }, { "input": "Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation.", "output": "There is no related enetity." }, { "input": "Comparing sorption behavior of pyrethroids between formulated and natural sediments.", "output": "pyrethroids." }, { "input": "Formulated sediments are recommended for use in toxicity tests to achieve standardized evaluations.", "output": "There is no related enetity." }, { "input": "However, the organic matter used in formulated sediments may differ qualitatively from that in natural sediments, which may lead to different chemical partition patterns and, hence, different toxicity effects.", "output": "There is no related enetity." }, { "input": "By deriving partition coefficients for organic carbon and dissolved organic carbon ( KOC and KDOC, respectively ) for eight pyrethroid insecticides from three formulated and five natural sediments, the authors characterized the differences between formulated and natural sediments in pesticide sorption.", "output": "carbon, carbon, pyrethroid." }, { "input": "For all pyrethroids, the mean values of KOC and KDOC of formulated sediments were two to three, and three to 10 times smaller than those of natural sediments, respectively.", "output": "pyrethroids." }, { "input": "The two formulated sediments containing alpha - cellulose or Manitoba peat showed significantly ( p < 0. 0001 ) smaller KOC and KDOC values than natural sediments based on statistical analyses, while the difference was not significant for the formulated sediment containing New Brunswick peat.", "output": "There is no related enetity." }, { "input": "The KOC values were closely correlated ( p < 0. 001 ) with soot carbon content, while the amount of carboxylic or phenolic functional groups may have affected KDOC.", "output": "carbon, carboxylic, phenolic." }, { "input": "Therefore, the source and quality of organic matter are likely the most important factors in formulated sediments and must be standardized to provide consistency in sediment toxicity tests.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 1033 - 1039.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Bifunctional Star - Burst Amorphous Molecular Materials for OLEDs: Achieving Highly Efficient Solid - State Luminescence and Carrier Transport Induced by Spontaneous Molecular Orientation.", "output": "There is no related enetity." }, { "input": "Bifunctional star - burst amorphous molecular materials displaying both efficient solid - state luminescence and high hole - transport properties are developed in this study.", "output": "There is no related enetity." }, { "input": "A high external electroluminescence quantum efficiency up to 5. 9 % is attained in OLEDs employing the developed amorphous materials.", "output": "There is no related enetity." }, { "input": "It is revealed that the spontaneous horizontal orientation of these light - emitting molecules in their molecular - condensed states leads to a remarkable enhancement of the electroluminescence efficiencies and carrier - transport properties.", "output": "There is no related enetity." }, { "input": "Hemifluorinated maltose - neopentyl glycol ( HF - MNG ) amphiphiles for membrane protein stabilisation.", "output": "maltose - neopentyl glycol, MNG." }, { "input": "SOAP OPERA: Fluorinated amphiphile F4 - MNG confers greater stability on Rhodobacter capsulatus superassembly relative to conventional detergents and nonfluorinated MNGs.", "output": "MNGs." }, { "input": "Such amphiphiles are attractive as tools for membrane science because of their ease of preparation and structure variation.", "output": "There is no related enetity." }, { "input": "Plant consumption by grizzly bears reduces biomagnification of salmon - derived polychlorinated biphenyls, polybrominated diphenyl ethers, and organochlorine pesticides.", "output": "polychlorinated biphenyls, polybrominated diphenyl ethers, organochlorine." }, { "input": "The present study characterizes the uptake and loss of persistent organic pollutants ( POPs ) in grizzly bears ( Ursus arctos horribilis ) by sampling and analyzing their terrestrial and marine foods and fecal material from a remote coastal watershed in British Columbia, Canada.", "output": "There is no related enetity." }, { "input": "The authors estimate that grizzly bears consume 341 to 1, 120 micro g of polychlorinated biphenyls ( PCBs ) and 3. 9 to 33 micro g of polybrominated diphenyl ethers daily in the fall when they have access to an abundant supply of returning salmon.", "output": "polychlorinated biphenyls, PCBs, polybrominated diphenyl ethers." }, { "input": "The authors also estimate that POP elimination by grizzly bears through defecation is very low following salmon consumption ( typically < 2 % of intake ) but surprisingly high following plant consumption ( > 100 % for PCBs and organochlorine pesticides ).", "output": "PCBs, organochlorine." }, { "input": "Excretion of individual POPs is largely driven by a combination of fugacity ( differences between bear and food concentrations ) and the digestibility of the food.", "output": "There is no related enetity." }, { "input": "The results of the present study are substantiated by a principal components analysis, which also demonstrates a strong role for log KOW in governing the excretion of different POPs in grizzly bears.", "output": "There is no related enetity." }, { "input": "Collectively, the present study ' s results reveal that grizzly bears experience a vegetation - associated drawdown of POPs previously acquired through the consumption of salmon, to such an extent that net biomagnification is reduced.", "output": "There is no related enetity." }, { "input": "Environ.", "output": "There is no related enetity." }, { "input": "Toxicol.", "output": "There is no related enetity." }, { "input": "Chem.", "output": "There is no related enetity." }, { "input": "2013; 32: 995 - 1005.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Formation of nanostructured MnO / Co / solid - electrolyte interphase ternary composites as a durable anode material for lithium - ion batteries.", "output": "MnO, Co, lithium." }, { "input": "Nanoporous MnO frameworks with highly dispersed Co nanoparticles were produced from MnCO3 precursors prepared in a gel matrix.", "output": "MnO, Co, MnCO3." }, { "input": "The MnO frameworks that contain 20 mol % Co exhibited excellent cycle performance as an anode material for Li - ion batteries.", "output": "MnO, Co, Li." }, { "input": "The solid - electrolyte interphase ( SEI ) formed in the frameworks through the electrochemical reaction mediates the active materials, such as MnO, Mn, and Li2O, during the conversion reaction in the charge - discharge cycle.", "output": "MnO, Mn, Li2O." }, { "input": "The Co nanoparticles and SEI provide the electron and Li - ion conductive networks, respectively.", "output": "Co, Li." }, { "input": "The ternary nanocomposites of the MnO framework, metallic Co nanoparticles, and embedded SEI are categorized as durable anode materials for Li - ion batteries.", "output": "MnO, Co, Li." }, { "input": "From spots to beads - PTM - peptide bead arrays for the characterization of anti - histone antibodies.", "output": "There is no related enetity." }, { "input": "Antibodies that recognize PTMs of histones play a central role in epigenetic proteomic research.", "output": "There is no related enetity." }, { "input": "Modification - specific antibodies are employed in chromatin immunoprecipitation, for Western blotting and during the immunoprecipitation steps for MS - based global proteomic analyses.", "output": "There is no related enetity." }, { "input": "Knowledge about the antibodies ' off - target binding is essential for the interpretation of experimental data.", "output": "There is no related enetity." }, { "input": "To address this challenge we developed a fast and cost efficient system for generating peptide bead arrays.", "output": "There is no related enetity." }, { "input": "We employed this method to establish a bead - based peptide array containing 384 peptides displaying phosphorylated, acetylated, methylated, and citrullinated N - terminal regions of histones H2A, H2B, H3 and H4 and controls.", "output": "N." }, { "input": "We profiled the binding of 40 PTM - specific antibodies important for epigenetic proteomic research.", "output": "There is no related enetity." }, { "input": "Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney.", "output": "There is no related enetity." }, { "input": "Human UDP - glucuronosyltransferase ( UGT ) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds such as bilirubin and SN - 38.", "output": "UDP, bilirubin, SN - 38." }, { "input": "UGT1A1 is predominantly expressed in the liver and intestine, but not in the kidney.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to uncover the mechanism of the tissue - specific expression of UGT1A1, focusing on its epigenetic regulation.", "output": "There is no related enetity." }, { "input": "Bisulfite sequence analysis revealed that the CpG - rich region near the UGT1A1 promoter ( - 85 to + 40 ) was hypermethylated ( 83 % ) in the kidney, whereas it was hypomethylated ( 37 % ) in the liver.", "output": "Bisulfite, CpG." }, { "input": "A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but was hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of HNF1 alpha to the promoter.", "output": "There is no related enetity." }, { "input": "The UGT1A1 promoter in human kidney - derived HK - 2 cells that do not express UGT1A1 was fully methylated, but was relatively unmethylated in human liver - derived HuH - 7 cells that express UGT1A1.", "output": "There is no related enetity." }, { "input": "Treatment with 5 - aza - 2 ' - deoxycytidine ( 5 - Aza - dC ), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK - 2 cells than in HuH - 7 cells.", "output": "5 - aza - 2 ' - deoxycytidine, 5 - Aza - dC." }, { "input": "The transfection of an HNF1 alpha expression plasmid into the HK - 2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5 - Aza - dC.", "output": "5 - Aza - dC." }, { "input": "In summary, we found that DNA hypermethylation along with histone hypoacetylation interferes with the binding of HNF1 alpha, resulting in the defective expression of UGT1A1 in the human kidney.", "output": "There is no related enetity." }, { "input": "Thus, epigenetic regulation is a crucial determinant of tissue - specific expression of UGT1A1.", "output": "There is no related enetity." }, { "input": "Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice.", "output": "linoleic acid." }, { "input": "The objective of this study was to examine the mechanism by which conjugated linoleic acid ( CLA ) reduces body fat.", "output": "linoleic acid." }, { "input": "Young male mice were fed three combinations of fatty acids at three doses ( 0. 06 %, 0. 2 %, and 0. 6 %, w / w ) incorporated into AIN76 diets for 7 weeks.", "output": "fatty acids." }, { "input": "The types of fatty acids were linoleic acid ( control ), an equal mixture of trans - 10, cis - 12 ( 10, 12 ) CLA plus linoleic acid, and an equal isomer mixture of 10, 12 plus cis - 9, trans - 11 ( 9, 11 ) CLA.", "output": "fatty acids, linoleic acid, linoleic acid." }, { "input": "Mice receiving the 0. 2 % and 0. 6 % dose of 10, 12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue ( WAT ) and brown adipose tissue ( BAT ) mass and increased incorporation of CLA isomers in epididymal WAT and liver.", "output": "linoleic acid." }, { "input": "Notably, in mice receiving 0. 2 % of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 ( UCP1 ), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT.", "output": "There is no related enetity." }, { "input": "CLA - induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation.", "output": "There is no related enetity." }, { "input": "Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment.", "output": "There is no related enetity." }, { "input": "These data suggest a linkage between decreased adiposity, browning in WAT, and low - grade inflammation due to consumption of 10, 12 CLA.", "output": "There is no related enetity." }, { "input": "Measuring in situ primary and competitive DNA hybridization activity on microspheres.", "output": "There is no related enetity." }, { "input": "Microspheres serve as convenient substrates for studying DNA activity on surfaces.", "output": "There is no related enetity." }, { "input": "Here, in addition to employing conventional sample preparation involving multiple wash and resuspension steps prior to flow cytometry measurements, we also directly sampled the reaction volume to acquire in situ measurements of primary and competitive hybridization events.", "output": "There is no related enetity." }, { "input": "Even in the absence of post hybridization wash steps, nonspecific binding events were negligible and thus allowed for direct, quantitative assessment of hybridization events as they occurred on colloidal surfaces.", "output": "There is no related enetity." }, { "input": "The in situ results indicate that primary duplex formation between immobilized probes and soluble targets on microsphere surfaces is less favorable than predicted by solution models.", "output": "There is no related enetity." }, { "input": "The kinetics of competitive displacement of primary hybridization partners by secondary targets measured in situ or post washing also deviate from expectations based on theoretical solution thermodynamics, but are consistent with predicted kinetic trends stemming from differences in either the toehold base length or branch migration.", "output": "There is no related enetity." }, { "input": "Binding between proteins and cationic spherical polyelectrolyte brushes: effect of pH, ionic strength, and stoichiometry.", "output": "There is no related enetity." }, { "input": "Cationic spherical polyelectrolyte brushes ( SPBs ) were synthesized by photoemulsion polymerization, consisting of a polystyrene core with a diameter around 80 nm and a poly ( 2 - aminoethylmethacrylate hydrochloride ) ( PAEMH ) shell with a thickness from 10 to 50 nm densely grafted on the core surface.", "output": "polystyrene, poly ( 2 - aminoethylmethacrylate hydrochloride ), PAEMH." }, { "input": "The binding of various proteins onto SPBs was observed by turbidimetric titration, dynamic light scattering ( DLS ), zeta potential, and isothermal titration calorimetry ( ITC ).", "output": "There is no related enetity." }, { "input": "The binding, aggregation, and releasing of proteins by SPB can be tuned by modulating pH.", "output": "There is no related enetity." }, { "input": "The pH regions of binding for bovine serum albumin ( BSA ), beta - lactoglobulin ( BLG ), and papain onto SPBs are markedly different and tunable by ionic strength and stoichiometry between protein and SPB.", "output": "There is no related enetity." }, { "input": "Binding energetics, affinity, and amount of various proteins onto cationic SPBs were determined by ITC.", "output": "There is no related enetity." }, { "input": "These findings lay the foundation for SPB applications in the protein purification and selective immobilization of different proteins, enzymes, and antibodies.", "output": "There is no related enetity." }, { "input": "Characterization of the acyl - adenylate linked metabolite of mefenamic Acid.", "output": "acyl, adenylate, mefenamic Acid." }, { "input": "Mefenamic acid, ( MFA ), a carboxylic acid - containing nonsteroidal anti - inflammatory drug ( NSAID ), is metabolized into the chemically reactive conjugates MFA - 1 - O - acyl - glucuronide ( MFA - 1 - O - G ) and MFA - S - acyl - CoA ( MFA - CoA ), which are both implicated in the formation of MFA - S - acyl - glutathione ( MFA - GSH ) conjugates, protein - adduct formation, and thus the potential toxicity of the drug.", "output": "Mefenamic acid, MFA, carboxylic acid, MFA - 1 - O - acyl - glucuronide, MFA - 1 - O - G, MFA - S - acyl - CoA, MFA - CoA, MFA - S - acyl - glutathione, MFA - GSH." }, { "input": "However, current studies suggest that an additional acyl - linked metabolite may be implicated in the formation of MFA - GSH.", "output": "acyl, MFA - GSH." }, { "input": "In the present study, we investigated the ability of MFA to become bioactivated into the acyl - linked metabolite, mefenamyl - adenylate ( MFA - AMP ).", "output": "MFA, acyl, mefenamyl, adenylate, MFA - AMP." }, { "input": "In vitro incubations in rat hepatocytes with MFA ( 100 mu M ), followed by LC - MS / MS analyses of extracts, led to the detection of MFA - AMP.", "output": "MFA, MFA - AMP." }, { "input": "In these incubations, the initial rate of MFA - AMP formation was rapid, leveling off at a maximum concentration of 90. 1 nM ( 20 s ), while MFA - GSH formation increased linearly, reaching a concentration of 1. 7 mu M after 60 min of incubation.", "output": "MFA - AMP, MFA - GSH." }, { "input": "In comparison, MFA - CoA was undetectable in incubation extracts until the 4 min time point, achieving a concentration of 45. 6 nM at the 60 min time point, and MFA - 1 - O - G formation was linear, attaining a concentration of 42. 2 mu M after 60 min of incubation.", "output": "MFA - CoA, MFA - 1 - O - G." }, { "input": "In vitro incubation in buffer with the model nucleophile glutathione ( GSH ) under physiological conditions showed MFA - AMP to be reactive toward GSH, but 11 - fold less reactive than MFA - CoA, while MFA - 1 - O - G exhibited little reactivity.", "output": "glutathione, GSH, MFA - AMP, GSH, MFA - CoA, MFA - 1 - O - G." }, { "input": "However, in the presence of glutathione - S - transferase ( GST ), MFA - AMP mediated formation of MFA - GSH increased 6 - fold, while MFA - CoA mediated formation of MFA - GSH only increased 1. 4 - fold.", "output": "glutathione, S, MFA - AMP, MFA - GSH, MFA - CoA, MFA - GSH." }, { "input": "Collectively, in addition to the MFA - 1 - O - G, these results demonstrate that mefenamic acid does become bioactivated by acyl - CoA synthetase enzyme ( s ) in vitro in rat hepatocytes into the reactive transacylating derivatives MFA - AMP and MFA - CoA, both of which contribute to the transacylation of GSH and may be involved in the formation of protein adducts and potentially elicit an idiosyncratic toxicity.", "output": "MFA - 1 - O - G, mefenamic acid, acyl - CoA, MFA - AMP, MFA - CoA, GSH." }, { "input": "Role of nitric oxide in the chemistry and anticancer activity of etoposide ( VP - 16, 213 ).", "output": "nitric oxide, etoposide, VP - 16 , 213." }, { "input": "Originally identified as an innate cytotoxin, nitric oxide ( (. ) NO ) formation in tumors can influence chemotherapy and exacerbate cancer progression.", "output": "nitric oxide, ( . ) NO." }, { "input": "Here, we examined the hypothesis that (. ) NO generation contributes to cancer cell drug resistance toward the widely used anticancer drug Etoposide ( VP - 16 ).", "output": "( . ) NO, Etoposide, VP - 16." }, { "input": "The UV - vis spectrum of VP - 16 was not changed by exposure of VP - 16 to (. ) NO in aqueous buffer.", "output": "VP - 16, VP - 16, ( . ) NO." }, { "input": "In contrast, reddish - orange compound ( s ) characteristic of o - quinone - and nitroso - VP - 16 were readily generated in a hydrophobic medium ( chloroform ) in an oxygen - dependent manner.", "output": "o - quinone - and nitroso - VP - 16, chloroform, oxygen." }, { "input": "Similar products were also formed when the VP - 16 radical, generated from VP - 16 and horseradish peroxidase / H2O2, was exposed directly to (. ) NO in chloroform in the presence of oxygen.", "output": "VP - 16, VP - 16, H2O2, ( . ) NO, chloroform, oxygen." }, { "input": "Separation and spectral analysis of VP - 16 reaction extracts by electron spin resonance and UV - vis indicated the generation of the phenoxy radical and the o - quinone of VP - 16, as well as putative nitroxide, iminoxyl, and other nitrogen oxide intermediates.", "output": "VP - 16, phenoxy, o - quinone, VP - 16, nitroxide, iminoxyl, nitrogen oxide." }, { "input": "Nitric oxide products of VP - 16 displayed significantly diminished topoisomerase II - dependent cleavage of DNA and cytotoxicity to human HL - 60 leukemia cells.", "output": "Nitric oxide, VP - 16." }, { "input": "LPS - mediated induction of nitric oxide synthase in murine macrophages resulted in VP - 16 resistance compared to Raw cells.", "output": "nitric oxide, VP - 16." }, { "input": "Furthermore, (. ) NO products derived from iNOS rapidly reacted with VP - 16 leading to decreased DNA damage and cytotoxicity.", "output": "( . ) NO, VP - 16." }, { "input": "Together, these observations suggest that the formation of (. ) NO in tumors ( associated macrophages ) can contribute to VP - 16 resistance via the detoxification of VP - 16.", "output": "( . ) NO, VP - 16, VP - 16." }, { "input": "Conducting the temperature - dependent conformational change of macrocyclic compounds to the lattice dilation of quantum dots for achieving an ultrasensitive nanothermometer.", "output": "There is no related enetity." }, { "input": "We report a ligand decoration strategy to enlarge the lattice dilation of quantum dots ( QDs ), which greatly enhances the characteristic sensitivity of a QD - based thermometer.", "output": "There is no related enetity." }, { "input": "Upon a multiple covalent linkage of macrocyclic compounds with QDs, for example, thiolated cyclodextrin ( CD ) and CdTe, the conformation - related torsional force of CD is conducted to the inner lattice of CdTe under altered temperature.", "output": "CdTe, CdTe." }, { "input": "The combination of the lattice expansion / contraction of CdTe and the stress from CD conformation change greatly enhances the shifts of both UV - vis absorption and photoluminescence ( PL ) spectra, thus improving the temperature sensitivity.", "output": "CdTe." }, { "input": "As an example, beta - CD - decorated CdTe QDs exhibit the 0. 28 nm shift of the spectra per degree centigrade ( 0. 28 nm / degrees C ), 2. 4 - fold higher than those of monothiol - ligand - decorated QDs.", "output": "CdTe, monothiol." }, { "input": "Polymerase chain reaction - free variable - number tandem repeat typing using gold nanoparticle - DNA monoconjugates.", "output": "There is no related enetity." }, { "input": "In this work, we report a novel polymerase chain reaction ( PCR ) - free variable - number tandem repeat ( VNTR ) typing method using a T - shaped gold nanoparticle - DNA monoconjugate, called the \" watching - gene assay \".", "output": "There is no related enetity." }, { "input": "The T - shaped DNA probe was synthesized by \" click \" chemistry and linked with the gold nanoparticle to form the gold nanoparticle - DNA monoconjugate ( a VNTR probe ).", "output": "There is no related enetity." }, { "input": "Through a simple annealing and ligation reaction of the VNTR probe on a synthetic DNA template mimicking the human D1S80 VNTR locus, the number of tandem repeat units could be deciphered by counting the self - assembled gold nanoparticles.", "output": "There is no related enetity." }, { "input": "The number of tandem repeat units could be identified with more than 50 % yield if the repeat number was less than four.", "output": "There is no related enetity." }, { "input": "In the case of the real human genomic DNA, the 18 repeat unit number could be successfully revealed by observing the 18 - gold - nanoparticle cluster, which exactly corresponded to the number of tandem repeats of the real sample.", "output": "There is no related enetity." }, { "input": "Our \" watching - gene assay \" is rapid, simple, and direct for data interpretation, thereby providing an advanced PCR - free genetic polymorphism analysis platform.", "output": "There is no related enetity." }, { "input": "Health benefits of blue - green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease.", "output": "There is no related enetity." }, { "input": "Blue - green algae ( BGA ) are among the most primitive life forms on earth and have been consumed as food or medicine by humans for centuries.", "output": "There is no related enetity." }, { "input": "BGA contain various bioactive components, such as phycocyanin, carotenoids, gamma - linolenic acid, fibers, and plant sterols, which can promote optimal health in humans.", "output": "gamma - linolenic acid, sterols." }, { "input": "Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride - lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression.", "output": "cholesterol, triglyceride, cholesterol." }, { "input": "BGA can also reduce inflammation by inhibiting the nuclear factor kappa B activity, consequently reducing the production of proinflammatory cytokines.", "output": "There is no related enetity." }, { "input": "Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress.", "output": "There is no related enetity." }, { "input": "The aforementioned effects of BGA can contribute to the prevention of metabolic and inflammatory diseases.", "output": "There is no related enetity." }, { "input": "This review provides an overview of the current knowledge of the health - promoting functions of BGA against cardiovascular disease and nonalcoholic fatty liver disease, which are major health threats in the developed countries.", "output": "There is no related enetity." }, { "input": "Iron ( II ) - catalyzed intramolecular aminohydroxylation of olefins with functionalized hydroxylamines.", "output": "Iron ( II ), olefins, hydroxylamines." }, { "input": "A diastereoselective aminohydroxylation of olefins with a functionalized hydroxylamine is catalyzed by new iron ( II ) complexes.", "output": "olefins, hydroxylamine, iron ( II )." }, { "input": "This efficient intramolecular process readily affords synthetically useful amino alcohols with excellent selectivity ( dr up to > 20: 1 ).", "output": "amino alcohols." }, { "input": "Asymmetric catalysis with chiral iron ( II ) complexes and preliminary mechanistic studies reveal an iron nitrenoid is a possible intermediate that can undergo either aminohydroxylation or aziridination, and the selectivity can be controlled by careful selection of counteranion / ligand combinations.", "output": "iron ( II ), iron nitrenoid." }, { "input": "Ionic liquid mediated synthesis and surface modification of multifunctional mesoporous Eu: GdF3 nanoparticles for biomedical applications.", "output": "Eu, GdF3." }, { "input": "A procedure for the synthesis of multifunctional europium ( III ) - doped gadolinium ( III ) fluoride ( Eu: GdF3 ) nanoparticles ( ~ 85 nm ) with quasispherical shape by precipitation at 120 degrees C from diethylene glycol solutions containing lanthanide chlorides and an ionic liquid ( 1 - Butyl, 2 - methylimidazolium tetrafluoroborate ) as fluoride source has been developed.", "output": "europium ( III ), gadolinium ( III ) fluoride, Eu, GdF3, diethylene glycol, lanthanide chlorides, 1 - Butyl, 2 - methylimidazolium tetrafluoroborate, fluoride." }, { "input": "These nanoparticles were polycrystalline and crystallized into a hexagonal structure, which is unusual for GdF3.", "output": "GdF3." }, { "input": "They were also mesoporous ( pore size = 3. 5 A ), having a rather high BET surface area ( 75 m ( 2 ) g ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "The luminescent and magnetic ( relaxivity ) properties of the Eu: GdF3 nanoparticles have been also evaluated in order to assess their potentiality as \" in vitro \" optical biolabels and contrast agent for magnetic resonance imaging.", "output": "Eu, GdF3." }, { "input": "Finally, a procedure for their functionalization with aspartic - dextran polymers is also reported.", "output": "There is no related enetity." }, { "input": "The functionalized Eu: GdF3 nanoparticles presented negligible toxicity for Vero cells, which make them suitable for biotecnological applications.", "output": "Eu, GdF3." }, { "input": "Interactive design of generic chemical patterns.", "output": "There is no related enetity." }, { "input": "Every medicinal chemist has to create chemical patterns occasionally for querying databases, applying filters or describing functional groups.", "output": "There is no related enetity." }, { "input": "However, the representations of chemical patterns have been so far limited to languages with highly complex syntax, handicapping the application of patterns.", "output": "There is no related enetity." }, { "input": "Graphic pattern editors similar to chemical editors can facilitate the work with patterns.", "output": "There is no related enetity." }, { "input": "In this article, we review the interfaces of frequently used web search engines for chemical patterns.", "output": "There is no related enetity." }, { "input": "We take a look at pattern editing concepts of standalone chemical editors and finally present a completely new, unpublished graphical approach to pattern design, the SMARTSeditor.", "output": "There is no related enetity." }, { "input": "Nano bioresearch approach by microtechnology.", "output": "There is no related enetity." }, { "input": "To progress in basic science and drug development, convenient methodology for detecting specific biological molecules and their interaction in living organism is in high demand.", "output": "There is no related enetity." }, { "input": "After more than 20 years of increasing research efforts, micro and nanotechnologies are now mature to propose a new class of miniature devices and principles enabling compartmentalized bioassays.", "output": "There is no related enetity." }, { "input": "Among them, this review proposes various examples that include array of electro - active microwells for highly parallel single cell analysis, cost - effective nanofluidic for DNA separation, parallel enzymatic reaction in 100pL droplet and high - throughput platform for membrane proteins assays.", "output": "There is no related enetity." }, { "input": "The micro devices are presented with relevant experiments to foresee their future contribution to translational research and drug discovery.", "output": "There is no related enetity." }, { "input": "Anti - inflammatory activity of edible brown alga Saccharina japonica and its constituents pheophorbide a and pheophytin a in LPS - stimulated RAW 264. 7 macrophage cells.", "output": "pheophorbide a, pheophytin a." }, { "input": "Anti - inflammatory activity of Saccharina japonica and its active components was evaluated via in vitro inhibitory activities against lipopolysaccharide ( LPS ) - induced nitric oxide ( NO ) production, inducible nitric oxide synthase ( iNOS ), and cyclooxygenase - 2 ( COX - 2 ) expression in RAW 264. 7 murine macrophage cells.", "output": "nitric oxide, NO, nitric oxide." }, { "input": "Since the methanolic extract of S. japonica showed strong anti - inflammatory activity, it was fractionated with several solvents.", "output": "There is no related enetity." }, { "input": "Among the fractions, the ethyl acetate fraction demonstrated the highest inhibition of LPS - induced NO production ( IC50 = 25. 32 mu g / mL ), followed by the CH2Cl2 fraction ( IC50 = 75. 86 mu g / mL ).", "output": "NO, CH2Cl2." }, { "input": "Considering the yield and anti - inflammatory potential together, the CH2Cl2 fraction was selected for chromatographic separation to yield two active porphyrin derivatives, pheophorbide a and pheophytin a, together with an inactive fucoxanthin.", "output": "CH2Cl2, porphyrin, pheophorbide a, pheophytin a, fucoxanthin." }, { "input": "In contrast to fucoxanthin, pheophorbide a and pheophytin a showed dose - dependent inhibition against LPS - induced NO production at nontoxic concentrations in RAW 264. 7 cells.", "output": "fucoxanthin, pheophorbide a, pheophytin a, NO." }, { "input": "Both compounds also suppressed the expression of iNOS proteins, while they did not inhibit the COX - 2 expression in LPS - stimulated macrophages.", "output": "There is no related enetity." }, { "input": "These results indicate that pheophorbide a and pheophytin a are two important candidates of S. japonica as anti - inflammatory agents which can inhibit the production of NO via inhibition of iNOS protein expression.", "output": "pheophorbide a, pheophytin a, NO." }, { "input": "Thus, these compounds hold great promise for use in the treatment of various inflammatory diseases.", "output": "There is no related enetity." }, { "input": "Chlorpyrifos induced hepatotoxic and hematologic changes in rats: the role of quercetin and catechin.", "output": "Chlorpyrifos, quercetin, catechin." }, { "input": "Chlorpyrifos is an organophosphorus insecticide which is widely used throughout in the world and it caused toxic effects on nontarget organisms especially mammalian.", "output": "Chlorpyrifos, organophosphorus." }, { "input": "In the present study, catechin, quercetin, chlorpyrifos, catechin + chlorpyrifos, quercetin + chlorpyrifos were given to male rats through gavage for 4weeks.", "output": "catechin, quercetin, chlorpyrifos, catechin, chlorpyrifos, quercetin, chlorpyrifos." }, { "input": "Serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, trigliceride, total cholesterol levels, hematological changes, superoxide dismutase, catalase, glutathione peroxidase, glutathione - S - transferase activities and malondialdehyde content in liver tissues and also histopathological changes of liver were investigated in the rats compared to control group.", "output": "aspartate, alanine, lactate, trigliceride, cholesterol, superoxide, glutathione, glutathione, malondialdehyde." }, { "input": "No significant differences in all investigated parameters were observed between control, catechin and quercetin groups.", "output": "catechin, quercetin." }, { "input": "There were statistically significantly changes in liver function tests, some hematological parameters, antioxidant enzyme activities and malondialdehyde levels in chlorpyrifos treated group compared to control group.", "output": "malondialdehyde, chlorpyrifos." }, { "input": "In catechin + chlorpyrifos treated group and quercetin + chlorpyrifos treated group we observed the protective effects of catechin and quercetin on examining parameters but not completely.", "output": "catechin, chlorpyrifos, quercetin, chlorpyrifos, catechin, quercetin." }, { "input": "While some histopathological changes detected in liver tissues in chlorpyrifos treated group, less histopathological changes were observed in catechin + chlorpyrifos and quercetin + chlorpyrifos treated groups at the end of the 4thweek.", "output": "chlorpyrifos, catechin, chlorpyrifos, quercetin, chlorpyrifos." }, { "input": "As a result, catechin and quercetin significantly reduce chlorpyrifos induced hepatotoxicity in rats.", "output": "catechin, quercetin, chlorpyrifos." }, { "input": "A comparative study of the modulatory effects of ( - ) - cubebin on the mutagenicity / recombinogenicity induced by different chemical agents.", "output": "( - ) - cubebin." }, { "input": "( - ) - Cubebin ( CUB ) is a lignan isolated from dry seeds of Piper cubeba.", "output": "( - ) - Cubebin, CUB, lignan." }, { "input": "We aimed to assess its genotoxic potential and influence on chromosomal damage ( frequency of micronuclei - MN ) induced by doxorubicin ( DXR ) in V79 cells and by urethane ( URE ) in somatic Drosophila melanogaster cells.", "output": "doxorubicin, DXR, urethane, URE." }, { "input": "Our findings indicate an absence of a CUB - mediated genotoxic effect at the concentrations tested.", "output": "CUB." }, { "input": "The results also revealed that CUB significantly reduced the frequency of MN induced by DXR, with a mean reduction of 63. 88 %.", "output": "CUB, DXR." }, { "input": "In a previous study, our research group demonstrated an absence of CUB - mediated mutagenic effects through the wing Somatic Mutation and Recombination Test ( SMART ) in Drosophila.", "output": "CUB." }, { "input": "In the present study, we used the standard and high bioactivation versions of the SMART to estimate the antigenotoxic effects of CUB associated with URE.", "output": "CUB, URE." }, { "input": "At lower concentrations, the recombination level decreased, but at the highest concentration, the recombination level increased.", "output": "There is no related enetity." }, { "input": "Our data and previous studies suggest that CUB may act as a free radical scavenger at low concentrations, a pro - oxidant at higher concentrations when it interacts with the enzymatic system that catalyzes the metabolic detoxification of DXR or URE, and / or an inducer of recombinational DNA repair.", "output": "CUB, DXR, URE." }, { "input": "Biotransformation and toxicokinetics of the insect repellent IR3535 (R) in male and female human subjects after dermal exposure.", "output": "IR3535." }, { "input": "The absorption and excretion of the insect repellent IR3535 ( (R) ) was studied in human subjects ( five males and five females ) after dermal application of approx. 3g of a formulation containing 20 % IR3535 ( (R) ), i. e. the amounts of IR3535 ( (R) ) applied were between 1. 94 and 3. 4 mmol / person ( 418 - 731 mg / person ).", "output": "IR3535, IR3535, IR3535." }, { "input": "Blood and urinary concentrations of IR3535 ( (R) ) and its only metabolite, IR3535 ( (R) ) - free acid, were determined over time.", "output": "IR3535, IR3535." }, { "input": "In plasma, concentrations of the parent compound IR3535 ( (R) ) were at or below the limit of quantification ( 0. 037 mu mol / L ).", "output": "IR3535." }, { "input": "IR3535 ( (R) ) - free acid peaked in plasma samples 2 - 6h after dermal application.", "output": "IR3535." }, { "input": "Cmax mean values were 5. 7 mu mol / L in males, 3. 0 mu mol / L in females and 4. 2 mu mol / L in all volunteers.", "output": "There is no related enetity." }, { "input": "Mean AUC values were 41. 6, 24. 5 and 33. 9 mu molL ( - 1 ) h in males, females and all subjects, respectively.", "output": "There is no related enetity." }, { "input": "In urine samples from all human subjects, both IR3535 ( (R) ) and IR3535 ( (R) ) - free acid were detectable, however, only very small amounts of IR3535 ( (R) ) were found.", "output": "IR3535, IR3535, IR3535." }, { "input": "Concentrations of IR3535 ( (R) ) - free acid were several thousand - fold higher than the parent compound and peaked at the first two sampling points ( 4h and 8h after dermal application ).", "output": "IR3535." }, { "input": "Overall, IR3535 ( (R) ) and IR3535 ( (R) ) - free acid excreted with urine over 48 h representing 13. 3 +/- 3. 05 % of the dose applied.", "output": "IR3535, IR3535." }, { "input": "Since IR3535 ( (R) ) is rapidly and extensively metabolized, and IR3535 ( (R) ) - free acid has a low molecular weight and high water solubility, it is expected that urinary excretion of IR3535 ( (R) ) - free acid and IR3535 ( (R) ) represents the total extent of absorption of IR3535 ( (R) ) in humans.", "output": "IR3535, IR3535, IR3535, IR3535, IR3535." }, { "input": "Based on the results of this study, the skin penetration rate of IR3535 ( (R) ) is 13. 3 % in humans after dermal application.", "output": "IR3535." }, { "input": "RP TLC data in correlation studies with in silico pharmacokinetic properties of benzimidazole and benztriazole derivatives.", "output": "benzimidazole, benztriazole." }, { "input": "Reversed - phase thin - layer chromatographic ( RP TLC ) retention constants for a newly designed series benzimidazole / benztriazole with expected biological activity were determined as parameters of their lipophilicity and this series was recognized as congeneric.", "output": "benzimidazole, benztriazole." }, { "input": "Pharmacokinetic descriptors of the compounds investigated were calculated in silico with the use of the established drug design software.", "output": "There is no related enetity." }, { "input": "The bioactivity descriptors, which are assumed to predicted drug absorption, distribution, metabolism, elimination and toxicity ( ADMETox ) in humans, were correlated with retention constants and good statistical parameters were obtained.", "output": "There is no related enetity." }, { "input": "Multiple regression analysis which was introduced suggested that the absorption through different epithelial membranes ( intestinal, blood - brain or erythrocyte membrane ) and distribution process depend on retention constants ( as measure of lipophilicty ) and total polar surface area and molar weight / volume of the analyte.", "output": "There is no related enetity." }, { "input": "Finally, the compounds with halogen substituent ( compounds A4 / A7 and A5 / A8 in Table 1 ), were suggested as the best drug candidates, because of their predicted proper pharmacokinetics and have been proposed for further biological tests.", "output": "There is no related enetity." }, { "input": "Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.", "output": "indinavir." }, { "input": "Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability.", "output": "There is no related enetity." }, { "input": "Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco - 2 system, exploring food effects during drug development can be quite challenging.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice.", "output": "indinavir." }, { "input": "Although the solubility of indinavir was 6 - fold higher in fed state human intestinal fluids ( FeHIF ) as compared to fasted state HIF ( FaHIF ), the intestinal permeation of indinavir was 22 - fold lower in FeHIF as compared to FaHIF.", "output": "indinavir, indinavir." }, { "input": "Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation.", "output": "indinavir." }, { "input": "The presence of ritonavir, a known P - gp inhibitor, increased the intestinal permeation of indinavir by 2 - fold in FaHIF, while there was no increase when using FeHIF.", "output": "ritonavir, indinavir." }, { "input": "These data confirm that drug - food interactions form a complex interplay between solubility and permeability effects.", "output": "There is no related enetity." }, { "input": "The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility / permeability interplay on drug absorption.", "output": "There is no related enetity." }, { "input": "Synthesis and anti - Candida activity of novel 2 - hydrazino - 1, 3 - thiazole derivatives.", "output": "2 - hydrazino - 1 , 3 - thiazole." }, { "input": "Eighteen new hydrazino - 1, 3 - thiazole derivatives were evaluated against 8 strains of multi - resistant Candida spp.", "output": "hydrazino - 1 , 3 - thiazole." }, { "input": "Introduction of an indolyl moiety linked to the hydrazone function enhanced the in vitro anti - Candida activity, with an activity spectrum towards Candida albicans strains.", "output": "indolyl, hydrazone." }, { "input": "Introduction of a ( S ) - 2 - aminoethyl chain on the thiazole nucleus largely enhanced the in vitro antifungal activity, with a selectivity oriented towards non - C. albicans species.", "output": "( S ) - 2 - aminoethyl, thiazole." }, { "input": "The PprA protein is required for accurate cell division of gamma - irradiated Deinococcus radiodurans bacteria.", "output": "There is no related enetity." }, { "input": "Deinococcus radiodurans, one of the most radioresistant organisms known to date is able to reconstruct an intact genome from hundreds of DNA fragments.", "output": "There is no related enetity." }, { "input": "Here, we investigate the in vivo role of PprA, a radiation - induced Deinococcus specific protein.", "output": "There is no related enetity." }, { "input": "We report that DNA double strand break repair in cells devoid of PprA and exposed to 3800Gy gamma - irradiation takes place efficiently with a delay of only 1h as compared to the wild type, whereas massive DNA synthesis begins 90min after irradiation as in the wild type, a phenotype insufficient to explain the severe radiosensitivity of the Delta pprA mutant.", "output": "There is no related enetity." }, { "input": "We show that the slow kinetics of reassembly of DNA fragments in a Delta pprA Delta recA double mutant was the same as that observed in a Delta recA single mutant demonstrating that PprA does not play a major role in DNA repair through RecA - independent pathways.", "output": "There is no related enetity." }, { "input": "Using a tagged PprA protein and immunofluorescence microscopy, we show that PprA is recruited onto the nucleoid after gamma - irradiation before DNA double strand break repair completion, and then is found as a thread across the septum in dividing cells.", "output": "There is no related enetity." }, { "input": "Moreover, whereas untreated cells devoid of PprA displayed a wild type morphology, they showed a characteristic cell division abnormality after irradiation not found in other radiosensitive mutants committed to die, as DNA is present equally in the two daughter cells but not separated at the division septum.", "output": "There is no related enetity." }, { "input": "We propose that PprA may play a crucial role in the control of DNA segregation and / or cell division after DNA double strand break repair.", "output": "There is no related enetity." }, { "input": "Targeted co - delivery of docetaxel, cisplatin and herceptin by vitamin E TPGS - cisplatin prodrug nanoparticles for multimodality treatment of cancer.", "output": "docetaxel, cisplatin, vitamin E, TPGS, cisplatin." }, { "input": "We developed a nanocarrier system of herceptin - conjugated nanoparticles of d - alpha - tocopheryl - co - poly ( ethylene glycol ) 1000 succinate ( TPGS ) - cisplatin prodrug ( HTCP NPs ) for targeted co - delivery of cisplatin, docetaxel and herceptin for multimodality treatment of breast cancer of high human epidermal growth factor receptor 2 ( HER2 ) overexpression.", "output": "d - alpha - tocopheryl - co - poly ( ethylene glycol ) 1000 succinate, TPGS, cisplatin, cisplatin, docetaxel." }, { "input": "Co - polymers poly ( lactic acid ) - TPGS ( PLA - TPGS ) and carboxyl group - terminated TPGS ( TPGS - COOH ) were also added in the polymeric matrix to stabilize the prodrug nanoparticles and to facilitate herceptin conjugation.", "output": "poly ( lactic acid ) - TPGS, PLA - TPGS, carboxyl, TPGS, TPGS, COOH." }, { "input": "The HTCP NPs of high, moderate and low docetaxel versus cisplatin ratio were prepared by the nanoprecipitation method, which showed a pH - sensitive release for both anticancer drugs.", "output": "docetaxel, cisplatin." }, { "input": "The therapeutic effects of HTCP NPs were evaluated in vitro and compared with Taxotere (R) and cisplatin.", "output": "Taxotere, cisplatin." }, { "input": "The HTCP NPs of high docetaxel versus cisplatin ratio were found to have better efficacy than those of moderate and low docetaxel versus cisplatin ratio.", "output": "docetaxel, cisplatin, docetaxel, cisplatin." }, { "input": "The targeting effects of the HTCP NPs were demonstrated by a much lower IC50 value of 0. 0201 + 0. 00780 + 0. 1629 mu g / mL of docetaxel + cisplatin + herceptin for SK - BR - 3 cells, which are of high HER2 overexpression, than that of 0. 225 + 0. 0875 + 1. 827 mu g / mL for NIH3T3 cells, which are of low HER2 overexpression, after 24h incubation.", "output": "docetaxel, cisplatin." }, { "input": "The same design of TPGS prodrug nanoparticles can also be applied for targeted co - delivery of other hydrophilic and hydrophobic drugs.", "output": "There is no related enetity." }, { "input": "Accurate quantum chemical energies for tetrapeptide conformations: why MP2 data with an insufficient basis set should be handled with caution.", "output": "tetrapeptide." }, { "input": "High - level quantum chemical calculations have been carried out for biologically - relevant conformers of tetrapeptides.", "output": "tetrapeptides." }, { "input": "Our results indicate potential problems if the widely - applied MP2 approach is used in such situations with basis sets of insufficient size.", "output": "There is no related enetity." }, { "input": "Efficient alternatives are discussed.", "output": "There is no related enetity." }, { "input": "Comparative study of artificial chromosome centromeres in human and murine cells.", "output": "There is no related enetity." }, { "input": "Human artificial chromosomes ( HAC ) are a valuable tool in the analysis of complex chromatin structures such as the human centromere because of their small size and relative simplicity compared with normal human chromosomes.", "output": "There is no related enetity." }, { "input": "This report includes a comprehensive study of the centromere and chromatin composition of HAC, expressing human genes, generated in human cells and transferred to murine cells.", "output": "There is no related enetity." }, { "input": "The analysis involved chromatin immuno - precipitation and immuno - FISH on metaphase chromosomes and chromatin fibres.", "output": "There is no related enetity." }, { "input": "In both the cell types, the HAC consisted of alphoid and non - alphoid DNA and were mainly euchromatic in composition, although a pericentromeric heterochromatic region was present on all the HAC.", "output": "There is no related enetity." }, { "input": "Fibre - FISH and chromatin immuno - precipitation data indicated that the position of the centromere differed between HAC in human cells and in murine cells.", "output": "There is no related enetity." }, { "input": "Our work highlights the importance and utilisation of HAC for understanding the epigenetic aspects of chromosome biology. European Journal of Human Genetics advance online publication, 13 February 2013; doi: 10. 1038 / ejhg. 2012. 296.", "output": "There is no related enetity." }, { "input": "Synergistic effects between CA1 mu opioid and dopamine D1 - like receptors in impaired passive avoidance performance induced by hepatic encephalopathy in mice.", "output": "dopamine." }, { "input": "BACKGROUND AND AIM: Numerous investigations have indicated that hepatic encephalopathy ( HE ) alters the levels of various neurotransmitters.", "output": "There is no related enetity." }, { "input": "However, comprehensive data regarding the effects of CA1 opioidergic and dopaminergic ( DAergic ) systems on HE - induced amnesia are still lacking.", "output": "There is no related enetity." }, { "input": "METHODS: Following intra - dorsal hippocampal ( CA1 ) injection of mu opioid and dopamine D1 - and D2 - like receptors antagonists in male mice, one - trial step - down and hole - board paradigms were used to assess memory and exploratory behaviors, respectively.", "output": "dopamine." }, { "input": "RESULTS: Our data demonstrated that HE impairs memory 24 days after bile duct ligation ( BDL ).", "output": "There is no related enetity." }, { "input": "Furthermore, while the higher dose of DA D1 - like receptor antagonist ( SCH23390, 0. 5 mu g / mouse ) induced amnesia and anxiogenic - like behaviors, mu receptor antagonist ( naloxone: 0. 0125, 0. 025 and 0. 05 mu g / mouse ) and DA D2 - like receptor antagonist ( sulpiride: 0. 0625, 0. 125 and 0. 25 mu g / mouse ) by themselves, could not exert an effect on memory performance in passive avoidance task.", "output": "SCH23390, naloxone, sulpiride." }, { "input": "On the other hand, pre - test injection of all drugs reversed the HE - induced amnesia 24 days after BDL, while having no effect on exploratory behaviors.", "output": "There is no related enetity." }, { "input": "Pre - test co - administration of the subthreshold dose SCH23390 ( 0. 25 mu g / mouse ) and sulpiride ( 0. 0625 mu g / mouse ) or naloxone ( 0. 0125 mu g / mouse ) could likewise reverse the BDL - induced amnesia.", "output": "SCH23390, sulpiride, naloxone." }, { "input": "However, when the subthreshold sulpiride plus naloxone were co - administered, BDL - induced amnesia was not blocked.", "output": "sulpiride, naloxone." }, { "input": "CONCLUSIONS: Memory performance is impaired 24 days post BDL and CA1 mu opioid and DA D1 - like receptors antagonist synergistic effects are likely involved in this phenomenon.", "output": "There is no related enetity." }, { "input": "TRIM16 overexpression induces apoptosis through activation of caspase - 2 in cancer cells.", "output": "There is no related enetity." }, { "input": "TRIM16 exhibits tumour suppressor functions by interacting with cytoplasmic vimentin and nuclear E2F1 proteins in neuroblastoma and squamous cell carcinoma cells, reducing cell migration and replication.", "output": "There is no related enetity." }, { "input": "Reduced TRIM16 expression in a range of human primary malignant tissues correlates with increased malignant potential.", "output": "There is no related enetity." }, { "input": "TRIM16 also induces apoptosis in breast and lung cancer cells, by unknown mechanisms.", "output": "There is no related enetity." }, { "input": "Here we show that overexpression of TRIM16 induces apoptosis in human breast cancer ( MCF7 ) and neuroblastoma ( BE ( 2 ) - C ) cells, but not in non - malignant HEK293 cells.", "output": "There is no related enetity." }, { "input": "TRIM16 increased procaspase - 2 protein levels in MCF7 and induced caspase - 2 activity in both MCF7 and BE ( 2 ) - C cells.", "output": "There is no related enetity." }, { "input": "We show that TRIM16 and caspase - 2 proteins directly interact in both MCF7 and BE ( 2 ) - C cells and co - localise in MCF7 cells.", "output": "There is no related enetity." }, { "input": "Most importantly, the induction of caspase - 2 activity is required for TRIM16 to initiate apoptosis.", "output": "There is no related enetity." }, { "input": "Our data suggest a novel mechanism by which TRIM16 can promote apoptosis by directly modulating caspase - 2 activity.", "output": "There is no related enetity." }, { "input": "Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control.", "output": "There is no related enetity." }, { "input": "AIMS / HYPOTHESIS: We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control.", "output": "There is no related enetity." }, { "input": "We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon - like peptide - 1 ( GLP - 1 ), will decrease vagal control.", "output": "There is no related enetity." }, { "input": "METHODS: Respiration and ECGs were recorded for 130 healthy participants undergoing clamps.", "output": "There is no related enetity." }, { "input": "Three variables of cardiac vagal effects ( the root mean square of successive differences [ rMSSD ] in the interbeat interval of the heart rate [ IBI ], heart - rate variability [ HRV ] caused by peak - valley respiratory sinus arrhythmia [ pvRSA ], and high - frequency power [ HF ] ) and heart rate ( HR ) were obtained at seven time points during the clamps, characterised by increasing levels of insulin ( achieved by administering insulin plus glucose, glucose only, glucose and GLP - 1, and glucose and GLP - 1 combined with arginine ).", "output": "glucose, glucose, glucose, glucose, arginine." }, { "input": "RESULTS: Serum insulin level was positively associated with HR at all time points during the clamps except the first - phase hyperglycaemic clamp.", "output": "There is no related enetity." }, { "input": "Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log ( 10 ) HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp ( hyperglycaemic second phase, GLP - 1 first and second phases, and arginine ).", "output": "arginine." }, { "input": "These associations disappeared when adjusted for age, BMI and insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Administration of the beta cell secretagogues GLP - 1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures.", "output": "arginine." }, { "input": "CONCLUSION / INTERPRETATION: Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index.", "output": "There is no related enetity." }, { "input": "Our findings suggest that exposure to a GLP - 1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.", "output": "There is no related enetity." }, { "input": "Composition and distribution of elements and ultrastructural topography of a human cardiac calculus.", "output": "There is no related enetity." }, { "input": "Trace elements ( TEs ) may contribute to the formation of calculi or stones or be involved in the aetiopathogenesis of stone diseases.", "output": "There is no related enetity." }, { "input": "The compositions and spatial distribution of elements from the inner nucleus to outer crust of the cardiac calculus were investigated by energy - dispersive X - ray fluorescence ( EDXRF ) spectrometer.", "output": "There is no related enetity." }, { "input": "The surface topograph, distribution map of elements, elemental and chemical compositions were also determined by environmental scanning electron microscope ( ESEM ) - energy - dispersive X - ray ( EDX ) analysis.", "output": "There is no related enetity." }, { "input": "Twenty - five elements were identifiable from 18 positions on the cardiac calculus by EDXRF spectrometer, in which the highest concentrations of toxic TEs ( Ni, Pt, Hg, Sn, Pb, W, Au, Al, Si ) and higher levels of essential TEs ( Ca, Sr, Cr, P ) were detected.", "output": "Ni, Pt, Hg, Sn, Pb, W, Au, Al, Si, Ca, Sr, Cr, P." }, { "input": "A moderate positive Pearson ' s correlation between TEs concentrations of Mg, Ca or P and location differences from centre to periphery in the cardiac calculus was observed.", "output": "Mg, Ca, P." }, { "input": "A positive correlation was also found for Ca / Zn and Ca / Cu, indicating the gradual increase of calcium concentration from inner nucleus to outer crust of cardiac calculus.", "output": "Ca, Zn, Ca, Cu, calcium." }, { "input": "The drop - like nodules / crystals on the surface of petrous part of cardiac calculus were observed from ESEM analysis.", "output": "There is no related enetity." }, { "input": "ESEM - EDX analysis determined the calculus to be predominantly composed of calcium hydroxyapatite and cholesterol, as indicated by the petrous surface and drop - like nodules / crystals, respectively.", "output": "calcium hydroxyapatite, cholesterol." }, { "input": "This composition was confirmed using a portable Raman analyser.", "output": "There is no related enetity." }, { "input": "The spatial distribution analysis indicated a gradual increase in Mg, P and Ca concentrations from the inner nucleus to the outer crust of the cardiac calculus.", "output": "Mg, P, Ca." }, { "input": "The major chemical compositions of calcium hydroxyapatite and cholesterol were detected on this cardiac calculus.", "output": "calcium hydroxyapatite, cholesterol." }, { "input": "alpha 1A - Adrenergic Receptors Regulate Cardiac Hypertrophy In Vivo Through Interleukin - 6 Secretion.", "output": "There is no related enetity." }, { "input": "The role of alpha 1 - adrenergic receptors ( ARs ) in the regulation of cardiac hypertrophy is still unclear, because transgenic mice demonstrated hypertrophy or the lack of it despite high receptor overexpression.", "output": "There is no related enetity." }, { "input": "To further address the role of the alpha 1 - ARs in cardiac hypertrophy, we analyzed unique transgenic mice that overexpress constitutively active mutation ( CAM ) alpha 1A - ARs or CAM alpha 1B - ARs under the regulation of large fragments of their native promoters.", "output": "There is no related enetity." }, { "input": "These constitutively active receptors are expressed in all tissues that endogenously express their wild - type counterparts as opposed to only myocyte - targeted transgenic mice.", "output": "There is no related enetity." }, { "input": "In this study, we discovered that CAM alpha 1A - AR mice in vivo have cardiac hypertrophy independent of changes in blood pressure, corroborating earlier studies, but in contrast to myocyte - targeted alpha 1A - AR mice.", "output": "There is no related enetity." }, { "input": "We also found cardiac hypertrophy in CAM alpha 1B - AR mice, in agreement with previous studies, but hypertrophy only developed in older mice.", "output": "There is no related enetity." }, { "input": "We also discovered unique alpha 1 - AR - mediated hypertrophic signaling that was AR subtype - specific with CAM alpha 1A - AR mice secreting atrial naturietic factor and interleukin - 6 ( IL - 6 ), whereas CAM alpha 1B - AR mice expressed activated nuclear factor - kappa B ( NF - kappa B ).", "output": "There is no related enetity." }, { "input": "These particular hypertrophic signals were blocked when the other AR subtype was coactivated.", "output": "There is no related enetity." }, { "input": "We also discovered that crossbreeding the two CAM models ( double CAM alpha 1A / B - AR ) inhibited the development of hypertrophy and was reversible with single receptor activation, suggesting that coactivation of the receptors can lead to novel antagonistic signal transduction.", "output": "There is no related enetity." }, { "input": "This was confirmed by demonstrating antagonistic signals that were even lower than normal controls in the double CAM alpha 1A / B - AR mice for p38, NF - kappa B, and the IL - 6 / glycoprotein 130 / signal transducer and activator of transcription 3 pathway.", "output": "There is no related enetity." }, { "input": "Because alpha 1A / B double knockout mice fail to develop hypertrophy in response to IL - 6, our results suggest that IL - 6 is a major mediator of alpha 1A - AR cardiac hypertrophy.", "output": "There is no related enetity." }, { "input": "Optimization of marine triterpene sipholenols as inhibitors of breast cancer migration and invasion.", "output": "triterpene, sipholenols." }, { "input": "Sipholenol A, a sipholane triterpene isolated from the Red Sea sponge Callyspongia siphonella, has the ability to reverse multidrug resistance in cancer cells that overexpress P - glycoprotein ( P - gp ).", "output": "Sipholenol A, sipholane triterpene." }, { "input": "Here, the antimigratory activity of sipholenol A and analogues are reported against the highly metastatic human breast cancer cell line MDA - MB - 231 in a wound - healing assay.", "output": "sipholenol A." }, { "input": "Sipholenol A and sipholenone A were semisynthetically optimized using ligand - based strategies to generate structurally diverse analogues in an attempt to maximize their antimigratory activity.", "output": "Sipholenol A, sipholenone A." }, { "input": "A total of 22 semisynthetic ester, ether, oxime, and carbamate analogues were generated and identified by extensive one - and two - dimensional NMR spectroscopy and high - resolution mass spectrometry analyses.", "output": "ester, ether, oxime, carbamate." }, { "input": "Sipholenol A 4 beta - 4 - chlorobenzoate and 19, 20 - anhydrosipholenol A 4 beta - 4 - chlorobenzoate esters were the most potent of all tested analogues in the wound - healing assay, with IC ( 50 ) values of 5. 3 and 5. 9 mu M, respectively.", "output": "Sipholenol A 4 beta - 4 - chlorobenzoate, 19 , 20 - anhydrosipholenol A 4 beta - 4 - chlorobenzoate, esters." }, { "input": "Generally, ester derivatives showed better antimigratory activities than the carbamate analogues.", "output": "carbamate." }, { "input": "A KINOMEscan of 19, 20 - anhydrosipholenol A 4 beta - benzoate ester against 451 human protein kinases identified protein tyrosine kinase 6 ( PTK6 ) as a potential target.", "output": "19 , 20 - anhydrosipholenol A 4 beta - benzoate ester, tyrosine." }, { "input": "In breast tumor cells, PTK6 promotes growth factor signaling and migration, and as such the semisynthetic sipholanes were evaluated for their ability to inhibit PTK6 phosphorylation in vitro.", "output": "sipholanes." }, { "input": "The two analogues with the highest antimigratory activities, sipholenol A 4 beta - 4 - chlorobenzoate and 19, 20 - anhydrosipholenol A 4 beta - 4 - chlorobenzoate esters, also exhibited the most potent inhibition of PTK6 phosphorylation inhibition.", "output": "sipholenol A 4 beta - 4 - chlorobenzoate, 19 , 20 - anhydrosipholenol A 4 beta - 4 - chlorobenzoate, esters." }, { "input": "None of the compounds exhibited cytotoxicity in a normal epithelial breast cell line.", "output": "There is no related enetity." }, { "input": "These derivatives were evaluated in an in vitro invasion assay, where sipholenol A succinate potently inhibited MDA - MB - 231 cell invasion at 10 mu M.", "output": "sipholenol A succinate." }, { "input": "These results highlight sipholane triterpenoids as novel antimigratory marine natural products with potential for further development as agents for the control of metastatic breast malignancies.", "output": "sipholane triterpenoids." }, { "input": "Computational studies identifying entry inhibitor scaffolds targeting the Phe43 cavity of HIV - 1 gp120.", "output": "Phe43." }, { "input": "Targeting protein - protein interactions, such as the HIV - 1 gp120 - CD4 interface, has become a cutting - edge approach in the current drug discovery scenario.", "output": "There is no related enetity." }, { "input": "Many small molecules have been developed so far as inhibitors of the interaction between CD4 and HIV - 1 gp120.", "output": "There is no related enetity." }, { "input": "However, due to a variety of reasons such as solubility, drug toxicity and drug resistance, these inhibitors have failed to prove clinically useful.", "output": "There is no related enetity." }, { "input": "As such, the identification of novel compounds that bind to protein - protein interactions is still a research area of considerable interest.", "output": "There is no related enetity." }, { "input": "Here, a structure - based virtual screening approach was successfully applied with the aim of identifying novel HIV - 1 entry inhibitors targeting the Phe43 pocket of HIV - 1 gp120.", "output": "There is no related enetity." }, { "input": "Several compounds able to inhibit viral replication in cell culture were identified, with the best agent endowed with an EC ( 50 ) value of 0. 9 mu M.", "output": "There is no related enetity." }, { "input": "Inactivity of all the identified hits toward a mutant ( Met475Ile ) strain strongly suggests that they interact in the Phe43 cavity of gp120, as intended.", "output": "Phe43." }, { "input": "Remarkably, all of these small molecules have a chemical scaffold unrelated to any known class of entry inhibitors reported thus far.", "output": "There is no related enetity." }, { "input": "Overall, our strategy led to the identification of four novel chemical scaffolds that inhibit HIV - 1 replication through the destabilization of the HIV - 1 gp120 - CD4 interface.", "output": "There is no related enetity." }, { "input": "Design and evaluation of 4 - aminophenol and salicylate derivatives as free - radical scavenger.", "output": "4 - aminophenol, salicylate." }, { "input": "This theoretical and experimental study describes the design and evaluation of the free - radical scavenging effect for the molecular association of 4 - aminophenol and salicylate derivatives.", "output": "4 - aminophenol, salicylate." }, { "input": "For this purpose, we employed theoretical methods for the selection of antioxidant drugs and the rapid methods of evaluation: the 1, 1 - diphenyl - 2 - picrylhydrazyl radical and the thiobarbituric acid reactive substances in the lipid peroxidation initiated by Fe ( 2 + ) and ascorbic acid in human erythrocytes.", "output": "1 , 1 - diphenyl - 2 - picrylhydrazyl, thiobarbituric acid, Fe ( 2 + ), ascorbic acid." }, { "input": "The associate derivatives exhibited a more potent inhibition than the salicylic acid, while the benzoyl compound exhibited a more potent inhibition than paracetamol.", "output": "salicylic acid, benzoyl, paracetamol." }, { "input": "The molecular parameters related to the electron distribution and structure ( ionization potential and energy of the highest occupied molecular orbital ) correlated very well with the antioxidant action of the compounds studied here in different tests.", "output": "There is no related enetity." }, { "input": "A new O - prenylated flavonol from the roots of Sophora interrupta.", "output": "O - prenylated flavonol." }, { "input": "A new O - prenylated flavonol, 3 ', 4 ' - dimethoxy - 7 - ( gamma, gamma - dimethylallyloxy ) flavonol ( 1 ), together with three known compounds, 2 ' - hydroxy - 3, 4 - dimethoxychalcone ( 2 ), biochanin A ( 3 ) and kaempferol - 3 - O - beta - d - glucopyranoside ( 4 ), were isolated from the roots of Sophora interrupta Bedd.", "output": "O - prenylated flavonol, 3 ' , 4 ' - dimethoxy - 7 - ( gamma , gamma - dimethylallyloxy ) flavonol, 2 ' - hydroxy - 3 , 4 - dimethoxychalcone, biochanin A, kaempferol - 3 - O - beta - d - glucopyranoside." }, { "input": "The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectral studies.", "output": "There is no related enetity." }, { "input": "Interactions of binuclear ruthenium ( II ) complexes with oligonucleotides in hydrogel matrix: enantioselective threading intercalation into GC context.", "output": "ruthenium ( II )." }, { "input": "A stretched poly ( vinyl alcohol ) ( PVA ) film provides a unique matrix that enables also short DNA oligonucleotide duplex to be oriented and studied by linear dichroism ( LD ).", "output": "poly ( vinyl alcohol ), PVA." }, { "input": "This matrix further allows controlling DNA secondary structure by proper hydration ( A or B form ), and such humid films could potentially also mimic the molecular crowding in cellular contexts.", "output": "There is no related enetity." }, { "input": "However, early attempts to study intercalators and groove binders for probing DNA in PVA failed due to competitive matrix binding.", "output": "PVA." }, { "input": "Here we report the successful orientation in PVA of DNA oligonucleotide duplex hairpins with thread - intercalated binuclear complex [ mu - ( 11, 11 ' - bidppz ) ( phen ) 4Ru2 ] ( 4 + ), and how LD depends on oligonucleotide sequence and metal center chirality.", "output": "PVA, [ mu - ( 11 , 11 ' - bidppz ) ( phen ) 4Ru2 ] ( 4 + )." }, { "input": "Opposite enantiomers of the ruthenium complex, Delta Delta and Lambda Lambda, were investigated with respect to enantioselectivity toward GC stretches as long as 22 bp.", "output": "ruthenium." }, { "input": "LD, supported by emission kinetics, reveals that threading intercalation occurs only with Delta Delta whereas Lambda Lambda remains externally bound, probably in either or both of the grooves of the GC - DNA.", "output": "There is no related enetity." }, { "input": "Enantioselective binding properties of sterically rigid DNA probes such as the ruthenium complexes could find applications for targeting nucleic acids, e. g., to inhibit transcription in therapeutic context such as treatment of malaria or cancer.", "output": "ruthenium." }, { "input": "Computational study of chain transfer to monomer reactions in high - temperature polymerization of alkyl acrylates.", "output": "alkyl acrylates." }, { "input": "This article presents a computational study of chain transfer to monomer ( CTM ) reactions in self - initiated high - temperature homopolymerization of alkyl acrylates ( methyl, ethyl, and n - butyl acrylate ).", "output": "alkyl acrylates, methyl , ethyl , and n - butyl acrylate." }, { "input": "Several mechanisms of CTM are studied.", "output": "There is no related enetity." }, { "input": "The effects of the length of live polymer chains and the type of monoradical that initiated the live polymer chains on the energy barriers and rate constants of the involved reaction steps are investigated theoretically.", "output": "There is no related enetity." }, { "input": "All calculations are carried out using density functional theory.", "output": "There is no related enetity." }, { "input": "Three types of hybrid functionals ( B3LYP, X3LYP, and M06 - 2X ) and four basis sets ( 6 - 31G ( d ), 6 - 31G ( d, p ), 6 - 311G ( d ), and 6 - 311G ( d, p ) ) are applied to predict the molecular geometries of the reactants, products and transition sates, and energy barriers.", "output": "There is no related enetity." }, { "input": "Transition state theory is used to estimate rate constants.", "output": "There is no related enetity." }, { "input": "The results indicate that abstraction of a hydrogen atom ( by live polymer chains ) from the methyl group in methyl acrylate, the methylene group in ethyl acrylate, and methylene groups in n - butyl acrylate are the most likely mechanisms of CTM.", "output": "hydrogen, methyl, methyl acrylate, methylene, ethyl acrylate, methylene, n - butyl acrylate." }, { "input": "Also, the rate constants of CTM reactions calculated using M06 - 2X are in good agreement with those estimated from polymer sample measurements using macroscopic mechanistic models.", "output": "There is no related enetity." }, { "input": "The rate constant values do not change significantly with the length of live polymer chains.", "output": "There is no related enetity." }, { "input": "Abstraction of a hydrogen atom by a tertiary radical has a higher energy barrier than abstraction by a secondary radical, which agrees with experimental findings.", "output": "hydrogen." }, { "input": "The calculated and experimental NMR spectra of dead polymer chains produced by CTM reactions are comparable.", "output": "There is no related enetity." }, { "input": "This theoretical / computational study reveals that CTM occurs most likely via hydrogen abstraction by live polymer chains from the methyl group of methyl acrylate and methylene group ( s ) of ethyl ( n - butyl ) acrylate.", "output": "hydrogen, methyl, methyl acrylate, methylene, ethyl ( n - butyl ) acrylate." }, { "input": "Novel triaryl sulfonamide derivatives as selective cannabinoid receptor 2 inverse agonists and osteoclast inhibitors: discovery, optimization, and biological evaluation.", "output": "triaryl sulfonamide." }, { "input": "Cannabinoid receptors have gained increasing attention as drug targets for developing potential therapeutic ligands.", "output": "There is no related enetity." }, { "input": "Here, we report the discovery and optimization of triaryl sulfonamides as a novel series possessing significant CB2 receptor affinity and selectivity.", "output": "triaryl sulfonamides." }, { "input": "Four sets of triaryl ligands were designed and synthesized for further structural modifications and led to the identification of eight compounds as potent and selective CB2 inverse agonists with high binding affinity ( CB2K ( i ) < 10 nM ).", "output": "triaryl." }, { "input": "Especially, compound 57 exhibited the strongest binding affinity on the CB2 receptor ( CB2K ( i ) of 0. 5 nM ) and the best selectivity over the CB1 receptor ( selectivity index of 2594 ).", "output": "There is no related enetity." }, { "input": "Importantly, 57 also showed potent inhibitory activity on osteoclast formation, and it was confirmed by a cell viability assay that the inhibition effects were not derived from the cytotoxicity.", "output": "There is no related enetity." }, { "input": "Finally, 3D QSAR studies confirmed our SAR findings that three bulky groups play an important role for CB2 receptor binding affinity.", "output": "There is no related enetity." }, { "input": "Cell type determines the light - induced endosomal escape kinetics of multifunctional mesoporous silica nanoparticles.", "output": "silica." }, { "input": "We investigated uptake and individual endosome lysis events in fibroblast, normal, and carcinoma cell lines using a colloidal mesoporous silica ( CMS ) nanoparticle ( NP ) - based reporter system with a covalently attached photosensitizer.", "output": "silica." }, { "input": "Endosome lysis was induced through the activation of protoporphyrin IX ( PpIX ).", "output": "protoporphyrin IX, PpIX." }, { "input": "Surprisingly, this release - on - demand system resulted in more broadly distributed lysis times than expected, particularly for Renca, a renal carcinoma cell line.", "output": "There is no related enetity." }, { "input": "An analysis of the NP load per endosome, endosome size, and uptake characteristics indicate that Renca cells not only take up a lower amount of NPs in comparison with the fibroblast cells but also have larger endosomes and a lower NP load per endosome.", "output": "There is no related enetity." }, { "input": "We then created a stochastic model detailing steps downstream of uptake to understand how much factors that cannot be directly measured, such as variations in the PpIX load per NP, affect the lysis time distributions.", "output": "PpIX." }, { "input": "Model results indicate that the distributions are primarily determined by the endosome properties, rather than variations across NPs.", "output": "There is no related enetity." }, { "input": "Visualizing RNA base - pairing probabilities with RNAbow diagrams.", "output": "There is no related enetity." }, { "input": "There are many effective ways to represent a minimum free energy RNA secondary structure that make it easy to locate its helices and loops.", "output": "There is no related enetity." }, { "input": "It is a greater challenge to visualize the thermal average probabilities of all folds in a partition function sum; dot plot representations are often puzzling.", "output": "There is no related enetity." }, { "input": "Therefore, we introduce the RNAbows visualization tool for RNA base pair probabilities.", "output": "There is no related enetity." }, { "input": "RNAbows represent base pair probabilities with line thickness and shading, yielding intuitive diagrams.", "output": "There is no related enetity." }, { "input": "RNAbows aid in disentangling incompatible structures, allow comparisons between clusters of folds, highlight differences between wild - type and mutant folds, and are also rather beautiful.", "output": "There is no related enetity." }, { "input": "Imogolite - like nanotubes: structure, stability, electronic and mechanical properties of the phosphorous and arsenic derivatives.", "output": "Imogolite, phosphorous, arsenic." }, { "input": "Imogolite is a single - walled aluminosilicate nanotube ( NT ) found in nature that can be easily synthesized, as well as its analogue aluminogermanate NT.", "output": "Imogolite, aluminosilicate, aluminogermanate." }, { "input": "Based on geometrical assumptions and pKa values, species such as H3PO4, H3PO3, H3AsO3, H3AsO4 could also be candidates to form imogolite - like structures.", "output": "H3PO4, H3PO3, H3AsO3, H3AsO4, imogolite." }, { "input": "In the present work, we provide insights about the stability, electronic, structural and mechanical properties of possible imogolite like NTs by means of self - consistent charge density - functional tight - binding method ( SCC - DFTB ).", "output": "imogolite." }, { "input": "Similarly to aluminogermanate, where the tetrahedral silicate groups are replaced by germanate, in this work tetrahedral silicate groups are substituted by phosphate, phosphite, arsenate and arsenite units in the imogolite structure.", "output": "aluminogermanate, silicate, germanate, silicate, phosphate, phosphite, arsenate, arsenite, imogolite." }, { "input": "Detailed analysis is focused on structural properties, strain energy, band gap and Mulliken charges distribution.", "output": "There is no related enetity." }, { "input": "The calculated strain energy curves for all studied zigzag imogolite - like NTs present well - defined minima, which change as a consequence of composition variation.", "output": "imogolite." }, { "input": "Moreover, the strain energy curves of armchair imogolite - like NTs also present minima, although in all cases less stable than zigzags by at least 2. 2 meV per atom.", "output": "imogolite." }, { "input": "The insulating NT behaviour changes after internal modification from silicate to phosphate, phosphite, arsenate and arsenite, as well as the charge distribution inside and outside the nanotubes.", "output": "silicate, phosphate, phosphite, arsenate, arsenite." }, { "input": "The UDP - Glucuronosyltransferase ( UGT ) 1A Polymorphism c. 2042C > G ( rs8330 ) Is Associated with Increased Human Liver Acetaminophen Glucuronidation, Increased UGT1A Exon 5a / 5b Splice Variant mRNA Ratio, and Decreased Risk of Unintentional Acetaminophen - Induced Acute Liver Failure.", "output": "UDP, Acetaminophen, Acetaminophen." }, { "input": "Acetaminophen is cleared primarily by hepatic glucuronidation.", "output": "Acetaminophen." }, { "input": "Polymorphisms in genes encoding the acetaminophen UDP - glucuronosyltransferase ( UGT ) enzymes could explain interindividual variability in acetaminophen glucuronidation and variable risk for liver injury after acetaminophen overdose.", "output": "acetaminophen, UDP, acetaminophen, acetaminophen." }, { "input": "In this study, human liver bank samples were phenotyped for acetaminophen glucuronidation activity and genotyped for the major acetaminophen - glucuronidating enzymes ( UGTs 1A1, 1A6, 1A9, and 2B15 ).", "output": "acetaminophen, acetaminophen." }, { "input": "Of these, only three linked single nucleotide polymorphisms ( SNPs ) located in the shared UGT1A - 3 ' UTR region ( rs10929303, rs1042640, rs8330 ) were associated with acetaminophen glucuronidation activity, with rs8330 consistently showing higher acetaminophen glucuronidation at all the tested concentrations of acetaminophen.", "output": "acetaminophen, acetaminophen, acetaminophen." }, { "input": "Mechanistic studies using luciferase - UGT1A - 3 ' UTR reporters indicated that these SNPs do not alter mRNA stability or translation efficiency.", "output": "There is no related enetity." }, { "input": "However, there was evidence for allelic imbalance and a gene - dose proportional increase in the amount of exon 5a versus exon 5b containing UGT1A mRNA spliced transcripts in livers with the rs8330 variant allele.", "output": "There is no related enetity." }, { "input": "Cotransfection studies demonstrated an inhibitory effect of exon 5b containing cDNAs on acetaminophen glucuronidation by UGT1A1 and UGT1A6 cDNAs containing exon 5a.", "output": "acetaminophen." }, { "input": "In silico analysis predicted that rs8330 creates an exon splice enhancer site that could favor exon 5a ( over exon 5b ) utilization during splicing.", "output": "There is no related enetity." }, { "input": "Finally, the prevalence of rs8330 was significantly lower ( P = 0. 027, chi ( 2 ) test ) in patients who had acute liver failure from unintentional acetaminophen overdose compared with patients with acute liver failure from other causes or a race - or ethnicity - matched population.", "output": "acetaminophen." }, { "input": "Together, these findings suggest that rs8330 is an important determinant of acetaminophen glucuronidation and could affect an individual ' s risk for acetaminophen - induced liver injury.", "output": "acetaminophen, acetaminophen." }, { "input": "Anthelmintic activity of the natural compound ( + ) - limonene epoxide against Schistosoma mansoni.", "output": "( + ) - limonene epoxide." }, { "input": "Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide.", "output": "There is no related enetity." }, { "input": "The treatment for this disease relies heavily on a single drug, praziquantel.", "output": "praziquantel." }, { "input": "Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs.", "output": "praziquantel." }, { "input": "Currently, natural products have been a good source for drug development.", "output": "There is no related enetity." }, { "input": "( + ) - Limonene epoxide is a mixture of cis and trans isomers found in many plants.", "output": "( + ) - Limonene epoxide." }, { "input": "Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms.", "output": "There is no related enetity." }, { "input": "In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy.", "output": "There is no related enetity." }, { "input": "The effects of ( + ) - limonene epoxide at 25 micro g / mL on S. mansoni adult worms were similar to those of the positive control ( praziquantel ), with reduction in motility and death of all worms after 120 h.", "output": "( + ) - limonene epoxide, praziquantel." }, { "input": "Confocal laser scanning microscopy revealed that ( + ) - limonene epoxide - mediated worm killing was associated with tegumental destruction.", "output": "( + ) - limonene epoxide." }, { "input": "Our results, along with the low toxicity of the ( + ) - limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents.", "output": "( + ) - limonene epoxide." }, { "input": "Neuronatin - mediated aberrant calcium signaling and endoplasmic reticulum stress underlie neuropathology in Lafora disease.", "output": "calcium." }, { "input": "Lafora disease ( LD ) is a teenage - onset inherited progressive myoclonus epilepsy characterized by the accumulations of intracellular inclusions called Lafora bodies and caused by mutations in protein phosphatase laforin or ubiquitin ligase malin.", "output": "There is no related enetity." }, { "input": "But how the loss of function of either laforin or malin causes disease pathogenesis is poorly understood.", "output": "There is no related enetity." }, { "input": "Recently, neuronatin was identified as a novel substrate of malin that regulates glycogen synthesis.", "output": "There is no related enetity." }, { "input": "Here we demonstrate that the level of neuronatin is significantly up - regulated in the skin biopsy sample of LD patients having mutations in both malin and laforin.", "output": "There is no related enetity." }, { "input": "Neuronatin is highly expressed in human fetal brain with gradual decrease in expression in developing and adult brain.", "output": "There is no related enetity." }, { "input": "However, in adult brain, neuronatin is predominantly expressed in parvalbumin - positive GABAergic interneurons and localized in their processes.", "output": "There is no related enetity." }, { "input": "The level of neuronatin is increased and accumulated as insoluble aggregates in the cortical area of LD brain biopsy samples, and there is also a dramatic loss of parvalbumin - positive GABAergic interneurons.", "output": "There is no related enetity." }, { "input": "Ectopic expression of neuronatin in cultured neuronal cells results in increased intracellular Ca ( 2 + ), endoplasmic reticulum stress, proteasomal dysfunction, and cell death that can be partially rescued by malin.", "output": "Ca ( 2 + )." }, { "input": "These findings suggest that the neuronatin - induced aberrant Ca ( 2 + ) signaling and endoplasmic reticulum stress might underlie LD pathogenesis.", "output": "Ca ( 2 + )." }, { "input": "Quantitative analysis of TALE - DNA interactions suggests polarity effects.", "output": "There is no related enetity." }, { "input": "Transcription activator - like effectors ( TALEs ) have revolutionized the field of genome engineering.", "output": "There is no related enetity." }, { "input": "We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays.", "output": "There is no related enetity." }, { "input": "Within TALE proteins, tandem 34 - amino acid repeats recognize one base pair each and direct sequence - specific DNA binding through repeat variable di - residues ( RVDs ).", "output": "amino acid." }, { "input": "We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ~ NN >> NI > NK.", "output": "There is no related enetity." }, { "input": "The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10 ( 3 ) - fold lower affinity.", "output": "There is no related enetity." }, { "input": "We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD - base combinations, with a designed TALE that precisely matches ' standard ' RVDs with the target bases.", "output": "There is no related enetity." }, { "input": "This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5 ' - T.", "output": "There is no related enetity." }, { "input": "Another surprising observation was that base mismatches at the 5 ' end of the target site had more disruptive effects on affinity than those at the 3 ' end, particularly in designed TALEs.", "output": "There is no related enetity." }, { "input": "These results provide evidence that TALE - DNA recognition exhibits a hitherto un - described polarity effect, in which the N - terminal repeats contribute more to affinity than C - terminal ones.", "output": "N, C." }, { "input": "Transient receptor potential channels - emerging novel drug targets for the treatment of pain.", "output": "There is no related enetity." }, { "input": "In mammals several members of the Transient Receptor Potential channel family ( TRPs ), expressed mainly in the sensory neurons and skin keratinocytes, are implicated in relevant physiological functions, including thermosensation, nociception and vision.", "output": "There is no related enetity." }, { "input": "Since the TRPV1 - 4, TRPA1 and TRPM8 channels from this family play a pivotal role in both the detection and possibly modulation of painful stimuli, they are regarded as a very promising target of novel analgesic drugs.", "output": "There is no related enetity." }, { "input": "A few agents acting at TRPs, such as capsaicin or menthol, have a long history of their application as analgesics, whereas others ( e. g. SB705498, JTS653, JNJ17203212, AP18, A967079, Chembridge - 5861528 or PBMC ) are currently being evaluated both in animals and in humans.", "output": "capsaicin, menthol, SB705498, JTS653, JNJ17203212, AP18, A967079, Chembridge - 5861528." }, { "input": "In this review we discuss pain physiology, as well as the pharmacological properties of the TRPs involved in pain detection as potential critical peripheral analgesic targets.", "output": "There is no related enetity." }, { "input": "We present one of the most relevant strategies in the search for novel analgesic drugs, namely the TRP channels and their ligands, both agonists and antagonists as potential novel therapeutics for inflammatory and neuropathic pain syndromes.", "output": "There is no related enetity." }, { "input": "The safety profile of these agents, in particular their impact on thermosensation, is also discussed below.", "output": "There is no related enetity." }, { "input": "Photoactive analogs of farnesyl diphosphate and related isoprenoids: design and applications in studies of medicinally important isoprenoid - utilizing enzymes.", "output": "farnesyl diphosphate, isoprenoids, isoprenoid." }, { "input": "Farnesyl diphosphate ( FPP ) is an important metabolic intermediate in the biosynthesis of a variety of molecules including sesquiterpenes and the side chains of a number of cofactors.", "output": "Farnesyl diphosphate, FPP, sesquiterpenes." }, { "input": "FPP is also the source of isoprenoid side chains found attached to proteins.", "output": "FPP, isoprenoid." }, { "input": "Enzymes that employ FPP as a substrate are of interest because they are involved in the semisynthesis of drugs as well as targets for drug design.", "output": "FPP." }, { "input": "Photoactive analogs of FPP have been useful for identifying enzymes that use this molecule as a substrate.", "output": "FPP." }, { "input": "A variety of photocrosslinking groups have been employed to prepare FPP analogs for use in such experiments including aryl azides, diazotrifluoropropionates and benzophenones.", "output": "FPP, aryl azides, diazotrifluoropropionates, benzophenones." }, { "input": "In this review, the design of these probes is described along with an examination of how they have been used in crosslinking experiments.", "output": "There is no related enetity." }, { "input": "Impact of quaternary structure dynamics on allosteric drug discovery.", "output": "There is no related enetity." }, { "input": "The morpheein model of allosteric regulation draws attention to proteins that can exist as an equilibrium of functionally distinct assemblies where: one subunit conformation assembles into one multimer; a different subunit conformation assembles into a different multimer; and the various multimers are in a dynamic equilibrium whose position can be modulated by ligands that bind to a multimer - specific ligand binding site.", "output": "There is no related enetity." }, { "input": "The case study of porphobilinogen synthase ( PBGS ) illustrates how such an equilibrium holds lessons for disease mechanisms, drug discovery, understanding drug side effects, and identifying proteins wherein drug discovery efforts might focus on quaternary structure dynamics.", "output": "porphobilinogen." }, { "input": "The morpheein model of allostery has been proposed as applicable for a wide assortment of disease - associated proteins ( Selwood, T., Jaffe, E., ( 2012 ) Arch. Bioch. Biophys, 519: 131 - 143 ).", "output": "There is no related enetity." }, { "input": "Herein we discuss quaternary structure dynamics aspects to drug discovery for the disease - associated putative morpheeins phenylalanine hydroxylase, HIV integrase, pyruvate kinase, and tumor necrosis factor alpha.", "output": "phenylalanine, pyruvate." }, { "input": "Also highlighted is the quaternary structure equilibrium of transthyretin and successful drug discovery efforts focused on controlling its quaternary structure dynamics.", "output": "There is no related enetity." }, { "input": "Mechanistic insights into water - protein interactions of filamentous bacteriophage.", "output": "There is no related enetity." }, { "input": "Water plays a major structural and functional role around proteins.", "output": "There is no related enetity." }, { "input": "In an attempt to explore this mechanistic structural aspect of proteins, we present site - specific interaction of hydration water with the major coat protein subunit of filamentous virus Pf1 by magic angle spinning ( MAS ) solid - state NMR.", "output": "There is no related enetity." }, { "input": "The interaction of surrounding water with 36 MDa Pf1 virion is investigated in uniformly ( 13 ) C, ( 15 ) N isotopically labeled; polyethylene glycol precipitated fully hydrated samples by solid - state nuclear magnetic resonance spectroscopy.", "output": "( 13 ) C, ( 15 ) N, polyethylene glycol." }, { "input": "Dipolar edited two - dimensional ( 2D ) ( 1 ) H - ( 15 ) N heteronuclear correlation ( HETCOR ) experiments lead to unambiguous assignments of cross - peaks originating exclusively from ( 1 ) H resonances of water molecules correlating to the protein amide nitrogen.", "output": "( 1 ) H, ( 15 ) N, ( 1 ) H, amide nitrogen." }, { "input": "An enhanced resolved ( 1 ) H chemical shift dimension in these experiments also precludes the need of perdeuteration.", "output": "( 1 ) H." }, { "input": "We report seven residues spanning the 40 - residue continuous alpha - helical conformation assembly of Pf1 interacting with surrounding water.", "output": "There is no related enetity." }, { "input": "It shows a highly hydrated inner core inside this viral filamentous assembly.", "output": "There is no related enetity." }, { "input": "The results obtained also suggest the first evidence of a water - mediated interface cluster formed at the site of Arg44 with the single - stranded DNA genome of the filamentous phage supramolecular assembly.", "output": "Arg44." }, { "input": "Multifunctional carboxymethyl cellulose - based magnetic nanovector as a theragnostic system for folate receptor targeted chemotherapy, imaging, and hyperthermia against cancer.", "output": "carboxymethyl, folate." }, { "input": "A multifunctional biocompatible nanovector based on magnetic nanoparticle and carboxymethyl cellulose ( CMC ) was developed.", "output": "carboxymethyl." }, { "input": "The nanoparticles have been characterized using TEM, SEM, DLS, FT - IR spectra, VSM, and TGA studies.", "output": "There is no related enetity." }, { "input": "We found that the synthesized carboxymethyl cellulose magnetic nanoparticles ( CMC MNPs ) were spherical in shape with an average size of 150 nm having low aggregation and superparamagnetic properties.", "output": "carboxymethyl." }, { "input": "We found that the folate - tagged CMC MNPs were delivered to cancer cells by a folate - receptor - mediated endocytosis mechanism.", "output": "folate, folate." }, { "input": "5 - FU was encapsulated as a model drug for delivering cytotoxicity, and we could demonstrate the sustained release of 5 - FU.", "output": "5 - FU, 5 - FU." }, { "input": "It was also observed that the FITC - labeled CMC MNPs could effectively enter cells, and the fate of nanoparticles was tracked with Lysotracker.", "output": "FITC." }, { "input": "The CMC MNPs could induce significant cell death when an alternating magnetic field was applied.", "output": "There is no related enetity." }, { "input": "These results indicate that the multifunctional CMC MNPs possess a high drug loading efficiency and high biocompatibility and with low cell cytotoxicity and can be considered to be promising candidates for CMC - based targeted drug delivery, cellular imaging, and magnetic hyperthermia ( MHT ).", "output": "There is no related enetity." }, { "input": "Rotational dynamics of metal azide ion pairs in dimethylsulfoxide solutions.", "output": "metal azide, dimethylsulfoxide." }, { "input": "Azide ion is an excellent vibrational probe for studying ion - ion and ion - dipole interactions in solutions because its frequency is sensitively dependent on its local environments.", "output": "Azide." }, { "input": "When azide ion forms contact ion pairs with cations in dimethylsulfoxide ( DMSO ), free azide ion and contact ion pairs are spectrally well distinguished in FTIR spectra.", "output": "azide, dimethylsulfoxide, DMSO, azide." }, { "input": "Here, we investigated vibrational population relaxation, P ( t ), and orientational relaxation dynamics, r ( t ), of free azide ion and contact ion pairs ( LiN3, NaN3, NH4N3, MgN3 ( + ), and CaN3 ( + ) ) in DMSO by IR pump - probe spectroscopy.", "output": "azide, LiN3, NaN3, NH4N3, MgN3 ( + ), CaN3 ( + ), DMSO." }, { "input": "For metal azide ion pairs, the metal ion slowed down the vibrational relaxation of azide ion by acting like a thermal insulator.", "output": "metal azide, azide." }, { "input": "Biexponential behavior of r ( t ) was analyzed in the wobbling - in - a - cone model.", "output": "There is no related enetity." }, { "input": "The long time component of r ( t ) of free azide ion was found to be viscosity - dependent.", "output": "azide." }, { "input": "The wobbling motion of azide ion within the frame of metal azide ion pairs was weakly dependent on the countercation.", "output": "azide, metal azide." }, { "input": "When the overall orientational relaxation of metal azide ion pairs was analyzed by the extended Debye - Stokes - Einstein equation, it was well described under stick or superstick boundary conditions due to a strong interaction between the metal ion and DMSO molecules.", "output": "metal azide, DMSO." }, { "input": "Our experimental results provide important insight in understanding the rotational dynamics of small ionic species in polar solvents when the size of the ionic species is smaller than or comparable to that of the solvent molecule.", "output": "There is no related enetity." }, { "input": "The metalloproteases meprin alpha and meprin beta: unique enzymes in inflammation, neurodegeneration, cancer and fibrosis.", "output": "There is no related enetity." }, { "input": "The metalloproteases meprin alpha and meprin beta exhibit structural and functional features that are unique among all extracellular proteases.", "output": "There is no related enetity." }, { "input": "Although meprins were discovered more than 30 years ago, their precise substrates and physiological roles have been elusive.", "output": "There is no related enetity." }, { "input": "Both enzymes were originally found to be highly expressed in kidney and intestine, which focused research on these particular tissues and associated pathologies.", "output": "There is no related enetity." }, { "input": "Only recently it has become evident that meprins exhibit a much broader expression pattern, implicating functions in angiogenesis, cancer, inflammation, fibrosis and neurodegenerative diseases.", "output": "There is no related enetity." }, { "input": "Different animal models, as well as proteomics approaches for the identification of protease substrates, have helped to reveal more precise molecular signalling events mediated by meprin activity, such as activation and release of pro - inflammatory cytokines.", "output": "There is no related enetity." }, { "input": "APP ( amyloid precursor protein ) is cleaved by meprin beta in vivo, reminiscent of the beta - secretase BACE1 ( beta - site APP - cleaving enzyme 1 ).", "output": "There is no related enetity." }, { "input": "The subsequent release of A beta ( amyloid beta ) peptides is thought to be the major cause of the neurodegenerative Alzheimer ' s disease.", "output": "There is no related enetity." }, { "input": "On the other hand, ADAM10 ( a disintegrin and metalloprotease domain 10 ), which is the constitutive alpha - secretase, was shown to be activated by meprin beta, which is itself shed from the cell surface by ADAM10.", "output": "There is no related enetity." }, { "input": "In skin, both meprins are overexpressed in fibrotic tumours, characterized by massive accumulation of fibrillar collagens.", "output": "There is no related enetity." }, { "input": "Indeed, procollagen III is processed to its mature form by meprin alpha and meprin beta, an essential step in collagen fibril assembly.", "output": "There is no related enetity." }, { "input": "The recently solved crystal structure of meprin beta and the unique cleavage specificity of these proteases identified by proteomics will help to generate specific inhibitors that could be used as therapeutics to target meprins under certain pathological conditions.", "output": "There is no related enetity." }, { "input": "Isolation and structures of axistatins 1 - 3 from the Republic of Palau marine sponge Agelas axifera Hentschel.", "output": "axistatins 1 - 3." }, { "input": "An investigation begun in 1979 directed at the Republic of Palau marine sponge Agelas axifera Hentschel for cancer cell growth inhibitory constituents subsequently led to the isolation of three new pyrimidine diterpenes designated axistatins 1 ( 1 ), 2 ( 2 ), and 3 ( 3 ), together with the previously reported formamides 4, 5, and agelasine F ( 6 ).", "output": "pyrimidine, diterpenes, axistatins 1 ( 1 ) , 2 ( 2 ) , and 3 ( 3 ), formamides, agelasine F." }, { "input": "The structures were elucidated by analysis of 2D - NMR spectra and by HRMS.", "output": "There is no related enetity." }, { "input": "All of the isolated compounds were found to be moderate inhibitors of cancer cell growth.", "output": "There is no related enetity." }, { "input": "Axistatins 1 - 3 ( 1 - 3 ), formamide 4, and agelasine F ( 6 ) also exhibited antimicrobial activity.", "output": "Axistatins 1 - 3, formamide, agelasine F." }, { "input": "Toward a physically based quantitative modeling of impact sensitivities.", "output": "There is no related enetity." }, { "input": "Among the subsequent steps leading from impact to explosive decomposition in nitro compounds, the ability of early exothermic reactions to trigger the decomposition of neighboring molecules before the released energy has dissipated away is assumed to be critical.", "output": "nitro." }, { "input": "The rate of this process is roughly estimated using as inputs the energy content and the dissociation energy of the weakest X - NO2 bonds.", "output": "X - NO2." }, { "input": "While the sensitivity index thus obtained was previously shown to exhibit striking correlations with gap test pressures, its correlation with drop weight impact test data is poorer.", "output": "There is no related enetity." }, { "input": "Nevertheless, considering four different subsets of molecules depending on the environment of the most labile nitro groups, straightforward regressions against this sensitivity index yield a practical method to estimate impact sensitivity, whose combination of fair performance and generality is provided by no alternative approach, except purely empirical models based on extensive parametrization.", "output": "nitro." }, { "input": "Insight into the medicinal chemistry of the endocannabinoid hydrolase inhibitors.", "output": "There is no related enetity." }, { "input": "Endocannabinoid hydrolases are nowadays increasingly considered as potential therapeutic targets for treating several pathological states.", "output": "There is no related enetity." }, { "input": "So far, numerous classes of endocannabinoid hydrolase inhibitors have been described.", "output": "There is no related enetity." }, { "input": "We herein review the medicinal chemistry of these inhibitors with a particular emphasis on the basis of their design, chemical structure, structure - activity relationships, and inhibition mechanisms.", "output": "There is no related enetity." }, { "input": "The economics of polypharmacology: fixed dose combinations and drug cocktails.", "output": "There is no related enetity." }, { "input": "The history of Fixed Dose Combination ( FDC ) oral drug products has been tumultuous over its history.", "output": "There is no related enetity." }, { "input": "Some FDCs were prepared for marketing purposes and others for clinical improvements.", "output": "There is no related enetity." }, { "input": "Often, the products prepared for marketing advantage ended up causing negative outcomes.", "output": "There is no related enetity." }, { "input": "However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS / HIV and for oral contraceptives, just to name two examples.", "output": "There is no related enetity." }, { "input": "International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs.", "output": "There is no related enetity." }, { "input": "The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient ' s medication taking compliance.", "output": "There is no related enetity." }, { "input": "On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually.", "output": "There is no related enetity." }, { "input": "Overall, there is a great deal of evidence in favor of appropriate FDCs.", "output": "There is no related enetity." }, { "input": "Polypharmacology in a single drug: multitarget drugs.", "output": "There is no related enetity." }, { "input": "Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases.", "output": "There is no related enetity." }, { "input": "It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these.", "output": "There is no related enetity." }, { "input": "Polypharmacology can involve combinations and / or multitarget drugs ( MTD ).", "output": "There is no related enetity." }, { "input": "Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations.", "output": "There is no related enetity." }, { "input": "This review article focuses on MTDs from a medicinal chemistry perspective.", "output": "There is no related enetity." }, { "input": "I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.", "output": "There is no related enetity." }, { "input": "Multi - target compounds acting in the central nervous system designed from natural products.", "output": "There is no related enetity." }, { "input": "Modern medicinal chemistry has come to its bottleneck and is full of challenges, specially when facing with long - term central nervous system ( CNS ) disorders induced by several factors, such as Alzheimer ' s disease ( AD ) or Parkinson ' s disease ( PD ).", "output": "There is no related enetity." }, { "input": "In order to probe these challenges, multi - target directed ligands ( MTDLs ) design has been applied recently by medicinal scientists trying to get single compounds that can simultaneously modulate multiple targets.", "output": "There is no related enetity." }, { "input": "In addition, natural products have drawn the attention of drug developers again in recent years, as they have been used by human race for thousands of years and are full of diversity with their concomitant high potential to exhibit biological activities.", "output": "There is no related enetity." }, { "input": "We hereby review some of the research within the last few years focusing on multiple - target compounds acting in the CNS using natural products as lead resources.", "output": "There is no related enetity." }, { "input": "The target compounds obtained and described here represent bioactive hybrids either covalently connected or obtained by fusion of different bioactive moieties with at least one part derived from or representing directly natural products, along with some natural compounds themselves showing multiple pharmacological activities.", "output": "There is no related enetity." }, { "input": "We describe suitable ways to connect the drug components chemically, how to use the approach to enhance biological activity and selectivity, as well as potential drawbacks of the hybrid approach.", "output": "There is no related enetity." }, { "input": "This review will also show the rationale that these MTDLs are more than just the sum of their components but in many cases should be considered as new pharmacological entities in their own respect.", "output": "There is no related enetity." }, { "input": "Rationally designed multitarget anticancer agents.", "output": "There is no related enetity." }, { "input": "Balanced modulation of multiple targets is an attractive therapeutic strategy in treating complex diseases including cancer.", "output": "There is no related enetity." }, { "input": "Comparing with drugs combination, single molecule modulating desirable multiple targets has advantages in pharmacokinetic and pharmacodynamics.", "output": "There is no related enetity." }, { "input": "Different from previous reviews, we provided an overview of reported multitarget antitumor agents from the viewpoint of pharmacophores.", "output": "There is no related enetity." }, { "input": "These multitarget antitumor agents were designed by combination of pharmacophores or by high - throughput screening plus structural modification, which were exemplified by the privileged pharmacophore quinazoline and several other popular pharmacophores, including phenylaminopyrimidine, anthracycline and naphthalimide.", "output": "phenylaminopyrimidine, anthracycline, naphthalimide." }, { "input": "Previous research demonstrated the importance of in - depth validation against multiple targets not only in cell - free system, but also in cancer cells.", "output": "There is no related enetity." }, { "input": "Furthermore, the multitarget compounds were also effective for resistance cell lines which highlighted their antitumor potency in the era of increasing drug resistance in cancer patients.", "output": "There is no related enetity." }, { "input": "Recent developments in rationally designed multitarget antiprotozoan agents.", "output": "There is no related enetity." }, { "input": "Protozoan infections are the leading cause of morbidity and mortality among parasitic infections of humans, accounting for approximately 800 thousand mortalities and a loss of more than 30 million disability - adjusted life years annually.", "output": "There is no related enetity." }, { "input": "The major protozoan infections of humans, namely malaria, Chagas disease, human African trypanosomiasis, and leishmaniasis, are primarily centered in the tropics, with a reach into some subtropical regions of the world.", "output": "There is no related enetity." }, { "input": "Though globally massive in their impact, these diseases mostly afflict the least economically endowed and geographically marginalized populations in low - income countries.", "output": "There is no related enetity." }, { "input": "As such, there is no sufficient market incentive for industrial businessdriven antiprotozoal drug discovery due to poor marketing prospects and low returns on investment.", "output": "There is no related enetity." }, { "input": "Consequently, the pharmacopoeia for majority of these diseases, composed mainly of agents with poor efficacy and unsatisfactory safety profiles, has essentially remained unchanged for decades, creating a compelling need for more efficacious and better tolerated medicines.", "output": "There is no related enetity." }, { "input": "The policy makers and the scientific community are seeking effective ways to meet this need.", "output": "There is no related enetity." }, { "input": "So far, two approaches have emerged promising in this regard: combination chemotherapy and drug repositioning.", "output": "There is no related enetity." }, { "input": "Molecular hybridization has been cited as a potential third approach that could be used to deliver new antiprotozoal chemical entities.", "output": "There is no related enetity." }, { "input": "In this review article, recent applications of this novel strategy in antimalarial, antichagasic, antitrypanosomal, and antileishmanial drug discovery research and development over the last five years will be presented and discussed.", "output": "There is no related enetity." }, { "input": "Rationally Designed Multitarget Anti - HIV Agents.", "output": "There is no related enetity." }, { "input": "Multitarget - directed ligands ( MTDLs ), an emerging and appealing drug discovery strategy, utilizing a single chemical entity to inhibit multitargets, was confirmed to be effective in reducing the likelihood of drug resistance, diminishing problems of dosing complexity, drug - drug interactions and toxicities, as well as improving patient compliance.", "output": "There is no related enetity." }, { "input": "The exploration of MTDL strategy should be valuable in anti - HIV drug discovery.", "output": "There is no related enetity." }, { "input": "In this article, current knowledge and strategies for the rational design of the multitarget and selective anti - HIV agents are described and a number of illustrative examples are given.", "output": "There is no related enetity." }, { "input": "Moreover, the challenges, limitations and outlook of such novel drug design strategies are also presented, with a goal to highlight the representative paradigms in the rational design of MTDLs, and to help medicinal chemists discover the next generation of multitarget anti - HIV agents.", "output": "There is no related enetity." }, { "input": "Design of multifunctional compounds for cardiovascular disease: from natural scaffolds to \" classical \" multitarget approach.", "output": "There is no related enetity." }, { "input": "Cardiovascular disease represents the main cause of death worldwide.", "output": "There is no related enetity." }, { "input": "Novel therapies to reduce elevated blood pressure and treat resistant hypertension, to consequently reduce the associated cardiovascular risk factors, are still required.", "output": "There is no related enetity." }, { "input": "Among the different strategies commonly used in medicinal chemistry to develop new molecules, the synthesis of multitarget / hybrid compounds combining two or more pharmacophore groups targeting simultaneously selected factors involved in cardiovascular diseases, has gained increasing interest.", "output": "There is no related enetity." }, { "input": "This review will focus on the most recent literature on multifunctional cardiovascular drugs, paying particular attention on hybrid compounds bearing natural scaffolds, considering that compounds derived from medicinal extracts are generally appealing for the medicinal chemist as they often bear the so - called \" privileged structures \".", "output": "There is no related enetity." }, { "input": "Moreover, taking into account many excellent reviews dealing with multitarget cardiovascular drugs published in the last few years, mainly devoted to RAAS inhibition and / or NO donors hybrid drugs, herein the most significant results obtained and the benefits and limitations of these approaches will be highlighted.", "output": "There is no related enetity." }, { "input": "Rationally designed multitarget agents against inflammation and pain.", "output": "There is no related enetity." }, { "input": "Arachidonic acid ( ARA ) undergoes enzyme - mediated oxidative metabolism, resulting in the formation of a number of biologically active metabolites.", "output": "Arachidonic acid, ARA." }, { "input": "For over a century, these biochemical transformations have been the target of numerous pharmacological drugs for inflammation and pain.", "output": "There is no related enetity." }, { "input": "In particular, non - steroidal anti - inflammatory drugs ( NSAIDs ) and cyclooxygenase - 2 ( COX - 2 ) selective inhibitors ( coxibs ) are widely used in the treatment of inflammation and pain.", "output": "There is no related enetity." }, { "input": "However, gastrointestinal ( GI ) and cardiovascular adverse effects of NSAIDs and coxibs, and recent findings demonstrating that there are significant risks from the disruption of oxylipin levels when pharmacologically inhibiting a single ARA cascade metabolic pathway, have led to studies involving the simultaneous inhibition of multiple pathways in ARA cascade.", "output": "oxylipin, ARA, ARA." }, { "input": "These studies suggest that multitarget inhibition represents a new and valuable option to enhance efficacy or reduce side - effects in the treatment of inflammation and pain.", "output": "There is no related enetity." }, { "input": "This review focuses on the crosstalk within the three pathways of the ARA cascade ( cyclooxygenase ( COX ), lipoxygenase ( LOX ), and cytochrome P450 ( CYP450 ) ), and summarizes the current and future approaches of multitarget inhibitors for the treatment of eicosanoid driven inflammation and pain.", "output": "ARA, eicosanoid." }, { "input": "Time series analysis of oxidative stress response patterns in HepG2: A toxicogenomics approach.", "output": "There is no related enetity." }, { "input": "Oxidative stress plays an important role in chemically induced liver injury, however, our insight into molecular responses to different oxygen radicals is fragmentary.", "output": "oxygen." }, { "input": "Since these cellular responses will differ over time, examining time - dependent changes in gene expression, and correlating these with markers for oxidative stress, may provide new insights into responses to oxidants.", "output": "There is no related enetity." }, { "input": "We used the human hepatoma cell line HepG2 to investigate the effects of oxidative stress on the transcriptome level by micro - arrays at seven time points ( 0. 5, 1, 2, 4, 6, 8 and 24h ) following exposure to the oxidants menadione, hydrogen peroxide and tert - butyl hydroperoxide including the effects on cell cycle and apoptosis by flow cytometry, protein carbonyl formation by spectrophotometry and oxidative DNA damage by FPG - comet.", "output": "menadione, hydrogen peroxide, tert - butyl hydroperoxide, carbonyl." }, { "input": "In total, 3429 genes were differentially expressed, including 136 genes that were significantly modified by all oxidants.", "output": "There is no related enetity." }, { "input": "Time - dependent biological pathway analysis showed that these genes were particularly involved in inflammatory responses, cell cycle processes and glutathione signaling.", "output": "glutathione." }, { "input": "These responses were confirmed and supported by phenotypic anchoring to the different cellular endpoints.", "output": "There is no related enetity." }, { "input": "In addition, using an innovative temporal analysis we established an oxidative stress - related gene expression time cluster.", "output": "There is no related enetity." }, { "input": "Altogether, this study provides new insights in temporal oxidative stress mechanisms and demonstrates sequential cellular responses that may contribute to a better hazard identification and the mechanisms of toxicological responses in the liver induced by oxidative stress.", "output": "There is no related enetity." }, { "input": "Association of nephrolithiasis with metabolic syndrome and its components.", "output": "There is no related enetity." }, { "input": "OBJECTIVE: Both metabolic syndrome ( MetS ) and nephrolithiasis ( NL ) are common and clinically important disorders.", "output": "There is no related enetity." }, { "input": "Therefore, we conducted this study to assess the association of MetS and NL.", "output": "There is no related enetity." }, { "input": "MATERIALS / METHODS: Data were obtained from 116, 536 individuals who underwent health screening tests between January 2010 and December 2010 at a health promotion center in Seoul, Korea.", "output": "There is no related enetity." }, { "input": "All subjects were asked to respond to a questionnaire including medical history of each subject.", "output": "There is no related enetity." }, { "input": "Anthropometric and biochemical measurements were applied to each subject.", "output": "There is no related enetity." }, { "input": "Presence of NL was evaluated by an abdominal ultrasonography.", "output": "There is no related enetity." }, { "input": "The subjects were classified into MetS and non - MetS group according to the criteria for MetS ( National Cholesterol Education Program Adult Treatment Panel III ).", "output": "Cholesterol." }, { "input": "Compared to the non - MetS group, we estimated the Odds Ratios ( ORs ) and 95 % Confidence Intervals ( CIs ) of the presence of NL in the MetS group adjusting for age, serum levels of creatinine and uric acid, and past medical history of NL based on the multivariate logistic regression analysis.", "output": "creatinine, uric acid." }, { "input": "RESULTS: The prevalence of MetS was 15. 9 % ( N = 1129 / 7107 ) in the NL group, and 11. 2 % ( N = 12, 287 / 109, 429 ) in the non - NL group, respectively.", "output": "There is no related enetity." }, { "input": "After adjusting for the potential confounding factors, male MetS patients had a higher presence of NL than non - MetS subjects ( OR 1. 11; 95 % CI 1. 02 - 1. 20; p = 0. 01 ).", "output": "There is no related enetity." }, { "input": "Of MetS components, only high blood pressure ( BP ) was a significantly related factor to the presence of NL ( male; OR 1. 08; 95 % CI 1. 01 - 1. 15; p = 0. 043, female; OR 1. 24; 95 % CI 1. 08 - 1. 42; p = 0. 002 ).", "output": "There is no related enetity." }, { "input": "As the number MetS components increased, the presence of NL was significantly higher in male subjects ( P for trend < 0. 001 ), but not in female subjects ( P for trend = 0. 961 ).", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: We found that NL was associated with MetS and high BP.", "output": "There is no related enetity." }, { "input": "Arylglycine derivatives as potent transient receptor potential melastatin 8 ( TRPM8 ) antagonists.", "output": "Arylglycine." }, { "input": "A series of arylglycine - based analogs was synthesized and tested for TRPM8 antagonism in a cell - based functional assay.", "output": "arylglycine." }, { "input": "Following structure - activity relationship studies in vitro, a number of compounds were identified as potent TRPM8 antagonists and were subsequently evaluated in an in vivo pharmacodynamic assay of icilin - induced ' wet - dog ' shaking in which compound 12 was fully effective.", "output": "icilin." }, { "input": "TRPM8 antagonists of the type described here may be useful in treating pain conditions wherein cold hypersensitivity is a dominant feature.", "output": "There is no related enetity." }, { "input": "Design, synthesis and structure - activity relationship of rhenium 2 - arylbenzothiazoles as beta - amyloid plaque binding agents.", "output": "rhenium 2 - arylbenzothiazoles." }, { "input": "To continue our efforts toward the development of ( 99m ) Tc PiB analogs, we have synthesized 24 neutral and lipophilic Re ( as a surrogate of ( 99m ) Tc ) 2 - arylbenzothiazoles, and explored their structure - activity relationship for binding to A beta 1 - 40 fibrils.", "output": "( 99m ) Tc, Re, ( 99m ) Tc, 2 - arylbenzothiazoles." }, { "input": "These Re complexes were designed and synthesized via the integrated approach, so their ( 99m ) Tc analogs would have a greater chance of crossing the blood - brain barrier.", "output": "Re, ( 99m ) Tc." }, { "input": "While the lipophilicities ( logPC18 = 1. 59 - 3. 53 ) of these Re 2 - arylbenzothiazoles were all within suitable range, their binding affinities ( Ki = 30 - 617nM ) to A beta 1 - 40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2 - phenylbenzothiazole pharmacophore.", "output": "Re 2 - arylbenzothiazoles, 2 - phenylbenzothiazole." }, { "input": "For potential clinical applications, further refinement to obtain Re 2 - arylbenzothiazoles with better binding affinities ( < 10nM ) will likely be needed.", "output": "Re 2 - arylbenzothiazoles." }, { "input": "The integrated approach reported here to generate compact, neutral and lipophilic Re 2 - arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current A beta PET tracers to their ( 99m ) Tc analogs for more widespread application via the use of SPECT scanners.", "output": "Re 2 - arylbenzothiazoles, ( 99m ) Tc." }, { "input": "Steroidal constituents from the leaves of Hosta longipes and their inhibitory effects on nitric oxide production.", "output": "Steroidal, nitric oxide." }, { "input": "Hosta longipes ( FR. et SAV. ) MATSUMURA ( Liliaceae ) is an edible vegetable in Korea.", "output": "There is no related enetity." }, { "input": "This study was conducted with the aim of evaluating the potential of H. longipes as a functional food for the treatment of neurodegenerative diseases such as Alzheimer ' s disease and Parkinson ' s disease.", "output": "There is no related enetity." }, { "input": "In this respect, the study resulted in the identification of three new steroidal compounds, longipenane ( 1 ), longipenane 26 - O - beta - d - glucopyranoside ( 2 ) and neogitogenin 3 - O - alpha - l - rhamnopyranosyl - ( 1 --> 2 ) - O - [ beta - d - glucopyranosyl - ( 1 --> 4 ) ] - beta - d - galactopyranoside ( 3 ), along with two known steroidal saponins ( 4 and 5 ).", "output": "steroidal, longipenane, longipenane 26 - O - beta - d - glucopyranoside, neogitogenin 3 - O - alpha - l - rhamnopyranosyl - ( 1 --> 2 ) - O - [ beta - d - glucopyranosyl - ( 1 --> 4 ) ] - beta - d - galactopyranoside, steroidal saponins." }, { "input": "The identification and structural elucidation of these compounds were based on 1D and 2D NMR measurements, high - resolution FAB mass spectroscopy ( HR - FAB - MS ), and chemical methods.", "output": "There is no related enetity." }, { "input": "A proinflammatory mediator, nitric oxide ( NO ), in murine microglial BV - 2 cells was used to assess the anti - neuroinflammatory effect of the isolated compounds from H. longipes.", "output": "nitric oxide, NO." }, { "input": "Among them, compounds 4 and 5 showed strong inhibitory effects on NO production without high cell toxicity in lipopolysaccharide - activated BV - 2 cells ( IC50 = 17. 66 and 13. 16 mu M, respectively ).", "output": "NO." }, { "input": "Complexation of Hypocrellin A with Al3 + in water solution and the photodynamic therapy study.", "output": "Hypocrellin A, Al3 +." }, { "input": "The complex of Hypocrellin A with Al ( 3 + ) is prepared in water solution by a facile method.", "output": "Hypocrellin A, Al ( 3 + )." }, { "input": "The water - solubility and stability of complexes are improved.", "output": "There is no related enetity." }, { "input": "Irradiation of Al ( 3 + ) - HA complex results in higher efficient generation of singlet oxygen ( ( 1 ) O2 ) and photocleavage ability to CT DNA than HA.", "output": "Al ( 3 + ), oxygen, ( 1 ) O2." }, { "input": "In vitro studies have illustrated that the Al ( 3 + ) - HA complex has anti - cancer activity.", "output": "Al ( 3 + )." }, { "input": "Development of the simple and sensitive method for lipoxygenase assay in AOT / isooctane reversed micelles.", "output": "AOT, isooctane." }, { "input": "In this study, we investigated the possibility of reversed micelles, widely used as an enzyme reactor for lipases, for the determination of lipoxygenase activity.", "output": "There is no related enetity." }, { "input": "Although it is rapid and simple, reversed micelles have some limitations, such as interference by UV - absorbing materials and surfactant.", "output": "There is no related enetity." }, { "input": "Lipoxygenase activity in the reversed micelles was determined by reading the absorbance of the lipid hydroperoxidation product ( conjugated diene ) at 234 nm.", "output": "diene." }, { "input": "Among surfactants and organic media, AOT and isooctane were most effective for the dioxygenation of linoleic acid in reversed micelles.", "output": "AOT, isooctane, linoleic acid." }, { "input": "The strong absorbance of AOT in the UV region is a major obstacle for the direct application of the AOT / isooctane reversed micelles to lipoxygenase activity determination.", "output": "AOT, AOT, isooctane." }, { "input": "To prevent interference by AOT, we added an AOT removal step in the procedure for lipoxygenase activity determination in reversed micelles.", "output": "AOT, AOT." }, { "input": "The lipoxygenase activity was dependent on water content, and maximum activity was obtained at an R - value of 10.", "output": "There is no related enetity." }, { "input": "Nutritional and antinutritional evaluation of raw and processed Australian wattle ( Acacia saligna ) seeds.", "output": "There is no related enetity." }, { "input": "Raw and processed ( soaked, soaked / boiled, roasted ) wattle, Acacia saligna subspecies ( subsp. ) saligna, pruinescens, stolonifera and lindleyi, seeds were analysed for nutritional and antinutritional qualities.", "output": "There is no related enetity." }, { "input": "Whole wattle seeds mainly comprised proteins ( 27. 6 - 32. 6 % ) and carbohydrates ( 30. 2 - 36. 4 % ), which had approximately 12. 0 - 14. 0 % fat and 13. 0 - 15. 0 % crude fibre.", "output": "carbohydrates." }, { "input": "Palmitic ( 9. 6 % ), stearic ( 2. 0 % ), oleic ( 20. 0 % ) and linoleic ( 64. 3 % ) acids were identified by gas chromatography ( GC ) analysis.", "output": "Palmitic, stearic, oleic, linoleic." }, { "input": "Phenolic ( ~ 0. 2 % ), oxalate ( 2. 2 - 3. 4 % ) and saponin ( 2. 6 - 3. 0 % ) contents were fairly high; phytate content was low.", "output": "oxalate, saponin, phytate." }, { "input": "All untreated samples contained a high level of trypsin inhibitor ( 2474. 3 - 3271. 4 trypsin inhibitor units per gramme ( TIU / g ) of flour ) and low level of alpha - chymotrypsin inhibitor ( 120. 4 - 150. 6 CIU / g ).", "output": "There is no related enetity." }, { "input": "Soaking overnight following with 2 - min boiling led to a significant reduction of protease inhibitor activity.", "output": "There is no related enetity." }, { "input": "Roasting at 2 min or longer was sufficient to reduce both trypsin and alpha - chymotrypsin inhibitors to negligible values, also to reduce phytate, oxalate and saponin contents, simultaneously enhanced the nutritional values of wattle seeds.", "output": "phytate, oxalate, saponin." }, { "input": "Interaction and digestibility of phaseolin / polyphenol in the common bean.", "output": "polyphenol." }, { "input": "The polyphenols and phaseolin interaction in common bean varieties was studied.", "output": "polyphenols." }, { "input": "Raw beans of three different colours were analysed: black ( BRS Supremo ), brown ( BRS Pontal ) and white ( WAF - 75 ).", "output": "There is no related enetity." }, { "input": "Based on the phaseolin digestibility in vitro and phaseolin - polyphenol complexation obtained by SDS - PAGE on a 10 % polyacrylamide gel, it was observed that the polyphenols interfere with the digestibility of beans by decreasing the hydrolysis of phaseolin, especially in the darker ones.", "output": "polyphenol, polyacrylamide, polyphenols." }, { "input": "Furthermore it was possible to verify a difference in the electrophoretic pattern of phaseolin, indicating an interaction between phaseolin and polyphenols.", "output": "polyphenols." }, { "input": "Influence of seasonality on the chemical composition of oysters ( Crassostrea rhizophorae ).", "output": "There is no related enetity." }, { "input": "This paper aimed to evaluate the influence of seasonality on the chemical composition of oysters ( Crassostrea rhizophorae ).", "output": "There is no related enetity." }, { "input": "Samples were collected during summer and winter from the estuary and lagoon complex of the municipality of Barra de S a o Miguel, Alagoas, Brazil.", "output": "There is no related enetity." }, { "input": "Statistical differences ( p < 0. 05 ) between summer and winter were observed in relation to chemical composition.", "output": "There is no related enetity." }, { "input": "The oysters cultivated in the winter presented some nutritional advantages because of the higher levels of proteins and functional nutrients, such as the eicosapentaenoic - docosahexaenoic acid combination and percentages of polyunsaturated fatty acids ( n - 3 and n - 6 ), and the lower levels of saturated fatty acids.", "output": "eicosapentaenoic - docosahexaenoic acid, polyunsaturated fatty acids, saturated fatty acids." }, { "input": "Therefore, the animals in winter presented a higher content of cholesterol oxides.", "output": "cholesterol oxides." }, { "input": "The levels of cholesterol oxides found in these products during winter may encourage researchers to investigate the composition of oysters cultivated in different climates all over the world.", "output": "cholesterol oxides." }, { "input": "Simultaneous determination of 2 - naphthol and 1 - hydroxypyrene in fish and shellfish contaminated with crude oil by gas chromatography - mass spectrometry.", "output": "2 - naphthol, 1 - hydroxypyrene." }, { "input": "This paper describes a gas chromatography - mass spectrometric method of l - hydroxypyrene ( 1 - HOP ) and 2 - naphthol ( 2 - NAP ) in fish and shellfish.", "output": "l - hydroxypyrene, 1 - HOP, 2 - naphthol, 2 - NAP." }, { "input": "Alkali hydrolysis method in this study was chosen and optimized to the reaction condition for 90 min at 90 degrees C in a 2. 0M KOH solution.", "output": "KOH." }, { "input": "For five independent determinations at 0. 2 and 1. 0 mu g / kg, the coefficient of variation was less than 5. 1 %.", "output": "There is no related enetity." }, { "input": "This method was used to assess the long - term influence of spilled crude oil on marine ecosystems and analyze fifty - two shellfish samples taken in the near of the accident region of the Hebei Spirit oil spill.", "output": "There is no related enetity." }, { "input": "2 - NAP and 1 - HOP were detected in the mean concentration range of 0. 09 - 12. 42 and 0. 03 - 0. 06 mu g / kg, respectively.", "output": "2 - NAP, 1 - HOP." }, { "input": "2 - NAP was detected in a high concentration range in shellfishes gathered in 2 months after the accident and it decreased rapidly to 6 months after that.", "output": "2 - NAP." }, { "input": "The results showed that 2 - NAP might be an important biomarker in biota contaminated with crude oil.", "output": "2 - NAP." }, { "input": "In vitro biological activity of essential oils and isolated furanosesquiterpenes from the neglected vegetable Smyrnium olusatrum L.", "output": "furanosesquiterpenes." }, { "input": "( Apiaceae ).", "output": "There is no related enetity." }, { "input": "Smyrnium olusatrum, better known as Alexanders or wild celery, is a biennal herb used in cuisine for many centuries by Romans in many dishes, where it has now been replaced by celery.", "output": "There is no related enetity." }, { "input": "In order to provide additional evidences so that this forgotten vegetable can be reconsidered in the human diet, as well as in pharmaceutics, the essential oils obtained from different parts and its main isolated furanosesquiterpenes were in vitro biologically assayed for antiproliferative activity on human tumor cell lines by MTT assay, for antioxidant potential by DPPH, ABTS and FRAP assays, and for antimicrobial activity by the agar disc diffusion method.", "output": "furanosesquiterpenes, MTT, DPPH, ABTS." }, { "input": "The essential oils showed cytotoxic effects on tested human tumor cell lines, related to the furanosesquiterpenoid content; the IC ( 50 ) values on colon carcinoma, glioblastoma, and breast adenocarcinoma cells were 8. 51, 13. 35, and 14. 81 mu g / ml, respectively.", "output": "There is no related enetity." }, { "input": "Isofuranodiene and 1 beta - acetoxyfuranoeudesm - 4 ( 15 ) - ene resulted the most active constituents.", "output": "Isofuranodiene, 1 beta - acetoxyfuranoeudesm - 4 ( 15 ) - ene." }, { "input": "The essential oils possessed also radical scavenging activity.", "output": "There is no related enetity." }, { "input": "Quantification of organic acids using voltammetric tongues.", "output": "There is no related enetity." }, { "input": "Recently, electronic tongues ( ET ) have appeared as an excellent alternative to traditional techniques for the evaluation of food quality and processes.", "output": "There is no related enetity." }, { "input": "ET systems are based on arrays of low selectivity sensors that are simultaneously sensitive to several components in a measured sample ( cross - sensitivity ).", "output": "There is no related enetity." }, { "input": "The aim of this study was to determine the ability of an ET based on pulse voltammetry to quantify organic acids ( ascorbic, citric and malic acids ) in simple ( SS ) and binary solutions ( BS ) using different electrodes.", "output": "ascorbic , citric and malic acids." }, { "input": "The most significant electrodes for ascorbic acid prediction were Ni and Ag for SS, and Ag and Ir for BS where positive pulses were more suitable than negative ones.", "output": "ascorbic acid, Ni, Ag, Ag, Ir." }, { "input": "The prediction of citric and malic acids in SS and BS were suitable using Ir, Rh, Pt, Ag and Cu electrodes, using both positive and negative pulses.", "output": "citric and malic acids, Ir, Rh, Pt, Ag, Cu." }, { "input": "Quality enhancement in refrigerated red drum ( Sciaenops ocellatus ) fillets using chitosan coatings containing natural preservatives.", "output": "There is no related enetity." }, { "input": "The present work was undertaken to examine the influence of grape seed extract ( GS ) and tea polyphenols ( TP ), as natural preservatives, combined with chitosan ( Ch ), on the quality of red drum ( Sciaenops ocellatus ) fillets during refrigerated storage.", "output": "polyphenols." }, { "input": "Two different treatments ( Ch + GS and Ch + TP ) and a control were prepared.", "output": "There is no related enetity." }, { "input": "The samples were stored ( 4 +/- 1 degrees C ) for 20 days and the sampling was done at 0, 4, 8, 12, 16, 20 days.", "output": "There is no related enetity." }, { "input": "Microbiological, physicochemical and sensory attributes were periodically assessed.", "output": "There is no related enetity." }, { "input": "The results indicated that the two pretreatments could more effectively maintain quality and could extend the shelf life by 6 - 8 days compared with the control group during refrigerated storage.", "output": "There is no related enetity." }, { "input": "Multi - class method for determination of veterinary drug residues and other contaminants in infant formula by ultra performance liquid chromatography - tandem mass spectrometry.", "output": "There is no related enetity." }, { "input": "A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed.", "output": "There is no related enetity." }, { "input": "The method comprised of extraction with acetonitrile, clean - up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry ( UPLC - ESI - MS - MS ) using multiple reaction monitoring ( MRM ) mode.", "output": "acetonitrile." }, { "input": "Most fat materials in acetonitrile extract were eliminated by low temperature clean - up.", "output": "acetonitrile." }, { "input": "The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes ( avermectins, ionophores ).", "output": "avermectins." }, { "input": "Average recoveries for spiked infant formula were in the range from 57 % to 147 % with associated RSD values between 1 % and 28 %.", "output": "There is no related enetity." }, { "input": "For over 80 % of the analytes, the recoveries were between 70 % and 120 % with RSD values in the range of 1 - 15 %.", "output": "There is no related enetity." }, { "input": "The limits of quantification ( LOQs ) were from 0. 01 to 5 mu g / kg, which were usually sufficient to verify the compliance of products with legal tolerances.", "output": "There is no related enetity." }, { "input": "Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time.", "output": "There is no related enetity." }, { "input": "Comparative analysis of nutritional compositions of transgenic high iron rice with its non - transgenic counterpart.", "output": "iron." }, { "input": "Iron is an essential micronutrient for human nutrition and polished rice contains very low amount of iron.", "output": "Iron, iron." }, { "input": "Rice with high iron content in seed endosperm has been developed by insertion of soybean ferritin gene under the control of the endosperm specific glutelin promoter into the genome of indica rice line IR68144.", "output": "iron." }, { "input": "The nutritional composition of the brown and milled rice grain has been compared with that of the non - transgenic rice of the same variety.", "output": "There is no related enetity." }, { "input": "In this study, the nutritional components, as well as the anti - nutrient levels, were measured.", "output": "There is no related enetity." }, { "input": "Our studies established that apart from the increased level of iron and zinc in transgenic seeds, the nutritional quality of both the brown and milled rice grains from the transgenic line was substantially equivalent to that of the non - transgenic rice plants.", "output": "iron, zinc." }, { "input": "The result clearly shows that the measured amounts of the nutritional components are well within the range of values reported for other commercial lines.", "output": "There is no related enetity." }, { "input": "Determination of ethylenediaminetetraacetic acid in foods by reversed - phase high - performance liquid chromatography.", "output": "ethylenediaminetetraacetic acid." }, { "input": "A convenient HPLC method for the quantitative determination of EDTA in foods was developed.", "output": "EDTA." }, { "input": "EDTA in food samples was easily extracted with water by ultrasonication.", "output": "EDTA." }, { "input": "After converting to Fe ( III ) complex in the presence of Fe ( III ) ions, EDTA was separated on a reversed - phase C30 column and detected with ultraviolet detection ( 260 nm ).", "output": "Fe ( III ), Fe ( III ), EDTA." }, { "input": "Citrate and malate, which are present in many foods, also formed Fe ( III ) complexes but they did not interfere the chromatographic detection of EDTA.", "output": "Citrate, malate, Fe ( III ), EDTA." }, { "input": "The method allowed determination of EDTA in foods at concentrations as low as 0. 01 mmol / kg.", "output": "EDTA." }, { "input": "Good recoveries ( 95. 2 - 101 % ) were obtained by the standard addition method on four samples with high repeatability ( RSD, 0. 8 - 3. 4 % ).", "output": "There is no related enetity." }, { "input": "The method was successfully applied to the analysis of EDTA in carbonated drinks, jellies, canned beans, canned corn and food supplements.", "output": "EDTA." }, { "input": "Increase in antioxidant and anticancer effects of ginsenoside Re - lysine mixture by Maillard reaction.", "output": "ginsenoside Re, lysine." }, { "input": "Ginsenosides are the main active components of Panax ginseng.", "output": "Ginsenosides." }, { "input": "Structural changes in diol type ginsenosides along with generation of Maillard reaction products ( MRPs ) are strongly associated with increased free radical - scavenging activities.", "output": "diol, ginsenosides." }, { "input": "Ginsenoside Re, one of the major triol type ginsenosides of P. ginseng, possesses a hydrophobic four - ring steroid - like structure with hydrophilic sugar moieties at carbons - 3 and - 20.", "output": "Ginsenoside Re, triol, ginsenosides, sugar, carbons." }, { "input": "The aim of the present study was to identify changes in the structure, antioxidant and anticancer effects of ginsenoside Re upon Maillard reaction.", "output": "ginsenoside Re." }, { "input": "Ginsenoside Re was transformed into less - polar ginsenosides, namely Rg ( 2 ), Rg ( 6 ) and F ( 4 ) by heat - processing.", "output": "Ginsenoside Re, ginsenosides , namely Rg ( 2 ) , Rg ( 6 ) and F ( 4 )." }, { "input": "Free radical - scavenging activity of the ginsenoside Re - lysine mixture increased upon heat processing.", "output": "ginsenoside Re, lysine." }, { "input": "This improved free radical - scavenging activity mediated by antioxidant MRPs, which were generated through Maillard reaction of a glucosyl moiety separated from carbon - 20 of ginsenoside Re and lysine.", "output": "glucosyl, carbon, ginsenoside Re, lysine." }, { "input": "The increased anticancer effect of ginsenoside Re - lysine mixture upon heat processing was mainly derived from the generation of less - polar ginsenosides through the regulation of Bcl - 2 and Bax, as well as caspase - dependent apoptotic pathway.", "output": "ginsenoside Re, lysine, ginsenosides." }, { "input": "These results reported here have shed significant new lights on the mechanism of increased antioxidant and anticancer effects of P. ginseng upon heat processing.", "output": "There is no related enetity." }, { "input": "Effects of twin - screw extrusion on soluble dietary fibre and physicochemical properties of soybean residue.", "output": "There is no related enetity." }, { "input": "Extrusion cooking technology was applied for soluble dietary fibre extraction from soybean residue.", "output": "There is no related enetity." }, { "input": "Response surface methodology ( RSM ) was used to optimise the effects of extrusion parameters, namely extrusion temperature ( 90 - 130 degrees C ), feed moisture ( 25 - 35 % ) and screw speed ( 160 - 200 rpm ) on the content of soluble dietary fibre.", "output": "There is no related enetity." }, { "input": "According to the regression coefficients significance of the quadratic polynomial model, the optimum extrusion parameters were as follows: extrusion temperature, 115 degrees C; feed moisture, 31 %; and screw speed, 180 rpm.", "output": "There is no related enetity." }, { "input": "Under these conditions, the soluble dietary fibre content of soybean residue could reach to 12. 65 % which increased 10. 60 % compared with the unextruded soybean residue.", "output": "There is no related enetity." }, { "input": "In addition, the dietary fibre in extrude soybean residue had higher water retention capacity, oil retention capacity and swelling capacity than those of dietary fibre in unextruded soybean residue.", "output": "There is no related enetity." }, { "input": "Adhesive microbeads for the targeting delivery of anticaries agents of vegetable origin.", "output": "There is no related enetity." }, { "input": "The formulation of quinic acid, a food constituent demonstrating potential anticaries and antigingivitis properties, was investigated in an adhesive microparticulate delivery system with the goal of improving its effect by prolonging its residence time at the site of action.", "output": "quinic acid." }, { "input": "Alginate and chitosan were selected as mucoadhesive polymers.", "output": "There is no related enetity." }, { "input": "The microspheres were prepared by coacervation.", "output": "There is no related enetity." }, { "input": "Different types of alginates, polymers blends and crosslinking agent concentrations were considered and evaluated.", "output": "There is no related enetity." }, { "input": "The best results in terms of encapsulation efficiency, in vitro active agent release profile and in vitro adhesive properties, both to oral mucosa and to teeth surface, were obtained with a blend of Alginate Protanal LF200S: Alginate Protanal LF120LS 1: 1. 5 w / w, 0. 1M CaCl ( 2 ), and chitosan coating, prepared by a one - step complex coacervation method.", "output": "There is no related enetity." }, { "input": "This microparticulate delivery system showed prolonged release of quinic acid, and could be used as an active component in chewing gums or mouthwashes for both caries and gingivitis prevention.", "output": "quinic acid." }, { "input": "Odour quality of spray - dried hens ' egg powders: the influence of composition, processing and storage conditions.", "output": "There is no related enetity." }, { "input": "This study aimed to determine whether compositional or processing parameters have an influence on the odour quality of egg powders.", "output": "There is no related enetity." }, { "input": "The parameters tested were: whole egg vs. egg yolk, polyunsaturated fatty acid ( PUFA ) enrichment, spray - drying temperature ( 160 degrees C vs. 180 degrees C ), production scale ( industrial vs. pilot plant ), storage temperature ( 15 degrees C vs. 30 degrees C ) and time ( 1, 2, 4 and 8 months ).", "output": "polyunsaturated fatty acid, PUFA." }, { "input": "The quality of egg powders was evaluated by sensory analysis using free sorting, and by gas chromatography coupled to mass spectrometry and olfactometry.", "output": "There is no related enetity." }, { "input": "PUFA enrichment and spray - drying temperature do not affect the odour of egg yolk powders.", "output": "PUFA." }, { "input": "There are significant differences between the odour of whole - egg and egg - yolk powders as well as between powders produced on an industrial scale or in a pilot plant.", "output": "There is no related enetity." }, { "input": "An increase in the odour intensity of egg powders was observed during storage, while unpleasant odours were perceived when the egg powders were stored at 30 degrees C.", "output": "There is no related enetity." }, { "input": "Quantification by UHPLC of total individual polyphenols in fruit juices.", "output": "polyphenols." }, { "input": "The present work proposes a new UHPLC - PDA - fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28 - min chromatogram.", "output": "polyphenols." }, { "input": "The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices.", "output": "anthocyanins." }, { "input": "Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols ( 23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan - 3 - ols and 2 stilbenes ).", "output": "polyphenols, anthocyanins, flavonols, hydroxybenzoic acids, hydroxycinnamic acids, flavanones, dihydrochalcones, flavan - 3 - ols, stilbenes." }, { "input": "One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice.", "output": "polyphenol, polyphenol." }, { "input": "Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols ( TIP ).", "output": "polyphenols, polyphenols." }, { "input": "A good correlation ( r ( 2 ) = 0. 966 ) was observed between calculated TIP, and total polyphenols ( TP ) determined by the well - known colorimetric Folin - Ciocalteu method.", "output": "polyphenols." }, { "input": "In this work, the higher TIP value corresponded to bilberry juice ( 607. 324 mg / 100mL fruit juice ) and the lower to orange juice ( 32. 638 mg / 100mL fruit juice ).", "output": "There is no related enetity." }, { "input": "This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices.", "output": "polyphenols." }, { "input": "Effects of amylosucrase treatment on molecular structure and digestion resistance of pre - gelatinised rice and barley starches.", "output": "There is no related enetity." }, { "input": "Structural modification of rice and barley starches with Neisseria polysaccharea amylosucrase ( NpAS ) was conducted, and relationship between structural characteristics and resistant starch ( RS ) contents of NpAS - treated starches was investigated.", "output": "There is no related enetity." }, { "input": "Pre - gelatinised rice and barley starches were treated with NpAS.", "output": "There is no related enetity." }, { "input": "NpAS - treated starches were characterised with respect to morphology, X - ray diffraction pattern, amylopectin branch - chain distribution, and RS content, and their structural characteristics were correlated to RS contents.", "output": "There is no related enetity." }, { "input": "Regardless of amylose contents of native starches, NpAS - treated ( relative to native ) starches possessed lower and higher proportions of shorter ( DP 6 - 12 ) and intermediate ( DP 13 - 36 ) amylopectin ( AP ) branch - chains, respectively.", "output": "There is no related enetity." }, { "input": "RS contents were higher for NpAS - treated starches relative to native starches, and maximum RS contents were obtained for NpAS - treated starches of waxy rice and barley genotypes.", "output": "There is no related enetity." }, { "input": "Amylose contents were not associated with RS contents of NpAS - treated starches.", "output": "There is no related enetity." }, { "input": "However, shorter and intermediate AP branch - chain portions were negatively and positively correlated to RS contents of NpAS - treated starches, respectively.", "output": "There is no related enetity." }, { "input": "Simultaneous detection of multiple adulterants in dry milk using macro - scale Raman chemical imaging.", "output": "There is no related enetity." }, { "input": "The potential of Raman chemical imaging for simultaneously detecting multiple adulterants in milk powder was investigated.", "output": "There is no related enetity." }, { "input": "Potential chemical adulterants, including ammonium sulphate, dicyandiamide, melamine, and urea, were mixed together into skim dry milk in the concentration range of 0. 1 - 5. 0 % for each adulterant.", "output": "ammonium sulphate, dicyandiamide, melamine, urea." }, { "input": "Using a 785 - nm laser, a Raman imaging system acquired hyperspectral images in the wavenumber range of 102 - 2538 cm ( - 1 ) for a 25 x 25 mm ( 2 ) area of each mixture sample, with a spatial resolution of 0. 25 mm.", "output": "There is no related enetity." }, { "input": "Self - modelling mixture analysis ( SMA ) was used to extract pure component spectra, by which the four types of the adulterants were identified at all concentration levels based on their spectral information divergence values to the reference spectra.", "output": "There is no related enetity." }, { "input": "Raman chemical images were created using the contribution images from SMA, and their use to effectively visualise identification and spatial distribution of the multiple adulterant particles in the dry milk was demonstrated.", "output": "There is no related enetity." }, { "input": "Alteration of alpha - tocopherol - associated protein ( TAP ) expression in human breast epithelial cells during breast cancer development.", "output": "alpha - tocopherol." }, { "input": "Breast cancer is the most common malignancy among women and has an age - specific incidence profile.", "output": "There is no related enetity." }, { "input": "Over the last decade, many studies have demonstrated the anticancer activity of alpha - tocopherol, the main and most active form of natural vitamin E.", "output": "alpha - tocopherol, vitamin E." }, { "input": "alpha - Tocopherol - associated protein ( TAP ) was found to be one of the major alpha - tocopherol binding proteins in human serum and in liver, brain, and prostate tissues.", "output": "alpha - Tocopherol, alpha - tocopherol." }, { "input": "In this study, we found that reduced TAP expression was significantly correlated with Her2 / neu receptor expression, breast cancer stage and nodal stage in paired normal and cancerous breast tissue samples from 93 patients using real - time PCR analysis.", "output": "There is no related enetity." }, { "input": "A cell viability assay showed that alpha - tocopheryl succinate ( alpha - TOS ), a synthetic derivative of alpha - tocopherol, enhanced the cells ' sensitivity to doxorubicin and resulted in a reduction in cell viability in breast cancers.", "output": "alpha - tocopheryl succinate, alpha - TOS, alpha - tocopherol, doxorubicin." }, { "input": "Taken together, these data suggest that the use of vitamin E or its analogue as a dietary supplement may be beneficial for the treatment of cancer.", "output": "vitamin E." }, { "input": "Neuroprotective effects of oral gallic acid against oxidative stress induced by 6 - hydroxydopamine in rats.", "output": "gallic acid, 6 - hydroxydopamine." }, { "input": "Free radical - induced neural damage is implicated in neurodegenerative diseases and antioxidants have protective activity.", "output": "There is no related enetity." }, { "input": "In the present study, we examined the effect of gallic acid ( GA; 50, 100 and 200mg / kg, p. o. for 10 days ) on memory deficit and cerebral oxidative stress induced by 6 - hydroxydopamine ( 6 - OHDA; 8 mu g / 2 mu L ) injected into the medial forebrain bundle ( MFB, full nigral lesion ) as an animal model of Parkinson ' s disease ( PD ).", "output": "gallic acid, 6 - hydroxydopamine, 6 - OHDA." }, { "input": "The results showed that 6 - OHDA significantly reduced the passive avoidance memory performance, non - enzymatic ( total thiol ) and enzymatic [ glutathione peroxidase ( GPx ) ] antioxidant contents and increased the level of malondialdehyde ( MDA ) in the hippocampus and striatum of vehicle - treated group as compared to sham - operated rats.", "output": "6 - OHDA, thiol, glutathione, malondialdehyde, MDA." }, { "input": "Furthermore, oral administration of GA significantly increased the passive avoidance memory, total thiol and GPx contents and also decreased MDA levels in the above tissues.", "output": "thiol, MDA." }, { "input": "The results suggest that GA has neuroprotective activity against 6 - OHDA - induced oxidative stress via enhancement of cerebral antioxidant defence.", "output": "6 - OHDA." }, { "input": "Cannabisin B induces autophagic cell death by inhibiting the AKT / mTOR pathway and S phase cell cycle arrest in HepG2 cells.", "output": "Cannabisin B." }, { "input": "This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells.", "output": "cannabisin B." }, { "input": "The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis.", "output": "cannabisin B." }, { "input": "Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations.", "output": "cannabisin B." }, { "input": "Cannabisin B - induced changes in cell viability were completely inhibited by pre - treatment with 3 - methyladenine ( 3 - MA ), indicating that the induction of autophagy by cannabisin B caused cell death.", "output": "Cannabisin B, 3 - methyladenine, 3 - MA, cannabisin B." }, { "input": "Additionally, cannabisin B induced S phase cell cycle arrest in a dose - dependent manner.", "output": "cannabisin B." }, { "input": "Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down - stream targets of the mammalian target of rapamycin ( mTOR ).", "output": "cannabisin B, rapamycin." }, { "input": "These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.", "output": "cannabisin B." }, { "input": "Vitamin D and 25 - hydroxyvitamin D determination in meats by LC - IT - MS.", "output": "Vitamin D, 25 - hydroxyvitamin D." }, { "input": "This paper reports a method for the rapid, sensitive and simultaneous analysis of vitamin D ( Vit D ) and 25 - hydroxyvitamin D ( 25OH - Vit D ) in meats.", "output": "vitamin D, Vit D, 25 - hydroxyvitamin D, 25OH - Vit D." }, { "input": "Samples were saponified and underwent solid phase extraction with analysis by normal phase liquid chromatography ( LC ) with ion trap mass spectroscopy ( IT - MS ), using positive polarity atmospheric pressure chemical ionisation ( APCI ).", "output": "There is no related enetity." }, { "input": "Limits of detection ( LOD ) and quantification ( LOQ ) for Vit D and 25OH - Vit D were 0. 03 and 0. 05 mu g / 100g respectively.", "output": "Vit D, 25OH - Vit D." }, { "input": "Deuterium labelled Vit D and 25OH - Vit D internal standards were added as surrogates prior to saponification, correcting for extraction inefficiencies and potential MS matrix enhancement or suppression effects.", "output": "Deuterium, Vit D, 25OH - Vit D." }, { "input": "Recoveries using internal / surrogate standard correction ranged from 80 % to 100 % for all vitamers.", "output": "There is no related enetity." }, { "input": "Measurement uncertainty ranged from 6 % to 15 % for all vitamers in this method.", "output": "There is no related enetity." }, { "input": "This process required only 7. 5 g of sample per extraction and a batch of 28 extractions could be completed in six hours.", "output": "There is no related enetity." }, { "input": "Simultaneous determination of aflatoxin B ( 1 ) and ochratoxin A in licorice roots and fritillary bulbs by solid - phase extraction coupled with high - performance liquid chromatography - tandem mass spectrometry.", "output": "aflatoxin B ( 1 ), ochratoxin A." }, { "input": "An effective method was developed for screening licorice roots and fritillary bulbs for contamination by aflatoxin B ( 1 ) and ochratoxin A using high - performance liquid chromatography connected to tandem mass spectrometry ( HPLC - MS / MS ).", "output": "aflatoxin B ( 1 ), ochratoxin A." }, { "input": "The samples were pre - concentrated and purified using solid - phase extraction, which provided satisfactory results.", "output": "There is no related enetity." }, { "input": "The separation was performed on a Waters Xbridge ( TM ) C18 column with a linear gradient of acetonitrile - water containing 5mM ammonium acetate.", "output": "acetonitrile, ammonium acetate." }, { "input": "The MS spectrum was acquired in positive mode with both single quadrupole ( Q1 ) and multiple reaction monitoring ( MRM ).", "output": "There is no related enetity." }, { "input": "The optimised method offered a good linear correlation ( r ( 2 ) > 0. 9967 ), excellent precision ( RSD < 2. 83 % ) and acceptable recovery ( from 92. 78 to 105. 37 % ).", "output": "There is no related enetity." }, { "input": "The limits of detection ( LOD ) and the limits of quantification ( LOQ ) were less than 0. 024 mu g / kg and 0. 095 mu g / kg, respectively.", "output": "There is no related enetity." }, { "input": "The validated method was successfully applied to the rapid screening for AFB ( 1 ) and OTA in licorice roots and fritillary bulbs.", "output": "There is no related enetity." }, { "input": "Peyer ' s patch - mediated intestinal immune system modulating activity of pectic - type polysaccharide from peel of Citrus unshiu.", "output": "There is no related enetity." }, { "input": "An intestinal immune system modulating polysaccharide ( CUI - 3IIb - 3 - 2, 18kDa ) was purified from Citrus unshiu peel.", "output": "There is no related enetity." }, { "input": "CUI - 3IIb - 3 - 2 mainly comprised GalA, GlcA, Ara, Gal and Rha, and it consisted of 4 - linked GalA, terminal Araf, 4 - or 5 - linked / 3, 4 - or 3, 5 - branched Ara, terminal Gal, and 2 - linked / 2, 4 - branched Rha.", "output": "GalA, GlcA, Ara, Gal, Rha, GalA, Araf, Ara, Gal, Rha." }, { "input": "After CUI - 3IIb - 3 - 2 digestion by endo - alpha - d - ( 1 --> 4 ) - polygalacturonase, its hydrolysate was fractionated into PG - 1 and PG - 2.", "output": "There is no related enetity." }, { "input": "Methylation analyses of PG - 1 and PG - 2 using base - catalysed beta - elimination suggested that CUI - 3IIb - 3 - 2 be assumed as pectic - type polysaccharide.", "output": "There is no related enetity." }, { "input": "Since the activities of PG - 1 and PG - 2 were potently decreased, the whole polysaccharide structure of CUI - 3IIb - 3 - 2 would be essential to maintain the activity.", "output": "There is no related enetity." }, { "input": "Meanwhile, when CUI - 3IIb was orally administered in mice, bone marrow cell proliferation and GM - CSF / IL - 6 production from Peyer ' s patch cell were significantly higher ( 1. 76 - and 2. 03 / 2. 51 - fold, respectively ) than a saline.", "output": "There is no related enetity." }, { "input": "Therefore, a pectic - type polysaccharide from citrus peel could stimulate Peyer ' s patches and produce hematopoietic growth factors resulted in bone marrow cell proliferation.", "output": "There is no related enetity." }, { "input": "An electrospray ionisation - mass spectrometry screening of triacylglycerols in developing cultivated and wild peanut kernels ( Arachis hypogaea L. ).", "output": "triacylglycerols." }, { "input": "The accumulation of triacylglycerols during the development of three varieties of peanuts was monitored in two Tunisian cultivated peanut ( Trabelsia ( AraT ) and Chounfakhi ( AraC ) ) and one wild Tunisian peanut ( Arbi ( AraA ) ).", "output": "triacylglycerols." }, { "input": "The presence of TAGs composed of rare fatty acid residues such as hexacosanoic acid ( C ( 23: 0 ) ) and heneicosanoic acid ( C ( 21: 0 ) ) among the triacylglycerols C ( 23: 0 ) LL, C ( 23: 0 ) OO and C ( 21: 0 ) LL was noted.", "output": "fatty acid, hexacosanoic acid, heneicosanoic acid, triacylglycerols." }, { "input": "The major molecular species of triacylglycerol detected in the three peanut varieties were dioleoyl linoleoyl ( OOL ), 1, 2, 3 - trioleyl ( OOO ), 1, 2 - dioleyl - 3 - palmitoyl ( POO ), 1, 2 - dilinoleoyl - 3 - oleyl ( OLL ) and 1 - oleoyl - 2 - linoleoyl - 3 - linolenoyl ( OLLn ).", "output": "triacylglycerol, dioleoyl linoleoyl, OOL, 1 , 2 , 3 - trioleyl, OOO, 1 , 2 - dioleyl - 3 - palmitoyl, POO, 1 , 2 - dilinoleoyl - 3 - oleyl, OLL, 1 - oleoyl - 2 - linoleoyl - 3 - linolenoyl, OLLn." }, { "input": "The TAG composition and content were significantly different among the three peanut varieties.", "output": "There is no related enetity." }, { "input": "The three major TAGs were OOL ( 20. 6 % ), OOO ( 15. 6 % ) and OLLn ( 13. 2 % ) in AraA; OOL ( 21. 4 % ), OOO ( 20. 1 % ) and POO ( 17. 5 % ) in AraC and finally OLL ( 20. 7 % ), OOO ( 19. 8 % ) and OLL ( 17. 7 % ) in AraT.", "output": "OOO, OOL, OOO, POO, OLL, OOO, OLL." }, { "input": "Film forming ability of gelatins from splendid squid ( Loligo formosana ) skin bleached with hydrogen peroxide.", "output": "hydrogen peroxide." }, { "input": "Properties of gelatin films from splendid squid ( Loligo formosana ) skin bleached with hydrogen peroxide ( H ( 2 ) O ( 2 ) ) at various concentrations ( 0 - 8 % w / v ) were investigated.", "output": "hydrogen peroxide, H ( 2 ) O ( 2 )." }, { "input": "Tensile strength ( TS ) and water vapour permeability ( WVP ) of films decreased, but elongation at break ( EAB ) increased ( p < 0. 05 ) as the concentration of H ( 2 ) O ( 2 ) increased.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Among all films, that prepared from gelatin with 2 % H ( 2 ) O ( 2 ) bleaching showed the lowest Delta E ( * ) - value ( total colour difference ), which was concomitant with the highest L ( * ) - value ( lightness ).", "output": "H ( 2 ) O ( 2 )." }, { "input": "Generally, higher concentration of H ( 2 ) O ( 2 ) resulted in increased b ( * ) - value ( yellowness ) of resulting films.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Electrophoretic study revealed that alpha - chains of gelatin in films became lowered with increasing H ( 2 ) O ( 2 ) concentrations used for bleaching.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Thermogravimetric analysis indicated that heat susceptibility and weight loss of different films varied with H ( 2 ) O ( 2 ) concentrations.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Rougher surface was obtained in gelatin films prepared from skin bleached with H ( 2 ) O ( 2 ) concentrations above 4 %.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Thus, the concentrations of H ( 2 ) O ( 2 ) used for bleaching of squid skin prior to gelatin extraction directly affected the properties of corresponding gelatin films.", "output": "H ( 2 ) O ( 2 )." }, { "input": "Geographical origin identification of Romanian wines by ICP - MS elemental analysis.", "output": "There is no related enetity." }, { "input": "Trace elemental analysis, besides its ability to determine stable isotopes ratios, represents a possible complementary tool useful to differentiate wines based on their regional origins.", "output": "There is no related enetity." }, { "input": "Wines and their provenance soils from two major wine producing areas in Southeast Romania ( ' Valea Calugareasca ' and ' Murfatlar ' ), and also wine from the region of Moldova ( Eastern Romania ) were analyzed by inductively coupled plasma mass spectrometry ( ICP - MS ), and statistical data of elemental composition was used to differentiate these wines according to grape type and geographical origin.", "output": "There is no related enetity." }, { "input": "Moreover, this study gathers relevant elemental trace composition of wines produced in most important Romanian vineyards, thus offering a useful wine differentiation tool by their production district.", "output": "There is no related enetity." }, { "input": "The results show that the differentiation of Romanian wines according to their provenance is based on the following main elements: Ni, Ag, Cr, Sr, Zn, and Cu for Valea Calugareasca, Rb, Zn, and Mn for Murfatlar, and Pb, Co, and V for Moldova.", "output": "Ni, Ag, Cr, Sr, Zn, Cu, Rb, Zn, Mn, Pb, Co, V." }, { "input": "Quantification of vitamin D3 and its hydroxylated metabolites in waxy leaf nightshade ( Solanum glaucophyllum Desf. ), tomato ( Solanum lycopersicum L. ) and bell pepper ( Capsicum annuum L. ).", "output": "vitamin D3." }, { "input": "Changes in vitamin D ( 3 ) and its metabolites were investigated following UVB - and heat - treatment in the leaves of Solanum glaucophyllum Desf., Solanum lycopersicum L. and Capsicum annuum L.", "output": "vitamin D ( 3 )." }, { "input": "The analytical method used was a sensitive and selective liquid chromatography electrospray ionisation tandem mass spectrometry ( LC - ESI - MS / MS ) method including Diels - Alder derivatisation.", "output": "There is no related enetity." }, { "input": "Vitamin D ( 3 ) and 25 - hydroxy vitamin D ( 3 ) were found in the leaves of all plants after UVB - treatment.", "output": "Vitamin D ( 3 ), 25 - hydroxy vitamin D ( 3 )." }, { "input": "S. glaucophyllum had the highest content, 200 ng vitamin D ( 3 ) / g dry weight and 31 ng 25 - hydroxy vitamin D ( 3 ) / g dry weight, and was the only plant that also contained 1, 25 dihydroxy vitamin D ( 3 ) in both free ( 32 ng / g dry weight ) and glycosylated form ( 17 ng / g dry weight ).", "output": "vitamin D ( 3 ), 25 - hydroxy vitamin D ( 3 ), 1 , 25 dihydroxy vitamin D ( 3 )." }, { "input": "Purification and characterisation of a novel chitinase from persimmon ( Diospyros kaki ) with antifungal activity.", "output": "There is no related enetity." }, { "input": "A novel chitinase from the persimmon fruit was isolated, purified and characterised in this report.", "output": "There is no related enetity." }, { "input": "The Diospyros kaki chitinase ( DKC ) was found to be a monomer with a molecular mass of 29 kDa.", "output": "There is no related enetity." }, { "input": "It exhibited optimal activity at pH 4. 5 with broad pH stability from pH 4. 0 - 9. 0.", "output": "There is no related enetity." }, { "input": "It has an optimal temperature of 60 degrees C and thermostable up to 60 degrees C when incubated for 30 min.", "output": "There is no related enetity." }, { "input": "The internal peptide sequences of DKC showed similarity with other reported plant chitinases.", "output": "There is no related enetity." }, { "input": "It has the ability to hydrolyse colloidal chitin into chito - oligomers such as chitotriose, chitobiose and into its monomer N - acetylglucosamine.", "output": "chitotriose, chitobiose, N - acetylglucosamine." }, { "input": "It can be used to degrade chitin waste into useful products such as chito - oligosacchaarides.", "output": "There is no related enetity." }, { "input": "DKC exhibited antifungal activity towards pathogenic fungus Trichoderma viride.", "output": "There is no related enetity." }, { "input": "Chitinases with antifungal property can be used as biocontrol agents replacing chemical fungicides.", "output": "There is no related enetity." }, { "input": "Development of apple certified reference material for quantification of organophosphorus and pyrethroid pesticides.", "output": "organophosphorus, pyrethroid." }, { "input": "An apple certified reference material for the analysis of pesticide residues was issued by the National Metrology Institute of Japan.", "output": "There is no related enetity." }, { "input": "Organophosphorus and pyrethroid pesticides were sprayed on apples, and these were used as raw materials of certified reference material.", "output": "Organophosphorus, pyrethroid." }, { "input": "The harvested apples were cut into small pieces, freeze - dried, pulverized, sieved, placed into 200 brown glass bottles ( 3g each ), and sterilized by gamma - irradiation.", "output": "There is no related enetity." }, { "input": "Stability and homogeneity assessment was performed, and the relative uncertainties due to instability ( for an expiry date of 32 months ) and inhomogeneity were 10. 3 - 25. 0 % and 4. 0 - 6. 8 %, respectively.", "output": "There is no related enetity." }, { "input": "The characterization was carried out using multiple analytical methods to ensure the reliability of analytical results; the values of target pesticides were obtained by isotope dilution mass spectrometry.", "output": "There is no related enetity." }, { "input": "Certified values were 2. 28 +/- 0. 82 mg / kg for diazinon, 3. 14 +/- 0. 79 mg / kg for fenitrothion, 1. 55 +/- 0. 81 mg / kg for cypermethrin, and 2. 81 +/- 0. 70 mg / kg for permethrin.", "output": "diazinon, fenitrothion, cypermethrin, permethrin." }, { "input": "Antioxidant and antimicrobial activity of xylan - chitooligomer - zinc complex.", "output": "zinc." }, { "input": "In this study, a ternary complex based on natural polysaccharides was explored as a novel food preservative.", "output": "There is no related enetity." }, { "input": "Chitooligomer was obtained by enzyme hydrolysis of chitosan with immobilised neutral protease, and the degree of polymerisation ( DP ) was mainly from 2 to 5.", "output": "There is no related enetity." }, { "input": "Chitooligomer - zinc complex ( CGZC ) was first produced and then co - heated with xylan to prepare xylan - chitooligomer - zinc complex ( XCGZC ).", "output": "zinc, zinc." }, { "input": "XCGZC showed higher antioxidant and antibacterial activity than chitooligomer, chitooligomer - zinc and xylan - chitooligomer.", "output": "zinc." }, { "input": "The IC ( 50 ) of XCGZC was 5. 37 mg / mL, which was equal to the antioxidant ability of 3. 28 mg / mL BHT.", "output": "There is no related enetity." }, { "input": "The diameter of the inhibition zone for XCGZC against Escherichia coli and Staphylococcus aureus was 17. 2 +/- 0. 4 and 30. 3 +/- 0. 6mm vs. control of 6. 0mm.", "output": "There is no related enetity." }, { "input": "Besides, XCGZC had excellent antibacterial activity against Bacillus subtilis, Salmonella typhimurium, Bacillus megaterium.", "output": "There is no related enetity." }, { "input": "Therefore, XCGZC can be used as a novel promising preservative with antibacterial and antioxidant properties in the food industry.", "output": "There is no related enetity." }, { "input": "A critical study of use of the Fe ( II ) / 3 - hydroxy - 4 - nitroso - 2, 7 - naphthalenedisulfonic acid complexes in the quantification of polyphenols in medicinal plants.", "output": "Fe ( II ), 3 - hydroxy - 4 - nitroso - 2 , 7 - naphthalenedisulfonic acid, polyphenols." }, { "input": "A critical study of the use of the Fe ( III ) / 3 - hydroxy - 4 - nitroso - 2, 7 - naphthalenedisulfonic acid ( NRS ) complexes on the quantification of the polyphenols content in aqueous extracts of plants, expressed as pyrogallic acid, [ PA ], is presented.", "output": "Fe ( III ), 3 - hydroxy - 4 - nitroso - 2 , 7 - naphthalenedisulfonic acid, NRS, polyphenols, pyrogallic acid." }, { "input": "The reaction used is based on the reduction of Fe ( III ) to Fe ( II ) by [ PA ] in the presence of NRS in a buffered medium ( Tris; pH 8. 0 ) with formation of Fe ( II ) / NRS complexes.", "output": "Fe ( III ), Fe ( II ), NRS, Fe ( II ), NRS." }, { "input": "A calibration curve of absorbance ( at 730 nm ) vs. [ PA ] is linear ( r = 0. 998; n = 7 ) from 1. 0 to 7. 0 mu molL ( - 1 ) [ PA ].", "output": "There is no related enetity." }, { "input": "LD and RSD were 0. 5 mu molL ( - 1 ) and 2. 5 % ( 6. 0 mu molL ( - 1 ) [ PA ], n = 10 ), respectively.", "output": "There is no related enetity." }, { "input": "The influence of pH, type of buffer solution and interfering species possibly present in the samples were evaluated.", "output": "There is no related enetity." }, { "input": "Aqueous extracts of twelve medicinal plants used in the Brazilian folk medicine were analysed by using both Fe ( III ) / NRS complexes and the Folin - Ciocalteu reagent.", "output": "Fe ( III ), NRS." }, { "input": "A simple HPLC method for the comprehensive analysis of cis / trans ( Z / E ) geometrical isomers of carotenoids for nutritional studies.", "output": "There is no related enetity." }, { "input": "Geometrical isomers of carotenoids behave differently in aspects like stability towards oxidants, bioavailability, vitamin A activity and specificity for enzymes.", "output": "vitamin A." }, { "input": "The availability of HPLC methods for their detailed profiling is therefore advisable to expand our knowledge on their metabolism and biological role.", "output": "There is no related enetity." }, { "input": "In this paper the development of a methodology to determine the highest number of geometrical isomers of major carotenoids in humans ( phytoene, phytofluene, lutein, zeaxanthin, beta - cryptoxanthin, alpha - carotene, beta - carotene and lycopene ) is described.", "output": "phytoene, phytofluene, lutein, zeaxanthin, beta - cryptoxanthin, alpha - carotene, beta - carotene, lycopene." }, { "input": "To assess its usefulness with biological samples both postprandial human plasma and lung samples from ferrets were analysed.", "output": "There is no related enetity." }, { "input": "Up to 48 isomers of the main human carotenoids were separated in 62 min.", "output": "There is no related enetity." }, { "input": "This is to the best of our knowledge the report of the highest number of carotenoid geometrical isomers separated with a HPLC method.", "output": "There is no related enetity." }, { "input": "Twenty - six different carotenoid isomers were readily detected in the biological samples.", "output": "There is no related enetity." }, { "input": "Understanding the degradation of ascorbic acid and glutathione in relation to the levels of oxidative stress biomarkers in broccoli ( Brassica oleracea L. italica cv. Bellstar ) during storage and mechanical processing.", "output": "ascorbic acid, glutathione." }, { "input": "The purpose of this research was to understand the degradation of ascorbic acid and glutathione content in broccoli florets ( Brassica oleracea L. italica cv. Bellstar ) during prolonged storage and subsequent mechanical processing.", "output": "ascorbic acid, glutathione." }, { "input": "The initial content of total ascorbic acid and glutathione in broccoli florets averaged at 5. 18 +/- 0. 23 and 0. 70 +/- 0. 03 mu mol / g fresh weight, respectively.", "output": "ascorbic acid, glutathione." }, { "input": "Results showed that the content of ascorbic acid and glutathione in broccoli degraded during storage at 23 degrees C, for at least 4. 5 - fold after 6 days of storage.", "output": "ascorbic acid, glutathione." }, { "input": "On each day of storage, broccoli florets were mechanically processed, but the content of total ascorbic acid and glutathione was not significantly affected.", "output": "ascorbic acid, glutathione." }, { "input": "When the mechanically processed broccoli florets were further incubated for up to 6h, the amount of ascorbic acid was greatly reduced as compared to glutathione.", "output": "ascorbic acid, glutathione." }, { "input": "To obtain an in - depth understanding on the degradation of ascorbic acid and glutathione, the activity of enzymes involved in plant antioxidative system via ascorbate - glutathione cycle, as a response towards oxidative stress that took place during storage was determined in this study.", "output": "ascorbic acid, glutathione, ascorbate, glutathione." }, { "input": "The content of total ascorbic acid and glutathione in broccoli florets before and after mechanical processing were found to decrease concurrently with the activity of ascorbic acid peroxidase and glutathione reductase over the experimental storage duration.", "output": "ascorbic acid, glutathione, ascorbic acid, glutathione." }, { "input": "Meanwhile, the effect of oxidative stress on the content of ascorbic acid and glutathione was apparent during the 6h of incubation after mechanical processing.", "output": "ascorbic acid, glutathione." }, { "input": "This phenomenon was demonstrated by the level of oxidative stress biomarkers examined, in which the formation of lipid peroxides, protein carbonyls and DNA oxidised products was positively associated with the degradation of total ascorbic acid and glutathione.", "output": "peroxides, carbonyls, ascorbic acid, glutathione." }, { "input": "Phytosteryl sinapates and vanillates: chemoenzymatic synthesis and antioxidant capacity assessment.", "output": "Phytosteryl sinapates, vanillates." }, { "input": "Phytosterols and their derivatives have attracted much attention because of their health benefits to humans and are widely used in food, pharmaceuticals, and cosmetics in the past decades.", "output": "Phytosterols." }, { "input": "While most of the research has focused on free phytosterols and phytosteryl esters of fatty acids, few researches reported on phytosteryl phenolates, the esters of phytosterols with phenolic acids.", "output": "phytosterols, phytosteryl esters of fatty acids, phytosteryl phenolates, phytosterols, phenolic acids." }, { "input": "Two novel group phytosteryl phenolates, namely phytosteryl sinapates and vanillates, were successfully chemoenzymatically synthesised in this work and their structures confirmed.", "output": "phytosteryl phenolates, phytosteryl sinapates, vanillates." }, { "input": "Fourier transform infrared ( FTIR ) and high performance chromatography - mass spectrometry / mass spectrometry ( HPLC - MS / MS ) using atmospheric pressure chemical ionisation ( APCI ) under both positive and negative ion modes were employed for this purpose.", "output": "There is no related enetity." }, { "input": "High antioxidant capacity of phytosteryl sinapates was observed using both oxygen radical absorbance capacity ( ORAC ) assay and cooked ground meat model system.", "output": "phytosteryl sinapates, oxygen." }, { "input": "Although phytosteryl vanillates showed lower antioxidant capacity than phytosteryl sinapates, they were stronger antioxidants than vanillic acid and vinyl vanillate in both assays employed.", "output": "phytosteryl vanillates, phytosteryl sinapates, vanillic acid, vinyl vanillate." }, { "input": "Conjugation of phytosterols with sinapic or vanillic acid rendered higher antioxidant capacity.", "output": "phytosterols, sinapic or vanillic acid." }, { "input": "Further studies on health benefits of phytosteryl sinapates and vanillates are necessary.", "output": "phytosteryl sinapates, vanillates." }, { "input": "Characterization of oils and fats by 1H NMR and GC / MS fingerprinting: classification, prediction and detection of adulteration.", "output": "1H." }, { "input": "The correct identification of oils and fats is important to consumers from both commercial and health perspectives.", "output": "There is no related enetity." }, { "input": "Proton nuclear magnetic resonance ( ( 1 ) H NMR ) spectroscopy, gas chromatography - mass spectrometry ( GC / MS ) fingerprinting and chemometrics were employed successfully for the quality control of oils and fats.", "output": "( 1 ) H." }, { "input": "Principal component analysis ( PCA ) of both techniques showed group clustering of 14 types of oils and fats.", "output": "There is no related enetity." }, { "input": "Partial least squares discriminant analysis ( PLS - DA ) and orthogonal projections to latent structures discriminant analysis ( OPLS - DA ) using GC / MS data had excellent classification sensitivity and specificity compared to models using NMR data.", "output": "There is no related enetity." }, { "input": "Depending on the availability of the instruments, data from either technique can effectively be applied for the establishment of an oils and fats database to identify unknown samples.", "output": "There is no related enetity." }, { "input": "Partial least squares ( PLS ) models were successfully established for the detection of as low as 5 % of lard and beef tallow spiked into canola oil, thus illustrating possible applications in Islamic and Jewish countries.", "output": "There is no related enetity." }, { "input": "Chemical evidence for the synergistic effect of a cysteinyl thiol on the antioxidant activity of caffeic and dihydrocaffeic esters.", "output": "cysteinyl thiol, caffeic and dihydrocaffeic esters." }, { "input": "Antioxidant activity of methyl caffeate and methyl dihydrocaffeate in the presence of a cysteinyl thiol was measured in an azo - initiator - induced lipid oxidation system.", "output": "methyl caffeate, methyl dihydrocaffeate, cysteinyl thiol, azo." }, { "input": "The coexistence of the thiol was observed to display a synergistic effect on the antioxidant activity of both caffeates.", "output": "thiol, caffeates." }, { "input": "The synergism was observed mainly with respect to the elongation of the induction period, rather than the inhibition rate for lipid oxidation.", "output": "There is no related enetity." }, { "input": "For methyl caffeate, the maximum elongation of the induction period was observed in the presence of more than two equivalents of the thiol, whereas the maximum effect on the activity of methyl dihydrocaffeate was observed in the presence of more than three equivalents of the thiol.", "output": "methyl caffeate, thiol, methyl dihydrocaffeate, thiol." }, { "input": "These synergistic effects were analysed by high - performance liquid chromatography and liquid chromatography - mass spectrometry analyses of the intermediates produced during the antioxidation period.", "output": "There is no related enetity." }, { "input": "The analytical results clarified that the mono - thiol adduct of methyl caffeate and the mono - and di - thiol adducts of methyl dihydrocaffeate contributed to the synergism in the antioxidant activity of both caffeates.", "output": "thiol, methyl caffeate, thiol, methyl dihydrocaffeate, caffeates." }, { "input": "Oligomeric procyanidins of lotus seedpod inhibits the formation of advanced glycation end - products by scavenging reactive carbonyls.", "output": "procyanidins, carbonyls." }, { "input": "It has been reported that oligomeric procyanidins of lotus seedpod ( LSOPC ) is effective in the alleviation of Alzheimer ' s disease and diabetes through its antioxidant and insulin - potentiating activities.", "output": "procyanidins." }, { "input": "This study investigated the anti - glycative activity of LSOPC in a bovine serum albumin ( BSA ) - glucose model.", "output": "glucose." }, { "input": "The level of glycation and conformational alterations were assessed by specific fluorescence, Congo red binding assay and circular dichroism.", "output": "There is no related enetity." }, { "input": "The results show that LSOPC has a significant anti - glycative activity in vitro and it can also effectively protect the secondary structure of BSA during glycation.", "output": "There is no related enetity." }, { "input": "LSOPC or catechin ( a major constituent unit of LSOPC ), were used to react with methylglyoxal.", "output": "catechin, methylglyoxal." }, { "input": "The structures of their carbonyl adducts were tentatively identified using HPLC - MS ( 2 ).", "output": "carbonyl." }, { "input": "Their capacity to scavenge methylglyoxal suggested carbonyl scavenging as a major mechanism of antiglycation.", "output": "methylglyoxal, carbonyl." }, { "input": "Therefore, LSOPC could be helpful to prevent AGEs - associated diseases, and with the potential to be used as functional food ingredients.", "output": "There is no related enetity." }, { "input": "Biguanide related compounds in traditional antidiabetic functional foods.", "output": "Biguanide." }, { "input": "Biguanides such as metformin are widely used worldwide for the treatment of type - 2 diabetes.", "output": "Biguanides, metformin." }, { "input": "The identification of guanidine and related compounds in French lilac plant ( Galega officinalis L. ) led to the development of biguanides.", "output": "guanidine, biguanides." }, { "input": "Despite of their plant origin, biguanides have not been reported in plants.", "output": "biguanides." }, { "input": "The objective of this study was to quantify biguanide related compounds ( BRCs ) in experimentally or clinically substantiated antidiabetic functional plant foods and potatoes.", "output": "biguanide." }, { "input": "The corrected results of the Voges - Proskauer ( V - P ) assay suggest that the highest amounts of BRCs are present in green curry leaves ( Murraya koenigii ( L. ) Sprengel ) followed by fenugreek seeds ( Trigonella foenum - graecum L. ), green bitter gourd ( Momordica charantia Descourt. ), and potato ( Solanum tuberosum L. ).", "output": "There is no related enetity." }, { "input": "Whereas, garlic ( Allium sativum L. ), and sweet potato ( Ipomea batatas ( L. ) Lam. ) contain negligible amounts of BRCs.", "output": "There is no related enetity." }, { "input": "In addition, the possible biosynthetic routes of biguanide in these plant foods are discussed.", "output": "biguanide." }, { "input": "Thermal protection of beta - carotene in re - assembled casein micelles during different processing technologies applied in food industry.", "output": "beta - carotene." }, { "input": "beta - Carotene is a carotenoid usually applied in the food industry as a precursor of vitamin A or as a colourant.", "output": "beta - Carotene, vitamin A." }, { "input": "beta - Carotene is a labile compound easily degraded by light, heat and oxygen.", "output": "beta - Carotene, oxygen." }, { "input": "Casein micelles were used as nanostructures to encapsulate, stabilise and protect beta - carotene from degradation during processing in the food industry.", "output": "beta - carotene." }, { "input": "Self - assembly method was applied to re - assemble nanomicelles containing beta - carotene.", "output": "beta - carotene." }, { "input": "The protective effect of the nanostructures against degradation during the most common industrial treatments ( sterilisation, pasteurisation, high hydrostatic pressure and baking ) was proven.", "output": "There is no related enetity." }, { "input": "Casein micelles protected beta - carotene from degradation during heat stabilisation, high pressure processing and the processes most commonly used in the food industry including baking.", "output": "beta - carotene." }, { "input": "This opens new possibilities for introducing thermolabile ingredients in bakery products.", "output": "There is no related enetity." }, { "input": "Determination of seven synthetic dyes in animal feeds and meat by high performance liquid chromatography with diode array and tandem mass detectors.", "output": "There is no related enetity." }, { "input": "An efficient method was developed for the simultaneous determination of seven commonly used synthetic sulfonate dyes ( Ponceau 4RC, Sunset yellow, Allura red, Azophloxine, Ponceau xylidine, Erythrosine and Orange II ) in animal feed and meat using high performance liquid chromatography ( HPLC - DAD ) and tandem mass spectrometry ( HPLC - MS / MS ).", "output": "sulfonate, Ponceau 4RC, Sunset yellow, Allura red, Azophloxine, Ponceau xylidine, Erythrosine, Orange II." }, { "input": "Ethanol - ammonia - water ( 80: 1: 19, V / V / V ) solution was used as extract solution, which can extract target species while reducing interference from the sample matrices.", "output": "Ethanol, ammonia." }, { "input": "The recoveries of these 7 dyes in animal feed and chicken meat were between 71 % and 97 % with relative standard deviations less than 14. 8 %.", "output": "There is no related enetity." }, { "input": "HPLC - MS / MS was employed as a further means of confirmation to assure accuracy of the results.", "output": "There is no related enetity." }, { "input": "Limits of detection for these dyes were in the range of 0. 02 - 21. 83 ng mL ( - 1 ).", "output": "There is no related enetity." }, { "input": "The proposed method can be applied to confirmative screening of seven commonly used food colorants in feed and meat samples.", "output": "There is no related enetity." }, { "input": "Fatty acid composition of cooked chicken meat and chicken meat products as influenced by price range at retail.", "output": "Fatty acid." }, { "input": "The primary objective was to determine fatty acid composition of skinless chicken breast and leg meat portions and chicken burgers and nuggets from the economy price range, standard price range ( both conventional intensive rearing ) and the organic range from four leading supermarkets.", "output": "fatty acid." }, { "input": "Few significant differences in the SFA, MUFA and PUFA composition of breast and leg meat portions were found among price ranges, and supermarket had no effect.", "output": "SFA, MUFA, PUFA." }, { "input": "No significant differences in fatty acid concentrations of economy and standard chicken burgers were found, whereas economy chicken nuggets had higher C16: 1, C18: 1 cis, C18: 1 trans and C18: 3 n - 3 concentrations than had standard ones.", "output": "fatty acid." }, { "input": "Overall, processed chicken products had much higher fat contents and SFA than had whole meat.", "output": "There is no related enetity." }, { "input": "Long chain n - 3 fatty acids had considerably lower concentrations in processed products than in whole meat.", "output": "fatty acids." }, { "input": "Overall there was no evidence that organic chicken breast or leg meat had a more favourable fatty acid composition than had meat from conventionally reared birds.", "output": "fatty acid." }, { "input": "Determination of the degree of oxidation in highly - oxidised lipids using profile changes of fatty acids.", "output": "fatty acids." }, { "input": "The degree of highly oxidised lipids was determined by a modified method using profile changes of fatty acids in lard and soybean oil heated at 180 degrees C.", "output": "fatty acids." }, { "input": "The usefulness of the modified method was compared through conjugated dienoic acid ( CDA ) and / or p - anisidine value ( p - AV ) methods.", "output": "dienoic acid, p - anisidine." }, { "input": "Absolute values, which were expressed as equivalent to an internal standard ( C11: 0 ), of both unsaturated fatty acids ( UFAs ) and saturated fatty acids ( SFAs ) decreased significantly during thermal oxidation ( p < 0. 05 ) while relative percentage of SFA increased and those of UFA decreased significantly ( p < 0. 05 ).", "output": "C11 : 0, unsaturated fatty acids, UFAs, saturated fatty acids, SFAs, SFA, UFA." }, { "input": "The content of caprylic acid ( C8: 0 ) increased significantly ( p < 0. 05 ) as thermal oxidation time increased.", "output": "caprylic acid, C8 : 0." }, { "input": "The ratio of total saturated over total unsaturated fatty acids ( SFAs / UFAs ) or caprylic acid ( C8: 0 ) over UFAs could be useful markers to determine the degree of oxidation.", "output": "unsaturated fatty acids, SFAs, UFAs, caprylic acid, C8 : 0, UFAs." }, { "input": "Antioxidant capacity of sesamol, a free radical scavenger, was determined using the ratio of fatty acids.", "output": "sesamol, fatty acids." }, { "input": "The modified method can be applied to determine the quality control of fried foods containing highly oxidised and abused oils, which may not be measured correctly using CDA and p - AV.", "output": "There is no related enetity." }, { "input": "Thermal stability of anthocyanins and colourless phenolics in pomegranate ( Punica granatum L. ) juices and model solutions.", "output": "anthocyanins." }, { "input": "The present study aimed at a systematic assessment of the factors influencing the anthocyanin ( AC ) stability and colour retention of pomegranate juices and less complex model solutions with particular focus on the effects of colourless phenolic copigments ( CP ).", "output": "anthocyanin." }, { "input": "The thermal stability of ACs in three pomegranate juices obtained from isolated arils and the entire fruit with and without previous steaming, in model solutions with AC: CP ratios ranging from 1: 0 to 1: 4 ( m / m ), and in two purified extracts from pomegranate juices characterised by different phenolic profiles, respectively, was investigated upon heating at 60, 70, 80 and 90 degrees C for 15 min to 5h.", "output": "ACs." }, { "input": "The thermal impact on the AC and CP contents, and the formation of 5 - hydroxymethylfurfural ( HMF ) and AC degradation products were monitored using HPLC - DAD - MS ( n ).", "output": "5 - hydroxymethylfurfural, HMF." }, { "input": "Total phenolic contents, antioxidant capacity and colour properties were determined spectrophotometrically.", "output": "There is no related enetity." }, { "input": "Heating at 90 degrees C for 5h resulted in total AC losses ranging from 76 % to 87 % of the initial AC levels in the juices, 78 % in both extracts as well as 57 % and ~ 78 % in the model solutions, showing the best stability at an AC: CP ratio of 1: 2 and in juices having the highest initial AC contents, respectively.", "output": "There is no related enetity." }, { "input": "In contrast, the AC stability was independent of total phenolic contents, and low and high molecular pomegranate matrix components ( such as organic acids and sugars ).", "output": "sugars." }, { "input": "Good correlation of the AC contents with red colour ( a ( * ) ) was observed for all samples at elevated temperatures ( 70 - 90 degrees C ).", "output": "There is no related enetity." }, { "input": "The stability of putative health - promoting polyphenols of pomegranate juices was not markedly affected by the thermal treatment.", "output": "polyphenols." }, { "input": "Unexpectedly, the HMF contents only slightly increased upon forced heating.", "output": "HMF." }, { "input": "Therefore, the visual appearance does not adequately reflect the quality and storage stability of pomegranate juices.", "output": "There is no related enetity." }, { "input": "Valuable compounds in macroalgae extracts.", "output": "There is no related enetity." }, { "input": "Bioactive compounds present in ethanolic extracts from 18 macroalgae of the Portuguese coast were analysed by gas chromatography - mass spectrometry ( GC - MS ), leading to the characterization of 14 compounds: proline, phloroglucinol, mannitol, 8 fatty acids and 3 sterols.", "output": "proline, phloroglucinol, mannitol, fatty acids, sterols." }, { "input": "A dose - dependent response against enzymes with biological significance ( alpha - glucosidase, acetylcholinesterase and butyrylcholinesterase ) and free radicals ( DPPH, nitric oxide, superoxide and hydroxyl ) was found, Phaeophyta being the most promising group.", "output": "DPPH, nitric oxide, superoxide, hydroxyl." }, { "input": "A PCA analysis was performed and allowed the establishment of a correlation between the algae chemical composition and the biological activity.", "output": "There is no related enetity." }, { "input": "Cystoseira tamariscifolia ( Hudson ) Papenfuss, Cystoseira nodicaulis ( Withering ) M.", "output": "There is no related enetity." }, { "input": "Roberts, Cystoseira usneoides ( Linnaeus ) M.", "output": "There is no related enetity." }, { "input": "Roberts and Fucus spiralis Linnaeus are among the most active species, which is in accordance with their higher contents in phloroglucinol, mannitol, oleic, arachidonic and eicosapentaenoic acids, and fucosterol.", "output": "phloroglucinol, mannitol, oleic , arachidonic and eicosapentaenoic acids, fucosterol." }, { "input": "The results point to the potential interest of the use of Phaeophyta species as food additives, due to their potent antiradical activities, and especially highlights the importance of F. spiralis in the food chain of Mediterranean countries.", "output": "There is no related enetity." }, { "input": "Moreover, the incorporation of the extracts of these species in food products, nutraceutical and pharmaceutical preparations for human health should also be instigated, since they can suppress hyperglycemia and inhibit cholinesterases.", "output": "There is no related enetity." }, { "input": "Near - infrared hyperspectral imaging and partial least squares regression for rapid and reagentless determination of Enterobacteriaceae on chicken fillets.", "output": "There is no related enetity." }, { "input": "Bacterial pathogens are the main culprits for outbreaks of food - borne illnesses.", "output": "There is no related enetity." }, { "input": "This study aimed to use the hyperspectral imaging technique as a non - destructive tool for quantitative and direct determination of Enterobacteriaceae loads on chicken fillets.", "output": "There is no related enetity." }, { "input": "Partial least squares regression ( PLSR ) models were established and the best model using full wavelengths was obtained in the spectral range 930 - 1450 nm with coefficients of determination R ( 2 ) >= 0. 82 and root mean squared errors ( RMSEs ) <= 0. 47 log ( 10 ) CFUg ( - 1 ).", "output": "There is no related enetity." }, { "input": "In further development of simplified models, second derivative spectra and weighted PLS regression coefficients ( BW ) were utilised to select important wavelengths.", "output": "There is no related enetity." }, { "input": "However, the three wavelengths ( 930, 1121 and 1345 nm ) selected from BW were competent and more preferred for predicting Enterobacteriaceae loads with R ( 2 ) of 0. 89, 0. 86 and 0. 87 and RMSEs of 0. 33, 0. 40 and 0. 45 log ( 10 ) CFUg ( - 1 ) for calibration, cross - validation and prediction, respectively.", "output": "There is no related enetity." }, { "input": "Besides, the constructed prediction map provided the distribution of Enterobacteriaceae bacteria on chicken fillets, which cannot be achieved by conventional methods.", "output": "There is no related enetity." }, { "input": "It was demonstrated that hyperspectral imaging is a potential tool for determining food sanitation and detecting bacterial pathogens on food matrix without using complicated laboratory regimes.", "output": "There is no related enetity." }, { "input": "Redox properties of catechins and enriched green tea extracts effectively preserve L - 5 - methyltetrahydrofolate: assessment using cyclic voltammetry analysis.", "output": "catechins, L - 5 - methyltetrahydrofolate." }, { "input": "A cyclic voltammetry ( CV ) study was performed in pH 5. 5 Britton - Robinson buffer at room temperature to study the stability of 1mM l - 5 - methyltetrahydrofolate ( l - 5 - MTHF ) in combination with epigallocatechin - gallate - enriched extract ( EGCGe ) and epigallocatechin - enriched extract ( EGCe ).", "output": "l - 5 - methyltetrahydrofolate, l - 5 - MTHF, epigallocatechin - gallate." }, { "input": "The combination of l - 5 - MTHF with enriched catechin extracts provided enhanced stability of l - 5 - MTHF over a period of 12h under ambient air conditions at pH 5. 5.", "output": "l - 5 - MTHF, catechin, l - 5 - MTHF." }, { "input": "CV experiments showed that increasing the concentrations of EGCGe or EGCe extracts from 80 to 400mg / L produced a decrease in the second oxidation peak of l - 5 - MTHF.", "output": "l - 5 - MTHF." }, { "input": "Thus, we calculated that l - 5 - MTHF remained at nearly 90 % when in the presence of enriched tea extracts, compared to 74 % without the tea antioxidants.", "output": "l - 5 - MTHF." }, { "input": "The catechins responsible for this preservation were EGCG and C, confirmed by LC - MS.", "output": "catechins, EGCG." }, { "input": "Compared to covalent link only low interaction ( hydrogen bonds ) between the different catechins present in the tea extract would stabilise l - 5 - MTHF.", "output": "hydrogen, catechins, l - 5 - MTHF." }, { "input": "Rather, it was hypothesised that EGCGe and EGCe were effective agents to preserve l - 5 - MTHF, through a mechanism that also involved the redox potential of catechins to maintain l - 5 - MTHF in its reduced form.", "output": "l - 5 - MTHF, l - 5 - MTHF." }, { "input": "Physicochemical responses and microbial characteristics of shiitake mushroom ( Lentinus edodes ) to gum arabic coating enriched with natamycin during storage.", "output": "natamycin." }, { "input": "Physicochemical responses and microbial characteristics of shiitake mushroom ( Lentinus edodes ) to gum arabic ( GA ) coating incorporating natamycin ( NA ) during storage were investigated.", "output": "natamycin." }, { "input": "Mushroom weight loss, firmness, total soluble solids, total sugar, reducing sugar, ascorbic acid, and microbial and sensory quality were measured.", "output": "sugar, sugar, ascorbic acid." }, { "input": "Mushroom coated with gum arabic + natamycin ( GANA ) maintained tissue firmness and showed reduction in microbial counts from yeasts and moulds compared with the control.", "output": "natamycin." }, { "input": "In addition, GANA coating also delayed changes in the soluble solids concentration, total sugar and ascorbic acid.", "output": "sugar, ascorbic acid." }, { "input": "Sensory evaluation proved the efficacy of GANA coating by maintaining the overall quality of shiitake mushroom during the storage period.", "output": "There is no related enetity." }, { "input": "The efficiency was better than that of GA or NA treatment alone.", "output": "There is no related enetity." }, { "input": "Our study suggests that GANA has the potential to improve the quality of shiitake mushroom and extend its shelf - life up to 16d.", "output": "There is no related enetity." }, { "input": "Redox spectrophotometric method involving electrolytically generated manganese ( III ) sulphate with diphenylamine for the determination of ascorbic acid present in the samples of various fruits, commercial juices and sprouted food grains.", "output": "manganese ( III ) sulphate, diphenylamine, ascorbic acid." }, { "input": "A spectrophotometric method was developed for ascorbic acid present in various fruits, commercial fruit juices and sprouted food grains.", "output": "ascorbic acid." }, { "input": "The method involves the oxidation of ascorbic acid with excess manganese ( III ) following reduction of unreacted manganese ( III ) with diphenylamine or barium diphenylamine sulphonate forming a product lambda ( max ) 570 nm the system 1 or 540 nm the system 2 and decrease in the colour intensity is proportional to the concentration of vitamin C with quantification range 0. 3 - 3. 0 mu g ml ( - 1 ).", "output": "ascorbic acid, manganese ( III ), manganese ( III ), diphenylamine, barium diphenylamine sulphonate, vitamin C." }, { "input": "The molar absorptivity and Sandell ' s sensitivity values of the system 1 and the system 2 were 1. 829 x 10 ( 4 ) and 1. 813 x 10 ( 4 ) mol ( - 1 ) cm ( - 1 ) and 0. 0096 and 0. 0097 mu g cm ( - 2 ) respectively.", "output": "There is no related enetity." }, { "input": "The stoichiometry was 4: 1 between manganese ( III ) and diphenylamine.", "output": "manganese ( III ), diphenylamine." }, { "input": "The ascorbic acid contents of the same samples were determined separately following the procedures of the developed method as well as the reference method and the results were comparable.", "output": "ascorbic acid." }, { "input": "Synthesis and characterisation of nano structure lead ( II ) ion - imprinted polymer as a new sorbent for selective extraction and preconcentration of ultra trace amounts of lead ions from vegetables, rice, and fish samples.", "output": "There is no related enetity." }, { "input": "This paper describes the preparation of new Pb ( II ) - imprinted polymeric particles using 2 - vinylpyridine as a functional monomer, ethylene glycol dimethacrylate as the cross - linker, 2, 2 ' - azobisisobutyronitrile as the initiator, diphenylcarbazone as the ligand, acetonitril as the solvent, and Pb ( NO ( 3 ) ) ( 2 ) as the template ion, through bulk polymerisation technique.", "output": "Pb ( II ), 2 - vinylpyridine, ethylene glycol dimethacrylate, 2 , 2 ' - azobisisobutyronitrile, diphenylcarbazone, acetonitril, Pb ( NO ( 3 ) ) ( 2 )." }, { "input": "The imprinted lead ions were removed from the polymeric matrix using 5 mL of HCl ( 2 mol. L ( - 1 ) ) as the eluting solvent.", "output": "HCl." }, { "input": "The lead ion concentration was determined by flame atomic absorption spectrometry.", "output": "There is no related enetity." }, { "input": "Optimum pH for maximum sorption was obtained at 6. 0.", "output": "There is no related enetity." }, { "input": "Sorption and desorption of Pb ( II ) ions on the IIP particles were quite fast and achieved fully over 5 min.", "output": "Pb ( II )." }, { "input": "In the proposed method, the maximum sorbent capacity of the ion - imprinted polymer was calculated to be 75. 4 mg g ( - 1 ).", "output": "There is no related enetity." }, { "input": "The preconcentration factor, relative standard deviation, and limit of detection of the method were found to be 245, 2. 1 %, and 0. 42 ng mL ( - 1 ), respectively.", "output": "There is no related enetity." }, { "input": "The prepared ion - imprinted polymer particles have an increased selectivity toward Pb ( II ) ions over a range of competing metal ions with the same charge and similar ionic radius.", "output": "Pb ( II )." }, { "input": "This ion - imprinted polymer is an efficient solid phase for extraction and preconcentration of lead ions in complex matrixes.", "output": "There is no related enetity." }, { "input": "For proving that the proposed method is reliable, a wide range of food samples with different and complex matrixes was used.", "output": "There is no related enetity." }, { "input": "Interactive effects of a bacterial parasite and the insecticide carbaryl to life - history and physiology of two Daphnia magna clones differing in carbaryl sensitivity.", "output": "carbaryl, carbaryl." }, { "input": "Natural and chemical stressors occur simultaneously in the aquatic environment.", "output": "There is no related enetity." }, { "input": "Their combined effects on biota are usually difficult to predict from their individual effects due to interactions between the different stressors.", "output": "There is no related enetity." }, { "input": "Several recent studies have suggested that synergistic effects of multiple stressors on organisms may be more common at high compared to low overall levels of stress.", "output": "There is no related enetity." }, { "input": "In this study, we used a three - way full factorial design to investigate whether interactive effects between a natural stressor, the bacterial parasite Pasteuria ramosa, and a chemical stressor, the insecticide carbaryl, were different between two genetically distinct clones of Daphnia magna that strongly differ in their sensitivity to carbaryl.", "output": "carbaryl, carbaryl." }, { "input": "Interactive effects on various life - history and physiological endpoints were assessed as significant deviations from the reference Independent Action ( IA ) model, which was implemented by testing the significance of the two - way carbaryl x parasite interaction term in two - way ANOVA ' s on log - transformed observational data for each clone separately.", "output": "carbaryl." }, { "input": "Interactive effects ( and thus significant deviations from IA ) were detected in both the carbaryl - sensitive clone ( on survival, early reproduction and growth ) and in the non - sensitive clone ( on growth, electron transport activity and prophenoloxidase activity ).", "output": "carbaryl." }, { "input": "No interactions were found for maturation rate, filtration rate, and energy reserve fractions ( carbohydrate, protein, lipid ).", "output": "carbohydrate." }, { "input": "Furthermore, only antagonistic interactions were detected in the non - sensitive clone, while only synergistic interactions were observed in the carbaryl sensitive clone.", "output": "carbaryl." }, { "input": "Our data clearly show that there are genetically determined differences in the interactive effects following combined exposure to carbaryl and Pasteuria in D. magna.", "output": "carbaryl." }, { "input": "Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion: Results of a randomized, placebo - controlled study.", "output": "Canagliflozin, Glucose, Glucose, Glucose." }, { "input": "OBJECTIVECanagliflozin, a sodium glucose cotransporter 2 ( SGLT2 ) inhibitor, is also a low - potency SGLT1 inhibitor.", "output": "OBJECTIVECanagliflozin, sodium, glucose." }, { "input": "This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODSThis two - period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual - tracer method.", "output": "canagliflozin, glucose, canagliflozin, glucose." }, { "input": "Placebo or canagliflozin 300 mg was given 20 min before a 600 - kcal mixed - meal tolerance test.", "output": "canagliflozin." }, { "input": "Plasma glucose, ( 3 ) H - glucose, ( 14 ) C - glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose ( R ( a ) O ) in plasma, endogenous glucose production, and glucose disposal. RESULTSCompared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions ( incremental 0 - to 2 - h area under the curve [ AUC ( 0 - 2h ) ] reductions of 35 % and 43 %, respectively; P < 0. 001 for both ), increased 0 - to 6 - h urinary glucose excretion ( UGE ( 0 - 6h ), 18. 2 +/- 5. 6 vs < 0. 2 g; P < 0. 001 ), and delayed R ( a ) O.", "output": "glucose, ( 3 ) H - glucose, ( 14 ) C - glucose, glucose, glucose, glucose, canagliflozin, glucose, glucose." }, { "input": "Canagliflozin reduced AUC R ( a ) O by 31 % over 0 to 1 h ( geometric means, 264 vs. 381 mg / kg; P < 0. 001 ) and by 20 % over 0 to 2 h ( 576 vs. 723 mg / kg; P = 0. 002 ).", "output": "Canagliflozin." }, { "input": "Over 2 to 6 h, canagliflozin increased R ( a ) O such that total AUC R ( a ) O over 0 to 6 h was < 6 % lower versus placebo ( 960 vs. 1, 018 mg / kg; P = 0. 003 ).", "output": "canagliflozin." }, { "input": "A modest ( ~ 10 % ) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in R ( a ) O.", "output": "acetaminophen." }, { "input": "Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONSCanagliflozin reduces postprandial plasma glucose and insulin by increasing UGE ( via renal SGLT2 inhibition ) and delaying R ( a ) O, likely due to intestinal SGLT1 inhibition.", "output": "glucose, CONCLUSIONSCanagliflozin, glucose." }, { "input": "Repeated Low Dose Administration of the Monoacylglycerol Lipase Inhibitor JZL184 Retains CB1 Receptor Mediated Antinociceptive and Gastroprotective Effects.", "output": "Monoacylglycerol, JZL184." }, { "input": "The monoacylglycerol lipase ( MAGL ) inhibitor JZL184 produces antinociceptive and anti - inflammatory effects.", "output": "monoacylglycerol, JZL184." }, { "input": "However, repeated administration of high dose JZL184 ( 40 mg / kg ) causes dependence, antinociceptive tolerance, cross - tolerance to the pharmacological effects of cannabinoid receptor agonists, and CB ( 1 ) receptor downregulation and desensitization.", "output": "JZL184." }, { "input": "This functional CB ( 1 ) receptor tolerance poses a hurdle in the development of MAGL inhibitors for therapeutic use.", "output": "There is no related enetity." }, { "input": "Consequently, the present study tested whether repeated administration of low dose JZL184 maintains its antinociceptive actions in the chronic constrictive injury ( CCI ) of the sciatic nerve neuropathic pain model and protective effects in a model of NSAlD - induced gastric hemorrhages.", "output": "JZL184." }, { "input": "Mice given daily injections of high dose JZL184 ( >= 16 mg / kg ) for six days displayed decreased CB ( 1 ) receptor density and function in brain, as assessed in [ ( 3 ) H ] SR141716A binding and CP55, 940 - stimulated [ ( 35 ) S ] GTP gamma S binding assays, respectively.", "output": "JZL184, [ ( 3 ) H ] SR141716A, CP55 , 940, ( 35 ) S." }, { "input": "In contrast, normal CB ( 1 ) receptor expression and function were maintained following repeated administration of low dose JZL184 ( <= 8 mg / kg ).", "output": "JZL184." }, { "input": "Likewise, the antinociceptive and gastroprotective effects of high dose JZL184 underwent tolerance following repeated administration, but these effects were maintained following repeated low dose JZL184 treatment.", "output": "JZL184, JZL184." }, { "input": "Consistent with these observations, repeated high dose JZL184, but not repeated low dose JZL184, elicited cross - tolerance to the common pharmacological effects of Delta ( 9 ) - tetrahydrocannabinol ( THC ).", "output": "JZL184, JZL184, Delta ( 9 ) - tetrahydrocannabinol, THC." }, { "input": "This same pattern of effects was found in a rimonabant - precipitated withdrawal model of cannabinoid dependence.", "output": "rimonabant." }, { "input": "Taken together, these results indicate that prolonged, partial MAGL inhibition maintains potentially beneficial antinociceptive and anti - inflammatory effects, without producing functional CB ( 1 ) receptor tachyphylaxsis / tolerance or cannabinoid dependence.", "output": "There is no related enetity." }, { "input": "Computational Investigation of Cancer - Associated Molecular Mechanism in Aurora A ( S155R ) Mutation.", "output": "There is no related enetity." }, { "input": "Centrosomes are the key - regulating element of cell cycle progression.", "output": "There is no related enetity." }, { "input": "Aberrations in their functional mechanism lead to several cancer - related disorders.", "output": "There is no related enetity." }, { "input": "Aurora A protein is a centrosome - associated protein that regulates the centriole duplication and its abberations are associated with multiple cases of aneuploidy and cancer - related disorders.", "output": "There is no related enetity." }, { "input": "S155R mutation in Aurora A is reported to induce cancer like phenotype and disrupt its binding with TPX2 protein.", "output": "There is no related enetity." }, { "input": "In this study, we have demonstrated the structural consequences of Aurora A S155R mutation and the atomic changes that influenced the loss of TPX2 - binding affinity.", "output": "There is no related enetity." }, { "input": "Docking and molecular dynamics simulation results suggested significant loss in atomic contacts between mutant Aurora A and TPX2 protein.", "output": "There is no related enetity." }, { "input": "Further, we observed a notable changes in conformation of mutant Aurora A - TPX2 docked complex as compared to the native.", "output": "There is no related enetity." }, { "input": "Loss of binding affinity rendered the TPX2 domain free which then induced unfolding in its coiled region and enabled the overall expansion of mutant complex as compared to the native.", "output": "There is no related enetity." }, { "input": "The significant outcomes obtained from this study will facilitate in future cancer researches and in developing the potent drug therapies.", "output": "There is no related enetity." }, { "input": "Cardiotonic steroids - mediated Na + / K + - ATPase targeting could circumvent various chemoresistance pathways.", "output": "Na +, K +." }, { "input": "Many cancer patients fail to respond to chemotherapy because of the intrinsic resistance of their cancer to pro - apoptotic stimuli or the acquisition of the multidrug resistant phenotype during chronic treatment.", "output": "There is no related enetity." }, { "input": "Previous data from our groups and from others point to the sodium / potassium pump ( the Na + / K + - ATPase, i. e., NaK ) with its highly specific ligands ( i. e., cardiotonic steroids ) as a new target for combating cancers associated with dismal prognoses, including gliomas, melanomas, non - small cell lung cancers, renal cell carcinomas, and colon cancers.", "output": "sodium, potassium, Na +, K +, NaK, steroids." }, { "input": "Cardiotonic steroid - mediated Na + / K + - ATPase targeting could circumvent various resistance pathways.", "output": "Na +, K +." }, { "input": "The most probable pathways include the involvement of Na + / K + - ATPase beta subunits in invasion features and Na + / K + - ATPase alpha subunits in chemosensitisation by specific cardiotonic steroid - mediated apoptosis and ano i kis - sensitisation; the regulation of the expression of multidrug resistant - related genes; post - translational regulation, including glycosylation and ubiquitinylation of multidrug resistant - related proteins; c - Myc downregulation; hypoxia - inducible factor downregulation; NF - kappa B downregulation and deactivation; the inhibition of the glycolytic pathway with a reduction of intra - cellular ATP levels and an induction of non - apoptotic cell death.", "output": "Na +, K +, Na +, K +, steroid, ATP." }, { "input": "The aims of this review are to examine the various molecular pathways by which the NaK targeting can be more deleterious to biologically aggressive cancer cells than to normal cells.", "output": "NaK." }, { "input": "Fine - tuning of Voltage Sensitivity of the Kv1. 2 Potassium Channel by Interhelix Loop Dynamics.", "output": "Potassium." }, { "input": "Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment.", "output": "There is no related enetity." }, { "input": "Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function.", "output": "There is no related enetity." }, { "input": "Voltage - gated ion channels are membrane proteins that open and close an ion - selective pore in response to changes in transmembrane voltage.", "output": "There is no related enetity." }, { "input": "The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non - covalent interactions between adjacent helices and covalent interactions along the peptide backbone.", "output": "There is no related enetity." }, { "input": "However, the structural basis for the wide variation in the V50 value between different voltage - gated potassium channels is not well defined.", "output": "potassium." }, { "input": "To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1. 2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3.", "output": "There is no related enetity." }, { "input": "We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures.", "output": "There is no related enetity." }, { "input": "Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels.", "output": "There is no related enetity." }, { "input": "Population - based efficacy modeling of omalizumab in patients with severe allergic asthma inadequately controlled with standard therapy.", "output": "There is no related enetity." }, { "input": "Omalizumab, a recombinant humanized monoclonal antibody, is the first approved anti - immunoglobulin E ( IgE ) agent for the treatment of subjects with moderate to severe persistent allergic asthma that are inadequately controlled by the standard of care.", "output": "There is no related enetity." }, { "input": "The objective of this study was to quantitatively characterize relationships between serum free IgE and pulmonary function ( as measured by forced expiratory volume in 1 s [ FEV1 ] ) as well as serum free IgE and airway inflammation ( as measured by fractional exhaled nitric oxide [ FeNO ] ) using population - based efficacy models.", "output": "nitric oxide." }, { "input": "Data were collected from patients in the EXTRA trial who received omalizumab or placebo 150 to 375 mg subcutaneously every 2 or 4 weeks from week 0 to 48 with constant standard of care as background therapy.", "output": "There is no related enetity." }, { "input": "None of the covariates evaluated, including demographics, disease status, and baseline pharmacodynamic biomarkers, were significant in explaining the variability in the FEV1 or FeNO response to omalizumab.", "output": "There is no related enetity." }, { "input": "Results from the efficacy models further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng / ml and quantified the variability for the target.", "output": "There is no related enetity." }, { "input": "In addition, the resulting population models could be used to predict population FEV1 or FeNO response for omalizumab and / or other anti - IgE therapeutics for which PK - IgE models are constructed.", "output": "There is no related enetity." }, { "input": "Tumor necrosis factor receptor - associated factor 5 is an essential mediator of ischemic brain infarction.", "output": "There is no related enetity." }, { "input": "Tumor necrosis factor receptor - associated factor 5 ( TRAF5 ) is an adaptor protein of the tumor necrosis factor ( TNF ) receptor superfamily and the interleukin - 1 receptor / Toll - like receptor superfamily and plays important roles in regulating multiple signaling pathways.", "output": "There is no related enetity." }, { "input": "This study was conducted to investigate the role of TRAF5 in the context of brain ischemia / reperfusion ( I / R ) injury.", "output": "There is no related enetity." }, { "input": "Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice ( KO ), neuron - specific TRAF5 transgene ( TG ), and the appropriate controls.", "output": "There is no related enetity." }, { "input": "Compared with the WT mice, the TRAF5 KO mice showed lower infarct volumes and better outcomes in the neurological tests.", "output": "There is no related enetity." }, { "input": "A low neuronal apoptosis level, an attenuated blood - brain barrier ( BBB ) disruption and an inhibited inflammatory response were exhibited in TRAF5 KO mice.", "output": "There is no related enetity." }, { "input": "TRAF5 TG mice exhibited an opposite phenotype.", "output": "There is no related enetity." }, { "input": "Moreover, the Akt / FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice.", "output": "There is no related enetity." }, { "input": "These results provide the first demonstration that TRAF5 is a critical mediator of I / R injury in an experimental stroke model.", "output": "There is no related enetity." }, { "input": "The Akt / FoxO1 signaling pathway probably plays an important role in the biological function of TRAF5 in this model.", "output": "There is no related enetity." }, { "input": "Evidence of dynamical constraints imposed by water organization around a bio - hydrophobic interface.", "output": "There is no related enetity." }, { "input": "Molecular dynamics simulations and elastic neutron scattering experiments have been used to highlight how the structural organization of hydration water is able in some cases to locally constrain atomic movements at biologic interfaces.", "output": "There is no related enetity." }, { "input": "Using fully hydrated small peptides as models of protein interfaces, we show that the length of the side chains and the hydrophilic backbone have specific signatures.", "output": "There is no related enetity." }, { "input": "The dynamics of the side chain, which is part of biomolecules, have not only a crucial role in the whole flexibility as compared to the backbone, but also modify the values of transition temperatures.", "output": "There is no related enetity." }, { "input": "The analysis of the activation energies of methyl group dynamics suggests that the interaction between hydrophobic side chain and surrounding water plays an important role in the whole flexibility as well.", "output": "methyl." }, { "input": "We suggest that the progressive water cluster organization, around hydrophobic interfaces increases the activation energy and that a plateau regime is reached only when an extended hydrogen - bond network is established.", "output": "hydrogen." }, { "input": "The cluster size corresponds to a single layer of water molecules.", "output": "There is no related enetity." }, { "input": "Glial reactivity in resistance to methamphetamine - induced neurotoxicity.", "output": "methamphetamine." }, { "input": "Neurotoxic regimens of methamphetamine ( METH ) result in reactive microglia and astrocytes in striatum.", "output": "methamphetamine, METH." }, { "input": "Prior data indicate that rats with partial dopamine ( DA ) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re - exposed to METH 30 days later.", "output": "dopamine, METH, METH." }, { "input": "Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH - induced neurotoxicity.", "output": "METH." }, { "input": "To date, the astrocyte response in such resistance has not been examined.", "output": "There is no related enetity." }, { "input": "Thus, this study examined glial - fibrillary acidic protein ( GFAP ) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on post - natal days 60 and / or 90 ( Saline: Saline, Saline: METH, METH: Saline, METH: METH ).", "output": "METH, METH, METH, METH, METH." }, { "input": "Consistent with previous work, animals experiencing acute toxicity ( Saline: METH ) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity ( METH: METH ) did not show activated microglia.", "output": "METH, METH, METH." }, { "input": "Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 ( METH: Saline ), and was not elevated further in resistant rats treated for the second time with METH ( METH: METH ).", "output": "METH, METH, METH." }, { "input": "These data suggest that astrocytes remain reactive up to 30 days post - METH exposure.", "output": "METH." }, { "input": "In addition, these data indicate that astrocyte reactivity does not reflect acute, METH - induced DA terminal toxicity, whereas microglial reactivity does.", "output": "METH." }, { "input": "Discovery of novel 2 - hydroxydiarylamide derivatives as TMPRSS4 inhibitors.", "output": "2 - hydroxydiarylamide." }, { "input": "TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells.", "output": "There is no related enetity." }, { "input": "In this study, a novel series of 2 - hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion.", "output": "2 - hydroxydiarylamide, serine." }, { "input": "These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti - invasive activity of colon cancer cells overexpressing TMPRSS4.", "output": "serine." }, { "input": "A novel concept of radiosynthesis of a ( 99m ) Tc - labeled dimeric RGD peptide as a potential radiotracer for tumor imaging.", "output": "( 99m ) Tc." }, { "input": "Radiolabeled Arg - Gly - Asp ( RGD ) peptides are promising agents for non invasive imaging of alpha v beta 3 expression in malignant tumors.", "output": "Arg - Gly - Asp." }, { "input": "The integrin alpha v beta 3 binding affinity and consequent tumor uptake could be improved when a dimeric RGD peptide is used as the targeting moiety instead of a monomer.", "output": "There is no related enetity." }, { "input": "Towards this, a novel approach was envisaged to synthesize a ( 99m ) Tc labeled dimeric RGD derivative using a RGD monomer and [ ( 99m ) TcN ] ( + 2 ) intermediate.", "output": "( 99m ) Tc, [ ( 99m ) TcN ] ( + 2 )." }, { "input": "The dithiocarbamate derivative of cyclic RGD peptide G3 - c ( RGDfK ) ( G3 = Gly - Gly - Gly, f = Phe, K = Lys ) was synthesized and radiolabeled with [ ( 99m ) TcN ] ( + 2 ) intermediate to form the ( 99m ) TcN - [ G3 - c ( RGDfK ) ] 2 complex in high yield ( ~ 98 % ).", "output": "dithiocarbamate, G3 - c ( RGDfK ), G3 = Gly - Gly - Gly, f = Phe, K = Lys, [ ( 99m ) TcN ] ( + 2 ), ( 99m ) TcN - [ G3 - c ( RGDfK ) ] 2." }, { "input": "Biodistribution studies carried out in C57 / BL6 mice bearing melanoma tumors showed good tumor uptake [ 4. 61 +/- 0. 04 % IA / g at 30min post - injection ] with fast clearance of the activity from non - target organs / tissue.", "output": "There is no related enetity." }, { "input": "Scintigraphic imaging studies showed visible accumulation of activity in the tumor with appreciable target to background ratio.", "output": "There is no related enetity." }, { "input": "Androgen / androgen receptor pathway regulates expression of the genes for cyclooxygenase - 2 and amphiregulin in periovulatory granulosa cells.", "output": "Androgen, androgen." }, { "input": "It is well known that the androgen / androgen receptor ( AR ) pathway is involved in both male and female fertility in mammals.", "output": "androgen, androgen." }, { "input": "AR knockout female mice are reported to exhibit various abnormalities in follicle development, and a subfertile phenotype.", "output": "There is no related enetity." }, { "input": "In exogenous gonadotropin - induced superovulation, serum androgen levels were robustly elevated in female mice at the periovulatory stage after human chorionic gonadotropin ( hCG ) treatment.", "output": "androgen." }, { "input": "At this stage, ovarian AR proteins were strongly expressed in cumulus cells.", "output": "There is no related enetity." }, { "input": "Because these results suggested that the androgen / AR pathway is involved in ovulation, we investigated the expression of ovulation - related genes in the mouse ovary treated with the nonaromatizable androgen, 5 alpha - dihydrotestosterone ( DHT ).", "output": "androgen, androgen, 5 alpha - dihydrotestosterone, DHT." }, { "input": "DHT treatment induced the expression of the genes for cyclooxyganase - 2 ( Cox - 2 or prostaglandin endoperoxidase synthase 2 ) and the epidermal growth factor - like factor, amphiregulin ( Areg ), in the ovary, whereas their hCG - induced expression was suppressed by the AR antagonist flutamide.", "output": "DHT, prostaglandin, flutamide." }, { "input": "These genes were also induced by DHT in AR - expressing primary granulosa and granulosa tumor - derived cells.", "output": "DHT." }, { "input": "Reporter assays, electrophoretic shift mobility assays and chromatin immunoprecipitation assays demonstrated that androgen response sequence ( s ) existing upstream of each gene were responsible for androgen responsiveness and were occupied by the AR in periovulatory granulosa cells.", "output": "androgen, androgen." }, { "input": "Our results suggest that the androgen / AR pathway is involved in the ovulatory process via expression of the Cox - 2 and Areg genes in periovulatory granulosa cells.", "output": "androgen." }, { "input": "Targeted drug delivery to renal proximal tubule epithelial cells mediated by 2 - glucosamine.", "output": "2 - glucosamine." }, { "input": "In order to develop a novel kidney - targeted drug delivery system, we synthesized prednisolone carbamate - glucosamine conjugate ( PCG ) using 2 - glucosamine as a ligand, and investigated its potential targeting efficacy.", "output": "prednisolone carbamate, glucosamine, 2 - glucosamine." }, { "input": "In vitro studies demonstrated that PCG could remarkably improve the uptake of drug by kidney cells.", "output": "There is no related enetity." }, { "input": "And the specific uptake of PCG could be largely reduced by the inhibitors of megalin receptor.", "output": "There is no related enetity." }, { "input": "More importantly, PCG showed an excellent kidney targeting property in vivo, and the concentration of the conjugate in the kidney was 8. 1 - fold higher than that of prednisolone group at 60 min after intravenous injection.", "output": "There is no related enetity." }, { "input": "Besides, PCG could significantly reverse the disease progression in renal ischemia - reperfusion ( I / R ) injury animal models.", "output": "There is no related enetity." }, { "input": "Furthermore, PCG presented no adverse effect on bone density while prednisolone resulted in severe osteoporosis.", "output": "prednisolone." }, { "input": "Thus, it indicated that 2 - glucosamine could be a potential ligand for kidney - targeted delivery of prednisolone.", "output": "2 - glucosamine, prednisolone." }, { "input": "Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule.", "output": "isatin." }, { "input": "This Letter describes the further optimization of an MLPCN probe molecule ( ML137 ) through the introduction of 5 - and 6 - membered spirocycles in place of the isatin ketone.", "output": "spirocycles, isatin, ketone." }, { "input": "Interestingly divergent structure - activity relationships, when compared to earlier M1 PAMs, are presented.", "output": "There is no related enetity." }, { "input": "These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype.", "output": "There is no related enetity." }, { "input": "A nitrophenyl - based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib.", "output": "nitrophenyl, prednisolone, budesonide, celecoxib." }, { "input": "Celecoxib is a COX - 2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma.", "output": "Celecoxib." }, { "input": "Glucocorticoids are used in the treatment of inflammatory bowel disease.", "output": "There is no related enetity." }, { "input": "A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects.", "output": "There is no related enetity." }, { "input": "The prodrug systems introduced here involve forming a nitro - substituted acylsulfonamide group in the case of celecoxib and a nitro - substituted 21 - ester for the glucocorticoids.", "output": "nitro - substituted acylsulfonamide, celecoxib, nitro - substituted 21 - ester." }, { "input": "Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species.", "output": "nitro." }, { "input": "The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco - 2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.", "output": "There is no related enetity." }, { "input": "Glucagon - induced acetylation of Foxa2 regulates hepatic lipid metabolism.", "output": "There is no related enetity." }, { "input": "Circulating levels of insulin and glucagon reflect the nutritional state of animals and elicit regulatory responses in the liver that maintain glucose and lipid homeostasis.", "output": "glucose." }, { "input": "The transcription factor Foxa2 activates lipid metabolism and ketogenesis during fasting and is inhibited via insulin - PI3K - Akt signaling - mediated phosphorylation at Thr156 and nuclear exclusion.", "output": "There is no related enetity." }, { "input": "Here we show that, in addition, Foxa2 is acetylated at the conserved residue Lys259 following inhibition of histone deacetylases ( HDACs ) class I - III and the cofactors p300 and SirT1 are involved in Foxa2 acetylation and deacetylation, respectively.", "output": "There is no related enetity." }, { "input": "Physiologically, fasting states and glucagon stimulation are sufficient to induce Foxa2 acetylation.", "output": "There is no related enetity." }, { "input": "Introduction of the acetylation - mimicking ( K259Q ) or - deficient ( K259R ) mutations promotes or inhibits Foxa2 activity, respectively, and adenoviral expression of Foxa2 - K259Q augments expression of genes involved in fatty acid oxidation and ketogenesis.", "output": "fatty acid." }, { "input": "Our study reveals a molecular mechanism by which glucagon signaling activates a fasting response through acetylation of Foxa2.", "output": "There is no related enetity." }, { "input": "Anti - diabetic and anti - lipidemic effects of chlorogenic acid are mediated by ampk activation.", "output": "chlorogenic acid." }, { "input": "Chlorogenic acid ( CGA ) has been shown to stimulate glucose uptake in skeletal muscle through the activation of AMPK.", "output": "Chlorogenic acid, CGA, glucose." }, { "input": "However, its effect on other metabolic pathways and likewise its effects after long - term consumption have yet to be understood.", "output": "There is no related enetity." }, { "input": "We investigated the effects of CGA on glucose tolerance, insulin sensitivity, hepatic gluconeogenesis, lipid metabolism and skeletal muscle glucose uptake in Lepr ( db / db ) mice.", "output": "CGA, glucose, glucose." }, { "input": "Hepatoma HepG2 was used to investigate CGA ' s effect on hepatic glucose production and fatty acid synthesis.", "output": "CGA, glucose, fatty acid." }, { "input": "Subsequently, we attempted to evaluate whether these effects of CGA are associated with the activation of AMPK.", "output": "CGA." }, { "input": "In Lepr ( db / db ) mice, acute treatment with CGA lowered AUCglucose in an OGTT.", "output": "CGA, AUCglucose." }, { "input": "Chronic administration of CGA inhibited hepatic G6Pase expression and activity, attenuated hepatic steatosis, improved lipid profiles and skeletal muscle glucose uptake, which in turn improved fasting glucose level, glucose tolerance, insulin sensitivity and dyslipidemia in Lepr ( db / db ) mice.", "output": "CGA, glucose, glucose, glucose." }, { "input": "CGA activated AMPK, leading to subsequent beneficial metabolic outcomes, such as suppression of hepatic glucose production and fatty acid synthesis.", "output": "CGA, glucose, fatty acid." }, { "input": "Inhibition and knockdown of AMPK abrogated these metabolic alterations.", "output": "There is no related enetity." }, { "input": "In conclusion, CGA improved glucose and lipid metabolism, via the activation of AMPK.", "output": "CGA, glucose." }, { "input": "Fragment - based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy.", "output": "HJC0123." }, { "input": "Fragment - based drug design ( FBDD ) is a promising approach for the generation of lead molecules with enhanced activity and especially drug - like properties against therapeutic targets.", "output": "There is no related enetity." }, { "input": "Herein, we report the fragment - based drug design, systematic chemical synthesis and pharmacological evaluation of novel scaffolds as potent anticancer agents by utilizing six privileged fragments from known STAT3 inhibitors.", "output": "There is no related enetity." }, { "input": "Several new molecules such as compounds 5, 12, and 19 that may act as advanced chemical leads have been identified.", "output": "There is no related enetity." }, { "input": "The most potent compound 5 ( HJC0123 ) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase - 3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values.", "output": "HJC0123." }, { "input": "Furthermore, compound 5 significantly suppressed estrogen receptor ( ER ) - negative breast cancer MDA - MB - 231 xenograft tumor growth in vivo ( p. o. ), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy.", "output": "estrogen." }, { "input": "Synthesis and pharmacological evaluation of some novel 2 - ( 5 - hydroxy - 5 - trifluoromethyl - 4, 5 - dihydropyrazol - 1 - yl ) - 4 - ( coumarin - 3 - yl ) thiazoles.", "output": "2 - ( 5 - hydroxy - 5 - trifluoromethyl - 4 , 5 - dihydropyrazol - 1 - yl ) - 4 - ( coumarin - 3 - yl ) thiazoles." }, { "input": "A series of novel 2 - ( 5 - hydroxy - 5 - trifluoromethyl - 4, 5 - dihydropyrazol - 1 - yl ) - 4 - ( coumarin - 3 - yl ) thiazoles ( 6 ) were synthesized by condensing 3 - ( 2 - bromoacetyl ) coumarins ( 4 ) with various 5 - hydroxy - 5 - trifluoromethyl - 4, 5 - dihydropyrazol - 1 - thiocarboxamides ( 5 ), obtained by the reaction of thiosemicarbazide with trifluoromethyl - beta - diketones.", "output": "2 - ( 5 - hydroxy - 5 - trifluoromethyl - 4 , 5 - dihydropyrazol - 1 - yl ) - 4 - ( coumarin - 3 - yl ) thiazoles, 3 - ( 2 - bromoacetyl ) coumarins, 5 - hydroxy - 5 - trifluoromethyl - 4 , 5 - dihydropyrazol - 1 - thiocarboxamides, thiosemicarbazide, trifluoromethyl - beta - diketones." }, { "input": "All the tested compounds displayed significant to moderate in vivo anti - inflammatory activity when compared to the standard drug indomethacin, and good broad spectrum in vitro antibacterial activity against three Gram - positive and four Gram - negative bacteria when compared with cefixime.", "output": "indomethacin, cefixime." }, { "input": "A novel method to analyze nucleocytoplasmic transport in vivo by using short Peptide tags.", "output": "There is no related enetity." }, { "input": "Regulated nucleocytoplasmic transport is of vital importance for maintaining the physiology of the cell, and disturbed nucleocytoplasmic shuttling of certain proteins has been found in a variety of diseases including cancer.", "output": "There is no related enetity." }, { "input": "The most frequently used procedure to analyze those processes is to fuse the protein of interest to a fluorescent protein such as GFP ( green fluorescent protein ) - a technique that is prone to impair normal protein function and subcellular localization.", "output": "There is no related enetity." }, { "input": "We report a novel approach to monitor nucleocytoplasmic transport processes in vivo by combining short TetR inducing peptide tags ( TIP ) with a TetR - controlled reporter gene in a human cell line.", "output": "There is no related enetity." }, { "input": "The technology is exemplified by demonstrating nucleocytoplasmic shuttling of the glucocorticoid receptor and activity of two further TIP fusions to cancer - related proteins.", "output": "There is no related enetity." }, { "input": "The technology presented provides the basis for efficient screening systems to isolate compounds altering the nucleocytoplasmic distribution of a protein of interest.", "output": "There is no related enetity." }, { "input": "Alpha neurotoxins.", "output": "There is no related enetity." }, { "input": "alpha - Neurotoxins have been isolated from hydrophid, elapid and, more recently, colubrid snake venoms.", "output": "There is no related enetity." }, { "input": "Also referred to as postsynaptic neurotoxins or ' curare mimetic ' neurotoxins, they play an important role in the capture and / or killing of prey by binding to the nicotinic acetylcholine receptor on the skeletal muscle disrupting neurotransmission.", "output": "acetylcholine." }, { "input": "They are also thought to cause respiratory paralysis in envenomed humans.", "output": "There is no related enetity." }, { "input": "This review will discuss the historical background into the discovery, isolation, structure and mechanism of action of the alpha - neurotoxins, including targets and cellular outcomes, and then will examine the potential uses of alpha - neurotoxins as pharmacological tools and / or as drug leads.", "output": "There is no related enetity." }, { "input": "A cell - based, multiparametric sensor approach characterises drug - induced cytotoxicity in human liver HepG2 cells.", "output": "There is no related enetity." }, { "input": "Drug - induced toxicity is of considerable concern in drug discovery and development, placing emphasis on the need for predictive in vitro technologies that identify potential cytotoxic side effects of drugs.", "output": "There is no related enetity." }, { "input": "A label - free, real - time, multiparametric cytosensor system has therefore been established for in vitro assessment of drug - induced toxicity.", "output": "There is no related enetity." }, { "input": "The system is based on monitoring cellular oxygen consumption, acidification and impedance of human hepatocarcinoma - derived HepG2 cells.", "output": "oxygen." }, { "input": "The read - out derived from the multiparametric cytosensor system has been optimised and permits sensitive, reliable, and simultaneous recording of cell physiological signals, such as metabolic activity, cellular respiration and morphological changes and cell adhesion upon exposure to a drug.", "output": "There is no related enetity." }, { "input": "Analysis of eight prototypic reference drugs revealed distinct patterns of drug - induced physiological signals.", "output": "There is no related enetity." }, { "input": "Effects proved to be rigidly concentration - dependent.", "output": "There is no related enetity." }, { "input": "Based on signal patterns and reversibility of the observed effects, compounds could be classified based as triggering mechanisms of respiratory or metabolic stress or conditions leading to cell death ( necrosis - like and apoptosis - like ).", "output": "There is no related enetity." }, { "input": "A test - flag - risk mitigation strategy is proposed to address potential risks for drug - induced cytotoxicity.", "output": "There is no related enetity." }, { "input": "In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells.", "output": "aldehydes." }, { "input": "Tobacco smoke consists of thousands of harmful components.", "output": "There is no related enetity." }, { "input": "A major class of chemicals found in tobacco smoke is formed by aldehydes, in particular formaldehyde, acetaldehyde and acrolein.", "output": "aldehydes, formaldehyde, acetaldehyde, acrolein." }, { "input": "The present study investigates the gene expression changes in human lung alveolar epithelial cells upon exposure to formaldehyde, acrolein and acetaldehyde at sub - cytotoxic levels.", "output": "formaldehyde, acrolein, acetaldehyde." }, { "input": "We exposed A549 cells in vitro to aldehydes and non - aldehyde chemicals ( nicotine, hydroquinone and 2, 5 - dimethylfuran ) present in tobacco smoke and used microarrays to obtain a global view of the transcriptomic responses.", "output": "aldehydes, aldehyde, nicotine, hydroquinone, 2 , 5 - dimethylfuran." }, { "input": "We compared responses of the individual aldehydes with that of the non - aldehydes.", "output": "aldehydes, aldehydes." }, { "input": "We also studied the response of the aldehydes when present in a mixture at relative concentrations as present in cigarette smoke.", "output": "aldehydes." }, { "input": "Formaldehyde gave the strongest response; a total of 66 genes were more than 1. 5 - fold differentially expressed mostly involved in apoptosis and DNA damage related processes, followed by acetaldehyde ( 57 genes ), hydroquinone ( 55 genes ) and nicotine ( 8 genes ).", "output": "Formaldehyde, acetaldehyde, hydroquinone, nicotine." }, { "input": "For acrolein and the mixture only one gene was upregulated involved in oxidative stress.", "output": "acrolein." }, { "input": "No gene expression effect was found for exposure to 2, 5 - dimethylfuran.", "output": "2 , 5 - dimethylfuran." }, { "input": "Overall, aldehyde responses are primarily indicative for genotoxicity and oxidative stress.", "output": "aldehyde." }, { "input": "These two toxicity mechanisms are linked to respiratory diseases such as cancer and COPD, respectively.", "output": "There is no related enetity." }, { "input": "The present findings could be important in providing further understanding of the role of aldehydes emitted from cigarette smoke in the onset of pulmonary diseases.", "output": "aldehydes." }, { "input": "Levels of PAH - DNA adducts in placental tissue and the risk of fetal neural tube defects in a Chinese population.", "output": "PAH." }, { "input": "We examined the relationship between PAH - DNA adduct levels in the placental tissue, measured by a highly sensitive ( 32 ) P - postlabeling assay, and the risk of fetal neural tube defects ( NTDs ).", "output": "PAH, ( 32 ) P." }, { "input": "We further explored the interaction between PAH - DNA adducts and placental PAHs with respect to NTD risk.", "output": "PAH, PAHs." }, { "input": "Placental tissues from 80 NTD - affected pregnancies and 50 uncomplicated normal pregnancies were included in this case - control study.", "output": "There is no related enetity." }, { "input": "Levels of PAH - DNA adducts were lower in the NTD group ( 8. 12 per 10 ( 8 ) nucleotides ) compared to controls ( 9. 92 per 10 ( 8 ) nucleotides ).", "output": "PAH, nucleotides, nucleotides." }, { "input": "PAH - DNA adduct concentrations below the median was associated with a 3 - fold increased NTD risk.", "output": "PAH." }, { "input": "Women with a low PAH - DNA adduct level in concert with a high placental PAH level resulted in a 10 - fold elevated risk of having an NTD - complicated pregnancy.", "output": "PAH, PAH." }, { "input": "A low level of placental PAH - DNA adducts was associated with an increased risk of NTDs; this risk increased dramatically when a low adduct level was coupled with a high placental PAH concentration.", "output": "PAH, PAH." }, { "input": "Quantitative proteomic analysis reveals the mode - of - action for chronic mercury hepatotoxicity to marine medaka ( Oryzias melastigma ).", "output": "mercury." }, { "input": "Mercury ( Hg ) is a widespread persistent pollutant in aquatic ecosystems.", "output": "Mercury, Hg." }, { "input": "We investigated the protein profiles of medaka ( Oryzias melastigma ) liver chronically exposed to different mercuric chloride ( HgCl2 ) concentrations ( 1 or 10 mu g / L ) for 60 d using two - dimensional difference gel electrophoresis ( 2D - DIGE ), as well as cell ultrastructure and Hg content analysis of the hepatic tissue.", "output": "mercuric chloride, HgCl2, Hg." }, { "input": "The results showed that Hg exposure significantly increased metal accumulation in the liver, and subsequently damaged liver ultrastructure.", "output": "Hg." }, { "input": "Comparison of the 2D - DIGE protein profiles of the exposed and control groups revealed that the abundance of 45 protein spots was remarkably altered in response to Hg treatment.", "output": "Hg." }, { "input": "The altered spots were subjected to matrix - assisted laser desorption / ionization tandem time - of - flight mass spectrometry analysis, with the resultant identification of 33 spots.", "output": "There is no related enetity." }, { "input": "These proteins were mainly involved in cytoskeleton assembly, oxidative stress, and energy production.", "output": "There is no related enetity." }, { "input": "Among them, several proteins related to mitochondrial function ( e. g. respiratory metabolism ) were significantly altered in the treated hepatocytes, implying that this organelle might be the primary target for Hg attack in the cells.", "output": "Hg." }, { "input": "This study provided new insights into the molecular mechanisms and / or toxic pathways by which chronic Hg hepatotoxicity affects aquatic organisms, and also provided basic information for screening potential biomarkers for aquatic Hg monitoring.", "output": "Hg, Hg." }, { "input": "Single and 90 - day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague - Dawley rats.", "output": "There is no related enetity." }, { "input": "Fermented Rhus verniciflua stem bark ( FRVSB ) extract, an urushiol - free extract of Rhus verniciflua Stokes ( RVS ) fermented with Fomitella fraxinea, has various biological activities.", "output": "urushiol." }, { "input": "The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague - Dawley rats.", "output": "There is no related enetity." }, { "input": "In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10, 000mg / kg.", "output": "There is no related enetity." }, { "input": "No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15 - day period following administration.", "output": "There is no related enetity." }, { "input": "In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90days at doses of 0, 556, 1667, and 5000mg / kg / day.", "output": "There is no related enetity." }, { "input": "There were no treatment - related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested.", "output": "There is no related enetity." }, { "input": "The approximate lethal dose of the FRVSB extract was > 10, 000mg / kg in both genders, the oral no - observed - adverse - effect level of the FRVSB extract was > 5000mg / kg / day in both genders, and no target organs were identified.", "output": "There is no related enetity." }, { "input": "The production and characterization of anti - bothropic and anti - crotalic IgY antibodies in laying hens: a long term experiment.", "output": "There is no related enetity." }, { "input": "Ophidian accidents represent a great public health problem in developing countries.", "output": "There is no related enetity." }, { "input": "Recent studies have shown that antibodies produced in laying hens could be an alternative method for producing antivenin in mammals.", "output": "There is no related enetity." }, { "input": "In this study we analyzed the production of IgY antibodies in laying hens inoculated with snake venom from the Bothrops and Crotalus genera over a 360 - day period.", "output": "There is no related enetity." }, { "input": "IgY antibodies present in the serum and egg yolks were analyzed according to avidity, antigen recognition pattern and efficiency in neutralizing the venom.", "output": "There is no related enetity." }, { "input": "The levels of anti - bothropic and anti - crotalic IgY antibodies increased significantly after the third immunization, and remained at these levels until the end of the experiment.", "output": "There is no related enetity." }, { "input": "Significantly high avidity levels were observed for anti - bothropic IgY antibodies on the 142nd day and for anti - crotalic antibodies on the 232nd day after the first immunization.", "output": "There is no related enetity." }, { "input": "Anti - bothropic IgY antibodies recognized antigens with molecular masses ranging from 25 kDa to 50 kDa, whereas anti - crotalic IgY antibodies mainly recognized antigens with molecular masses of 14 kDa and 30 kDa.", "output": "There is no related enetity." }, { "input": "An increase in the antigens recognized by the antivenins was observed during the experimental period.", "output": "There is no related enetity." }, { "input": "Samples of bothropic IgY antivenin antibodies presented an efficiency of 290 mu l / 3 DL50, a potency of 0. 307 mg / ml and a specific activity of 0. 230.", "output": "There is no related enetity." }, { "input": "Samples of anti - crotalic IgY antibodies presented an efficiency of 246 mu l / 4 DL50, a potency of 0. 829 mg / ml and a specific activity of 0. 271.", "output": "There is no related enetity." }, { "input": "These results show that the administration of successive doses of the venoms for more than 6 months results in an antivenin with higher avidity that is able to recognize a greater number of antigens present in the venoms.", "output": "There is no related enetity." }, { "input": "These characteristics indicate a more efficient and potent antivenin than what has been described in other studies.", "output": "There is no related enetity." }, { "input": "A review of mouse critical size defect models in weight bearing bones.", "output": "There is no related enetity." }, { "input": "Current and future advances in orthopedic treatment are aimed at altering biological interactions to enhance bone healing.", "output": "There is no related enetity." }, { "input": "Currently, several clinical scenarios exist for which there is no definitive treatment, specifically segmental bone loss from high - energy trauma or surgical resection - and it is here that many are aiming to find effective solutions.", "output": "There is no related enetity." }, { "input": "To test experimental interventions and better understand bone healing, researchers employ critical size defect ( CSD ) models in animal studies.", "output": "There is no related enetity." }, { "input": "Here, an overview of CSDs is given that includes the specifications of varying models, a discussion of current scaffold and bone graft designs, and current outcome measures used to determine the extent of bone healing.", "output": "There is no related enetity." }, { "input": "Many promising graft designs have been discovered along with promising adjunctive treatments, yet a graft that offers biomechanical support while allowing for neovascularization with eventual complete resorption and remodeling remains to be developed.", "output": "There is no related enetity." }, { "input": "An overview of this important topic is needed to highlight current advances and provide a clear understanding of the ultimate goal in CSD research - develop a graft for clinical use that effectively treats the orthopedic conundrum of segmental bone loss.", "output": "There is no related enetity." }, { "input": "Autophagy in ageing and ageing - associated diseases.", "output": "There is no related enetity." }, { "input": "Autophagy is a cell self - digestion process via lysosomes that clears \" cellular waste \", including aberrantly modified proteins or protein aggregates and damaged organelles.", "output": "There is no related enetity." }, { "input": "Therefore, autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis.", "output": "There is no related enetity." }, { "input": "Dysfunctional autophagy has been observed in ageing tissues and several ageing - associated diseases.", "output": "There is no related enetity." }, { "input": "Lifespan of model organisms such as yeast, worms, flies, and mice can be extended through promoting autophagy, either by genetic manipulations such as over - expression of Sirtuin 1, or by administrations of rapamycin, resveratrol or spermidine.", "output": "rapamycin, resveratrol, spermidine." }, { "input": "The evidence supports that autophagy may play an important role in delaying ageing or extending lifespan.", "output": "There is no related enetity." }, { "input": "In this review, we summarize the current knowledge about autophagy and its regulation, outline recent developments ie the genetic and pharmacological manipulations of autophagy that affects the lifespan, and discuss the role of autophagy in the ageing - related diseases.", "output": "There is no related enetity." }, { "input": "Excess androgen during puberty disrupts circadian organization in female rats.", "output": "androgen." }, { "input": "Circadian clocks have been described in each tissue of the hypothalamo - pituitary - ovarian axis.", "output": "There is no related enetity." }, { "input": "Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks ' role in the etiology of these pathologies has yet to be fully appreciated.", "output": "There is no related enetity." }, { "input": "Polycystic ovary syndrome ( PCOS ) is a particularly devastating endocrinopathy, affecting approximately 10 % of women at childbearing age.", "output": "There is no related enetity." }, { "input": "Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen.", "output": "androgen." }, { "input": "Approximately 40 % of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia.", "output": "There is no related enetity." }, { "input": "It has been suggested that excess androgen is a critical factor in the etiology of PCOS.", "output": "androgen." }, { "input": "We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo - pituitary - ovarian axes.", "output": "androgen." }, { "input": "Female period1 - luciferase ( per1 - luc ) rats were exposed to androgen ( 5 alpha - dihydrotestosterone [ DHT ] ) or placebo for 4 - 6 weeks ( short term ) or 9 - 15 weeks ( long term ).", "output": "androgen, 5 alpha - dihydrotestosterone, DHT." }, { "input": "As expected, DHT - treated animals gained more weight than controls and had disrupted estrous cycles.", "output": "DHT." }, { "input": "At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1 - luc expression in each was recorded.", "output": "There is no related enetity." }, { "input": "Analysis of per1 - luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals.", "output": "DHT." }, { "input": "These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.", "output": "androgen." }, { "input": "Estimating population - level HC5 for copper using a species sensitivity distribution approach.", "output": "copper." }, { "input": "Estimation of population - level benchmark concentrations for protecting aquatic organisms from chemicals is important for value - relevant ecological risk assessments.", "output": "There is no related enetity." }, { "input": "By employing a species sensitivity distribution ( SSD ) approach, the authors aimed to derive the population - level hazardous concentration for 5 % of species ( PHC5 ) for copper.", "output": "copper." }, { "input": "Based on available information on copper toxicity and population models, the authors estimated population threshold concentrations at which the population size is stable ( that is, 0 net population growth ) for 13 freshwater species ( 3 algal, 6 invertebrate, and 4 fish species ).", "output": "copper." }, { "input": "The PHC5 for copper was then estimated ( 6. 8 micro g / L; 95 % confidence interval [ CI ], 1. 8 - 13. 6 micro g / L ), by fitting a log - normal distribution to the population threshold concentrations obtained.", "output": "copper." }, { "input": "The close overlap between the present study ' s estimate of the PHC5 and a field - derived threshold concentration suggests that the population - level SSD approach provides a reasonable level of protection for species richness in the natural environment.", "output": "There is no related enetity." }, { "input": "By contrast, and counterintuitively, the authors ' estimate was comparable with the individual - level HC5 reported in the European Union risk assessment.", "output": "There is no related enetity." }, { "input": "Although the present study cannot determine the underlying reasons for the similar figures, the result provides an indication that the margin between individual - level and population - level benchmarks derived from SSD approaches can be very small.", "output": "There is no related enetity." }, { "input": "The results therefore suggest that attention is needed to achieve population - level protection using an individual - level SSD approach.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1396 - 1402.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Determination of mercury speciation in fish tissue with a direct mercury analyzer.", "output": "mercury, mercury." }, { "input": "Knowledge of Hg speciation in tissue is valuable for assessing potential toxicological effects in fish.", "output": "Hg." }, { "input": "Direct Hg analyzers, which use thermal decomposition and atomic absorption spectrometry, have recently gained popularity for determining organic Hg after procedural solvent extraction from some environmental media, although quantitative recovery from lipid - rich materials, such as fish liver, has been problematic.", "output": "Hg, Hg." }, { "input": "The authors developed a new method by which organic Hg in fish liver and muscle is estimated by the difference between direct measurements of inorganic Hg in an acid extract and total Hg in whole tissue.", "output": "Hg, Hg, Hg." }, { "input": "The method was validated by analysis of a certified reference material ( DOLT - 4 dogfish liver ) and naturally contaminated fish tissues with comparison to an established Hg speciation method ( gas chromatography cold vapor atomic fluorescence spectrometry ).", "output": "Hg." }, { "input": "Recovery of organic Hg from DOLT - 4, estimated by difference, averaged 99 +/- 5 % of the mean certified value for methylmercury.", "output": "Hg, methylmercury." }, { "input": "In most liver samples and all muscle samples, estimates of organic Hg from the proposed method were indiscernible from direct speciation measurements of methylmercury ( 99 % +/- 6 % ).", "output": "Hg, methylmercury." }, { "input": "Estimation of organic Hg by the difference between total Hg and inorganic Hg was less accurate in liver samples with a high percentage of inorganic Hg ( 90 % ).", "output": "Hg, Hg, Hg, Hg." }, { "input": "This was because of the increased uncertainty that results from estimating a third value ( i. e., organic Hg ) by using the difference between two large concentrations ( inorganic and total Hg ).", "output": "Hg, Hg." }, { "input": "The proposed method is a useful tool for examining the speciation of Hg in fish muscle and liver, and by extension, potentially other tissues and environmental media.", "output": "Hg." }, { "input": "Environ Toxicol Chem 2013; 32: 1237 - 1241.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Versatile Nanostructured Materials via Direct Reaction of Functionalized Catechols.", "output": "Catechols." }, { "input": "A facile one - step polymerization strategy is explored to achieve novel catechol - based materials.", "output": "catechol." }, { "input": "Depending on the functionality of the catechol, the as - prepared product can be used to modify at will the surface tension of nano and bulk structures, from oleo - / hydrophobic to highly hydrophilic.", "output": "catechol." }, { "input": "A hydrophobic catechol prepared thus polymerized shows the ability to self - assemble as solid nanoparticles with sticky properties in polar solvent media.", "output": "catechol." }, { "input": "Such a versatile concept is ideal for the development of catechol - based multifunctional materials.", "output": "catechol." }, { "input": "Structural insights into the recovery of aldolase activity in N - acetylneuraminic acid lyase by replacement of the catalytically active lysine with gamma - thialysine by using a chemical mutagenesis strategy.", "output": "N - acetylneuraminic acid, lysine, gamma - thialysine." }, { "input": "Chemical modification has been used to introduce the unnatural amino acid gamma - thialysine in place of the catalytically important Lys165 in the enzyme N - acetylneuraminic acid lyase ( NAL ).", "output": "amino acid, gamma - thialysine, Lys165, N - acetylneuraminic acid." }, { "input": "The Staphylococcus aureus nanA gene, encoding NAL, was cloned and expressed in E. coli.", "output": "There is no related enetity." }, { "input": "The protein, purified in high yield, has all the properties expected of a class I NAL.", "output": "There is no related enetity." }, { "input": "The S. aureus NAL which contains no natural cysteine residues was subjected to site - directed mutagenesis to introduce a cysteine in place of Lys165 in the enzyme active site.", "output": "cysteine, cysteine, Lys165." }, { "input": "Subsequently chemical mutagenesis completely converted the cysteine into gamma - thialysine through dehydroalanine ( Dha ) as demonstrated by ESI - MS.", "output": "cysteine, gamma - thialysine, dehydroalanine, Dha." }, { "input": "Initial kinetic characterisation showed that the protein containing gamma - thialysine regained 17 % of the wild - type activity.", "output": "gamma - thialysine." }, { "input": "To understand the reason for this lower activity, we solved X - ray crystal structures of the wild - type S. aureus NAL, both in the absence of, and in complex with, pyruvate.", "output": "pyruvate." }, { "input": "We also report the structures of the K165C variant, and the K165 - gamma - thialysine enzyme in the presence, or absence, of pyruvate.", "output": "gamma - thialysine, pyruvate." }, { "input": "These structures reveal that gamma - thialysine in NAL is an excellent structural mimic of lysine.", "output": "gamma - thialysine, lysine." }, { "input": "Measurement of the pH - activity profile of the thialysine modified enzyme revealed that its pH optimum is shifted from 7. 4 to 6. 8.", "output": "thialysine." }, { "input": "At its optimum pH, the thialysine - containing enzyme showed almost 30 % of the activity of the wild - type enzyme at its pH optimum.", "output": "thialysine." }, { "input": "The lowered activity and altered pH profile of the unnatural amino acid - containing enzyme can be rationalised by imbalances of the ionisation states of residues within the active site when the pK ( a ) of the residue at position 165 is perturbed by replacement with gamma - thialysine.", "output": "amino acid, gamma - thialysine." }, { "input": "The results reveal the utility of chemical mutagenesis for the modification of enzyme active sites and the exquisite sensitivity of catalysis to the local structural and electrostatic environment in NAL.", "output": "There is no related enetity." }, { "input": "Cytophilic / Cytophobic Design of Nanomaterials at Biointerfaces.", "output": "There is no related enetity." }, { "input": "To control interactions between cells and nanomaterials has been a great challenge because numerous nanomaterials have been intensively explored in the fields of biology and medicine.", "output": "There is no related enetity." }, { "input": "However, current surface modification of nanomaterials is mainly carried out in an empirical way.", "output": "There is no related enetity." }, { "input": "Herein, a general strategy to tune the surface chemistry of nanomaterials is proposed based on cell affinity, that is, cytophilic or cytophobic.", "output": "There is no related enetity." }, { "input": "The cell affinity of nanomaterials directly affects cellular response to materials at the very early stage of cell - material interactions before other events, such as endocytosis, cell spreading, and cell differentiation, occur.", "output": "There is no related enetity." }, { "input": "In this Concept, it is suggested that there is a developing library of cytophilic and cytophobic moieties, and how the cell affinity of nanomaterials functions at biointerfaces is discussed by exemplifying several applications, namely therapy, tissue engineering, and biosensors.", "output": "There is no related enetity." }, { "input": "It is believed that control of the cytophilic / cytophobic property will be helpful in guiding the design of functional nanomaterials for their biomedical applications.", "output": "There is no related enetity." }, { "input": "Forty - seven days of decay does not change persistent organic pollutant levels in loggerhead sea turtle eggs.", "output": "There is no related enetity." }, { "input": "Reptile and bird eggs are priority samples for specimen banking programs that assess spatial and temporal trends of environmental contaminants.", "output": "There is no related enetity." }, { "input": "From endangered species, such as sea turtles, nonlethal sampling is required ( e. g., unhatched eggs collected postemergence ).", "output": "There is no related enetity." }, { "input": "Previous contaminant monitoring studies have used unhatched sea turtle eggs, but no study has tested whether their concentrations represent levels found in fresh eggs ( e. g., eggs collected within 24 h of oviposition ).", "output": "There is no related enetity." }, { "input": "The author analyzed three fresh eggs from different nest depths and up to three unhatched eggs from 10 loggerhead sea turtle ( Caretta caretta ) nests in South Carolina, USA, for a suite of persistent organic pollutants ( POPs ).", "output": "There is no related enetity." }, { "input": "Lipid - normalized POP concentrations were not significantly different ( p > 0. 05 ) between fresh and unhatched eggs or among different depths from the same nest.", "output": "There is no related enetity." }, { "input": "The POP concentrations in loggerhead eggs from South Carolina were higher than previously measured concentrations in eggs from Florida and slightly lower than concentrations in eggs from North Carolina.", "output": "There is no related enetity." }, { "input": "This pattern agrees with previously observed trends of increasing POP concentrations in loggerhead turtles inhabiting northern latitudes along the U. S.", "output": "There is no related enetity." }, { "input": "East Coast.", "output": "There is no related enetity." }, { "input": "Contaminant profiles are discussed, including a higher chlorinated pattern of polychlorinated biphenyls possibly associated with a Superfund site in nearby Brunswick, Georgia, USA, and unusual polybrominated diphenylether patterns seen in this and previous sea turtle studies.", "output": "polychlorinated biphenyls, polybrominated diphenylether." }, { "input": "Concentrations correlated with one of eight measurements of reproductive success; levels were negatively correlated with egg mass ( p < 0. 05 ), which may have implications for hatchling fitness.", "output": "There is no related enetity." }, { "input": "The present study suggests that unhatched eggs can be used for POP - monitoring projects.", "output": "There is no related enetity." }, { "input": "Lifelong exposure to bisphenol a alters cardiac structure / function, protein expression, and DNA methylation in adult mice.", "output": "bisphenol a." }, { "input": "Bisphenol A ( BPA ) is an estrogenizing endocrine disruptor compound of concern.", "output": "Bisphenol A, BPA." }, { "input": "Our objective was to test whether lifelong BPA would impact cardiac structure / function, calcium homeostasis protein expression, and the DNA methylation of cardiac genes.", "output": "BPA, calcium." }, { "input": "We delivered 0. 5 and 5. 0 micro g / kg / day BPA lifelong from gestation day 11 or 200 micro g / kg / day from gestation day 11 to postnatal day 21 via the drinking water to C57bl / 6n mice.", "output": "BPA." }, { "input": "BPA 5. 0 males and females had increased body weight, body mass index, body surface area, and adiposity.", "output": "BPA." }, { "input": "Echocardiography identified concentric remodeling in all BPA - treated males.", "output": "BPA." }, { "input": "Systolic and diastolic cardiac functions were essentially similar, but lifelong BPA enhanced male and reduced female sex - specific differences in velocity of circumferential shortening and ascending aorta velocity time integral.", "output": "BPA." }, { "input": "Diastolic blood pressure was increased in all BPA females.", "output": "BPA." }, { "input": "The calcium homeostasis proteins sarcoendoplasmic reticulum ATPase 2a ( SERCA2a ), sodium calcium exchanger - 1, phospholamban ( PLB ), phospho - PLB, and calsequestrin 2 are important for contraction and relaxation.", "output": "calcium, sodium, calcium, phospho." }, { "input": "Changes in their expression suggest increased calcium mobility in males and reduced calcium mobility in females supporting the cardiac function changes.", "output": "calcium, calcium." }, { "input": "DNA methyltransferase 3a expression was increased in all BPA males and BPA 0. 5 females and reduced in BPA 200 females.", "output": "BPA, BPA, BPA." }, { "input": "Global DNA methylation was increased in BPA 0. 5 males and reduced in BPA 0. 5 females.", "output": "BPA, BPA." }, { "input": "BPA induced sex - specific altered DNA methylation in specific CpG pairs in the calsequestrin 2 CpG island.", "output": "BPA, CpG." }, { "input": "These results suggest that continual exposure to BPA impacts cardiac structure / function, protein expression, and epigenetic DNA methylation marks in males and females.", "output": "BPA." }, { "input": "The sorting of proglucagon to secretory granules is mediated by carboxypeptidase E and intrinsic sorting signals.", "output": "There is no related enetity." }, { "input": "Proglucagon is expressed in pancreatic alpha cells, intestinal L cells and brainstem neurons.", "output": "There is no related enetity." }, { "input": "Tissue - specific processing of proglucagon yields the peptide hormones glucagon in the alpha cell and glucagon - like peptide ( GLP ) - 1 and GLP - 2 in L cells.", "output": "There is no related enetity." }, { "input": "Both glucagon and GLP - 1 are secreted in response to nutritional status and are critical for regulating glycaemia.", "output": "There is no related enetity." }, { "input": "The sorting of proglucagon to the dense - core secretory granules of the regulated secretory pathway is essential for the appropriate secretion of glucagon and GLP - 1.", "output": "There is no related enetity." }, { "input": "We examined the roles of carboxypeptidase E ( CPE ), a prohormone sorting receptor, the processing enzymes PC1 / 3 and PC2 and putative intrinsic sorting signals in proglucagon sorting.", "output": "There is no related enetity." }, { "input": "In Neuro 2a cells that lacked CPE, PC1 / 3 and PC2, proglucagon co - localised with the Golgi marker p115 as determined by quantitative immunofluorescence microscopy.", "output": "There is no related enetity." }, { "input": "Expression of CPE, but not of PC1 / 3 or PC2, enhanced proglucagon sorting to granules.", "output": "There is no related enetity." }, { "input": "siRNA - mediated knockdown of CPE disrupted regulated secretion of glucagon from pancreatic - derived alphaTC1 - 6 cells, but not of GLP - 1 from intestinal cell - derived GLUTag cells.", "output": "There is no related enetity." }, { "input": "Mutation of the PC cleavage site K70R71, the dibasic R17R18 site within glucagon or the alpha - helix of glucagon, all significantly affected the sub - cellular localisation of proglucagon.", "output": "There is no related enetity." }, { "input": "Protein modelling revealed that alpha helices corresponding to glucagon, GLP - 1 and GLP - 2, are arranged within a disordered structure, suggesting some flexibility in the sorting mechanism.", "output": "There is no related enetity." }, { "input": "We conclude that there are multiple mechanisms for sorting proglucagon to the regulated secretory pathway, including a role for CPE in pancreatic alpha cells, initial cleavage at K70R71 and multiple sorting signals.", "output": "There is no related enetity." }, { "input": "Development of a cell - based high - throughput peroxisome proliferator - activated receptors ( PPARs ) screening model and its application for evaluation of the extracts from Rhizoma Coptis.", "output": "There is no related enetity." }, { "input": "To date, peroxisome proliferator - activated receptors ( PPARs ) are becoming the new therapeutic targets for the treatment of metabolic diseases, such as Type 2 diabetes, obesity, and cardiovascular disease.", "output": "There is no related enetity." }, { "input": "In this study, a cell - based high - throughput PPARs ( PPAR alpha / beta / gamma ) model was developed for the screening of PPARs agonists.", "output": "There is no related enetity." }, { "input": "The screening conditions were evaluated through analyzing the expression value of luciferase.", "output": "There is no related enetity." }, { "input": "Finally, 24 h of drug acting time, 5 times of the dilution factor of luciferase zymolyte, and about 2 x 10 ( 4 ) cells / well on HeLa cells in 96 - well plates were used, respectively.", "output": "There is no related enetity." }, { "input": "Furthermore, the quality of high - throughput screening ( HTS ) in stability and reliability was evaluated by the Z ' - factor.", "output": "There is no related enetity." }, { "input": "Additionally, different extracts of Rhizoma Coptis and berberine were tested by the developed method.", "output": "berberine." }, { "input": "The results suggested that both the EtOAc extract and berberine were able to activate PPAR alpha / beta / gamma, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.", "output": "EtOAc, berberine, berberine." }, { "input": "In conclusion, the developed HTS assay is a simple, rapid, stable, and specific method for the screening of PPARs natural agonists.", "output": "There is no related enetity." }, { "input": "Salidroside attenuates myocardial ischemia - reperfusion injury via PI3K / Akt signaling pathway.", "output": "Salidroside." }, { "input": "To investigate the cardioprotective effects of salidroside on myocardial ischemia - reperfusion injury ( IRI ) in rabbits and the underlying action mechanisms in PI3K / Akt signaling pathway, a rabbit ischemia / reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min.", "output": "salidroside." }, { "input": "Salidroside or salidroside + PI3K inhibitor ( LY294002 ) was administered via intracoronary injections at the onset of reperfusion.", "output": "Salidroside, salidroside, LY294002." }, { "input": "Apoptosis of cardiomyocytes was assessed by terminal dUTP nick - end labeling assay, and the expression of apoptosis - related proteins was observed by immunohistochemistry.", "output": "dUTP." }, { "input": "The expressions of total Akt and phosphorylated Akt ( p - Akt ) were detected by western blot analysis.", "output": "There is no related enetity." }, { "input": "The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl - 2 and p - Akt proteins expressions and decreasing Bax and caspase - 3 expressions in the hearts subjected to ischemia followed by 120 - min reperfusion.", "output": "salidroside." }, { "input": "However, the anti - apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt.", "output": "salidroside, LY294002." }, { "input": "These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI - induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K - Akt signaling pathway.", "output": "salidroside." }, { "input": "A new antibacterial denitroaristolochic acid from the tubers of Stephania succifera.", "output": "denitroaristolochic acid." }, { "input": "A new denitroaristolochic acid, demethylaristofolin C ( 1 ), together with six known alkaloids, crebanine N - oxide ( 2 ), ( - ) - sukhodianine - beta - N - oxide ( 3 ), palmatine ( 4 ), corydalmine ( 5 ), dehydrocorydalmine ( 6 ), and corynoxidine ( 7 ), was isolated from the tubers of Stephania succifera.", "output": "denitroaristolochic acid, demethylaristofolin C, crebanine N - oxide, ( - ) - sukhodianine - beta - N - oxide, palmatine, corydalmine, dehydrocorydalmine, corynoxidine." }, { "input": "The structure of demethylaristofolin C was elucidated by spectroscopic techniques ( UV, IR, 1D, and 2D NMR ) and HR - ESI - MS analyses.", "output": "demethylaristofolin C." }, { "input": "These compounds exhibited antibacterial activities against Staphylococcus aureus and methicillin - resistant S. aureus strains in different degrees.", "output": "methicillin." }, { "input": "Preparation and characterization of progesterone dispersions using supercritical carbon dioxide.", "output": "progesterone, carbon dioxide." }, { "input": "Abstract Context: Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable.", "output": "There is no related enetity." }, { "input": "Objective: To design, develop and construct a unit for the particles from a gas - saturated suspension / solution ( PGSS ) method and form endogenous progesterone ( PGN ) dispersion systems using SC - CO ( 2 ).", "output": "progesterone, PGN, CO ( 2 )." }, { "input": "Materials and methods: The PGN dispersions were manufactured using three selected excipients: polyethylene glycol ( PEG ) 400 / 4000 ( 50: 50 ), Gelucire 44 / 14 and D - alpha - tocopheryl PEG 1000 succinate ( TPGS ).", "output": "PGN, polyethylene glycol, PEG, Gelucire, D - alpha - tocopheryl PEG 1000 succinate, TPGS." }, { "input": "Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting ( CM ), cosolvent ( CS ) and physical mixing ( PM ).", "output": "PGN." }, { "input": "The dispersion systems made were characterized by Raman and Fourier transform infrared ( FTIR ) spectroscopies, X - ray powder diffraction ( XRPD ), scanning electron microscopy ( SEM ), PGN recovery, uniformity and in vitro dissolution, analyzed by high - performance liquid chromatography ( HPLC ).", "output": "PGN." }, { "input": "Results: Raman spectra revealed no changes in the crystalline structure of PGN treated with SC - CO ( 2 ) compared to that of untreated PGN.", "output": "PGN, CO ( 2 ), PGN." }, { "input": "XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient.", "output": "PGN, PGN." }, { "input": "All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min ( p value < 0. 05 ).", "output": "PGN, PGN, PGN." }, { "input": "Conclusion: The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.", "output": "PGN, PGN." }, { "input": "Incorporation of rapid thermodynamic data in fragment - based drug discovery.", "output": "There is no related enetity." }, { "input": "Fragment - based drug discovery ( FBDD ) has enjoyed increasing popularity in recent years.", "output": "There is no related enetity." }, { "input": "We introduce SITE ( single - injection thermal extinction ), a novel thermodynamic methodology that selects high - quality hits early in FBDD.", "output": "There is no related enetity." }, { "input": "SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources.", "output": "There is no related enetity." }, { "input": "We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.", "output": "ketosteroid." }, { "input": "In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK - NOG mice.", "output": "thalidomide, midazolam." }, { "input": "In vivo drug interactions of the teratogen thalidomide with the model cytochrome P450 ( P450 ) 3A substrate midazolam were investigated in mice with humanized livers.", "output": "thalidomide, midazolam." }, { "input": "The clearance of midazolam ( administered intravenously, 10 mg kg ( - 1 ) ) in chimeric mice was enhanced by orally co - administered thalidomide ( 100 mg kg ( - 1 ) ).", "output": "midazolam, thalidomide." }, { "input": "A larger area under the curve of the major metabolite 1 ' - hydroxymidazolam ( 1. 7 - fold ) was obtained with thalidomide because of the heterotropic cooperativity of human P450 3A enzymes.", "output": "1 ' - hydroxymidazolam, thalidomide." }, { "input": "A larger area under the curve of the minor metabolite 4 - hydroxymidazolam ( 3. 5 - fold ) was seen with daily pretreatment with thalidomide for 3 days, presumably because of human P450 3A induction.", "output": "4 - hydroxymidazolam, thalidomide." }, { "input": "These results demonstrate that livers of humanized mice mediate drug interactions of thalidomide and suggest interactions of therapeutic agents during therapies with thalidomide.", "output": "thalidomide, thalidomide." }, { "input": "Electrically conductive gold - and copper - metallized DNA origami nanostructures.", "output": "copper." }, { "input": "This work demonstrates the use of a circuit - like DNA origami structure as a template to fabricate conductive gold and copper nanostructures on Si surfaces.", "output": "copper, Si." }, { "input": "We improved over previous results by using multiple Pd seeding steps to increase seed uniformity and density.", "output": "Pd." }, { "input": "Our process has also been characterized through atomic force microscopy, particle size distribution analysis, and scanning electron microscopy.", "output": "There is no related enetity." }, { "input": "We found that four successive Pd seeding steps yielded the best results for electroless metal plating on DNA origami.", "output": "Pd." }, { "input": "Electrical resistance measurements were done on both Au - and Cu - metallized nanostructures, with each showing ohmic behavior.", "output": "Au, Cu." }, { "input": "Gold - plated DNA origami structures made under optimal conditions had an average resistivity of 7. 0 x 10 ( - 5 ) Omega. m, whereas copper - metallized structures had a resistivity as low as 3. 6 x 10 ( - 4 ) Omega. m.", "output": "copper." }, { "input": "Importantly, this is the first demonstration of electrically conductive Cu nanostructures fabricated on either DNA or DNA origami templates.", "output": "Cu." }, { "input": "Although resistivities for both gold and copper samples were larger than those of the bulk metal, these metal nanostructures have the potential for use in electrically connecting small structures.", "output": "copper." }, { "input": "In addition, these metallized objects might find use in surface - enhanced Raman scattering experiments.", "output": "There is no related enetity." }, { "input": "Temporal relationship between aquaporin - 4 and glial fibrillary acidic protein in cerebellum of neonate and adult rats administered a BBB disrupting spider venom.", "output": "There is no related enetity." }, { "input": "Two astrocyte markers, the glial water channel aquaporin - 4 ( AQP4 ) and the glial fibrillary acidic protein ( GFAP ), have been implicated in several physiological and pathological conditions in the central nervous system ( CNS ) as well as in blood - brain barrier breakdown ( BBBb ).", "output": "There is no related enetity." }, { "input": "By color segmentation the immunoreactivity of both proteins, we demonstrate that the expression of AQP4 and GFAP was increased in the cerebellum of neonate ( 14 - day - old, P14 ) and adult ( 8 - week - old ) rats administered Phoneutria nigriventer spider venom ( PNV ) known to cause perivascular edema, BBBb and convulsion.", "output": "There is no related enetity." }, { "input": "In the cerebellum ' s gray matter, PNV produced a major response, especially in the granular layer.", "output": "There is no related enetity." }, { "input": "Parallel increases in AQP4 and GFAP expression occurred 24 h after envenomation in the white matter of P14 and in the molecular layer of adults, as well as in the granular layer 2 h after envenomation.", "output": "There is no related enetity." }, { "input": "In the Purkinje layer there was a tendency of increased AQP4, for both, neonates ( 5 h ), and adults ( 2 and 24 h ).", "output": "There is no related enetity." }, { "input": "Moreover, PNV also provoked nonparallel upregulation of both markers with prevalence of upregulation of AQP 4 for P14 rats, and GFAP for adults.", "output": "There is no related enetity." }, { "input": "The major expression of both proteins was in the gray matter.", "output": "There is no related enetity." }, { "input": "The data indicates a venom effect in water / electrolyte balance in the cerebellum and the participation of AQP4 in these effects.", "output": "There is no related enetity." }, { "input": "Age - related and time - related regional differences probably reflect specificity in AQP4 distribution in different astrocytic membrane domains as well as its participation in K ( + ) buffering and neural activity.", "output": "K ( + )." }, { "input": "This study is the first to associate astrocytic AQP4 expression and reactive gliosis in a model of BBB permeability promoted by P. nigriventer venom.", "output": "There is no related enetity." }, { "input": "Our data provide compelling evidence that AQP4 expression was increased in the cerebellum of rats administered PNV.", "output": "There is no related enetity." }, { "input": "Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T.", "output": "Pelargonidin." }, { "input": "We examined the effects of anthocyanidins ( cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin ) on the aryl hydrocarbon receptor ( AhR ) - CYP1A1 signaling pathway in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cells.", "output": "anthocyanidins, cyanidin, delphinidin, malvidin, peonidin, petunidin, pelargonidin, aryl hydrocarbon." }, { "input": "AhR - dependent reporter gene expression in transfected HepG2 cells was increased by pelargonidin in a concentration - dependent manner at 24h.", "output": "pelargonidin." }, { "input": "Similarly, pelargonidin induced the expression of CYP1A1 mRNA up to 5 - fold in HepG2 and LS174T cells relative to the induction by 5 nM 2, 3, 7, 8 - tetrachlorodibenzodioxin ( TCDD ), the most potent activator of AhR.", "output": "pelargonidin, 2 , 3 , 7 , 8 - tetrachlorodibenzodioxin, TCDD." }, { "input": "CYP1A1 and CYP1A2 mRNAs were also increased by pelargonidin in three primary human hepatocytes cultures ( approximately 5 % of TCDD potency ) and the increase in CYP1A1 protein in HepG2 and LS174T cells was comparable to the increase in catalytic activity of CYP1A1 enzyme.", "output": "pelargonidin, TCDD." }, { "input": "Ligand binding analysis demonstrated that pelargonidin was a weak ligand of AhR.", "output": "pelargonidin." }, { "input": "Enzyme kinetic analyses using human liver microsomes revealed inhibition of CYP1A1 activity by delphinidin ( IC50 78 mu M ) and pelargonidin ( IC50 33 mu M ).", "output": "delphinidin, pelargonidin." }, { "input": "Overall, although most anthocyanidins had no effects on AhR - CYP1A1 signaling, pelargonidin can bind to and activate the AhR and AhR - dependent gene expression, and pelargonidin and delphinidin inhibit the CYP1A1 catalytic activity.", "output": "anthocyanidins, pelargonidin, pelargonidin, delphinidin." }, { "input": "Metformin and Sulfonylureas in Relation to Cancer Risk in Type II Diabetes Patients: A Meta - analysis using primary data of published studies.", "output": "Metformin, Sulfonylureas." }, { "input": "INTRODUCTION: Accumulating evidence suggests that patients with type 2 diabetes mellitus ( T2DM ) and hyperinsulinemia are at increased risk for developing malignancies.", "output": "There is no related enetity." }, { "input": "It remains to be fully elucidated whether use of metformin, an insulin sensitizer, and / or sulfonylureas, insulin secretagogues, affect cancer incidence in subjects with T2DM.", "output": "metformin, sulfonylureas." }, { "input": "MATERIAL & METHODS: We performed a meta - analysis using PubMed, of randomized control trials ( RCTs ), cohorts, and case - control studies published through July 2012 that assess effects of metformin and / or sulfonylurea sulfonylureas on cancer risk at any site, in subjects with T2DM.", "output": "metformin, sulfonylurea, sulfonylureas." }, { "input": "Fixed and random effects meta - analysis models were used, and the effect size was summarized as relative risk ( RR ) for RCTs / cohorts and as odds ratio ( OR ) for the case - control studies.", "output": "There is no related enetity." }, { "input": "RESULTS: Analysis of 24 metformin studies in subjects with T2DM showed that metformin use is associated with reduced risk for the development of cancer, in both cohort ( RR = 0. 70 [ 95 % CI = 0. 67 - 0. 73 ] ) and case - control studies ( OR = 0. 90 [ 95 % CI = 0. 84 - 0. 98 ] ), but this finding was not supported by RCTs ( RR = 1. 01 [ 95 % CI = 0. 81 - 1. 26 ] ).", "output": "metformin, metformin." }, { "input": "Data from 18 sulfonylurea studies in subjects with T2DM showed that sulfonylurea use is associated with an increase in all - cancer risk, in cohort studies ( RR = 1. 55 [ 95 % CI = 1. 48 - 1. 63 ] ), though data from RCTs ( RR = 1. 17 [ 95 % CI = 0. 95 - 1. 45 ] ) and case - control studies ( OR = 1. 02 [ 95 % CI = 0. 93 - 1. 13 ] ) failed to demonstrate a statistically significant effect.", "output": "sulfonylurea, sulfonylurea." }, { "input": "CONCLUSIONS: This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM.", "output": "metformin, sulfonylurea." }, { "input": "These findings need to be confirmed in large - scale RCTs before they are translated into clinical practice.", "output": "There is no related enetity." }, { "input": "Dextran - pegylated microparticles for enhanced cellular uptake of hydrophobic drugs.", "output": "There is no related enetity." }, { "input": "Polyethylene glycol monosubstituted with a polymerizable acrylic moiety was linked to 6 - carboxy free position on dextran side chains and then subjected to radical polymerization with a comonomer in order to obtain microspheres for the oral controlled release of ketoconazole, a hydrophobic model drug.", "output": "Polyethylene glycol, acrylic, 6 - carboxy, ketoconazole." }, { "input": "Microparticles were submitted to studies on their ability to absorb and retain water.", "output": "There is no related enetity." }, { "input": "Cell uptake studies, in the presence and absence of mucus, across two different monolayers, respectively, HT29 - MTX - E12 and Caco - 2, were done.", "output": "There is no related enetity." }, { "input": "Cytotoxicity studies were carried out to calculate the IC50 value.", "output": "There is no related enetity." }, { "input": "The ability of microspheres to open monolayers tight junctions was tested by measuring their TEER values.", "output": "There is no related enetity." }, { "input": "Images of cell uptake were visualized by CLSM.", "output": "There is no related enetity." }, { "input": "In HT29 - MTX - E12 cells, more mucoadhesion and drug internalization is seen thanks to the presence of PEG and dextran chains.", "output": "PEG." }, { "input": "The transdermal delivery of fentanyl.", "output": "fentanyl." }, { "input": "The fentanyl patch is one of the great commercial successes in transdermal drug delivery.", "output": "fentanyl." }, { "input": "The suitability of this molecule for delivery through skin had been identified in the 1970s, and subsequently, a number of transdermal formulations became available on the market.", "output": "There is no related enetity." }, { "input": "This article reviews the development of fentanyl patch technology with particular emphasis on the pharmacokinetics and disposition of the drug when delivered through the skin.", "output": "fentanyl." }, { "input": "The various patch designs are considered as well as the bioequivalence of the different designs.", "output": "There is no related enetity." }, { "input": "The influence of heat on fentanyl permeation is highlighted.", "output": "fentanyl." }, { "input": "Post - mortem redistribution of fentanyl is discussed in light of the reported discrepancies in serum levels reported in patients after death compared with therapeutic levels in living subjects.", "output": "fentanyl." }, { "input": "Finally, alternatives to patch technology are considered, and recent novel transdermal formulations are highlighted.", "output": "There is no related enetity." }, { "input": "Optimization of cell receptor - specific targeting through multivalent surface decoration of polymeric nanocarriers.", "output": "There is no related enetity." }, { "input": "Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non - compliance, and pathogen resistance to existing therapies.", "output": "There is no related enetity." }, { "input": "The mannose receptor ( MR ) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis.", "output": "mannose." }, { "input": "We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically - controlled, block copolymer - directed assembly.", "output": "mannose." }, { "input": "Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties.", "output": "PEG." }, { "input": "Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation.", "output": "hydroxyl, methoxy, mannoside." }, { "input": "Association of nanocarriers protected by a hydroxyl - terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy - terminated PEG coronas do not associate with cells, regardless of size.", "output": "hydroxyl, PEG, methoxy, PEG." }, { "input": "Specific targeting of the MR is investigated using nanocarriers having 0 - 75 % mannoside - terminated PEG chains in the PEG corona.", "output": "mannoside, PEG, PEG." }, { "input": "This is a wider range of mannose densities than has been previously studied.", "output": "mannose." }, { "input": "Maximum nanocarrier association is attained with 9 % mannoside - terminated PEG chains, increasing uptake more than 3 - fold compared to non - targeted nanocarriers with a 5kgmol ( - 1 ) methoxy - terminated PEG corona.", "output": "mannoside, PEG, methoxy, PEG." }, { "input": "While a 5kgmol ( - 1 ) methoxy - terminated PEG corona prevents non - specific uptake, a 1. 8kgmol ( - 1 ) methoxy - terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association.", "output": "methoxy, PEG, methoxy, PEG." }, { "input": "There is continuous uptake of MR - targeted nanocarriers at 37 degrees C, but a saturation of association at 4 degrees C.", "output": "There is no related enetity." }, { "input": "The majority of targeted nanocarriers associated with J774E cells are internalized at 37 degrees C and uptake is receptor - dependent, diminishing with competitive inhibition by dextran.", "output": "There is no related enetity." }, { "input": "This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites.", "output": "There is no related enetity." }, { "input": "Psychopharmacology of theobromine in healthy volunteers.", "output": "theobromine." }, { "input": "BACKGROUND: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate.", "output": "Theobromine, methylxanthine, caffeine." }, { "input": "However, current evidence for this is limited.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We conducted a within - subjects placebo - controlled study of a wide range of oral theobromine doses ( 250, 500, and 1, 000 mg ) using an active control dose of caffeine ( 200 mg ) in 80 healthy participants.", "output": "theobromine, caffeine." }, { "input": "RESULTS: Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters.", "output": "Caffeine." }, { "input": "Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses.", "output": "Theobromine." }, { "input": "It also dose - dependently increased heart rate.", "output": "There is no related enetity." }, { "input": "In secondary analyses, we also examined individual differences in the drug ' s effects in relation to genes related to their target receptors, but few associations were detected.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: This study represents the highest dose of theobromine studied in humans.", "output": "theobromine." }, { "input": "We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.", "output": "theobromine." }, { "input": "Theoretical studies on the thermodynamic properties, densities, detonation properties, and pyrolysis mechanisms of trinitromethyl - substituted aminotetrazole compounds.", "output": "trinitromethyl - substituted aminotetrazole." }, { "input": "Trinitromethyl - substituted aminotetrazoles with - NH ( 2 ), - NO ( 2 ), - N ( 3 ), and - NHC ( NO ( 2 ) ) ( 3 ) groups were investigated at the B3LYP / 6 - 31G ( d ) level of density functional theory.", "output": "Trinitromethyl - substituted aminotetrazoles, NH ( 2 ), NO ( 2 ), N ( 3 ), NHC ( NO ( 2 ) ) ( 3 )." }, { "input": "Their sublimation enthalpies, thermodynamic properties, and heats of formation were calculated.", "output": "There is no related enetity." }, { "input": "The thermodynamic properties of these compounds increase with temperature as well as with the number of nitro groups attached to the tetrazole ring.", "output": "nitro, tetrazole." }, { "input": "In addition, the detonation velocities and detonation pressures of these compounds were successfully predicted using the Kamlet - Jacobs equations.", "output": "There is no related enetity." }, { "input": "It was found that these compounds exhibit good detonation properties, and that compound G ( D = 9. 2 km / s, P = 38. 8 GPa ) has the most powerful detonation properties, which are similar to those of the well - known explosive HMX ( 1, 3, 5, 7 - tetranitro - 1, 3, 5, 7 - tetrazocine ).", "output": "HMX, 1 , 3 , 5 , 7 - tetranitro - 1 , 3 , 5 , 7 - tetrazocine." }, { "input": "Finally, the electronic structures and bond dissociation energies of these compounds were calculated.", "output": "There is no related enetity." }, { "input": "The BDEs of their C - NO ( 2 ) bonds were found to range from 101. 9 to 125. 8 kJ / mol ( - 1 ).", "output": "C - NO ( 2 )." }, { "input": "All of these results should provide useful fundamental information for the design of novel HEDMs.", "output": "There is no related enetity." }, { "input": "TiO2 nanowire electron transport pathways inside organic photovoltaics.", "output": "TiO2." }, { "input": "Charge transport is one of the five main steps in the operation of organic photovoltaics, but achieving balanced hole and electron transport with high mobility has been challenging in devices.", "output": "There is no related enetity." }, { "input": "Here, we report improved charge transport in organic photovoltaics via incorporation of nanostructured inorganic electron transport materials into the active layers of devices.", "output": "There is no related enetity." }, { "input": "Co - depositing TiO2 nanowires with the organic active layer solution embeds the nanowires directly within active layers of the solar cell.", "output": "TiO2." }, { "input": "The ability of these nanowires to transport electrons is compared with neat P3HT: PCBM active layers and also devices containing TiO2 nanotube aggregates.", "output": "P3HT, PCBM, TiO2." }, { "input": "Incorporation of TiO2 nanowires yields a six - fold increase in the electron mobility relative to unmodified devices, leading to a 19 % improvement in the power conversion efficiency.", "output": "TiO2." }, { "input": "Lower energetic disorder of the film and more balanced charge transport are also observed upon incorporating TiO2 nanowires.", "output": "TiO2." }, { "input": "These advantageous effects correlate with the TiO2 nanowire length.", "output": "TiO2." }, { "input": "Protein - specific force field derived from the fragment molecular orbital method can improve protein - ligand binding interactions.", "output": "There is no related enetity." }, { "input": "Accurate computational estimate of the protein - ligand binding affinity is of central importance in rational drug design.", "output": "There is no related enetity." }, { "input": "To improve accuracy of the molecular mechanics ( MM ) force field ( FF ) for protein - ligand simulations, we use a protein - specific FF derived by the fragment molecular orbital ( FMO ) method and by the restrained electrostatic potential ( RESP ) method.", "output": "There is no related enetity." }, { "input": "Applying this FMO - RESP method to two proteins, dodecin, and lysozyme, we found that protein - specific partial charges tend to differ more significantly from the standard AMBER charges for isolated charged atoms.", "output": "There is no related enetity." }, { "input": "We did not see the dependence of partial charges on the secondary structure.", "output": "There is no related enetity." }, { "input": "Computing the binding affinities of dodecin with five ligands by MM PBSA protocol with the FMO - RESP charge set as well as with the standard AMBER charges, we found that the former gives better correlation with experimental affinities than the latter.", "output": "There is no related enetity." }, { "input": "While, for lysozyme with five ligands, both charge sets gave similar and relatively accurate estimates of binding affinities.", "output": "There is no related enetity." }, { "input": "(c) 2013 Wiley Periodicals, Inc.", "output": "There is no related enetity." }, { "input": "Systematic and efficient side chain optimization for molecular docking using a cheapest - path procedure.", "output": "There is no related enetity." }, { "input": "Molecular docking of small - molecules is an important procedure for computer - aided drug design.", "output": "There is no related enetity." }, { "input": "Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding.", "output": "There is no related enetity." }, { "input": "However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem.", "output": "There is no related enetity." }, { "input": "Here we describe a new docking approach with a very fast, graph - based optimization algorithm for assignment of the near - optimal set of residue rotamers.", "output": "There is no related enetity." }, { "input": "We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking ( average ROC AUC of 0. 693 vs. 0. 623 ).", "output": "There is no related enetity." }, { "input": "Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures.", "output": "There is no related enetity." }, { "input": "Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement.", "output": "There is no related enetity." }, { "input": "(c) 2013 Wiley Periodicals, Inc.", "output": "There is no related enetity." }, { "input": "Potential Genotoxicity of Traditional Chinese Medicinal Plants and Phytochemicals: An Overview.", "output": "There is no related enetity." }, { "input": "In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines ( CHMs ) are occasionally involved.", "output": "There is no related enetity." }, { "input": "The experience gained from traditional use is efficient to detect immediate or near - immediate relationship between administration and toxic effects but is quite unlikely to detect medium - to long - term toxicities; thorough investigations of herbal medicines ( toxicity assessments, active pharmacovigilance ) appear then essential for their safe use.", "output": "There is no related enetity." }, { "input": "Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation.", "output": "There is no related enetity." }, { "input": "The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Once - daily initiation of basal insulin as add - on to metformin: a 26 - week, randomized, treat - to - target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes.", "output": "metformin." }, { "input": "AIMS: This study assessed the efficacy and safety of once - daily insulin initiation using insulin detemir ( detemir ) or insulin glargine ( glargine ) added to existing metformin in type 2 diabetes ( T2D ).", "output": "metformin." }, { "input": "METHODS: This 26 - week, multinational, randomized, treat - to - target trial involved 457 insulin - na i ve adults with T2D ( HbA1c 7 - 9 % ).", "output": "There is no related enetity." }, { "input": "Detemir or glargine was added to current metformin therapy [ any second oral antidiabetic drug ( OAD ) discontinued ] and titrated to a target fasting plasma glucose ( FPG ) <= 90 mg / dl ( <= 5. 0 mmol / l ).", "output": "metformin, glucose." }, { "input": "Primary efficacy endpoint was change in HbA1c.", "output": "There is no related enetity." }, { "input": "RESULTS: Mean ( s. d. ) HbA1c decreased with detemir and glargine by 0. 48 and 0. 74 % - points, respectively, to 7. 48 % ( 0. 91 % ) and 7. 13 % ( 0. 72 % ) [ estimated between - treatment difference, 0. 30 ( 95 % CI: 0. 14 - 0. 46 ) ].", "output": "There is no related enetity." }, { "input": "Non - inferiority for detemir at the a priori level of 0. 4 % - points was not established.", "output": "There is no related enetity." }, { "input": "The proportions of patients reaching HbA1c <= 7 % at 26 weeks were 38 % and 53 % ( p = 0. 026 ) with detemir and glargine, respectively.", "output": "There is no related enetity." }, { "input": "FPG decreased ~ 43. 2 mg / dl ( ~ 2. 4 mmol / l ) in both groups [ non - significant ( NS ) ].", "output": "There is no related enetity." }, { "input": "Treatment satisfaction was good for both insulins.", "output": "There is no related enetity." }, { "input": "Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [ rate ratio 0. 73 ( 95 % CI 0. 54 - 0. 98 ) ].", "output": "There is no related enetity." }, { "input": "The proportions of patients reaching HbA1c <= 7 % without hypoglycaemia in the detemir and glargine groups were 32 % and 38 % ( NS ), respectively.", "output": "There is no related enetity." }, { "input": "Weight decreased with detemir [ - 0. 49 ( 3. 3 ) kg ] and increased with glargine [ + 1. 0 ( 3. 1 ) kg ] ( 95 % CI for difference: - 2. 17 to - 0. 89 kg ).", "output": "There is no related enetity." }, { "input": "CONCLUSION: While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.", "output": "metformin." }, { "input": "Impact of model perfume molecules on the self - assembly of anionic surfactant sodium dodecyl 6 - benzene sulfonate.", "output": "sodium dodecyl 6 - benzene sulfonate." }, { "input": "The impact of two model perfumes with differing degrees of hydrophobicity / hydrophilicity, linalool ( LL ) and phenylethanol ( PE ), on the solution structure of anionic surfactant sodium dodecyl 6 - benzene sulfonate, LAS - 6, has been studied by small angle neutron scattering, SANS.", "output": "linalool, phenylethanol, sodium dodecyl 6 - benzene sulfonate, LAS - 6." }, { "input": "For both types of perfume molecules, complex phase behavior is observed.", "output": "There is no related enetity." }, { "input": "The phase behavior depends upon the concentration, surfactant / perfume composition, and type of perfume.", "output": "There is no related enetity." }, { "input": "The more hydrophilic perfume PE promotes the formation of more highly curved structures.", "output": "There is no related enetity." }, { "input": "At relatively low surfactant concentrations, small globular micelles, L1, are formed.", "output": "There is no related enetity." }, { "input": "These become perfume droplets, L ( sm ), stabilized by the surfactant at much higher perfume solution compositions.", "output": "There is no related enetity." }, { "input": "At higher surfactant concentrations, the tendency of LAS - 6 to form more planar structures is evident.", "output": "LAS - 6." }, { "input": "The more hydrophobic linalool promotes the formation of more planar structures.", "output": "linalool." }, { "input": "Combined with the greater tendency of LAS - 6 to form planar structures, this results in the planar structures dominating the phase behavior for the LAS - 6 / linalool mixtures.", "output": "LAS - 6, LAS - 6, linalool." }, { "input": "For the LAS - 6 / linalool mixture, the self - assembly is in the form of micelles only at the lowest surfactant and perfume concentrations.", "output": "LAS - 6, linalool." }, { "input": "Over most of the concentration - composition space explored, the structures are predominantly lamellar, L ( alpha ), or vesicle, L ( v ), or in the form of a lamellar / micellar coexistence.", "output": "There is no related enetity." }, { "input": "At low and intermediate amounts of LL, a significantly different structure is observed, and the aggregates are in the form of small, relatively monodisperse vesicles ( i. e., nanovesicles ), L ( sv ).", "output": "There is no related enetity." }, { "input": "( M ) - and ( P ) - Bicelaphanol A, Dimeric Trinorditerpenes with Promising Neuroprotective Activity from Celastrus orbiculatus.", "output": "( M ) - and ( P ) - Bicelaphanol A, Trinorditerpenes." }, { "input": "( M ) - Bicelaphanol A ( 1 ) and ( P ) - bicelaphanol A ( 2 ), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A ( 3 ), were isolated from the root bark of Celastrus orbiculatus.", "output": "( M ) - Bicelaphanol A, ( P ) - bicelaphanol A, celaphanol A." }, { "input": "The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single - crystal X - ray diffraction analyses.", "output": "There is no related enetity." }, { "input": "Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide - induced cell viability decrease in PC12 cells at 1 mu M, while compounds 2 and 3 showed such effects at 10 mu M.", "output": "hydrogen peroxide." }, { "input": "Novel microbial transformation of desacetylcinobufagin by Fusarium avenaceum AS 3. 4594.", "output": "desacetylcinobufagin." }, { "input": "In this paper, the microbial transformation of desacetylcinobufagin ( 1 ) by Fusarium avenaceum AS 3. 4594 was investigated, and four metabolites were isolated and characterized as 3 - keton - desacetylcinobufagin ( 2 ), 3 - epi - desacetylcinobufagin ( 3 ), bufadienolide A ( 4 ), and 15 beta, 16 alpha - dihydroxyl - 17 beta H - bufalin ( 5 ), respectively.", "output": "desacetylcinobufagin, 3 - keton - desacetylcinobufagin, 3 - epi - desacetylcinobufagin, bufadienolide A, 15 beta , 16 alpha - dihydroxyl - 17 beta H - bufalin." }, { "input": "Among them, 4 and 5 are new compounds.", "output": "There is no related enetity." }, { "input": "The cytotoxicities of transformed products ( 2 - 5 ) against Hela cells were also investigated.", "output": "There is no related enetity." }, { "input": "Dorsamin - A ' s, Glycerolipids Carrying a Dehydrophenylalanine Ester Moiety from the Seed - Eating Larvae of the Bruchid Beetle Bruchidius dorsalis.", "output": "Dorsamin - A, Dehydrophenylalanine, Ester." }, { "input": "Using a TLC autographic assay for radical - scavenging activity with the ABTS radical, the presence of lipophilic antioxidants in the larvae of the wild bruchid seed beetle Bruchidius dorsalis was detected.", "output": "ABTS." }, { "input": "Assay - guided fractionation of the CHCl ( 3 ) - soluble fraction of the larvae resulted in the isolation of new glycerolipids, designated dorsamin - A763, - A737, - A765, - A739, and - A767, comprising 1, 2 - diacyl - sn - glycero - 3 - dehydrophenylalanine ester structural units.", "output": "CHCl ( 3 ), dorsamin - A763 , - A737 , - A765 , - A739 , and - A767, 1 , 2 - diacyl - sn - glycero - 3 - dehydrophenylalanine ester." }, { "input": "The ABTS radical scavenging activity of the dorsamin - A ' s was comparable with or stronger than that of Trolox.", "output": "ABTS, dorsamin - A, Trolox." }, { "input": "Colloidal nanoplasmonics: from building blocks to sensing devices.", "output": "There is no related enetity." }, { "input": "Nanoplasmonics is a rapidly developing field of research and technology that is based on the ability of small metal particles to interact strongly with light of wavelength significantly larger than their size.", "output": "There is no related enetity." }, { "input": "The development of nanoplasmonics has been closely associated with the application of colloid science to the controlled growth of metal nanocrystals in solution and to directing the self - assembly of such nanocrystals into organized arrays with enhanced collective properties.", "output": "There is no related enetity." }, { "input": "Engineering the morphology and the assembly of metal nanoparticles is a key step toward the fabrication of devices with great potential in detection and diagnosis as well as in a wide variety of other fields.", "output": "There is no related enetity." }, { "input": "In this Feature Article, we provide an overview of the recent work in our laboratory, which in our view somehow reflects the evolution of the field itself and provides guidelines for future research.", "output": "There is no related enetity." }, { "input": "Four new eudesmane - type sesquiterpenoid lactones from atractylenolide II by biotransformation of rat hepatic microsomes.", "output": "eudesmane, sesquiterpenoid lactones, atractylenolide II." }, { "input": "The biotransformation of atractylenolide II, a major bioactive principle of the rhizomes of Atractylodes macrocephala Koidz., was investigated in vitro by incubation with rat hepatic microsomes pretreated with sodium phenobarbital.", "output": "atractylenolide II, sodium phenobarbital." }, { "input": "The biotransformation products were extracted and purified by chromatographic methods.", "output": "There is no related enetity." }, { "input": "Seven biotransformation products ( BP1 - BP7 ) were obtained and their structures were elucidated by NMR and MS data analyses and by comparison with the previously reported values, including four new compounds, namely 4 ( R ), 15 - epoxy - atractylenolide II ( BP1 ), 4 ( R ), 15 - epoxy - 13 - hydroxyatractylenolide II ( BP5 ), 4 ( R ), 15 - epoxy - 1 beta - hydroxyatractylenolide II ( BP6 ), and 4 ( R ), 15 - dihydroxyatractylenolide II ( BP7 ).", "output": "4 ( R ) , 15 - epoxy - atractylenolide II, 4 ( R ) , 15 - epoxy - 13 - hydroxyatractylenolide II, 4 ( R ) , 15 - epoxy - 1 beta - hydroxyatractylenolide II, 4 ( R ) , 15 - dihydroxyatractylenolide II." }, { "input": "The biotransformation pathway of atractylenolide II by hepatic microsomes was deducted based on the structure resolution of the products.", "output": "atractylenolide II." }, { "input": "Resveratrol enhances exercise training responses in rats selectively bred for high running performance.", "output": "Resveratrol." }, { "input": "High Capacity Runner ( HCR ) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology - disease connection.", "output": "There is no related enetity." }, { "input": "The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated.", "output": "resveratrol, resveratrol." }, { "input": "In this study we examine whether 12weeks of treadmill exercise training and / or resveratrol can enhance performance in HCR.", "output": "resveratrol." }, { "input": "Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats.", "output": "resveratrol." }, { "input": "Moreover, we have found that resveratrol activated the AMP - activated protein kinase, SIRT1, and mitochondrial transcription factor A ( p < 0. 05 ).", "output": "resveratrol, AMP." }, { "input": "The changes in mitochondrial fission / fusion and Lon protease / HSP78 levels suggest that exercise training does not significantly induce damage of proteins.", "output": "There is no related enetity." }, { "input": "Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls.", "output": "resveratrol." }, { "input": "Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity.", "output": "There is no related enetity." }, { "input": "These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK - SIRT1 - PGC - 1 alpha pathway.", "output": "resveratrol." }, { "input": "Antimicrobial, antiviral and antioxidant activities of \" a gua - mel \" from Portugal.", "output": "There is no related enetity." }, { "input": "\" A gua - mel \" is a honey - based product produced in Portugal for ancient times.", "output": "There is no related enetity." }, { "input": "Several attributes have been reported to \" a gua - mel \" particularly in the alleviation of simple symptoms of upper respiratory tract.", "output": "There is no related enetity." }, { "input": "Samples of \" a gua - mel \" from diverse beekeepers from different regions of Portugal were studied in what concerns antimicrobial, antioxidant and antiviral properties.", "output": "There is no related enetity." }, { "input": "The amounts of phenol and brown pigment were also evaluated and correlated with the antioxidant activities.", "output": "phenol." }, { "input": "A great variability on the levels of these compounds was found among samples which were responsible for the variability detected also on the antioxidant activities, independent on the method used.", "output": "There is no related enetity." }, { "input": "Generally, antioxidant activity correlated better with brown pigments ' amount than with phenols ' content.", "output": "phenols." }, { "input": "The antimicrobial activity found for \" a gua - mel \" samples confirm the virtues reported by popular findings.", "output": "There is no related enetity." }, { "input": "In addition, this work also reveals the antiviral properties of \" a gua - mel \" evidenced by a decrease on the infectivity of the Q beta bacteriophage.", "output": "There is no related enetity." }, { "input": "Lanostane - type triterpenoid and steroid from the stem bark of Klainedoxa gabonensis.", "output": "Lanostane, triterpenoid, steroid." }, { "input": "A new lanostane triterpenoid, 2 - hydroxy - 24 - methylenelanostan - 1, 8 - dien - 3 - one named klainedoxalanostenone ( 1 ) with one new steroid, 6 - O - acyl - beta - d - glucosyl - beta - sitosterol named klainedoxasterol ( 2 ) together with ten known compounds including six triterpenoids ( 3 - 8 ), two steroids ( 9, 10 ) and two tanins ( 11, 12 ) were isolated from the stem bark of Klainedoxa gabonensis.", "output": "lanostane triterpenoid, 2 - hydroxy - 24 - methylenelanostan - 1 , 8 - dien - 3 - one, klainedoxalanostenone, steroid, 6 - O - acyl - beta - d - glucosyl - beta - sitosterol, klainedoxasterol, triterpenoids, steroids, tanins." }, { "input": "To the best of our knowledge, this is the first report of lanostane - type triterpenoids from this genus.", "output": "lanostane, triterpenoids." }, { "input": "Their structures were determined by extensive analysis of spectroscopic data ( 1D and 2D NMR, MS ) and by comparison with literature data.", "output": "There is no related enetity." }, { "input": "The xanthine oxidase inhibitory activity of nine compounds ( 1 - 6, 8, 10 and 11 ) were evaluated.", "output": "xanthine." }, { "input": "Compound 5 showed a good xanthine oxidase inhibitory activity; the other tested compounds were moderately active.", "output": "xanthine." }, { "input": "Cytotoxic sesquiterpenes from Hedychium spicatum: Isolation, structure elucidation and structure - activity relationship studies.", "output": "sesquiterpenes." }, { "input": "Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes ( 1 - 6 ) along with fifteen known compounds ( 7 - 21 ).", "output": "chloroform, sesquiterpenes." }, { "input": "Their structures were elucidated on the basis of the extensive spectroscopic analyses ( IR, Mass and NMR ) and by comparison of the data with those reported in the literature.", "output": "There is no related enetity." }, { "input": "Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A - 549, B - 16, Hela, HT - 29, NCI - H460, PC - 3, IEC - 6 and L - 6 cancer cell lines.", "output": "There is no related enetity." }, { "input": "Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC50 value of 0. 3 mu g / mL and 1. 80 mu g / mL, respectively.", "output": "There is no related enetity." }, { "input": "Investigation of the cumulative body burden of estrogen - 3, 4 - quinone in breast cancer patients and controls using albumin adducts as biomarkers.", "output": "estrogen - 3 , 4 - quinone." }, { "input": "Both 17 beta - estradiol - 2, 3 - quinone ( E2 - 2, 3 - Q ) and 17 beta - estradiol - 3, 4 - quinone ( E2 - 3, 4 - Q ) are reactive metabolites of estrogen.", "output": "17 beta - estradiol - 2 , 3 - quinone, E2 - 2 , 3 - Q, 17 beta - estradiol - 3 , 4 - quinone, E2 - 3 , 4 - Q, estrogen." }, { "input": "Elevation of E2 - 3, 4 - Q to E2 - 2, 3 - Q ratio is thought to be an important indicator of estrogen - induced carcinogenesis.", "output": "E2 - 3 , 4 - Q, E2 - 2 , 3 - Q, estrogen." }, { "input": "Our current study compared the cumulative body burden of these estrogen quinones in serum samples taken from Taiwanese women with breast cancer ( n = 152 ) vs healthy controls ( n = 75 ) by using albumin ( Alb ) adducts as biomarkers.", "output": "estrogen quinones." }, { "input": "Results clearly demonstrated the presence of cysteinyl adducts of E2 - 2, 3 - Q - 4 - S - Alb and E2 - 3, 4 - Q - 2 - S - Alb in all study population at levels ranging from 61. 7 - 1330 to 66. 6 - 1, 590 pmol / g, respectively.", "output": "cysteinyl, E2 - 2 , 3 - Q, E2 - 3 , 4 - Q." }, { "input": "Correlation coefficient between E2 - 2, 3 - Q - 4 - S - Alb and E2 - 3, 4 - Q - 2 - S - Alb was 0. 610 for controls and 0. 767 for breast cancer patients ( p < 0. 001 ).", "output": "E2 - 2 , 3 - Q, E2 - 3 , 4 - Q." }, { "input": "We also noticed that in premenopausal subjects with body mass index ( BMI ) less than 27, background levels of E2 - 3, 4 - Q - 2 - S - Alb was inversely proportional to BMI with about 25 % increase in E2 - 3, 4 - Q - 2 - S - Alb per 5 kg / m ( 2 ) decrease in BMI ( p < 0. 001 ).", "output": "E2 - 3 , 4 - Q, E2 - 3 , 4 - Q." }, { "input": "In addition, we confirmed that mean levels of E2 - 3, 4 - Q - 2 - S - Alb in breast cancer patients were ~ 5 - fold greater than in those of controls ( p < 0. 001 ).", "output": "E2 - 3 , 4 - Q." }, { "input": "Overall, this evidence suggests that disparity in estrogen disposition and the subsequent elevation of cumulative body burden of E2 - 3, 4 - Q may play a role in the development of breast cancer.", "output": "estrogen, E2 - 3 , 4 - Q." }, { "input": "Co - extrusion as manufacturing technique for multilayer mini - matrices with dual drug release.", "output": "There is no related enetity." }, { "input": "The aim of this work was to develop by means of co - extrusion a multilayered dosage form characterized by a dual release profile of the same drug.", "output": "There is no related enetity." }, { "input": "Co - extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character.", "output": "There is no related enetity." }, { "input": "Diclofenac sodium ( DS ) was incorporated as model drug in both layers.", "output": "Diclofenac sodium." }, { "input": "Several polymers were screened on the basis of their processability via hot melt extrusion ( HME ) and in vitro drug release.", "output": "There is no related enetity." }, { "input": "Polymer combinations with suitable properties ( i. e., similar extrusion temperature, appropriate drug release profile ) were processed via co - extrusion.", "output": "There is no related enetity." }, { "input": "( Co - ) extruded samples were characterized in terms of solid state ( XRD, SEM ), in vitro drug release, core / coat adhesion, and bioavailability.", "output": "There is no related enetity." }, { "input": "Based on the polymer screening, two polymer combinations were selected for co - extrusion: ethylcellulose ( core ) combined with Soluplus (R) ( coat ) and polycaprolactone ( core ) with PEO ( coat ).", "output": "Soluplus, polycaprolactone, PEO." }, { "input": "These combinations were successfully co - extruded.", "output": "There is no related enetity." }, { "input": "XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus (R), polycaprolactone, and PEO.", "output": "Soluplus, polycaprolactone, PEO." }, { "input": "The polycaprolactone / PEO combination could be processed at a lower temperature ( 70 degrees C ), vs. 140 degrees C for ethylcellulose / Soluplus (R).", "output": "polycaprolactone, PEO, Soluplus." }, { "input": "The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature.", "output": "There is no related enetity." }, { "input": "In vitro drug release from the co - extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat ( i. e., faster drug release ) resulted in higher Cmax and higher AUC values.", "output": "There is no related enetity." }, { "input": "Co - extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release.", "output": "There is no related enetity." }, { "input": "NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites.", "output": "There is no related enetity." }, { "input": "ATR and ATM kinases are central to the checkpoint activation in response to DNA damage and replication stress.", "output": "There is no related enetity." }, { "input": "However, the nature of the signal, which initially activates these kinases in response to UV damage, is unclear.", "output": "There is no related enetity." }, { "input": "Here, we have shown that DDB2 and XPC, two early UV damage recognition factors, are required for the damage - specific ATR and ATM recruitment and phosphorylation.", "output": "There is no related enetity." }, { "input": "ATR and ATM physically interacted with XPC and promptly localized to the UV damage sites.", "output": "There is no related enetity." }, { "input": "ATR and ATM recruitment and their phosphorylation were negatively affected in cells defective in DDB2 or XPC functions.", "output": "There is no related enetity." }, { "input": "Consequently, the phosphorylation of ATR and ATM substrates, Chk1, Chk2, H2AX, and BRCA1 was significantly reduced or abrogated in mutant cells.", "output": "There is no related enetity." }, { "input": "Furthermore, UV exposure of cells defective in DDB2 or XPC resulted in a marked decrease in BRCA1 and Rad51 recruitment to the damage site.", "output": "There is no related enetity." }, { "input": "Conversely, ATR - and ATM - deficiency failed to affect the recruitment of DDB2 and XPC to the damage site, and therefore did not influence the NER efficiency.", "output": "There is no related enetity." }, { "input": "These findings demonstrate a novel function of DDB2 and XPC in maintaining a vital cross - talk with checkpoint proteins, and thereby coordinating subsequent repair and checkpoint activation.", "output": "There is no related enetity." }, { "input": "Balancing societal needs and regulatory certainty: the case study of peramivir in Japan.", "output": "peramivir." }, { "input": "Regulators must balance societal and medical requirements against the need for certainty about benefit and risk for new medicines.", "output": "There is no related enetity." }, { "input": "This is described in a case study of the expedited review and approval of peramivir, a novel neuraminidase inhibitor, in Japan in the context of the emergence of new strain of influenza in 2009.", "output": "peramivir." }, { "input": "The case illustrates the importance of regulatory science and transparency in supporting such decision making.", "output": "There is no related enetity." }, { "input": "Characterisation of non - warfarin - associated bleeding events reported to the Norwegian spontaneous reporting system.", "output": "warfarin." }, { "input": "OBJECTIVE: The aim of the study was to analyse non - warfarin - associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions.", "output": "warfarin." }, { "input": "In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied.", "output": "There is no related enetity." }, { "input": "METHODS: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database.", "output": "There is no related enetity." }, { "input": "RESULTS: Of 327 case reports of non - warfarin - associated bleeding events, 270 reports ( 82. 6 % ) were characterised as serious and 69 ( 21. 1 % ) had a fatal outcome.", "output": "warfarin." }, { "input": "One hundred and eighty - seven bleeds ( 57. 5 % ) were gastrointestinal, 57 ( 17. 4 % ) were cerebral, and 81 ( 24. 8 % ) were from other bleeding sites.", "output": "There is no related enetity." }, { "input": "The bleeding sites differed with respect to the patient ' s age, drug use, diagnoses and outcomes.", "output": "There is no related enetity." }, { "input": "Of drugs associated with bleeding, nonsteroidal anti - inflammatory drugs ( NSAIDs ) / COX - 2 inhibitors ( 145 reports ) and acetylsalicylic acid ( 128 reports ) were most frequently used.", "output": "acetylsalicylic acid." }, { "input": "Only fibrinolytics were associated with increased mortality.", "output": "There is no related enetity." }, { "input": "There was a 67. 4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding ( P < 0. 001 ), with considerable variation in concordance between drug groups.", "output": "There is no related enetity." }, { "input": "CONCLUSION: Non - warfarin - associated bleeding events are associated with substantial mortality.", "output": "warfarin." }, { "input": "Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality.", "output": "There is no related enetity." }, { "input": "The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers.", "output": "acetylsalicylic acid." }, { "input": "Translational repression of thymidylate synthase by targeting its mRNA.", "output": "There is no related enetity." }, { "input": "Resistance to drugs targeting human thymidylate synthase ( TS ) poses a major challenge in the field of anti - cancer therapeutics.", "output": "There is no related enetity." }, { "input": "Overexpression of the TS protein has been implicated as one of the factors leading to the development of resistance.", "output": "There is no related enetity." }, { "input": "Therefore, repressing translation by targeting the TS mRNA could help to overcome this problem.", "output": "There is no related enetity." }, { "input": "In this study, we report that the compound Hoechst 33258 ( HT ) can reduce cellular TS protein levels without altering TS mRNA levels, suggesting that it modulates TS expression at the translation level.", "output": "Hoechst 33258." }, { "input": "We have combined nuclear magnetic resonance, UV - visible and fluorescence spectroscopy methods with docking and molecular dynamics simulations to study the interaction of HT with a region in the TS mRNA.", "output": "There is no related enetity." }, { "input": "The interaction predominantly involves intercalation of HT at a CC mismatch in the region near the translational initiation site.", "output": "There is no related enetity." }, { "input": "Our results support the use of HT - like compounds to guide the design of therapeutic agents targeting TS mRNA.", "output": "There is no related enetity." }, { "input": "An investigation of the photophysical properties of minor groove bound and intercalated DAPI through quantum - mechanical and spectroscopic tools.", "output": "DAPI." }, { "input": "The fluorescent probe 4 ', 6 - diamidino - 2 - phenylindole ( DAPI ) is a dye known to interact with polynucleotides in a non - univocal manner, both intercalation and minor groove binding modes being possible, and to specifically change its photophysical properties according to the different environments.", "output": "4 ' , 6 - diamidino - 2 - phenylindole, DAPI." }, { "input": "To investigate this behavior, quantum - mechanical calculations using time - dependent density functional theory ( TDDFT ), coupled with polarizable continuum and / or atomistic models, were performed in combination with spectroscopic measurements of the probe in the different environments, ranging from a homogeneous solution to the minor groove or intercalation pockets of double stranded nucleic acids.", "output": "There is no related enetity." }, { "input": "According to our simulation, the electronic transition involves a displacement of the electron charge towards the external amidine groups and this feature makes the absorption energies very environment - sensitive while a much smaller sensitivity is seen in the fluorescence energies.", "output": "amidine." }, { "input": "Moreover, the calculations show that the DAPI molecule, when minor groove bound to the nucleic acid, presents both a reduced geometrical flexibility because of the rigid DNA pocket and a reduced polarization due to the very \" apolar \" microenvironment.", "output": "DAPI." }, { "input": "All these effects can be used to better understand the observed enhancement of the fluorescence, which makes it an excellent marker for DNA.", "output": "There is no related enetity." }, { "input": "Type 2 Diabetes With Partial Lipodystrophy of the Limbs: A new lipodystrophy phenotype.", "output": "There is no related enetity." }, { "input": "OBJECIVELipodystrophies are categorized by the extent of fat loss ( generalized vs. partial ) and by inheritance ( congenital vs. acquired ).", "output": "There is no related enetity." }, { "input": "We examined whether a group of patients with partial lipodystrophy of the limbs ( PLL ), type 2 diabetes mellitus ( T2DM ), and an absence of a family history of lipodystrophy constitute a new clinical subtype. RESEARCH AND DESIGN METHODSTen women with T2DM and PLL were identified in academic diabetes clinics and were matched by age, sex, BMI, ethnicity, and diabetes status with 10 women with control T2DM without lipodystrophy.", "output": "There is no related enetity." }, { "input": "All patients were characterized by clinical evaluation and hyperinsulinemic clamp. RESULTSPatients with T2DM and PLL exhibited symmetrical loss of subcutaneous fat in forearms, or forearms plus calves, and acanthosis nigricans.", "output": "There is no related enetity." }, { "input": "Maximally stimulated glucose disposal rates were markedly reduced by 56 % in the T2DM with PLL group compared with the control T2DM patients, whether normalized by body weight or surface area.", "output": "glucose." }, { "input": "Most PLL patients exhibited little or no insulin - mediated glucose uptake after subtraction of non - insulin - mediated glucose uptake.", "output": "glucose, glucose." }, { "input": "The T2DM with PLL group also had greater elevations in hepatic transaminases and triglycerides and earlier onset of diabetes compared with control T2DM. CONCLUSIONST2DM with PLL represents a previously unrecognized phenotype of lipodystrophy and of T2DM.", "output": "triglycerides." }, { "input": "These T2DM patients exhibit symmetrical lipodystrophy of the distal limbs, acanthosis nigricans, marked insulin resistance with little insulin - mediated glucose uptake, hypertriglyceridemia, and hepatic transaminase elevations, which are greater in severity than observed in patients with common T2DM.", "output": "glucose." }, { "input": "5 - Aza - 2 ' - deoxycytidine inhibited PDGF - induced rat airway smooth muscle cell phenotypic switching.", "output": "5 - Aza - 2 ' - deoxycytidine." }, { "input": "Airway smooth muscle ( ASM ) cell phenotypic switching played an important role in airway remodeling in asthma.", "output": "There is no related enetity." }, { "input": "In vitro platelet - derived growth factor ( PDGF ) induced ASM cell phenotypic switching from a mature to pro - remodeling phenotype, but the mechanism remained incompletely understood.", "output": "There is no related enetity." }, { "input": "This study was to explore the effect of DNA methyltransferase inhibitor 5 - Aza - 2 ' - deoxycytidine ( Aza - CdR ) on PDGF - induced rat ASM cell phenotypic switching and biological behaviors.", "output": "5 - Aza - 2 ' - deoxycytidine, Aza - CdR." }, { "input": "Rat airway smooth muscle ( RASM ) cells were obtained by primary explant techniques.", "output": "There is no related enetity." }, { "input": "Western blot, 3 - dimensional gel contraction, transwell and wound healing assay, and MTT were applied to detect cell phenotypic switching, contractility, migration and proliferation, respectively.", "output": "MTT." }, { "input": "Cytoskeleton rearrangement was observed by immunofluorescence.", "output": "There is no related enetity." }, { "input": "Results showed Aza - CdR inhibited PDGF - induced down - regulation of contractile markers in RASM cells and increased cell contractility.", "output": "Aza - CdR." }, { "input": "Aza - CdR inhibited PDGF - induced RASM cell migration by abrogating cell morphology change and cytoskeletal reorganization and attenuated the effect of PDGF on proliferating cell nuclear antigen expression and cell cycle progression, ultimately cell proliferation.", "output": "Aza - CdR." }, { "input": "PDGF - induced DNA methyltransferase 1 ( DNMT1 ) expression was mediated by activation of PI3K / Akt and ERK signaling in RASM cells.", "output": "There is no related enetity." }, { "input": "Selective depletion of DNMT1 protein by Aza - CdR inhibited PDGF - induced RASM cell phenotypic switching, revealing DNMT1 - mediated DNA methylation was implicated in asthmatic ASM remodeling.", "output": "Aza - CdR." }, { "input": "We proposed for the first time that DNMT1 played a key role in PDGF - induced RASM cell phenotypic switching and Aza - CdR is promising in intervening ASM remodeling in asthma.", "output": "Aza - CdR." }, { "input": "Although study of abnormal DNA methylation in PDGF - stimulated ASM cells is in its infancy, this work contributes to providing new insights into the mechanism of ASM remodeling and may be helpful for developing effective treatments for airway remodeling in asthma.", "output": "There is no related enetity." }, { "input": "Use of gene expression data to determine effects on gonad phenotype in japanese medaka after exposure to trenbolone or estradiol.", "output": "trenbolone, estradiol." }, { "input": "Various aquatic bioassays using one of several fish species have been developed or are in the process of being developed by organizations like the US Environmental Protection Agency and the Office of Economic Cooperation and Development for testing potential endocrine - disrupting chemicals ( EDCs ).", "output": "There is no related enetity." }, { "input": "Often, these involve assessment of the gonad phenotype of individuals as a key endpoint that is inputted into a risk or hazard assessment.", "output": "There is no related enetity." }, { "input": "Typically, gonad phenotype is determined histologically, which involves specialized and time - consuming techniques.", "output": "There is no related enetity." }, { "input": "The methods detailed here utilize an entirely different methodology, reverse - transcription quantitative polymerase chain reaction, to determine the relative expression levels of 4 genes after exposure to either 17 beta - estradiol or 17 beta - trenbolone and, by extension, the effects of EDCs on the phenotypic status of the gonad.", "output": "17 beta - estradiol, 17 beta - trenbolone." }, { "input": "The 4 genes quantified, Sox9b, protamine, Fig1 alpha, and ZPC1, are all involved in gonad development and maintenance in Japanese medaka ( Oryzias latipes ); these data were then inputted into a permutational multivariate analysis of variance to determine whether significant differences exist between treatment groups.", "output": "There is no related enetity." }, { "input": "This information in conjunction with the sexual genotype, which can be determined in medaka, can be used to determine adverse effects of exposure to EDCs in a similar fashion to the histologically determined gonad phenotype.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1344 - 1353.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Absorption, distribution, and biotransformation of hexahydro - 1, 3, 5 - trinitro - 1, 3, 5 - triazine in B6C3F1 mice ( Mus musculus ).", "output": "hexahydro - 1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine." }, { "input": "Absorption, distribution, and biotransformation are 3 critical aspects affecting toxicant action in animals.", "output": "There is no related enetity." }, { "input": "In the present study, B6C3F1 mice ( Mus musculus ) were exposed for 28 d to contaminated feed that contained 1 of 5 different hexahydro - 1, 3, 5 - trinitro - 1, 3, 5 - triazine ( RDX ) concentrations: 0 mg / kg, 0. 5 mg / kg, 5 mg / kg, 50 mg / kg, and 500 mg / kg.", "output": "hexahydro - 1 , 3 , 5 - trinitro - 1 , 3 , 5 - triazine." }, { "input": "The authors quantified RDX and its reductive transformation products hexahydro - 1 - nitroso - 3, 5 - dinitro - 1, 3, 5 - triazine ( MNX ), hexahydro - 1, 3 - dinitroso - 5 - nitro - 1, 3, 5 - triazine ( DNX ), and hexahydro - 1, 3, 5 - trinitroso - 1, 3, 5 - triazine ( TNX ) in the stomach, intestine, plasma, liver, and brain of these mice.", "output": "hexahydro - 1 - nitroso - 3 , 5 - dinitro - 1 , 3 , 5 - triazine, hexahydro - 1 , 3 - dinitroso - 5 - nitro - 1 , 3 , 5 - triazine, hexahydro - 1 , 3 , 5 - trinitroso - 1 , 3 , 5 - triazine." }, { "input": "Average RDX concentrations followed a dose - dependent pattern for all matrices tested.", "output": "There is no related enetity." }, { "input": "No controls had concentrations above limits of detection.", "output": "There is no related enetity." }, { "input": "Average RDX concentrations in tissues of exposed mice ranged from 11. 1 ng / mL to 182 ng / mL, 25. 6 ng / g to 3319 ng / g, 123 ng / g to 233 ng / g, 144 ng / g to 35 900 ng / g, and 51. 1 ng / g to 2697 ng / g in the plasma, brain, liver, stomach, and intestine, respectively.", "output": "There is no related enetity." }, { "input": "A considerable amount of RDX was present in the brain, especially in the highest - exposure group.", "output": "There is no related enetity." }, { "input": "This is consistent with the widely observed central nervous system effects caused by gamma - aminobutyric acid inhibition associated with RDX exposure.", "output": "gamma - aminobutyric acid." }, { "input": "N - nitroso metabolites of RDX were also present in tested tissues in a dose - dependent pattern.", "output": "N - nitroso." }, { "input": "Average MNX concentrations in the stomachs of mice exposed to RDX ranged from nondetectable in control exposures to 490 ng / g in the highest - exposure groups.", "output": "There is no related enetity." }, { "input": "In the brain, MNX accumulated at a maximum average concentration of 165. 1 ng / g, suggesting the potential formation of MNX from RDX within the brain.", "output": "There is no related enetity." }, { "input": "At higher exposures, DNX and TNX were present in the stomach, plasma, and brain of mice.", "output": "There is no related enetity." }, { "input": "The presence of RDX metabolites at notable amounts in different tissues suggests that RDX can transform into its N - nitroso metabolites in vivo by an undefined mechanism.", "output": "N - nitroso." }, { "input": "Environ Toxicol Chem 2013; 32: 1295 - 1303.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Cytotoxic triterpenoid saponins from the stems of Gordonia longicarpa.", "output": "triterpenoid saponins." }, { "input": "Nine new triterpenoid saponins named longicarposides A - I ( 1 - 9 ), together with three known saponins ( 10 - 12 ), were isolated from the stems of Gordonia longicarpa.", "output": "triterpenoid saponins, longicarposides A - I, saponins." }, { "input": "The structures of the saponins were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods.", "output": "saponins." }, { "input": "They were characterized to be oleanane - type saponins with sugar moieties linked to C - 3 of the aglycone.", "output": "oleanane, saponins, sugar." }, { "input": "Cytotoxic activities of these saponins were evaluated against five human tumor cell lines ( HCT - 8, Bel - 7402, BGC - 823, A549, and A2780 ) by using the MTT in vitro assay.", "output": "saponins, MTT." }, { "input": "Compounds 5, 7, 8, 10, and 11 exhibited potent cytotoxic activity with IC50 values of 1. 42 - 8. 42 micro M, while 6, 9, and 12 showed selective cytotoxic activity toward the tested cell lines.", "output": "There is no related enetity." }, { "input": "Bioavailability - based chronic toxicity measurements of permethrin to Chironomus dilutus.", "output": "permethrin." }, { "input": "Compared with acute toxicity, chronic exposures to low levels of contaminants are more environmentally relevant, but fewer data are available.", "output": "There is no related enetity." }, { "input": "In the present study, sediment toxicity of the pyrethoid permethrin to Chironomus dilutus was determined.", "output": "pyrethoid permethrin." }, { "input": "The whole - life - cycle toxicity testing was conducted with the endpoints covering survival, growth, emergence, and reproduction.", "output": "There is no related enetity." }, { "input": "Permethrin caused 50 % lethality in C. dilutus at 1. 83 +/- 1. 13 micro g / g organic carbon ( OC ) and 1. 20 +/- 0. 55 micro g / g OC after exposures of 20 d ( before pupation ) and 58 d ( the end of the testing ), respectively.", "output": "Permethrin, carbon." }, { "input": "The 5 % and median effect concentrations ( EC5 and EC50 ) represented the marginal and toxic levels of the sublethal effects, respectively, and effect data were all normalized to the controls before Probit analysis.", "output": "There is no related enetity." }, { "input": "The EC5s for growth, emergence, and reproduction were 0. 034 +/- 0. 006 micro g / g OC, 0. 016 +/- 0. 008 micro g / g OC, and 0. 009 +/- 0. 008 micro g / g OC, respectively; the respective EC50s were 1. 09 +/- 0. 56 micro g / g OC, 0. 838 +/- 0. 077 micro g / g OC, and 0. 039 +/- 0. 105 micro g / g OC.", "output": "There is no related enetity." }, { "input": "In addition, a 24 - h Tenax extraction was employed to better assess permethrin bioavailability.", "output": "permethrin." }, { "input": "Ultimately, response spectra with a series of endpoints were developed for permethrin using either OC - normalized bulk sediment concentrations or bioavailability - based Tenax extractable concentrations as the dose metric.", "output": "permethrin." }, { "input": "The development of bioavailability - based chronic toxicity endpoints for sediment - associated permethrin would provide valuable benchmarks for evaluating ecological risk of this contaminant and contributing to improve sediment management policies.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1403 - 1411.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Air - plant exchange of brominated flame retardants at a rural site: Influencing factor, interspecies difference, and forest scavenging.", "output": "There is no related enetity." }, { "input": "Brominated flame retardants ( BFRs ) in eucalyptus leaves and pine needles from a rural site in southern China were measured to investigate the air - plant exchange.", "output": "There is no related enetity." }, { "input": "Mean concentrations of BFRs were higher in pine needles ( 79. 8 ng / g dry wt ) than in eucalyptus leaves ( 74. 5 ng / g ), whereas an inverse result was found for the leaf surface particles, with mean concentrations of 3490 ng / g and 5718 ng / g, respectively.", "output": "There is no related enetity." }, { "input": "For most of the BFRs, the correlations between their concentrations in plants and those in the vapor phase, atmospheric particles, leaf surface particles, and the environmental variables ( temperature, wind speed, and relative humidity ) at this site were in contrast to the results the authors observed at an electronic waste site previously, indicating that ambient air level plays a vital role in the relationships.", "output": "There is no related enetity." }, { "input": "The interspecies difference in the BFR profiles and the correlations above implied that pine needles likely have more advantages for uptake of BFRs from gaseous deposition than eucalyptus leaves, for which particle - bound deposition is more important.", "output": "There is no related enetity." }, { "input": "Like the electronic waste site, the leaf scavenging ratios of BFRs were also controlled by their octanol - air partition coefficient.", "output": "There is no related enetity." }, { "input": "It was estimated that approximately 154 kg of BFRs in the atmosphere are scavenged annually by forest in this region, which was 1. 7 times larger than that via atmospheric deposition to nonforest ground.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1248 - 1253.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Rutin - and Selenium - attenuated cadmium - induced testicular pathophysiology in rats.", "output": "Rutin, Selenium, cadmium." }, { "input": "Cadmium ( Cd ) is known to cause oxidative damage in the testes of rats.", "output": "Cadmium, Cd." }, { "input": "The aim of this study was to investigate the protective role of rutin ( RUT, 30 mg / kg ) and selenium ( Se, 0. 15 ppm ) alone or in combination against Cd ( 200 ppm ) - induced lipid peroxidation, steroidogenesis and changes in antioxidant defence system in the rat testes.", "output": "rutin, RUT, selenium, Se, Cd." }, { "input": "The obtained results showed that Cd increased lipid peroxidation and abnormal sperm count and decreased plasma testosterone, lactate dehydrogenase, acid phosphatase, alkaline phosphatase and testicular steroidogenic enzymes: 3 beta - hydroxysteroid dehydrogenase ( HSD ), 17 beta - HSD activities as well as epididymal sperm counts and motility, while RUT and Se treatment reversed this change to control values.", "output": "Cd, testosterone, lactate, 3 beta - hydroxysteroid, RUT, Se." }, { "input": "Acute intoxication with Cd was also followed by significantly decreased activity of the antioxidant defence system ( superoxide dismutase ( SOD ), catalase ( CAT ), glutathione peroxidase ( GSH - Px ), glutathione reductase ( GR ), glutathione ( GSH ), and glutathione - S - transferase ( GST ) ).", "output": "Cd, superoxide, glutathione, GSH, glutathione, glutathione, GSH, glutathione, S." }, { "input": "Treatment with RUT and Se reversed Cd - induced alterations of antioxidant defence system and significantly prevented Cd - induced testes damage and depletion of plasma and testicular Se levels.", "output": "RUT, Se, Cd, Cd, Se." }, { "input": "RUT and Se appear not to have more profound effects than their separate effects against Cd - induced testicular toxicity, although Se was more potent than RUT in the recovery of testosterone levels.", "output": "RUT, Se, Cd, Se, RUT, testosterone." }, { "input": "These results suggest that both RUT and Se do not have synergistic role against Cd - induced testicular injury.", "output": "RUT, Se, Cd." }, { "input": "Probucol and the cholesterol synthesis inhibitors simvastatin and triparanol regulate Iks channel function differently.", "output": "Probucol, cholesterol, simvastatin, triparanol." }, { "input": "Channels responsible for slowly activating delayed - rectifier potassium current ( I ( Ks ) ) are composed of KCNQ1 and KCNE1 subunits, and these channels play a role in the repolarization of cardiac action potentials.", "output": "potassium." }, { "input": "Recently, we showed that the antihyperlipidemic drug probucol, which induces QT prolongation, decreases the I ( Ks ) after 24 - h treatment.", "output": "probucol." }, { "input": "In the present study, we investigated the effects of three cholesterol - lowering agents ( probucol, an enhancer of cholesterol efflux; simvastatin, a 3 - hydroxy - 3 - methylglutaryl coenzyme A reductase inhibitor; and triparanol, a 3 beta - hydroxysterol - ^ 24 - reductase inhibitor ) on cholesterol synthesis, the KCNQ1 current ( I ( KCNQ1 ) ), and the I ( Ks ) to clarify the differences in the modes of action of these agents on the I ( Ks ).", "output": "cholesterol, probucol, cholesterol, simvastatin, 3 - hydroxy - 3 - methylglutaryl, triparanol, 3 beta - hydroxysterol, cholesterol." }, { "input": "Probucol did not inhibit cholesterol synthesis and had no effect on I ( KCNQ1 ), while I ( Ks ) decreased after 24 - h treatment.", "output": "Probucol, cholesterol." }, { "input": "Simvastatin inhibited cholesterol synthesis and decreased I ( KCNQ1 ) and I ( Ks ).", "output": "Simvastatin, cholesterol." }, { "input": "Additionally, the activation kinetics of I ( Ks ) became faster, compared with that of control I ( Ks ).", "output": "There is no related enetity." }, { "input": "Triparanol inhibited cholesterol synthesis but did not reduce I ( KCNQ1 ) and I ( Ks ).", "output": "Triparanol, cholesterol." }, { "input": "However, the activation kinetics of I ( Ks ) became faster.", "output": "There is no related enetity." }, { "input": "Our data indicated that the mechanism by which probucol inhibits I ( Ks ) was not mediated by the inhibition of cholesterol synthesis but depended on an interaction with the KCNQ1 / KCNE1 complex.", "output": "probucol, cholesterol." }, { "input": "Meanwhile, the reduction in cholesterol induced by simvastatin and triparanol is one of the mechanisms that affects the kinetics of I ( ks ).", "output": "cholesterol, simvastatin, triparanol." }, { "input": "Resveratrol ameliorates methotrexate - induced hepatotoxicity in rats via inhibition of lipid peroxidation.", "output": "Resveratrol, methotrexate." }, { "input": "Hepatotoxicity is one of the major complications of methotrexate ( MTX ) therapy.", "output": "methotrexate, MTX." }, { "input": "This study was carried out to evaluate the possible protective effect of resveratrol ( trans - 3, 5, 4 ' - trihydroxystilbene, RVT ) against MTX - induced hepatotoxicity.", "output": "resveratrol, trans - 3 , 5 , 4 ' - trihydroxystilbene, RVT, MTX." }, { "input": "Rats were randomly divided into four groups as control, MTX treated ( 7 mg / kg / day, intraperitoneally ( i. p. ), once daily for 3 consecutive days ), MTX + RVT treated ( 20 mg / kg / day, i. p. ), and RVT treated.", "output": "MTX, MTX, RVT, RVT." }, { "input": "First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days.", "output": "RVT, MTX." }, { "input": "Histopathology of liver was evaluated by light microscopy.", "output": "There is no related enetity." }, { "input": "Aspartate aminotransferase ( AST ), alanine aminotransferase ( ALT ), and alkaline phosphatase ( ALP ) were used as biochemical markers of MTX - induced hepatic injury.", "output": "Aspartate, alanine, MTX." }, { "input": "The levels of thiobarbituric acid reactive substances ( TBARS, a marker of lipid peroxidation ) and activities of hepatic antioxidant enzymes such as catalase ( CAT ) and glutathione - S - transferase ( GST ) were used to analyze the oxidative stress - mediated lipid peroxidation in liver sections.", "output": "thiobarbituric acid, glutathione, S." }, { "input": "Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels.", "output": "MTX." }, { "input": "TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration.", "output": "MTX." }, { "input": "RVT treatment significantly prevented MTX - induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology.", "output": "RVT, MTX." }, { "input": "Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX - treated group.", "output": "RVT, MTX." }, { "input": "These results revealed that RVT may have a protective effect against MTX - induced hepatotoxicity by inhibiting oxidative stress - mediated lipid peroxidation.", "output": "RVT, MTX." }, { "input": "Consequently, RVT treatment might be a promising strategy against MTX - induced hepatotoxicity.", "output": "RVT, MTX." }, { "input": "Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation - induced hepatic fibrosis in rats.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum ( BC703 ) on bile duct ligation ( BDL ) - induced hepatic fibrosis in rats.", "output": "There is no related enetity." }, { "input": "BDL rats were divided into three groups, which orally received distilled water or BC703 ( 10 or 50 mg / kg / day ) for consecutive 28 days.", "output": "There is no related enetity." }, { "input": "Antifibrotic effects of BC703 on BDL - induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), total bilirubin ( TBIL ), blood urea nitrogen ( BUN ), transforming growth factor - beta 1 ( TGF - beta 1 ) and hepatic levels of malondialdehyde ( MDA ), glutathione ( GSH ), total superoxide dismutase ( SOD ) and nitric oxide ( NO ).", "output": "alanine, aspartate, bilirubin, urea, nitrogen, malondialdehyde, MDA, glutathione, GSH, superoxide, nitric oxide, NO." }, { "input": "The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson ' s trichrome stain.", "output": "hematoxylin, eosin." }, { "input": "ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham - operated group.", "output": "There is no related enetity." }, { "input": "These elevations were significantly decreased by BC703 treatment.", "output": "There is no related enetity." }, { "input": "Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group.", "output": "GSH." }, { "input": "In addition, increases in hepatic MDA and NO levels in the BDL - induced cholestasis were attenuated by BC703 treatment.", "output": "MDA, NO." }, { "input": "Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF - beta 1.", "output": "There is no related enetity." }, { "input": "Histopathological studies further substantiated the protective effect of BC703 on BDL - induced hepatic fibrosis in rat.", "output": "There is no related enetity." }, { "input": "BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease.", "output": "There is no related enetity." }, { "input": "Clinical development of biosimilars: an evolving landscape.", "output": "There is no related enetity." }, { "input": "Biosimilars, or similar biological medicinal products, can provide a meaningful option for patients and physicians provided they deliver the therapeutic value of a reference product at a more modest cost.", "output": "There is no related enetity." }, { "input": "Unlike generic small - molecule drugs that require primarily the demonstration of pharmaceutical equivalence, the complex nature of protein therapeutics warrants a rigorous evaluation of both pharmaceutical and therapeutic equivalence to the reference product in an abbreviated clinical program.", "output": "There is no related enetity." }, { "input": "Furthermore, the lack of comprehensive structure - activity relationship data increases the burden on appropriately designed human clinical studies with predefined acceptance criteria to demonstrate the absence of clinically meaningful differences between the biosimilar and reference product.", "output": "There is no related enetity." }, { "input": "Although a number of biosimilar proteins have been approved, especially in Europe, issues on substitutability, extrapolation to other disease indications, and selection of reference standards and comparators, remains to be standardized at a global level.", "output": "There is no related enetity." }, { "input": "Structure of iron ions in some acetone based electrolytes.", "output": "iron, acetone." }, { "input": "X - ray absorption, M o ssbauer, and Raman spectroscopy were combined to determine the local environment of iron ions in acetone based solutions of FeCl2.", "output": "iron, acetone, FeCl2." }, { "input": "It is shown that part of the Fe ( II ) ions change their oxidation state, accompanied by symmetry change from octahedral Fe ( H2O ) 6 ( 2 + ) to tetrahedral [ FeCl4 ] ( - ) at large acetone concentrations.", "output": "Fe ( II ), Fe ( H2O ) 6 ( 2 + ), [ FeCl4 ] ( - ), acetone." }, { "input": "The ratio of Fe ( II ) / Fe ( III ) determined by M o ssbauer spectroscopy agrees well with that determined by the X - ray absorption studies.", "output": "Fe ( II ), Fe ( III )." }, { "input": "Raman measurements confirm quantitative estimations of [ FeCl4 ] ( - ) species in acetone rich solutions.", "output": "[ FeCl4 ] ( - ), acetone." }, { "input": "Biotransformation of ursolic acid by Syncephalastrum racemosum CGMCC 3. 2500 and anti - HCV activity.", "output": "ursolic acid." }, { "input": "Microbial transformation of ursolic acid ( UA, 3 beta - hydroxy - urs - 12 - en - 28 - oic acid, 1 ) by filamentous fungus Syncephalastrum racemosum CGMCC 3. 2500 was conducted.", "output": "ursolic acid, 3 beta - hydroxy - urs - 12 - en - 28 - oic acid." }, { "input": "Five metabolites 3 beta, 7 beta, 21 beta - trihydroxy - urs - 12 - en - 28 - oic acid ( 2 ); 3 beta, 21 beta - dihydroxy - urs - 11 - en - 28 - oic acid - 13 - lactone ( 3 ); 1 beta, 3 beta, 21 beta - trihydroxy - urs - 12 - en - 28 - oic acid ( 4 ); 3 beta, 7 beta, 21 beta - trihydroxy - urs - 1 - en - 28 - oic acid - 13 - lactone ( 5 ); and 21 - oxo - 1 beta, 3 beta - dihydroxy - urs - 12 - en - 28 - oic acid ( 6 ) were afforded.", "output": "3 beta , 7 beta , 21 beta - trihydroxy - urs - 12 - en - 28 - oic acid, 3 beta , 21 beta - dihydroxy - urs - 11 - en - 28 - oic acid - 13 - lactone, 1 beta , 3 beta , 21 beta - trihydroxy - urs - 12 - en - 28 - oic acid, 3 beta , 7 beta , 21 beta - trihydroxy - urs - 1 - en - 28 - oic acid - 13 - lactone, 21 - oxo - 1 beta , 3 beta - dihydroxy - urs - 12 - en - 28 - oic acid." }, { "input": "Elucidation of the structures of these metabolites was primarily based on 1D and 2D NMR and HR - MS data.", "output": "There is no related enetity." }, { "input": "Metabolite 2 was a new compound.", "output": "There is no related enetity." }, { "input": "In addition, the anti - HCV activity of compounds 1 - 6 was evaluated.", "output": "There is no related enetity." }, { "input": "Biomarkers of Exposure and Effect in Human Lymphoblastoid TK6 Cells Following [ 13C2 ] - Acetaldehyde Exposure.", "output": "[ 13C2 ] - Acetaldehyde." }, { "input": "The dose - response relationship for biomarkers of exposure ( N ( 2 ) - ethylidene - dG adducts ) and effect ( cell survival and micronucleus formation ) was determined across 4. 5 orders of magnitude ( 50nM - 2mM ) using [ ( 13 ) C2 ] - acetaldehyde exposures to human lymphoblastoid TK6 cells for 12h.", "output": "N ( 2 ) - ethylidene - dG, [ ( 13 ) C2 ] - acetaldehyde." }, { "input": "There was a clear increase in exogenous N ( 2 ) - ethylidene - dG formation at exposure concentrations >= 1 micro M, whereas the endogenous adducts remained nearly constant across all exposure concentrations, with an average of 3. 0 adducts / 10 ( 7 ) dG.", "output": "N ( 2 ) - ethylidene - dG." }, { "input": "Exogenous adducts were lower than endogenous adducts at concentrations <= 10 micro M and were greater than endogenous adducts at concentrations >= 250 micro M.", "output": "There is no related enetity." }, { "input": "When the endogenous and exogenous adducts were summed together, statistically significant increases in total adduct formation over the endogenous background occurred at 50 micro M.", "output": "There is no related enetity." }, { "input": "Cell survival and micronucleus formation were monitored across the exposure range and statistically significant decreases in cell survival and increases in micronucleus formation occurred at >= 1000 micro M.", "output": "There is no related enetity." }, { "input": "This research supports the hypothesis that endogenously produced reactive species, including acetaldehyde, are always present and constitute the majority of the observed biological effects following very low exposures to exogenous acetaldehyde.", "output": "acetaldehyde, acetaldehyde." }, { "input": "These data can replace default assumptions of linear extrapolation to very low doses of exogenous acetaldehyde for risk prediction.", "output": "acetaldehyde." }, { "input": "The role of de novo catecholamine synthesis in mediating methylmercury - induced vesicular dopamine release from rat pheochromocytoma ( PC12 ) cells.", "output": "catecholamine, methylmercury, dopamine." }, { "input": "The purpose of this study was to characterize methylmercury ( MeHg ) - induced dopamine ( DA ) release from undifferentiated pheochromocytoma ( PC12 ) cells and to examine the potential role for DA synthesis in this process.", "output": "methylmercury, MeHg, dopamine." }, { "input": "MeHg caused a significant increase in DA release that was both concentration - and time - dependent.", "output": "MeHg." }, { "input": "DA release was significantly increased by 2 micro M MeHg at 60min and by 5 micro M MeHg at 30min; 1 micro M MeHg was without effect.", "output": "MeHg, MeHg, MeHg." }, { "input": "Because DA release induced by 5 micro M MeHg was associated with a significant percentage of cell death at 60 and 120min, 2 micro M MeHg was chosen for further characterization of release mechanisms.", "output": "MeHg, MeHg." }, { "input": "MeHg - induced DA release was attenuated but not abolished in the absence of extracellular calcium, whereas the vesicular content depleting drug reserpine ( 50nM ) abolished release.", "output": "MeHg, calcium." }, { "input": "Thus, MeHg - induced DA release requires vesicular exocytosis but not extracellular calcium.", "output": "MeHg, calcium." }, { "input": "MeHg also increased intracellular DA and the rate of DA storage utilization, suggesting a role for DA synthesis in MeHg - induced DA release.", "output": "MeHg, MeHg." }, { "input": "The tyrosine hydroxylase inhibitor alpha - methyltyrosine ( 300 micro M, 24h ) completely abolished MeHg - induced DA release.", "output": "tyrosine, alpha - methyltyrosine, MeHg." }, { "input": "MeHg significantly increased DA precursor accumulation in cells treated with 3 - hydroxybenzylhydrazine ( 10 micro M ), revealing that MeHg increases tyrosine hydroxylase activity.", "output": "MeHg, 3 - hydroxybenzylhydrazine, MeHg, tyrosine." }, { "input": "Overall, these data demonstrate that MeHg facilitates DA synthesis, increases intracellular DA, and augments vesicular exocytosis.", "output": "MeHg." }, { "input": "Nfil3 is a glucocorticoid - regulated gene required for glucocorticoid - induced apoptosis in male murine T cells.", "output": "There is no related enetity." }, { "input": "Glucocorticoids ( GCs ) have essential roles in the regulation of development, integrated metabolism, and immune and neurological responses, and act primarily via the glucocorticoid receptor ( GR ).", "output": "There is no related enetity." }, { "input": "In most cells, GC treatment results in down - regulation of GR mRNA and protein levels via negative feedback mechanisms.", "output": "There is no related enetity." }, { "input": "However, in GC - treated thymocytes, GR protein levels are maintained at a high level, increasing sensitivity of thymocytes to GCs, resulting in apoptosis termed glucocorticoid - induced cell death ( GICD ).", "output": "There is no related enetity." }, { "input": "CD4 ( + ) CD8 ( + ) double - positive thymocytes and thymic natural killer T cells in particular are highly sensitive to GICD.", "output": "There is no related enetity." }, { "input": "Although GICD is exploited via the use of synthetic GC analogues in the treatment of hematopoietic malignancies, the intracellular molecular pathway of GICD is not well understood.", "output": "There is no related enetity." }, { "input": "To explore GICD in thymocytes, the authors performed whole genome expression microarray analysis in mouse GR exon 2 null vs wild - type thymus RNA 3 hours after dexamethasone treatment.", "output": "There is no related enetity." }, { "input": "Identified and validated direct GR targets included P21 and Bim, in addition to an important transcriptional regulator Nfil3, which previously has been associated with GICD and is essential for natural killer cell development in vivo.", "output": "There is no related enetity." }, { "input": "Immunostaining of NFIL3 in whole thymus localized NFIL3 primarily to the medullary region, and double labeling colocalized NFIL3 to apoptotic cells.", "output": "There is no related enetity." }, { "input": "In silico analysis revealed a putative GC response element 5 kb upstream of the Nfil3 promoter that is strongly conserved in the rat genome and was confirmed to bind GR by chromatin immunoprecipitation.", "output": "There is no related enetity." }, { "input": "The knockdown of Nfil3 mRNA levels to 20 % of normal using specific small interfering RNAs abrogated GICD, indicating that NFIL3 is required for normal GICD in CTLL - 2 T cells.", "output": "There is no related enetity." }, { "input": "Prescription of antiepileptics and the risk of road traffic crash.", "output": "There is no related enetity." }, { "input": "Studies assessing the impact of epilepsy and its medication on the risk of road traffic crashes have shown inconsistent results.", "output": "There is no related enetity." }, { "input": "The aim in this study was to assess this risk using French databases.", "output": "There is no related enetity." }, { "input": "Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes.", "output": "There is no related enetity." }, { "input": "Only antiepileptics prescribed predominantly in epilepsy were studied ( phenobarbital, phenytoin, ethosuximide, valproic acid, vigabatrin, tiagabin, levitiracetam, zonisamide, and lacosamide ).", "output": "phenobarbital, phenytoin, ethosuximide, valproic acid, vigabatrin, tiagabin, levitiracetam, zonisamide, lacosamide." }, { "input": "A case - control analysis comparing responsible and non - responsible drivers and a case - crossover analysis were performed.", "output": "There is no related enetity." }, { "input": "Drivers ( 72 685 ) involved in an injurious crash in France between July 2005 and May 2008, were included.", "output": "There is no related enetity." }, { "input": "Drivers exposed to prescribed antiepileptic medicines ( n = 251 ) had an increased risk of being responsible for a crash ( OR 1. 74 [ 1. 29 - 2. 34 ] ).", "output": "There is no related enetity." }, { "input": "The association was also significant for the most severe epileptic patients ( n = 99; OR = 2. 20 [ 1. 31 - 3. 69 ] ).", "output": "There is no related enetity." }, { "input": "Case - crossover analysis found no association between crash risk and treatment prescription.", "output": "There is no related enetity." }, { "input": "Patients with prescription of antiepileptic drugs should be cautioned about their potential risk of road traffic crash.", "output": "There is no related enetity." }, { "input": "This risk is however more likely to be related to seizures than to the effect of antiepileptic medicines.", "output": "There is no related enetity." }, { "input": "Anti - inflammatory profile of paricalcitol in hemodialysis patients: a prospective, open - label, pilot study.", "output": "paricalcitol." }, { "input": "Inflammation is a strong predictor of increased morbidity and mortality in hemodialysis ( HD ) patients.", "output": "There is no related enetity." }, { "input": "Paricalcitol, a selective vitamin D receptor activator used for prevention and treatment of secondary hyperparathyroidism, has shown anti - inflammatory properties in experimental studies, although clinical data are scarce.", "output": "Paricalcitol, vitamin D." }, { "input": "In an open - label, prospective, single center, pilot study, 25 stable HD patients, previously receiving calcitriol, completed 12 weeks of therapy with oral paricalcitol.", "output": "calcitriol, paricalcitol." }, { "input": "Serum and peripheral blood mononuclear cell ( PBMC ) expression profiles of inflammatory cytokines were analyzed.", "output": "There is no related enetity." }, { "input": "Serum interleukin ( IL ) - 1, IL - 10, and IL - 18 did not change, unlike high - sensitivity C - reactive protein ( hs - CRP ), tumor necrosis factor - alpha ( TNF - alpha ), and IL - 6, which experienced a significant mean percent decrease of 14. 3 %, 4. 7 %, and 5 %, respectively.", "output": "There is no related enetity." }, { "input": "There was a significant reduction in the TNF - alpha / IL - 10 and the IL - 6 / IL - 10 ratios ( P <. 05 ).", "output": "There is no related enetity." }, { "input": "Serum intact parathyroid hormone concentration experienced a mild but significant reduction.", "output": "There is no related enetity." }, { "input": "In addition, expression levels of TNF - alpha and IL - 6 decreased by 19. 1 % ( P <. 01 ) and 17. 5 % ( P <. 001 ), respectively, whereas expression of IL - 10 increased by 17. 7 % ( P <. 01 ) after treatment.", "output": "There is no related enetity." }, { "input": "In conclusion, paricalcitol administration to HD patients is associated with a beneficial effect on the inflammatory cytokine serum and gene expression profile of PBMC.", "output": "paricalcitol." }, { "input": "This effect may contribute to the survival benefits of paricalcitol observed in clinical studies.", "output": "paricalcitol." }, { "input": "Novel Insights into CB1 Cannabinoid Receptor Signaling: A Key Interaction Identified between the Extracellular - 3 Loop and Transmembrane Helix 2.", "output": "There is no related enetity." }, { "input": "Activation of the cannabinoid CB1 receptor ( CB1 ) is modulated by aspartate residue D2. 63 ( 176 ) in transmembrane helix ( TMH ) 2.", "output": "aspartate." }, { "input": "Interestingly, D2. 63 does not affect the affinity for ligand binding at the CB1 receptor.", "output": "There is no related enetity." }, { "input": "Studies in class A G protein - coupled receptors have suggested an ionic interaction between residues of TMH2 and 7.", "output": "There is no related enetity." }, { "input": "In this report, modeling studies identified residue K373 in the extracellular - 3 ( EC - 3 ) loop in charged interactions with D2. 63.", "output": "There is no related enetity." }, { "input": "We investigated this possibility by performing reciprocal mutations and biochemical studies.", "output": "There is no related enetity." }, { "input": "D2. 63 ( 176 ) A, K373A, D2. 63 ( 176 ) A - K373A, and the reciprocal mutant with the interacting residues juxtaposed D2. 63 ( 176 ) K - K373D were characterized using radioligand binding and guanosine 5 ' - 3 - O - ( thio ) triphosphate functional assays.", "output": "guanosine 5 ' - 3 - O - ( thio ) triphosphate." }, { "input": "None of the mutations resulted in a significant change in the binding affinity of N - ( piperidiny - 1 - yl ) - 5 - ( 4 - chlorophenyl ) - 1 - ( 2, 4 - dichloro - phenyl ) - 4 - methyl - 1H - pyrazole - 3 - carboxamide hydrochloride ( SR141716A ) or ( - ) - 3cis - [ 2 - hydroxyl - 4 - ( 1, 1 - dimethyl - heptyl ) phenyl ] - trans - 4 - [ 3 - hydroxyl - propyl ] cyclohexan - 1 - ol ( CP55, 940 ).", "output": "N - ( piperidiny - 1 - yl ) - 5 - ( 4 - chlorophenyl ) - 1 - ( 2 , 4 - dichloro - phenyl ) - 4 - methyl - 1H - pyrazole - 3 - carboxamide hydrochloride, SR141716A, ( - ) - 3cis - [ 2 - hydroxyl - 4 - ( 1 , 1 - dimethyl - heptyl ) phenyl ] - trans - 4 - [ 3 - hydroxyl - propyl ] cyclohexan - 1 - ol, CP55 , 940." }, { "input": "Modeling studies indicated that binding - site interactions and energies of interaction for CP55, 940 were similar between wild - type and mutant receptors.", "output": "CP55 , 940." }, { "input": "However, the signaling of CP55, 940, and ( R ) - ( + ) - [ 2, 3 - dihydro - 5 - methyl - 3 - [ ( 4 - morpholinyl ) methyl ] - pyrrolo [ 1, 2, 3 - de ] - 1, 4 - benzoxazin - 6 - yl ] ( 1 - naphthalenyl ) - methanone mesylate ( WIN55, 212 - 2 ) was impaired at the D2. 63 ( 176 ) A - K373A and the single - alanine mutants.", "output": "CP55 , 940, ( R ) - ( + ) - [ 2 , 3 - dihydro - 5 - methyl - 3 - [ ( 4 - morpholinyl ) methyl ] - pyrrolo [ 1 , 2 , 3 - de ] - 1 , 4 - benzoxazin - 6 - yl ] ( 1 - naphthalenyl ) - methanone mesylate, WIN55 , 212 - 2, alanine." }, { "input": "In contrast, the reciprocal D2. 63 ( 176 ) K - K373D mutant regained function for both CP55, 940 and WIN55, 212 - 2.", "output": "CP55 , 940, WIN55 , 212 - 2." }, { "input": "Computational results indicate that the D2. 63 ( 176 ) - K373 ionic interaction strongly influences the conformation ( s ) of the EC - 3 loop, providing a structure - based rationale for the importance of the EC - 3 loop to signal transduction in CB1.", "output": "There is no related enetity." }, { "input": "The putative ionic interaction results in the EC - 3 loop pulling over the top ( extracellular side ) of the receptor; this EC - 3 loop conformation may serve protective and mechanistic roles.", "output": "There is no related enetity." }, { "input": "These results suggest that the ionic interaction between D2. 63 ( 176 ) and K373 is important for CB1 signal transduction.", "output": "There is no related enetity." }, { "input": "Theoretical Study on the Photodegradation Mechanism of Nona - BDEs in Methanol.", "output": "Nona - BDEs, Methanol." }, { "input": "Polybrominated diphenyl ethers ( PBDEs ) have received special environmental concern due to their potential toxicity to humans and wildlife worldwide, however, it is difficult to reveal their dominant photochemical degradation pathways by experiment.", "output": "Polybrominated diphenyl ethers, PBDEs." }, { "input": "We explored the reaction mechanisms of photochemical degradation - debromination of three nona - BDEs in methanol using theoretical calculations, in which time - dependent density functional theory ( TDDFT ) combined with the polarizable continuum ( PCM ) model is applied.", "output": "nona - BDEs, methanol." }, { "input": "The selectivity of debromination was studied, and the major octa - BDE products photochemically debrominated from nona - BDEs were identified.", "output": "octa - BDE, nona - BDEs." }, { "input": "We find that the debromination reaction results from the electronic transitions from pi to sigma * orbitals when nona - BDEs are exposed to UV - light in the sunlight region, at which point the two low - lying excited states for each nona - BDE are pi sigma * ( 5Br ) and pi sigma * ( 4Br ), which correlate to the sigma * orbitals located on the penta - Br and tetra - Br substituted phenyls, respectively.", "output": "nona - BDEs, nona - BDE, 5Br, 4Br, penta - Br, tetra - Br, phenyls." }, { "input": "Our calculations indicate that each nona - BDE may degrade to form three kinds of octa - BDE products via the pi sigma * ( 5Br ) state, whereas only one kind of octa - BDEs can be formed via the pi sigma * ( 4Br ) state.", "output": "nona - BDE, octa - BDE, 5Br, octa - BDEs, 4Br." }, { "input": "Our calculations can interpret the recent experiments successfully.", "output": "There is no related enetity." }, { "input": "Meal conditions affect the absorption of supplemental vitamin D ( 3 ) but not the plasma 25 - hydroxyvitamin D response to supplementation.", "output": "vitamin D ( 3 ), 25 - hydroxyvitamin D." }, { "input": "It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established.", "output": "vitamin D, vitamin D." }, { "input": "This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25 - hydroxyvitamin D ( 25OHD ) response to supplemental vitamin D ( 3 ).", "output": "vitamin D, 25 - hydroxyvitamin D, 25OHD, vitamin D ( 3 )." }, { "input": "Based on earlier studies in rats we postulated that absorption would be greatest in the low - fat meal group.", "output": "There is no related enetity." }, { "input": "Sixty two healthy older men and women were randomly assigned to one of three meal groups: no meal, high - fat meal or low - fat meal; each was given a monthly 50, 000 IU vitamin D ( 3 ) supplement with the test breakfast meal ( or after a fast for the no - meal group ) and followed for 90 days.", "output": "vitamin D ( 3 )." }, { "input": "Plasma vitamin D ( 3 ) was measured by LC / MS before and 12 hrs after the first dose; plasma 25OHD was measured by radioimmunoassay at baseline and after 30 and 90 days.", "output": "vitamin D ( 3 ), 25OHD." }, { "input": "The mean 12 - hr increments in vitamin D ( 3 ), after adjusting for age and sex, were 200. 9 nmol / L in the no - meal group, 207. 4 nmol / L in the high - fat meal group, and 241. 1 nmol / L in the low - fat meal group ( P = 0. 038 ), with the increase in the low - fat group being significantly greater than the increases in the other two groups.", "output": "vitamin D ( 3 )." }, { "input": "However, increments in 25OHD levels at 30 and 90 days didn ' t differ significantly in the three groups.", "output": "25OHD." }, { "input": "We conclude that absorption was increased when a 50, 000 IU dose of vitamin D was taken with a low - fat meal, compared with a high - fat meal and no meal, but that the greater absorption didn ' t result in higher plasma 25OHD levels in the low - fat meal group.", "output": "vitamin D, 25OHD." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Exendin - 4, a GLP - 1 receptor agonist, prevents osteopnia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats.", "output": "There is no related enetity." }, { "input": "Osteoporosis mainly affects postmenopausal women and older men.", "output": "There is no related enetity." }, { "input": "Gastrointestinal hormones released after meal ingestion, such as glucose - dependent insulinotropic peptide ( GIP ) and glucagon - like peptide ( GLP ) - 2, have been shown to regulate bone turnover.", "output": "glucose." }, { "input": "However, whether GLP - 1, another important gastrointestinal hormone, and its analogues also have anti - osteoporotic effects, especially in aged postmenopausal situation, is not confirmed yet.", "output": "There is no related enetity." }, { "input": "In the present study, we evaluated the effects of the GLP - 1 receptor agonist exendin - 4 on ovariectomy ( OVX ) induced osteoporosis in old rats.", "output": "There is no related enetity." }, { "input": "Twelve - month - old female Sprague - Dawley rats were subjected to OVX, and exendin - 4 were administrated 4 weeks after the surgery and lasted for 16 weeks.", "output": "There is no related enetity." }, { "input": "Bone characters and related serum and gene biomarkers were analyzed.", "output": "There is no related enetity." }, { "input": "Sixteen weeks treatment of exendin - 4 slowed down the body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats.", "output": "There is no related enetity." }, { "input": "Exendin - 4 also enhanced the bone strength and prevented the deterioration of trabecular microarchitecture.", "output": "There is no related enetity." }, { "input": "Moreover, exendin - 4 decreased urinary DPD / creatinine ratio and serum CTX - I and increased serum ALP, OC and P1NP levels, key biochemical markers of bone turnover.", "output": "creatinine." }, { "input": "Interestingly, gene expression results further showed that exendin - 4 not only inhibited bone resorption by increasing OPG / RANKL ratio, but also promoted bone formation by increasing the expressions of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous anti - osteoporotic agents.", "output": "There is no related enetity." }, { "input": "In conclusion, these findings demonstrated for the first time the anti - osteoporotic effects of exendin - 4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Nanoscale poling of polymer films.", "output": "There is no related enetity." }, { "input": "Spots of second harmonic generation ( SHG ) are produced from nanopatterned sub - micrometer areas of nonlinear polymer media.", "output": "There is no related enetity." }, { "input": "Information is written by using a biased - AFM tip, a highly nonlinear polymer ( poly ( methyl metha - acrylate ) - co - Disperse Red 1 ), and a novel \" floating - tip nanolithography \" ( FTN ) technique.", "output": "poly ( methyl metha - acrylate ), Disperse Red 1." }, { "input": "Dipoles are oriented and aligned at the nanoscale under the biased - AFM tip, resulting in SHG production.", "output": "There is no related enetity." }, { "input": "The information is storable over weeks.", "output": "There is no related enetity." }, { "input": "Interactive effects of contaminants and climate - related stressors: High temperature increases sensitivity to cadmium.", "output": "cadmium." }, { "input": "An emerging issue in environmental toxicology is in understanding how climate change will alter responses of organisms to chemical contaminants.", "output": "There is no related enetity." }, { "input": "The objective of the present study was to characterize the interactive effects of cadmium and elevated temperature on life - stage - specific responses in the freshwater snail Physa pomilia.", "output": "cadmium." }, { "input": "We exposed developing eggs, juveniles, and adults to Cd ( 5 micro g / L, 15 micro g / L, and 25 micro g / L for eggs, and 250 micro g / L for juveniles and adults ) and 2 temperatures of 25 degrees C ( control ) and 35 degrees C ( upper range of tolerance ).", "output": "Cd." }, { "input": "In the absence of Cd, time to hatch was shorter at 35 degrees C compared with 25 degrees C, demonstrating a stimulatory effect of the higher temperature.", "output": "Cd." }, { "input": "However, when egg masses were reared at 35 degrees C and exposed to Cd, hatching success was significantly lower, and time - to - hatching was significantly longer.", "output": "Cd." }, { "input": "The effects of the higher temperature and Cd on newly hatched neonate survival were additive, except at the highest Cd concentration, at which effects of the 2 stressors were greater than additive.", "output": "Cd, Cd." }, { "input": "Overall, within the combined stressor treatments, adult snails generally survived significantly longer than did juvenile snails, and both were more tolerant than developing snails.", "output": "There is no related enetity." }, { "input": "Many climate projection models predict future increases in global temperatures.", "output": "There is no related enetity." }, { "input": "The present study shows that combined stressors may produce greater - than - additive effects, challenging predictive power.", "output": "There is no related enetity." }, { "input": "More studies are needed to better characterize the interactive effects of chemical contaminants and stressors related to climate change.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1337 - 1343.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Dechlorane plus monoadducts in a lake ontario ( Canada ) food web and biotransformation by lake trout ( Salvelinus namaycush ) liver microsomes.", "output": "Dechlorane plus." }, { "input": "Compounds related to the high - production - volume flame retardant Dechlorane Plus ( DP ) were measured in a Lake Ontario food web located downstream of a DP manufacturing plant.", "output": "Dechlorane Plus." }, { "input": "These compounds, 1, 3 - and 1, 5 - DP - monoadducts ( DPMA ), are positional isomers and are thought to arise from the incomplete reaction of DP or impurities in the DP starting material during its manufacture.", "output": "1 , 3 - and 1 , 5 - DP." }, { "input": "The 1, 3 - DPMA isomer was measured ( 0. 12 - 199 ng g ( - 1 ) lipid wt ) in all trophic levels, whereas 1, 5 - DPMA was measured only sporadically in the food web and was not detectable in the apex predator, lake trout ( Salvelinus namaycush ).", "output": "There is no related enetity." }, { "input": "Concentrations of DPMA isomers when detected in Lake Ontario biota were greater than that of total DP for all trophic levels.", "output": "There is no related enetity." }, { "input": "The prevalence of 1, 3 - DPMA in the food web, and especially in lake trout, may be due to obstruction of the existing carbon double bond to enzyme attack, rendering it less readily metabolized.", "output": "carbon." }, { "input": "To examine this hypothesis, biotransformation kinetic experiments using in vitro lake trout liver microsomal exposures were performed.", "output": "There is no related enetity." }, { "input": "Zero - order depletion rate constants for 1, 3 - and 1, 5 - DPMA were 92. 2 and 134. 6 pmole h ( - 1 ), respectively, with corresponding half - lives of 2. 03 +/- 0. 14 h ( 1, 3 - DPMA ) and 1. 39 +/- 0. 09 h ( 1, 5 - DPMA ).", "output": "There is no related enetity." }, { "input": "Furthermore, the 1, 5 - isomer was depleted to a greater extent than 1, 3 - DPMA.", "output": "There is no related enetity." }, { "input": "Specific biotransformation products were not identified.", "output": "There is no related enetity." }, { "input": "These data support the hypothesis that 1, 5 - DPMA is more readily metabolized than 1, 3 - DPMA by lake trout.", "output": "There is no related enetity." }, { "input": "The present study also shows that the concentrations of these isomers, which the authors speculate might be unintended impurities or byproducts in some technical DP formulations, exceed that of the intended product in biota.", "output": "There is no related enetity." }, { "input": "Environ Toxicol Chem 2013; 32: 1376 - 1381.", "output": "There is no related enetity." }, { "input": "(c) 2013 SETAC.", "output": "There is no related enetity." }, { "input": "Addressable organic structure by anisotropic wetting.", "output": "There is no related enetity." }, { "input": "The anisotropic wetting of functional organic molecules on a patterned surface and the development of a photolithography - compatible method to fabricate addressable organic structures is reported.", "output": "There is no related enetity." }, { "input": "For example, DtCDQA is grown on a SiO2 surface with a Au prepattern, achieving a high resolution cross - over organic structure.", "output": "SiO2, Au." }, { "input": "In vivo overexpression of tissue - nonspecific alkaline phosphatase increases skeletal mineralization and affects the phosphorylation status of osteopontin.", "output": "There is no related enetity." }, { "input": "Functional ablation of tissue - nonspecific alkaline phosphatase ( TNAP ) ( Alpl ( - / - ) mice ) leads to hypophosphatasia, characterized by rickets / osteomalacia attributable to elevated levels of extracellular inorganic pyrophosphate, a potent mineralization inhibitor.", "output": "pyrophosphate." }, { "input": "Osteopontin ( OPN ) is also elevated in the plasma and skeleton of Alpl ( - / - ) mice.", "output": "There is no related enetity." }, { "input": "Phosphorylated OPN is known to inhibit mineralization, however, the phosphorylation status of the increased OPN found in Alpl ( - / - ) mice is unknown.", "output": "There is no related enetity." }, { "input": "Here, we generated a transgenic mouse line expressing human TNAP under control of an osteoblast - specific Col1a1 promoter ( Col1a1 - Tnap ).", "output": "There is no related enetity." }, { "input": "The transgene is expressed in osteoblasts, periosteum, and cortical bones, and plasma levels of TNAP in mice expressing Col1a1 - Tnap are 10 - 20 times higher than those of wild - type mice.", "output": "There is no related enetity." }, { "input": "The Col1a1 - Tnap animals are healthy and exhibit increased bone mineralization by microCT analysis.", "output": "There is no related enetity." }, { "input": "Crossbreeding of Col1a1 - Tnap transgenic mice to Alpl ( - / - ) mice rescues the lethal hypophosphatasia phenotype characteristic of this disease model.", "output": "There is no related enetity." }, { "input": "Osteoblasts from [ Col1a1 - Tnap ] mice mineralize better than non - transgenic controls and osteoblasts from [ Col1a1 - Tnap ( + / - ); Alpl ( - / - ) ] mice are able to mineralize to the level of Alpl ( + / - ) heterozygous osteoblasts, while Alpl ( - / - ) osteoblasts show no mineralization.", "output": "There is no related enetity." }, { "input": "We found that the increased levels of OPN in bone tissue of Alpl ( - / - ) mice are comprised of phosphorylated forms of OPN while WT and [ Col1a1 - Tnap ( + / - ); Alpl ( - / - ) ] mice had both phosphorylated and dephosphorylated forms of OPN.", "output": "There is no related enetity." }, { "input": "OPN from [ Col1a1 - Tnap ] osteoblasts were more phosphorylated than non - transgenic control cells.", "output": "There is no related enetity." }, { "input": "Titanium dioxide - liquid chromatography and tandem mass spectrometry analysis revealed that OPN peptides derived from Alpl ( - / - ) bone and osteoblasts yielded a higher proportion of phosphorylated peptides than samples from WT mice, and at least two phosphopeptides, p ( S ( 174 ) FQVS ( 178 ) DEQY ( 182 ) PDAT ( 186 ) DEDLT ( 191 ) ) SHMK and FRIp ( S ( 299 ) HELES ( 304 ) S ( 305 ) S ( 306 ) S ( 307 ) ) EVN, with one non - localized site each, appear to be preferred sites of TNAP action on OPN.", "output": "Titanium dioxide." }, { "input": "Our data suggest that the pro - mineralization role of TNAP may be related not only to its accepted pyrophosphatase activity but also to its ability to modify the phosphorylation status of OPN.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "A liquid crystalline phase with uniform tilt, local polar order and capability of symmetry breaking.", "output": "There is no related enetity." }, { "input": "A new liquid crystalline ( LC ) phase with uniform tilt, local polar order and capability of symmetry breaking is found for a bent - core mesogen combining a 4 - cyanoresorcinol unit with two azobenzene wings.", "output": "4 - cyanoresorcinol, azobenzene." }, { "input": "The combination of local polar order and long range synclinic tilt in this SmCs PR phase leads, under special conditions, to macroscopic domains with opposite chirality, though the molecules themselves are achiral.", "output": "There is no related enetity." }, { "input": "Surface - confined electroactive molecules for multistate charge storage information.", "output": "There is no related enetity." }, { "input": "Bi - stable molecular systems with potential for applications in binary memory devices are raising great interest for device miniaturization.", "output": "There is no related enetity." }, { "input": "Particular appealing are those systems that operate with electrical inputs since they are compatible with existing electronic technologies.", "output": "There is no related enetity." }, { "input": "The processing of higher memory densities in these devices could be accomplished by increasing the number of memory states in each cell, although this strategy has not been much explored yet.", "output": "There is no related enetity." }, { "input": "Here we highlight the recent advances devoted to the fabrication of charge - storage molecular surface - confined devices exhibiting multiple states.", "output": "There is no related enetity." }, { "input": "Mainly, this goal has been realized immobilizing a variety ( or a combination ) of electroactive molecules on a surface, although alternative approaches employing non - electroactive systems have also been described.", "output": "There is no related enetity." }, { "input": "Undoubtedly, the use of molecules with chemically tunable properties and nanoscale dimensions are raising great hopes for the devices of the future in which molecules can bring new perspectives such as multistability.", "output": "There is no related enetity." }, { "input": "Formation of a polymer surface with a gradient of pore size using a microfluidic chip.", "output": "There is no related enetity." }, { "input": "Here we demonstrate the generation of polymer monolithic surfaces possessing a gradient of pore and polymer globule sizes from ~ 0. 1 to ~ 0. 5 mu m defined by the composition of two polymerization mixtures injected into a microfluidic chip.", "output": "There is no related enetity." }, { "input": "To generate the gradient, we used a PDMS microfluidic chip with a cascade micromixer with a subsequent reaction chamber for the formation of a continuous gradient film.", "output": "PDMS." }, { "input": "The micromixer has zigzag channels of 400 x 680 mu m ( 2 ) cross section and six cascades.", "output": "There is no related enetity." }, { "input": "The chip was used with a reversible bonding connection, realized by curing agent coating.", "output": "There is no related enetity." }, { "input": "After polymerization in the microfluidic chip the reversible bond was opened, resulting in a 450 mu m thick polymer film possessing the pore size gradient.", "output": "There is no related enetity." }, { "input": "The gradient formation in the microfluidic reaction chamber was studied using microscopic laser - induced fluorescence ( mu LIF ) and different model fluids.", "output": "There is no related enetity." }, { "input": "Formation of linear gradients was shown using the fluids of the same density by both diffusive mixing at flow rates of 0. 001 mL / min and in a convective mixing regime at flow rates of 20 mL / min.", "output": "There is no related enetity." }, { "input": "By using different density fluids, formation of a two - dimensional wedge - like gradient controlled by the density difference and orientation of the microfluidic chip was observed.", "output": "There is no related enetity." }, { "input": "Solubility - driven optimization of ( pyridin - 3 - yl ) benzoxazinyl - oxazolidinones leading to a promising antibacterial agent.", "output": "( pyridin - 3 - yl ) benzoxazinyl - oxazolidinones." }, { "input": "The solubility - driven structural modification of ( pyridin - 3 - yl ) benzoxazinyl - oxazolidinones is described, which resulted in the development of a new series of benzoxazinyl - oxazolidinone analogues with high antibacterial activity against Gram - positive pathogens, including that against linezolid - resistant strains and low hERG inhibition.", "output": "( pyridin - 3 - yl ) benzoxazinyl - oxazolidinones, benzoxazinyl - oxazolidinone, linezolid." }, { "input": "With regard to structure - activity relationship ( SAR ) trends among the various substituents on the pyridyl ring, relatively small and nonbasic substituents were preferable to sterically demanding or basic substituents.", "output": "pyridyl." }, { "input": "Oxazolidinone ring substitution on the pyridyl ring generated analogues with antibacterial activity superior to imidazolidinone ring.", "output": "Oxazolidinone, pyridyl, imidazolidinone." }, { "input": "Solubility was enhanced by the incorporation of polar groups, especially when compounds were converted to their prodrugs.", "output": "There is no related enetity." }, { "input": "Among the prodrugs, compound 85 exhibited excellent solubility and a good pharmacokinetic profile.", "output": "There is no related enetity." }, { "input": "In a MRSA systemic infection model, compound 85 displayed an ED50 = 5. 00 mg / kg, a potency that is 2 - fold better than that of linezolid.", "output": "linezolid." }, { "input": "Transparent, Conductive, and Printable Composites Consisting of TEMPO - Oxidized Nanocellulose and Carbon Nanotube.", "output": "TEMPO, Carbon." }, { "input": "Ultrastrong, transparent, conductive and printable nanocomposites were successfully prepared by mixing single - walled carbon nanotubes ( CNTs ) with 2, 2, 6, 6 - tetramethylpiperidine - 1 - oxyl ( TEMPO ) - oxidized cellulose nanofibrils ( TOCNs ) with abundant sodium carboxyl groups on the crystalline nanocellulose surfaces.", "output": "carbon, 2 , 2 , 6 , 6 - tetramethylpiperidine - 1 - oxyl, TEMPO, sodium carboxyl." }, { "input": "The surface - anionic cellulose nanofibrils had reinforcing and nanodispersing effects on the CNTs both in water used as the dispersed medium and in the dried composite film, providing highly conductive and printable nanocomposites with a small amount of CNTs.", "output": "There is no related enetity." }, { "input": "TOCNs are therefore expected as an effective flexible matrix that can be used as an alternative to conventional polymers for various electrical materials, when nanocomposited with CNTs and also graphene.", "output": "graphene." }, { "input": "Our findings provide a promising route to realize green and flexible electronics.", "output": "There is no related enetity." }, { "input": "Plant development: brassinosteroids go out of bounds.", "output": "brassinosteroids." }, { "input": "Patterning in plants requires defining boundary domains that separate and organize the development of the neighboring organs.", "output": "There is no related enetity." }, { "input": "Two papers now show how the interplay between brassinosteroid phytohormones and frontier genes contributes to boundary formation in plants.", "output": "brassinosteroid." }, { "input": "Bortezomib enhances antigen - specific cytotoxic T cell responses against immune - resistant cancer cells generated by STAT3 - ablated dendritic cells.", "output": "Bortezomib." }, { "input": "Dendritic cell ( DC ) - based vaccines have received attention as a new therapeutic modality against cancer.", "output": "There is no related enetity." }, { "input": "However, increased STAT3 activity in the tumor microenvironment makes DCs tolerogenic and suppresses their antitumor activity.", "output": "There is no related enetity." }, { "input": "In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3 - ablated ( STAT3 ( - / - ) ) DC - based vaccine on the control of TC - 1 ( P3 ) tumors, a p53 - degraded immune resistant cancer cells.", "output": "bortezomib." }, { "input": "We found that E7 - antigen expressing STAT3 ( - / - ) DC ( E7 - DC - 1STAT3 ( - / - ) ) vaccination enhanced generation of E7 - specific CD8 ( + ) T cells, but was not enough to control TC - 1 ( P3 ) cancer cells.", "output": "There is no related enetity." }, { "input": "Therefore, we investigated whether bortezomib could create a synergistic effect with E7 - DC - 1STAT3 ( - / - ) vaccination.", "output": "bortezomib." }, { "input": "We found that apoptosis via down - regulation of STAT3 and NF - kappa B and up - regulation of Fas and death receptor 5 ( DR5 ) expression in TC - 1 ( P3 ) induced by bortezomib was independent of p53 status.", "output": "bortezomib." }, { "input": "We also observed that TC - 1 ( P3 ) cells pretreated with bortezomib had markedly enhanced anti - tumor effects on E7 - specific CD8 ( + ) T cells through a Fas / DR5 - mediated mechanism.", "output": "bortezomib." }, { "input": "In addition, TC - 1 ( P3 ) tumor - bearing mice treated with bortezomib prior to vaccination with E7 - DC - 1STAT3 ( - / - ) demonstrated enhanced generation of E7 - specific CD8 ( + ) T cells and prolonged survival compared to those treated with monotherapy.", "output": "bortezomib." }, { "input": "These results suggest that the anti - tumor effects against a p53 - degraded immune resistant variant generated by antigen - expressing STAT3 - ablated mature DCs may be enhanced by bortezomib via death receptor - mediated apoptosis.", "output": "bortezomib." }, { "input": "Lecithin / chitosan controlled release nanopreparations of tamoxifen citrate: Loading, enzyme - trigger release and cell uptake.", "output": "Lecithin, tamoxifen citrate." }, { "input": "Tamoxifen citrate ( TAM ), an anticancer drug with amphiphilic properties, was loaded in lecithin / chitosan nanoparticles ( LCN ) with a view to oral administration.", "output": "Tamoxifen citrate, TAM, lecithin." }, { "input": "The influence of tamoxifen loading on the physico - chemical properties of nanoparticles was studied.", "output": "tamoxifen." }, { "input": "Size, surface charge and morphological properties of tamoxifen - loaded nanoparticles ( LCN - TAM ) were assessed.", "output": "tamoxifen, TAM." }, { "input": "The increase in the tamoxifen amount in the LCN - TAM preparation up to 60mg / 100ml maintained the positive zeta potential value of about + 45mV.", "output": "tamoxifen, TAM." }, { "input": "A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg.", "output": "TAM." }, { "input": "A strong influence of loaded tamoxifen on the structure of lecithin / chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis.", "output": "tamoxifen, lecithin." }, { "input": "A loading of tamoxifen in nanoparticles of around 19 % was obtained.", "output": "tamoxifen." }, { "input": "The release of the drug from the LCN - TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro - intestinal fluids without enzymes.", "output": "TAM, tamoxifen citrate." }, { "input": "When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner.", "output": "There is no related enetity." }, { "input": "Tamoxifen - loaded nanoparticles showed cytotoxicity towards MCF - 7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release.", "output": "Tamoxifen, tamoxifen citrate." }, { "input": "Caco - 2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively.", "output": "TAM." }, { "input": "Estimation of the safe use concentrations of the preservative 1, 2 - benzisothiazolin - 3 - one ( BIT ) in consumer cleaning products and sunscreens.", "output": "1 , 2 - benzisothiazolin - 3 - one, BIT." }, { "input": "1, 2 - Benzisothiazolin - 3 - one ( BIT; CAS # 2634 - 33 - 5 ) is a preservative used in consumer products.", "output": "1 , 2 - Benzisothiazolin - 3 - one, BIT, 2634 - 33 - 5." }, { "input": "Dermal exposure to BIT at sufficient dose and duration can produce skin sensitization and allergic contact dermatitis in animals and susceptible humans. The purpose of this study is to derive a maximal concentration of BIT in various consumer products that would result in exposures below the No Expected Sensitization Induction Level ( NESIL ), a dose below which skin sensitization should not occur.", "output": "BIT, BIT." }, { "input": "A screening level exposure estimate was performed for several product use scenarios with sunscreen, laundry detergent, dish soap, and spray cleaner.", "output": "There is no related enetity." }, { "input": "We calculated that BIT concentrations below the following concentrations of 0. 0075 %, 0. 035 %, 0. 035 %, 0. 021 % in sunscreen, laundry detergent, dish soap, and spray cleaner, respectively, are unlikely to induce skin sensitization.", "output": "BIT." }, { "input": "We completed a pilot study consisting of bulk sample analysis of one representative product from each category labelled as containing BIT, and found BIT concentrations of 0. 0009 % and 0. 0027 % for sunscreen and dish soap, respectively.", "output": "BIT, BIT." }, { "input": "BIT was not detected in the laundry detergent and spray cleaner products above the limit of detection of 0. 0006 %.", "output": "BIT." }, { "input": "Based on publically available data for product formulations and our results, we were able to establish that cleaning products and sunscreens likely contain BIT at concentrations similar to or less than our calculated maximal safe concentrations and that exposures are unlikely to induce skin sensitization in most users.", "output": "BIT." }, { "input": "Biochemical properties and comparative pharmacology of a coagulant from Deinagkistrodon acutus snake venom.", "output": "There is no related enetity." }, { "input": "A number of snake venom thrombin - like enzymes ( TLEs ) have already been characterized.", "output": "There is no related enetity." }, { "input": "Some TLEs play significant roles in vessel injury hemostasis.", "output": "There is no related enetity." }, { "input": "A novel TLE ( Agacutase ) was purified from Deinagkistrodon acutus snake venom by the means of Sephadex G - 75, DEAE - Sepharose FF, and Sephadex G - 25 column chromatography.", "output": "There is no related enetity." }, { "input": "Structural analysis indicated that Agacutase is a single - chain glycoprotein with a molecular mass of 31, 084Da, isoelectric point of 4. 38, optimal activity at 37 degrees C and pH 6. 6, sugar content of 7. 6 %.", "output": "There is no related enetity." }, { "input": "Its N - terminal 44 amino acid sequence was determined to be VIGGNECDTNEHRFLAAFFTSRPWIFQCAGTLIHEEWVLAAAHC, showing maximum identity of 80 % with that of Dav - X protease.", "output": "N." }, { "input": "The Agacutase - induced clotting activity was not influenced by heparin, hirudin, or Dextran 40, but activated by Ca ( 2 + ) and inhibited by PMSF or lactose, which suggests that Agacutase is a serine protease and the coagulation activity is independent of Thrombin.", "output": "Ca ( 2 + ), PMSF, lactose, serine." }, { "input": "Agacutase with arginine esterase activity specifically cleaves the alpha - chain of fibrinogen.", "output": "There is no related enetity." }, { "input": "Agacutase iv ( 0. 03 - 0. 12U / kg ) shortened 16 - 68 % of the rabbit blood clotting time.", "output": "There is no related enetity." }, { "input": "No significant influence was indicated on platelet, Factor II and XIII, or fibrinolytic system.", "output": "There is no related enetity." }, { "input": "It converts fibrinogen into the soluble fibrin that accelerates hemostasis at wound.", "output": "There is no related enetity." }, { "input": "Pharmacological comparison showed the hemostatic effect of Agacutase lasted 24h while Reptilase did 8h.", "output": "There is no related enetity." }, { "input": "Its maximum tolerated, abnormal toxicity, allergic, and hemorrhagin doses were 80U / kg, 1U, 2U, and 50U, respectively, whereas those of Reptilase or Agacutin were 35U / kg, 0. 25U, 0. 25U, and 0. 2U, respectively.", "output": "There is no related enetity." }, { "input": "The results indicated that Agacutase may be a predominant coagulant.", "output": "There is no related enetity." }, { "input": "Brain metastasis in pancreatic cancer.", "output": "There is no related enetity." }, { "input": "Pancreatic cancer is a fatal disease with a 5 - year survival rate below 5 %.", "output": "There is no related enetity." }, { "input": "Most patients are diagnosed at an advanced tumor stage and existence of distant metastases.", "output": "There is no related enetity." }, { "input": "However, involvement of the central nervous system is rare in pancreatic cancer.", "output": "There is no related enetity." }, { "input": "We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival.", "output": "There is no related enetity." }, { "input": "Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified.", "output": "There is no related enetity." }, { "input": "In three patients brain metastases were the first manifestation of pancreatic cancer.", "output": "There is no related enetity." }, { "input": "All other patients developed brain metastases during their clinical course.", "output": "There is no related enetity." }, { "input": "In most cases, the disease progressed rapidly and the patients died within weeks or months.", "output": "There is no related enetity." }, { "input": "However, two patients showed long - term survival.", "output": "There is no related enetity." }, { "input": "Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases.", "output": "There is no related enetity." }, { "input": "Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis.", "output": "There is no related enetity." }, { "input": "However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient ' s survival, even with the chance for cure.", "output": "There is no related enetity." }, { "input": "Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases.", "output": "There is no related enetity." }, { "input": "Endothelial cell response to ( co ) polymer nanoparticles depending on the inflammatory environment and comonomer ratio.", "output": "There is no related enetity." }, { "input": "Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue.", "output": "There is no related enetity." }, { "input": "For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells ( HUVECs ) in vitro, a series of monomodal poly [ acrylonitrile - co - ( N - vinylpyrrolidone ) ] model nanoparticles with increasing hydrophilicity as related to their increasing content ( 0 - 30mol. % ) of N - vinylpyrrolidone ( NVP ) were synthesized by miniemulsion polymerization.", "output": "poly [ acrylonitrile - co - ( N - vinylpyrrolidone ) ], N - vinylpyrrolidone, NVP." }, { "input": "Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10 - 30 % of the cells incorporated particles with <= 20mol. % NVP.", "output": "NVP, NVP." }, { "input": "Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL - 1 beta stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents <= 20mol. %.", "output": "NVP." }, { "input": "Importantly, the secretion of functional biological mediators by HUVEC was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions.", "output": "There is no related enetity." }, { "input": "These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions.", "output": "There is no related enetity." }, { "input": "Additionally, rapidly endocytized RhodaminB loaded particles with low NVP content may be explored for cell labeling and tracking.", "output": "RhodaminB, NVP." }, { "input": "Sources of secondary metabolite variation in Dysidea avara ( Porifera: Demospongiae ): the importance of having good neighbors.", "output": "There is no related enetity." }, { "input": "Several studies report temporal, geographical, and intra - individual variation in sponge metabolite yields.", "output": "There is no related enetity." }, { "input": "However, the internal and / or external factors that regulate the metabolite production remain poorly understood.", "output": "There is no related enetity." }, { "input": "Dysidea avara is a demosponge that produces sesquiterpenoids ( avarol and derivatives ) with interesting medical properties, which has prompted addressed studies to obtain enough amounts of these metabolites for research on drug discovery.", "output": "sesquiterpenoids, avarol." }, { "input": "Within this framework, specimens of Dysidea avara from a population of the Northwest Mediterranean were sampled and their secondary metabolites quantified to assess their variability and the possible relationship with external ( seasonality, interactions with neighbors ) and internal ( reproductive stages ) factors.", "output": "There is no related enetity." }, { "input": "The results show a variation of the amount of both avarol and its monoacetate derivative with time, with no clear relationship with seawater temperature.", "output": "avarol and its monoacetate." }, { "input": "A trade - off with sponge reproduction was not found either.", "output": "There is no related enetity." }, { "input": "However, our results showed for the first time that sponges are able to increase production or accumulation of secondary metabolites in their peripheral zone depending on the nature of their neighbors.", "output": "There is no related enetity." }, { "input": "This finding could explain part of the high variability in the amount of secondary metabolites usually found in chemical ecology studies on sponges and opens new biotechnological approaches to enhance the metabolite yield in sponge cultures.", "output": "There is no related enetity." }, { "input": "Murine oatp1a / 1b uptake transporters control rosuvastatin systemic exposure without affecting its apparent liver exposure.", "output": "rosuvastatin." }, { "input": "Organic anion - transporting polypeptides ( OATPs ) mediate the liver uptake and hence plasma clearance of a broad range of drugs.", "output": "There is no related enetity." }, { "input": "For rosuvastatin, a cholesterol - lowering drug and OATP1A / 1B substrate, the liver represents both its main therapeutic target and its primary clearance organ.", "output": "rosuvastatin, cholesterol." }, { "input": "Here we studied the impact of Oatp1a / 1b uptake transporters on the pharmacokinetics of rosuvastatin using wild - type and Oatp1a / 1b - null mice.", "output": "rosuvastatin." }, { "input": "After oral administration ( 15 mg / kg ), intestinal absorption of rosuvastatin was not impaired in Oatp1a / 1b - null mice, but systemic exposure ( area under the curve ) was 8 - fold higher in these mice compared with wild - type.", "output": "rosuvastatin." }, { "input": "Although liver exposure was comparable between the two mouse strains ( despite the increased blood exposure ), the liver - to - blood ratios were markedly decreased ( > 10 - fold ) in the absence of Oatp1a / 1b transporters.", "output": "There is no related enetity." }, { "input": "After intravenous administration ( 5 mg / kg ), systemic exposure was 3 - fold higher in Oatp1a / 1b - null mice than in the wild - type mice.", "output": "There is no related enetity." }, { "input": "Liver, small intestinal, and kidney exposure were slightly, but not significantly, increased in Oatp1a / 1b - null mice.", "output": "There is no related enetity." }, { "input": "The biliary excretion of rosuvastatin was very fast, with 60 % of the dose eliminated within 15 minutes after intravenous administration, and also not significantly altered in Oatp1a / 1b - null mice.", "output": "rosuvastatin." }, { "input": "Rosuvastatin renal clearance, although still minor, was increased ~ 15 - fold in Oatp1a / 1b - null males, suggesting a role of Oatp1a1 in the renal reabsorption of rosuvastatin.", "output": "Rosuvastatin, rosuvastatin." }, { "input": "Absence of Oatp1a / 1b uptake transporters increases the systemic exposure of rosuvastatin by reducing its hepatic extraction ratio.", "output": "rosuvastatin." }, { "input": "However, liver concentrations are not significantly affected, most likely due to the compensatory activity of high - capacity, low - affinity alternative uptake transporters at higher systemic rosuvastatin levels and the absence of efficient alternative rosuvastatin clearance mechanisms.", "output": "rosuvastatin, rosuvastatin." }, { "input": "Molecular mechanism regulating 24 - hour rhythm of dopamine d3 receptor expression in mouse ventral striatum.", "output": "dopamine." }, { "input": "The dopamine D3 receptor ( DRD3 ) in the ventral striatum is thought to influence motivation and motor functions.", "output": "dopamine." }, { "input": "Although the expression of DRD3 in the ventral striatum has been shown to exhibit 24 - hour variations, the mechanisms underlying the variation remain obscure.", "output": "There is no related enetity." }, { "input": "Here, we demonstrated that molecular components of the circadian clock act as regulators that control the 24 - hour variation in the expression of DRD3.", "output": "There is no related enetity." }, { "input": "The transcription of DRD3 was enhanced by the retinoic acid - related orphan receptor alpha ( ROR alpha ), and its activation was inhibited by the orphan receptor REV - ERB alpha, an endogenous antagonist of ROR alpha.", "output": "retinoic acid." }, { "input": "The serum or dexamethasone - induced oscillation in the expression of DRD3 in cells was abrogated by the downregulation or overexpression of REV - ERB alpha, suggesting that REV - ERB alpha functions as a regulator of DRD3 oscillations in the cellular autonomous clock.", "output": "dexamethasone." }, { "input": "Chromatin immunoprecipitation assays of the DRD3 promoter indicated that the binding of the REV - ERB alpha protein to the DRD3 promoter increased in the early dark phase.", "output": "There is no related enetity." }, { "input": "DRD3 protein expression varied with higher levels during the dark phase.", "output": "There is no related enetity." }, { "input": "Moreover, the effects of the DRD3 agonist 7 - hydroxy - N, N - dipropyl - 2 - aminotetralin ( 7 - OH - DPAT ) - induced locomotor hypoactivity were significantly increased when DRD3 proteins were abundant.", "output": "7 - hydroxy - N , N - dipropyl - 2 - aminotetralin, 7 - OH - DPAT." }, { "input": "These results suggest that ROR alpha and REV - ERB alpha consist of a reciprocating mechanism wherein ROR alpha upregulates the expression of DRD3, whereas REV - ERB alpha periodically suppresses the expression at the time of day when REV - ERB alpha is abundant.", "output": "There is no related enetity." }, { "input": "Our present findings revealed that a molecular link between the circadian clock and the function of DRD3 in the ventral striatum acts as a modulator of the pharmacological actions of DRD3 agonists / antagonists.", "output": "There is no related enetity." }, { "input": "Inflammation and immune system interactions in atherosclerosis.", "output": "There is no related enetity." }, { "input": "Cardiovascular disease ( CVD ) is the leading cause of mortality worldwide, accounting for 16. 7 million deaths each year.", "output": "There is no related enetity." }, { "input": "The underlying cause of the majority of CVD is atherosclerosis.", "output": "There is no related enetity." }, { "input": "In the past, atherosclerosis was considered to be the result of passive lipid accumulation in the vessel wall.", "output": "There is no related enetity." }, { "input": "Today ' s picture is far more complex.", "output": "There is no related enetity." }, { "input": "Atherosclerosis is considered a chronic inflammatory disease that results in the formation of plaques in large and mid - sized arteries.", "output": "There is no related enetity." }, { "input": "Both cells of the innate and the adaptive immune system play a crucial role in its pathogenesis.", "output": "There is no related enetity." }, { "input": "By transforming immune cells into pro - and anti - inflammatory chemokine - and cytokine - producing units, and by guiding the interactions between the different immune cells, the immune system decisively influences the propensity of a given plaque to rupture and cause clinical symptoms like myocardial infarction and stroke.", "output": "There is no related enetity." }, { "input": "In this review, we give an overview on the newest insights in the role of different immune cells and subtypes in atherosclerosis.", "output": "There is no related enetity." }, { "input": "The metabolic effects of growth hormone in adipose tissue.", "output": "There is no related enetity." }, { "input": "There is a general consensus that a reduction in growth hormone ( GH ) secretion results in obesity.", "output": "There is no related enetity." }, { "input": "However, the pathophysiologic role of GH in the metabolism of lipids is yet to be fully understood.", "output": "There is no related enetity." }, { "input": "The major somatic targets of GH are bones and muscles, but GH stimulates lipolysis and seems to regulate lipid deposition in adipose tissue.", "output": "There is no related enetity." }, { "input": "Patients with isolated GH deficiency ( GHD ) have enlarged fat depots due to higher fat cell volume, but their fat cell numbers are lower than those of matched controls.", "output": "There is no related enetity." }, { "input": "The treatment of patients with GH results in a relative loss of body fat and shifts both fat cell number and fat cell volume toward normal, indicating an adipogenic effect of GH.", "output": "There is no related enetity." }, { "input": "Adults with GHD are characterized by perturbations in body composition, lipid metabolism, cardiovascular risk profile, and bone mineral density.", "output": "There is no related enetity." }, { "input": "It is well established that GHD is usually accompanied by an increase in fat accumulation; GH replacement in GHD results in the reduction of fat mass, particularly abdominal fat mass.", "output": "There is no related enetity." }, { "input": "In addition, abdominal obesity results in a secondary reduction in GH secretion that is reversible with weight loss.", "output": "There is no related enetity." }, { "input": "However, whereas GH replacement in patients with GHD leads to specific depletion of intra - abdominal fat, administering GH to obese individuals does not seem to result in a consistent reduction or redistribution of body fat.", "output": "There is no related enetity." }, { "input": "Although administering GH to obese non - GHD subjects has only led to equivocal results, more recent studies indicate that GH still remains a plausible metabolic candidate.", "output": "There is no related enetity." }, { "input": "A toxicokinetic model for thiamethoxam in rats: implications for higher - tier risk assessment.", "output": "thiamethoxam." }, { "input": "Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose.", "output": "There is no related enetity." }, { "input": "So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding.", "output": "There is no related enetity." }, { "input": "Internal concentration is the net result of absorption, distribution, metabolism and excretion ( ADME ).", "output": "There is no related enetity." }, { "input": "We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD50 dose either as a bolus or eaten at different feeding rates.", "output": "thiamethoxam." }, { "input": "Kinetic parameters were determined in male and female rats after an intravenous and oral administration of ( 14 ) C labelled by fitting one - compartment models to measured pesticide concentrations in blood for each individual separately.", "output": "( 14 ) C." }, { "input": "The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body.", "output": "thiamethoxam." }, { "input": "Body burden model simulations showed that maximum body weight - normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose.", "output": "thiamethoxam." }, { "input": "This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD50.", "output": "There is no related enetity." }, { "input": "The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail.", "output": "There is no related enetity." }, { "input": "Design and evaluation of ondansetron liquid suppository for the treatment of emesis.", "output": "ondansetron." }, { "input": "The thermosensitive - mucoadhesive ondansetron liquid suppository ( tmOLS ) was developed to enhance patient compliance and bioavailability in high - risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive - mucoadhesive liquid suppository bases were formulated using poloxamers ( P407 and P188 ) and hydroxypropylmethyl cellulose ( HPMC ).", "output": "ondansetron, poloxamers, P407, P188, hydroxypropylmethyl." }, { "input": "The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release.", "output": "There is no related enetity." }, { "input": "Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy.", "output": "There is no related enetity." }, { "input": "Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally.", "output": "ondansetron." }, { "input": "The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18: 20: 0. 8, was in the liquid state at room temperature, underwent gelation at body temperature.", "output": "P407, P188." }, { "input": "Area under the curve and half - life ( t ( 1 / 2 ) ) of ondansetron were significantly higher in the tmOLS - treated group, indicating that the formulation bypassed the first - pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state.", "output": "ondansetron." }, { "input": "Furthermore, the t ( 1 / 2 ) of tmOLS was two - fold that of the oral solution.", "output": "There is no related enetity." }, { "input": "Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed.", "output": "There is no related enetity." }, { "input": "Gd - based Macromolecules and Nanoparticles as Magnetic Resonance Contrast Agents for Molecular Imaging.", "output": "Gd." }, { "input": "As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice.", "output": "There is no related enetity." }, { "input": "Magnetic resonance ( MR ) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes.", "output": "There is no related enetity." }, { "input": "One promising new direction in the development of MR contrast agents involves the labeling and / or loading of nanoparticles with gadolinium ( Gd ).", "output": "gadolinium, Gd." }, { "input": "These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies.", "output": "Gd." }, { "input": "In this review, we discuss some of the progress that has recently been made in the development of Gd - based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high \" relaxivity per particle \" and \" relaxivity density \", and biodegradability.", "output": "Gd, Gd." }, { "input": "( 89 ) Zr - PET Radiochemistry in the Development and Application of Therapeutic Monoclonal Antibodies and Other Biologicals.", "output": "( 89 ) Zr." }, { "input": "Positron emission tomography with ( 89 ) Zr can be used to follow the behaviour of therapeutic monoclonal antibodies ( mAbs ) and other biologicals in vivo.", "output": "( 89 ) Zr." }, { "input": "The favourable radiophysical characteristics of ( 89 ) Zr allow multiple days PET scanning after injection.", "output": "( 89 ) Zr." }, { "input": "For the coupling of ( 89 ) Zr to proteins six desferrioxamine ( DFO ) - based bifunctional chelators have been described, five of which forming stable complexes in vivo.", "output": "( 89 ) Zr, desferrioxamine, DFO." }, { "input": "Of the methods that give stable complexes three are based on random lysine modification of mAbs and two on site - specific engineering.", "output": "lysine." }, { "input": "Up to now only two methods, random lysine modification with N - suc - DFO or DFO - Bz - NCS, have been used in clinical studies.", "output": "lysine, N - suc - DFO, DFO - Bz - NCS." }, { "input": "In this review firstly aspects of the physicochemical properties and production of ( 89 ) Zr are emphasized as well as important items that have to be taken into account for current good manufacturing practice ( cGMP ) compliant production of ( 89 ) Zr - labeled proteins.", "output": "( 89 ) Zr, ( 89 ) Zr." }, { "input": "Next, the different DFO - based conjugation strategies will be discussed with respect to synthesis, and their ( pre ) clinical evaluation particularly in the field of oncology.", "output": "There is no related enetity." }, { "input": "Chemistry and theranostic applications of radiolabeled nanoparticles for cardiovascular, oncological, and pulmonary research.", "output": "There is no related enetity." }, { "input": "Labeling nanoparticles with radionuclides has been widely used to form multifunctional and multivalency agents for various biomedical applications.", "output": "There is no related enetity." }, { "input": "A variety of nanostructures including inorganic, organic and lipid nanoparticles have been labeled with positron or gamma emitting radioisotopes through versatile radiochemistry in a number of disease models to track their in vivo fate, image biomarkers, and monitor treatment response.", "output": "There is no related enetity." }, { "input": "This review briefly summarizes the recent applications of nanoparticles labeled with radionuclides for oncological, cardiovascular, and pulmonary theranostics.", "output": "There is no related enetity." }, { "input": "TRP Channels as Targets for Therapeutic Intervention in Obesity: Focus on TRPV1 and TRPM5.", "output": "There is no related enetity." }, { "input": "The disease of obesity is one of the greatest healthcare challenges of our time.", "output": "There is no related enetity." }, { "input": "The increasing urgency for effective treatment is driving an intensive search for new targets for anti - obesity drug discovery.", "output": "There is no related enetity." }, { "input": "The TRP channel super family represents a class of proteins now recognized to serve many functions in physiology related to maintenance of health and the development of diseases.", "output": "There is no related enetity." }, { "input": "A few of these might offer new potential for therapeutic intervention in obesity.", "output": "There is no related enetity." }, { "input": "Among the TRP channels, TRPV1 appears most closely associated with body weight homeostasis through its influence on energy expenditure.", "output": "There is no related enetity." }, { "input": "TRPM5 has been thoroughly characterized as a critical component of taste signaling and recently has been implicated in insulin release.", "output": "There is no related enetity." }, { "input": "Because of its role in taste signaling, we argue that drugs designed to modulate TRPM5 could be useful in controlling energy consumption by impacting taste sensory signals.", "output": "There is no related enetity." }, { "input": "As drug targets for obesity, both TRPV1 and TRPM5 offer the advantage of operating in compartments that could limit drug distribution to the site of action.", "output": "There is no related enetity." }, { "input": "The potential for other TRP channels as anti - obesity drug targets also is discussed.", "output": "There is no related enetity." }, { "input": "Possible Involvement of TRP Channels in Cardiac Hypertrophy and Arrhythmia.", "output": "There is no related enetity." }, { "input": "Over the past 20 years, studies of transient receptor potential ( TRP ) channels have significantly extended our knowledge regarding the molecular basis of Ca2 + signals in cardiac myocytes.", "output": "Ca2 +." }, { "input": "The functional significance of cardiac TRP channels is likely connected to the alteration of membrane potential or Ca2 + entry into a noncontractile compartment, where gene expression responsible for various cardiac diseases is induced.", "output": "Ca2 +." }, { "input": "This review highlights some aspects of TRP channels with anticipated roles in cardiac disease.", "output": "There is no related enetity." }, { "input": "Evidence suggests that ( a ) increased activities of TRPC1, TRPC3, or TRPC6 are involved in the development of cardiac hypertrophy, where these TRPC channels act as unique sensors for a wide range of hypertrophic stimuli, and ( b ) mutations in TRPM4 are now recognized as causes of human cardiac conduction disorders.", "output": "There is no related enetity." }, { "input": "Ultimately, TRP channels may become novel pharmacological targets in the treatment of human cardiac disease.", "output": "There is no related enetity." }, { "input": "Transient receptor potential channels and dermatological disorders.", "output": "There is no related enetity." }, { "input": "Transient receptor potential ( TRP ) cation channels are an emerging field of research in dermatology.", "output": "There is no related enetity." }, { "input": "Beyond their classical role in skin sensory perception, TRPs are involved in various cutaneous functions that include keratinocyte differentiation, apoptosis and melanocyte pigmentation.", "output": "There is no related enetity." }, { "input": "In addition, they have a role as pharmacological targets in many inflammatory skin diseases including psoriasis, chronic itch, hair disorders and skin cancers.", "output": "There is no related enetity." }, { "input": "Moreover, mutations in TRPs have recently been related to rare skin conditions such as Olmsted syndrome.", "output": "There is no related enetity." }, { "input": "This review will cover the role of TRPs in dermatologic conditions with special emphasis on itch and skin inflammatory diseases.", "output": "There is no related enetity." }, { "input": "Development of potent and selective indomethacin analogues for the inhibition of AKR1C3 ( Type 5 17 beta - hydroxysteroid dehydrogenase / prostaglandin F synthase ) in castrate - resistant prostate cancer.", "output": "indomethacin, 17 beta - hydroxysteroid." }, { "input": "Castrate - resistant prostate cancer ( CRPC ) is a fatal, metastatic form of prostate cancer.", "output": "There is no related enetity." }, { "input": "CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and / or adaptive intratumoral androgen biosynthesis.", "output": "androgen, androgen, androgen." }, { "input": "AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens.", "output": "androgens." }, { "input": "This makes AKR1C3 a target for the treatment of CRPC.", "output": "There is no related enetity." }, { "input": "AKR1C3 inhibitors should not inhibit AKR1C1 / AKR1C2, which inactivate 5 alpha - dihydrotestosterone.", "output": "5 alpha - dihydrotestosterone." }, { "input": "Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1 / AKR1C2.", "output": "Indomethacin." }, { "input": "Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity.", "output": "indomethacin." }, { "input": "The lead compounds inhibited AKR1C3 with nanomolar potency, displayed > 100 - fold selectivity over AKR1C1 / AKR1C2, and blocked testosterone formation in LNCaP - AKR1C3 cells.", "output": "testosterone." }, { "input": "The AKR1C3. NADP ( + ). 2 ' - des - methyl - indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode.", "output": "NADP ( + ), 2 ' - des - methyl - indomethacin." }, { "input": "The compounds reported are promising agents for the development of therapeutics for CRPC.", "output": "There is no related enetity." }, { "input": "Five new secondary metabolites from Monascus purpureus - fermented Hordeum vulgare and Sorghum bicolor.", "output": "There is no related enetity." }, { "input": "Long grains of Hordeum vulgare and Sorghum bicolor were individually fermented with Monascus purpureus MTCC 369 under solid state fermentation.", "output": "There is no related enetity." }, { "input": "The aqueous extract of Monascus which fermented H. vulgare and S. bicolor was found to contain five different new metabolites.", "output": "There is no related enetity." }, { "input": "Silica gel column chromatography of the aqueous extract with a linear gradient of ethyl acetate, acetonitrile and carbon tetrachloride ( v / v ) yielded five new metabolites named benzopranyl capriate ( 9H - 1 - isoprenyl - benzopyran - 5 - isopropanoic acid - 6 - ol - 6 - n - decanoate ), shorghumoic acid ( n - octadec - 8, 11 - dien - 7 alpha - ol - 1 - oic acid ) and sorghumflavin A ( 2 - n - butyloxo - 6 - beta - hydroxy - 7 - beta - isoprenyl ankaflavin ) from Monascus - fermented S. bicolor, while hordeumflavin B ( 2 - n - undecanyloxo - 7 - beta - isoprenyl ankaflavin ) and vulgaredilone ( 2 - dodecanyl - 7 - beta isopranyl monoscodilone ) from Monascus - fermented H. vulgare.", "output": "Silica gel, ethyl acetate, acetonitrile, carbon tetrachloride, benzopranyl capriate, 9H - 1 - isoprenyl - benzopyran - 5 - isopropanoic acid - 6 - ol - 6 - n - decanoate, shorghumoic acid, n - octadec - 8 , 11 - dien - 7 alpha - ol - 1 - oic acid, sorghumflavin A, 2 - n - butyloxo - 6 - beta - hydroxy - 7 - beta - isoprenyl ankaflavin, hordeumflavin B, 2 - n - undecanyloxo - 7 - beta - isoprenyl ankaflavin, vulgaredilone, 2 - dodecanyl - 7 - beta isopranyl monoscodilone." }, { "input": "Development and characterization of monomeric N - end rule inhibitors through in vitro model substrates.", "output": "There is no related enetity." }, { "input": "In the N - end rule pathway, a set of N - terminal amino acids, called N - degrons, are recognized and ubiquitinated by the UBR proteins.", "output": "N, amino acids." }, { "input": "Here we examined various N - end rule inhibitors to identify essential structural components of the system.", "output": "There is no related enetity." }, { "input": "Our study using in vitro biochemical assay indicated that the l - conformation and protonated alpha - amino group of the first residue were critical for N - degrons to properly interact with the UBR proteins.", "output": "alpha - amino." }, { "input": "The monomeric molecules with minimum interacting motifs showed endopeptidase resistance and better inhibitory activities than traditional dipeptide inhibitors.", "output": "There is no related enetity." }, { "input": "Collectively, our study identifies a pharmacophore of N - end rule inhibitors, which provides a structural platform to improve the efficiency and druggable properties of inhibitors.", "output": "There is no related enetity." }, { "input": "Considering that the N - end rule has been implicated in many pathophysiological processes in cells, inhibitors of this pathway, such as p - chloroamphetamine, are potentially of clinical interest in a novel aspect of action mechanisms.", "output": "p - chloroamphetamine." }, { "input": "Montiporic acid D, a new polyacetylene carboxylic acid from scleractinian coral Montipora digitata.", "output": "Montiporic acid D, polyacetylene carboxylic acid." }, { "input": "A new polyacetylene carboxylic acid named montiporic acid D ( 1 ) was isolated along with a known polyacetylene alcohol, ( Z ) - 13, 15 - hexadecadien - 2, 4 - diyn - 1 - ol ( 2 ) from scleractinian coral Montipora digitata.", "output": "polyacetylene carboxylic acid, montiporic acid D, polyacetylene alcohol, ( Z ) - 13 , 15 - hexadecadien - 2 , 4 - diyn - 1 - ol." }, { "input": "The structures of compounds were determined by analyses of NMR and MS spectra.", "output": "There is no related enetity." }, { "input": "RNAi in Clinical Studies.", "output": "There is no related enetity." }, { "input": "RNA interference ( RNAi ) is an efficient process of posttranscriptional gene silencing.", "output": "There is no related enetity." }, { "input": "In recent years it has been developed into a new technology in biopharmaceutical fields of science.", "output": "There is no related enetity." }, { "input": "RNAi products include short interference RNA ( siRNA ) but also short hairpin RNA ( shRNA ), bifunctional short hairpin RNA ( bi - shRNA ) and microRNA ( miRNA ).", "output": "There is no related enetity." }, { "input": "They combine with homologous fragments of the mRNA and cause its degradation.", "output": "There is no related enetity." }, { "input": "It results in inhibition of protein synthesis, or in mutation in the gene encoding it.", "output": "There is no related enetity." }, { "input": "RNAi has been used in analysis of genomes and creation of new animal models to test drugs.", "output": "There is no related enetity." }, { "input": "From the pharmaceutical point of view, what is the most important is its therapeutic application.", "output": "There is no related enetity." }, { "input": "So far the basic and clinical research has been focused on the following targets: macular degeneration, cancer and antiviral therapy.", "output": "There is no related enetity." }, { "input": "But there are also reports on clinical trials in asthma, hypercholesterolemia and genetic diseases such as inherited skin disorders and amyloidosis.", "output": "There is no related enetity." }, { "input": "Among over 20 therapeutics that reached clinical trials, only few are still investigated.", "output": "There is no related enetity." }, { "input": "Another few are clinical candidates.", "output": "There is no related enetity." }, { "input": "The review focuses on RNAi products under clinical evaluation and their most promising new applications.", "output": "There is no related enetity." }, { "input": "Bisacylimidoselenocarbamates Cause G2 / M Arrest Associated with the Modulation of CDK1 and Chk2 in Human Breast Cancer MCF - 7 Cells.", "output": "Bisacylimidoselenocarbamates." }, { "input": "Bisacylimidoselenocarbamate derivatives ( BSC ) are potent anticancer agents with a strong cytotoxic activity against different types of tumour cells.", "output": "Bisacylimidoselenocarbamate, BSC." }, { "input": "Based in phosphatidylserine exposure on the cell membranes we show that BSC treatment resulted in enhanced cell death in leukaemia CCRF - CEM cells.", "output": "phosphatidylserine, BSC." }, { "input": "DNA fragmentation detection in breast adenocarcinoma MCF - 7 cells showed that BSC triggered cell death is concentration and time dependent.", "output": "BSC." }, { "input": "We also show that two of these compounds, BSC 3g and 3n, cause cell - cycle arrest in the late G2 / M in MCF - 7 cells.", "output": "BSC." }, { "input": "Consistent with this, a reduction in CDK1 and CDK2 expression with no change in cyclin A an B1 was observed in this cell line.", "output": "There is no related enetity." }, { "input": "Activation of caspase - 2 was also detected.", "output": "There is no related enetity." }, { "input": "However, the involvement of the caspase - dependent pathway in the process of cell death induced by either BSC 3g or 3n is discarded since cell death could not be prevented by pretreatment with the pancaspase inhibitor z - VAD - fmk.", "output": "BSC, z - VAD - fmk." }, { "input": "Moreover, since reduced levels of p21CIP1 and Chk2 proteins but no change in p53 levels could be detected in MCF - 7 cells after BSC 3g or 3n treatment our results suggest that BSC treated cells die from lethal mitosis.", "output": "BSC, BSC." }, { "input": "Immunophilins are Involved in the Altered Platelet Aggregation Observed in Patients with Type 2 Diabetes Mellitus.", "output": "There is no related enetity." }, { "input": "Platelet hyperaggregability might contribute to vascular complications associated with type 2 diabetes mellitus ( DM2 ). Experimental evidence supports a direct link between altered Ca2 + entry and hyperaggregability in DM2 patients.", "output": "Ca2 +." }, { "input": "Objectives: We aimed to investigate whether altered immunophilin expression and function are involved in the abnormal Ca2 + entry observed in platelets from DM2 patients.", "output": "Ca2 +." }, { "input": "Results: Inhibition of immunophilins by tacrolimus ( FK506 ) and sirolimus ( rapamycin ) reduced Ca2 + entry in platelets from healthy donors and DM2 patients.", "output": "tacrolimus, FK506, sirolimus, rapamycin, Ca2 +." }, { "input": "Similarly, immunophilin inhibitors reduced platelet degranulation in both healthy and DM2 subjects.", "output": "There is no related enetity." }, { "input": "Nevertheless, alpha - granule secretion reduction was greater than that observed for dense granules in platelets from DM2 patients.", "output": "There is no related enetity." }, { "input": "However, no difference was observed in the inhibition of secretion in platelets from healthy subjects.", "output": "There is no related enetity." }, { "input": "Additionally, altered expression of FK506 binding protein - 52 ( FKBP52 ) and coupling to Ca ( 2 + ) channels were found in platelets from DM2 patients compared to healthy subjects.", "output": "FK506, Ca ( 2 + )." }, { "input": "Finally, reduction in platelet function from healthy subjects and DM2 patients in the presence of immunophilin antagonists was observed, being this dysfunction more evident in platelets from DM2 patients.", "output": "There is no related enetity." }, { "input": "Conclusions: We suggest that, among others, FKBP52 expression and function are altered in platelets from DM2 patients, contributing to the altered Ca ( 2 + ) entry and hyperaggregability in these cells.", "output": "Ca ( 2 + )." }, { "input": "Aminophosphonate metal complexes of biomedical potential.", "output": "Aminophosphonate." }, { "input": "Metals and their complexes with organic ligands have an important role in biochemical systems such as enzymatic catalysis, metal ion transfer across the cell membranes, treatment of malignancy, rheumatoid arthritis, ulcer and other types of diseases.", "output": "There is no related enetity." }, { "input": "Special attention is directed to metal complexes with ligands which are important in biological systems, as their incorporation into metallo - organic compounds offers much scope for design of potential metal - based agents that provide new opportunities in the medicinal chemistry.", "output": "There is no related enetity." }, { "input": "In view of this, derivatives of aminophosphonic acids, owing to their broad spectrum of biological activities and wide range of applications in the medicinal and agrochemical fields, are very attractive metal - ligand agents that might form biomedical important metal complexes.", "output": "aminophosphonic acids." }, { "input": "Thus, a number of aminophosphonate complexes of platinum group metals have been found to possess remarkable antitumor activity while complexes of some other transition and rare - earth metals like technetium, rhenium, samarium and gadolinium have been used either as therapeutic and diagnostic radiopharmaceuticals or as magnetic resonance imaging ( MRI ) contrast agents.", "output": "aminophosphonate, platinum, technetium, rhenium, samarium, gadolinium." }, { "input": "In addition, the high phosphonate affinity towards bone and other calcified tissues may be utilized for the drug targeting based on synthesis of metal complexes linked to bioactive carrier systems, affording better modalities of attack to the site of pathology.", "output": "phosphonate." }, { "input": "In this review article, aminophosphonate metal - based compounds with potential biomedical applications are described.", "output": "aminophosphonate." }, { "input": "Ab initio MRCI + Q study on low - lying states of CS including spin - orbit coupling.", "output": "There is no related enetity." }, { "input": "Carbon monosulfide ( CS ), which plays an important role in a variety of research fields, has long received considerable interest.", "output": "Carbon monosulfide, CS." }, { "input": "Due to its transient nature and large state density, the electronic states of CS have not been well understood, especially the interactions between different states.", "output": "CS." }, { "input": "In this paper, we performed a detail ab initio study on the low - lying electronic states of CS by means of the internally contracted multireference configuration interaction method ( including Davidson correction ) with scalar relativistic correction using the Douglas - Kroll - Hess Hamiltonian.", "output": "CS." }, { "input": "We focused on the spin - orbit coupling of the states via the state interaction method with the full Breit - Pauli Hamiltonian.", "output": "There is no related enetity." }, { "input": "The potential energy curves ( PECs ) of 18 Lambda - S states correlated with the lowest dissociation limit of the CS molecule were calculated, as well as those of 50 Omega states generated from the Lambda - S states.", "output": "CS." }, { "input": "The spectroscopic constants of the bound states were obtained, which are in good agreement with previous available experimental and theoretical results.", "output": "There is no related enetity." }, { "input": "The state perturbations of the a ( 3 ) Pi and A ( 1 ) Pi states with other low - lying electronic states are discussed in detail, based on the calculated spin - orbit matrix as well as the PECs of the Omega states.", "output": "There is no related enetity." }, { "input": "Avoided crossing in the states of CS was indicated when spin - orbit coupling was taken into account.", "output": "CS." }, { "input": "Finally, the allowed transition dipole moments as well as the lifetimes of the five lowest vibrational states of the A ( 1 ) Pi 1, A ' ( 1 ) Sigma ( + ) 0 ( + ) and a ( 3 ) Pi i states were obtained.", "output": "There is no related enetity." }, { "input": "Structural and mechanistic principles of intramembrane proteolysis - - lessons from rhomboids.", "output": "There is no related enetity." }, { "input": "Intramembrane proteases cleave membrane proteins in their transmembrane helices to regulate a wide range of biological processes.", "output": "There is no related enetity." }, { "input": "They catalyse hydrolytic reactions within the hydrophobic environment of lipid membranes where water is normally excluded.", "output": "There is no related enetity." }, { "input": "How?", "output": "There is no related enetity." }, { "input": "Do the different classes of intramembrane proteases share any mechanistic principles?", "output": "There is no related enetity." }, { "input": "In this review these questions will be discussed in view of the crystal structures of prokaryotic members of the three known catalytic types of intramembrane proteases published over the past 7 years.", "output": "There is no related enetity." }, { "input": "Rhomboids, the intramembrane serine proteases that are the best understood family, will be the initial area of focus, and the principles that have arisen from a number of structural and biochemical studies will be considered.", "output": "There is no related enetity." }, { "input": "The site - 2 metalloprotease and GXGD - type aspartyl protease structures will then be discussed, with parallels drawn and differences highlighted between these enzymes and the rhomboids.", "output": "There is no related enetity." }, { "input": "Despite the significant advances achieved so far, to obtain a detailed understanding of the mechanism of any intramembrane protease, high - resolution structural information on the substrate - enzyme complex is required.", "output": "There is no related enetity." }, { "input": "This remains a major challenge for the field.", "output": "There is no related enetity." }, { "input": "Reduction of dNTP levels enhances DNA replication fidelity in vivo.", "output": "dNTP." }, { "input": "ATP is the most important energy source for the maintenance and growth of living cells.", "output": "ATP." }, { "input": "Here we report that the impairment of the aerobic respiratory chain by inactivation of the ndh gene, or the inhibition of glycolysis with arsenate, both of which reduce intracellular ATP, result in a significant decrease in spontaneous mutagenesis in Escherichia coli.", "output": "arsenate, ATP." }, { "input": "The genetic analyses and mutation spectra in the ndh strain revealed that the decrease in spontaneous mutagenesis resulted from an enhanced accuracy of the replicative DNA polymerase.", "output": "There is no related enetity." }, { "input": "Quantification of the dNTP content in the ndh mutant cells and in the arsenate - treated cells showed reduction of the dNTP pool, which could explain the observed broad antimutator effects.", "output": "dNTP, arsenate, dNTP." }, { "input": "In conclusion, our work indicates that the cellular energy supply could affect spontaneous mutation rates and that a reduction of the dNTP levels can be antimutagenic.", "output": "dNTP." }, { "input": "Identification and characterization of small molecule inhibitors of signal transducer and activator of transcription 3 ( STAT3 ) signaling pathway by virtual screening.", "output": "There is no related enetity." }, { "input": "Inhibition of the signal transducer and activator of transcription 3 ( STAT3 ) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly - active STAT3.", "output": "There is no related enetity." }, { "input": "In this study, a series of small molecules were identified as novel inhibitors of STAT3 signaling pathway through virtual screening.", "output": "There is no related enetity." }, { "input": "A tricyclic scaffold containing compound, 6, was identified as an inhibitor of IL - 6 / STAT3 signaling with an IC50 of 26. 68 mu M.", "output": "There is no related enetity." }, { "input": "In addition, this compound inhibited Tyr705 phosphorylation of STAT3 and had no obvious effect on upstream tyrosine kinases.", "output": "Tyr705, tyrosine." }, { "input": "Thus, compound 6 is a potential lead structure and valuable for further drug development.", "output": "There is no related enetity." }, { "input": "Synthesis and photochemical behavior of coumarin - caged cholesterol.", "output": "coumarin, cholesterol." }, { "input": "The syntheses of three coumarin - caged cholesterols are reported that contain the 6 - diethylaminocoumarin ( DEACM ), 6 - bromo - 7 - hydroxycoumarin ( BHC ) and 6 - bromo - 7 - methoxycoumarin ( BMCM ) photocleavable groups.", "output": "coumarin, cholesterols, 6 - diethylaminocoumarin, DEACM, 6 - bromo - 7 - hydroxycoumarin, BHC, 6 - bromo - 7 - methoxycoumarin, BMCM." }, { "input": "Upon photolysis, the best caged derivative was found to be BHC - cholesterol whose quantum yield was determined to be 0. 032 at 350 nm.", "output": "BHC, cholesterol." }, { "input": "Dynamic readers for 5 - ( hydroxy ) methylcytosine and its oxidized derivatives.", "output": "5 - ( hydroxy ) methylcytosine." }, { "input": "Tet proteins oxidize 5 - methylcytosine ( mC ) to generate 5 - hydroxymethyl ( hmC ), 5 - formyl ( fC ), and 5 - carboxylcytosine ( caC ).", "output": "5 - methylcytosine, 5 - hydroxymethyl, hmC, 5 - formyl, 5 - carboxylcytosine, caC." }, { "input": "The exact function of these oxidative cytosine bases remains elusive.", "output": "cytosine." }, { "input": "We applied quantitative mass - spectrometry - based proteomics to identify readers for mC and hmC in mouse embryonic stem cells ( mESC ), neuronal progenitor cells ( NPC ), and adult mouse brain tissue.", "output": "hmC." }, { "input": "Readers for these modifications are only partially overlapping, and some readers, such as Rfx proteins, display strong specificity.", "output": "There is no related enetity." }, { "input": "Interactions are dynamic during differentiation, as for example evidenced by the mESC - specific binding of Klf4 to mC and the NPC - specific binding of Uhrf2 to hmC, suggesting specific biological roles for mC and hmC.", "output": "hmC, hmC." }, { "input": "Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation.", "output": "There is no related enetity." }, { "input": "Euryspongins A - C, three new unique sesquiterpenes from a marine sponge Euryspongia sp.", "output": "Euryspongins A - C, sesquiterpenes." }, { "input": "Three new unique sesquiterpenes, euryspongins A - C ( 1 - 3 ), were isolated from a marine sponge Euryspongia sp. collected at Iriomote Island, Okinawa, Japan.", "output": "sesquiterpenes, euryspongins A - C." }, { "input": "Compound 1 possessed a bicyclic furanosesquiterpene structure with six - and eight - membered rings, whereas compounds 2 and 3 had an alpha, beta - unsaturated - gamma - lactone ring instead of the furan ring in 1.", "output": "bicyclic furanosesquiterpene, alpha , beta - unsaturated - gamma - lactone, furan." }, { "input": "Only five natural products in this class have been reported, and compounds 1 - 3 are the sixth - eighth examples of natural products.", "output": "There is no related enetity." }, { "input": "Compounds 1 - 3 had no inhibition effect against PTP1B, an important target enzyme for the treatment of diabetes, while the dehydro derivative of 1 [ dehydroeuryspongin A ( 4 ) ] exhibited inhibitory activity ( IC ( 50 ) = 3. 6 mu M ).", "output": "dehydroeuryspongin A." }, { "input": "Mucous hypersecretion and relationship to cough.", "output": "There is no related enetity." }, { "input": "A variety of foreign \" invaders \" such as viruses, bacteria and other particulates e. g., cigarette smoke, are inhaled, deposit on the airway surface and invade the \" host. \" Mucins produced by the surface airway epithelium and by the submucosal glands are secreted into the airway lumen.", "output": "There is no related enetity." }, { "input": "Deposited particulates adhere to the mucus and are cleared via mucociliary transport and via cough.", "output": "There is no related enetity." }, { "input": "Mucins are major constituents of mucus, which is important in the clearance of inhaled materials.", "output": "There is no related enetity." }, { "input": "Normally, secreted mucus is cleared without symptoms or interference with lung function.", "output": "There is no related enetity." }, { "input": "However, in obstructive airway diseases such as COPD, asthma, and cystic fibrosis, excessive mucus is produced.", "output": "There is no related enetity." }, { "input": "Because of the prominence of mucous hypersecretion as a cause of cough, this discussion focuses on mechanisms regulating normal production of mucins and the mechanisms underlying exaggerated mucin secretion in chronic obstructive airway diseases.", "output": "There is no related enetity." }, { "input": "Mucins are produced by airway epithelial cells via a cascade of signals ( the Epidermal Growth Factor Cascade ) and secreted on the luminal epithelial surface, often in response to the deposition of inhaled irritants.", "output": "There is no related enetity." }, { "input": "Normally, only minimal amounts of mucins are secreted, which assist in clearance of the inhaled particulates.", "output": "There is no related enetity." }, { "input": "However, in disease, additional pathways are induced via positive feedback systems, which lead to mucous hypersecretion.", "output": "There is no related enetity." }, { "input": "In the large conducting airways, where cough receptors are concentrated, mucous hypersecretion causes stimulation of neural receptors that result in cough.", "output": "There is no related enetity." }, { "input": "However, in small airways ( e. g., bronchioles ), because of their small diameters, mucous hypersecretion leads to plugging of the airways.", "output": "There is no related enetity." }, { "input": "Because there are so many small airways, their plugging is difficult to detect early, and this locus is known as a \" silent zone. \" In chronic obstructive airway diseases, plugging of small airways may persist and increase over time, finally resulting in severe airway obstruction.", "output": "There is no related enetity." }, { "input": "Different obstructive airway diseases induce inflammatory signaling ( including mucous hypersecretion ) via different stimuli, but often via similar signaling pathways.", "output": "There is no related enetity." }, { "input": "Application of present knowledge of signaling that occurs with mucous hypersecretion can lead to novel therapies for hypersecretion and cough induced in conducting airways and could prevent plugging in small airways that can lead to clinical deterioration and death.", "output": "There is no related enetity." }, { "input": "Interaction of 17 beta - estradiol and ketoconazole on endocrine function in goldfish ( Carassius auratus ).", "output": "17 beta - estradiol, ketoconazole." }, { "input": "An understanding of the effects of toxic mixtures of endocrine disrupting chemicals ( EDCs ) on aquatic organisms is challenging as these organisms are exposed to multiple classes of contaminants in their natural habitat.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the interactions of two classes of EDCs, 17 beta - estradiol ( E2 ) and ketoconazole ( KTC ), on endocrine function in male goldfish ( Carassius auratus ), including vitellogenesis, metabolic capability and serum steroid synthesis.", "output": "17 beta - estradiol, E2, ketoconazole, KTC." }, { "input": "Changes in vitellogenin ( VTG ) concentration, liver 7 - ethoxyresorufin - O - deethylase ( EROD ) activity and circulating serum E2 level were examined.", "output": "7 - ethoxyresorufin, O, E2." }, { "input": "The expression of related genes was also determined using quantitative real - time polymerase chain reaction.", "output": "There is no related enetity." }, { "input": "Exposure to E2 caused a significant increase in VTG concentrations which corresponded with the gene expression of VTG and estrogen receptor ( ER ) in males, which were further elevated after combined exposure to E2 and KTC, indicative of a synergetic relationship.", "output": "E2, estrogen, E2, KTC." }, { "input": "Exposure to E2 also resulted in a distinct increase in serum steroid biosynthesis and associated cytochrome P450 ( CYP ) aromatase expression after 10 days.", "output": "E2, steroid." }, { "input": "However, these changes were inhibited by the presence of KTC, which acted as a steroidogenic inhibitor in fish.", "output": "KTC." }, { "input": "Moreover, KTC significantly decreased liver EROD activity and increased the related gene expression of CYP1A.", "output": "KTC." }, { "input": "However, these KTC - mediated metabolic reactions in goldfish were up - regulated following exposure to KTC in combination with E2.", "output": "KTC, KTC, E2." }, { "input": "These findings reveal complex interactions on endocrine functions in male goldfish when exposed to multiple contaminations and may provide a better understanding of the effects of toxic mixtures.", "output": "There is no related enetity." }, { "input": "New 2 - benzylsulfanyl - nicotinic acid based 1, 3, 4 - oxadiazoles: Their synthesis and biological evaluation.", "output": "2 - benzylsulfanyl - nicotinic acid, 1 , 3 , 4 - oxadiazoles." }, { "input": "A novel series of 5 - ( 2 - benzylsulfanyl - pyridin - 3 - yl ) - 2 - ( substituted ) - sulfanyl - 1, 3, 4 - oxadiazoles 6a - j were synthesized from key intermediate 5 - ( 2 - benzylsulfanyl - pyridin - 3 - yl ) - 3H - [ 1, 3, 4 ] oxadiazole - 2 - thione 5.", "output": "5 - ( 2 - benzylsulfanyl - pyridin - 3 - yl ) - 2 - ( substituted ) - sulfanyl - 1 , 3 , 4 - oxadiazoles, 5 - ( 2 - benzylsulfanyl - pyridin - 3 - yl ) - 3H - [ 1 , 3 , 4 ] oxadiazole - 2 - thione." }, { "input": "Nucleophilic substitution reactions with different electrophiles ( E + ), such as haloacetate and haloalkyl groups, were performed to get target compounds 6a - j.", "output": "haloacetate, haloalkyl." }, { "input": "Compounds were characterized by NMR, mass, IR spectra and C, H, N analyses.", "output": "C, H, N." }, { "input": "All compounds were evaluated for their antimicrobial and antimycobacterial activities; selected analogs were screened for their anticancer activity on 60 tumor cell lines at single dose 1. 00 ( - 5 ) M.", "output": "There is no related enetity." }, { "input": "Unfortunately, none of the compounds showed a significant antitumor activity on 60 human tumor cell lines.", "output": "There is no related enetity." }, { "input": "However, compounds 6g and 6f with benzothiazole moiety ( 12. 5 and 25 mu g / ml ) showed promising activity against Escherichia coli compared to ampicillin; compounds 6d, 6j bearing triazole and morpholine, respectively, showed promising antitubercular activity ( 25 mu g / ml ) compared to rifampicin.", "output": "benzothiazole, ampicillin, triazole, morpholine, rifampicin." }, { "input": "Structural Characterization of an LPA1 Second Extracellular Loop Mimetic with a Self - Assembling Coiled - Coil Folding Constraint.", "output": "There is no related enetity." }, { "input": "G protein - coupled receptor ( GPCR ) structures are of interest as a means to understand biological signal transduction and as tools for therapeutic discovery.", "output": "There is no related enetity." }, { "input": "The growing number of GPCR crystal structures demonstrates that the extracellular loops ( EL ) connecting the membrane - spanning helices show tremendous structural variability relative to the more structurally - conserved seven transmembrane alpha - helical domains.", "output": "There is no related enetity." }, { "input": "The EL of the LPA ( 1 ) receptor have not yet been conclusively resolved, and bear limited sequence identity to known structures.", "output": "LPA." }, { "input": "This study involved development of a peptide to characterize the intrinsic structure of the LPA ( 1 ) GPCR second EL.", "output": "LPA." }, { "input": "The loop was embedded between two helices that assemble into a coiled - coil, which served as a receptor - mimetic folding constraint ( LPA ( 1 ) - CC - EL2 peptide ).", "output": "LPA." }, { "input": "The ensemble of structures from multi - dimensional NMR experiments demonstrated that a robust coiled - coil formed without noticeable deformation due to the EL2 sequence.", "output": "There is no related enetity." }, { "input": "In contrast, the EL2 sequence showed well - defined structure only near its C - terminal residues.", "output": "C." }, { "input": "The NMR ensemble was combined with a computational model of the LPA ( 1 ) receptor that had previously been validated.", "output": "LPA." }, { "input": "The resulting hybrid models were evaluated using docking.", "output": "There is no related enetity." }, { "input": "Nine different hybrid models interacted with LPA 18: 1 as expected, based on prior mutagenesis studies, and one was additionally consistent with antagonist affinity trends.", "output": "LPA." }, { "input": "Chemical Inhibitors and microRNAs ( miRNA ) Targeting the Mammalian Target of Rapamycin ( mTOR ) Pathway: Potential for Novel Anticancer Therapeutics.", "output": "Rapamycin." }, { "input": "The mammalian target of rapamycin ( mTOR ) is a critical regulator of many fundamental features in response to upstream cellular signals, such as growth factors, energy, stress and nutrients, controlling cell growth, proliferation and metabolism through two complexes, mTORC1 and mTORC2.", "output": "rapamycin." }, { "input": "Dysregulation of mTOR signalling often occurs in a variety of human malignant diseases making it a crucial and validated target in the treatment of cancer.", "output": "There is no related enetity." }, { "input": "Tumour cells have shown high susceptibility to mTOR inhibitors.", "output": "There is no related enetity." }, { "input": "Rapamycin and its derivatives ( rapalogs ) have been tested in clinical trials in several tumour types and found to be effective as anticancer agents in patients with advanced cancers.", "output": "Rapamycin." }, { "input": "To block mTOR function, they form a complex with FKBP12 and then bind the FRB domain of mTOR.", "output": "There is no related enetity." }, { "input": "Furthermore, a new generation of mTOR inhibitors targeting ATP - binding in the catalytic site of mTOR showed potent and more selective inhibition.", "output": "ATP." }, { "input": "More recently, microRNAs ( miRNA ) have emerged as modulators of biological pathways that are essential in cancer initiation, development and progression.", "output": "There is no related enetity." }, { "input": "Evidence collected to date shows that miRNAs may function as tumour suppressors or oncogenes in several human neoplasms.", "output": "There is no related enetity." }, { "input": "The mTOR pathway is a promising target by miRNAs for anticancer therapy.", "output": "There is no related enetity." }, { "input": "Extensive studies have indicated that regulation of the mTOR pathway by miRNAs plays a major role in cancer progression, indicating a novel way to investigate the tumorigenesis and therapy of cancer.", "output": "There is no related enetity." }, { "input": "Here, we summarize current findings of the role of mTOR inhibitors and miRNAs in carcinogenesis through targeting mTOR signalling pathways and determine their potential as novel anti - cancer therapeutics.", "output": "There is no related enetity." }, { "input": "Amelioration of Hypoglycemia via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats.", "output": "Somatostatin." }, { "input": "Selective antagonism of somatostatin receptor type 2 ( SSTR2 - ) normalizes glucagon and corticosterone responses to hypoglycemic clamp in diabetic rats.", "output": "somatostatin, corticosterone." }, { "input": "The purpose of this study is to determine if SSTR2 antagonism ( SSTR2a ) ameliorates hypoglycemia in response to overinsulinization in diabetic rats previously exposed to recurrent hypoglycemia.", "output": "There is no related enetity." }, { "input": "Streptozotocin - diabetic rats ( n = 19 ), previously subjected to 5 hypoglycemia events over 3 days, received an i. v. insulin bolus ( 10 U / kg ) + insulin infusion ( 50 mU / kg / min ) until hypoglycemia ensued ( <= 3. 9 mM ) ( Expt - D1 ).", "output": "Streptozotocin." }, { "input": "The next day ( Expt - D2 ), rats were allocated to receive either placebo treatment ( n = 7 ) or SSTR2a infusion ( 3000 nmol / kg / min, n = 12 ) 60 - min prior to same insulin regimen.", "output": "There is no related enetity." }, { "input": "On Expt - D1, all rats developed hypoglycemia by ~ 90 minutes, while on Expt - D2 hypoglycemia was attenuated with SSTR2a treatment ( nadir = 3. 7 +/- 0. 3 mM vs. 2. 7 +/- 0. 3 mM in SSTR2a and controls, p < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Glucagon response to hypoglycemia on Expt - D2 deteriorated by 20 - fold in the placebo group ( P < 0. 001 ) but improved in the SSTR2a group ( 3 - fold increase in AUC, P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Corticosterone response deteriorated in the placebo treated rats on Expt - D2 but increased 2 - fold in the SSTR2a group.", "output": "Corticosterone." }, { "input": "Catecholamine responses were not affected by antagonism.", "output": "Catecholamine." }, { "input": "Thus, SSTR2 antagonism following recurrent hypoglycemia improves the glucagon and corticosterone responses and largely ameliorates insulin - induced hypoglycemia in diabetic rats.", "output": "corticosterone." }, { "input": "TCF7L2 Variation and Proliferative Diabetic Retinopathy.", "output": "There is no related enetity." }, { "input": "Proliferative diabetic retinopathy ( PDR ) is the most severe vision - threatening complication of diabetes.", "output": "There is no related enetity." }, { "input": "To investigated genetic association between TCF7L2 and PDR in Caucasian type 2 diabetes mellitus ( T2DM ) and its functional consequences, 383 T2DM patients with PDR ( T2DM - PDR ) and 756 T2DM patients without diabetic retinopathy ( T2DM - no DR ) were genotyped with rs7903146 in TCF7L2.", "output": "There is no related enetity." }, { "input": "We found that risk allele ( T ) frequency of rs7903146 was significantly higher in T2DM - PDR patients ( allelic P = 2. 52E - 04 ).", "output": "There is no related enetity." }, { "input": "In lymphoblastoid cells induced to undergo endoplasmic reticulum ( ER ) stress by treatment of tunicamycin, higher fold change of TCF7L2 and VEGFA mRNA levels were observed in rs7903146 - TT cells than that in rs7903146 - CC cells ( P = 0. 02 for TCF7L2; P = 0. 004 for VEGFA ), suggesting ER stress plays a role in PDR pathogenesis.", "output": "tunicamycin." }, { "input": "Silencing TCF7L2 resulted in decreased mRNA levels of both TCF7L2 and VEGFA ( P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Retinas of oxygen - induced retinopathy ( OIR ) mice ( a model for PDR ) had higher TCF7L2 and VEGFA mRNA levels than controls ( P = 2. 9E - 04 for TCF7L2; P = 1. 9E - 07 for VEGFA ).", "output": "oxygen." }, { "input": "Together, our study showed that TCF7L2 - rs7903146 is associated with PDR in Caucasian T2DM and suggested TCF7L2 promoted pathological retinal neovascularization via ER stress - dependent upregulation of VEGFA.", "output": "There is no related enetity." }, { "input": "From SNP to Transcriptional Mechanism: A Model for FRMD3 in Diabetic Nephropathy.", "output": "There is no related enetity." }, { "input": "Genome wide association studies ( GWAS ) have proven to be highly effective at defining causal relationships between single nucleotide polymorphisms ( SNP ) and clinical phenotypes in complex diseases.", "output": "nucleotide." }, { "input": "Establishing a mechanistic link between a non - coding SNP and the clinical outcome is a significant hurdle in translating associations into biological insight.", "output": "There is no related enetity." }, { "input": "We demonstrate an approach to assess the functional context of a diabetic nephropathy ( DN ) associated SNP located in the promoter region of the gene FRMD3.", "output": "There is no related enetity." }, { "input": "The approach integrates pathway analyses with transcriptional regulatory pattern based promoter modeling and allows the identification of a transcriptional framework impacted by the DN - associated SNP in the FRMD3 promoter.", "output": "There is no related enetity." }, { "input": "This framework provides a testable hypothesis for mechanisms of genomic variation and transcriptional regulation in the context of DN.", "output": "There is no related enetity." }, { "input": "Our model proposes a possible transcriptional link through which the polymorphism in the FRMD3 promoter could influence transcriptional regulation within the bone morphogenetic protein ( BMP ) signaling pathway.", "output": "There is no related enetity." }, { "input": "These findings provide the rationale to interrogate the biological link between FRMD3 and the BMP pathway, and serve as an example of functional genomics - based hypothesis generation.", "output": "There is no related enetity." }, { "input": "Botulinum toxins: Mechanisms of action, antinociception and clinical applications.", "output": "There is no related enetity." }, { "input": "Botulinum toxin ( BoNT ) is a potent neurotoxin that is produced by the gram - positive, spore - forming, anaerobic bacterium, Clostridum botulinum.", "output": "There is no related enetity." }, { "input": "There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G.", "output": "There is no related enetity." }, { "input": "Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150kDa, which is cleaved by tissue proteinases into an active di - chain molecule: a heavy chain ( H ) of ~ 100kDa and a light chain ( L ) of ~ 50kDa held together by a single disulfide bond.", "output": "disulfide." }, { "input": "Each serotype demonstrates its own varied mechanisms of action and duration of effect.", "output": "There is no related enetity." }, { "input": "The heavy chain of each BoNT serotype binds to its specific neuronal ecto - acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs.", "output": "There is no related enetity." }, { "input": "The light chain acts to cleave SNAP - 25, which inhibits synaptic exocytosis, and therefore, disables neural transmission.", "output": "There is no related enetity." }, { "input": "The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin ' s apparent analgesic activity.", "output": "acetylcholine." }, { "input": "Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions.", "output": "There is no related enetity." }, { "input": "Tryptophan hydroxylase - 2: An emerging therapeutic target for stress disorders.", "output": "Tryptophan." }, { "input": "Serotonin ( 5 - HT ) has been long recognized to modulate the stress response, and dysfunction of 5 - HT has been implicated in numerous stress disorders.", "output": "Serotonin, 5 - HT, 5 - HT." }, { "input": "Accordingly, the 5 - HT system has been targeted for the treatment of stress disorders.", "output": "5 - HT." }, { "input": "Tryptophan hydroxylase ( TPH ) is the rate - limiting enzyme in 5 - HT synthesis, and the recent identification of a second, neuron - specific TPH isoform ( TPH2 ) opened up a new area of research.", "output": "Tryptophan, 5 - HT." }, { "input": "With a decade of extensive investigation, it is now recognized that: ( 1 ) TPH2 exhibits a highly flexible gene expression that is modulated by an increasing number of internal and external environmental factors including the biological clock, stressors, endogenous hormones, and antidepressant therapies; and ( 2 ) genetically determined TPH2 activity is linked to a growing body of stress - related neuronal correlates and behavioral traits.", "output": "There is no related enetity." }, { "input": "These findings reveal an active role of TPH2 in the stress response and provide new insights into the long recognized but not yet fully understood 5 - HT - stress interaction.", "output": "5 - HT." }, { "input": "As a major modulator of 5 - HT neurotransmission and the stress response, TPH2 is of both pathophysiological and pharmacological significance, and is emerging as a new therapeutic target for the treatment of stress disorders.", "output": "5 - HT." }, { "input": "Given that numerous antidepressant therapies influence TPH2 gene expression, TPH2 is already inadvertently targeted for the treatment of stress disorders.", "output": "There is no related enetity." }, { "input": "With increased understanding of the regulation of TPH2 activity we can now purposely utilize TPH2 as a target to develop new or optimize current therapies, which are expected to greatly improve the prevention and treatment of a wide variety of stress disorders.", "output": "There is no related enetity." }, { "input": "Activation of beta - catenin / TCF targets following loss of the tumor suppressor SNF5.", "output": "There is no related enetity." }, { "input": "The SWI / SNF chromatin remodeling complex is a master regulator of developmental cell - fate decisions, although the key target pathways are poorly characterized.", "output": "There is no related enetity." }, { "input": "Here, we interrogated the contribution of the SWI / SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models.", "output": "There is no related enetity." }, { "input": "We find that loss of SNF5 phenocopies beta - catenin hyperactivation and that SNF5 is essential for regulating Wnt / beta - catenin pathway target expression.", "output": "There is no related enetity." }, { "input": "These data provide insight into chromatin - based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control. Oncogene advance online publication, 25 February 2013; doi: 10. 1038 / onc. 2013. 37.", "output": "There is no related enetity." }, { "input": "The ( R ) - omeprazole hydroxylation index reflects CYP2C19 activity in healthy Japanese volunteers.", "output": "( R ) - omeprazole." }, { "input": "PURPOSE: Omeprazole has ( R ) - and ( S ) - enantiomers, which exhibit different pharmacokinetics ( PK ) among patients with cytochrome P450 ( CYP ) 2C19 genotype groups.", "output": "Omeprazole." }, { "input": "The aim of this study was to investigate whether the 1 - point, 4 - h postdose ( R ) - omeprazole hydroxylation index ( HI ) of racemic omeprazole reflects the three CYP2C19 genotype groups in Japanese individuals.", "output": "( R ) - omeprazole, racemic omeprazole." }, { "input": "METHODS: Ninety healthy Japanese individuals were enrolled and classified into the three different CYP2C19 genotype groups: homozygous extensive metabolizers ( hmEMs; n = 34 ), heterozygous EMs ( htEMs; n = 44 ), and poor metabolizers ( PMs; n = 12 ).", "output": "There is no related enetity." }, { "input": "Blood samples were drawn 4 h after the intake of an oral dose of omeprazole 40 mg, and plasma levels of omeprazole and its metabolites were analyzed by high - performance liquid chromatography ( HPLC ) using a chiral column.", "output": "omeprazole, omeprazole." }, { "input": "RESULTS: Mean plasma concentrations of ( R ) - and ( S ) - omeprazole in PMs were significantly higher than those in hmEMs and htEMs, and similar results were obtained in the case of omeprazole sulfone.", "output": "( R ) - and ( S ) - omeprazole, omeprazole sulfone." }, { "input": "Additionally, there was a significant difference in plasma concentrations of ( R ) - 5 - hydroxyomeprazole among CYP2C19 genotype groups, whereas no significant differences were observed in that of ( S ) - 5 - hydroxyomeprazole.", "output": "( R ) - 5 - hydroxyomeprazole, ( S ) - 5 - hydroxyomeprazole." }, { "input": "Similarly, ( R ) - omeprazole HI in hmEMs, htEMs, and PMs were 5. 6, 3. 1, and 0. 3, respectively, which were significantly different, but no significant difference was present in the ( S ) - omeprazole HI.", "output": "( R ) - omeprazole, ( S ) - omeprazole." }, { "input": "CONCLUSION: Our findings demonstrate that ( R ) - omeprazole HI correlated better with CYP2C19 genotype groups than racemic - omeprazole HI, and these results may be useful for classification among patients in CYP2C19 genotype groups prior to omeprazole treatment.", "output": "( R ) - omeprazole, racemic - omeprazole." }, { "input": "Marine ecosystem health status assessment through integrative biomarker indices: a comparative study after the Prestige oil spill \" Mussel Watch \".", "output": "There is no related enetity." }, { "input": "Five integrative biomarker indices are compared: Bioeffects Assessment Index ( BAI ), Health Status Index ( HSI ), integrated biological response ( IBR ), ecosystem health condition chart ( EHCC ) and Integrative Biomarker Index ( IBI ).", "output": "There is no related enetity." }, { "input": "They were calculated on the basis of selected biomarker data collected in the framework of the Prestige oil spill ( POS ) Mussel Watch monitoring ( 2003 - 2006 ) carried out in Galicia and the Bay of Biscay.", "output": "There is no related enetity." }, { "input": "According to the BAI, the health status of mussels was severely affected by POS and signals of recovery were evidenced in Galicia after April - 04 and in Biscay Bay after April - 05.", "output": "There is no related enetity." }, { "input": "The HSI ( computed by an expert system ) revealed high levels of environmental stress in 2003 and a recovery trend from April - 04 to April - 05.", "output": "There is no related enetity." }, { "input": "In July - 05, the health status of mussels worsened but in October - 05 and April - 06 healthy condition was again recorded in almost all localities.", "output": "There is no related enetity." }, { "input": "IBR / n and IBI indicated that mussel health was severely affected in 2003 and improved from 2004 onwards.", "output": "There is no related enetity." }, { "input": "EHCC reflected a deleterious environmental condition in 2003 and a recovery trend after April - 04, although a healthy ecosystem condition was not achieved in April - 06 yet.", "output": "There is no related enetity." }, { "input": "Whereas BAI and HSI provide a basic indication of the ecosystem health status, star plots accompanying IBR / n and IBI provide complementary information concerning the mechanisms of biological response to environmental insult.", "output": "There is no related enetity." }, { "input": "Overall, although the integrative indices based on biomarkers show different sensitivity, resolution and informative output, all of them provide coherent information, useful to simplify the interpretation of biological effects of pollution in marine pollution monitoring.", "output": "There is no related enetity." }, { "input": "Each others ' advantages, disadvantages and applicability for ecosystem health assessment are discussed.", "output": "There is no related enetity." }, { "input": "Effect of sinapic acid against dimethylnitrosamine - induced hepatic fibrosis in rats.", "output": "sinapic acid, dimethylnitrosamine." }, { "input": "Sinapic acid is a member of the phenylpropanoid family and is abundant in cereals, nuts, oil seeds, and berries.", "output": "Sinapic acid, phenylpropanoid." }, { "input": "It exhibits a wide range of pharmacological properties.", "output": "There is no related enetity." }, { "input": "In this study, we investigated the hepatoprotective and antifibrotic effects of sinapic acid on dimethylnitrosamine ( DMN ) - induced chronic liver injury in rats.", "output": "sinapic acid, dimethylnitrosamine, DMN." }, { "input": "Sinapic acid remarkably prevented DMN - induced loss of body weight.", "output": "Sinapic acid, DMN." }, { "input": "This was accompanied by a significant increase in levels of serum alanine transaminase, aspartate transaminase, and liver malondialdehyde content.", "output": "alanine, aspartate, malondialdehyde." }, { "input": "Furthermore, sinapic acid reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of type I collagen mRNA and histological analysis of collagen in liver tissue.", "output": "sinapic acid, hydroxyproline." }, { "input": "Additionally, the expression of hepatic fibrosis - related factors such as alpha - smooth muscle actin and transforming growth factor - beta 1 ( TGF - beta 1 ), were reduced in rats treated with sinapic acid.", "output": "sinapic acid." }, { "input": "Sinapic acid exhibited strong scavenging activity.", "output": "Sinapic acid." }, { "input": "In conclusion, we find that sinapic acid exhibits hepatoprotective and antifibrotic effects against DMN - induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress TGF - beta 1 and its ability to attenuate activation of hepatic stellate cells.", "output": "sinapic acid, DMN." }, { "input": "This suggests that sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis.", "output": "sinapic acid." }, { "input": "Simple and sensitive liquid chromatography - tandem mass spectrometry methods for quantification of tadalafil in rat plasma: application to pharmacokinetic study in rats.", "output": "tadalafil." }, { "input": "A simple and sensitive liquid chromatography - tandem mass spectrometry method was developed and validated in rat plasma for quantification of tadalafil, a novel therapeutic agent for erectile dysfunction.", "output": "tadalafil." }, { "input": "Tadalafil and acebutolol ( internal standard ) were extracted by liquid - liquid extraction with tert - butyl methyl ether.", "output": "Tadalafil, acebutolol, tert - butyl methyl ether." }, { "input": "The chromatographic separation was performed on a reverse phase C18 column with a mobile phase consisting of 0. 1 % formic acid and acetonitrile ( 45: 55, v / v ) at a flow rate of 0. 3 mL / min.", "output": "formic acid, acetonitrile." }, { "input": "The protonated analyte was quantitated by multiple reaction monitoring with a Waters Quattro micro (TM) API mass spectrometer.", "output": "There is no related enetity." }, { "input": "The calibration curve was linear over a concentration range of 2 - 2000 ng / mL, and the lower limit of quantification was 2 ng / mL with a precision ( CV % ) of 10. 9 %.", "output": "There is no related enetity." }, { "input": "Acceptable intra - day and inter - day precision and accuracy were obtained at 3 concentration levels ( 3, 200, and 1500 ng / mL ).", "output": "There is no related enetity." }, { "input": "Tadalafil was found to be stable in a battery of studies, including bench top, freeze - thaw, and autosampler conditions.", "output": "Tadalafil." }, { "input": "The validated method was successfully used to determine tadalafil concentration in rat plasma samples after oral administration at a dose of 1 mg / kg.", "output": "tadalafil." }, { "input": "Anti - inflammatory effect of pristimerin on lipopolysaccharide - induced inflammatory responses in murine macrophages.", "output": "pristimerin." }, { "input": "Pristimerin, a quinonemethide triterpenoid derived from Celastraceae and Hippocrateaceae, has recently been found to suppress tumor promotion, metastasis and angiogenesis.", "output": "Pristimerin, quinonemethide triterpenoid." }, { "input": "In the present study, we evaluated the anti - inflammatory potentials of pristimerin in a cell culture system.", "output": "pristimerin." }, { "input": "Pristimerin suppressed not only the generation of nitric oxide ( NO ) and prostaglandin E2, but also the expression of inducible NO synthase and cyclooxygenase - 2 induced by lipopolysacharide ( LPS ) in murine macrophage RAW264. 7 cells.", "output": "Pristimerin, nitric oxide, NO, prostaglandin E2, NO." }, { "input": "Similarly, pristimerin inhibited the release of pro - inflammatory cytokines, namely, tumor necrosis factor - alpha and interleukin - 6, induced by LPS.", "output": "pristimerin." }, { "input": "The underlying mechanism of the anti - inflammatory action of pristimerin was correlated with down - regulation of nuclear factor - kappa B and the mitogen - activated protein kinase signal pathway.", "output": "pristimerin." }, { "input": "A review on cholinesterase inhibitors for Alzheimer ' s disease.", "output": "There is no related enetity." }, { "input": "Alzheimer ' s disease ( AD ), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid ( A beta ) in the form of neurofibrillary tangles and amyloid plaques.", "output": "There is no related enetity." }, { "input": "Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti - Alzheimer ' s drugs.", "output": "There is no related enetity." }, { "input": "Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase ( AChE ) which hydrolyses acetylcholine.", "output": "acetylcholine." }, { "input": "Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase ( BuChE ) play an important role in A beta - aggregation during the early stages of senile plaque formation.", "output": "There is no related enetity." }, { "input": "Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the A beta deposition.", "output": "acetylcholine." }, { "input": "This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para - aminobenzoic acid, coumarin, flavonoid, and pyrrolo - isoxazole analogues developed for the treatment of AD.", "output": "tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para - aminobenzoic acid, coumarin, flavonoid, pyrrolo - isoxazole." }, { "input": "Potent alpha - glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris.", "output": "tyrosine." }, { "input": "As a part of our ongoing effort to identify anti - diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against alpha - glucosidase and protein tyrosine phosphatase 1B ( PTP1B ).", "output": "methanol, tyrosine." }, { "input": "The methanol extracts of different species exhibited promising alpha - glucosidase and PTP1B inhibitory activities.", "output": "methanol." }, { "input": "Since the methanol extract of Artemisia capillaris exhibited the highest alpha - glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation.", "output": "methanol." }, { "input": "Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins ( esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7 - methoxy coumarin, scoparone, scopoletin, 6 - methoxy artemicapin C ), 8 flavonoids ( hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3 - robinobioside, linarin, isorhamnetin 3 - glucoiside ), 6 phenolic compounds ( 1, 5 - dicaffeoylquinic acid, 3, 4 - dicaffeoylquinic acid, 3, 5 - dicaffeoylquinic acid, 3, 5 - dicaffeoylquinic acid methyl ester, 4, 5 - dicaffeoylquinic acid, 3 - caffeoylquinic acid ), and one chromone ( capillarisin ).", "output": "coumarins, esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7 - methoxy coumarin, scoparone, scopoletin, 6 - methoxy artemicapin C, flavonoids, hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3 - robinobioside, linarin, isorhamnetin 3 - glucoiside, phenolic, 1 , 5 - dicaffeoylquinic acid, 3 , 4 - dicaffeoylquinic acid, 3 , 5 - dicaffeoylquinic acid, 3 , 5 - dicaffeoylquinic acid methyl ester, 4 , 5 - dicaffeoylquinic acid, 3 - caffeoylquinic acid, chromone, capillarisin." }, { "input": "Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3, 5 - dicaffeoylquinic acid methyl ester, 3, 4 - dicaffeoylquinic acid, and 1, 5 - dicaffeoylquinic acid exhibited potent alpha - glucosidase inhibitory activity when compared to the positive control acarbose.", "output": "esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3 , 5 - dicaffeoylquinic acid methyl ester, 3 , 4 - dicaffeoylquinic acid, 1 , 5 - dicaffeoylquinic acid, acarbose." }, { "input": "In addition, esculetin and 6 - methoxy artemicapin C displayed PTP1B inhibitory activity.", "output": "esculetin, 6 - methoxy artemicapin C." }, { "input": "Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity.", "output": "dicaffeoylquinic acids." }, { "input": "Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit alpha - glucosidase and PTP1B.", "output": "There is no related enetity." }, { "input": "These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes.", "output": "coumarins, flavonoids, dicaffeoylquinic acids." }, { "input": "Impact of acamprosate on behavior and brain - derived neurotrophic factor: an open - label study in youth with fragile X syndrome.", "output": "acamprosate." }, { "input": "RATIONALE: Fragile X syndrome ( FXS ) is an inherited form of developmental disability and a single gene cause of autism.", "output": "There is no related enetity." }, { "input": "As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts.", "output": "There is no related enetity." }, { "input": "Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma - aminobutyric acid ( GABA ) neurotransmission.", "output": "glutamate, gamma - aminobutyric acid, GABA." }, { "input": "METHODS: We conducted a prospective open - label 10 - week trial of acamprosate in 12 youth aged 6 - 17 years ( mean age: 11. 9 years ) with FXS.", "output": "acamprosate." }, { "input": "RESULTS: Acamprosate use ( mean dose: 1, 054 +/- 422 mg / day ) was associated with treatment response ( defined by a Clinical Global Impressions Improvement ( CGI - I ) scale score of \" very much improved \" or \" much improved \" ) in nine of 12 ( 75 % ) subjects.", "output": "Acamprosate." }, { "input": "Improvement was noted in social behavior and inattention / hyperactivity using multiple standard behavioral outcome measures.", "output": "There is no related enetity." }, { "input": "No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate.", "output": "acamprosate." }, { "input": "Additionally, pre - and post - treatment blood biomarker analyses looking at brain - derived neurotrophic factor ( BDNF ) levels found a significant increase in BDNF with treatment.", "output": "There is no related enetity." }, { "input": "In our pilot sample, treatment response did not correlate with change in BDNF with treatment.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention / hyperactivity.", "output": "Acamprosate." }, { "input": "The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies.", "output": "acamprosate." }, { "input": "Given these findings, a double - blind, placebo - controlled study of acamprosate in youth with FXS is warranted.", "output": "acamprosate." }, { "input": "Clinical risk factors for adverse events in allopurinol users.", "output": "allopurinol." }, { "input": "Allopurinol, one of the most commonly used uric acid - lowering agents, can cause serious adverse events.", "output": "Allopurinol, uric acid." }, { "input": "To investigate the risk factors for allopurinol - induced adverse events, the authors enrolled 94 patients who developed allopurinol - induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study.", "output": "allopurinol, allopurinol, allopurinol." }, { "input": "Univariate analysis showed that patients who developed allopurinol - induced adverse events had more chronic kidney disease ( 46 % vs 30 %, P =. 005 ), more hypertension ( 42 % vs 30 %, P =. 036 ), less tumor lysis syndrome ( P =. 030 ), higher cholesterol ( P =. 013 ), and lower aspartate aminotransferase ( P =. 002 ) and alanine aminotransferase levels ( P =. 033 ) and more commonly used angiotensin receptor blockers ( 27 % vs 15 %, P =. 007 ), colchicines ( 16 % vs 5 %, P =. 010 ), or statins ( 19 % vs 8 %, P =. 002 ) than those who did not.", "output": "allopurinol, cholesterol, aspartate, alanine, colchicines, statins." }, { "input": "In multiple logistic regression analysis, the use of colchicines ( odds ratio, 3. 11; 95 % confidence interval, 1. 28 - 7. 58; P =. 012 ) and statins ( 2. 10; 1. 03 - 4. 25; P =. 041 ) was an independent risk factor predicting adverse events in allopurinol users.", "output": "colchicines, statins, allopurinol." }, { "input": "In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol - induced adverse events.", "output": "colchicine, statins, allopurinol." }, { "input": "Vemurafenib - associated pancreatitis: case report.", "output": "Vemurafenib." }, { "input": "Vemurafenib is a novel BRAF kinase inhibitor indicated in metastatic melanoma patients with V600E mutation.", "output": "Vemurafenib." }, { "input": "We report the first case of vemurafenib - associated pancreatitis.", "output": "vemurafenib." }, { "input": "Two weeks after initiation of vemurafenib, a patient presented to the emergency department with severe epigastric pain and a serum lipase of 1544 units / L.", "output": "vemurafenib." }, { "input": "Drug - induced pancreatitis was diagnosed on exclusion of all other potential causes.", "output": "There is no related enetity." }, { "input": "Vemurafenib was rechallenged at half the daily dose and the patient subsequently developed exacerbated symptoms of pancreatitis after two doses.", "output": "Vemurafenib." }, { "input": "The strong temporal relationship between drug exposure and toxicity, along with the positive results from a rechallenge study, strongly support a conclusion of causality.", "output": "There is no related enetity." }, { "input": "To our knowledge, this is the first report of vemurafenib - induced pancreatitis.", "output": "vemurafenib." }, { "input": "Weak - field, multiple - cycle carrier envelope phase effects in laser excitation.", "output": "There is no related enetity." }, { "input": "Although the absolute or carrier envelope phase ( CEP ) of a laser pulse is usually assumed to be effective for ultrashort and / or ultrastrong pulses only, it is demonstrated that these limitations can eventually be removed.", "output": "There is no related enetity." }, { "input": "Therefore, the excitation of a model positively charged homonuclear diatomic molecule, in which four electronic states are coupled by the laser field, is studied.", "output": "There is no related enetity." }, { "input": "In an initial step, nuclear wave packets in two dissociative states are prepared.", "output": "There is no related enetity." }, { "input": "Upon reaching the fragment channel, a weak pulse interacts with the system and prepares CEP - dependent asymmetries associated with electron density localized on one or the other fragmentation product.", "output": "There is no related enetity." }, { "input": "Thermal and Electrical Conduction in Ultrathin Metallic Films: 7 nm down to Sub - Nanometer Thickness.", "output": "There is no related enetity." }, { "input": "For ultrathin metallic films ( e. g., less than 5 nm ), no knowledge is yet available on how electron scattering at surface and grain boundaries reduces the electrical and thermal transport.", "output": "There is no related enetity." }, { "input": "The thermal and electrical conduction of metallic films is characterized down to 0. 6 nm average thickness.", "output": "There is no related enetity." }, { "input": "The electrical and thermal conductivities of 0. 6 nm Ir film are reduced by 82 % and 50 % from the respective bulk values.", "output": "There is no related enetity." }, { "input": "The Lorenz number is measured as 7. 08 x 10 ( - 8 ) W Omega K ( - 2 ), almost a twofold increase of the bulk value.", "output": "There is no related enetity." }, { "input": "The Mayadas - Shatzkes model is used to interpret the experimental results and reveals very strong electron reflection ( > 90 % ) at grain boundaries.", "output": "There is no related enetity." }, { "input": "A combination strategy to inhibit Pim - 1: synergism between noncompetitive and ATP - competitive inhibitors.", "output": "ATP." }, { "input": "Pim - 1 is a serine / threonine kinase critically involved in the initiation and progression of various types of cancer, especially leukemia, lymphomas and solid tumors such as prostate, pancreas and colon, and is considered a potential drug target against these malignancies.", "output": "serine, threonine." }, { "input": "In an effort to discover new potent Pim - 1 inhibitors, a previously identified ATP - competitive indolyl - pyrrolone scaffold was expanded to derive structure - activity relationship data.", "output": "ATP, indolyl - pyrrolone." }, { "input": "A virtual screening campaign was also performed, which led to the discovery of additional ATP - competitive inhibitors as well as a series of 2 - aminothiazole derivatives, which are noncompetitive with respect to both ATP and peptide substrate.", "output": "ATP, 2 - aminothiazole, ATP." }, { "input": "This mechanism of action, which resembles allosteric inhibition, has not previously been characterized for Pim - 1.", "output": "There is no related enetity." }, { "input": "Notably, further evaluation of the 2 - aminothiazoles indicated a synergistic inhibitory effect in enzymatic assays when tested in combination with ATP - competitive inhibitors.", "output": "2 - aminothiazoles, ATP." }, { "input": "A synergistic effect in the inhibition of cell proliferation by ATP - competitive and ATP - noncompetitive compounds was also observed in prostate cancer cell lines ( PC3 ), where all Pim - 1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel.", "output": "ATP, ATP, paclitaxel." }, { "input": "These results further establish Pim - 1 as a target in cancer therapy, and highlight the potential of these agents for use as adjuvant agents in the treatment of cancer diseases in which Pim - 1 is associated with chemotherapeutic resistance.", "output": "There is no related enetity." }, { "input": "Discovery of Novel Dual Inhibitors of the Wild - Type and the Most Prevalent Drug - Resistant Mutant, S31N, of the M2 Proton Channel from Influenza A Virus.", "output": "There is no related enetity." }, { "input": "Anti - influenza drugs, amantadine and rimantadine, targeting the M2 channel from influenza A virus are no longer effective because of widespread drug resistance.", "output": "amantadine, rimantadine." }, { "input": "S31N is the predominant and amantadine - resistant M2 mutant, present in almost all of the circulating influenza A strains as well as in the pandemic 2009 H1N1 and the highly pathogenic H5N1 flu strains.", "output": "amantadine." }, { "input": "Thus, there is an urgent need to develop second - generation M2 inhibitors targeting the S31N mutant.", "output": "There is no related enetity." }, { "input": "However, the S31N mutant presents a huge challenge to drug discovery, and it has been considered undruggable for several decades.", "output": "There is no related enetity." }, { "input": "Using structural information, classical medicinal chemistry approaches, and M2 - specific biological testing, we discovered benzyl - substituted amantadine derivatives with activity against both S31N and WT, among which 4 - ( adamantan - 1 - ylaminomethyl ) - benzene - 1, 3 - diol ( 44 ) is the most potent dual inhibitor.", "output": "benzyl, amantadine, 4 - ( adamantan - 1 - ylaminomethyl ) - benzene - 1 , 3 - diol." }, { "input": "These inhibitors demonstrate that S31N is a druggable target and provide a new starting point to design novel M2 inhibitors that address the problem of drug - resistant influenza A infections.", "output": "There is no related enetity." }, { "input": "Evidence for the Involvement of Descending Pain - Inhibitory Mechanisms in the Antinociceptive Effect of Hecogenin Acetate.", "output": "Hecogenin Acetate." }, { "input": "Hecogenin is a sapogenin present in the leaves of species from the Agave genus, with a wide spectrum of reported pharmacological activities.", "output": "Hecogenin." }, { "input": "The present study was undertaken to evaluate whether hecogenin acetate ( 1 ) has antinociceptive properties and to determine its mechanism of action.", "output": "hecogenin acetate." }, { "input": "The nociceptive threshold was evaluated using the tail flick test in mice.", "output": "There is no related enetity." }, { "input": "Mice motor performance was evaluated in a Rotarod test.", "output": "There is no related enetity." }, { "input": "By using Fos expression as a marker of neural activation, the involvement of the periaqueductal gray in 1 - induced antinociception was evaluated.", "output": "There is no related enetity." }, { "input": "Intraperitoneal administration of 1 ( 5 - 40 mg / kg ) produced a dose - dependent increase in the tail flick latency time compared to vehicle - treated group ( p < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Mice treated with 1 ( 40 mg / kg ) did not show motor performance alterations.", "output": "There is no related enetity." }, { "input": "The antinociception of 1 ( 40 mg / kg ) was prevented by naloxone ( nonselective opioid receptor antagonist; 5 mg / kg ), CTOP ( mu - opioid receptor antagonist; 1 mg / kg ), nor - BNI ( kappa - opioid receptor antagonist; 0. 5 mg / kg ), naltrindole ( delta - opioid receptor antagonist; 3 mg / kg ), or glibenclamide ( ATP - sensitive K ( + ) channel blocker; 2 mg / kg ).", "output": "naloxone, CTOP, nor - BNI, naltrindole, glibenclamide, ATP, K ( + )." }, { "input": "Systemic administration of 1 ( 5 - 40 mg / kg ) increased the number of Fos positive cells in the periaqueductal gray.", "output": "There is no related enetity." }, { "input": "The present study has demonstrated for the first time that 1 produces consistent antinociception mediated by opioid receptors and endogenous analgesic mechanisms.", "output": "There is no related enetity." }, { "input": "Consequences of Membrane Topography.", "output": "There is no related enetity." }, { "input": "The surface of mammalian cells is neither smooth nor flat and cells have several times more plasma membrane than the minimum area required to accommodate their shape.", "output": "There is no related enetity." }, { "input": "We discuss the biological function of this apparent excess membrane that allows the cells to migrate, undergo shape changes and probably plays a role in signal transduction.", "output": "There is no related enetity." }, { "input": "Methods for studying membrane folding and topography; atomic force microscopy, scanning ion conductance microscopy, fluorescence polarisation microscopy and linear dichroism, are described and evaluated.", "output": "There is no related enetity." }, { "input": "Membrane folding and topography is frequently ignored when interpreting microscopy data.", "output": "There is no related enetity." }, { "input": "This has resulted in several misconceptions for instance regarding colocalisation, membrane organisation and molecular clustering.", "output": "There is no related enetity." }, { "input": "We suggest simple ways to avoid these pitfalls and invoke Occam ' s razor - that simple explanations are preferable to complex ones.", "output": "There is no related enetity." }, { "input": "Topography, i. e. deviations from a smooth surface, should always be ruled out as the cause of anomalous data before other explanations are presented.", "output": "There is no related enetity." }, { "input": "(c) 2013 The Authors Journal compilation (c) 2013 FEBS.", "output": "There is no related enetity." }, { "input": "Quantitative analysis of the coverage density of Br - ions on Pd { 100 } facets and its role in controlling the shape of Pd nanocrystals.", "output": "Br -, Pd, Pd." }, { "input": "We report an approach based on a combination of inductively coupled plasma mass spectrometry and X - ray photoelectron spectroscopy for quantitative analysis of the role played by Br ( - ) ions in the synthesis of Pd nanocrystals.", "output": "Br ( - ), Pd." }, { "input": "The Br ( - ) ions were found to adsorb onto Pd { 100 } facets selectively with a coverage density of ca.", "output": "Br ( - ), Pd." }, { "input": "0. 8 ion per surface Pd atom.", "output": "Pd." }, { "input": "The chemisorbed Br ( - ) ions could be removed via desorption at an elevated temperature under reductive conditions.", "output": "Br ( - )." }, { "input": "They could also be gradually released from the surface when Pd cubic seeds grew into cuboctahedrons and then octahedrons.", "output": "Pd." }, { "input": "On the basis of the coverage density information, we were able to estimate the minimum concentration of Br ( - ) ions needed for the formation of Pd nanocubes with a specific size.", "output": "Br ( - ), Pd." }, { "input": "If the concentration of Br ( - ) ions was below this minimum value, not all of the { 100 } facets could be stabilized by the capping agent, leading to the formation of nanocubes with truncated corners.", "output": "Br ( - )." }, { "input": "The quantitative analysis developed in this study is potentially extendable to other systems involving chemisorbed capping agents.", "output": "There is no related enetity." }, { "input": "Systematic review of atomoxetine data in childhood and adolescent attention - deficit hyperactivity disorder 2009 - 2011: Focus on clinical efficacy and safety.", "output": "atomoxetine." }, { "input": "Background: Clinicians obtain critical prescribing knowledge from clinical papers and review articles.", "output": "There is no related enetity." }, { "input": "This is the first published systematic review of clinical atomoxetine data covering 2009 - 2011. Objective: We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy.", "output": "atomoxetine, atomoxetine." }, { "input": "These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications. Methods: A formal systematic review of atomoxetine data from January 2009 - June 2011 was conducted.", "output": "atomoxetine, atomoxetine." }, { "input": "The search term used was \" atomoxetine \" in the English language.", "output": "atomoxetine." }, { "input": "The search yielded 747 citations from which 106 are clinical data.", "output": "There is no related enetity." }, { "input": "This paper includes clinical efficacy and safety data and excludes quality - of - life and review papers. Results: Atomoxetine has an onset of action within 4 weeks ( possibly within 1 week in subsequent responders ) but requires at least 12 weeks for full response to be demonstrated.", "output": "Atomoxetine." }, { "input": "Treatment - na i ve cohorts ( 6 - 12 weeks ) report effect sizes of 0. 6 - 1. 3.", "output": "There is no related enetity." }, { "input": "Using minimum 6 - week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta - analysis, although the diversity of the data makes interpretation complex.", "output": "atomoxetine, methylphenidate." }, { "input": "From epidemiological databases, cardiovascular and suicide - related events were similar to those seen in patients taking methylphenidate. Conclusions: Incremental response time to atomoxetine should be considered in the design of future comparative efficacy trials.", "output": "methylphenidate, atomoxetine." }, { "input": "A network model of the molecular organization of chromatin in Drosophila.", "output": "There is no related enetity." }, { "input": "Chromatin governs gene regulation and genome maintenance, yet a substantial fraction of the chromatin proteome is still unexplored.", "output": "There is no related enetity." }, { "input": "Moreover, a global model of the chromatin protein network is lacking.", "output": "There is no related enetity." }, { "input": "By screening > 100 candidates we identify 42 Drosophila proteins that were not previously associated with chromatin, which all display specific genomic binding patterns.", "output": "There is no related enetity." }, { "input": "Bayesian network modeling of the binding profiles of these and 70 known chromatin components yields a detailed blueprint of the in vivo chromatin protein network.", "output": "There is no related enetity." }, { "input": "We demonstrate functional compartmentalization of this network, and predict functions for most of the previously unknown chromatin proteins, including roles in DNA replication and repair, and gene activation and repression.", "output": "There is no related enetity." }, { "input": "Orthogonal patterning of multiple biomolecules using an organic fluorinated resist and imprint lithography.", "output": "There is no related enetity." }, { "input": "The ability to spatially deposit multiple biomolecules onto a single surface with high - resolution while retaining biomolecule stability and integrity is critical to the development of micro - and nanoscale biodevices.", "output": "There is no related enetity." }, { "input": "While conventional lithographic patterning methods are attractive for this application, they typically require the use of UV exposure and / or harsh solvents and imaging materials, which may be damaging to fragile biomolecules.", "output": "There is no related enetity." }, { "input": "Here, we report the development of a new patterning process based on a fluorinated patterning material that is soluble in hydrofluoroether solvents, which we show to be benign to biomolecules, including proteins and DNA.", "output": "hydrofluoroether." }, { "input": "We demonstrate the implementation of these materials into an orthogonal processing system for patterning multibiomolecule arrays by imprint lithography at room temperature.", "output": "There is no related enetity." }, { "input": "We further showcase this method ' s capacity for fabricating patterns of receptor - specific ligands for fundamental cell studies.", "output": "There is no related enetity." }, { "input": "Microfluidic synthesis of cell - type - specific artificial extracellular matrix hydrogels.", "output": "There is no related enetity." }, { "input": "Droplet microfluidic technology is applied for the high - throughput synthesis via Michael - type addition of reactive, micrometer - sized poly ( ethylene glycol ) ( PEG ) hydrogels ( \" microgels \" ) with precisely controlled dimension and physicochemical properties.", "output": "poly ( ethylene glycol ), PEG." }, { "input": "A versatile chemical scheme is used to modify the reactive PEG microgels with tethered biomolecules to tune their bioactive properties for the bioreactor culture and manipulation of various ( stem ) cell types.", "output": "PEG." }, { "input": "Post - partum variation in the expression of paternal care is unrelated to urinary steroid metabolites in marmoset fathers.", "output": "steroid." }, { "input": "The organization and activation of maternal care are known to be highly regulated by hormones and there is growing evidence that expression of paternal care is also related to endocrine substrates.", "output": "There is no related enetity." }, { "input": "We examined the relationship between paternal behavior and steroid hormones in marmoset fathers ( Callithrix geoffroyi ) and evaluated whether hormone - paternal behavior relationships were altered by previous offspring - care experience in males.", "output": "steroid." }, { "input": "Based on previous findings, we predicted that testosterone, estradiol, and cortisol would decrease following the birth of offspring and would be lowest during the period of maximal infant carrying.", "output": "testosterone, estradiol, cortisol." }, { "input": "Furthermore, we predicted that post - partum changes in carrying effort and hormone levels would be influenced by the level of offspring - care experience.", "output": "There is no related enetity." }, { "input": "Carrying effort and other paternal care behaviors underwent temporal changes over the post - partum period, but these patterns were not related to variation in hormone concentrations over the same period.", "output": "There is no related enetity." }, { "input": "There was a limited effect of offspring - care experience on hormone concentrations, but experience was found to play a role in the expression of paternal care, with experienced fathers engaging in significantly more infant allogrooming than inexperienced fathers.", "output": "There is no related enetity." }, { "input": "Furthermore, inexperienced fathers increased the frequency of food sharing in response to infant begging across the post - partum period, while experienced fathers displayed consistently low levels.", "output": "There is no related enetity." }, { "input": "We posit that a combination of experiential factors and an increased role for alloparents in offspring - care led to these changes.", "output": "There is no related enetity." }, { "input": "However, it appears that hormonal changes may not influence paternal responsiveness in white - faced marmoset fathers and that hormone - paternal behavior relationships are not critically dependent on a male ' s previous offspring - care experience.", "output": "There is no related enetity." }, { "input": "pH - gradient PAMPA - based in vitro model assay for drug - induced phospholipidosis in early stage of drug discovery.", "output": "There is no related enetity." }, { "input": "In the present study we validated a widely used, high - throughput in vitro permeability model ( PAMPA ) to be used at the early stage of drug discovery for the phospholipidosis ( PLD ) prediction of drug - like compounds.", "output": "There is no related enetity." }, { "input": "Regarding the mechanism of action of PLD, our pH - gradient PAMPA system is the first noncell based model to mimic one - way transport of cationic amphiphilic drugs ( CADs ) from cytosol to the lysosome.", "output": "There is no related enetity." }, { "input": "Moreover, due to the fact that PLD can mainly occur in lung, liver, brain, kidney and heart, we have used similar commercially available original tissue - derived lipid fractions ( heart, liver, brain ), and in the case mimicking membrane of kidney and lung tissue we prepared tissue - mimetic artificial lipid mixtures in house.", "output": "There is no related enetity." }, { "input": "Metabolism of a drug can change the degree of PLD depending on the physicochemical properties of metabolites and the rate of metabolism.", "output": "There is no related enetity." }, { "input": "Our data from 57 drugs and 4 metabolites of earlier and 2 metabolites of newly recognized outliers ( phenacetin and bupropion ) using our pH - gradient PAMPA system show a good correlation with in vivo PLD data.", "output": "phenacetin, bupropion." }, { "input": "Moreover, predictive ability of our best system, the lung specific pH - gradient PAMPA model was significantly better than widely used in silico models and it was also slightly better than that of the known noncell based models on our selection of compounds.", "output": "There is no related enetity." }, { "input": "Our pH - gradient PAMPA systems therefore offer mechanistically alternative, accurate and cost - effective screening tools for the early prediction of PLD potential of drug - like compounds.", "output": "There is no related enetity." }, { "input": "NADPH Oxidase NOX5 - S and Nuclear Factor kappa B1 Mediate Acid - Induced Microsomal Prostaglandin E Synthase - 1 Expression in Barrett ' s Esophageal Adenocarcinoma Cells.", "output": "NADPH, Prostaglandin E." }, { "input": "The mechanisms of progression from Barrett ' s esophagus ( BE ) to esophageal adenocarcinoma ( EA ) are not known.", "output": "There is no related enetity." }, { "input": "Cycloxygenase - 2 ( COX - 2 ) - derived prostaglandin E2 ( PGE2 ) has been shown to be important in esophageal tumorigenesis.", "output": "prostaglandin E2, PGE2." }, { "input": "We have shown that COX - 2 mediates acid - induced PGE2 production.", "output": "PGE2." }, { "input": "The prostaglandin E synthase ( PGES ) responsible for acid - induced PGE2 production in BE, however, is not known.", "output": "prostaglandin E, PGE2." }, { "input": "We found that microsomal PGES1 ( mPGES1 ), mPGES2, and cytosolic PGES ( cPGES ) were present in FLO EA cells.", "output": "There is no related enetity." }, { "input": "Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA.", "output": "There is no related enetity." }, { "input": "Knockdown of mPGES1 by mPGES1 small interfering RNA ( siRNA ) blocked acid - induced increase in PGE2 production and thymidine incorporation.", "output": "PGE2, thymidine." }, { "input": "Knockdown of NADPH oxidase, NOX5 - S, a variant lacking calcium - binding domains, by NOX5 siRNA significantly inhibited acid - induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production.", "output": "NADPH, calcium, thymidine, PGE2." }, { "input": "Overexpression of NOX5 - S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor kappa B ( NF - kappa B ) in vivo activation reporter plasmid pNF - kappa B - Luc.", "output": "There is no related enetity." }, { "input": "Knockdown of NF - kappa B1 p50 by p50 siRNA significantly decreased acid - induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production.", "output": "thymidine, PGE2." }, { "input": "Two novel NF - kappa B binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter.", "output": "There is no related enetity." }, { "input": "We conclude that mPGES1 mediates acid - induced increase in PGE2 production and cell proliferation.", "output": "PGE2." }, { "input": "Acid - induced mPGES1 expression depends on activation of NOX5 - S and NF - kappa B1 p50.", "output": "There is no related enetity." }, { "input": "Microsomal PGES1 may be a potential target to prevent or treat EA.", "output": "There is no related enetity." }, { "input": "E6AP / UBE3A Ubiquitin Ligase Harbors Two E2 ~ ubiquitin Binding Sites.", "output": "There is no related enetity." }, { "input": "By exploiting ( 125 ) I - polyubiquitin chain formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP / UBE3A for the first time.", "output": "( 125 ) I." }, { "input": "Initial rate studies identify UbcH7 as the cognate E2 carrier protein for E6AP, although related Ubc5 isoforms and the ISG15 - specific UbcH8 paralog also support E6AP with reduced efficacy due to impaired binding and catalytic competence.", "output": "There is no related enetity." }, { "input": "Initial rates of polyubiquitin chain formation displayed hyperbolic kinetics with respect to UbcH7 concentration ( Km = 57. 6 +/- 5. 7 nm and kcat = 0. 032 +/- 0. 001 s ( - 1 ) ) and substrate inhibition above 2 mu m.", "output": "There is no related enetity." }, { "input": "Competitive inhibition by an isosteric UbcH7C86S - ubiquitin oxyester substrate analog ( Ki = 64 +/- 18 nm ) demonstrates that Km reflects intrinsic substrate affinity.", "output": "oxyester." }, { "input": "In contrast, noncompetitive inhibition by a UbcH7C86A product analog ( Ki = 7 +/- 0. 7 mu m ) and substrate inhibition at high concentrations require two functionally distinct E2 ~ ubiquitin substrate binding sites.", "output": "There is no related enetity." }, { "input": "The kinetics of polyubiquitin chain formation reflect binding at a cryptic Site 1 not previously recognized that catalyzes E6AP ~ ubiquitin thioester formation.", "output": "thioester." }, { "input": "Subsequent binding of E2 ~ ubiquitin at the canonical Site 2 present in the extant crystal structure is responsible for polyubiquitin chain elongation.", "output": "There is no related enetity." }, { "input": "Other rate studies show that the conserved - 4 Phe ( 849 ) residue is required for polyubiquitin chain formation rather than target protein conjugation as originally suggested.", "output": "Phe." }, { "input": "The present studies unambiguously preclude earlier models for the mechanism of Hect domain - catalyzed conjugation through the canonical binding site suggested by the crystal structure and define a novel two - step mechanism for formation of the polyubiquitin degradation signal.", "output": "There is no related enetity." }, { "input": "Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone.", "output": "oxycodone." }, { "input": "Perturbations of the expression of transporters and drug - metabolizing enzymes ( DMEs ) by opioids can be the locus of deleterious drug - drug interactions ( DDIs ).", "output": "There is no related enetity." }, { "input": "Many transporters and DMEs are regulated by xenobiotic receptors [ XRs; e. g., pregnane X receptor ( PXR ), constitutive androstane receptor ( CAR ), and Aryl hydrocarbon receptor ( AhR ) ]; however, there is a paucity of information regarding the influence of opioids on XRs.", "output": "androstane, Aryl hydrocarbon." }, { "input": "The objective of this study was to determine the influence of oxycodone administration ( 15 mg / kg intraperitoneally twice daily for 8 days ) on liver expression of XRs, transporters, and DMEs in rats.", "output": "oxycodone." }, { "input": "Microarray, quantitative real - time polymerase chain reaction and immunoblotting analyses were used to identify significantly regulated genes.", "output": "There is no related enetity." }, { "input": "Three XRs ( e. g., PXR, CAR, and AhR ), 27 transporters ( e. g., ABCB1 and SLC22A8 ), and 19 DMEs ( e. g., CYP2B2 and CYP3A1 ) were regulated ( P < 0. 05 ) with fold changes ranging from - 46. 3 to 17. 1.", "output": "There is no related enetity." }, { "input": "Using MetaCore ( computational platform ), we identified a unique gene - network of transporters and DMEs assembled around PXR, CAR, and AhR.", "output": "There is no related enetity." }, { "input": "Therefore, a series of transactivation / translocation assays were conducted to determine whether the observed changes of transporters / DMEs are mediated by direct activation of PXR, CAR, or AhR by oxycodone or its major metabolites ( noroxycodone and oxymorphone ).", "output": "oxycodone, noroxycodone, oxymorphone." }, { "input": "Neither oxycodone nor its metabolites activated PXR, CAR, or AhR.", "output": "oxycodone." }, { "input": "Taken together, these findings identify a signature hepatic gene - network associated with repeated oxycodone administration in rats and demonstrate that oxycodone alters the expression of many transporters and DMEs ( without direct activation of PXR, CAR, and AhR ), which could lead to undesirable DDIs after coadministration of substrates of these transporters / DMEs with oxycodone.", "output": "oxycodone, oxycodone, oxycodone." }, { "input": "Conformation - dependent conductance through a molecular break junction.", "output": "There is no related enetity." }, { "input": "Ab initio molecular dynamics simulations have been performed of a gold - 1, 4 - benzenedithiol ( BDT ) - gold nanojunction under mechanical stress.", "output": "gold - 1 , 4 - benzenedithiol, BDT." }, { "input": "For three different pulling rates between 10 and 40 m s ( - 1 ), it is found that the nanowire always ruptures between the second and third Au atom from the thiol sulfur.", "output": "Au, thiol sulfur." }, { "input": "Larger rupture forces and longer extensions are required at higher pulling rates and vice versa.", "output": "There is no related enetity." }, { "input": "The electrical conductance was calculated along a pulling trajectory using the DFT - NEGF method to study the effect of thermal and stress - induced structural changes on the electrical transport properties.", "output": "There is no related enetity." }, { "input": "While the mechanically induced stretching of the junction is seen to lower the time - averaged conductance, thermal conformational changes are capable of altering the conductance by one order of magnitude.", "output": "There is no related enetity." }, { "input": "No single geometric quantity could be identified as the main contributor to the conductance fluctuations.", "output": "There is no related enetity." }, { "input": "Small modulations, however, can be explained in terms of C = C double bond vibrations in the BDT molecule.", "output": "C = C, BDT." }, { "input": "The dependence of the conductance on different geometric variables has further been investigated systematically by performing constrained geometry optimizations along a number of angle and dihedral coordinates.", "output": "There is no related enetity." }, { "input": "The largest changes in the conductance are observed when the Au - S - C angle and the Au - S - C - C dihedral are simultaneously constrained.", "output": "Au - S - C, Au - S - C - C." }, { "input": "A practical and scalable manufacturing process for an anti - fungal agent, Nikkomycin Z.", "output": "Nikkomycin Z." }, { "input": "A scalable and reliable manufacturing process for Nikkomycin Z HCl on a 170 g scale has been developed and optimized.", "output": "Nikkomycin Z, HCl." }, { "input": "The process is characterized by a 2. 3 g / L fermentation yield, 79 % purification yield, and > 98 % relative purity of the final product.", "output": "There is no related enetity." }, { "input": "This method is suitable for further scale up and cGMP production.", "output": "cGMP." }, { "input": "The Streptomyces tendae Delta NikQ strain developed during the course of this study is superior to any previously reported strain in terms of higher yield and purity of Nikkomycin Z.", "output": "Nikkomycin Z." }, { "input": "Graphene - Bonded and - Encapsulated Si Nanoparticles for Lithium Ion Battery Anodes.", "output": "Graphene, Si, Lithium." }, { "input": "Silicon ( Si ) has been considered a very promising anode material for lithium ion batteries due to its high theoretical capacity.", "output": "Silicon, Si, lithium." }, { "input": "However, high - capacity Si nanoparticles usually suffer from low electronic conductivity, large volume change, and severe aggregation problems during lithiation and delithiation.", "output": "Si." }, { "input": "In this paper, a unique nanostructured anode with Si nanoparticles bonded and wrapped by graphene is synthesized by a one - step aerosol spraying of surface - modified Si nanoparticles and graphene oxide suspension.", "output": "Si, graphene, Si, graphene oxide." }, { "input": "The functional groups on the surface of Si nanoparticles ( 50 - 100 nm ) not only react with graphene oxide and bind Si nanoparticles to the graphene oxide shell, but also prevent Si nanoparticles from aggregation, thus contributing to a uniform Si suspension.", "output": "Si, graphene oxide, Si, graphene oxide, Si, Si." }, { "input": "A homogeneous graphene - encapsulated Si nanoparticle morphology forms during the aerosol spraying process.", "output": "graphene, Si." }, { "input": "The open - ended graphene shell with defects allows fast electrochemical lithiation / delithiation, and the void space inside the graphene shell accompanied by its strong mechanical strength can effectively accommodate the volume expansion of Si upon lithiation.", "output": "graphene, graphene, Si." }, { "input": "The graphene shell provides good electronic conductivity for Si nanoparticles and prevents them from aggregating during charge / discharge cycles.", "output": "graphene, Si." }, { "input": "The functionalized Si encapsulated by graphene sample exhibits a capacity of 2250 mAh g ( - 1 ) ( based on the total mass of graphene and Si ) at 0. 1C and 1000 mAh g ( - 1 ) at 10C, and retains 85 % of its initial capacity even after 120 charge / discharge cycles.", "output": "Si, graphene, graphene, Si." }, { "input": "The exceptional performance of graphene - encapsulated Si anodes combined with the scalable and one - step aerosol synthesis technique makes this material very promising for lithium ion batteries.", "output": "graphene, Si, lithium." }, { "input": "Associations of gender and age with the reporting of drug - induced hepatic failure: data from the VigiBase (TM).", "output": "There is no related enetity." }, { "input": "Patient gender and age are considered to be the risk factors for developing drug - induced liver injury ( DILI ).", "output": "There is no related enetity." }, { "input": "The aim of this study was to analyze gender and age differences in reporting of drug - induced hepatic failure ( HF ) to the VigiBase (TM).", "output": "There is no related enetity." }, { "input": "VigiBase (TM) was screened for the HF reports submitted from 2000 to 2009.", "output": "There is no related enetity." }, { "input": "The information retrieved referred to the suspected drug, age, gender, and a reporting country.", "output": "There is no related enetity." }, { "input": "Variables were examined by using descriptive statistics and the binomial test.", "output": "There is no related enetity." }, { "input": "During the 10 - year period there were in total 6, 370 HF reports from 38 countries.", "output": "There is no related enetity." }, { "input": "After the exclusion of cases with missing gender data ( 379 cases ), females counted for 54. 03 %.", "output": "There is no related enetity." }, { "input": "The largest portion of HF cases referred to age < 55 ( 42. 57 % ) with female predominance ( 56. 81 % ), whereas age >= 55 ( 32. 57 % ) showed almost even gender distribution.", "output": "There is no related enetity." }, { "input": "Overall, there were 941 different drugs or their combinations reported.", "output": "There is no related enetity." }, { "input": "Females significantly predominated in HF cases associated with analgesics, antiepileptics, antiinflamatory and antirheumatic drugs, psychoanaleptics, antibacterials for systemic use, and antidiabetic drugs.", "output": "There is no related enetity." }, { "input": "Males were significantly overrepresented in HF cases associated with antivirals for systemic use.", "output": "There is no related enetity." }, { "input": "Differences between genders and / or age groups in the reporting of drug - induced HF depend on drug and / or drug class but may be influenced by multiple factors.", "output": "There is no related enetity." }, { "input": "Loading and distribution of a model small molecule drug in poly ( N - isopropylacrylamide ) brushes: a neutron reflectometry and AFM study.", "output": "poly ( N - isopropylacrylamide )." }, { "input": "The structure of a hydrated poly ( N - isopropylacrylamide ) brush loaded with 5 vol % Isoniazid is studied as a function of temperature using neutron reflectometry ( NR ) and atomic force microscopy ( AFM ).", "output": "hydrated poly ( N - isopropylacrylamide ), Isoniazid." }, { "input": "NR measurements show that Isoniazid increases the thickness of the brush before, during and after the polymer collapse, and it is retained inside the brush at all measured temperatures.", "output": "Isoniazid." }, { "input": "The Isoniazid concentration in the expanded brush is ~ 14 % higher than in the bulk solution, and the concentration nearly doubles in the collapsed polymer, suggesting stronger binding between Isoniazid and the polymer compared to water, even at temperatures below the lower critical solution temperature ( LCST ) where the polymer is hydrophilic.", "output": "Isoniazid, Isoniazid." }, { "input": "Typically, additives that bind strongly to the polymer backbone and increase the hydrophilicity of the polymer will delay the onset of the LCST, which is suggested by AFM and NR measurements.", "output": "There is no related enetity." }, { "input": "The extent of small - molecule loading and distribution throughout a thermo - responsive polymer brush, such as pNIPAAm, will have important consequences for applications such as drug delivery and gating.", "output": "pNIPAAm." }, { "input": "Ca ( 2 + ) - calmodulin interacts with DdCAD - 1 and promotes DdCAD - 1 transport by contractile vacuoles in Dictyostelium cells.", "output": "Ca ( 2 + )." }, { "input": "The Ca ( 2 + ) - dependent cell - cell adhesion molecule DdCAD - 1, encoded by the cadA gene of Dictyostelium discoideum, is synthesized at the onset of development as a soluble protein and then transported to the plasma membrane by contractile vacuoles.", "output": "Ca ( 2 + )." }, { "input": "Calmodulin associates with contractile vacuoles in a Ca ( 2 + ) - dependent manner, and co - localizes with DdCAD - 1 on the surface of contractile vacuoles.", "output": "Ca ( 2 + )." }, { "input": "Bioinformatics analysis revealed multiple calmodulin - binding motifs in DdCAD - 1.", "output": "There is no related enetity." }, { "input": "Co - immunoprecipitation and pull - down studies showed that only Ca ( 2 + ) - bound calmodulin was able to bind DdCAD - 1.", "output": "Ca ( 2 + )." }, { "input": "Structural integrity of DdCAD - 1, but not the native conformation, was required for its interaction with calmodulin.", "output": "There is no related enetity." }, { "input": "To investigate the role of calmodulin in the import of DdCAD - 1 into contractile vacuoles, an in vitro import assay consisting of contractile vacuoles derived from cadA ( - ) cells and recombinant proteins was employed.", "output": "There is no related enetity." }, { "input": "Prior stripping of the bound calmodulin from contractile vacuoles by EGTA impaired import of DdCAD - 1, which was restored by addition of exogenous calmodulin.", "output": "There is no related enetity." }, { "input": "The calmodulin antagonists W - 7 and compound 48 / 80 blocked the binding of calmodulin onto stripped contractile vacuoles, and inhibited the import of DdCAD - 1.", "output": "There is no related enetity." }, { "input": "Together, the data show that calmodulin forms a complex with DdCAD - 1 and promotes the docking and import of DdCAD - 1 into contractile vacuoles.", "output": "There is no related enetity." }, { "input": "STRUCTURED DIGITAL ABSTRACT: CaM physically interacts with DdCAD - 1 by pull down ( View Interaction: 1, 2 ) DdCAD - 1 binds to CaM by far western blotting ( View interaction ) DdCAD - 1 physically interacts with CaM by anti bait coimmunoprecipitation ( View interaction ).", "output": "There is no related enetity." }, { "input": "Double C - H bond activation of hydrocarbons by a gas phase neutral oxide cluster: the importance of spin state.", "output": "C - H, hydrocarbons, oxide." }, { "input": "The neutral cluster V2O5 is generated and detected in the gas phase.", "output": "V2O5." }, { "input": "Its reactivity toward butane is studied both experimentally and theoretically.", "output": "There is no related enetity." }, { "input": "Experimental results show clearly that neutral V2O5 can react with n - butane ( C4H10 ) to generate V2O5H2, indicating double hydrogen atom transfer from C4H10 to V2O5 to produce C4H8.", "output": "V2O5, n - butane, C4H10, V2O5H2, hydrogen, C4H10, V2O5, C4H8." }, { "input": "Further experimental evidence indicates that V2O5 is only partially reacted even at very high concentrations of C4H10.", "output": "V2O5, C4H10." }, { "input": "Density functional theory ( DFT ) studies show that the lowest energy triplet state of V2O5 is reactive toward C4H10, whereas the ground state singlet V2O5 is inert.", "output": "V2O5, C4H10, V2O5." }, { "input": "Calculated results are in agreement with experimental findings, and a detailed reaction mechanism is provided.", "output": "There is no related enetity." }, { "input": "Reactions of V2O5H2 with several oxidants are also studied theoretically to find a path to regenerate V2O5.", "output": "V2O5H2, V2O5." }, { "input": "Neutral ( 3 ) V2O5 can also react with C2H6 to form V2O5H2 and C2H4, but only as a minor reaction channel; the major product is the adsorption product V2O5 ( C2H6 ).", "output": "V2O5, C2H6, V2O5H2, C2H4, V2O5, C2H6." }, { "input": "Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z - ligustilide and Radix angelica sinensis via promoter CpG demethylation.", "output": "Z - ligustilide." }, { "input": "Cancer development has been linked to epigenetic modifications of cancer oncogenes and tumor suppressor genes; in advanced metastatic cancers, severe epigenetic modifications are present.", "output": "There is no related enetity." }, { "input": "We previously demonstrated that the progression of prostate tumors in TRAMP mice is associated with methylation silencing of the Nrf2 promoter and a reduced level of transcription of Nrf2 and Nrf2 target genes.", "output": "There is no related enetity." }, { "input": "Radix Angelicae Sinensis ( RAS; Danggui ) is a medicinal herb and health food supplement that has been widely used in Asia for centuries.", "output": "There is no related enetity." }, { "input": "Z - Ligustilide ( Lig ) is one of the bioactive components of RAS.", "output": "Z - Ligustilide, Lig." }, { "input": "We investigated the potential of Lig and RAS to restore Nrf2 gene expression through epigenetic modification in TRAMP C1 cells.", "output": "Lig." }, { "input": "Lig and RAS induced the mRNA and protein expression of endogenous Nrf2 and Nrf2 downstream target genes, such as HO - 1, NQO1, and UGT1A1.", "output": "Lig." }, { "input": "Bisulfite genomic sequencing revealed that Lig and RAS treatment decreased the level of methylation of the first five CpGs of the Nrf2 promoter.", "output": "Bisulfite, Lig." }, { "input": "A methylation DNA immunoprecipitation assay demonstrated that Lig and RAS significantly decreased the relative amount of methylated DNA in the Nrf2 gene promoter region.", "output": "Lig." }, { "input": "Lig and RAS also inhibited DNA methyltransferase activity in vitro.", "output": "Lig." }, { "input": "Collectively, these results suggest that Lig and RAS are able to demethylate the Nrf2 promoter CpGs, resulting in the re - expression of Nrf2 and Nrf2 target genes.", "output": "Lig." }, { "input": "Epigenetic modifications of genes, including Nrf2, may therefore contribute to the overall health benefits of RAS, including the anticancer effect of RAS and its bioactive component, Lig.", "output": "Lig." }, { "input": "Probing the Photoisomerization of CHBr3 and CHI3 in Solution with Transient Vibrational and Electronic Spectroscopy.", "output": "CHBr3, CHI3." }, { "input": "Transient infrared absorption spectroscopy monitors condensed - phase photodissociation dynamics of 30 mM CHBr3 and 50 mM CHI3 in liquid CCl4.", "output": "CHBr3, CHI3, CCl4." }, { "input": "The experiments have picosecond time resolution and monitor the C - H stretch region of both the parent polyhalomethanes and their photolytically generated isomers.", "output": "C, H, polyhalomethanes." }, { "input": "The C - H stretching transitions of these isomers, in which the emergent halogen atom returns to form a C - X - X bonding motif, appear about 9 ps after photolysis for iso - CHBr2 - Br and in about 46 ps for iso - CHI2 - I.", "output": "C, H, halogen, C, CHBr2, Br, CHI2, I." }, { "input": "These time scales are consistent with, but differ from, the time evolution of the transient electronic absorption spectra of the same samples, highlighting the subtle differences between monitoring the vibrational and electronic chromophores.", "output": "There is no related enetity." }, { "input": "The specificity of using vibrational transitions to track condensed - phase reaction dynamics permits reassessment of the transient electronic spectrum of photolysis in neat CHBr3, which has an additional prompt feature near 400 nm.", "output": "CHBr3." }, { "input": "Calculations show that this feature, which arises from a precursor to the isomer, is a charge - transfer transition of a contact pair between the nascent Br fragment and a nearby CHBr3 molecule.", "output": "Br, CHBr3." }, { "input": "Dilution and solvent studies show that transition is independent of the solvent.", "output": "There is no related enetity." }, { "input": "The iso - CHBr2 - Br transition wavelength, however, shifts over the range of 400 to 510 nm depending on the solvent.", "output": "CHBr2, Br." }, { "input": "Time - dependent density functional calculations faithfully reproduce these trends.", "output": "There is no related enetity." }, { "input": "Density Functional Study of Organocatalytic Cross - Aldol Reactions between Two Aliphatic Aldehydes: Insight into Their Functional Differentiation and Origins of Chemo - and Stereoselectivities.", "output": "Aliphatic Aldehydes." }, { "input": "The chemo -, diastereo -, and enantioselectivities in proline and axially chiral amino sulfonamide - catalyzed direct aldol reactions between two enolizable aldehydes with different electronic nature have been studied with the aid of density functional theory ( DFT ) method.", "output": "proline, amino sulfonamide, aldehydes." }, { "input": "The potential energy profiles for the enamine formation between each aliphatic aldehyde and the catalyst confirm that two subject catalysts can successfully differentiate between 3 - methylbutanal as an enamine component and alpha - chloroaldehydes as a carbonyl component.", "output": "enamine, aliphatic aldehyde, 3 - methylbutanal, enamine, alpha - chloroaldehydes, carbonyl." }, { "input": "Transition states associated with the stereochemistry - determining C - C bond - forming step with the enamine intermediate addition to the aldehyde acceptor for proline and chiral amino sulfonamide - promoted aldol reactions are reported.", "output": "C, C, enamine, aldehyde, proline, amino sulfonamide." }, { "input": "DFT calculations not only provide a good explanation for the formation of the sole cross - aldol product between two aliphatic aldehydes both bearing alpha - methylene protons but also well reproduce the opposite syn vs anti diastereoselectivities in the chiral amino sulfonamide and proline - catalyzed aldol reactions.", "output": "aliphatic aldehydes, alpha - methylene, amino sulfonamide, proline." }, { "input": "On the generation of the hydrated electron during the sonolysis of aqueous solutions.", "output": "There is no related enetity." }, { "input": "The formation of the hydrated electron through the secondary reaction, H + OH ( - ) --> H ( 2 ) O + e ( aq ), has been examined in the sonolysis of argon - saturated aqueous solutions at an ultrasound frequency of 355 kHz.", "output": "H, OH ( - ), H ( 2 ) O, argon." }, { "input": "The detection of the hydrated electron was achieved by measuring its reaction with the one - electron acceptors Fe ( CN ) ( 6 ) ( 3 - ) and methyl viologen.", "output": "Fe ( CN ) ( 6 ) ( 3 - ), methyl." }, { "input": "The results obtained indicate that hydrated electrons are produced predominately at the bubble / aqueous solution interface at comparatively high local concentrations, estimated to be > 1. 5 x 10 ( - 3 ) M.", "output": "There is no related enetity." }, { "input": "The half life of the hydrated electron under such conditions is estimated to be < 60 ns.", "output": "There is no related enetity." }, { "input": "Phenol formation in gamma radiolysis of aqueous benzene solution with sodium hypochlorite.", "output": "Phenol, benzene, sodium hypochlorite." }, { "input": "Phenol formation by gamma radiolysis of an aqueous benzene solution containing sodium hypochlorite is reported.", "output": "Phenol, benzene, sodium hypochlorite." }, { "input": "The phenol formation in a benzene solution containing sodium hypochlorite irradiated with ( 60 ) Co gamma - rays is about six times higher than that without sodium hypochlorite.", "output": "benzene, sodium hypochlorite, sodium hypochlorite." }, { "input": "Ten micromolar sodium hypochlorite enhanced the formation of phenol up to a total dose of 6 Gy.", "output": "sodium hypochlorite, phenol." }, { "input": "Above 6 Gy in solutions containing sodium hypochlorite, the rate of phenol yield sharply decreased and was essentially the same as that without sodium hypochlorite.", "output": "sodium hypochlorite, phenol, sodium hypochlorite." }, { "input": "The yield of phenol with sodium hypochlorite is 0. 89 mu mol J ( - 1 ) and is larger than the sum of yield for the radicals and reactive oxygen species by water radiolysis such as * OH, e ( - ), H, H2, and H2O2.", "output": "phenol, sodium hypochlorite, oxygen, * OH, H, H2, H2O2." }, { "input": "The formation of phenol with sodium hypochlorite was reduced by NaCl.", "output": "phenol, sodium hypochlorite, NaCl." }, { "input": "Results suggest that the radiolytic formation of phenol in a benzene solution with sodium hypochlorite relates to the reaction process involving chlorine atoms.", "output": "phenol, benzene, sodium hypochlorite, chlorine." }, { "input": "Sodium hypochlorite can be applied as a sensitizer for a benzene chemical dosimetry system.", "output": "Sodium hypochlorite, benzene." }, { "input": "The lower limit of dose detection calculated from the detection limit of phenol and the G value of phenol was estimated to be 1 x 10 ( - 3 ) Gy.", "output": "phenol, phenol." }, { "input": "Analysis and refactoring of the A - 74528 biosynthetic pathway.", "output": "A - 74528." }, { "input": "A - 74528 is a C30 polyketide natural product that functions as an inhibitor of 2 ', 5 ' - oligoadenylate phosphodiesterase ( 2 ' - PDE ), a key regulatory enzyme of the interferon pathway.", "output": "A - 74528, C30 polyketide." }, { "input": "Modulation of 2 ' - PDE represents a unique therapeutic approach for regulating viral infections.", "output": "There is no related enetity." }, { "input": "The gene cluster responsible for biosynthesis of A - 74528 yields minute amounts of this natural product together with considerably larger quantities of a structurally dissimilar C30 cytotoxic agent, fredericamycin.", "output": "A - 74528, fredericamycin." }, { "input": "Through construction and analysis of a series of knockout mutants, we identified the genes necessary for A - 74528 biosynthesis.", "output": "A - 74528." }, { "input": "Remarkably, the formation of six stereocenters and the regiospecific formation of six rings in A - 74528 appear to be catalyzed by only two tailoring enzymes, a cyclase and an oxygenase, in addition to the core polyketide synthase.", "output": "A - 74528." }, { "input": "The inferred pathway was genetically refactored in a heterologous host, Streptomyces coelicolor CH999, to produce 3 mg / L A - 74528 in the absence of fredericamycin.", "output": "A - 74528, fredericamycin." }, { "input": "Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction.", "output": "There is no related enetity." }, { "input": "It is likely that mesenchymal stem cells will find use in many autologous regenerative therapies.", "output": "There is no related enetity." }, { "input": "However, our ability to control cell stem growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture.", "output": "There is no related enetity." }, { "input": "Also, the large number of cells required to be clinically useful is currently a hurdle to using materials - based ( stiffness, chemistry, nanotopography, etc. ) culture substrates.", "output": "There is no related enetity." }, { "input": "Here we give a first demonstration of using nanoscale sinusoidal mechanotransductive protocols ( 10 - 14 nm displacements at 1 kHz frequency ), \" nanokicking \", to promote osteoblastogenesis in human mesenchymal stem cell cultures.", "output": "There is no related enetity." }, { "input": "On the basis of application of the reverse piezo effect, we use interferometry to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used.", "output": "There is no related enetity." }, { "input": "A combination of immunofluorescence, PCR, and microarray has then been used to demonstrate osteoblastogenesis, and the arrays implicate RhoA as central to osteoblastic differentiation in agreement with materials - based strategies.", "output": "There is no related enetity." }, { "input": "We validate this with pharmacological inhibition of RhoA kinase.", "output": "There is no related enetity." }, { "input": "It is easy to envisage such stimulation protocols being up - scaled to form large - scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol.", "output": "There is no related enetity." }, { "input": "The influence of clan structure on the genetic variation in a single Ghanaian village.", "output": "There is no related enetity." }, { "input": "Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure.", "output": "There is no related enetity." }, { "input": "To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations.", "output": "There is no related enetity." }, { "input": "In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north - eastern Ghana.", "output": "There is no related enetity." }, { "input": "We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village.", "output": "There is no related enetity." }, { "input": "We also observed a deep male substructure within one of the clans in this village.", "output": "There is no related enetity." }, { "input": "Among all males, we observed only three Y - single - nucleotide polymorphism ( SNP ) haplogroups: E1b1a * - M2, E1b1a7a * - U174 and E1b1a8a * - U209, P277, P278.", "output": "There is no related enetity." }, { "input": "In contrast to the marked Y - chromosomal substructure, mitochondrial DNA HVS - 1 sequence variation and autosomal short - tandem repeats variation patterns indicate high genetic diversities and a virtually random female - mediated gene flow among clans.", "output": "There is no related enetity." }, { "input": "On the extreme micro - geographical scale of this single Bimoba village, correspondence between the Y - chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure.", "output": "There is no related enetity." }, { "input": "If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale.", "output": "There is no related enetity." }, { "input": "Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large. European Journal of Human Genetics advance online publication, 27 February 2013; doi: 10. 1038 / ejhg. 2013. 12.", "output": "There is no related enetity." }, { "input": "Regulation of Translation Initiation under Biotic and Abiotic Stresses.", "output": "There is no related enetity." }, { "input": "Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to.", "output": "There is no related enetity." }, { "input": "Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations.", "output": "There is no related enetity." }, { "input": "Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response.", "output": "There is no related enetity." }, { "input": "In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery.", "output": "There is no related enetity." }, { "input": "Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation.", "output": "There is no related enetity." }, { "input": "In others, the mechanisms leading to the control of translation are viral - or stress - specific.", "output": "There is no related enetity." }, { "input": "In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants.", "output": "There is no related enetity." }, { "input": "In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.", "output": "There is no related enetity." }, { "input": "Low temperature solution - processed high performance photodiode based on Si - ZnO core - shell structure.", "output": "Si, ZnO." }, { "input": "Radial heterojunction photodiodes based on a silicon nanowire arrays ( SiNWs ) - zinc oxide ( ZnO ) core - shell structure is demonstrated in this report.", "output": "silicon, zinc oxide, ZnO." }, { "input": "The heterojunction can be constructed by spin - coating ZnO nanoparticles onto SiNWs and a low temperature post - annealing process ( < 270 degrees C ).", "output": "ZnO." }, { "input": "The photodiode displays typical diode rectifying characteristics with an ideality factor of as low as 1. 28, and shows an excellent photoresponse in both visible and near infrared regions in which a peak value of 0. 54 A / W at zero bias was attained.", "output": "There is no related enetity." }, { "input": "The sensitivity is superior to that of previously reported devices fabricated with vacuum - deposition methods.", "output": "There is no related enetity." }, { "input": "In contrast, the planar silicon - ZnO junction only displays the peak photoresponsivity of 0. 34 A / W.", "output": "silicon, ZnO." }, { "input": "The superior performance of radial junction is ascribed to the highlight - harvesting capability, large interfacial area and efficient charge carrier collection arising from the core ( SiNWs ) - shell ( ZnO ) structure.", "output": "ZnO." }, { "input": "Here, high temperature processes are dispensable by using facile solution - processed techniques, which avoid thermal minority lifetime degradation of silicon and simplify the fabrication process of the photodiodes.", "output": "silicon." }, { "input": "In vivo evaluation of the interaction between titanium dioxide nanoparticle and rat liver DNA.", "output": "titanium dioxide." }, { "input": "Titanium dioxide nanoparticles ( TiO2 NPs ) are massively produced and widely used in daily life, which may pose potential risk to human health via uncharacterized interaction between DNAs.", "output": "Titanium dioxide, TiO2." }, { "input": "This research aims to examine the interaction between DNA and three types of TiO2 NPs of different sizes and crystallines.", "output": "TiO2." }, { "input": "The interaction between TiO2 NPs and liver DNA molecules obtained from Sprague - Dawley rats was systematically evaluated in vivo using atomic force microscopy, transmission electron microscopy, various spectroscopic techniques and gel electrophoresis.", "output": "TiO2." }, { "input": "We found that TiO2 NPs ( diameter < 25 nm and < 100 nm ) in anatase crystalline can covalently interact with liver DNA by either inserting itself in between DNA base pairs or binding to DNA nucleotide via P - O - Ti - O bond.", "output": "TiO2, nucleotide, O - Ti - O." }, { "input": "Such interaction may not be NP size - dependent but may be crystalline phase - dependent, because such interaction did not occur in rutile crystal phase, in which the DNA damage was potentially caused by reactive oxygen species.", "output": "oxygen." }, { "input": "A population - based study of dosing and persistence with anti - dementia medications.", "output": "There is no related enetity." }, { "input": "PURPOSE: Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer ' s disease ( AD ).", "output": "memantine." }, { "input": "This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the ' real world ' ( outside the clinical trial setting ).", "output": "There is no related enetity." }, { "input": "METHODS: The Health Service Executive - Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1. 6 million people.", "output": "There is no related enetity." }, { "input": "Patients aged > 70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study.", "output": "donepezil, rivastigmine, galantamine, memantine." }, { "input": "Rates of dose - maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations.", "output": "There is no related enetity." }, { "input": "Non - persistence was defined by a gap in prescribing of more than 63 consecutive days.", "output": "There is no related enetity." }, { "input": "Predictors of dose - maximisation and non - persistence were also analysed.", "output": "There is no related enetity." }, { "input": "RESULTS: Between January 2006 and December 2010, 20, 729 patients aged > 70 years received a prescription for an AD medication.", "output": "There is no related enetity." }, { "input": "Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two - thirds of patients.", "output": "donepezil, memantine." }, { "input": "Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years ( 2010 vs. 2007 ).", "output": "donepezil, memantine." }, { "input": "Rates of non - persistence were 30. 1 % at 6 months and 43. 8 % at 12 months.", "output": "There is no related enetity." }, { "input": "Older age [ 75 + vs. < 75 years; hazards ratio ( HR ) 1. 16, 95 % confidence interval ( CI ) 1. 06 - 1. 27 ] and drug type ( rivastigmine vs. donepezil; HR 1. 15, 95 % CI 1. 03 - 1. 27 ) increased the risk of non - persistence.", "output": "rivastigmine, donepezil." }, { "input": "Non - persistence was lower for those commencing therapy in more recent years ( 2010 vs. 2007; HR 0. 81, 95 % CI 0. 73 - 0. 89, p < 0. 001 ) and for those on multiple anti - dementia medications ( HR 0. 59, 95 % CI 0. 54 - 0. 65, p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Persistence was significantly higher when memantine was co - prescribed with donepezil ( p < 0. 0001 ).", "output": "memantine, donepezil." }, { "input": "CONCLUSION: Future studies should explore the reasons underlying non - persistence and failure to maintain dose - maximisation in patients on AD medications.", "output": "There is no related enetity." }, { "input": "There may be scope to improve the dosing and persistence with these medications in the community.", "output": "There is no related enetity." }, { "input": "Microfluidic oxygen imaging using integrated optical sensor layers and a color camera.", "output": "oxygen." }, { "input": "In this work we present a high resolution oxygen imaging approach, which can be used to study 2D oxygen distribution inside microfluidic environments.", "output": "oxygen, oxygen." }, { "input": "The presented setup comprises a fabrication process of microfluidic chips with integrated luminescent sensing films combined with referenced oxygen imaging applying a color CCD - camera.", "output": "oxygen." }, { "input": "Enhancement of the sensor performance was achieved by applying the principle of light harvesting.", "output": "There is no related enetity." }, { "input": "This principle enabled ratiometric imaging employing the red and the green channel of a color CCD - camera.", "output": "There is no related enetity." }, { "input": "The oxygen sensitive emission of platinum ( ii ) - 5, 10, 15, 20 - tetrakis - ( 2, 3, 4, 5, 6 - pentafluorphenyl ) - porphyrin ( PtTFPP ) was detected by the red channel, while the emission of a reference dye was detected by the green channel.", "output": "oxygen, platinum ( ii ) - 5 , 10 , 15 , 20 - tetrakis - ( 2 , 3 , 4 , 5 , 6 - pentafluorphenyl ) - porphyrin, PtTFPP." }, { "input": "This measurement setup allowed for accurate real - time 2D oxygen imaging with superior quality compared to intensity imaging.", "output": "oxygen." }, { "input": "The sensor films were subsequently used to measure the respiratory activity of human cell cultures ( HeLa carcinoma cells and normal human dermal fibroblasts ) in a microfluidic system.", "output": "There is no related enetity." }, { "input": "The sensor setup is well suited for different applications from spatially and temporally resolving oxygen concentration inside microfluidic channels to parallelization of oxygen measurements and paves the way to novel cell based assays, e. g. in tissue engineering, tumor biology and hypoxia reperfusion phenomena.", "output": "oxygen, oxygen." }, { "input": "Emtricitabine / tenofovir disoproxil fumarate: a review of its use in HIV - 1 pre - exposure prophylaxis.", "output": "Emtricitabine, tenofovir disoproxil fumarate." }, { "input": "The fixed - dose combination of emtricitabine ( FTC ) 200 mg and tenofovir disoproxil fumarate ( TDF ) 300 mg ( Truvada ( (R) ) ), administered orally once daily, is widely used as part of first - line regimens for the treatment of HIV - 1 infection.", "output": "emtricitabine, FTC, tenofovir disoproxil fumarate, TDF, Truvada." }, { "input": "Recently, once - daily administration of FTC / TDF was approved in the USA for pre - exposure prophylaxis in conjunction with safer sex practices to reduce the risk of sexually acquired HIV - 1 in high - risk adults who are not infected.", "output": "FTC, TDF." }, { "input": "To date, results of four large, randomized, double - blind, placebo - controlled, multicentre trials with FTC / TDF as pre - exposure prophylaxis have been published.", "output": "FTC, TDF." }, { "input": "Three studies showed statistically significant reductions in the number of individuals with emergent HIV - 1 infection when FTC / TDF was compared with placebo over the =~ 1 - to 2 - year study periods.", "output": "FTC, TDF." }, { "input": "Efficacy ( i. e. risk reduction relative to placebo ) was 44 % in the iPrEx trial in men who have sex with men, 75 % in the Partners PrEP study in heterosexual HIV - 1 - serodiscordant couples and 62 % in the TDF2 trial in heterosexual men and women.", "output": "There is no related enetity." }, { "input": "The fourth study ( FEM - PrEP ) in heterosexual women did not show a statistically significant difference between FTC / TDF and placebo, although low adherence rates reported in this trial may have been a factor.", "output": "FTC, TDF." }, { "input": "No unexpected adverse events were reported in the trials.", "output": "There is no related enetity." }, { "input": "However, since pre - exposure prophylaxis involves long - term administration of drugs to healthy individuals, it is important to monitor the long - term safety of FTC / TDF ( e. g. renal function, bone mineral density ) in this setting.", "output": "FTC, TDF." }, { "input": "Other notable considerations include adherence, cost and the potential for development of drug resistance.", "output": "There is no related enetity." }, { "input": "Interim guidelines are available for prescribing FTC / TDF as pre - exposure prophylaxis.", "output": "FTC, TDF." }, { "input": "If used appropriately in selected high - risk individuals, pre - exposure prophylaxis with FTC / TDF represents an important additional strategy to reduce the spread of HIV - 1 infection, which continues to be a significant global concern.", "output": "FTC, TDF." }, { "input": "Population pharmacokinetic analysis of a nevirapine - based HIV - 1 prevention of mother - to - child transmission program in Uganda to assess the impact of different dosing regimens for newborns.", "output": "nevirapine." }, { "input": "Single - dose nevirapine for mothers and newborns at delivery is the simplest prevention strategy for vertical HIV - 1 transmission and hence widely used in resource - constrained settings.", "output": "nevirapine." }, { "input": "HIV - 1 - positive mothers and newborns received single - dose nevirapine in a prevention of mother - to - child HIV - 1 transmission ( PMTCT ) program in Uganda.", "output": "nevirapine." }, { "input": "In a pharmacokinetic investigation, breast milk and plasma samples of mothers and newborns were collected.", "output": "There is no related enetity." }, { "input": "The nonlinear mixed - effects modeling approach was suitable for analysis ( average: 1. 8 samples / matrix / individual ).", "output": "There is no related enetity." }, { "input": "For describing the nevirapine pharmacokinetics in mothers and newborns, a 1 - compartment model was demonstrated to be sufficient.", "output": "nevirapine." }, { "input": "The plasma - placenta transfer could be quantified, revealing a transfer fraction of 11 % to 25 % ( with a significant influence of time span between maternal nevirapine intake and birth ) and a high transfer rate constant from maternal drug administration.", "output": "nevirapine." }, { "input": "Interindividual variability was moderate between mothers and high between newborns.", "output": "There is no related enetity." }, { "input": "Simulations revealed that newborns born early ( < 1 hour ) after maternal nevirapine intake would benefit from a 3 - fold higher nevirapine dosage ( 6 mg / kg ) after birth for analogous protective plasma concentrations over the first 2 weeks.", "output": "nevirapine, nevirapine." }, { "input": "In contrast, postnatal nevirapine dosage seemed to be dispensable for newborns born late ( > 24 hours ) after maternal nevirapine intake.", "output": "nevirapine, nevirapine." }, { "input": "These dosing recommendations should be evaluated in prospective studies, including additional antiretroviral drugs in accordance with current PMTCT guidelines.", "output": "There is no related enetity." }, { "input": "A study on the effects of pica and iron - deficiency anemia on oxidative stress, antioxidant capacity and trace elements.", "output": "iron." }, { "input": "Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month.", "output": "There is no related enetity." }, { "input": "There are a few studies on serum trace element levels of patients with pica.", "output": "There is no related enetity." }, { "input": "The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron - deficiency anemia ( IDA ).", "output": "iron." }, { "input": "The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet.", "output": "There is no related enetity." }, { "input": "The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls.", "output": "zinc, selenium." }, { "input": "The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group.", "output": "selenium, zinc." }, { "input": "Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group.", "output": "There is no related enetity." }, { "input": "Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group.", "output": "There is no related enetity." }, { "input": "Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress.", "output": "There is no related enetity." }, { "input": "These effects should be kept in mind while managing patients with pica.", "output": "There is no related enetity." }, { "input": "Significance of reductive metabolism in human intestine and quantitative prediction of intestinal first - pass metabolism by cytosolic reductive enzymes.", "output": "There is no related enetity." }, { "input": "The number of new drug candidates that are cleared via non - cytochrome P450 ( P450 ) enzymes has increased.", "output": "There is no related enetity." }, { "input": "However, unlike oxidation by P450, the roles of reductive enzymes are less understood.", "output": "There is no related enetity." }, { "input": "The metabolism in intestine is especially not well known.", "output": "There is no related enetity." }, { "input": "The purposes of this study were to investigate the significance of reductive metabolism in human intestine, and to establish a quantitative prediction method of intestinal first - pass metabolism by cytosolic reductive enzymes, using haloperidol, mebendazole, and ziprasidone.", "output": "haloperidol, mebendazole, ziprasidone." }, { "input": "First, we estimated the metabolic activities for these compounds in intestine and liver using subcellular fractions.", "output": "There is no related enetity." }, { "input": "Metabolic activities were detected in human intestinal cytosol ( HIC ) for all three compounds, and the intrinsic clearance values were higher than those in human liver cytosol for haloperidol and mebendazole.", "output": "haloperidol, mebendazole." }, { "input": "These metabolic activities in HIC were NADPH - and / or NADH - dependent.", "output": "NADPH, NADH." }, { "input": "Furthermore, the metabolic activities for all three compounds in HIC were largely inhibited by menadione, which has been used as a carbonyl reductase ( CBR ) - selective chemical inhibitor.", "output": "menadione, carbonyl." }, { "input": "Therefore, considering subcellular location, cofactor requirement, and chemical inhibition, these compounds might be metabolized by CBRs in human intestine.", "output": "There is no related enetity." }, { "input": "Subsequently, we tried to quantitatively predict intestinal availability ( Fg ) for these compounds using human intestinal S9 ( HIS9 ).", "output": "There is no related enetity." }, { "input": "Our prediction model using apparent permeability of parallel artificial membrane permeability assay and metabolic activities in HIS9 could predict Fg in humans for the three compounds well.", "output": "There is no related enetity." }, { "input": "In conclusion, CBRs might have higher metabolic activities in human intestine than in human liver.", "output": "There is no related enetity." }, { "input": "Furthermore, our prediction method of human Fg using HIS9 is applicable to substrates of cytosolic reductive enzymes.", "output": "There is no related enetity." }, { "input": "Increased glucagon - like peptide - 1 secretion may be involved in antidiabetic effects of ginsenosides.", "output": "ginsenosides." }, { "input": "Panax ginseng is one of the most popular herbal remedies.", "output": "There is no related enetity." }, { "input": "Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood.", "output": "Ginsenosides." }, { "input": "Glucagon - like peptide - 1 ( GLP1 ) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals.", "output": "glucose." }, { "input": "The aim of this study was to investigate whether ginseng total saponins ( GTS ) exerts its antidiabetic effects via modulating GLP1 release.", "output": "saponins." }, { "input": "Ginsenoside Rb1 ( Rb1 ), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI - H716 cells.", "output": "Ginsenoside Rb1, Rb1." }, { "input": "Diabetic rats were developed by a combination of high - fat diet and low - dose streptozotocin injection.", "output": "streptozotocin." }, { "input": "The diabetic rats orally received GTS ( 150 or 300 mg / kg ) daily for 4 weeks.", "output": "There is no related enetity." }, { "input": "It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose - induced GLP1 secretion and upregulation of proglucagon gene expression.", "output": "glucose." }, { "input": "Data from NCI - H716 cells showed that both GTS and Rb1 promoted GLP1 secretion.", "output": "Rb1." }, { "input": "It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca ( 2 ) ( + ) concentration.", "output": "Rb1, ATP, ADP, Ca ( 2 ) ( + )." }, { "input": "The metabolic inhibitor azide ( 3 mM ), the KATP channel opener diazoxide ( 340 mu M ), and the Ca ( 2 ) ( + ) channel blocker nifedipine ( 20 mu M ) significantly reversed Rb1 - mediated GLP1 secretion.", "output": "azide, diazoxide, Ca ( 2 ) ( + ), nifedipine, Rb1." }, { "input": "All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro.", "output": "ginsenosides." }, { "input": "The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion.", "output": "ginsenosides." }, { "input": "Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen.", "output": "There is no related enetity." }, { "input": "Hepatitis B virus ( HBV ) is implicated in liver cancer.", "output": "There is no related enetity." }, { "input": "The aim of this study was to find out whether HBV or its components [ HBV surface antigen ( HBsAg ), HBV core protein ( HBc ), and HBV X protein ( HBx ) ] could interfere with the host DNA damage response and repair pathway.", "output": "There is no related enetity." }, { "input": "The full HBV genome or individual HBV open - reading frame ( ORF ) was introduced into HepG2 cells to examine the effect on host genomic stability, DNA repair efficacy in response to double - strand DNA damage, and DNA damage - induced cell death.", "output": "There is no related enetity." }, { "input": "Responses to apoptosis induction in the HBV ORF - transfected HepG2 cells were also compared with those in HBV - positive and HBV - negative human hepatocellular carcinoma ( HCC ) cells.", "output": "There is no related enetity." }, { "input": "In the absence of HBV replication, accumulation of HBsAg in liver cells without other HBV proteins enhanced DNA repair protein and tumor suppressor promyelocytic leukemia ( PML ) degradation, which resulted in resistance to apoptosis induction and deficient double - strand DNA repair.", "output": "There is no related enetity." }, { "input": "However, HBsAg - positive cells exhibited increased cell death with exposure to the poly ( ADP - ribose ) polymerase inhibitor that blocks single - strand DNA repair.", "output": "poly ( ADP - ribose )." }, { "input": "These results indicate that suppression of PML by HBsAg disrupts cellular mechanisms that respond to double - strand DNA damage for DNA repair or apoptosis induction, which may facilitate hepatocarcinogenesis and open up a synthetic lethality strategy for HBsAg - positive HCC treatment. - Chung, Y. - L.", "output": "There is no related enetity." }, { "input": "Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen.", "output": "There is no related enetity." }, { "input": "Fanconi anemia pathway - - the way of DNA interstrand cross - link repair.", "output": "There is no related enetity." }, { "input": "The study of rare genetic diseases usually inspires the research of cancer biology.", "output": "There is no related enetity." }, { "input": "Fanconi anemia ( FA ), is a rare cancer susceptibility syndrome with an incidence of only 1 per 350, 000 births.", "output": "There is no related enetity." }, { "input": "FA is an autosomal recessive disease with three main features: chromosome instability, hypersensitivity to DNA cross - linking agents such as mitomycin C ( MMC ), cisplatin and so on, and susceptible to a number of cancer types, mainly leukemia and squamous cell carcinomas of the head and neck or gynecologic system.", "output": "mitomycin C, MMC, cisplatin." }, { "input": "DNA crosslinking agents may led to DNA cross - linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross - linking.", "output": "There is no related enetity." }, { "input": "However, FA pathway is closely linked with carcinogenesis and tumor drug resistance.", "output": "There is no related enetity." }, { "input": "This paper mainly focuses on the FA pathway and its progress in cancer research.", "output": "There is no related enetity." }, { "input": "Effects of a new sustained - release microsphere formulation of exenatide, DA - 3091, on obese and non - alcoholic fatty liver disease mice.", "output": "There is no related enetity." }, { "input": "The aim of this study was to examine the effects of a new sustained - release ( SR ) microsphere formulation of exenatide, DA - 3091, on body weight gain and hepatic injury in high fat diet ( HFD ) - induced obese mice and high sucrose diet ( HSD ) - induced non - alcoholic fatty liver disease ( NAFLD ) mice.", "output": "There is no related enetity." }, { "input": "Then, we determined whether DA - 3091 has the potency as a drug for the treatment of metabolic disease.", "output": "There is no related enetity." }, { "input": "In obese mice, after 8 - week treatment, the body weight gain was significantly more suppressed by both 1 mg / kg and 2 mg / kg of DA - 3091, monthly subcutaneous administered, than by 10 mg / kg / day of sibutramin, a drug against obesity.", "output": "sibutramin." }, { "input": "In NAFLD mice, a significant reduction in serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels, representative markers of hepatic injury, was observed after biweekly subcutaneous administration of 1 mg / kg and 2 mg / kg of DA - 3091 for 8 weeks.", "output": "alanine, aspartate." }, { "input": "A significant reduction in hepatic lipid accumulation was observed in DA - 3091 treated groups as well.", "output": "There is no related enetity." }, { "input": "Based on these results, it is demonstrated that DA - 3091 has the potency as a drug for the treatment of metabolic disease.", "output": "There is no related enetity." }, { "input": "Effects of insulin - like growth factor - 1 on neurochemical phenotypes of cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.", "output": "glutamate." }, { "input": "Insulin - like growth factor - 1 ( IGF - 1 ) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion ( DRG ) neurons.", "output": "There is no related enetity." }, { "input": "The neuropeptide - and neurofilament ( NF ) - immunoreactive ( IR ) neurons are two major phenotypical classes in DRG.", "output": "There is no related enetity." }, { "input": "Whether IGF - 1 affects neurochemical phenotypes of DRG neurons remains unknown.", "output": "There is no related enetity." }, { "input": "In the present study, primary cultured DRG neurons were used to determine the effects of IGF - 1 on neurochemical phenotypes of the neurons with excitotoxicity induced by glutamate ( Glu ).", "output": "glutamate, Glu." }, { "input": "DRG neurons were dissociated and cultured for 48 hours and then exposed to IGF - 1 ( 20 nmol / L ), Glu ( 0. 2 mmol / L ), Glu ( 0. 2 mmol / L ) plus IGF - 1 ( 20 nmol / L ) for additional 24 hours.", "output": "Glu, Glu." }, { "input": "The DRG neurons were continuously exposed to culture media as control.", "output": "There is no related enetity." }, { "input": "After that, all above cultured DRG neurons were processed for detecting mRNA levels of calcitonin gene - related peptide ( CGRP ) and neurofilament - 200 ( NF - 200 ) by real time - PCR analysis.", "output": "There is no related enetity." }, { "input": "CGRP and NF - 200 expression in situ was determined by fluorescent labeling technique.", "output": "There is no related enetity." }, { "input": "The results showed that CGRP mRNA, but not NF - 200 mRNA, increased after IGF - 1 administration in the absence or presence of Glu.", "output": "Glu." }, { "input": "IGF - 1 could increase the percentage of CGRP - expressing neurons, but not NF - 200 - expressing neurons, in the absence or presence of Glu.", "output": "Glu." }, { "input": "The ability of IGF - 1 on CGRP expression may play a role in neurogenic inflammation or nociception.", "output": "There is no related enetity." }, { "input": "Incision wound healing activity of pine bark extract containing topical formulations: a study with histopathological and biochemical analyses in albino rats.", "output": "There is no related enetity." }, { "input": "The present study was designed to identify and compare the in vivo wound healing capacity of a bark extract from Pinus brutia and Pycnogenol in an incision wound model in rats.", "output": "There is no related enetity." }, { "input": "O / W cream formulations were prepared incorporating 2 % Pycnogenol and P. brutia bark extract.", "output": "There is no related enetity." }, { "input": "The rats were divided into three groups ( n = 8 ).", "output": "There is no related enetity." }, { "input": "Subsequently placebo and test formulations were applied to animals once a day from day \" 0 \" until the 9th day.", "output": "There is no related enetity." }, { "input": "Malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and catalase ( CAT ) were studied in addition to histopathological examinations.", "output": "Malondialdehyde, MDA, superoxide." }, { "input": "Treatment with F. brutia extract containing cream inhibited lipid peroxidation by a 35 % decrease in MDA and 46. 8 % increase in SOD activity, whereas 19. 3 % decrease in MDA and 34. 7 % increase in SOD activity were attained with Pynogenol compared to control.", "output": "MDA, MDA." }, { "input": "The histological data revealed a better performance of P. brutia extract enriched formulation in terms of degeneration of hair roots, increased vascularization and a decrease in necrotic area.", "output": "There is no related enetity." }, { "input": "Consequently, a high wound healing activity was observed in animals treated with P. brutia extract significantly accelerating the wound healing process.", "output": "There is no related enetity." }, { "input": "Isolation, Structure Elucidation, and Iron - Binding Properties of Lystabactins, Siderophores Isolated from a Marine Pseudoalteromonas sp.", "output": "Iron, Lystabactins." }, { "input": "The marine bacterium Pseudoalteromonas sp.", "output": "There is no related enetity." }, { "input": "S2B, isolated from the Gulf of Mexico after the Deepwater Horizon oil spill, was found to produce lystabactins A, B, and C ( 1 - 3 ), three new siderophores.", "output": "lystabactins A , B , and C." }, { "input": "The structures were elucidated through mass spectrometry, amino acid analysis, and NMR.", "output": "amino acid." }, { "input": "The lystabactins are composed of serine ( Ser ), asparagine ( Asn ), two formylated / hydroxylated ornithines ( FOHOrn ), dihydroxy benzoic acid ( Dhb ), and a very unusual nonproteinogenic amino acid, 4, 8 - diamino - 3 - hydroxyoctanoic acid ( LySta ).", "output": "lystabactins, serine, Ser, asparagine, Asn, formylated / hydroxylated ornithines, FOHOrn, dihydroxy benzoic acid, Dhb, nonproteinogenic amino acid, 4 , 8 - diamino - 3 - hydroxyoctanoic acid, LySta." }, { "input": "The iron - binding properties of the compounds were investigated through a spectrophotometric competition.", "output": "There is no related enetity." }, { "input": "Vectorization efforts to increase gram - negative intracellular drug concentration: a case study on HldE - K inhibitors.", "output": "There is no related enetity." }, { "input": "In this paper, we present different strategies to vectorize HldE kinase inhibitors with the goal to improve their gram - negative intracellular concentration.", "output": "There is no related enetity." }, { "input": "Syntheses and biological effects of siderophoric, aminoglycosidic, amphoteric, and polycationic vectors are discussed.", "output": "There is no related enetity." }, { "input": "While siderophoric and amphoteric vectorization efforts proved to be disappointing in this series, aminoglycosidic and polycationic vectors were able for the first time to achieve synergistic effects of our inhibitors with erythromycin.", "output": "erythromycin." }, { "input": "Although these effects proved to be nonspecific, this study provides information about the required stereoelectronic arrangement of the polycationic amines and their basicity requirements to fulfill outer membrane destabilization resulting in better erythromycin synergies.", "output": "amines, erythromycin." }, { "input": "Arylazanylpyrazolone derivatives as inhibitors of mutant superoxide dismutase 1 dependent protein aggregation for the treatment of amyotrophic lateral sclerosis.", "output": "Arylazanylpyrazolone, superoxide." }, { "input": "The arylsulfanylpyrazolone and aryloxanylpyrazolone scaffolds previously were reported to inhibit Cu / Zn superoxide dismutase 1 dependent protein aggregation and to extend survival in the ALS mouse model.", "output": "arylsulfanylpyrazolone, aryloxanylpyrazolone, Cu, Zn, superoxide." }, { "input": "However, further evaluation of these compounds indicated weak pharmacokinetic properties and a relatively low maximum tolerated dose.", "output": "There is no related enetity." }, { "input": "On the basis of an ADME analysis, a new series of compounds, the arylazanylpyrazolones, has been synthesized, and structure - activity relationships were determined.", "output": "arylazanylpyrazolones." }, { "input": "The SAR results showed that the pyrazolone ring is critical to cellular protection.", "output": "pyrazolone." }, { "input": "The NMR, IR, and computational analyses suggest that phenol - type tautomers of the pyrazolone ring are the active pharmacophore with the arylazanylpyrazolone analogues.", "output": "phenol, pyrazolone, arylazanylpyrazolone." }, { "input": "A comparison of experimental and calculated IR spectra is shown to be a valuable method to identify the predominant tautomer.", "output": "There is no related enetity." }, { "input": "Drug - initiated ring - opening polymerization of O - carboxyanhydrides for the preparation of anticancer drug - poly ( O - carboxyanhydride ) nanoconjugates.", "output": "O - carboxyanhydrides, poly ( O - carboxyanhydride )." }, { "input": "We report a novel synthetic strategy of polymer - drug conjugates for nanoparticulate drug delivery: hydroxyl - containing drug ( e. g., camptothecin, paclitaxel, doxorubicin and docetaxel ) can initiate controlled polymerization of phenyl O - carboxyanhydride ( Phe - OCA ) to afford drug - poly ( Phe - OCA ) conjugated nanoparticles, termed drug - PheLA nanoconjugates ( NCs ).", "output": "hydroxyl, camptothecin, paclitaxel, doxorubicin, docetaxel, phenyl O - carboxyanhydride, Phe - OCA, Phe - OCA, PheLA." }, { "input": "Our new NCs have well - controlled physicochemical properties, including high drug loading, quantitative drug loading efficiency, controlled particle size with narrow particle size distribution, and sustained drug release profile over days without \" burst \" release effect as observed in conventional polymer / drug encapsulates.", "output": "There is no related enetity." }, { "input": "Compared with polylactide NCs, the PheLA NCs have increased noncovalent hydrophobic interchain interactions and thereby result in remarkable stability in human serum with negligible particle aggregation.", "output": "polylactide, PheLA." }, { "input": "Such distinctive properties can reduce the premature disassembly of NCs upon dilution in the bloodstream and prolong NCs ' in vivo circulation with the enhancement of intratumoral accumulation of NCs, which has a bearing on therapeutic effectiveness.", "output": "There is no related enetity." }, { "input": "CYP2J2 overexpression increases EETs and protects against angiotensin II - induced abdominal aortic aneurysm in mice.", "output": "EETs." }, { "input": "Cytochrome P450 epoxygenase 2J2 ( CYP2J2 ) metabolizes arachidonic acids to form epoxyeicosatrienoic acids ( EETs ), which possess various beneficial effects on the cardiovascular system.", "output": "arachidonic acids, epoxyeicosatrienoic acids, EETs." }, { "input": "However, whether increasing EETs production by CYP2J2 overexpression in vivo could prevent abdominal aortic aneurysm ( AAA ) remains unknown.", "output": "EETs." }, { "input": "Here we investigated the effects of recombinant adeno - associated virus ( rAAV ) - mediated CYP2J2 overexpression on angiotensin ( Ang ) II - induced AAA in apoE - deficient mice.", "output": "There is no related enetity." }, { "input": "rAAV - CYP2J2 delivery led to an abundant aortic CYP2J2 expression and increased EETs generation.", "output": "EETs." }, { "input": "It was shown that CYP2J2 overexpression attenuated matrix metalloproteinase expression and activity, elastin degradation, and AAA formation, which was associated with reduced aortic inflammation and macrophage infiltration.", "output": "There is no related enetity." }, { "input": "In cultured vascular smooth muscle cells ( VSMCs ), rAAV - mediated CYP2J2 overexpression and EETs markedly suppressed Ang II - induced inflammatory cytokine expression.", "output": "EETs." }, { "input": "Moreover, overexpressed CYP2J2 and EETs inhibited Ang II - induced macrophage migration in a VSMC - macrophage coculture system.", "output": "EETs." }, { "input": "We further indicated that these protective effects were mediated by peroxisome proliferator - activated receptor ( PPAR ) gamma activation.", "output": "There is no related enetity." }, { "input": "Taken together, these results provide evidence that rAAV - mediated CYP2J2 overexpression prevents AAA development which is likely via PPAR gamma activation and anti - inflammatory action, suggesting that increasing EETs levels could be considered as a potential strategy to prevent and treat AAA.", "output": "EETs." }, { "input": "Single - molecule chemical denaturation of riboswitches.", "output": "There is no related enetity." }, { "input": "To date, single - molecule RNA science has been developed almost exclusively around the effect of metal ions as folding promoters and stabilizers of the RNA structure.", "output": "There is no related enetity." }, { "input": "Here, we introduce a novel strategy that combines single - molecule F o rster resonance energy transfer ( FRET ) and chemical denaturation to observe and manipulate RNA dynamics.", "output": "There is no related enetity." }, { "input": "We demonstrate that the competing interplay between metal ions and denaturant agents provides a platform to extract information that otherwise will remain hidden with current methods.", "output": "There is no related enetity." }, { "input": "Using the adenine - sensing riboswitch aptamer as a model, we provide strong evidence for a rate - limiting folding step of the aptamer domain being modulated through ligand binding, a feature that is important for regulation of the controlled gene.", "output": "adenine." }, { "input": "In the absence of ligand, the rate - determining step is dominated by the formation of long - range key tertiary contacts between peripheral stem - loop elements.", "output": "There is no related enetity." }, { "input": "In contrast, when the adenine ligand interacts with partially folded messenger RNAs, the aptamer requires specifically bound Mg ( 2 + ) ions, as those observed in the crystal structure, to progress further towards the native form.", "output": "adenine, Mg ( 2 + )." }, { "input": "Moreover, despite that the ligand - free and ligand - bound states are indistinguishable by FRET, their different stability against urea - induced denaturation allowed us to discriminate them, even when they coexist within a single FRET trajectory; a feature not accessible by existing methods.", "output": "urea." }, { "input": "Exchange protein directly activated by cAMP ( epac ): a multidomain cAMP mediator in the regulation of diverse biological functions.", "output": "cAMP, cAMP." }, { "input": "Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers.", "output": "cAMP." }, { "input": "The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes.", "output": "cAMP, calcium." }, { "input": "The discovery of Epac ( exchange protein directly activated by cAMP ) has ignited a new surge of cAMP - related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide - gated channels.", "output": "cAMP, cAMP, cAMP, nucleotide." }, { "input": "The multidomain architecture of Epac determines its activity state and allows cell - type specific protein - protein and protein - lipid interactions that control fine - tuning of pivotal biologic responses through the \" old \" second messenger cAMP.", "output": "cAMP." }, { "input": "Compartmentalization of cAMP in space and time, maintained by A - kinase anchoring proteins, phosphodiesterases, and beta - arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen - and lipid - activated kinases, and transcription factors.", "output": "cAMP." }, { "input": "These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses.", "output": "cAMP, cAMP." }, { "input": "Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac.", "output": "There is no related enetity." }, { "input": "This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, ( pulmonary ) hypertension, asthma, and chronic obstructive pulmonary disease.", "output": "There is no related enetity." }, { "input": "Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.", "output": "cAMP." }, { "input": "Ion - induced synthesis of uniform single - crystalline sulphide - based quaternary - alloy hexagonal nanorings for highly efficient photocatalytic hydrogen evolution.", "output": "sulphide, hydrogen." }, { "input": "Uniform single - crystalline quaternary sulphide nanoring photocatalysts are synthesized via the copper - ion - induced Kirkendall effect and is followed by a cation exchange reaction.", "output": "sulphide, copper." }, { "input": "The obtained Cu ( 2 + ) - doped ZnIn2 S4 nanorings show highly preserved morphology, and demonstrate high visible - light - driven photocatalytic activity for H2 evolution in water splitting.", "output": "Cu ( 2 + ), ZnIn2 S4, H2." }, { "input": "Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors.", "output": "serine." }, { "input": "Human and mouse marapsins ( Prss27 ) are serine proteases preferentially expressed by stratified squamous epithelia.", "output": "serine." }, { "input": "However, mouse marapsin contains a transmembrane anchor absent from the human enzyme.", "output": "There is no related enetity." }, { "input": "To gain insights into physical forms, activities, inhibition, and roles in epithelial differentiation, we traced tail loss in human marapsin to a nonsense mutation in an ancestral ape, compared substrate preferences of mouse and human marapsins with those of the epithelial peptidase prostasin, designed a selective substrate and inhibitor, and generated Prss27 - null mice.", "output": "There is no related enetity." }, { "input": "Phylogenetic analysis predicts that most marapsins are transmembrane proteins.", "output": "There is no related enetity." }, { "input": "However, nonsense mutations caused membrane anchor loss in three clades: human / bonobo / chimpanzee, guinea pig / degu / tuco - tuco / mole rat, and cattle / yak.", "output": "There is no related enetity." }, { "input": "Most marapsin - related proteases, including prostasins, are type I transmembrane proteins, but the closest relatives ( prosemins ) are not.", "output": "There is no related enetity." }, { "input": "Soluble mouse and human marapsins are tryptic with subsite preferences distinct from those of prostasin, lack general proteinase activity, and unlike prostasins resist antiproteases, including leupeptin, aprotinin, serpins, and alpha 2 - macroglobulin, suggesting the presence of non - canonical active sites.", "output": "There is no related enetity." }, { "input": "Prss27 - null mice develop normally in barrier conditions and are fertile without overt epithelial defects, indicating that marapsin does not play critical, non - redundant roles in development, reproduction, or epithelial differentiation.", "output": "There is no related enetity." }, { "input": "In conclusion, marapsins are conserved, inhibitor - resistant, tryptic peptidases.", "output": "tryptic." }, { "input": "Although marapsins are type I transmembrane proteins in their typical form, they mutated independently into anchorless forms in several mammalian clades, including one involving humans.", "output": "There is no related enetity." }, { "input": "Similar pathways appear to have been traversed by prosemins and tryptases, suggesting that mutational tail loss is an important means of evolving new functions of tryptic serine proteases from transmembrane ancestors.", "output": "serine." }, { "input": "The need for better insulin therapy.", "output": "There is no related enetity." }, { "input": "Insulin replacement therapy corrects a core defect of diabetes pathophysiology.", "output": "There is no related enetity." }, { "input": "Since its introduction as a therapeutic modality almost 100 years ago, insulin therapy has undergone remarkable changes in purity and ability to provide more physiologic control of blood glucose levels.", "output": "glucose." }, { "input": "With glucose - lowering potential limited only by risks of hypoglycaemia, which remains the major limitation in our ability to achieve glycaemic goals, insulin replacement therapy remains a cornerstone of therapy.", "output": "glucose." }, { "input": "Major progress in reducing the risks of hypoglycemia has occurred with the development of insulin analogs.", "output": "There is no related enetity." }, { "input": "This review article briefly chronicles the evolution of insulin replacement strategies, highlighting both challenges in pharmaceutical development and patient acceptance, underscoring achievements, as well as denoting what improvements are still needed.", "output": "There is no related enetity." }, { "input": "Large enhancement of nonlinear optical response in a hybrid nanobiomaterial consisting of bacteriorhodopsin and cadmium telluride quantum dots.", "output": "cadmium telluride." }, { "input": "We report wavelength - dependent enormous enhancement of the nonlinear refractive index of wild - type bacteriorhodopsin in the presence of semiconductor quantum dots.", "output": "There is no related enetity." }, { "input": "The effect is strongest in the region just below the absorption edge of both constituents of this hybrid material and in samples that show strong F o rster resonance energy transfer.", "output": "There is no related enetity." }, { "input": "We show that enhancements of up to 4000 % can be achieved by controlled engineering of the hybrid structure involving variations of the molar ratio of the constituents.", "output": "There is no related enetity." }, { "input": "This new hybrid material with exceptional nonlinear properties will have numerous photonic and optoelectronic applications employing its photochromic, energy transfer, and conversion properties.", "output": "There is no related enetity." }, { "input": "High - temperature and pressure - induced ferroelectricity in hydrogen - bonded supramolecular crystals of anilic acids and 2, 3 - di ( 2 - pyridinyl ) pyrazine.", "output": "hydrogen, anilic acids, 2 , 3 - di ( 2 - pyridinyl ) pyrazine." }, { "input": "Cocrystallization of anilic acids ( H2xa ) and 2, 3 - di ( 2 - pyridinyl ) pyrazine ( dppz ) affords a variety of molecular geometries, including hydrogen - bonding and supramolecular structures.", "output": "anilic acids, H2xa, 2 , 3 - di ( 2 - pyridinyl ) pyrazine, dppz, hydrogen." }, { "input": "Proton - transferred 1: 1 salts of [ H - dppz ] [ Hca ] and [ H - dppz ] [ Hba ] ( H2ca = chloranilic acid, H2ba = bromanilic acid ) were found to host room - temperature ferroelectricity with a spontaneous polarization of 3 - 4 mu C / cm ( 2 ) along the hydrogen - bonded chains.", "output": "[ H - dppz ] [ Hca ], [ H - dppz ] [ Hba ], H2ca, chloranilic acid, H2ba, bromanilic acid, hydrogen." }, { "input": "Compared with the Curie points of other supramolecular ferroelectrics, those of the salts are relatively high ( 402 K and > 420 K, respectively ) because of the elongated hydrogen bonds, which stabilize the proton - ordered state against thermal agitation.", "output": "hydrogen." }, { "input": "In addition to the ferroelectric black ( alpha ) form, dppz and H2ba gave two different crystal forms with a 2: 3 ratio: the brown beta form of [ H ( 1. 5 ) - dppz ] 2 [ Hba ] 3 and the brownish - red gamma form of [ H - dppz ] 2 [ Hba ] 2 [ H2ba ].", "output": "dppz, H2ba, [ H ( 1 . 5 ) - dppz ] 2 [ Hba ] 3, [ H - dppz ] 2 [ Hba ] 2 [ H2ba ]." }, { "input": "Mixed solutions of dppz with the less acidic fluoranilic acid ( H2fa ) exhibit valence instability; the H2fa molecules remain mostly neutral in absolute ethanol, whereas methanol ( MeOH ) solution apparently increases the deprotonated Hfa ( - ) content.", "output": "dppz, fluoranilic acid, H2fa, H2fa, ethanol, methanol, MeOH, Hfa ( - )." }, { "input": "Crystallizations of these solutions gave a neutral [ dppz ] [ H2fa ] cocrystal and ionic [ H - dppz ( + ) ] [ Hfa ( - ) ]. MeOH salt, respectively.", "output": "[ dppz ] [ H2fa ], [ H - dppz ( + ) ] [ Hfa ( - ) ] . MeOH." }, { "input": "The ferroelectricity induced by a modest hydrostatic pressure corroborates the conclusion that the ionic state with a dipolar [ H - dppz ( + ) ] [ Hfa ( - ) ] chain is energetically close to the nonpolar neutral ground state of the [ dppz ] [ H2fa ] crystal.", "output": "[ H - dppz ( + ) ] [ Hfa ( - ) ], [ dppz ] [ H2fa ]." }, { "input": "Multiple targeted drugs carrying biodegradable membrane barrier: anti - adhesion, hemostasis, and anti - infection.", "output": "There is no related enetity." }, { "input": "A multiple targeted drug carrying bilayer membrane for preventing an abdominal adhesion is prepared by electrospinning.", "output": "There is no related enetity." }, { "input": "Two bioactive drugs were successfully incorporated into this bilayer membrane and can be independently released from nanofibrous scaffolds without losing structural integrity and functionality of the anti - adhesion membrane.", "output": "There is no related enetity." }, { "input": "Besides, the drug release profile could be easily adjusted by optimizing the swelling behavior of the fibrous scaffold.", "output": "There is no related enetity." }, { "input": "The inner layer of the bilayered fibrous membranes loaded with carbazochrome sodium sulfonate ( CA ) showed an excellent vascular hemostatic efficacy and formed little clot during in vivo experiment.", "output": "carbazochrome sodium sulfonate." }, { "input": "The outer layer loaded with tinidazole ( TI ) had outstanding antibacterial effect against the anaerobe.", "output": "tinidazole." }, { "input": "We believe this approach could serve as a model technique to guide the design of implants with drug delivery functions.", "output": "There is no related enetity." }, { "input": "Synthetically tractable click hydrogels for three - dimensional cell culture formed using tetrazine - norbornene chemistry.", "output": "tetrazine, norbornene." }, { "input": "The implementation of bio - orthogonal click chemistries is a topic of growing importance in the field of biomaterials, as it is enabling the development of increasingly complex hydrogel materials capable of providing dynamic, cell - instructive microenvironments.", "output": "There is no related enetity." }, { "input": "Here, we introduce the tetrazine - norbornene inverse electron demand Diels - Alder reaction as a new cross - linking chemistry for the formation of cell laden hydrogels.", "output": "tetrazine, norbornene." }, { "input": "The fast reaction rate and irreversible nature of this click reaction allowed for hydrogel formation within minutes when a multifunctional PEG - tetrazine macromer was reacted with a dinorbornene peptide.", "output": "PEG, tetrazine, dinorbornene." }, { "input": "In addition, the cytocompatibility of the polymerization led to high postencapsulation viability of human mesenchymal stem cells, and the specificity of the tetrazine - norbornene reaction was exploited for sequential modification of the network via thiol - ene photochemistry.", "output": "tetrazine, norbornene, thiol, ene." }, { "input": "These advantages, combined with the synthetic accessibility of the tetrazine molecule compared to other bio - orthogonal click reagents, make this cross - linking chemistry an interesting and powerful new tool for the development of cell - instructive hydrogels for tissue engineering applications.", "output": "tetrazine." }, { "input": "Extremely low - frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats.", "output": "manganese." }, { "input": "The aim of the present study was to determine the effects of extremely low - frequency magnetic field ( ELF - MF ) on accumulation of manganese ( Mn ) in the kidney, liver and brain of rats.", "output": "manganese, Mn." }, { "input": "A total of 40 rats were randomly divided into eight groups.", "output": "There is no related enetity." }, { "input": "Four control groups received 0, 3. 75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively.", "output": "Mn." }, { "input": "The remaining four groups received same concentrations of Mn and were also exposed to ELF - MF ( 1. 5 mT; 50 Hz ) for 4 h for 5 days a week during 45 days.", "output": "Mn." }, { "input": "Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma - optical emission spectrometer.", "output": "Mn." }, { "input": "In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups.", "output": "Mn, Mn." }, { "input": "Mn levels in brain, kidney and liver were also higher in Mn plus ELF - MF groups than in Mn groups.", "output": "Mn, Mn, Mn." }, { "input": "In conclusion, result of the current study showed that the ELF - MF induced manganese accumulation in kidney, liver and brain of rats.", "output": "manganese." }, { "input": "Acute respiratory distress syndrome due to exposure to high - concentration mixture of ethenone and crotonaldehyde.", "output": "ethenone, crotonaldehyde." }, { "input": "INTRODUCTION: Acute inhalational exposure leads to rapidly progressive acute respiratory distress syndrome ( ARDS ).", "output": "There is no related enetity." }, { "input": "This report is the first one to present a patient with ARDS in relation to long - standing exposure to a high - concentration mixture of ethenone and crotonaldehyde.", "output": "ethenone, crotonaldehyde." }, { "input": "Case report: A male worker in a chemical plant was accidentally exposed to the mixture of high - concentrated ethenone and crotonaldehyde for 5 min in an open space and worked continuously in the polluted area for approximately 12 h.", "output": "ethenone, crotonaldehyde." }, { "input": "On admission, he was conscious with the following vital parameters: blood pressure, 151 / 91 mmHg; pulse rate, 107 beats / min; respiratory rate, 30 breaths / min; temperature, 37. 6 degrees C; oxygen saturation, 92 % supported by mask saturation 10 L / min; arterial blood gases showed P / F oxygen ratio of less than 200.", "output": "oxygen, oxygen." }, { "input": "Physical examination disclosed decreased bilateral vesicular sounds.", "output": "There is no related enetity." }, { "input": "A chest computed tomography revealed bilateral nonsegmental ground - glass opacities.", "output": "There is no related enetity." }, { "input": "The patient was mechanically ventilated and treated with corticosteroid.", "output": "There is no related enetity." }, { "input": "The patient was discharged without any symptoms.", "output": "There is no related enetity." }, { "input": "CONCLUSION: Exposure to mixtures of ethenone and crotonaldehyde can cause severe pulmonary injury leading to delayed ARDS.", "output": "ethenone, crotonaldehyde." }, { "input": "Influence of binder droplet dimension on granulation rate during fluidized bed granulation.", "output": "There is no related enetity." }, { "input": "Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process.", "output": "There is no related enetity." }, { "input": "Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone.", "output": "Lactose, hydroxypropyl, hydroxypropyl methyl, polyvinylpyrrolidone." }, { "input": "The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered.", "output": "lactose." }, { "input": "The Stokes number was defined as the ratio of the inertial force to the viscous - damping force of a particle.", "output": "There is no related enetity." }, { "input": "We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters.", "output": "There is no related enetity." }, { "input": "Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.", "output": "lactose, lactose." }, { "input": "Lasiodiplodin analogues from the endophytic fungus Sarocladium kiliense.", "output": "Lasiodiplodin." }, { "input": "A new 12 - membered ring lactone, ( 3S ), ( 6R ) - 6 - hydroxylasiodiplodin ( 1 ), with two known analogues, ( 3R ) - lasiodiplodin ( 2 ), and ( 3R ), ( 5S ) - 5 - hydroxylasiodiplodin ( 3 ) were isolated from the EtOH extracts of normal Apriona germari ( Hope ) - associated fungus Sarocladium kiliense grown in rice medium.", "output": "lactone, ( 3S ) , ( 6R ) - 6 - hydroxylasiodiplodin, ( 3R ) - lasiodiplodin, ( 3R ) , ( 5S ) - 5 - hydroxylasiodiplodin, EtOH." }, { "input": "The structures of compounds 1 - 3 were elucidated by a combination of spectroscopic data interpretation, single - crystal X - ray diffraction analysis, and modified Mosher ' s method.", "output": "There is no related enetity." }, { "input": "Development of modified siRNA molecules incorporating 5 - fluoro - 2 ' - deoxyuridine residues to enhance cytotoxicity.", "output": "5 - fluoro - 2 ' - deoxyuridine." }, { "input": "Therapeutic small interfering RNAs ( siRNAs ) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson - Crick base pairing.", "output": "There is no related enetity." }, { "input": "However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown.", "output": "There is no related enetity." }, { "input": "Previously, we demonstrated that deoxythymidine release from degraded siRNAs reversed the cytotoxicity of thymidylate synthase ( TS ) - targeted siRNAs and other TS inhibitor compounds.", "output": "deoxythymidine." }, { "input": "We hypothesized that siRNAs could be designed with specific nucleoside analogues that, once released, would enhance siRNA cytotoxicity.", "output": "There is no related enetity." }, { "input": "TS - targeted siRNAs were designed that contained 5 - fluoro - 2 ' - deoxyuridine ( FdU ) moieties at various locations within the siRNA.", "output": "5 - fluoro - 2 ' - deoxyuridine, FdU." }, { "input": "After transfection, these siRNAs suppressed TS protein and messenger RNA expression with different efficiencies depending on the location of the FdU modification.", "output": "FdU." }, { "input": "FdU was rapidly released from the siRNA as evidenced by formation of the covalent inhibitory ternary complex formed between TS protein and the FdU metabolite, FdUMP.", "output": "FdU, FdU, FdUMP." }, { "input": "These modified siRNAs exhibited 10 - 100 - fold greater cytotoxicity and induced multiple DNA damage repair and apoptotic pathways when compared with control siRNAs.", "output": "There is no related enetity." }, { "input": "The strategy of designing siRNA molecules that incorporate cytotoxic nucleosides represents a potentially novel drug development approach for the treatment of cancer and other human diseases.", "output": "There is no related enetity." }, { "input": "A far - upstream ( - 70 kb ) enhancer mediates Sox9 auto - regulation in somatic tissues during development and adult regeneration.", "output": "There is no related enetity." }, { "input": "SOX9 encodes a transcription factor that presides over the specification and differentiation of numerous progenitor and differentiated cell types, and although SOX9 haploinsufficiency and overexpression cause severe diseases in humans, including campomelic dysplasia, sex reversal and cancer, the mechanisms underlying SOX9 transcription remain largely unsolved.", "output": "There is no related enetity." }, { "input": "We identify here an evolutionarily conserved enhancer located 70 - kb upstream of mouse Sox9 and call it SOM because it specifically activates a Sox9 promoter reporter in most Sox9 - expressing somatic tissues in transgenic mice.", "output": "There is no related enetity." }, { "input": "Moreover, SOM - null fetuses and pups reduce Sox9 expression by 18 - 37 % in the pancreas, lung, kidney, salivary gland, gut and liver.", "output": "There is no related enetity." }, { "input": "Weanlings exhibit half - size pancreatic islets and underproduce insulin and glucagon, and adults slowly recover from acute pancreatitis due to a 2 - fold impairment in Sox9 upregulation.", "output": "There is no related enetity." }, { "input": "Molecular and genetic experiments reveal that Sox9 protein dimers bind to multiple recognition sites in the SOM sequence and are thereby both necessary and sufficient for enhancer activity.", "output": "There is no related enetity." }, { "input": "These findings thus uncover that Sox9 directly enhances its functions in somatic tissue development and adult regeneration through SOM - mediated positive auto - regulation.", "output": "There is no related enetity." }, { "input": "They provide thereby novel insights on molecular mechanisms controlling developmental and disease processes and suggest new strategies to improve disease treatments.", "output": "There is no related enetity." }, { "input": "Targeting pathological B cell receptor signalling in lymphoid malignancies.", "output": "There is no related enetity." }, { "input": "Signalling through the B cell receptor ( BCR ) is central to the development and maintenance of B cells.", "output": "There is no related enetity." }, { "input": "In light of the numerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant B cells would co - opt this receptor to promote their own growth and survival.", "output": "There is no related enetity." }, { "input": "However, direct evidence for BCR signalling in human lymphoma has only come to light recently.", "output": "There is no related enetity." }, { "input": "Roles for antigen - dependent and antigen - independent, or tonic, BCR signalling have now been described for several different lymphoma subtypes.", "output": "There is no related enetity." }, { "input": "Furthermore, correlative data implicate antigen - dependent BCR signalling in many other forms of lymphoma.", "output": "There is no related enetity." }, { "input": "A host of therapeutic agents targeting effectors of the BCR signalling pathway are now in clinical trials and have shown initial success against multiple forms of lymphoma.", "output": "There is no related enetity." }, { "input": "MAP / microtubule affinity - regulating kinases, microtubule dynamics, and spermatogenesis.", "output": "There is no related enetity." }, { "input": "During spermatogenesis, spermatids derived from meiosis simultaneously undergo extensive morphological transformation, to become highly specialized and metabolically quiescent cells, and transport across the seminiferous epithelium.", "output": "There is no related enetity." }, { "input": "Spermatids are also transported back - and - forth across the seminiferous epithelium during the epithelial cycle until they line up at the luminal edge of the tubule to prepare for spermiation at stage VIII of the cycle.", "output": "There is no related enetity." }, { "input": "Spermatid transport thus requires the intricate coordination of the cytoskeletons in Sertoli cells ( SCs ) as spermatids are nonmotile cells lacking the ultrastructures of lamellipodia and filopodia, as well as the organized components of the cytoskeletons.", "output": "There is no related enetity." }, { "input": "In the course of preparing this brief review, we were surprised to see that, except for some earlier eminent morphological studies, little is known about the regulation of the microtubule ( MT ) cytoskeleton and the coordination of MT with the actin - based cytoskeleton to regulate spermatid transport during the epithelia cycle, illustrating that this is a largely neglected area of research in the field.", "output": "There is no related enetity." }, { "input": "Herein, we summarize recent findings in the field regarding the significance of actin - and tubulin - based cytoskeletons in SCs that support spermatid transport; we also highlight specific areas of research that deserve attention in future studies.", "output": "There is no related enetity." }, { "input": "Highly luminescent water - soluble quaternary Zn - Ag - In - S quantum dots for tumor cell - targeted imaging.", "output": "Zn, Ag, In, S." }, { "input": "Exploring the synthesis and biomedical applications of biocompatible quantum dots ( QDs ) is currently one of the fastest growing fields of nanotechnology.", "output": "There is no related enetity." }, { "input": "Hence, in this work, we present a facile approach to produce water - soluble ( cadmium - free ) quaternary Zn - Ag - In - S ( ZAIS ) QDs.", "output": "cadmium, Zn, Ag, In, S, ZAIS." }, { "input": "Their efficient photoluminescence ( PL ) emissions can be tuned widely in the range of 525 - 625 nm by controlling the size and composition of the QDs with the PL quantum yields ( QYs ) of 15 - 30 %.", "output": "There is no related enetity." }, { "input": "These highly luminescent ZAIS QDs are less toxic due to the absence of highly toxic cadmium, and can be versatilely modified by a DHLA - PEG - based ligand.", "output": "ZAIS, cadmium, DHLA - PEG." }, { "input": "Importantly, after being modified by tumor cell - specific targeting ligands ( e. g., folate and RGD peptide ), the PEGylated quaternary QDs show potential applications in tumor cell imaging as a promising alternative for Cd - based QDs.", "output": "folate, Cd." }, { "input": "Enantiomeric separation of racemic 4 - aryl - 1, 4 - dihydropyridines and 4 - aryl - 1, 2, 3, 4 - tetrahydropyrimidines on a chiral tetraproline stationary phase.", "output": "4 - aryl - 1 , 4 - dihydropyridines, 4 - aryl - 1 , 2 , 3 , 4 - tetrahydropyrimidines, tetraproline." }, { "input": "The chromatographic chiral resolution of 4 - aryl - 1, 4 - dihydropyridines ( 1 - 32 ), 4 - aryl - 2 - thioxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 33 - 38 ), and 4 - aryl - 2 - oxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 39 - 41 ) was studied on a tetraproline - immobilized chiral column synthesized in our lab.", "output": "4 - aryl - 1 , 4 - dihydropyridines, 4 - aryl - 2 - thioxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines, 4 - aryl - 2 - oxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines, tetraproline." }, { "input": "This tetraproline chiral stationary phase can resolve most of these compounds.", "output": "tetraproline." }, { "input": "The 4 - aryl - 2 - thioxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 33 - 38 ) and 4 - aryl - 2 - oxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 39 - 41 ) were more efficiently resolved than the racemic 4 - aryl - 1, 4 - dihydropyridines on the tetraproline chiralstationary phase.", "output": "4 - aryl - 2 - thioxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines, 4 - aryl - 2 - oxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines, racemic 4 - aryl - 1 , 4 - dihydropyridines, tetraproline." }, { "input": "Analytes with 5, 5 - dimethyl groups ( 39 - 41 ) were less efficiently resolved than analytes without 5, 5 - dimethyl substituents ( 1 - 16 ).", "output": "5 , 5 - dimethyl, 5 , 5 - dimethyl." }, { "input": "The 4 - aryl - 2 - oxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 39 - 41 ) without a sulfur atom were much more efficiently resolved than 4 - aryl - 2 - thioxo - 1, 2, 3, 4 - tetrahydropyrimidines ( 33 - 38 ).", "output": "4 - aryl - 2 - oxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines, sulfur, 4 - aryl - 2 - thioxo - 1 , 2 , 3 , 4 - tetrahydropyrimidines." }, { "input": "No obvious electronic effects on the resolution of any of these analytes ( 1 - 41 ) were observed on the tetraproline chiral stationary phase.", "output": "tetraproline." }, { "input": "The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions.", "output": "tetraproline, hydrogen." }, { "input": "Exfoliated graphitic carbon nitride nanosheets as efficient catalysts for hydrogen evolution under visible light.", "output": "graphitic carbon nitride, hydrogen." }, { "input": "Graphitic carbon nitride nanosheets are extracted, produced via simple liquid - phase exfoliation of a layered bulk material, g - C3 N4.", "output": "Graphitic carbon nitride, C3 N4." }, { "input": "The resulting nanosheets, having =~ 2 nm thickness and N / C atomic ratio of 1. 31, show an optical bandgap of 2. 65 eV.", "output": "N, C." }, { "input": "The carbon nitride nanosheets are demonstrated to exhibit excellent photocatalytic activity for hydrogen evolution under visible light.", "output": "carbon nitride, hydrogen." }, { "input": "Biological Design for Simultaneous Optical Transparency and Mechanical Robustness in the Shell of Placuna placenta.", "output": "There is no related enetity." }, { "input": "The flat circular - shaped shells from Placenta placenta demonstrate high optical transparency in the visible light range while still maintaining mechanical robustness.", "output": "There is no related enetity." }, { "input": "The optical and mechanical design of this mineralized material system in correlation to its multiscale structural and crystallographical features are discussed in detail through both experimental and theoretical approaches.", "output": "There is no related enetity." }, { "input": "Hierarchically Structured Nanotubes for Highly Efficient Dye - Sensitized Solar Cells.", "output": "There is no related enetity." }, { "input": "Hierarchical TiO2 nanotube arrays grown on Ti foil are yielded by subjecting electrochemically anodized, vertically oriented TiO2 nanotube arrays to hydrothermal processing.", "output": "TiO2, Ti, TiO2." }, { "input": "The resulting DSSCs exhibit a significantly enhanced power conversion efficiency of 7. 24 %, which is a direct consequence of the synergy of higher dye loading, superior light - scattering ability, and fast electron transport.", "output": "There is no related enetity." }, { "input": "Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin - binding site.", "output": "There is no related enetity." }, { "input": "To discover promising sulfated allosteric modulators ( SAMs ) of glycosaminoglycan - binding proteins ( GBPs ), such as human factor XIa ( FXIa ), we screened a library of 26 synthetic, sulfated quinazolin - 4 ( 3H ) - ones ( QAOs ) resulting in the identification of six molecules that reduced the Vmax of substrate hydrolysis without influencing the KM.", "output": "sulfated quinazolin - 4 ( 3H ) - ones, QAOs." }, { "input": "Mutagenesis of residues of the heparin - binding site ( HBS ) of FXIa introduced a nearly 5 - fold loss in inhibition potency supporting recognition of an allosteric site.", "output": "There is no related enetity." }, { "input": "Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding.", "output": "There is no related enetity." }, { "input": "Competition with a positively charged, heparin - binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding.", "output": "There is no related enetity." }, { "input": "This discovery suggests the operation of a dual - element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch.", "output": "There is no related enetity." }, { "input": "The dual - element strategy may be widely applicable for discovering SAMs of other GBPs.", "output": "There is no related enetity." }, { "input": "A New Raman Spectroscopic Probe of Both the Protonation State and Noncovalent Interactions of Histidine Residues.", "output": "There is no related enetity." }, { "input": "The amino acid histidine ( His ) has a number of unique roles that can dictate function in proteins, and these roles are typically conferred through noncovalent interactions that depend on the protonation state of His ' s 4 - substituted imidazole ring.", "output": "amino acid, histidine, His, His, 4 - substituted imidazole." }, { "input": "His ' s protonation state can vary near physiological pH, and a probe of His ' s variable protonation state and its resulting noncovalent interactions that has both high time resolution and no sample limitations could find wide use in determining the role of particular His residues in proteins.", "output": "His, His, His." }, { "input": "Here we use a classic deuterium exchange reaction to replace the C2 - H hydrogen atom of the His imidazole ring with deuterium, leading to a unique aromatic C2 - D stretching vibration whose frequency is sensitive to environmental changes across the entire imidazole ring.", "output": "deuterium, C2 - H, hydrogen, His, imidazole, deuterium, C2 - D, imidazole." }, { "input": "Using nonresonant Raman spectroscopy, we demonstrate using model compounds that the frequency of this C2 - D vibration shifts by 35 cm ( - 1 ) upon changes in the His protonation state.", "output": "C2 - D, His." }, { "input": "The C2 - D band is a very weak infrared absorber, so this vibration is not expected to be useful in infrared transmission experiments for proteins.", "output": "C2 - D." }, { "input": "Solvent - dependent Raman experiments indicate that the C2 - D band of the neutral imidazole ring is sensitive to H - bonding interaction with donors and acceptors of varying strengths, suggesting that the C2 - D frequency can be used to identify H - bonding partners of specific His residues.", "output": "C2 - D, imidazole, H, C2 - D, H, His." }, { "input": "Raman spectra at varying concentrations of Cu ( 2 + ) also show the C2 - D band ' s sensitivity to metal coordination, with differences due to changes in the coordination environment.", "output": "Cu ( 2 + ), C2 - D." }, { "input": "The strong Raman signal of this band and the sampling flexibility of Raman spectroscopy suggest that this vibration could be very useful in documenting the local role of His residues in many His - containing proteins and protein assemblies.", "output": "His, His." }, { "input": "Structural Investigation and Biological Activity of Sesquiterpene Lactones from the Traditional Chinese Herb Inula racemosa.", "output": "Sesquiterpene Lactones." }, { "input": "Five new sesquiterpene lactones, racemosalactones A - E ( 1 - 5 ), along with 19 known sesquiterpene latones ( 6 - 24 ), were isolated from the roots of Inula racemosa.", "output": "sesquiterpene lactones, racemosalactones A - E, sesquiterpene latones." }, { "input": "Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X - ray diffraction analysis.", "output": "There is no related enetity." }, { "input": "Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0. 38 to 4. 19 mu g / mL against human non - small - cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells.", "output": "There is no related enetity." }, { "input": "Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2. 4 and 2. 5 mu g / mL, respectively.", "output": "There is no related enetity." }, { "input": "Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1. 0 mu g / mL.", "output": "There is no related enetity." }, { "input": "A method for the rapid and straightforward preparative - scale isolation of compound 6 from alantolides is described.", "output": "alantolides." }, { "input": "Digitized charge transfer magnitude determined by metal - organic coordination number.", "output": "There is no related enetity." }, { "input": "Well - ordered metal - organic nanostructures of Fe - PTCDA ( perylene - 3, 4, 9, 10 - tetracarboxylic - 3, 4, 9, 10 - dianhydride ) chains and networks are grown on a Au ( 111 ) surface.", "output": "Fe - PTCDA, perylene - 3 , 4 , 9 , 10 - tetracarboxylic - 3 , 4 , 9 , 10 - dianhydride, Au." }, { "input": "These structures are investigated by high - resolution scanning tunneling microscopy.", "output": "There is no related enetity." }, { "input": "Digitized frontier orbital shifts are followed in scanning tunneling spectroscopy.", "output": "There is no related enetity." }, { "input": "By comparing the frontier energies with the molecular coordination environments, we conclude that the specific coordination affects the magnitude of charge transfer onto each PTCDA in the Fe - PTCDA hybridization system.", "output": "PTCDA, Fe - PTCDA." }, { "input": "A basic model is derived, which captures the essential underlying physics and correlates the observed energetic shift of the frontier orbital with the charge transfer.", "output": "There is no related enetity." }, { "input": "Cryptocapsinepoxide - Type Carotenoids from Red Mamey, Pouteria sapota.", "output": "Cryptocapsinepoxide." }, { "input": "New carotenoids, cryptocapsin - 5, 6 - epoxide, 3 ' - deoxycapsanthin - 5, 6 - epoxide, and cryptocapsin - 5, 8 - epoxides, have been isolated from the ripe fruits of red mamey ( Pouteria sapota ).", "output": "cryptocapsin - 5 , 6 - epoxide, 3 ' - deoxycapsanthin - 5 , 6 - epoxide, cryptocapsin - 5 , 8 - epoxides." }, { "input": "Cryptocapsin - 5, 6 - epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the ( 5R, 6S ) - and ( 5S, 6R ) - stereoisomers were identified by HPLC - ECD analysis.", "output": "Cryptocapsin - 5 , 6 - epoxide, cryptocapsin." }, { "input": "Spectroscopic data of the natural ( anti ) and semisynthetic ( syn ) derivatives obtained by acid - catalyzed rearrangement of cryptocapsin - 5, 8 - epoxide stereoisomers were compared for structural elucidation.", "output": "cryptocapsin - 5 , 8 - epoxide." }, { "input": "Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin - 5, 8 - epoxides was performed, and HPLC - ECD analysis allowed configurational assignment of the separated stereoisomers.", "output": "cryptocapsin - 5 , 8 - epoxides." }, { "input": "Efficient Pro - survival / angiogenic miRNA Delivery by an MRI - Detectable Nanomaterial.", "output": "There is no related enetity." }, { "input": "Herein, we report the use of biodegradable nanoparticles ( NPs ) containing perfluoro - 1, 5 - crown ether ( PFCE ), a fluorine - based compound ( NP170 - PFCE ) with the capacity to track cells in vivo by magnetic ressonance imaging ( MRI ) and efficiently release miRNA.", "output": "perfluoro - 1 , 5 - crown ether, PFCE, fluorine, PFCE." }, { "input": "NP170 - PFCE complexed with miRNAs accumulate whitin the cell ' s endolysosomal compartment and interact with higher frequency with argonaute2 ( Ago2 ) and GW182 proteins, which are involved in the biological action of miRNAs, than commercial complexes formed by commercial reagents and miRNA, which in turn accumulate in the cell cytoplasm.", "output": "PFCE." }, { "input": "The release of miRNA132 ( miR132 ) from the NPs increased 3 - fold the survival of endothelial cells ( ECs ) transplanted in vivo and 3. 5 - fold the blood perfusion in ischemic limbs relatively to control.", "output": "There is no related enetity." }, { "input": "Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N - hydroxyarylamine O - acetyltransferase.", "output": "lysine, N - hydroxyarylamine, O." }, { "input": "CobB is a bacterial NAD ( + ) - dependent protein deacetylase.", "output": "NAD ( + )." }, { "input": "Although progress has been made in functional studies of this protein in recent years, its substrates and biological functions are still largely unclear.", "output": "There is no related enetity." }, { "input": "Using proteome microarray technology, potential substrates of Escherichia coli CobB were screened and nine proteins were identified, including N - hydroxyarylamine O - acetyltransferase ( NhoA ).", "output": "N - hydroxyarylamine, O." }, { "input": "In vitro acetylation / deacetylation of NhoA was verified by western blotting and mass spectrometry, and two acetylated lysine residues were identified.", "output": "lysine." }, { "input": "Site - specific mutagenesis experiments showed that mutation of each acetylated lysine decreased the acetylation level of NhoA in vitro.", "output": "lysine." }, { "input": "Further analysis showed that variant NhoA proteins carrying substitutions at the two acetylated lysine residues are involved in both the O - acetyltransferase and N - acetyltransferase activity of NhoA.", "output": "lysine, O, N." }, { "input": "Structural analyses were also performed to explore the effects of the acetylated lysine residues on the activity of NhoA.", "output": "lysine." }, { "input": "These results suggest that reversible acetylation may play a role in the activity of Escherichia coli NhoA.", "output": "There is no related enetity." }, { "input": "Autoprocessing mechanism of severe acute respiratory syndrome coronavirus 3C - like protease ( SARS - CoV 3CL ( pro ) ) from its polyproteins.", "output": "There is no related enetity." }, { "input": "Like many other RNA viruses, severe acute respiratory syndrome coronavirus ( SARS - CoV ) produces polyproteins containing several non - structural proteins, which are then processed by the viral proteases.", "output": "There is no related enetity." }, { "input": "These proteases often exist within the polyproteins, and are excised by their own proteolytic activity ( ' autoprocessing ' ).", "output": "There is no related enetity." }, { "input": "It is important to investigate the autoprocessing mechanism of these proteases from the point of view of anti - SARS - CoV drug design.", "output": "There is no related enetity." }, { "input": "In this paper, we describe a new method for investigating the autoprocessing mechanism of the main protease ( M ( pro ) ), which is also called the 3C - like protease ( 3CL ( pro ) ).", "output": "There is no related enetity." }, { "input": "Using our method, we measured the activities, under the same conditions, of the mature form and pro - forms with the N - terminal pro - sequence, the C - terminal pro - sequence or both pro - sequences, toward the pro - form with both N - and C - terminal pro - sequences.", "output": "N, C, N, C." }, { "input": "The data indicate that the pro - forms of the enzyme have proteolytic activity, and are stimulated by the same proteolytic activity.", "output": "There is no related enetity." }, { "input": "The stimulation occurs in two steps, with approximately eightfold stimulation by N - terminal cleavage, approximately fourfold stimulation by C - terminal cleavage, and 23 - fold stimulation by the cleavage of both termini, compared to the pro - form with both the N - and C - terminal pro - sequences.", "output": "N, C, N, C." }, { "input": "Such cleavage mainly occurs in a trans manner; i. e. the pro - form dimer cleaves the monomeric form.", "output": "There is no related enetity." }, { "input": "The stimulation by N - terminal pro - sequence removal is due to the cis ( intra - dimer and inter - protomer ) effect of formation of the new N - terminus, whereas that by C - terminal cleavage is due to removal of its trans ( inter - dimer ) inhibitory effect.", "output": "N, C." }, { "input": "A numerical simulation of the maturation pathway is presented.", "output": "There is no related enetity." }, { "input": "Computational design and biosensor applications of small molecule - sensing allosteric ribozymes.", "output": "There is no related enetity." }, { "input": "Here I describe accurate and time - efficient computational methods for designing small molecule - sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions.", "output": "There is no related enetity." }, { "input": "Theophylline - sensing ribozymes are engineered to have a high cleavage rate of 1. 3 min ( - 1 ) under physiologically relevant conditions.", "output": "Theophylline." }, { "input": "They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group.", "output": "theophylline, caffeine, methyl." }, { "input": "These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures.", "output": "theophylline." }, { "input": "Purine - sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions.", "output": "Purine, guanine, adenine." }, { "input": "I have developed high - throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery.", "output": "purine." }, { "input": "The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high - throughput screening arrays, and molecular computing.", "output": "There is no related enetity." }, { "input": "TDDFT studies on the determination of the absolute configurations and chiroptical properties of Strandberg - type polyoxometalates.", "output": "There is no related enetity." }, { "input": "The electronic circular dichroism ( ECD ) and UV - visible absorption ( UV - vis ) spectra of Strandberg - type polyoxometalates ( POMs ) ( R, R ) - [ ( R * PO3 ) 2M5O15 ] ( 2 - ) ( R * = CH3CH ( NH3 ), ( M = Mo, W ) ) have been explored using the time - dependent density functional theory ( TDDFT ) method.", "output": "polyoxometalates, POMs, ( R , R ) - [ ( R * PO3 ) 2M5O15 ] ( 2 - ), CH3CH ( NH3 ), Mo, W." }, { "input": "It demonstrates that the absolute configurations of chiral systems can be determined by chiroptical spectroscopic methods combined with DFT calculations.", "output": "There is no related enetity." }, { "input": "The calculated ECD spectra of the Strandberg - type molybdate were produced over the range of 3. 3 - 6. 5 eV, which are generally in agreement with the experimental spectra.", "output": "There is no related enetity." }, { "input": "In addition, the ECD spectra of ( R, R ) - [ ( R * PO3 ) 2W5O15 ] ( 2 - ) ( R * = CH3CH ( NH3 ) ) were produced over the range of 4. 5 - 8. 5 eV.", "output": "( R , R ) - [ ( R * PO3 ) 2W5O15 ] ( 2 - ), CH3CH ( NH3 )." }, { "input": "The Becke ' s half - and - half hybrid exchange - correlation functional ( BHandHLYP ) with the HF exchange fraction to 55 % hybrid functional was found to well predict the excitation energies of studied systems.", "output": "There is no related enetity." }, { "input": "The origins of the ECD bands of two systems are mainly ascribed to charge - transfer ( CT ) transitions from oxygen atoms to metal atoms in polyanion.", "output": "oxygen." }, { "input": "The results suggest that the polyanion are chiroptical chromophores.", "output": "There is no related enetity." }, { "input": "The polyanion plays a role as an optically active chromophore and contribute to the absorptions of ECD spectra.", "output": "There is no related enetity." }, { "input": "The difference of the UV - vis / ECD spectra between two systems shows that the transition metal atom significantly influences on the chiroptical properties of the studied Strandberg - type POMs.", "output": "transition metal, POMs." }, { "input": "Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.", "output": "There is no related enetity." }, { "input": "Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER.", "output": "There is no related enetity." }, { "input": "We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice.", "output": "There is no related enetity." }, { "input": "Cloning of a short - period circadian mutant, Past - time, revealed a glycine to glutamate missense mutation in Fbxl21, an F - box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation.", "output": "glycine, glutamate." }, { "input": "While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening.", "output": "There is no related enetity." }, { "input": "FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus.", "output": "There is no related enetity." }, { "input": "FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm.", "output": "There is no related enetity." }, { "input": "Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals.", "output": "There is no related enetity." }, { "input": "Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus.", "output": "NMDA." }, { "input": "The activation of N - methyl - D - aspartate - receptors ( NMDARs ) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration.", "output": "N - methyl - D - aspartate." }, { "input": "At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus.", "output": "There is no related enetity." }, { "input": "In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus.", "output": "There is no related enetity." }, { "input": "Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine - 180 by ERK1 / 2.", "output": "serine." }, { "input": "Long - distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament alpha - internexin hinders dephosphorylation of the Jacob / ERK complex during nuclear transit.", "output": "There is no related enetity." }, { "input": "In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity.", "output": "There is no related enetity." }, { "input": "Involvement of regucalcin in lipid metabolism and diabetes.", "output": "There is no related enetity." }, { "input": "Regucalcin ( RGN / SMP30 ) was originally discovered in 1978 as a unique calcium - binding protein that does not contain the EF - hand motif of calcium - binding domain.", "output": "calcium, calcium." }, { "input": "The regucalcin gene ( rgn ) is localized on the X chromosome and is identified in over 15 species consisting the regucalcin family.", "output": "There is no related enetity." }, { "input": "Regucalcin has been shown to play a multifunctional role in cell regulation; maintaining of intracellular calcium homeostasis and suppressing of signal transduction, translational protein synthesis, nuclear deoxyribonucleic acid ( DNA ) and ribonucleic acid ( RNA ) synthesis, proliferation, and apoptosis in many cell types.", "output": "calcium." }, { "input": "Moreover, regucalcin may play a pathophysiological role in metabolic disorder.", "output": "There is no related enetity." }, { "input": "The expression of regucalcin is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by streptozotocin administration in vivo.", "output": "streptozotocin." }, { "input": "Overexpression of endogenous regucalcin stimulates glucose utilization and lipid production in liver cells with glucose supplementation in vitro.", "output": "glucose, glucose." }, { "input": "Regucalcin reveals insulin resistance in liver cells.", "output": "There is no related enetity." }, { "input": "Deficiency of regucalcin induces an impairment of glucose tolerance and lipid accumulation in the liver of mice in vivo.", "output": "glucose." }, { "input": "Overexpression of endogenous regucalcin has been shown to decrease triglyceride, total cholesterol and glycogen contents in the liver of rats, inducing hyperlipidemia.", "output": "triglyceride, cholesterol." }, { "input": "Leptin and adiponectin mRNA expressions in the liver tissues are decreased in regucalcin transgenic rats.", "output": "There is no related enetity." }, { "input": "Decrease in hepatic regucalcin is associated with the development and progression of nonalcoholic fatty liver disease and fibrosis in human patients.", "output": "There is no related enetity." }, { "input": "Regucalcin may be a key molecule in lipid metabolic disorder and diabetes.", "output": "There is no related enetity." }, { "input": "Synthesis and evaluation against hepatitis C virus of 7 - deaza analogues of 2 ' - C - methyl - 6 - O - methyl guanosine nucleoside and L - Alanine ester phosphoramidates.", "output": "2 ' - C - methyl - 6 - O - methyl guanosine nucleoside, L - Alanine ester phosphoramidates." }, { "input": "7 - Deazapurines are known to possess broad antiviral activity, however the 2 ' - C - methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus ( HCV ) replication.", "output": "2 ' - C - methylguanosine." }, { "input": "We previously reported the 6 - O - methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2 ' - C - methyl - 6 - O - methylguanosine has lead to potent HCV inhibitors now in clinical trials.", "output": "6 - O - methyl, guanine nucleosides, 2 ' - C - methyl - 6 - O - methylguanosine." }, { "input": "In this Letter, we report the synthesis and biological evaluation of 2 ' - C - methyl - 6 - O - methyl - 7 - deaza guanosine and ProTide derivatives.", "output": "2 ' - C - methyl - 6 - O - methyl -, guanosine." }, { "input": "In contrast to prior studies, removal of the N - 7 of the nucleobase entirely negates anti - HCV activity compared to the 2 ' - C - methyl - 6 - O - methylguanosine analogues.", "output": "N, nucleobase, 2 ' - C - methyl - 6 - O - methylguanosine." }, { "input": "To understand better this significant loss of activity, enzymatic assays and molecular modeling were carried out and suggested 2 ' - C - methyl - 6 - O - methyl - 7 - deaza guanosine and related ProTides do not act as efficient prodrugs of the free nucleotide, in marked contrast to the case of the parent guanine analogue.", "output": "2 ' - C - methyl - 6 - O - methyl -, guanosine, nucleotide, guanine." }, { "input": "Discovery of 4 - alkylamino - 7 - aryl - 3 - cyanoquinoline LRRK2 kinase inhibitors.", "output": "4 - alkylamino - 7 - aryl - 3 - cyanoquinoline." }, { "input": "Mutations in leucine - rich repeat kinase 2 ( LRRK2 ) are associated with familial Parkinson ' s disease ( PD ).", "output": "leucine." }, { "input": "The kinase activity of this complex protein is increased by pathogenic mutations.", "output": "There is no related enetity." }, { "input": "Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD.", "output": "There is no related enetity." }, { "input": "Herein we report our findings on a series of 4 - alkylamino - 7 - aryl - 3 - cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2.", "output": "4 - alkylamino - 7 - aryl - 3 - cyanoquinolines." }, { "input": "Activity was determined in both biochemical and cellular assays.", "output": "There is no related enetity." }, { "input": "Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing.", "output": "Ser935." }, { "input": "Protective effects of propolis on female rats ' histopathological, biochemical and genotoxic changes during LPS induced endotoxemia.", "output": "There is no related enetity." }, { "input": "In recent years, propolis has been the object of extensive research for its antibacterial, antioxidant, anti - inflammatory, and antitumoral activities.", "output": "There is no related enetity." }, { "input": "This study aims to determine the hepatoprotective efficiency of propolis on experimental endotoxemia in rats.", "output": "There is no related enetity." }, { "input": "In the current study, fifty adult Sprague Dawley rats ( weighing 200 - 300g ) were randomly divided into five groups of ten rats each.", "output": "There is no related enetity." }, { "input": "Normal saline solution was administered to the rats in the control group, while in the second group LPS ( 30mg / kg ), in the third group propolis ( 250mg / kg ), in the fourth group first propolis and then LPS ( 30mg / kg ), and in the fifth group, first LPS ( 30mg / kg ) and then propolis were given.", "output": "There is no related enetity." }, { "input": "Six hours after the application, biochemical ( MDA levels ) and histopathological changes as well as global DNA methylation analysis in the liver tissue samples were determined, while in the blood tissue samples Genomic Template Stability ( GTS, % ) was evaluated using RAPD - PCR profiles.", "output": "MDA." }, { "input": "The results demonstrated that the administration of propolis could have a protective effect against changes of both genomic stability values and methylation profiles, and it minimized the increase in MDA and tissue damage caused by LPS.", "output": "MDA." }, { "input": "In conclusion, the application of propolis prior to LPS - induced endotoxemia has shown to reduce hepatic damage.", "output": "There is no related enetity." }, { "input": "Induction of apoptosis in human pancreatic MiaPaCa - 2 cells through the loss of mitochondrial membrane potential ( Delta Psi m ) by Gentiana kurroo root extract.", "output": "There is no related enetity." }, { "input": "The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line ( Miapaca - 2 ).", "output": "There is no related enetity." }, { "input": "The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays.", "output": "DPPH, hydroxyl." }, { "input": "The results were comparable to standard antioxidants like alpha - tocopherol, catechin and BHT used in such experiments.", "output": "alpha - tocopherol, catechin, BHT." }, { "input": "Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content ( 73 +/- 1. 02 and 46 +/- 2. 05mg / g extract respectively ).", "output": "flavonoid." }, { "input": "The anti - proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B ( SRB ) assay against Human colon cancer cell line ( HCT - 116 ), Lung carcinoma cell line ( A - 549 ), Pancreatic cancer cell line ( Miapaca - 2 ), Lung cancer cell line ( HOP - 62 ) and acute monocytic leukaemia cell line ( THP - 1 ).", "output": "sulphorhodamine B, SRB." }, { "input": "G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner.", "output": "There is no related enetity." }, { "input": "The extract induced cell cycle arrest in Miapaca - 2 cells at G0 / G1 phase of the cell cycle.", "output": "There is no related enetity." }, { "input": "The population of apoptotic cells increased from 11. 4 % in case of control to 49. 6 % at 100 mu g / ml of G. kurroo root extract.", "output": "There is no related enetity." }, { "input": "The extract also induced a remarkable decrease in mitochondrial membrane potential ( Delta Psi m ) leading to apoptosis of cancer cells used.", "output": "There is no related enetity." }, { "input": "The main chemical constituents identified by the liquid chromatography - tandem mass spectrometry ( LC - ESI - MSMS ) were found to be iridoid glucosides ( iridoids and secoiridoids ), xanthones and flavonoids.", "output": "iridoid glucosides, iridoids, secoiridoids, xanthones, flavonoids." }, { "input": "Iridoid glucosides are the bitter principles of Gentiana species.", "output": "Iridoid glucosides." }, { "input": "Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4 '' - O - beta - d - glucosyl - 6 ' - O - ( 4 - O - beta - d - glucosylcaffeoyl ) - linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo.", "output": "Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4 '' - O - beta - d - glucosyl - 6 ' - O - ( 4 - O - beta - d - glucosylcaffeoyl ) - linearoside, Swertisin, methanol." }, { "input": "Mechanism - based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals.", "output": "There is no related enetity." }, { "input": "The thyroid hormone ( TH ) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo - regulation, osmo - regulation, and axis of regulation of other endocrine systems, sexual behaviour and fertility and cardiovascular function.", "output": "There is no related enetity." }, { "input": "Therefore, concern about TH disruption ( THD ) has resulted in strategies being developed to identify THD chemicals ( THDCs ).", "output": "There is no related enetity." }, { "input": "Information on potential of chemicals causing THD is typically derived from animal studies.", "output": "There is no related enetity." }, { "input": "For the majority of chemicals, however, this information is either limited or unavailable.", "output": "There is no related enetity." }, { "input": "It is also unlikely that animal experiments will be performed for all THD relevant chemicals in the near future for ethical, financial and practical reasons.", "output": "There is no related enetity." }, { "input": "In addition, typical animal experiments often do not provide information on the mechanism of action of THDC, making it harder to extrapolate results across species.", "output": "There is no related enetity." }, { "input": "Relevant effects may not be identified in animal studies when the effects are delayed, life stage specific, not assessed by the experimental paradigm ( e. g., behaviour ) or only occur when an organism has to adapt to environmental factors by modulating TH levels.", "output": "There is no related enetity." }, { "input": "Therefore, in vitro and in silico alternatives to identify THDC and quantify their potency are needed.", "output": "There is no related enetity." }, { "input": "THDC have many potential mechanisms of action, including altered hormone production, transport, metabolism, receptor activation and disruption of several feed - back mechanisms.", "output": "There is no related enetity." }, { "input": "In vitro assays are available for many of these endpoints, and the application of modern ' - omics ' technologies, applicable for in vivo studies can help to reveal relevant and possibly new endpoints for inclusion in a targeted THDC in vitro test battery.", "output": "There is no related enetity." }, { "input": "Within the framework of the ASAT initiative ( Assuring Safety without Animal Testing ), an international group consisting of experts in the areas of thyroid endocrinology, toxicology of endocrine disruption, neurotoxicology, high - throughput screening, computational biology, and regulatory affairs has reviewed the state of science for ( 1 ) known mechanisms for THD plus examples of THDC; ( 2 ) in vitro THD tests currently available or under development related to these mechanisms; and ( 3 ) in silico methods for estimating the blood levels of THDC.", "output": "There is no related enetity." }, { "input": "Based on this scientific review, the panel has recommended a battery of test methods to be able to classify chemicals as of less or high concern for further hazard and risk assessment for THD.", "output": "There is no related enetity." }, { "input": "In addition, research gaps and needs are identified to be able to optimize and validate the targeted THD in vitro test battery for a mechanism - based strategy for a decision to opt out or to proceed with further testing for THD.", "output": "There is no related enetity." }, { "input": "Impact of co - administration of protonated nanostructured aluminum silicate ( cholesterol absorption inhibitor ) on the absorption of lipid soluble vitamins D3 and K1: An assessment of pharmacokinetic and in vitro intraluminal processing.", "output": "aluminum silicate, cholesterol, vitamins D3 and K1." }, { "input": "Protonated nanostructured aluminum silicate ( NSAS ) is a protonated montmorillonite clay that was shown to be effective as an inhibitor of intestinal cholesterol absorption.", "output": "aluminum silicate, montmorillonite, cholesterol." }, { "input": "The effect of NSAS on the intestinal absorption of nutrients is unknown.", "output": "There is no related enetity." }, { "input": "An in vitro lipolysis model was adapted to test the intraluminal processing of vitamin D3 and K1 in the presence of various amounts of NSAS.", "output": "vitamin D3 and K1." }, { "input": "Additionally, vitamin absorption was assessed in male Sprague - Dawley rats randomized in the following treatment groups: IV administration of 0. 1mg / kg vitamin D3 and 1mg / kg vitamin K1, and a single - dose gavage of 1mg / kg vitamin D3 and 5mg / kg of vitamin K1 in peanut oil with various doses of NSAS slurry, 2 % NSAS - fortified diet, or 50mg / kg stigmastanol.", "output": "vitamin D3, vitamin K1, vitamin D3, vitamin K1, stigmastanol." }, { "input": "The solubilized fraction of vitamin D3 in the lipolysis medium was reduced from 70 % to 46 % upon the addition of 120mg NSAS.", "output": "vitamin D3." }, { "input": "In contrast, the solubilized fractions of vitamin K1 were not significantly affected.", "output": "vitamin K1." }, { "input": "Although the NSAS - fortified diet did not significantly affect the absorbed fraction of both vitamins, NSAS slurry decreased the absorption of vitamin D3 as compared to the control.", "output": "vitamins, vitamin D3." }, { "input": "These results indicate that NSAS may be incorporated in diet to treat hypercholesterolemia; however, vitamin D3 monitoring may be required.", "output": "vitamin D3." }, { "input": "The effect of formulation on the penetration of coated and uncoated zinc oxide nanoparticles into the viable epidermis of human skin in vivo.", "output": "zinc oxide." }, { "input": "The use of nanoparticulate zinc oxide ( ZnO - NP ) in sunscreens and other cosmetic products has raised public health concerns.", "output": "zinc oxide, ZnO." }, { "input": "The two key issues are the extent of exposure to ZnO - NP and the likely hazard after the application of ZnO - NP in sunscreen and cosmetic products to humans in vivo.", "output": "ZnO, ZnO." }, { "input": "Our aims were to assess exposure by the extent of ZnO - NP penetration into the viable epidermis and hazard by changes in the viable epidermal redox state for a number of topical products.", "output": "ZnO." }, { "input": "Of particular interest is the role of the particle coating, formulation used, and the presence of any enhancers.", "output": "There is no related enetity." }, { "input": "Multiphoton tomography with fluorescence lifetime imaging microscopy ( MPT - FLIM ) was used to simultaneously observe ZnO - NP penetration and potential metabolic changes within the viable epidermis of human volunteers after topical application of various ZnO - NP products.", "output": "ZnO, ZnO." }, { "input": "Coated and uncoated ZnO - NP remained in the superficial layers of the SC and in the skin furrows.", "output": "ZnO." }, { "input": "We observed limited penetration of coated ZnO - NP dispersed in a water - in - oil emulsion formulation, which was predominantly localized adjacent to the skin furrow.", "output": "ZnO." }, { "input": "However, the presence of ZnO - NP in the viable epidermis did not alter the metabolic state or morphology of the cells.", "output": "ZnO." }, { "input": "In summary, our data suggest that some limited penetration of coated and uncoated ZnO - NP may occur into viable stratum granulosum epidermis adjacent to furrows, but that the extent is not sufficient to affect the redox state of those viable cells.", "output": "ZnO." }, { "input": "Characteristics of indomethacin - saccharin ( IMC - SAC ) co - crystals prepared by an anti - solvent crystallization process.", "output": "indomethacin, saccharin, IMC, SAC." }, { "input": "The creation of co - crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance.", "output": "There is no related enetity." }, { "input": "In this study, co - crystal powders of indomethacin and saccharin ( IMC - SAC ) were prepared by an anti - solvent ( water ) addition and compared with co - crystals by evaporation method.", "output": "indomethacin, saccharin, IMC, SAC." }, { "input": "No successful synthesis of a pharmaceutical co - crystal powder via an anti - solvent approach has been reported.", "output": "There is no related enetity." }, { "input": "Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC - SAC co - crystal powders by anti - solvent approach.", "output": "methanol, IMC, SAC." }, { "input": "The mechanism of a preferential formation of IMC - SAC co - crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept.", "output": "IMC, SAC, IMC." }, { "input": "Accordingly, the anti - solvent approach can be considered as a competitive route for producing pharmaceutical co - crystal powders with acceptable properties.", "output": "There is no related enetity." }, { "input": "Co - encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail.", "output": "There is no related enetity." }, { "input": "Co - encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered.", "output": "There is no related enetity." }, { "input": "In this work, a comprehensive study for the co - encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers ( NLC ) is presented.", "output": "olanzapine, simvastatin." }, { "input": "Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined.", "output": "There is no related enetity." }, { "input": "It comprises in vitro, in silico and cellular viability approaches.", "output": "There is no related enetity." }, { "input": "The optimization and rationalization of the systems are carried out using a two - step factorial design.", "output": "There is no related enetity." }, { "input": "It is shown that the external medium in the NLC dispersion strongly influences permeation.", "output": "There is no related enetity." }, { "input": "It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios ( 48 and 21, respectively for olanzapine and simvastatin ) relative to the drugs in solution.", "output": "olanzapine, simvastatin." }, { "input": "The developed formulations can be considered non - irritant.", "output": "There is no related enetity." }, { "input": "A correlation between enhancer positioning in a lipid bilayer, partially governed by a H - bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations.", "output": "H." }, { "input": "Effect of protein malnutrition on the metabolism and toxicity of cisplatin, 5 - fluorouracil and mitomycin C in rat stomach.", "output": "cisplatin, 5 - fluorouracil, mitomycin C." }, { "input": "This study investigated the effect of protein malnutrition on metabolism and toxicity of cisplatin ( CP ), 5 - fluorouracil ( FU ) and mitomycin C ( MMC ) in rat stomach.", "output": "cisplatin, 5 - fluorouracil, mitomycin C, MMC." }, { "input": "Weanling male Wistar rats received a normal ( 24 % ) or low ( 2. 5 % ) protein diet for 28days and were allocated into: normally - fed control, protein - malnourished control ( PM ), 3 normally - fed drug - treated groups and 3 protein - malnourished drug - treated groups ( PM - CP, PM - FU and PM - MMC ).", "output": "MMC." }, { "input": "Cisplatin and MMC were injected intraperitoneally ( 8mg / kg on day 26 and 1mg / kg / day for 7days, respectively ).", "output": "Cisplatin, MMC." }, { "input": "5 - Fluorouracil was given orally ( 50mg / kg / day for 5days ).", "output": "5 - Fluorouracil." }, { "input": "Compared with normally - fed counterparts, PM - CP rats exhibited higher glutathione S - transferase, aminopeptidase N and cysteine S - conjugate beta - lyase ( CCBL ) and lower gamma - glutamyltransferase activities, PM - FU rats exhibited decreased dihydropyrimidine dehydrogenase and cytochrome P450 1A1 / 2 activities and PM - MMC rats showed higher quinone reductase and depleted xanthine oxidase activities.", "output": "glutathione, S, N, cysteine, S, dihydropyrimidine, MMC, quinone, xanthine." }, { "input": "Protein - malnourished drug - treated groups exhibited exacerbated gastrotoxicity, relative to normally - fed counterparts, manifested by lower mucus levels, higher permeability and histopathological deterioration, along with increased oxidative stress in PM - CP rats and exaggerated prostaglandin E2 production in PM - MMC rats.", "output": "prostaglandin E2, MMC." }, { "input": "Conclusively, protein malnutrition alters CP, FU and MMC metabolism in rat stomach by enhancing CCBL pathway for CP activation, delaying FU elimination and activating two - electron reduction of MMC, potentiating their gastrotoxicity.", "output": "MMC, MMC." }, { "input": "Induction of endoplasmic reticulum stress - mediated apoptosis and non - canonical autophagy by luteolin in NCI - H460 lung carcinoma cells.", "output": "luteolin." }, { "input": "In this study, we investigated the anti - cancer effects of luteolin, a member of the flavonoid family, in NCI - H460 human lung carcinoma cells.", "output": "luteolin, flavonoid." }, { "input": "It was shown that luteolin induces apoptotic cell death through modulating both the extrinsic pathway and intrinsic pathways, which are suppressed by z - VAD - fmk, indicating that luteolin triggers caspase - dependant apoptosis.", "output": "luteolin, luteolin." }, { "input": "Furthermore, we found that the alpha subunit of the eukaryotic initiation factor 2 ( eIF2 alpha / C / EBP homologous protein pathway, but not the c - Jun N - terminal kinase pathway, played a critical role in induction of apoptosis by luteolin.", "output": "N, luteolin." }, { "input": "The data indicated that luteolin also induces autophagy; evidence for this is the accumulation of microtubule - associated protein light chain - 3 ( LC3 ) II protein, the increase of LC3 puncta as well as an enhanced autophagy flux.", "output": "luteolin." }, { "input": "In addition, inhibiting autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that luteolin - induced autophagy functions as a cell death mechanism.", "output": "bafilomycin A1, luteolin." }, { "input": "Notably, the activated caspases that appeared with luteolin treatment cleaved Beclin - 1, and the expression of LC3II remained the same even after cells were challenged with Beclin - 1 siRNA, demonstrating that luteolin induces Beclin - 1 - independent autophagy.", "output": "luteolin, luteolin." }, { "input": "Taken together, our findings showed that luteolin triggers both endoplasmic reticulum stress - related apoptosis and non - canonical autophagy, which function as a cell death mechanism in NCI - H460 human lung cancer cells.", "output": "luteolin." }, { "input": "Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.", "output": "Caffeic acid, adenine nucleotide." }, { "input": "This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase ( nucleoside triphosphate diphosphohydrolase ), Ecto - NPP ( nucleotide pyrophosphatase / phosphodiesterase ), 5 ' - nucleotidase and adenosine deaminase ( ADA ) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation.", "output": "caffeic acid, nucleoside triphosphate, nucleotide, adenosine." }, { "input": "Animals were divided into five groups: I ( control ); II ( oil ); III ( caffeic acid 10mg / kg ); IV ( caffeic acid 50mg / kg ); and V ( caffeic acid 100mg / kg ).", "output": "caffeic acid, caffeic acid, caffeic acid." }, { "input": "Animals were treated with caffeic acid diluted in oil for 30days.", "output": "caffeic acid." }, { "input": "In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control ( P < 0. 05 ).", "output": "caffeic acid, ATP, ADP." }, { "input": "The 5 ' - nucleotidase activity was decreased, while E - NPP and ADA activities were increased in platelets of rats of groups III, IV and V ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I ( P < 0. 05 ).", "output": "Caffeic acid." }, { "input": "In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control ( P < 0. 05 ).", "output": "caffeic acid." }, { "input": "These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.", "output": "caffeic acid, caffeic acid." }, { "input": "Prediction and characterization of the linear IgE epitopes for the major soybean allergen beta - conglycinin using immunoinformatics tools.", "output": "There is no related enetity." }, { "input": "The alpha subunit of beta - conglycinin is a major allergen in soybean.", "output": "There is no related enetity." }, { "input": "The objective of this study was to predict and identify the linear immunoglobulin ( Ig ) E epitopes of the soybean alpha subunit of beta - conglycinin.", "output": "There is no related enetity." }, { "input": "Three immunoinformatics tools were used to predict the potential epitopes and were confirmed by dot - blot inhibition using sera from soybean allergic subjects.", "output": "There is no related enetity." }, { "input": "As a result, 15 peptides were predicted and assembled by solid - phase synthesis.", "output": "There is no related enetity." }, { "input": "Eleven epitopes were identified by the dot - blot inhibition test.", "output": "There is no related enetity." }, { "input": "Moreover, peptide 3 had IgE binding capability with all sera ( 5 / 5 ) tested, while peptide 1, 4, 6, 8 and12 could bind to 4 / 5 of the sera samples.", "output": "There is no related enetity." }, { "input": "Secondary structure prediction of peptide 3 and circular dichroism test validated that the structure of peptide 3 was a random coil.", "output": "There is no related enetity." }, { "input": "Cytotoxicity of aluminium oxide nanoparticles towards fresh water algal isolate at low exposure concentrations.", "output": "aluminium oxide." }, { "input": "The growing commercial applications had brought aluminium oxide nanoparticles under toxicologists ' purview.", "output": "aluminium oxide." }, { "input": "In the present study, the cytotoxicity of two different sized aluminium oxide nanoparticles ( ANP ( 1 ), mean hydrodynamic diameter 82. 6 +/- 22nm and ANP ( 2 ), mean hydrodynamic diameter 246. 9 +/- 39nm ) towards freshwater algal isolate Chlorella ellipsoids at low exposure levels ( <= 1 mu g / mL ) using sterile lake water as the test medium was assessed.", "output": "aluminium oxide." }, { "input": "The dissolution of alumina nanoparticles and consequent contribution towards toxicity remained largely unexplored owing to its presumed insoluble nature.", "output": "alumina." }, { "input": "Herein, the leached Al ( 3 + ) ion mediated toxicity has been studied along with direct particulate toxicity to bring out the dynamics of toxicity through colloidal stability, biochemical, spectroscopic and microscopic analyses.", "output": "Al ( 3 + )." }, { "input": "The mean hydrodynamic diameter increased with time both for ANP ( 1 ) [ 82. 6 +/- 22nm ( 0h ) to 246. 3 +/- 59nm ( 24h ), to 1204 +/- 140nm ( 72h ) ] and ANP ( 2 ) [ 246. 9 +/- 39nm ( 0h ) to 368. 28 +/- 48nm ( 24h ), to 1225. 96 +/- 186nm ( 72h ) ] signifying decreased relative abundance of submicron sized particles ( < 1000nm ).", "output": "There is no related enetity." }, { "input": "The detailed cytotoxicity assays showed a significant reduction in the viability dependent on dose and exposure.", "output": "There is no related enetity." }, { "input": "A significant increase in ROS and LDH levels were noted for both ANPs at 1 mu g / mL concentration.", "output": "There is no related enetity." }, { "input": "The zeta potential and FT - IR analyses suggested surface chemical interaction between nanoparticles and algal cells.", "output": "There is no related enetity." }, { "input": "The substantial morphological changes and cell wall damage were confirmed through microscopic analyses ( SEM, TEM, and CLSM ).", "output": "There is no related enetity." }, { "input": "At 72h, significant Al ( 3 + ) ion release in the test medium [ 0. 092 mu g / mL for ANP ( 1 ), and 0. 19 mu g / mL for ANP ( 2 ) ] was noted, and the resulting suspension containing leached ions caused significant cytotoxicity, revealing a substantial ionic contribution.", "output": "Al ( 3 + )." }, { "input": "This study indicates that both the nano - size and ionic dissolution play a significant role in the cytotoxicity of ANPs towards freshwater algae, and the exposure period largely determines the prevalent mode of nano - toxicity.", "output": "There is no related enetity." }, { "input": "Food web analysis reveals effects of pH on mercury bioaccumulation at multiple trophic levels in streams.", "output": "mercury." }, { "input": "Biomagnification processes and the factors that govern them, including those for mercury ( Hg ), are poorly understood in streams.", "output": "mercury, Hg." }, { "input": "Total and methyl Hg concentrations and relative trophic position ( using delta ( 15 ) N ) were analyzed in biofilm and invertebrates from 21 streams in New Brunswick, Canada to assess food web biomagnification leading to the common minnow blacknose dace ( Rhinichthys atratulus ), a species known to have Hg concentrations that are higher in low pH waters.", "output": "methyl, Hg, ( 15 ) N, Hg." }, { "input": "Biomagnification slopes within stream food webs measured using Hg vs. delta ( 15 ) N or corresponding trophic levels ( TL ) differed depending on the chemical species analyzed, with total Hg exhibiting increases of 1. 3 - 2. 5 per TL ( mean slope of total Hg vs. delta ( 15 ) N = 0. 14 +/- 0. 06 S. D., range = 0. 06 - 0. 20 ) and methyl Hg showing a more pronounced increase of 2. 8 to 6. 0 per TL ( mean slope of methyl Hg vs. delta ( 15 ) N = 0. 30 +/- 0. 08 S. D., range = 0. 22 - 0. 39 ).", "output": "Hg, ( 15 ) N, Hg, Hg, ( 15 ) N, methyl, Hg, methyl, Hg, ( 15 ) N." }, { "input": "While Hg biomagnification slopes through the entire food web ( Trophic Magnification Factors, TMFs ) were not influenced by water chemistry ( pH ), dietary concentrations of methyl Hg strongly influenced biomagnification factors ( BMFs ) for consumer - diet pairs within the food web at lower trophic levels, and BMFs between dace and predatory invertebrates were significantly higher in low pH waters.", "output": "Hg, methyl, Hg." }, { "input": "These analyses, coupled with observations of higher Hg in primary producers in streams with low pH, suggest that pH influences both baseline concentrations and biomagnification of Hg in these systems.", "output": "Hg, Hg." }, { "input": "Because higher Hg concentrations in the diets of primary consumers and predatory insects in lower pH waters led to lower BMFs, these feeding groups showed insignificant relationships between Hg and pH; thus, altered BMFs associated with dietary concentrations can dampen the effects of environmental conditions on Hg concentrations.", "output": "Hg, Hg, Hg." }, { "input": "Light induced toxicity reduction of silver nanoparticles to Tetrahymena Pyriformis: Effect of particle size.", "output": "silver." }, { "input": "As a result of the extensive application of silver nanoparticles ( AgNPs ), their potential hazards, once they are released into the natural environment, are of great concern to people.", "output": "silver." }, { "input": "Since silver is very sensitive to light, the toxicity of AgNPs released into the natural environment will be inevitably affected by light.", "output": "silver." }, { "input": "The aim of this study was to investigate the relationship between light, toxicity, and particle size of AgNPs and deduce the possible mechanism of any interaction.", "output": "There is no related enetity." }, { "input": "Our study revealed that there was negative correlation between the particle size and the toxicity: small AgNPs ( 5 - 10nm ) had higher toxicity than large AgNPs ( 15 - 25nm ) to Tetrahymena pyriformis ( T. pyriformis ) under dark condition.", "output": "There is no related enetity." }, { "input": "Comparing the size dependent AgNPs toxicity under dark and light conditions, the effect of light to size dependent AgNPs toxicity was ascertained.", "output": "There is no related enetity." }, { "input": "The results indicated that AgNPs toxicity was decreased by light and the most important discovery was that the change of size dependent AgNPs toxicity had significant difference under light irradiation.", "output": "There is no related enetity." }, { "input": "The decrease of small AgNPs toxicity induced by light was more notable than large AgNPs.", "output": "There is no related enetity." }, { "input": "The decreased level of cell toxicity for small AgNPs was 32 +/- 0. 7 %, whereas it was only 10. 6 +/- 5. 2 % for large AgNPs kept 24h under light irradiation.", "output": "There is no related enetity." }, { "input": "The further investigation indicated that the above changes induced by light can be attributed to the decrease of released silver ions, particle growth and aggregation of AgNPs under light irradiation.", "output": "silver." }, { "input": "The obtained results showed that the light irradiation can promote the rapid growth of small AgNPs and result in the obvious increase of particle size and serious aggregation.", "output": "There is no related enetity." }, { "input": "These phenomena would induce the decrease of silver ions released from small AgNPs, which is responsible for the remarkable decrease of toxicity for small AgNPs.", "output": "silver." }, { "input": "Biodiversity of small molecules - a new perspective in screening set selection.", "output": "There is no related enetity." }, { "input": "How is the ' diversity ' of a compound set defined and how is the most appropriate compound subset identified for assay when screening the entire HTS deck is not an option?", "output": "There is no related enetity." }, { "input": "A common approach has so far been to cover as much of the chemical space as possible by screening a chemically diverse set of compounds.", "output": "There is no related enetity." }, { "input": "We show that, rather than chemical diversity, the biologic diversity of a compound library is an essential requirement for hit identification.", "output": "There is no related enetity." }, { "input": "We describe a simple and efficient approach for the design of a HTS library based on compound - target diversity.", "output": "There is no related enetity." }, { "input": "Biodiverse compound subsets outperform chemically diverse libraries regarding hit rate and the total number of unique chemical scaffolds present among hits.", "output": "There is no related enetity." }, { "input": "Specifically, by screening ~ 19 % of a HTS collection, we expect to discover ~ 50 - 80 % of all desired bioactive compounds.", "output": "There is no related enetity." }, { "input": "New quinazoline derivatives for telomeric G - quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability.", "output": "quinazoline, phenyl." }, { "input": "To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [ 17 ].", "output": "indoloquinoline, benzofuroquinoline, quinazoline." }, { "input": "These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond.", "output": "hydrogen." }, { "input": "Studies showed that these quinazoline derivatives were effective and selective telomeric G - quadruplex ligands.", "output": "quinazoline." }, { "input": "With this encouragement, here we synthesized a series of N - ( 2 - ( quinazolin - 2 - yl ) phenyl ) benzamide ( QPB ) compounds as modified quinazoline derivatives.", "output": "N - ( 2 - ( quinazolin - 2 - yl ) phenyl ) benzamide, QPB, quinazoline." }, { "input": "In this modification, a phenyl group was introduced to the aromatic core.", "output": "phenyl." }, { "input": "The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G - quadruplex DNA than LZ - 11, the most potential compound of reported quinazoline derivatives.", "output": "QPB, LZ - 11, quinazoline." }, { "input": "Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.", "output": "QPB." }, { "input": "Generation of intracellular reactive oxygen species and genotoxicity effect to exposure of nanosized polyamidoamine ( PAMAM ) dendrimers in PLHC - 1 cells in vitro.", "output": "oxygen, polyamidoamine, PAMAM." }, { "input": "Polyamidoamine ( PAMAM ) dendrimers have previously been demonstrated to elicit systematically variable cyto - and eco - toxic responses, promising as the basis for structure - activity relationships governing nanotoxicological responses.", "output": "Polyamidoamine, PAMAM." }, { "input": "In this study, increased production of intracellular reactive oxygen species ( ROS ), genotoxicity and apoptosis due to in vitro exposure of fish hepatocellular carcinoma cells to dendrimer generations G4, G5 and G6 is demonstrated.", "output": "oxygen." }, { "input": "A PAMAM dendrimer generation dependent increase in ROS and genotoxicity was observed, consistent with our previous studies.", "output": "PAMAM." }, { "input": "The toxicological responses correlate well with the nanoparticle surface chemistry, specifically, the number of surface amino groups per generation.", "output": "amino." }, { "input": "Although ROS production initially increases approximately linearly, it saturates at higher doses.", "output": "There is no related enetity." }, { "input": "Notably, normalized to the molar dose of surface amino groups, the dose - dependent ROS production for different generations overlap exactly, indicating that the response is due to these functional units.", "output": "amino." }, { "input": "The genotoxicity response is also well correlated to the number of surface amino groups and therefore generation of PAMAM dendrimers.", "output": "amino, PAMAM." }, { "input": "The observed genotoxicity, related to DNA damage, is related to the generation and dose dependent production of intracellular ROS, at low levels.", "output": "There is no related enetity." }, { "input": "At the higher ROS levels, increased DNA damage is associated with the onset of necrosis.", "output": "There is no related enetity." }, { "input": "Tissue Distribution and Identification of Radioactivity Components at Elimination Phase after Oral Administration of [ 14C ] CS - 1036, an alpha - Amylase Inhibitor, to Rats.", "output": "[ 14C ] CS - 1036." }, { "input": "( 2R, 3R, 4R ) - 4 - hydroxy - 2 - ( hydroxymethyl ) pyrrolidin - 3 - yl 4 - O - ( 6 - deoxy - beta - D - glucopyranosyl ) - alpha - D - glucopyranoside ( CS - 1036 ) is a potent inhibitor of pancreatic and salivary alpha - amylase.", "output": "( 2R , 3R , 4R ) - 4 - hydroxy - 2 - ( hydroxymethyl ) pyrrolidin - 3 - yl 4 - O - ( 6 - deoxy - beta - D - glucopyranosyl ) - alpha - D - glucopyranoside, CS - 1036." }, { "input": "After oral administration of [ ( 14 ) C ] CS - 1036 to rats, the radioactivity was still detectable up to 7 - 14 days after administration in various tissues, and its terminal phase in plasma could be explained neither by the exposure of CS - 1036 nor its major metabolite M1.", "output": "[ ( 14 ) C ] CS - 1036, CS - 1036." }, { "input": "The slow elimination of radioactivity in various tissues was hypothesized to be caused by covalent binding to macromolecules or use for biogenic components.", "output": "There is no related enetity." }, { "input": "To assess the use for biogenic components, amino acid analysis of plasma proteins and lipid analysis of adipose tissue were conducted after repeated oral administration of [ ( 14 ) C ] CS - 1036 by high - performance liquid chromatography and accelerated mass spectrometry and by thin layer chromatography and liquid chromatography / mass spectrometry, respectively.", "output": "amino acid, [ ( 14 ) C ] CS - 1036." }, { "input": "In amino acid analysis, glutamic acid, aspartic acid, alanine, and proline were identified as major radioactive amino acids, and radioactive nonessential amino acids occupied 76. 0 % of the radioactivity.", "output": "amino acid, glutamic acid, aspartic acid, alanine, proline, amino acids, amino acids." }, { "input": "In lipid analysis, a part of the radioactive lipids were identified as the fatty acids constituting the neutral lipids by lipase - hydrolysis.", "output": "fatty acids." }, { "input": "The radioactive fatty acids from neutral lipids were identified as palmitic acid, oleic acid, and 8, 11, 14 - eicosatrienoic acid.", "output": "fatty acids, palmitic acid, oleic acid, 8 , 11 , 14 - eicosatrienoic acid." }, { "input": "Intestinal flora were involved in CS - 1036 metabolism and are indicated to be involved in the production of small molecule metabolites, which are the sources for amino acids and fatty acids, from [ ( 14 ) C ] CS - 1036.", "output": "CS - 1036, amino acids, fatty acids, [ ( 14 ) C ] CS - 1036." }, { "input": "In conclusion, radioactivity derived from [ ( 14 ) C ] CS - 1036 was incorporated as the constituents of amino acids of plasma proteins and fatty acids of neutral lipids.", "output": "[ ( 14 ) C ] CS - 1036, amino acids, fatty acids." }, { "input": "Novel oleanolic vinyl boronates: Synthesis and antitumor activity.", "output": "oleanolic vinyl boronates." }, { "input": "A series of novel oleanane - type pentacyclic triterpenoids bearing a boronate ester moiety at C3 have been synthesized by palladium - catalyzed cross - coupling of bis ( pinacolato ) diboron with vinyl triflates, in the presence of base, and these compounds were fully characterized by 1D and 2D NMR techniques.", "output": "oleanane, triterpenoids, boronate ester, palladium, bis ( pinacolato ) diboron, vinyl triflates." }, { "input": "Evaluation of their antiproliferative effects on a panel of hematological - based and solid tumor cell lines identified three active oleanolic vinyl boronates that inhibited the growth of leukemia ( Jurkat, K562 ), Burkitt ' s lymphoma ( Jijoye ), cervix ( Hela ), colon ( SW480 ), and ovary ( SKOV - 3 ) cancer cells without concomitant inhibition of non - tumoral human fibroblasts.", "output": "oleanolic vinyl boronates." }, { "input": "Their mechanisms of action were investigated on the leukemia Jurkat cell line.", "output": "There is no related enetity." }, { "input": "The results show that the incorporation of boron in the oleanolic acid core combined with the presence of amide bonds afforded compounds with desirable biological effects such as apoptosis induction and inhibition of proteasomal activity on tumor cells, which makes them potential templates for further development in the anticancer drug setting.", "output": "boron, oleanolic acid, amide." }, { "input": "Microwave - assisted synthesis of arene ruthenium ( II ) complexes that induce S - phase arrest in cancer cells by DNA damage - mediated p53 phosphorylation.", "output": "arene ruthenium ( II )." }, { "input": "A series of arene ruthenium ( II ) complexes coordinated by phenanthroimidazole derivates, [ ( C6H6 ) Ru ( L ) Cl ] Cl. 2H2O ( 1b L = IP, 2b L = p - NMe2PIP, 3b L = p - MeOPIP, 4b L = p - HOPIP, 5b L = p - COOHPIP, 6b L = p - CF3PIP, 7b L = p - BrPIP ) have been synthesized in yields of 89 - 92 % under microwave irradiation in 30 min, and the crystal structure of 1b by XRD gives a typical \" piano stool \" conformation.", "output": "arene ruthenium ( II ), phenanthroimidazole, [ ( C6H6 ) Ru ( L ) Cl ] Cl . 2H2O, p - NMe2PIP, p - MeOPIP, p - HOPIP, p - COOHPIP, p - CF3PIP, p - BrPIP." }, { "input": "The antitumor activity of these complexes against various tumor cells have been evaluated by MTT assay, and the results show that this type of arene Ru ( II ) complexes exhibit acceptable inhibitory effect against all of these tumor cells, especially osteosarcoma MG - 63 cells, but with low toxicity toward HK - 2 human normal cells.", "output": "MTT, arene, Ru ( II )." }, { "input": "Studies on the mechanism revealed that cell cycle arrest at S - phase in MG - 63 cells induced by the arene Ru ( II ) complex 2b, which was confirmed by the increase in the percentage of cells at S - phase and down - regulator of cyclin A.", "output": "arene, Ru ( II )." }, { "input": "The further studies by Comet assay at single cell level indicated that DNA damage in MG - 63 cells was triggered by 2b, following with the up - regulation of phosphorylated p53 and histone.", "output": "There is no related enetity." }, { "input": "The studies by spectroscopy in vitro also indicate that 2b bind to DNA molecule by intercalative mode to disturb the bio - function of tumor cells.", "output": "There is no related enetity." }, { "input": "In conclusion, the synthetic arene Ru ( II ) complexes could serve as novel p53 activator with potential application in cancer chemotherapy.", "output": "arene, Ru ( II )." }, { "input": "Capping - agent - free synthesis of substrate - supported porous icosahedral gold nanoparticles.", "output": "There is no related enetity." }, { "input": "We report a new capping - agent - free strategy for the synthesis of substrate - supported porous icosahedral Au nanoparticles ( NPs ) with rough naked surfaces, based on the crystallization from substrate - supported thin solution layers followed by solid - phase thermolysis.", "output": "Au." }, { "input": "The plasmonic properties of icosahedral Au NPs have been studied using single particle dark - field scattering microscopy and spectroscopy.", "output": "Au." }, { "input": "The two distinct localized surface plasmon resonance ( LSPR ) bands observed in the single particle dark - field spectra can be ascribed to the quadrupole resonance at ca.", "output": "There is no related enetity." }, { "input": "425 nm and the size - dependent dipole resonance in the red region ( 645 - 708 nm ).", "output": "There is no related enetity." }, { "input": "The unique rough naked surface, the facile synthesis, together with the ability to control the nanoparticle size and to vary the LSPR frequency in the red region, would make the substrate - supported porous icosahedral Au NPs promising on multiple levels in the applications of catalysis, ultrasensitive biosensors, and in surface - enhanced Raman scattering ( SERS ).", "output": "Au." }, { "input": "Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid - Recognition Site in the BK Channel beta 1 - Subunit by a Novel Nonsteroidal Agent.", "output": "Cholane, Steroid." }, { "input": "The Ca ( 2 + ) / voltage - gated K ( + ) large conductance ( BK ) channel beta 1 subunit is particularly abundant in vascular smooth muscle.", "output": "Ca ( 2 +, K ( + )." }, { "input": "By determining their phenotype, BK beta 1 allows the BK channels to reduce myogenic tone, facilitating vasodilation.", "output": "There is no related enetity." }, { "input": "The endogenous steroid lithocholic acid ( LCA ) dilates cerebral arteries via BK channel activation, which requires recognition by a BK beta 1 site that includes Thr169.", "output": "steroid, lithocholic acid, LCA, Thr169." }, { "input": "Whether exogenous nonsteroidal agents can access this site to selectively activate beta 1 - containing BK channels and evoke vasodilation remain unknown.", "output": "There is no related enetity." }, { "input": "We performed a chemical structure database similarity search using LCA as a template, along with a two - step reaction to generate sodium 3 - hydroxyolean - 12 - en - 30 - oate ( HENA ).", "output": "LCA, sodium 3 - hydroxyolean - 12 - en - 30 - oate, HENA." }, { "input": "HENA activated the BK ( cbv1 + beta 1 ) channels cloned from rat cerebral artery myocytes with a potency ( EC50 = 53 mu M ) similar to and an efficacy ( x 2. 5 potentiation ) significantly greater than that of LCA.", "output": "HENA, LCA." }, { "input": "This HENA action was replicated on native channels in rat cerebral artery myocytes.", "output": "HENA." }, { "input": "HENA failed to activate the channels made of cbv1 + beta 2, beta 3, beta 4, or beta 1T169A, indicating that this drug selectively targets beta 1 - containing BK channels via the BK beta 1 steroid - sensing site.", "output": "HENA, steroid." }, { "input": "HENA ( 3 - 45 mu M ) dilated the rat and C57BL / 6 mouse pressurized cerebral arteries.", "output": "HENA." }, { "input": "Consistent with the electrophysiologic results, this effect was larger than that of LCA.", "output": "LCA." }, { "input": "HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK beta 1 ' s role in HENA action.", "output": "HENA, HENA." }, { "input": "Finally, carotid artery - infusion of HENA ( 45 mu M ) dilated the pial cerebral arterioles via selective BK - channel targeting.", "output": "HENA." }, { "input": "In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates beta 1 - containing BK channels by targeting the steroid - sensing site in BK beta 1, rendering vasodilation.", "output": "steroid." }, { "input": "Contribution of the m1 transmembrane helix and pre - m1 region to positive allosteric modulation and gating of N - methyl - d - aspartate receptors.", "output": "N - methyl - d - aspartate." }, { "input": "N - methyl - d - aspartate ( NMDA ) receptors are glutamate - gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions.", "output": "N - methyl - d - aspartate, NMDA." }, { "input": "NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules.", "output": "NMDA." }, { "input": "Elucidating the structural determinants and mechanism of action by which allosteric regulators control gating will enhance our understanding of NMDA receptor activation and facilitate the development of novel therapeutics.", "output": "NMDA." }, { "input": "Here, we investigated the structural determinants for ( 3 - chlorophenyl ) ( 6, 7 - dimethoxy - 1 - ( ( 4 - methoxyphenoxy ) methyl ) - 3, 4 - dihydroisoquinolin - 2 ( 1H ) - yl ) methanone ( CIQ ), a GluN2C / 2D - selective positive allosteric modulator.", "output": "( 3 - chlorophenyl ) ( 6 , 7 - dimethoxy - 1 - ( ( 4 - methoxyphenoxy ) methyl ) - 3 , 4 - dihydroisoquinolin - 2 ( 1H ) - yl ) methanone, CIQ." }, { "input": "We show that CIQ does not bind to the amino - terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist - binding domain dimer interface or ion channel pore.", "output": "CIQ, amino, NMDA." }, { "input": "Rather, we identified critical determinants of CIQ modulation in the region near the first transmembrane helix of GluN2D, including in a putative pre - M1 cuff helix that may influence channel gating.", "output": "CIQ." }, { "input": "We also show that mutations within the GluN2D pre - M1 region alter open probability of the NMDA receptor.", "output": "NMDA." }, { "input": "These results suggest a novel site of action for potentiation of NMDA receptors by small molecules and implicate the pre - M1 region in NMDA receptor gating.", "output": "NMDA, NMDA." }, { "input": "Properties and self - assembled packing morphology of long alkyl - chained substituted polyhedral oligomeric silsesquioxanes ( POSS ) cages.", "output": "polyhedral oligomeric silsesquioxanes, POSS." }, { "input": "Polyhedral oligomeric silsesquioxane ( POSS ) cubic cage systems ( octa - n - octadecyloctasilsesquioxane, ( T8C18 ) and octakis ( n - octadecyldimethylsiloxy ) octasilsesquioxane, ( Q8C18 ) ) were synthesised with eight long n - alkyl chain ( R = C18H37 ) substituent arms, as model nano - functionalized compounds.", "output": "Polyhedral oligomeric silsesquioxane, POSS, octa - n - octadecyloctasilsesquioxane, T8C18, octakis ( n - octadecyldimethylsiloxy ) octasilsesquioxane, Q8C18, C18H37." }, { "input": "The crystalline packing morphology of the cages was studied using time - resolved Small - and Wide - angle X - ray scattering ( SAXS / WAXS ), thermal and optical techniques.", "output": "There is no related enetity." }, { "input": "From thermal analysis the melting and crystallization temperatures of the Q8 cage were significantly less than those for the T8 cage.", "output": "There is no related enetity." }, { "input": "X - ray scattering showed that both cage systems have long - range crystalline ordering where the alkyl chains align in a parallel axial disposition from the POSS core giving a ' rod - like ' self - assembled packing morphology.", "output": "There is no related enetity." }, { "input": "The packing length - scale can be directly related to the overall dimensions of the POSS molecules.", "output": "There is no related enetity." }, { "input": "Compared to the T8 cages, the Q8 cages pack more efficiently allowing the interdigitation of the alkyl chain arms.", "output": "There is no related enetity." }, { "input": "Different packing modes and thermal behaviour observed for the T8 and Q8 cages is directly attributed to their structural chemistry.", "output": "There is no related enetity." }, { "input": "For the Q8 cage, the presence of the OSiMe2 spacer groups which tether the alkyl chain arms to the cage ( absent in the T8 cages ) allows greater flexibility of the arms letting them interdigitate with each other when packing which is not observed for the analogous T8 cages.", "output": "OSiMe2." }, { "input": "Glycosylation of conotoxins.", "output": "There is no related enetity." }, { "input": "Conotoxins are small peptides present in the venom of cone snails.", "output": "There is no related enetity." }, { "input": "The snail uses this venom to paralyze and capture prey.", "output": "There is no related enetity." }, { "input": "The constituent conopeptides display a high level of chemical diversity and are of particular interest for scientists as tools employed in neurological studies and for drug development, because they target with exquisite specificity membrane receptors, transporters, and various ion channels in the nervous system.", "output": "There is no related enetity." }, { "input": "However, these peptides are known to contain a high frequency and variability of post - translational modifications - including sometimes O - glycosylation - which are of importance for biological activity.", "output": "O." }, { "input": "The potential application of specific conotoxins as neuropharmalogical agents and chemical probes requires a full characterization of the relevant peptides, including the structure of the carbohydrate part.", "output": "carbohydrate." }, { "input": "In this review, the currently existing knowledge of O - glycosylation of conotoxins is described.", "output": "O." }, { "input": "Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin / orphanin FQ limiting its ability to reduce binge eating in female rats.", "output": "There is no related enetity." }, { "input": "RATIONALE: Nociceptin / orphanin FQ ( N / OFQ ) is a functional antagonist of corticotrophin - releasing factor, the main mediator of the stress response.", "output": "There is no related enetity." }, { "input": "Stress represents a key determinant of binge eating ( BE ) for highly palatable food ( HPF ).", "output": "There is no related enetity." }, { "input": "OBJECTIVES: In relation to the antistress properties of N / OFQ, we evaluated its effect on BE.", "output": "There is no related enetity." }, { "input": "After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N / OFQ was investigated after cycles of food restrictions.", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction / refeeding and then stressed, or not stressed.", "output": "There is no related enetity." }, { "input": "In the other experiments, two groups were used: rats exposed or not to food restriction.", "output": "There is no related enetity." }, { "input": "RESULTS: Only restricted and stressed rats exhibited BE for HPF ( containing chocolate cream ).", "output": "There is no related enetity." }, { "input": "Intracerebroventricular injections of N / OFQ of 0. 5 nmol / rat significantly reduced BE.", "output": "There is no related enetity." }, { "input": "N / OFQ 1 nmol / rat did not reduce BE but significantly increased HPF intake following food restrictions.", "output": "There is no related enetity." }, { "input": "Cycles of food restriction increased animals ' sensitivity to the hyperphagic effect of N / OFQ for HPF.", "output": "There is no related enetity." }, { "input": "In situ hybridization studies following food restrictions showed decreased ppN / OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN / OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: These findings indicate that N / OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.", "output": "There is no related enetity." }, { "input": "Neural substrates of acupuncture in the modulation of cravings induced by smoking - related visual cues: an FMRI study.", "output": "There is no related enetity." }, { "input": "RATIONALE: Cue reactivity is a key factor in modulating motivational and goal - directed behaviors associated with compulsive drug intake and relapse.", "output": "There is no related enetity." }, { "input": "Smoking - associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We investigated whether acupuncture ameliorates cravings induced by smoking - related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges.", "output": "There is no related enetity." }, { "input": "METHODS: After 36 h of smoking abstinence, 25 right - handed male smokers underwent fMRI, during which smoking - related and neutral visual cues were presented.", "output": "There is no related enetity." }, { "input": "Twelve subjects were treated with real acupuncture ( RA ) at HT7 and 13 subjects received sham acupuncture ( SA ).", "output": "There is no related enetity." }, { "input": "During the scanning sessions, craving scores to smoking - related visual cues were assessed before and after RA or SA treatment.", "output": "There is no related enetity." }, { "input": "The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three - way ANOVAs ( Cue x Session x Group ).", "output": "There is no related enetity." }, { "input": "RESULTS: After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group.", "output": "There is no related enetity." }, { "input": "When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: These findings suggest that acupuncture alleviates cue - induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase.", "output": "There is no related enetity." }, { "input": "Impacts of spinosad and lambda - cyhalothrin on spider communities in cabbage fields in south Texas.", "output": "spinosad, lambda - cyhalothrin." }, { "input": "Spiders are a principal arthropod group that preys on numerous pests of vegetables and other crops.", "output": "There is no related enetity." }, { "input": "In this study, we determined the effects of the two most commonly used insecticides, spinosad and lambda - cyhalothrin, on diversity of spiders on cabbage in south Texas.", "output": "spinosad, lambda - cyhalothrin." }, { "input": "In two seasons ( fall 2008 and spring 2009 ), we collected a total of 588 spiders belonging to 53 species in 11 families from spinosad and lambda - cyhalothrin - treated cabbages and the untreated control plants.", "output": "spinosad, lambda - cyhalothrin." }, { "input": "A great majority of spiders were collected from the pitfall traps ( 554 ) where only a few ( 34 ) were collected from the blower / vacuum sampling.", "output": "There is no related enetity." }, { "input": "In the insecticide - treated plots, there were significantly fewer spider individuals, species and families than in untreated fields.", "output": "There is no related enetity." }, { "input": "Spinosad had significantly less effect on spiders in total individuals, number of species and families than lambda - cyhalothrin.", "output": "Spinosad, lambda - cyhalothrin." }, { "input": "The effects of the two insecticides were further demonstrated by the Shannon - Weiner index ( H ' ) and the hierarchical richness index ( HRI ).", "output": "There is no related enetity." }, { "input": "Spider diversity in the spinosad - treated plots were not significantly different from that in the untreated fields but were greater than those in lambda - cyhalothrin - treated plots in both seasons when measured by H ' values.", "output": "spinosad, lambda - cyhalothrin." }, { "input": "In contrast, the H ' values of spider ' s diversity in the lambda - cyhalothrin - treated plots were significantly lower than spinosad - treated and untreated plots.", "output": "lambda - cyhalothrin, spinosad." }, { "input": "High values of HRI for spider richness in the spinosad - treated plots suggested that spinosad had less effect on spiders than lambda - cyhalothrin.", "output": "spinosad, spinosad, lambda - cyhalothrin." }, { "input": "We concluded that spinosad was more compatible with spiders on cabbage compared to lambda - cyhalothrin and that this information should be used when developing insecticide resistance management strategies.", "output": "spinosad, lambda - cyhalothrin." }, { "input": "Unraveling a phosphorylation event in a folded protein by NMR spectroscopy: phosphorylation of the Pin1 WW domain by PKA.", "output": "There is no related enetity." }, { "input": "The Pin1 protein plays a critical role in the functional regulation of the hyperphosphorylated neuronal Tau protein in Alzheimer ' s disease and is by itself regulated by phosphorylation.", "output": "There is no related enetity." }, { "input": "We have used Nuclear Magnetic Resonance ( NMR ) spectroscopy to both identify the PKA phosphorylation site in the Pin1 WW domain and investigate the functional consequences of this phosphorylation.", "output": "There is no related enetity." }, { "input": "Detection and identification of phosphorylation on serine / threonine residues in a globular protein, while mostly occurring in solvent - exposed flexible loops, does not lead to chemical shift changes as obvious as in disordered proteins and hence does not necessarily shift the resonances outside the spectrum of the folded protein.", "output": "serine, threonine." }, { "input": "Other complications were encountered to characterize the extent of the phosphorylation, as part of the ( 1 ) H, ( 15 ) N amide resonances around the phosphorylation site are specifically broadened in the unphosphorylated state.", "output": "( 1 ) H, ( 15 ) N, amide." }, { "input": "Despite these obstacles, NMR spectroscopy was an efficient tool to confirm phosphorylation on S16 of the WW domain and to quantify the level of phosphorylation.", "output": "There is no related enetity." }, { "input": "Based on this analytical characterization, we show that WW phosphorylation on S16 abolishes its binding capacity to a phosphorylated Tau peptide.", "output": "There is no related enetity." }, { "input": "A reduced conformational heterogeneity and flexibility of the phospho - binding loop upon S16 phosphorylation could account for part of the decreased affinity for its phosphorylated partner.", "output": "phospho." }, { "input": "Additionally, a structural model of the phospho - WW obtained by molecular dynamics simulation and energy minimization suggests that the phosphate moiety of phospho - S16 could compete with the phospho - substrate.", "output": "phospho, phosphate, phospho, phospho." }, { "input": "Combining NMR and small angle X - ray and neutron scattering in the structural analysis of a ternary protein - RNA complex.", "output": "There is no related enetity." }, { "input": "Many processes in the regulation of gene expression and signaling involve the formation of protein complexes involving multi - domain proteins.", "output": "There is no related enetity." }, { "input": "Individual domains that mediate protein - protein and protein - nucleic acid interactions are typically connected by flexible linkers, which contribute to conformational dynamics and enable the formation of complexes with distinct binding partners.", "output": "There is no related enetity." }, { "input": "Solution techniques are therefore required for structural analysis and to characterize potential conformational dynamics.", "output": "There is no related enetity." }, { "input": "Nuclear magnetic resonance spectroscopy ( NMR ) provides such information but often only sparse data are obtained with increasing molecular weight of the complexes.", "output": "There is no related enetity." }, { "input": "It is therefore beneficial to combine NMR data with additional structural restraints from complementary solution techniques.", "output": "There is no related enetity." }, { "input": "Small angle X - ray / neutron scattering ( SAXS / SANS ) data can be efficiently combined with NMR - derived information, either for validation or by providing additional restraints for structural analysis.", "output": "There is no related enetity." }, { "input": "Here, we show that the combination of SAXS and SANS data can help to refine structural models obtained from data - driven docking using HADDOCK based on sparse NMR data.", "output": "There is no related enetity." }, { "input": "The approach is demonstrated with the ternary protein - protein - RNA complex involving two RNA recognition motif ( RRM ) domains of Sex - lethal, the N - terminal cold shock domain of Upstream - to - N - Ras, and msl - 2 mRNA.", "output": "N." }, { "input": "Based on chemical shift perturbations we have mapped protein - protein and protein - RNA interfaces and complemented this NMR - derived information with SAXS data, as well as SANS measurements on subunit - selectively deuterated samples of the ternary complex.", "output": "There is no related enetity." }, { "input": "Our results show that, while the use of SAXS data is beneficial, the additional combination with contrast variation in SANS data resolves remaining ambiguities and improves the docking based on chemical shift perturbations of the ternary protein - RNA complex.", "output": "There is no related enetity." }, { "input": "OsSNDP1, a Sec14 - nodulin domain - containing protein, plays a critical role in root hair elongation in rice.", "output": "There is no related enetity." }, { "input": "Rice is cultivated in water - logged paddy lands.", "output": "There is no related enetity." }, { "input": "Thus, rice root hairs on the epidermal layers are exposed to a different redox status of nitrogen species, organic acids, and metal ions than root hairs growing in drained soil.", "output": "nitrogen." }, { "input": "To identify genes that play an important role in root hair growth, a forward genetics approach was used to screen for short - root - hair mutants.", "output": "There is no related enetity." }, { "input": "A short - root - hair mutant was identified and isolated by using map - based cloning and sequencing.", "output": "There is no related enetity." }, { "input": "The mutation arose from a single amino acid substitution of OsSNDP1 ( Oryza sativa Sec14 - nodulin domain protein ), which shows high sequence homology with Arabidopsis COW1 / AtSFH1 and encodes a phosphatidylinositol transfer protein ( PITP ).", "output": "amino acid, phosphatidylinositol." }, { "input": "By performing complementation assays with Atsfh1 mutants, we demonstrated that OsSNDP1 is involved in growth of root hairs.", "output": "There is no related enetity." }, { "input": "Cryo - scanning electron microscopy was utilized to further characterize the effect of the Ossndp1 mutation on root hair morphology.", "output": "There is no related enetity." }, { "input": "Aberrant morphogenesis was detected in root hair elongation and maturation zones.", "output": "There is no related enetity." }, { "input": "Many root hairs were branched and showed irregular shapes due to bulged nodes.", "output": "There is no related enetity." }, { "input": "Many epidermal cells also produced dome - shaped root hairs, which indicated that root hair elongation ceased at an early stage.", "output": "There is no related enetity." }, { "input": "These studies showed that PITP - mediated phospholipid signaling and metabolism is critical for root hair elongation in rice.", "output": "There is no related enetity." }, { "input": "Hierarchical porous surface for efficiently controlling microdroplets ' self - removal.", "output": "There is no related enetity." }, { "input": "Superhydrophobic porous surfaces with hydrophilic polymers adsorbed in pores are designed to control the coalescing behavior of microdroplets as well as their quick self - removal.", "output": "There is no related enetity." }, { "input": "The combination of chemical composition and surface structure are greatly important in the design of new materials for heat exchange, antifogging, and anti - icing.", "output": "There is no related enetity." }, { "input": "Life - threatening hypoglycemia associated with intentional insulin ingestion.", "output": "There is no related enetity." }, { "input": "There are reports of insulin overdose by injection, yet little is known regarding the potential harms of intentional oral ingestion of insulin.", "output": "There is no related enetity." }, { "input": "In this report, we describe a case of massive insulin ingestion and ensuing hypoglycemia.", "output": "There is no related enetity." }, { "input": "To our knowledge, there are no previously published cases of hypoglycemia caused by intentional insulin ingestion.", "output": "There is no related enetity." }, { "input": "A 51 - year - old man intentionally ingested three 10 - ml vials ( total of 3000 units ) of various insulins: one vial each of insulin aspart, lispro, and glargine.", "output": "There is no related enetity." }, { "input": "Four symptomatic hypoglycemic episodes, with blood glucose levels of 48, 25, 34, and 40 mg / dl, occurred approximately 1, 3, 4, and 5 hours, respectively, after ingestion.", "output": "glucose." }, { "input": "The hypoglycemia could not be explained other than the ingestion of the insulins.", "output": "There is no related enetity." }, { "input": "The patient was admitted for observation, and euglycemia occurred within 24 hours without any additional hypoglycemic episodes.", "output": "There is no related enetity." }, { "input": "Hypoglycemia treatment is reviewed in this case report, and factors that may affect systemic response of orally ingested insulin, including gastrointestinal absorption and insulin sensitivity, are discussed.", "output": "There is no related enetity." }, { "input": "In addition, the findings of our case report may provide useful insight into the development of novel oral insulin products that are currently in research.", "output": "There is no related enetity." }, { "input": "Despite poor bioavailability ( 1 % ) when taken orally, insulin may produce symptomatic hypoglycemia with a massive ingestion.", "output": "There is no related enetity." }, { "input": "Vigilant blood glucose monitoring, supportive care with glucose replacement therapy, and admission to the hospital for observation may be required.", "output": "glucose, glucose." }, { "input": "Effects of Urtica dioica on oxidative stress, proliferation and apoptosis after partial hepatectomy in rats.", "output": "There is no related enetity." }, { "input": "The present study was performed to investigate the effect of Urtica dioica ( UD ) on liver regeneration after partial hepatectomy ( PH ) in rats.", "output": "There is no related enetity." }, { "input": "A total of 24 male Sprague Dawley rats were divided into three groups: sham - operated, PH and PH + UD; each group contains eight animals.", "output": "There is no related enetity." }, { "input": "The rats in UD - treated groups were given UD oils ( 2 ml / kg / day ) once a day orally for 7 days starting 3 days prior to hepatectomy operation.", "output": "There is no related enetity." }, { "input": "At day 7 after resection, liver samples were collected.", "output": "There is no related enetity." }, { "input": "The levels of malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and glutathione ( GSH ) were estimated in liver homogenates.", "output": "malondialdehyde, MDA, superoxide, glutathione, GSH." }, { "input": "Moreover, histopathological examination, mitotic index ( MI ), proliferating cell nuclear antigen labeling, proliferation index ( PI ), transferase - mediated deoxyuridine triphosphate nick end - labeling assay, apoptotic index ( AI ) were evaluated at day 7 after hepatectomy.", "output": "deoxyuridine triphosphate." }, { "input": "As a result, UD significantly increased MI and PI, significantly decreased AI and also attenuated hepatic vacuolar degeneration and sinusoidal congestion in PH rats.", "output": "There is no related enetity." }, { "input": "UD treatment significantly decreased the elevated tissue MDA level and increased the reduced SOD activity and GSH level in the tissues.", "output": "MDA, GSH." }, { "input": "These results suggest that UD pretreatment was beneficial for rat liver regeneration after partial hepatectomy.", "output": "There is no related enetity." }, { "input": "A novel model approach for esophageal burns in rats: A comparison of three methods.", "output": "There is no related enetity." }, { "input": "BACKGROUND: Corrosive esophageal injury causes serious clinical problems.", "output": "There is no related enetity." }, { "input": "We aimed to create a new experimental esophageal burn model using a single catheter without a surgical procedure.", "output": "There is no related enetity." }, { "input": "Materials and methods: We conducted the study with two groups of 12 male rats that fasted for 12 h before application.", "output": "There is no related enetity." }, { "input": "A modified Foley balloon catheter was inserted into the esophageal lumen.", "output": "There is no related enetity." }, { "input": "The control group was given 0. 9 % sodium chloride, while the experimental group was given 37. 5 % sodium hydroxide with the other part of the catheter.", "output": "sodium chloride, sodium hydroxide." }, { "input": "After 60s, esophagus was washed with distilled water.", "output": "There is no related enetity." }, { "input": "The killed rats were examined using histopathological methods after 28 days.", "output": "There is no related enetity." }, { "input": "RESULTS: In comparison with the histopathological changes experienced by the study groups, the control groups were observed to have no pathological changes.", "output": "There is no related enetity." }, { "input": "Basal cell degeneration, dermal edema, and a slight increase in the keratin layer and collagen density of submucosa due to stenosis were all observed in the group subjected to esophageal corrosion.", "output": "There is no related enetity." }, { "input": "CONCLUSION: A new burn model can thus, we believe, be created without the involvement of invasive laparoscopic surgery and general anesthesia.", "output": "There is no related enetity." }, { "input": "The burn in our experiment was formed in both the distal and proximal esophagus, as in other models; it can also be formed optionally in the entire esophagus.", "output": "There is no related enetity." }, { "input": "The effect of rosiglitazone on bone mass and fragility is reversible and can be attenuated with alendronate.", "output": "rosiglitazone, alendronate." }, { "input": "Rosiglitazone ( RSG ) is an anti - diabetic drug that has been associated with increased peripheral fractures primarily in postmenopausal women.", "output": "Rosiglitazone, RSG." }, { "input": "In this report, we investigated the underlying mechanisms of RSG - associated bone loss in ovariectomized ( OVX ) rats and determine whether changes in bone parameters associated with RSG administration are reversible on treatment cessation or preventable by co - administration with an antiresorptive agent.", "output": "RSG, RSG." }, { "input": "Nine - month - old Sprague - Dawley rats underwent OVX or sham operation.", "output": "There is no related enetity." }, { "input": "Sham - operated rats received oral vehicle only; OVX animals were randomized to receive vehicle, RSG, alendronate ( ALN ) or RSG plus ALN for 12 weeks.", "output": "RSG, alendronate, ALN, RSG, ALN." }, { "input": "All treatment started the day after ovariectomy.", "output": "There is no related enetity." }, { "input": "After the 12 week treatment period, the OVX and RSG groups also underwent an 8 - week treatment - free recovery period.", "output": "RSG." }, { "input": "Bone densitometry measurements, bone turnover markers, biomechanical testing and histomorphometric analysis were conducted.", "output": "There is no related enetity." }, { "input": "Micro - computed tomography was also used to investigate changes in microarchitecture.", "output": "There is no related enetity." }, { "input": "RSG significantly increased deoxypyridinoline levels compared with OVX.", "output": "RSG, deoxypyridinoline." }, { "input": "Significant exacerbation of OVX - induced loss of bone mass, strength and microarchitectural deteriorations was observed in RSG - treated OVX animals compared with OVX controls.", "output": "RSG." }, { "input": "These effects were observed predominantly at sites rich in trabecular bone with less pronounced effects in cortical bone.", "output": "There is no related enetity." }, { "input": "Co - administration of RSG and ALN prevented the bone loss associated with RSG treatment.", "output": "RSG, ALN, RSG." }, { "input": "Following cessation of RSG treatment, effects on bone mass and strength showed evidence of reversal.", "output": "RSG." }, { "input": "Thus, treatment of OVX rats with RSG results in loss of bone mass and strength, primarily at sites rich in trabecular bone mainly due to increased bone resorption.", "output": "RSG." }, { "input": "These effects can be prevented by concomitant treatment with ALN and may be reversed following discontinuation of RSG.", "output": "ALN, RSG." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Plasminogen plays a crucial role in bone repair.", "output": "There is no related enetity." }, { "input": "The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction.", "output": "There is no related enetity." }, { "input": "Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver.", "output": "There is no related enetity." }, { "input": "However, the role of the fibrinolytic system in bone regeneration remains unknown.", "output": "There is no related enetity." }, { "input": "Herein, we investigated bone repair and ectopic bone formation using plasminogen deficient ( Plg ( - / - ) ) mice.", "output": "There is no related enetity." }, { "input": "Bone repair of the femur is delayed in Plg ( - / - ) mice, unlike that in the wild - type ( Plg ( + / + ) ) mice.", "output": "There is no related enetity." }, { "input": "The deposition of cartilage matrix and osteoblast formation were both decreased in Plg ( - / - ) mice.", "output": "There is no related enetity." }, { "input": "Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor ( VEGF ) and transforming growth factor - beta ( TGF - beta ) were decreased at the site of bone damage in Plg ( - / - ) mice.", "output": "There is no related enetity." }, { "input": "Conversely, heterotopic ossification was not significantly different between Plg ( + / + ) and Plg ( - / - ) mice.", "output": "There is no related enetity." }, { "input": "Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF - beta were comparable between Plg ( + / + ) and Plg ( - / - ) mice in heterotopic ossification.", "output": "There is no related enetity." }, { "input": "Our data provide novel evidence that plasminogen is essential for bone repair.", "output": "There is no related enetity." }, { "input": "The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF - beta, and VEGF, thereby leading to the enhancement of bone repair.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "[ 18F ] FDG - PET as an Imaging Biomarker to NMDA Receptor Antagonist - Induced Neurotoxicity.", "output": "[ 18F ] FDG, NMDA." }, { "input": "Positron emission tomography ( PET ) is an effective tool for noninvasive examination of the body and provides a range of functional information.", "output": "There is no related enetity." }, { "input": "PET imaging with [ ( 18 ) F ] fluoro - 2 - deoxy - d - glucose ( [ ( 18 ) F ] FDG ) has been used to image alterations in glucose metabolism in brain or cancer tissue in the field of clinical diagnosis but not in the field of toxicology.", "output": "[ ( 18 ) F ] fluoro - 2 - deoxy - d - glucose, [ ( 18 ) F ] FDG, glucose." }, { "input": "A single dose of N - methyl - d - aspartate ( NMDA ) receptor antagonist induces neuronal cell degeneration / death in the rat retrosplenial / posterior cingulate ( RS / PC ) cortex region.", "output": "N - methyl - d - aspartate, NMDA." }, { "input": "These antagonists also increase local cerebral glucose utilization.", "output": "glucose." }, { "input": "Here, we examined the potential of [ ( 18 ) F ] FDG - PET as an imaging biomarker of neurotoxicity induced by an NMDA receptor antagonist, MK - 801.", "output": "[ ( 18 ) F ] FDG, NMDA, MK - 801." }, { "input": "Using [ ( 18 ) F ] FDG - PET, we determined that increased glucose utilization involved the neurotoxicity induced by MK - 801.", "output": "[ ( 18 ) F ] FDG, glucose, MK - 801." }, { "input": "The accumulation of [ ( 18 ) F ] FDG was increased in the rat RS / PC cortex region showing neuronal cell degeneration / death and detected before the onset of neuronal cell death.", "output": "[ ( 18 ) F ] FDG." }, { "input": "This effect increased at a dose level at which neuronal cell degeneration recovered 24h after MK - 801 administration.", "output": "MK - 801." }, { "input": "Scopolamine prevented the neurotoxicity and [ ( 18 ) F ] FDG accumulation induced by MK - 801.", "output": "Scopolamine, [ ( 18 ) F ] FDG, MK - 801." }, { "input": "Furthermore, in cynomolgus monkeys that showed no neuronal cell degeneration / death when treated with MK - 801, we noted no differences in [ ( 18 ) F ] FDG accumulation between test and control subjects in any region of the brain.", "output": "MK - 801, [ ( 18 ) F ] FDG." }, { "input": "These findings suggest that [ ( 18 ) F ] FDG - PET, which is available for clinical trials, may be useful in generating a predictive imaging biomarker for detecting neurotoxicity against NMDA receptor antagonists with the same pharmacological activity as MK - 801.", "output": "[ ( 18 ) F ] FDG, NMDA, MK - 801." }, { "input": "Harnessing plasmon - induced ionic noise in metallic nanopores.", "output": "There is no related enetity." }, { "input": "The ionic properties of a metal - coated silicon nanopore were examined in a nanofluidic system.", "output": "silicon." }, { "input": "We observed a strong increase of the ionic noise upon laser light illumination.", "output": "There is no related enetity." }, { "input": "The effect appeared to be strongly mediated by the resonant excitation of surface plasmons in the nanopore as was demonstrated by means of ionic mapping of the plasmonic electromagnetic field.", "output": "There is no related enetity." }, { "input": "Evidence from both simulations and experiments ruled out plasmonic heating as the main source of the noise, and point toward photoinduced electrochemical catalysis at the semiconductor - electrolyte interface.", "output": "There is no related enetity." }, { "input": "This ionic mapping technique described is opening up new opportunities on noninvasive applications ranging from biosensing to energy conversion.", "output": "There is no related enetity." }, { "input": "Counterion condensation on heparin oligomers.", "output": "There is no related enetity." }, { "input": "The electropherogram of native heparin shows a broad distribution of mobilities mu, which truncates abruptly at a notably high mu = 4. 7 x 10 ( - 4 ) cm ( 2 ) V ( - 1 ) s ( - 1 ).", "output": "There is no related enetity." }, { "input": "This highly skewed mobility distribution is also found for the 20 - saccharide chain, which shows from mass spectrometry a more uniform ( symmetrical ) with respect to sulfation level.", "output": "saccharide." }, { "input": "Since a partially degraded heparin exhibits oligomer peaks with mu > 5 x 10 ( - 4 ) cm ( 2 ) V ( - 1 ) s ( - 1 ) ( appearing to escape the limitation of the mobility value for native heparin ), we examined the electrophoretic behavior of chain - length monodisperse heparin oligomers.", "output": "There is no related enetity." }, { "input": "Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm.", "output": "There is no related enetity." }, { "input": "The generality of this effect was indicated by similar behavior for oligomers of poly ( styrene sulfonate ).", "output": "poly ( styrene sulfonate )." }, { "input": "A recent theory of polyelectrolyte end effects ( Manning, G. S. Macromolecules2008, 41, 6217 - 6227 ), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results.", "output": "There is no related enetity." }, { "input": "A qualitative explanation for the anomalously high value of mu of native heparin, 10 - 20 % higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects ( Manning, G. S. Macromolecules2008, 41, 6217 - 6227 ), which reduce counterion condensation at the interfaces of regions of high and low sulfation.", "output": "There is no related enetity." }, { "input": "We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation ( NS / NA ) domains of heparan sulfate.", "output": "There is no related enetity." }, { "input": "Thermoresponsive Bacterial Cellulose Whisker / Poly ( NIPAM - co - BMA ) Nanogel Complexes: Synthesis, Characterization, and Biological Evaluation.", "output": "Poly ( NIPAM - co - BMA )." }, { "input": "Dispersions of poly ( N - isopropylacrylamide - co - butyl methacrylate ) ( PNB ) nanogels are known to exhibit reversible thermosensitive sol - gel phase behavior and can consequently be used in a wide range of biomedical applications.", "output": "poly ( N - isopropylacrylamide - co - butyl methacrylate ), PNB." }, { "input": "However, some dissatisfactory mechanical properties of PNB nanogels can limit their applications.", "output": "PNB." }, { "input": "In this paper, bacterial cellulose ( BC ) whiskers were first prepared by sulfuric acid hydrolysis and then nanosized by high - pressure homogenization for subsequent use in the preparation of BC whisker / PNB nanogel complexes ( designated as BC / PNB ).", "output": "sulfuric acid, PNB, PNB." }, { "input": "The mechanical properties of PNB was successfully enhanced, resulting in good biosafety.", "output": "PNB." }, { "input": "The BC / PNB nanogel dispersions exhibited phase transitions from swollen gel to shrunken gel with increasing temperature.", "output": "PNB." }, { "input": "In addition, differential scanning calorimetry ( DSC ) data showed that the thermosensitivity of PNB nanogels was retained.", "output": "PNB." }, { "input": "Rheological tests also indicated that BC / PNB nanogel complexes had stronger gel strengths when compared with PNB nanogels.", "output": "PNB, PNB." }, { "input": "The concentrated dispersions showed shear thinning behavior and improved toughness, both of which can play a key role in the medical applications of nanogel complexes.", "output": "There is no related enetity." }, { "input": "Furthermore, the BC / PNB nanogel complexes were noncytotoxic according to cytotoxicity and hemolysis tests.", "output": "PNB." }, { "input": "Concentrated BC / PNB nanogel dispersion displayed gel a forming capacity in situ by catheter injection, which indicates potential for a wide range of medical applications.", "output": "PNB." }, { "input": "PET studies in nonhuman primate models of cocaine abuse: Translational research related to vulnerability and neuroadaptations.", "output": "cocaine." }, { "input": "The current review highlights the utility of positron emission tomography ( PET ) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self - administration in nonhuman primate models of cocaine abuse.", "output": "cocaine, cocaine, cocaine." }, { "input": "Environmental ( e. g., social rank ) and sex - specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed.", "output": "cocaine." }, { "input": "Cocaine - related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models.", "output": "Cocaine." }, { "input": "Lastly, the long - term consequences of cocaine on neurobiology are discussed.", "output": "cocaine." }, { "input": "PET imaging and longitudinal, within - subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug - dependent treatment seekers.", "output": "There is no related enetity." }, { "input": "Non - invasive PET imaging will allow for individualized treatment strategies.", "output": "There is no related enetity." }, { "input": "Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' Neuroimaging '.", "output": "There is no related enetity." }, { "input": "Targeting mitochondria for cardiac protection.", "output": "There is no related enetity." }, { "input": "The critical role of mitochondria in cardiomyocyte survival and death has become an exciting field of research in cardiac biology.", "output": "There is no related enetity." }, { "input": "Indeed, it is accepted that mitochondrial dysfunction plays a crucial role in the pathogenesis of multiple cardiac diseases.", "output": "There is no related enetity." }, { "input": "Besides the obvious relevance of mitochondria in energy production, calcium homeostasis, and reactive oxygen species ( ROS ) production, new processes like mitochondrial fusion / fission, phosphorylation and nitrosylation modifications in mitochondrial proteins have been suggested to form part of a cast of key players in cardiac disease.", "output": "oxygen." }, { "input": "This review describes currently studied drugs and compounds that target mitochondria in the scenario of cardiovascular diseases.", "output": "There is no related enetity." }, { "input": "Raman spectroscopy and imaging: promising optical diagnostic tools in pediatrics.", "output": "There is no related enetity." }, { "input": "This review focuses on the use of Raman spectroscopy, an analytical technique based on the inelastic scattering of harmless laser light with biological tissues, as an innovative diagnostic tool in pediatrics.", "output": "There is no related enetity." }, { "input": "After a brief introduction to explain the fundamental concepts behind Raman spectroscopy and imaging, a short summary is given of the most important and common issues arising when handling spectral data with multivariate statistics.", "output": "There is no related enetity." }, { "input": "Then, the most relevant papers in which Raman spectroscopy or imaging has been applied with diagnostic purposes to pediatric patients are reviewed, and grouped according to the type of pathology: neoplastic, inflammatory, allergic, malformative as well as other kinds.", "output": "There is no related enetity." }, { "input": "Raman spectroscopy has been used both in vivo, mostly using optical fibers for tissue illumination, as well as on ex vivo tissue sections in a microscopic imaging approach defined as \" spectral histopathology \".", "output": "There is no related enetity." }, { "input": "According to the results reported so far, this technique showed a huge potential for mini - or non - invasive real - time, bedside and intra - operatory diagnosis, as well as for an ex vivo imaging tool in support to pathologists.", "output": "There is no related enetity." }, { "input": "Despite many studies are limited by the small sample size, this technique is extremely promising in terms of sensitivity and specificity.", "output": "There is no related enetity." }, { "input": "MDM2 Non - Genotoxic Inhibitors as Innovative Therapeutic Approaches for the Treatment of Pediatric Malignancies.", "output": "There is no related enetity." }, { "input": "Since the discovery of p53 as \" guardian of the genome \", a large number of efforts have been put in place in order to find molecular strategies aiming to restore p53 wild - type functions, particularly in the light of the fact that its pathway results ineffective in most tumors even though they have non - mutated p53.", "output": "There is no related enetity." }, { "input": "In this context, pediatric cancers, that are mostly p53 wild - type at the time of diagnosis, represent an ideal target for such therapeutic approach.", "output": "There is no related enetity." }, { "input": "Within the several mechanisms and proteins ruling p53 activity, the murine double minute 2 ( MDM2 ) is its crucial negative regulator, frequently found overexpressed in p53 - wild - type tumors.", "output": "There is no related enetity." }, { "input": "The development of new technologies such as nuclear magnetic resonance structure analyses, computational structure - based design studies, and library peptides screening have recently led to the discovery and characterization of a large number of compounds belonging to different chemical families that are able to target the interaction p53 - MDM2, rescuing the p53 wild - type pathway with an overall pro - apoptotic and anticancer activity.", "output": "There is no related enetity." }, { "input": "Within the preclinical assessment of these molecules, the cis - imidazoline analogue Nutlin - 3 has definitely attracted great interest for its in vitro and in vivo antitumor activity in several pediatric cancer models, either as single agent on in combination with standard chemotherapy.", "output": "cis - imidazoline, Nutlin - 3." }, { "input": "In this light, the aim of this review is to summarize the main preclinical evidences of the potential of MDM2 inhibitors for the treatment of childhood cancers and the key suggestions coming from their assessment in the treatment of adult cancers as proof of concept for future pediatric clinical studies.", "output": "There is no related enetity." }, { "input": "Luminescent silica nanoparticles for cancer diagnosis.", "output": "silica." }, { "input": "Fluorescence imaging techniques are becoming essential for preclinical investigations, necessitating the development of suitable tools for in vivo measurements.", "output": "There is no related enetity." }, { "input": "Nanotechnology entered this field to help overcome many of the current technical limitations, and luminescent nanoparticles ( NPs ) are one of the most promising materials proposed for future diagnostic implementation.", "output": "There is no related enetity." }, { "input": "NPs also constitute a versatile platform that can allow facile multi - functionalization to perform multimodal imaging or theranostics ( simultaneous diagnosis and therapy ).", "output": "There is no related enetity." }, { "input": "In this contribution we have mainly focused on dye doped silica or silica - based NPs conjugated with targeting moieties to enable imaging of specific cancer cells.", "output": "silica, silica." }, { "input": "We also cite and briefly discuss a few non - targeted systems for completeness.", "output": "There is no related enetity." }, { "input": "We summarize common synthetic approaches to these materials, and then survey the most recent imaging applications of silica - based nanoparticles in cancer.", "output": "silica." }, { "input": "The field of theranostics is particularly important and stimulating, so, even though it is not the central topic of this paper, we have included some significant examples.", "output": "There is no related enetity." }, { "input": "We conclude with a short section on NP - based systems already in clinical trials and examples of specific applications in childhood tumors.", "output": "There is no related enetity." }, { "input": "This review aims to describe and discuss, through focused examples, the great potential of these materials in the medical field, with the aim to encourage further research to implement applications, which today are still rare.", "output": "There is no related enetity." }, { "input": "Design, synthesis, and biological evaluation of highly potent small molecule - peptide conjugates as new HIV - 1 fusion inhibitors.", "output": "There is no related enetity." }, { "input": "The small molecule fusion inhibitors N - ( 4 - carboxy - 3 - hydroxyphenyl ) - 2, 5 - dimethylpyrrole ( NB - 2 ) and N - ( 3 - carboxy - 4 - hydroxyphenyl ) - 2, 5 - dimethylpyrrole ( A12 ) target a hydrophobic pocket of HIV - 1 gp41 and have moderate anti - HIV - 1 activity.", "output": "N - ( 4 - carboxy - 3 - hydroxyphenyl ) - 2 , 5 - dimethylpyrrole, NB - 2, N - ( 3 - carboxy - 4 - hydroxyphenyl ) - 2 , 5 - dimethylpyrrole, A12." }, { "input": "In this paper, we report the design, synthesis, and structure - activity relationship of a group of hybrid molecules in which the pocket - binding domain segment of the C34 peptide was replaced with NB - 2 and A12 derivatives.", "output": "NB - 2, A12." }, { "input": "In addition, the synergistic effect between the small molecule and peptide moieties was analyzed, and lead compounds with a novel scaffold were discovered.", "output": "There is no related enetity." }, { "input": "We found that either the nonpeptide or peptide part alone showed weak activity against HIV - 1 - mediated cell - cell fusion, but the conjugates properly generated a strong synergistic effect.", "output": "There is no related enetity." }, { "input": "Among them, conjugates Aoc - beta Ala - P26 and Noc - beta Ala - P26 exhibited a low nanomolar IC50 in the cell - cell fusion assay and effectively inhibited T20 - sensitive and - resistant HIV - 1 strains.", "output": "There is no related enetity." }, { "input": "Furthermore, the new molecules exhibited better stability against proteinase K digestion than T20 and C34.", "output": "There is no related enetity." }, { "input": "Concentration - dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats.", "output": "baicalin, dextromethorphan." }, { "input": "Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti - cancer and anti - inflammatory properties.", "output": "Baicalin." }, { "input": "In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan ( DXM ), a dual probe substrate of CYP2D and CYP3A, in rats.", "output": "baicalin, dextromethorphan, DXM." }, { "input": "Lineweaver - Burk plots demonstrated that baicalin inhibited the activities of CYP2D and CYP3A in a non - competitive manner in rat liver microsomes ( RLMs ).", "output": "baicalin." }, { "input": "Concomitant administration of baicalin ( 0. 90g / kg, i. v. ) and DXM ( 10mg / kg, i. v. ) increased the maximum drug concentration ( Cmax ) ( 37 % ) and the area under concentration - time curve ( AUC ) ( 42 % ) and decreased the clearance ( CL ) ( 27 % ) of DXM in a randomised, crossover study in rats ( P < 0. 01 ).", "output": "baicalin, DXM, DXM." }, { "input": "The change in the AUC of DXM was significantly correlated with the Cmax and AUC of baicalin ( P < 0. 05 ).", "output": "DXM, baicalin." }, { "input": "The inhibitory effects of multiple doses of baicalin ( 0. 90g / kg, i. v., 12days ) on the metabolism of DXM were similar to those observed following a single dose in rats.", "output": "baicalin, DXM." }, { "input": "The activity of CYP3A in excised liver samples from rats following multiple baicalin treatment was significantly decreased compared to that of the control group ( P < 0. 05 ), whereas multiple doses of baicalin had no obvious effect on the activity of CYP2D.", "output": "baicalin, baicalin." }, { "input": "Taken together, these data demonstrate that baicalin inhibits the metabolism of DXM in a concentration - dependent manner in rats, possibly through inhibiting hepatic CYP2D and CYP3A activities.", "output": "baicalin, DXM." }, { "input": "Increased vulnerability to beta - cell destruction and diabetes in mice lacking NAD ( P ) H: quinone oxidoreductase 1.", "output": "NAD ( P ) H, quinone." }, { "input": "NAD ( P ) H: quinone oxidoreductase 1 ( NQO1 ) has been known to protect cells against stressors, including the diabetogenic reagent streptozotocin ( STZ ).", "output": "NAD ( P ) H, quinone, streptozotocin, STZ." }, { "input": "The present study demonstrated that NQO1 deficiency resulted in increased pancreatic beta - cell death induced by multiple low dose of STZ ( MLDS ) injections.", "output": "STZ." }, { "input": "NQO1 knockout ( KO ) mice showed hyperglycemia, body weight loss, impaired glucose clearance rate and a lower plasma insulin level after MLDS treatment.", "output": "glucose." }, { "input": "Moreover, beta - cell mass and pancreatic insulin content were significantly lower in KO mice than in wild - type ( WT ) mice after MLDS treatment.", "output": "There is no related enetity." }, { "input": "Five days after the first STZ treatment, the islets of KO mice had substantially more TUNEL - positive beta - cells than those of WT mice, but there was no difference in the regeneration of beta - cells between KO mice and WT mice.", "output": "STZ." }, { "input": "At the same time, MLDS - treated KO mice showed significantly increased apoptotic markers in beta - cells, including cleaved caspase 3, Smac / DIABLO and AIF ( apoptosis inducing factor ) in the cytoplasm.", "output": "There is no related enetity." }, { "input": "These results suggest that mice deficient in NQO1 are vulnerable to MLDS - induced beta - cell destruction and diabetes, caused by increase of beta - cell apoptosis in pancreas.", "output": "There is no related enetity." }, { "input": "Effects of sodium fluoride on reproductive function in female rats.", "output": "sodium fluoride." }, { "input": "The aim of this study was to investigate the effects of sodium fluoride ( NaF ) on female reproductive function and examine the morphology of the ovaries and uteri of rats exposed to NaF.", "output": "sodium fluoride, NaF, NaF." }, { "input": "Eighty female Sprague - Dawley ( SD ) rats were divided randomly into four groups of 20: one control group and three NaF treated groups.", "output": "NaF." }, { "input": "The three NaF treated groups received 100, 150, and 200ppm, respectively, of NaF for 6months via their drinking water, while the control group ( GC ) received distilled water.", "output": "NaF, NaF." }, { "input": "The levels of follicle - stimulating hormone ( FSH ), luteinizing hormone ( LH ), testosterone ( T ), progesterone ( P ) and estradiol ( E2 ) were measured using an enzyme - linked immunosorbent assay.", "output": "testosterone, progesterone, estradiol." }, { "input": "Pathomorphological evaluation of the uteri and ovaries was conducted after staining with hematoxylin - eosin and immunohistochemistry.", "output": "hematoxylin, eosin." }, { "input": "The rate of successful pregnancy in the NaF - treated groups declined in a dose - dependent manner.", "output": "NaF." }, { "input": "The concentration of reproductive hormones was significantly lower in the three NaF - treated groups, and the endometrium was damaged.", "output": "NaF." }, { "input": "The maturation of follicles was inhibited.", "output": "There is no related enetity." }, { "input": "In addition, the total number of follicles of all types was significantly lower in the NaF - treated groups.", "output": "NaF." }, { "input": "These results suggest that female reproductive function is inhibited by NaF and that exposure to NaF causes ovarian and uterine structural damage.", "output": "NaF, NaF." }, { "input": "NaF may thus significantly reduce the fertility of female rats.", "output": "NaF." }, { "input": "Ninety - day dietary toxicity study of apple polyphenol extracts in Crl: CD ( SD ) rats.", "output": "There is no related enetity." }, { "input": "To examine the safety of Dietary Applephenon (R) ( AP ) in feed, Crl: CD ( SD ) rats of each sex were divided into four groups and given diets containing AP at 0 %, 1. 25 %, 2. 5 %, or 5. 0 % for 90days.", "output": "There is no related enetity." }, { "input": "All rats survived and toxic changes were not observed throughout the study.", "output": "There is no related enetity." }, { "input": "Body weight and food efficiency in the 5. 0 % AP group of both sexes were significantly decreased compared with that in controls.", "output": "There is no related enetity." }, { "input": "These changes were considered to be caused by the physiological effects of AP ( including the inhibitory effects on pancreatic lipase activity ).", "output": "There is no related enetity." }, { "input": "Slight hypertrophy in acinar cells in the parotid and submandibular glands appeared in the 2. 5 % and 5. 0 % groups.", "output": "There is no related enetity." }, { "input": "These were suggested not to be toxicological but physiologic adaptive responses to oral stimuli by the lower pH of AP - containing diets.", "output": "There is no related enetity." }, { "input": "In conclusion, dietary AP in feed, up to a maximum level of 5. 0 % for 90days, given to rats did not induce toxicological effects.", "output": "There is no related enetity." }, { "input": "Comparative Analysis of the Symbiotic Efficiency of Medicago truncatula and Medicago sativa under Phosphorus Deficiency.", "output": "Phosphorus." }, { "input": "Phosphorus ( P ) - deficiency is a major abiotic stress that limits legume growth in many types of soils.", "output": "Phosphorus, P." }, { "input": "The relationship between Medicago and Sinorhizobium, is known to be affected by different environmental conditions.", "output": "There is no related enetity." }, { "input": "Recent reports have shown that, in combination with S. meliloti 2011, Medicago truncatula had a lower symbiotic efficiency than Medicago sativa.", "output": "There is no related enetity." }, { "input": "However, little is known about how Medicago - Sinorhizobium is affected by P - deficiency at the whole - plant level.", "output": "P." }, { "input": "The objective of the present study was to compare and characterize the symbiotic efficiency of N2 fixation of M. truncatula and M. sativa grown in sand under P - limitation.", "output": "N2, P." }, { "input": "Under this condition, M. truncatula exhibited a significantly higher rate of N2 fixation.", "output": "N2." }, { "input": "The specific activity of the nodules was much higher in M. truncatula in comparison to M. sativa, partially as a result of an increase in electron allocation to N2 versus H +.", "output": "N2, H +." }, { "input": "Although the main organic acid, succinate, exhibited a strong tendency to decrease under P - deficiency, the more efficient symbiotic ability observed in M. truncatula coincided with an apparent increase in the content of malate in its nodules.", "output": "succinate, P." }, { "input": "Our results indicate that the higher efficiency of the M. truncatula symbiotic system is related to the ability to increase malate content under limited P - conditions.", "output": "P." }, { "input": "Arraying Cell Cultures Using PEG - DMA Micromolding in Standard Culture Dishes.", "output": "PEG - DMA." }, { "input": "A robust and effortless procedure is presented, which allows for the microstructuring of standard cell culture dishes.", "output": "There is no related enetity." }, { "input": "Cell adhesion and proliferation are controlled by three - dimensional poly ( ethylene glycol ) - dimethacrylate ( PEG - DMA ) microstructures.", "output": "poly ( ethylene glycol ) - dimethacrylate, PEG - DMA." }, { "input": "The spacing between microwells can be extended to millimeter size in order to enable the combination with robotic workstations.", "output": "There is no related enetity." }, { "input": "Cell arrays of microcolonies can be studied under boundary - free growth conditions by lift - off of the PEG - DMA layer in which the growth rate is accessible via the evolution of patch areas.", "output": "PEG - DMA." }, { "input": "Alternatively, PEG - DMA stencils can be used as templates for plasma - induced patterning.", "output": "PEG - DMA." }, { "input": "Thermoplastic Polyurethanes From Undecylenic Acid - Based Soft Segments: Structural Features and Release Properties.", "output": "Polyurethanes, Undecylenic Acid." }, { "input": "A set of thermoplastic polyurethanes is synthesized, combining undecylenic acid - derived telechelic diols as soft segments and 1, 4 - butanediol / 4, 4 ' - methylenebis ( phenylisocyanate ) as a hard segment ( HS ).", "output": "polyurethanes, undecylenic acid, telechelic diols, 1 , 4 - butanediol, 4 , 4 ' - methylenebis ( phenylisocyanate )." }, { "input": "These polymers are fully chemically and physically characterized by means of NMR and Fourier transform IR ( FTIR ) spectroscopy, size - exclusion chromatography ( SEC ), DSC, thermogravimetric analysis ( TGA ), tensile testing, and contact angle measurements.", "output": "There is no related enetity." }, { "input": "The obtained results reveal that both the molecular weight of the diol and the HS content greatly influence the physical and mechanical properties of these polymers.", "output": "diol." }, { "input": "In addition, given the potential use of these materials for biomedical applications, hydrolytic degradation, their biocompatibility using a human fibroblast cell line, and performance as drug delivery carriers are evaluated.", "output": "There is no related enetity." }, { "input": "Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteoporosis.", "output": "There is no related enetity." }, { "input": "Bone mass and inflammation are implicated in the pathogenesis of osteoporosis.", "output": "There is no related enetity." }, { "input": "We hypothesized that leptin and leptin receptor gene might be associated with osteoporosis by activating the inflammatory pathway.", "output": "There is no related enetity." }, { "input": "Therefore, we analyzed polymorphisms of the leptin ( gene symbol, LEP ) and leptin receptor ( gene symbol, LEPR ) genes and determined their associations with proinflammatory cytokine levels in patients with osteoporosis.", "output": "There is no related enetity." }, { "input": "We assessed polymorphisms in LEP ( - 2548G > A ) and LEPR ( Lys109Arg, Gln223Arg, and Lys656Asn ) and calculated odds ratios for the genotype and allele distributions between patients and controls.", "output": "There is no related enetity." }, { "input": "Serum leptin, soluble leptin receptor, interleukin ( IL ) - 1, IL - 6, IL - 7, and tumor necrosis factor ( TNF ) levels were measured by enzyme - linked immunosorbent assays ( ELISA ) and were verified by in vitro lymphocyte proliferation assays and ELISAs.", "output": "There is no related enetity." }, { "input": "We found a higher frequency of the A allele for LEP at - 2548 in patients with osteoporosis compared with the control group.", "output": "There is no related enetity." }, { "input": "The A allele was associated with differences in serum leptin, soluble leptin receptor, IL - 1, IL - 6, and TNF levels compared with the wild - type G allele ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "The G allele in Lys109Arg and Gln223Arg was associated with increased risk of osteoporosis and with differences in serum leptin, soluble leptin receptor, IL - 1, IL - 6, and TNF levels compared with the wild - type A allele ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "The Lys656Asn genotype was not associated with the risk of osteoporosis.", "output": "There is no related enetity." }, { "input": "In vitro lymphocyte proliferation assays and ELISAs confirmed these results.", "output": "There is no related enetity." }, { "input": "Polymorphisms in LEP and LEPR are associated with increased risk of osteoporosis, possibly by increasing the expression of proinflammatory cytokines.", "output": "There is no related enetity." }, { "input": "Mechanisms Underlying the Varied Mammary Carcinogenicity of the Environmental Pollutant 6 - Nitrochrysene and Its Metabolites ( - ) - [ R, R ] - and ( + ) - [ S, S ] - 1, 2 - Dihydroxy - 1, 2 - dihydro - 6 - nitrochrysene in the Rat.", "output": "6 - Nitrochrysene, ( - ) - [ R , R ] - and ( + ) - [ S , S ] - 1 , 2 - Dihydroxy - 1 , 2 - dihydro - 6 - nitrochrysene." }, { "input": "The mechanisms that can account for the remarkable mammary carcinogenicity of the environmental pollutant 6 - nitrochrysene ( 6 - NC ) in the rat remain elusive.", "output": "6 - nitrochrysene, 6 - NC." }, { "input": "In our previous studies, we identified several 6 - NC - derived DNA adducts in the rat mammary gland; one major adduct was derived from ( +/- ) - trans - 1, 2 - dihydroxy - 1, 2 - dihydro - 6 - nitrochrysene ( 1, 2 - DHD - 6 - NC ).", "output": "6 - NC, ( +/- ) - trans - 1 , 2 - dihydroxy - 1 , 2 - dihydro - 6 - nitrochrysene, 1 , 2 - DHD - 6 - NC." }, { "input": "In the present study, we resolved the racemic ( +/- ) - 1, 2 - DHD - 6 - NC into ( - ) - [ R, R ] - and ( + ) - [ S, S ] - 1, 2 - DHD - 6 - NC and compared their in vivo mutagenicity and carcinogenicity in the mammary glands of female transgenic ( BigBlue F344 x Sprague - Dawley ) F1 rats harboring lacI / cII and Sprague - Dawley rats, respectively.", "output": "( +/- ) - 1 , 2 - DHD - 6 - NC, ( - ) - [ R , R ] - and ( + ) - [ S , S ] - 1 , 2 - DHD - 6 - NC." }, { "input": "Both [ R, R ] - and [ S, S ] - isomers exerted similar mutagenicity and carcinogenicity but were less potent than 6 - NC.", "output": "6 - NC." }, { "input": "Additional in vivo and in vitro studies were then performed to explore possible mechanisms that can explain the higher potency of 6 - NC than 1, 2 - DHD - 6 - NC.", "output": "6 - NC, 1 , 2 - DHD - 6 - NC." }, { "input": "Using ELISA, we found that neither 6 - NC nor 1, 2 - DHD - 6 - NC increased the levels of several inflammatory cytokines in plasma obtained from rats 24 h after treatment.", "output": "6 - NC, 1 , 2 - DHD - 6 - NC." }, { "input": "In MCF - 7 cells, as determined by immunoblotting, the effects of 6 - NC and 1, 2 - DHD - 6 - NC on protein expression ( p53, Akt, p38, JNK, c - myc, bcl - 2, PCNA, and ER beta ) were comparable; however, the expressions of AhR and ER alpha proteins were decreased by 6 - NC but not 1, 2 - DHD - 6 - NC.", "output": "6 - NC, 1 , 2 - DHD - 6 - NC, 6 - NC, 1 , 2 - DHD - 6 - NC." }, { "input": "The expression of both receptors was decreased in mammary tissues of rats treated with 6 - NC.", "output": "6 - NC." }, { "input": "Our findings suggest that the differential effects of 6 - NC and 1, 2 - DHD - 6 - NC on AhR and ER alpha could potentially account for the higher carcinogenicity of 6 - NC in the rat mammary gland.", "output": "6 - NC, 1 , 2 - DHD - 6 - NC, 6 - NC." }, { "input": "Vibronic and Vibrational Coherences in Two - Dimensional Electronic Spectra of Supramolecular J - Aggregates.", "output": "There is no related enetity." }, { "input": "In J - aggregates of cyanine dyes, closely packed molecules form mesoscopic tubes with nanometer - diameter and micrometer - length.", "output": "cyanine." }, { "input": "Their efficient energy transfer pathways make them suitable candidates for artificial light harvesting systems.", "output": "There is no related enetity." }, { "input": "This great potential calls for an in - depth spectroscopic analysis of the underlying energy deactivation network and coherence dynamics.", "output": "There is no related enetity." }, { "input": "We use two - dimensional electronic spectroscopy with sub - 10 fs laser pulses in combination with two - dimensional decay - associated spectra analysis to describe the population flow within the aggregate.", "output": "There is no related enetity." }, { "input": "Based on the analysis of Fourier - transform amplitude maps, we distinguish between vibrational or vibronic coherence dynamics as the origin of pronounced oscillations in our two - dimensional electronic spectra.", "output": "There is no related enetity." }, { "input": "Tough Germanium Nanoparticles under Electrochemical Cycling.", "output": "Germanium." }, { "input": "Mechanical degradation of the electrode materials during electrochemical cycling remains a serious issue that critically limits the capacity retention and cyclability of rechargeable lithium - ion batteries.", "output": "lithium." }, { "input": "Here we report the highly reversible expansion and contraction of germanium nanoparticles under lithiation - delithiation cycling with in situ transmission electron microscopy ( TEM ).", "output": "germanium." }, { "input": "During multiple cycles to the full capacity, the germanium nanoparticles remained robust without any visible cracking despite ~ 260 % volume changes, in contrast to the size - dependent fracture of silicon nanoparticles upon the first lithiation.", "output": "germanium, silicon." }, { "input": "The comparative in situ TEM study of fragile silicon nanoparticles suggests that the tough behavior of germanium nanoparticles can be attributed to the weak anisotropy of the lithiation strain at the reaction front.", "output": "silicon, germanium." }, { "input": "The tough germanium nanoparticles offer substantial potential for the development of durable, high - capacity, and high - rate anodes for advanced lithium - ion batteries.", "output": "germanium, lithium." }, { "input": "Facile synthesis of silver nanoparticles stabilized by cationic polynorbornenes and their catalytic activity in 4 - nitrophenol reduction.", "output": "silver, polynorbornenes, 4 - nitrophenol." }, { "input": "We report the facile one - pot single - phase syntheses of silver nanoparticles stabilized by norbornene type cationic polymers.", "output": "silver, norbornene." }, { "input": "Silver nanoparticles ( AgNPs ) stabilized by polyguanidino oxanorbornenes ( PG ) at 5 and 25 kDa and polyamino oxanorbornenes ( PA ) at 3 and 15 kDa have been synthesized by the reduction of silver ions with NaBH4 in aqueous solutions at ambient temperature.", "output": "Silver, polyguanidino oxanorbornenes, polyamino oxanorbornenes, silver, NaBH4." }, { "input": "The four different silver nanoparticles have been characterized by UV - vis spectroscopy, Fourier transform infrared spectroscopy ( FTIR ), dynamic light scattering ( DLS ), and transmission electron microscopy ( TEM ) for their particle size distributions.", "output": "silver." }, { "input": "Interestingly, PG stabilizes the silver nanoparticles better than PA as evident from our spectroscopic data.", "output": "silver." }, { "input": "Furthermore, the AgNP - PG - 5K ( 5K = 5 kDa ) was found to serve as an effective catalyst for the reduction of 4 - nitrophenol to 4 - aminophenol in the presence of NaBH4.", "output": "4 - nitrophenol, 4 - aminophenol, NaBH4." }, { "input": "The reduction has a pseudo - first - order rate constant of 5. 50 x 10 ( - 3 ) s ( - 1 ) and an activity parameter of 1375 s ( - 1 ) g ( - 1 ), which is significantly higher than other systems reported in the literature.", "output": "There is no related enetity." }, { "input": "Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression.", "output": "There is no related enetity." }, { "input": "Orosomucoid - like 3 ( ORMDL3 ) has been associated with asthma and a series of autoimmune disorders, and is involved in endoplasmic reticulum - mediated inflammatory responses.", "output": "There is no related enetity." }, { "input": "However, its clinical significance and the molecular mechanism underlying its expression are still largely unclear.", "output": "There is no related enetity." }, { "input": "To elucidate the mechanisms of human ORMDL3 transcriptional regulation, we cloned a 1. 5 kb genomic DNA fragment containing the putative promoter region and evaluated its transcriptional activity in a luciferase reporter system by deletion analysis.", "output": "There is no related enetity." }, { "input": "We identified a 68 bp region that functions as a minimal promoter.", "output": "There is no related enetity." }, { "input": "Bioinformatics analysis predicted that the - 64 to - 56 bp region contained a signal transducer and activator of transcription 6 ( STAT6 ) binding site.", "output": "There is no related enetity." }, { "input": "Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrated that STAT6 bound to its binding site within the ORMDL3 promoter.", "output": "There is no related enetity." }, { "input": "STAT6 over - expression or knockdown trans - activated or trans - inhibited, respectively, the ORMDL3 promoter containing the STAT6 - binding motif.", "output": "There is no related enetity." }, { "input": "Treatment with interleukins 4 or 13 increased ORMDL3 promoter activity as well as endogenous ORMDL3 expression.", "output": "There is no related enetity." }, { "input": "Immunoprecipitation and ChIP / Re - ChIP assays revealed that STAT6 and p300 exist in the same protein complex that binds to the ORMDL3 promoter.", "output": "There is no related enetity." }, { "input": "Our study confirmed that STAT6 plays important roles in regulating the expression of human ORMDL3 by directly binding to the promoter region, which may shed light on a possible role in various human diseases.", "output": "There is no related enetity." }, { "input": "STRUCTURED DIGITAL ABSTRACT: p300 physically interacts with STAT6 by anti bait coimmunoprecipitation ( View Interaction: 1, 2 ).", "output": "There is no related enetity." }, { "input": "Serum free fatty acid levels in PCOS patients treated with glucophage, magnesium oxide and spironolactone.", "output": "fatty acid, magnesium oxide, spironolactone." }, { "input": "Abstract To assess the effect of glucophage, magnesium oxide and spironolactone in altering free fatty acids ( FFAs ), 36 PCOS women were randomly divided into three groups.", "output": "magnesium oxide, spironolactone, fatty acids." }, { "input": "Group 1 ( n = 14 ) was treated with 500 mg glucophage po bid, group 2 ( n = 10 ) was treated with 400 mg magnesium oxide po bid and group 3 ( n = 12 ) was treated with 50 mg spironolactone po bid for 12 weeks.", "output": "magnesium oxide, spironolactone." }, { "input": "A glucose tolerance test with 75 g glucose load was performed before and after treatment, collecting blood at 0, 1 and 2 h for insulin, glucose, FFA and aldosterone.", "output": "glucose, glucose, glucose, aldosterone." }, { "input": "Amount of FFA before and after treatment were compared by repeated measure ANOVA and represented as area under the curve.", "output": "There is no related enetity." }, { "input": "FFA levels before treatment were 0. 83 +/- 0. 23, 0. 77 +/- 0. 15 and 0. 85 +/- 0. 28 and after treatment were 0. 77 +/- 0. 48, 0. 71 +/- 0. 18 and 0. 66 +/- 0. 25 for glucophage, magnesium oxide and spironolactone - treated patients, respectively.", "output": "magnesium oxide, spironolactone." }, { "input": "The FFA levels were unchanged in the groups treated with glucophage and magnesium oxide but were significantly ( p < 0. 03 ) decreased in the group treated with spironolactone.", "output": "magnesium oxide, spironolactone." }, { "input": "Since FFAs are known to be involved in the development of insulin resistance, these results suggest that spironolactone may be useful for lowering insulin resistance in PCOS patients.", "output": "spironolactone." }, { "input": "Theoretical Characterization of Galanin Receptor Type 3 ( Gal3 ) and Its Interaction with Agonist ( GALANIN ) and Antagonists ( SNAP 37889 and SNAP 398299 ): An In Silico Analysis.", "output": "There is no related enetity." }, { "input": "In this study, we report on modeling of galanin receptor type 3 and its interaction with agonist and antagonists using in silico methodologies.", "output": "There is no related enetity." }, { "input": "Comparative structural modeling of galanin receptor type 3 was based on multiple templates.", "output": "There is no related enetity." }, { "input": "With the availability of reported selective galanin receptor type 3 antagonists, docking was carried out into the predicted binding site.", "output": "There is no related enetity." }, { "input": "Similarly, galanin, a reported agonist, was also modeled and then docked into the receptor ' s active site.", "output": "There is no related enetity." }, { "input": "CoMFA models were developed using ligand - based ( q ( 2 ) = 0. 537, r ( 2 ) = 0. 961, noc = 5 ), and receptor - guided ( docked mode 1: q ( 2 ) = 0. 574, r ( 2 ) = 0. 946, noc = 5 ), ( docked mode 2: q ( 2 ) = 0. 499, r ( 2 ) = 0. 954, noc = 5 ) alignment schemes.", "output": "There is no related enetity." }, { "input": "CoMFA contour analysis revealed that bulky substitution around the meta position of the phenyl ring, as well as optimal substitution ( para ) of the phenyl ring, could produce molecules with improved activity.", "output": "phenyl, phenyl." }, { "input": "We also found that Gln79, Ile82, Asp86, Trp88, His99, Ile102, Tyr103, Glu170, Pro174, Ala175, Asp185, Arg273, His277, and Tyr281 are crucial, and mutational studies on these residues could be helpful.", "output": "Gln79, Ile82, Asp86, Trp88, His99, Ile102, Tyr103, Glu170, Pro174, Ala175, Asp185, Arg273, His277, Tyr281." }, { "input": "The results obtained from this study can further be exploited for structure - based drug design and also help the researchers to identify novel antagonists targeting galanin receptor type 3.", "output": "There is no related enetity." }, { "input": "Effects of seaweed - restructured pork diets enriched or not with cholesterol on rat cholesterolaemia and liver damage.", "output": "cholesterol." }, { "input": "Seaweed enriched - restructured pork ( RP ) is a potential functional food.", "output": "There is no related enetity." }, { "input": "However, indications of adverse effects associated with herbal medications, which include among others liver failure, toxic hepatitis, and death have been reported.", "output": "There is no related enetity." }, { "input": "Cholesterol feeding produces hepatomegalia and fat liver infiltration.", "output": "Cholesterol." }, { "input": "The effect of seaweed - RP diet, cholesterol - enriched or not, on plasma cholesterol, liver damage markers, structure, and cytochrome CYP4A - 1 were evaluated after 5wk.", "output": "cholesterol, cholesterol." }, { "input": "Eight rat groups were fed a mix of 85 % AIN - 93M rodent - diet plus 15 % RP.", "output": "There is no related enetity." }, { "input": "The Cholesterol - control ( CC ), Cholesterol - Wakame ( CW ), Cholesterol - Nori ( CN ) and Cholesterol - Sea Spaghetti ( CS ) groups respectively consumed similar diets to control ( C ), Wakame ( W ), Nori ( N ), and Sea Spaghetti ( S ) but as part of hypercholesterolaemic diets.", "output": "Cholesterol, Cholesterol, Cholesterol, Cholesterol." }, { "input": "CN and CS significantly blocked the hypercholesterolaemic effect observed in CC group.", "output": "There is no related enetity." }, { "input": "After 5 - wk, N and S diets increased the CYP4A - 1 expression.", "output": "There is no related enetity." }, { "input": "However, seaweed - RPs were unable to reduce the histological liver alterations observed in CC group.", "output": "There is no related enetity." }, { "input": "Larger and more abundant hepatocellular alterations were found in CS and CN rats suggesting that the hypocholesterolaemic effects of these seaweed - RPs seem to be a two - edged sword as they increased liver damage.", "output": "There is no related enetity." }, { "input": "Future studies are needed to understand the involved mechanisms.", "output": "There is no related enetity." }, { "input": "Identification of nuclear factor - kappa B sites in the Slc2a4 gene promoter.", "output": "There is no related enetity." }, { "input": "Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis.", "output": "Glucose." }, { "input": "Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature.", "output": "There is no related enetity." }, { "input": "Inflammatory NF - kappa B transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site ( s ) in Slc2a4 promoter and the direct repressor effect have never been reported yet.", "output": "There is no related enetity." }, { "input": "A motif - based sequence analysis of mouse Slc2a4 promoter revealed two putative kappa B sites located inside - 83 / - 62 and - 134 / - 113bp.", "output": "There is no related enetity." }, { "input": "Eletrophoretic mobility assay showed that p50 and p65 NF - kappa B subunits bind to both putative kappa B sites.", "output": "There is no related enetity." }, { "input": "Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50 - and p65 - binding to Slc2a4 promoter.", "output": "There is no related enetity." }, { "input": "Moreover, transfection experiments revealed that NF - kappa B binds to the - 134 / - 113bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription.", "output": "There is no related enetity." }, { "input": "The current findings demonstrate the existence of two kappa B sites in Slc2a4 gene promote, and that NF - kappa B has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation.", "output": "There is no related enetity." }, { "input": "In vitro evaluation of the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma.", "output": "nevirapine." }, { "input": "Anaplastic thyroid carcinoma ( ATC ) is a severe thyroid malignancy with poor prognosis, due to its early metastasis and unresponsiveness to both radiation and chemotherapy.", "output": "There is no related enetity." }, { "input": "Nevirapine, a non - nucleoside reverse transcriptase inhibitor, has been used as a re - differentiation agent to treat cancers in several human cancer models.", "output": "Nevirapine." }, { "input": "So far, the effects of nevirapine on human thyroid anaplastic carcinoma cells have not been documented.", "output": "nevirapine." }, { "input": "The aim of this study was to evaluate the therapeutic potential of nevirapine in treatment of human thyroid anaplastic carcinoma.", "output": "nevirapine." }, { "input": "Cell proliferation was determined by methly thiazolyl tetrazolium ( MTT ) assay.", "output": "methly thiazolyl tetrazolium, MTT." }, { "input": "Cell apoptosis was analyzed by Hoechst 33258 staining.", "output": "Hoechst 33258." }, { "input": "The mRNA expression of NIS and TSHR was determined by real - time quantitative reverse transcription - polymerase chain reaction ( real time RT - PCR ).", "output": "There is no related enetity." }, { "input": "Iodine uptake was determined by ( 125 ) I radioactivity assay.", "output": "Iodine, ( 125 ) I." }, { "input": "At all doses ( 100, 200, 350, 500 mu mol / L ) tested, nevirapine significantly inhibited cell proliferation after 48h treatment.", "output": "nevirapine." }, { "input": "At high dose ( 500 mu mol / L ), nevirapine significantly increased the percentage of apoptotic cells compared with control ( P < 0. 01 ).", "output": "nevirapine." }, { "input": "At lower doses ( 200 mu mol / L and 350 mu mol / L ), nevirapine did not induce cell apoptosis, but up - regulated NIS and THSR mRNA expression in a dose - dependent manner.", "output": "nevirapine." }, { "input": "In FRO cells pre - treated with nevirapine, the increase in NIS expression had no obvious effect on iodine uptake.", "output": "nevirapine, iodine." }, { "input": "These findings indicate that nevirapine has an anti - proliferative effect on FRO cells, which correlates with an induction of cell differentiation.", "output": "nevirapine." }, { "input": "Anti - secretory and cyto - protective effects of chebulinic acid isolated from the fruits of Terminalia chebula on gastric ulcers.", "output": "chebulinic acid." }, { "input": "In continuation of our drug discovery program on Indian medicinal plants, the gastro protective mechanism of chebulinic acid isolated from Terminalia chebula fruit was investigated.", "output": "chebulinic acid." }, { "input": "Chebulinic acid was evaluated against cold restraint ( CRU ), aspirin ( AS ), alcohol ( AL ) and pyloric ligation ( PL ) induced gastric ulcer models in rats.", "output": "Chebulinic acid, aspirin, alcohol." }, { "input": "Potential anti - ulcer activity of chebulinic acid was observed against CRU ( 62. 9 % ), AS ( 55. 3 % ), AL ( 80. 67 % ) and PL ( 66. 63 % ) induced ulcer models.", "output": "chebulinic acid." }, { "input": "The reference drug omeprazole ( 10mg / kg, p. o. ) showed 77. 73 % protection against CRU, 58. 30 % against AS and 70. 80 % against PL model.", "output": "omeprazole." }, { "input": "Sucralfate, another reference drug ( 500mg / kg, p. o. ) showed 65. 67 % protection in AL induced ulcer model.", "output": "Sucralfate." }, { "input": "Chebulinic acid significantly reduced free acidity ( 48. 82 % ), total acidity ( 38. 29 % ) and upregulated mucin secretion by 59. 75 % respectively.", "output": "Chebulinic acid." }, { "input": "Further, chebulinic acid significantly inhibited H ( + ) K ( + ) - ATPase activity in vitro with IC50 of 65. 01 mu g / ml as compared to the IC50 value of omeprazole ( 30. 24 mu g / ml ) confirming its anti - secretory activity.", "output": "chebulinic acid, H ( + ), K ( + ), omeprazole." }, { "input": "A Chinese herb formula decreases the monocarboxylate transporter - mediated absorption of valproic acid in rats.", "output": "monocarboxylate, valproic acid." }, { "input": "Huang - Qin - Tang ( HQT ), a Chinese medicine prescription containing Scutellariae Radix ( SR ), Paeoniae Radix ( PR ), Glycyrrhizae Radix ( GR ) and JuJubae Fructus ( JF ), was used for the treatments of cold with symptoms of abdominalgia and diarrhea.", "output": "There is no related enetity." }, { "input": "Valproic acid ( VPA ) is an antiepileptic drug with narrow therapeutic window.", "output": "Valproic acid, VPA." }, { "input": "This study investigated the effect of coadministration of HQT on the pharmacokinetics of VPA, a probe drug for monocarboxylate transporter ( MCT ).", "output": "VPA, monocarboxylate." }, { "input": "Rats were administered VPA alone ( 200. 0mg / kg ) and coadministered HQT ( 8. 0g / kg ) at 0. 5h before VPA and 1. 5h after VPA in crossover designs.", "output": "VPA, VPA, VPA." }, { "input": "In addition, the chronic effect of HQT was also evaluated by coadministration of the 7th dose at 0. 5h before VPA.", "output": "VPA." }, { "input": "The serum concentration of VPA was determined by a fluorescence polarization immunoassay.", "output": "VPA." }, { "input": "The results showed that coadministration of HQT at 0. 5h before VPA significantly decreased the AUC0 - t and Cmax by 62 % and 77 %, respectively, whereas coadministration of HQT at 1. 5h after VPA exerted no significant influence.", "output": "VPA, VPA." }, { "input": "When the 7th dose of HQT was given at 0. 5h before VPA, the AUC0 - t and Cmax of VPA were markedly decreased by 65 % and 82 %, respectively.", "output": "VPA, VPA." }, { "input": "Mechanism study revealed that the MCT - mediated uptake of fluorescein was inhibited by HQT and each component herbs.", "output": "fluorescein." }, { "input": "In conclusion, the MCT - mediated absorption of VPA was significantly decreased by concomitant administration of HQT.", "output": "VPA." }, { "input": "The Beneficial Role of Thiamine in Parkinson Disease.", "output": "Thiamine." }, { "input": "Parkinson disease ( PD ) is the second most common form of neurodegeneration among elderly individuals.", "output": "There is no related enetity." }, { "input": "PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance.", "output": "There is no related enetity." }, { "input": "In this paper, we review the evidence for an association between PD and thiamine.", "output": "thiamine." }, { "input": "Interestingly, a significant association has been demonstrated between PD and low levels of serum thiamine, and thiamine supplements appear to have beneficial clinical effects against PD.", "output": "thiamine, thiamine." }, { "input": "Multiple studies have evaluated the connection between thiamine and PD pathology, and candidate pathways involve the transcription factor Sp1, p53, Bcl - 2, caspase - 3, tyrosine hydroxylase, glycogen synthase kinase - 3 beta, vascular endothelial growth factor, advanced glycation end products, nuclear factor kappa B, mitogen - activated protein kinase, and the reduced form of nicotinamide adenine dinucleotide phosphate.", "output": "thiamine, tyrosine, nicotinamide adenine dinucleotide phosphate." }, { "input": "Thus, a review of the literature suggests that thiamine plays a role in PD, although further investigation into the effects of thiamine in PD is needed.", "output": "thiamine, thiamine." }, { "input": "Absence of cell - surface EpCAM in congenital tufting enteropathy.", "output": "There is no related enetity." }, { "input": "Mutations in the epithelial cell adhesion molecule ( EpCAM; CD326 ) gene are causal for congenital tufting enteropathy ( CTE ), a disease characterized by intestinal abnormalities resulting in lethal diarrhea in newborns.", "output": "There is no related enetity." }, { "input": "Why the different mutations all lead to the same disease is not clear.", "output": "There is no related enetity." }, { "input": "Here, we report that most mutations, including a novel intronic variant, will result in lack of EpCAM ' s transmembrane domain, whereas two mutations allow transmembrane localization.", "output": "There is no related enetity." }, { "input": "We find that these mutants are not routed to the plasma membrane, and that truncated mutants are secreted or degraded.", "output": "There is no related enetity." }, { "input": "Thus, all epcam mutations lead to loss of cell - surface EpCAM, resulting in CTE.", "output": "There is no related enetity." }, { "input": "Ribosome - inactivating proteins: From toxins to useful proteins.", "output": "There is no related enetity." }, { "input": "Ribosome - inactivating proteins ( RIPs ) either single - chain ( type 1 ) or two - chain ( type 2 ) are frequent in plants, often in multiple forms.", "output": "There is no related enetity." }, { "input": "They are RNA N - glycosidases, have antiviral, antifungal and insecticidal activity.", "output": "N." }, { "input": "Their expression in plants is increased under stressful conditions.", "output": "There is no related enetity." }, { "input": "They are investigated for practical applications in medicine and in agriculture.", "output": "There is no related enetity." }, { "input": "In medicine, RIPs have been linked to, or fused with, appropriate antibodies or other carriers to form \" immunotoxins \" or other conjugates specifically toxic to the cells target of the carrier, with the aim of eliminating malignant or other undesired cells.", "output": "There is no related enetity." }, { "input": "In agriculture, it has been observed that an enhanced expression of RIPs confers to plants an increased resistance to viruses, fungi, insects, and also to drought and salinity.", "output": "There is no related enetity." }, { "input": "Non - front - fanged colubroid snakes: A current evidence - based analysis of medical significance.", "output": "There is no related enetity." }, { "input": "Non - front - fanged colubroid snakes ( NFFC; formerly and artificially taxonomically assembled as \" colubrids \" ) comprise about 70 % of extant snake species and include several taxa now known to cause lethal or life threatening envenoming in humans.", "output": "There is no related enetity." }, { "input": "Although the medical risks of bites by only a handful of species have been documented, a growing number of NFFC are implicated in medically significant bites.", "output": "There is no related enetity." }, { "input": "The majority of these snakes have oral products ( Duvernoy ' s secretions, or venoms ) with unknown biomedical properties and their potential for causing harm in humans is unknown.", "output": "There is no related enetity." }, { "input": "Increasingly, multiple NFFC species are entering the commercial snake trade posing an uncertain risk.", "output": "There is no related enetity." }, { "input": "Published case reports describing NFFC bites were assessed for evidence - based value, clinical detail and verified species identification.", "output": "There is no related enetity." }, { "input": "These data were subjected to meta - analysis and a hazard index was generated for select taxa.", "output": "There is no related enetity." }, { "input": "Cases on which we consulted or personally treated were included and subjected to the same assessment criteria.", "output": "There is no related enetity." }, { "input": "Cases involving approximately 120 species met the selection criteria, and a small subset designated Hazard Level 1 ( most hazardous ), contained 5 species with lethal potential.", "output": "There is no related enetity." }, { "input": "Recommended management of these cases included antivenom for 3 species, Dispholidus typus, Rhabdophis tiginis, Rhabdophis subminiatus, whereas others in this subset without commercially available antivenoms ( Thelotornis spp. ) were treated with plasma / erythrocyte replacement therapy and supportive care.", "output": "There is no related enetity." }, { "input": "Heparin, antifibrinolytics and / or plasmapheresis / exchange transfusion have been used in the management of some Hazard Level 1 envenomings, but evidence - based analysis positively contraindicates the use of any of these interventions.", "output": "There is no related enetity." }, { "input": "Hazard Level 2 / 3 species were involved in cases containing mixed quality data that implicated these taxa ( e. g. Boiga irregularis, Philodryas olfersii, Malpolon monspessulanus ) with bites that caused rare systemic effects.", "output": "There is no related enetity." }, { "input": "Recommended management may include use of acetylcholinesterase inhibitors ( e. g. neostigmine ) and wound care on a case - by - case basis.", "output": "neostigmine." }, { "input": "Hazard level 3 species comprised a larger group capable of producing significant local effects only, often associated with a protracted bite ( eg Heterodon nasicus, Borikenophis ( Alsophis ) portoricensis, Platyceps ( Coluber ) rhodorachis ).", "output": "There is no related enetity." }, { "input": "Management is restricted to wound care.", "output": "There is no related enetity." }, { "input": "Bites by Hazard level 4 species comprised the majority of surveyed taxa and these showed only minor effects of no clinical importance.", "output": "There is no related enetity." }, { "input": "This study has produced a comprehensive evidence - based listing of NFFC snakes tabulated against medical significance of bites, together with best - practice management recommendations.", "output": "There is no related enetity." }, { "input": "This analysis assumes increasing importance, as there is growing exposure to lesser - known NFFC snakes, particularly in captive collections that may uncover further species of significance in the future.", "output": "There is no related enetity." }, { "input": "Careful and accurate documentation of bites by verified species of NFFC snakes is required to increase the evidence base and establish the best medical management approach for each species.", "output": "There is no related enetity." }, { "input": "Cooperative activation of gene expression by agonists and antagonists mediated by estrogen receptor heteroligand dimer complexes.", "output": "estrogen." }, { "input": "Estrogen receptor ( ER ) antagonists are generally thought to inhibit estrogen action through competitive inhibition, resulting in receptor binding to antagonist rather than agonist.", "output": "Estrogen, estrogen." }, { "input": "However, microarray analyses reveal a group of genes for which ER agonist and antagonist cooperatively regulate expression, suggesting additional models of combined agonist / antagonist action must exist.", "output": "There is no related enetity." }, { "input": "In conjunction with a chimeric reporter gene and two modified ERs, one [ ER alpha ( GSCKV ) ] with a mutation in the DNA - binding domain and the other ( ER alpha - G521R ) with a ligand - binding specificity mutation, we herein demonstrate that ER agonist and antagonist cooperatively activate gene expression through an ER heteroligand dimer complex ( ER - HLD ) consisting of one subunit of the receptor dimer bound to agonist and another occupied by antagonist.", "output": "There is no related enetity." }, { "input": "Coimmunoprecipitation experiments confirmed interaction between the agonist - bound and antagonist - bound receptors.", "output": "There is no related enetity." }, { "input": "This cooperative activation of gene expression was enhanced by steroid receptor coactivator 3 coactivator, and required each ligand - bound subunit of the dimer to bind to DNA, as well as both activation function 1 domains for maximal transcriptional activity.", "output": "There is no related enetity." }, { "input": "Ligand combinations able to induce ER - HLD transcriptional activity include the agonists 17 beta - estradiol or conjugated estrogens with the antagonists tamoxifen, raloxifene, bazedoxifene, or fulvestrant.", "output": "17 beta - estradiol, tamoxifen, raloxifene, bazedoxifene, fulvestrant." }, { "input": "Moreover, ER - HLD can activate transcription in the context of a natural promoter.", "output": "There is no related enetity." }, { "input": "Taken together, these findings broaden our understanding of the complex relationship between ER agonist and antagonist, and suggest a novel model by which cell and tissue selective effects of antiestrogens may be achieved.", "output": "There is no related enetity." }, { "input": "Exenatide - Induced Reduction in Energy Intake Is Associated With Increase in Hypothalamic Connectivity.", "output": "There is no related enetity." }, { "input": "OBJECTIVEGlucagon - like peptide - 1 receptor agonists like exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake.", "output": "There is no related enetity." }, { "input": "In humans, however, significant weight loss has been observed in only a subgroup of patients.", "output": "There is no related enetity." }, { "input": "Why only some individuals respond with weight loss and others do not remains unclear.", "output": "There is no related enetity." }, { "input": "In this functional magnetic resonance imaging ( fMRI ) study, we investigated differences in hypothalamic connectivity between \" responders \" ( reduction in energy intake after exenatide infusion ) and \" nonresponders. \" RESEARCH DESIGN AND METHODSWe performed a randomized, double - blinded, placebo - controlled, cross - over fMRI study with intravenous administration of exenatide in obese male volunteers.", "output": "There is no related enetity." }, { "input": "During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images.", "output": "There is no related enetity." }, { "input": "After each scanning session, energy intake was measured using an ad libitum buffet.", "output": "There is no related enetity." }, { "input": "Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain. RESULTSResponders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo.", "output": "There is no related enetity." }, { "input": "Nonresponders did not show any significant exenatide - induced changes in hypothalamic connectedness. CONCLUSIONSOur results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide - dependent anorexigenic effect.", "output": "There is no related enetity." }, { "input": "These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.", "output": "There is no related enetity." }, { "input": "Significant Coronary Stenosis in Asymptomatic Chinese With Different Glycemic Status.", "output": "There is no related enetity." }, { "input": "OBJECTIVE To evaluate coronary artery stenosis in early diabetes or prediabetes asymptomatic of myocardial ischemia in community - dwelling Chinese adults. RESEARCH DESIGN AND METHODS Age - and sex - matched participants with normal glucose regulation ( NGR ), prediabetes, or diabetes diagnosed within 5 years, asymptomatic of coronary artery disease ( CAD ), were randomly selected from a community - dwelling Chinese population aged 40 - 60 years.", "output": "glucose." }, { "input": "Dual - source computed tomography coronary angiography was used to evaluate the existence and extent of coronary stenosis, which was considered significant if > 50 % narrowing of vessel lumen was detected. RESULTS After excluding uninterpretable segments attributable to motion artifacts, a total of 135 participants with NGR, 132 with prediabetes, and 134 with diabetes participated in data analysis.", "output": "There is no related enetity." }, { "input": "Significant coronary stenosis was detected in 10 ( 7. 4 % ), 10 ( 7. 6 % ), and 22 ( 16. 4 % ) individuals with NGR, prediabetes, and diabetes, respectively ( P for trend = 0. 029 ).", "output": "There is no related enetity." }, { "input": "Diabetes, rather than prediabetes, was associated with a significant 2. 34 - fold elevated risk [ odds ratio ( OR ) 2. 34 ( 95 % CI 1. 01 - 5. 43 ); P = 0. 047 ] of significant coronary stenosis as compared with that associated with NGR.", "output": "There is no related enetity." }, { "input": "Levels of glucose evaluation were independently and significantly associated with risks of significant coronary stenosis in diabetes.", "output": "glucose." }, { "input": "Each 1 - SD increase in fasting plasma glucose, 2 - h postload plasma glucose, and HbA1c conveyed 2. 11 - fold, 1. 73 - fold, and 1. 81 - fold higher risks of significant coronary stenosis, respectively, after adjustment for other conventional cardiovascular risk factors. CONCLUSIONSUsing a noninvasive CAD diagnostic modality such as dual - source computed tomography coronary angiography, we detected a markedly elevated risk of significant coronary stenosis with early diabetes in asymptomatic Chinese adults.", "output": "glucose, glucose." }, { "input": "Determination of robenidine residues in chicken muscle by high performance liquid chromatography with ultraviolet detection.", "output": "robenidine." }, { "input": "A simple, robust and reliable method for the determination of residual robenidine in chicken muscle using high performance liquid chromatography with ultraviolet ( UV ) detection was developed and validated according to the Codex Alimentarius Commission guidelines.", "output": "robenidine." }, { "input": "Chicken muscle was extracted by acetonitrile / formic acid ( 98: 2, v / v ) and defatted with hexane.", "output": "acetonitrile, formic acid, hexane." }, { "input": "Analytes were isocratically separated on a Luna C18 column ( 4. 6 x 150 mm, 5 mu m ) using 70 % methanol in water containing 0. 1 % trifluoroacetic acid at a flow rate of 1. 0 mL / min at 30 degrees C.", "output": "methanol, trifluoroacetic acid." }, { "input": "UV detection was performed at 312 nm.", "output": "There is no related enetity." }, { "input": "The method was validated by assessing performance parameters including selectivity, linearity, limit of quantification ( LOQ ), precision, accuracy, recovery, stability and robustness.", "output": "There is no related enetity." }, { "input": "A calibration curve that was constructed over 0. 05 - 0. 5 mu g / g showed correlation coefficients of more than 0. 999.", "output": "There is no related enetity." }, { "input": "The intra - and inter - day precisions ( as coefficient of variation ) were 1. 45 - 3. 32 and 2. 63 - 4. 99 %, respectively.", "output": "There is no related enetity." }, { "input": "The intra - and inter - day accuracies were 99. 4 - 105. 3 and 98. 3 - 101. 6 %, respectively.", "output": "There is no related enetity." }, { "input": "The recoveries were in the range of 76. 6 - 81. 8 % and the LOQ was 0. 05 mu g / g.", "output": "There is no related enetity." }, { "input": "The developed method showed suitable performance for the determination of robenidine residues in chicken muscle.", "output": "robenidine." }, { "input": "Formulation and pharmacokinetic evaluation of once - daily sustained - released system of nifedipine with solid dispersion and coating techniques.", "output": "nifedipine." }, { "input": "A novel sustained - release system was developed for poorly water - soluble drugs by applying solid dispersion ( SD ) technique to improve the solubility.", "output": "There is no related enetity." }, { "input": "The SD systems composed of polyvinyl pyrrolidone and stearic acid could not control the release of nifedipine.", "output": "polyvinyl pyrrolidone, stearic acid, nifedipine." }, { "input": "When the above SD granules were coated with ethylcellolulose ( EC10, 45 and 100cp ), the dissolution rate extended from 16 to 20 h.", "output": "There is no related enetity." }, { "input": "When the concentration of EC100cp was increased to 4 - 6 %, the sustained - release formulation F7 and F8 prepared with 4 % EC100cp and 6 % EC100cp, respectively, could control the drug release in a better manner, namely, they could control drug release in the initial hours with a high cumulative amount of drug at 24 h.", "output": "There is no related enetity." }, { "input": "The mechanism of drug release from F7 and F8 was diffusion coupled with erosion.", "output": "There is no related enetity." }, { "input": "When immediate - release capsules was orally administered to rabbits, its absorption was very rapid with a short elimination half - life, while a prolonged maintenance of the plasma drug level up to 24 h was obtained for F7 and F8.", "output": "There is no related enetity." }, { "input": "Furthermore, the oral bioavailability of F7 and F8 was significantly improved.", "output": "There is no related enetity." }, { "input": "The results suggested that this novel sustained - release system would be a promising system to improve the solubility and sustain the absorption of poorly water - soluble drugs.", "output": "There is no related enetity." }, { "input": "Effects of dried Citrus unshiu peels on gastrointestinal motility in rodents.", "output": "There is no related enetity." }, { "input": "Aqueous extracts of the dried mature ( ANP - W ) and immature Citrus unshiu peels ( CUP - W ) have been used as a traditional folk medicine for the treatment of gastrointestinal ( GI ) motility disorders in Korea.", "output": "There is no related enetity." }, { "input": "In the present study, neither ANP - W nor CUP - W exhibited significant toxicity even at an oral dose of 5 g / kg to mice.", "output": "There is no related enetity." }, { "input": "The effects of ANP - W and CUP - W on GI motor function were investigated by measuring the intestinal transit rate ( ITR ) of Evans blue in normal mice and rats with experimental GI motility dysfunctions ( GMDs ).", "output": "There is no related enetity." }, { "input": "In normal mice, the ITR was significantly increased by ANP - W ( 0. 1 - 1 g / kg ) in a dose dependent manner, whereas CUP - W elicited no significant change.", "output": "There is no related enetity." }, { "input": "GMD was induced by appropriate surgery or an intraperitoneal injection of acetic acid to the rats.", "output": "acetic acid." }, { "input": "The ITR in the GMD rats was significantly retarded compared to that in normal rats.", "output": "There is no related enetity." }, { "input": "However, the retardation was significantly inhibited by ANP - W ( 0. 1 - 1 g / kg ) in a dose dependent manner.", "output": "There is no related enetity." }, { "input": "The above results suggest that ANP - W has the potential for development as a prokinetic agent that may prevent or alleviate GMD in human patients.", "output": "There is no related enetity." }, { "input": "Transparent stretchable single - walled carbon nanotube - polymer composite films with near - infrared fluorescence.", "output": "carbon." }, { "input": "We report transparent stretchable single - walled carbon nanotube - polymer composite films that emit pronounced Raman and near - infrared fluorescence with a fine spatial resolution.", "output": "carbon." }, { "input": "The independent modulation in Raman and fluorescence spectra is demonstrated in response to touch and temperature.", "output": "There is no related enetity." }, { "input": "The optical signal transduction of transparent stretchable optoelectronic films may enable a paradigm shift in touch - sensing devices eliminating electrical interconnects.", "output": "There is no related enetity." }, { "input": "All - graphene core - sheath microfibers for all - solid - state, stretchable fibriform supercapacitors and wearable electronic textiles.", "output": "graphene." }, { "input": "Unique all - graphene core - sheath fibers composed of a graphene fiber core with a sheath of 3D graphene network have been developed.", "output": "graphene, graphene, graphene." }, { "input": "Used as flexible electrodes, all - solid - state fiber supercapacitors have been fabricated, which can be managed to highly compressible and stretchable spring supercapacitors and can also be woven into a textile for wearable electronics.", "output": "There is no related enetity." }, { "input": "Cyclodextrin Insulation Prevents Static Quenching of Conjugated Polymer Fluorescence at the Single Molecule Level.", "output": "There is no related enetity." }, { "input": "Conjugated polymers ( CPs ) are promising materials for fluorescence imaging application.", "output": "There is no related enetity." }, { "input": "However, a significant problem in this field is the unexplained abnormally low fluorescence brightness ( or number of fluorescence photons detected per one excitation photon ) exhibited by most of CP single chains in solid polymer hosts.", "output": "There is no related enetity." }, { "input": "Here it is shown that this detrimental effect can be fully avoided for short chains of polyfluorene - bis - vinylphenylene ( PFBV ) embedded in a host polymer matrix of PMMA, if the conjugated backbone is insulated by cyclodextrin rings to form a polyrotaxane ( PFBV - Rtx ).", "output": "polyfluorene - bis - vinylphenylene, PFBV, PMMA, PFBV." }, { "input": "Fluorescence kinetics and quantum yields are measured for the polymers in liquid solutions, pristine films, and solid PMMA blends.", "output": "PMMA." }, { "input": "The fluorescence brightness of PFBV - Rtx single chains dispersed in a solid PMMA is very close to that expected for a chain with 100 % fluorescence quantum yield, while the unprotected PFBV chains of the same length possess 4 times lower brightness.", "output": "PFBV, PMMA, PFBV." }, { "input": "Despite this, the fluorescence decay kinetics are the same for both polymers, suggesting the presence of static or ultrafast fluorescence quenching in the unprotected polymer.", "output": "There is no related enetity." }, { "input": "About 80 % of an unprotected PFBV chain is estimated to be completely quenched.", "output": "PFBV." }, { "input": "The hypothesis is that the cyclodextrin rings prevent the quenching by working as ' bumpers ' reducing the mechanical forces applied by the host polymer to the conjugated backbone and help retaining its conformational freedom.", "output": "There is no related enetity." }, { "input": "While providing a recipe for making CP fluorescence bright at the single - molecule level, these results identify a lack of fundamental understanding in the community of the influence of the environment on excited states in conjugated materials.", "output": "There is no related enetity." }, { "input": "Cyclic denaturation and renaturation of double - stranded DNA by redox - state switching of DNA intercalators.", "output": "There is no related enetity." }, { "input": "Hybridization of complementary nucleic acid strands is fundamental to nearly all molecular bioanalytical methods ranging from polymerase chain reaction and DNA biosensors to next generation sequencing.", "output": "There is no related enetity." }, { "input": "For nucleic acid amplification methods, controlled DNA denaturation and renaturation is particularly essential and achieved by cycling elevated temperatures.", "output": "There is no related enetity." }, { "input": "Although this is by far the most used technique, the management of rapid temperature changes requires bulky instrumentation and intense power supply.", "output": "There is no related enetity." }, { "input": "These factors so far precluded the development of true point - of - care tests for molecular diagnostics.", "output": "There is no related enetity." }, { "input": "To overcome this limitation we explored the possibility of using electrochemical means to control reversible DNA hybridization by using the electroactive intercalator daunomycin ( DM ).", "output": "daunomycin." }, { "input": "We show that redox - state switching of DM altered its properties from DNA binding to nonbinding, under otherwise constant conditions, and thus altered the thermodynamic stability of duplex DNA.", "output": "There is no related enetity." }, { "input": "The operational principle was demonstrated using complementary synthetic 20mer and 40mer DNA oligonucleotides.", "output": "There is no related enetity." }, { "input": "Absorbance - based melting curve analysis revealed significantly higher melting temperatures for DNA in the presence of oxidized compared to chemically reduced DM.", "output": "There is no related enetity." }, { "input": "This difference was exploited to drive cyclic electrochemically controlled denaturation and renaturation.", "output": "There is no related enetity." }, { "input": "Analysis with in situ UV - vis and circular dichroism spectroelectrochemistry, as two independent techniques, indicated that up to 80 % of the DNA was reversibly hybridized.", "output": "There is no related enetity." }, { "input": "This remarkable demonstration of electrochemical control of five cycles of DNA denaturation and renaturation, under otherwise constant conditions, could have wide - ranging implications for the future development of miniaturized analytical systems for molecular diagnostics and beyond.", "output": "There is no related enetity." }, { "input": "Three - dimensional in situ photocurrent mapping for nanowire photovoltaics.", "output": "There is no related enetity." }, { "input": "Devices based upon semiconductor nanowires provide many well - known advantages for next - generation photovoltaics, however, limited experimental techniques exist to determine essential electrical parameters within these devices.", "output": "There is no related enetity." }, { "input": "We present a novel application of a technique based upon two - photon induced photocurrent that provides a submicrometer resolution, three - dimensional reconstruction of photovoltaic parameters.", "output": "There is no related enetity." }, { "input": "This tool is used to characterize two GaAs nanowire - based devices, revealing the detail of current generation and collection, providing a path toward achieving the promise of nanowire - based photovoltaic devices.", "output": "There is no related enetity." }, { "input": "Microvascular complications and diabetic retinopathy: recent advances and future implications.", "output": "There is no related enetity." }, { "input": "Retinal microvascular alterations have been observed during diabetic retinopathy ( DR ) due to the retinal susceptibility towards subtle pathological alterations.", "output": "There is no related enetity." }, { "input": "Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR.", "output": "There is no related enetity." }, { "input": "In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined.", "output": "There is no related enetity." }, { "input": "In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed.", "output": "There is no related enetity." }, { "input": "Photoexcitation dynamics of coupled semiconducting carbon nanotube thin films.", "output": "carbon." }, { "input": "Carbon nanotubes are a promising means of capturing photons for use in solar cell devices.", "output": "Carbon." }, { "input": "We time - resolved the photoexcitation dynamics of coupled, bandgap - selected, semiconducting carbon nanotubes in thin films tailored for photovoltaics.", "output": "carbon." }, { "input": "Using transient absorption spectroscopy and anisotropy measurements, we found that the photoexcitation evolves by two mechanisms with a fast and long - range component followed by a slow and short - range component.", "output": "There is no related enetity." }, { "input": "Within 300 fs of optical excitation, 20 % of nanotubes transfer their photoexcitation over 5 - 10 nm into nearby nanotube fibers.", "output": "There is no related enetity." }, { "input": "After 3 ps, 70 % of the photoexcitation resides on the smallest bandgap nanotubes.", "output": "There is no related enetity." }, { "input": "After this ultrafast process, the photoexcitation continues to transfer on a ~ 10 ps time scale but to predominantly aligned tubes.", "output": "There is no related enetity." }, { "input": "Ultimately the photoexcitation hops twice on average between fibers.", "output": "There is no related enetity." }, { "input": "These results are important for understanding the flow of energy and charge in coupled nanotube materials and light - harvesting devices.", "output": "There is no related enetity." }, { "input": "Liquiritigenin prevents Staphylococcus aureus - mediated lung cell injury via inhibiting the production of alpha - hemolysin.", "output": "Liquiritigenin." }, { "input": "Staphylococcus aureus is a significant Gram - positive bacterium that is associated with a broad spectrum of diseases ranging from minor skin infections to lethal pneumonia, endocarditis, and toxinoses.", "output": "There is no related enetity." }, { "input": "alpha - Hemolysin is one of the most important exotoxins that contribute to the pathogenesis of S. aureus infections.", "output": "There is no related enetity." }, { "input": "Liquiritigenin is one of the most significant active components in licorice.", "output": "Liquiritigenin." }, { "input": "In this study, hemolysis, western blot, and real - time reverse transcription - PCR assays were performed to investigate the impact of liquiritigenin on the production of S. aureus alpha - hemolysin.", "output": "liquiritigenin." }, { "input": "The results showed that low concentrations of liquiritigenin remarkably decreased S. aureus alpha - hemolysin production in a dose - dependent manner.", "output": "liquiritigenin." }, { "input": "Using live / dead cell staining and lactate dehydrogenase assays, we found that liquiritigenin could protect human lung cells ( A549 ) from alpha - hemolysin - mediated injury.", "output": "lactate, liquiritigenin." }, { "input": "The data indicated that this compound could potentially be useful in developing drugs aiming at staphylococcal alpha - hemolysin.", "output": "There is no related enetity." }, { "input": "Selective Reduction of PHA Biopolyesters and Their Synthetic Analogues to Corresponding PHA Oligodiols Proved by Structural Studies.", "output": "PHA, PHA." }, { "input": "A highly selective method is described for controlling the degradation of polyhydroxyalkanoates, PHA, via a reduction reaction that uses lithium borohydride.", "output": "polyhydroxyalkanoates, PHA, lithium borohydride." }, { "input": "Using this method, oligo ( hydroxyalkanoate ) diols derived from a poly ( 3 - hydroxybutyrate - co - 4 - hydroxybutyrate ) biopolyester [ poly ( 3HB - co - 4HB ) ] and from synthetic atactic poly [ ( R, S ) - 3 - hydroxybutyrate ] ( a - PHB ) were obtained.", "output": "oligo ( hydroxyalkanoate ) diols, poly ( 3 - hydroxybutyrate - co - 4 - hydroxybutyrate ), poly ( 3HB - co - 4HB ), poly [ ( R , S ) - 3 - hydroxybutyrate ], PHB." }, { "input": "The structural characterization of the oligo ( hydroxyalkanoate ) diols was conducted using NMR and ESI - mass spectrometry analyses, which confirmed that oligomers that were terminated by two hydroxyl end groups were formed.", "output": "oligo ( hydroxyalkanoate ) diols, hydroxyl." }, { "input": "The reduction of the ester groups occurred in a statistical way regardless of the chemical structure of the comonomer units or of the microstructure of the polyester chain.", "output": "ester, polyester." }, { "input": "The presented method can be used to synthesize various PHA oligodiols that are potentially useful in the further synthesis of tailor - made biodegradable materials.", "output": "PHA." }, { "input": "Utilizing the Unique Properties of Nanowire MOSFETs for RF Applications.", "output": "There is no related enetity." }, { "input": "Nanostructures have attracted a great deal of attention because of their potential usefulness for high density applications.", "output": "There is no related enetity." }, { "input": "More importantly, they offer excellent avenues for improved scaling beyond conventional approaches.", "output": "There is no related enetity." }, { "input": "Less attention has been paid to their intrinsic potential for distinct circuit applications.", "output": "There is no related enetity." }, { "input": "Here we discuss how a combination of 1 - D transport, operation in the quantum capacitance limit, and ballistic transport can be utilized for certain RF applications.", "output": "There is no related enetity." }, { "input": "In particular this work explores how the above transport properties can provide a high degree of transconductance linearity at the device level.", "output": "There is no related enetity." }, { "input": "The article also discusses how device characteristics can be interpreted and analyzed in terms of device linearity if the above conditions are not ideally fulfilled.", "output": "There is no related enetity." }, { "input": "Using aggressively scaled silicon nanowire field - effect transistors as an example device in this work provides new insights toward the proper choice of channel material to improve linearity through the above - mentioned transport conditions.", "output": "silicon." }, { "input": "According to this study, a high degree of linearity occurs feasible while operating at low supply voltages making low - dimensional systems, and here in particular nanowires, an interesting candidate for portable RF applications.", "output": "There is no related enetity." }, { "input": "A General Strategy for Biocompatible, High - Effective Upconversion Nanocapsules Based on Triplet - Triplet Annihilation.", "output": "There is no related enetity." }, { "input": "A general strategy for constructing high - effective upconversion nanocapsules based on triplet - triplet annihilation ( TTA ) was developed by loading both sensitizer and annihilator into BSA - dextran stabilized oil droplets.", "output": "There is no related enetity." }, { "input": "This strategy can maintain high translational mobility of the chromophores, avoid luminescence quenching of chromophore by aggregation, and decrease the O2 - induced quenching of TTA - based upconversion emission.", "output": "O2." }, { "input": "Pt ( II ) - tetraphenyl - tetrabenzoporphyrin ( PtTPBP ) and BODIPY dyes ( BDP - G and BDP - Y with the maximal fluorescence emission at 528 and 546 nm, respectively ) were chosen as sensitizer / annihilator couples to fabricate green and yellow upconversion luminescent emissive nanocapsules, named UCNC - G and UCNC - Y, respectively.", "output": "Pt ( II ), tetraphenyl, tetrabenzoporphyrin, PtTPBP, BODIPY, BDP - G, BDP - Y." }, { "input": "In water under the atmospheric environment, interestingly, UCNC - G and UCNC - Y exhibit intense upconversion luminescence ( UCL ) emission ( lambda ex = 635 nm ) with the quantum efficiencies ( Phi UCL ) of 1. 7 % and 4. 8 %, respectively, whereas very weak UCL emission ( Phi UCL < 0. 1 % ) was observed for the corresponding previous reported SiO2 - coating nanosystems because of aggregation - induced fluorescence quenching of annihilators.", "output": "SiO2." }, { "input": "Furthermore, application of theses upconversion nanocapsules for high - contrast UCL bioimaging in vivo of living mice without removing the skin was demonstrated under 635 - nm excitation with low power density of 12. 5 mW cm ( - 2 ).", "output": "There is no related enetity." }, { "input": "Highly Responsive Ultrathin GaS Nanosheet Photodetectors on Rigid and Flexible Substrates.", "output": "GaS." }, { "input": "The first GaS nanosheet - based photodetectors are demonstrated on both mechanically rigid and flexible substrates.", "output": "GaS." }, { "input": "Highly crystalline, exfoliated GaS nanosheets are promising for optoelectronics due to strong absorption in the UV - visible wavelength region.", "output": "GaS." }, { "input": "Photocurrent measurements of GaS nanosheet photodetectors made on SiO2 / Si substrates and flexible polyethylene terephthalate ( PET ) substrates exhibit a photoresponsivity at 254 nm up to 4. 2 AW ( - 1 ) and 19. 2 AW ( - 1 ), respectively, which exceeds that of graphene, MoS2, or other 2D material - based devices.", "output": "GaS, SiO2, Si, polyethylene terephthalate, PET, graphene, MoS2." }, { "input": "Additionally, the linear dynamic range of the devices on SiO2 / Si and PET substrates are 97. 7 dB and 78. 73 dB, respectively.", "output": "SiO2, Si, PET." }, { "input": "Both surpass that of currently exploited InGaAs photodetectors ( 66 dB ).", "output": "There is no related enetity." }, { "input": "Theoretical modeling of the electronic structures indicates that the reduction of the effective mass at the valence band maximum ( VBM ) with decreasing sheet thickness enhances the carrier mobility of the GaS nanosheets, contributing to the high photocurrents.", "output": "GaS." }, { "input": "Double - peak VBMs are theoretically predicted for ultrathin GaS nanosheets ( thickness less than five monolayers ), which is found to promote photon absorption.", "output": "GaS." }, { "input": "These theoretical and experimental results show that GaS nanosheets are promising materials for high - performance photodetectors on both conventional silicon and flexible substrates.", "output": "GaS, silicon." }, { "input": "New GABA / Glutamate Receptor Target for [ ( 3 ) H ] Isoxazoline Insecticide.", "output": "GABA, Glutamate, [ ( 3 ) H ] Isoxazoline." }, { "input": "The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [ ( 3 ) H ] ethynylbicycloorthobenzoate ( [ ( 3 ) H ] EBOB ) binding to house fly head membranes with an IC50 of 0. 2 nM in a manner characteristic of GABA - gated chloride channel antagonists.", "output": "isoxazoline, A1443, [ ( 3 ) H ] ethynylbicycloorthobenzoate, [ ( 3 ) H ] EBOB, GABA, chloride." }, { "input": "To further define its mode of action, we prepared phenyl - labeled [ ( 3 ) H ] A1443 as described with a specific activity of 14 Ci / mmol.", "output": "phenyl, [ ( 3 ) H ] A1443." }, { "input": "This new radioligand with an apparent IC50 of about 0. 4 nM is poorly displaced by most insecticides acting at the [ ( 3 ) H ] EBOB site.", "output": "[ ( 3 ) H ] EBOB." }, { "input": "Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA / glutamate chloride channel activator site.", "output": "isoxazoline, avermectin, GABA, glutamate, chloride." }, { "input": "These findings revive interest in the insect GABA / glutamate receptor as an insecticide target.", "output": "GABA, glutamate." }, { "input": "Increased dietary fat contributes to dysregulation of the LKB1 / AMPK pathway and increased damage in a mouse model of early - stage ethanol - mediated steatosis.", "output": "ethanol." }, { "input": "OBJECTIVE: The objective of the study was to examine the interaction of moderate and high dietary fat and ethanol with respect to formation of steatosis and regulation of the AMP - activated protein kinase ( AMPK ) pathway in a mouse model of chronic ethanol consumption.", "output": "ethanol, AMP, ethanol." }, { "input": "METHODS: Male C57BL / 6J mice were pair - fed a modified Lieber - DeCarli diet composed of either moderate fat [ 30 % fat - derived calories ( MF ) ] or high fat [ 45 % fat - derived calories ( HF ) ] combined with increasing concentrations of ethanol ( 2 % - 6 % ) for 6 weeks.", "output": "ethanol." }, { "input": "RESULTS: Chronic ethanol consumption resulted in significant increases in plasma alanine aminotransferase in MF ( 1. 84 - fold ) and HF mice ( 2. 33 - fold ), yet liver triglycerides only increased significantly in the HF model ( 1. 62 - fold ).", "output": "ethanol, alanine, triglycerides." }, { "input": "Ethanol addition significantly increased plasma adiponectin under conditions of MF but not HF.", "output": "Ethanol." }, { "input": "In combination with MF, the addition of ethanol significantly decreased total and hepatic pThr ( 172 ) AMPK alpha and acetyl CoA Carboxylase ( ACC ).", "output": "ethanol, pThr, acetyl CoA." }, { "input": "HF plus ethanol decreased pSer ( 108 ) AMPK beta, yet a marked 1. 5 - fold increase in pThr ( 172 ) AMPK alpha occurred.", "output": "ethanol, pSer, pThr." }, { "input": "No change was evident in pSer ( 79 ) ACC under conditions of ethanol and HF ingestion.", "output": "pSer, ethanol." }, { "input": "In both models, nuclear levels of sterol response element binding protein 1c and carbohydrate response element binding protein were decreased.", "output": "sterol, carbohydrate." }, { "input": "Surprisingly, MF plus ethanol significantly elevated protein expression of medium - chain acyl - CoA dehydrogenase ( MCAD ), long - chain acyl - CoA dehydrogenase ( LCAD ) and very long chain acyl - CoA dehydrogenase but did not significantly affect mRNA expression of other proteins involved in beta - oxidation and fatty acid synthesis.", "output": "ethanol, acyl - CoA, acyl - CoA, acyl - CoA, fatty acid." }, { "input": "HF plus ethanol significantly reduced mRNA expression of both stearoyl CoA desaturase 1 and fatty acid elongase 5, but did not have an effect on MCAD or LCAD.", "output": "ethanol, stearoyl CoA, fatty acid." }, { "input": "CONCLUSION: These data suggest that, when co - ingested with ethanol, dietary fat differentially contributes to dysregulation of adiponectin - dependent activation of the AMPK pathway in the liver of mice.", "output": "ethanol." }, { "input": "Structure - based design of novel dihydroisoquinoline BACE - 1 inhibitors that do not engage the catalytic aspartates.", "output": "dihydroisoquinoline, aspartates." }, { "input": "The structure - activity relationship of a series of dihydroisoquinoline BACE - 1 inhibitors is described.", "output": "dihydroisoquinoline." }, { "input": "Application of structure - based design to screening hit 1 yielded sub - micromolar inhibitors.", "output": "There is no related enetity." }, { "input": "Replacement of the carboxylic acid of 1 was guided by X - ray crystallography, which allowed the replacement of a key water - mediated hydrogen bond.", "output": "carboxylic acid, hydrogen." }, { "input": "This work culminated in compounds such as 31, which possess good BACE - 1 potency, excellent permeability and a low P - gp efflux ratio.", "output": "There is no related enetity." }, { "input": "Changes in hypothalamic - pituitary - adrenal stress responsiveness before and after puberty in rats.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue \" Puberty and Adolescence \".", "output": "There is no related enetity." }, { "input": "Many endocrine changes are associated with pubertal and adolescent development.", "output": "There is no related enetity." }, { "input": "One such change is the responsiveness of the hypothalamic - pituitary - adrenal ( HPA ) axis to physical and / or psychological stressors.", "output": "There is no related enetity." }, { "input": "Recent human and non - human animal studies have shown that hormonal stress reactivity increases significantly throughout puberty and adolescence.", "output": "There is no related enetity." }, { "input": "Specifically, exposure to various stressors results in greater adrenocorticotropic hormone ( ACTH ) and glucocorticoid responses in peripubertal compared to adult animals.", "output": "There is no related enetity." }, { "input": "This review will focus on how stress reactivity changes throughout puberty and adolescence, as well as potential mechanisms that mediate these changes in stress responsiveness.", "output": "There is no related enetity." }, { "input": "Though the implications of these pubertal shifts in stress responsiveness are not fully understood, the significant increase in stress - related mental and physical dysfunctions during this stage of development highlights the importance of studying pubertal and adolescent maturation of HPA function and its reactivity to stress.", "output": "There is no related enetity." }, { "input": "[ 11C ] olanzapine, radiosynthesis and lipophilicity of a new potential PET 5 - HT2 and D2 receptor radioligand.", "output": "[ 11C ] olanzapine." }, { "input": "Olanzapine and its precursor desmethyl - Olanzapine were synthesized from malononitrile, propionaldehyde, 1 - fluoro - 2 - nitrobenzene, and substituted piperazine in 4, 4, 5, and 5 steps with 35 %, 32 %, 26 %, and 32 % overall chemical yield, respectively.", "output": "Olanzapine, malononitrile, propionaldehyde, 1 - fluoro - 2 - nitrobenzene, piperazine." }, { "input": "[ ( 11 ) C ] Olanzapine was prepared from desmethyl - Olanzapine with [ ( 11 ) C ] CH3OTf through N - [ ( 11 ) C ] methylation and isolated by HPLC combined with solid - phase extraction ( SPE ) in 40 - 50 % radiochemical yield based on [ ( 11 ) C ] CO2 and decay corrected to end of bombardment ( EOB ), with 370 - 740 GBq / mu mol specific activity at EOB.", "output": "[ ( 11 ) C ] Olanzapine, [ ( 11 ) C ] CH3OTf, N, ( 11 ) C, [ ( 11 ) C ] CO2." }, { "input": "The calculated LogP ( CLogP ) value of [ ( 11 ) C ] Olanzapine is 3. 39.", "output": "[ ( 11 ) C ] Olanzapine." }, { "input": "Pregna - 5, 17 ( 20 ) - dien - 21 - oyl amides affecting sterol and triglyceride biosynthesis in Hep G2 cells.", "output": "Pregna - 5 , 17 ( 20 ) - dien - 21 - oyl amides, sterol, triglyceride." }, { "input": "Synthesis of series [ 17 ( 20 ) Z ] - and [ 17 ( 20 ) E ] - pregna - 5, 17 ( 20 ) - dien - 21 - oyl amides, containing polar substituents in amide moiety, based on rearrangement of 17 alpha - bromo - 21 - iodo - 3 beta - acetoxypregn - 5 - en - 20 - one caused by amines, is presented.", "output": "[ 17 ( 20 ) Z ] - and [ 17 ( 20 ) E ] - pregna - 5 , 17 ( 20 ) - dien - 21 - oyl amides, 17 alpha - bromo - 21 - iodo - 3 beta - acetoxypregn - 5 - en - 20 - one." }, { "input": "The titled compounds were evaluated for their potency to regulate sterol and triglyceride biosynthesis in human hepatoma Hep G2 cells in comparison with 25 - hydroxycholesterol.", "output": "sterol, triglyceride, 25 - hydroxycholesterol." }, { "input": "Three [ 17 ( 20 ) E ] - pregna - 5, 17 ( 20 ) - dien - 21 - oyl amides at a concentrations of 5 mu M inhibited sterol biosynthesis and stimulated triglyceride biosynthesis; their regulatory potency was dependent on the structure of amide moiety; the isomeric [ 17 ( 20 ) Z ] - pregna - 5, 17 ( 20 ) - dien - 21 - oyl amides were inactive.", "output": "[ 17 ( 20 ) E ] - pregna - 5 , 17 ( 20 ) - dien - 21 - oyl amides, triglyceride, amide, [ 17 ( 20 ) Z ] - pregna - 5 , 17 ( 20 ) - dien - 21 - oyl amides." }, { "input": "Discovery of non - peptide inhibitors of Plasmepsin II by structure - based virtual screening.", "output": "There is no related enetity." }, { "input": "Plasmepsin II ( PM II ) is an attractive target for anti - malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole.", "output": "There is no related enetity." }, { "input": "In this study, we demonstrated the successful use of structure - based virtual screening to identify inhibitors of PM II from two chemical database.", "output": "There is no related enetity." }, { "input": "Five novel non - peptide inhibitors were identified and revealed moderate inhibitory potencies with IC50 ranged from 4. 62 +/- 0. 39 to 9. 47 +/- 0. 71 mu M.", "output": "There is no related enetity." }, { "input": "The detailed analysis of binding modes using docking simulations for five inhibitors showed that the inhibitors could be stabilized by forming multiple hydrogen bonds with catalytic residues ( Asp 34 and Asp 214 ) and also with other key residues.", "output": "hydrogen, Asp, Asp." }, { "input": "Pro - inflammatory properties and neutrophil activation by Helicobacter pylori urease.", "output": "There is no related enetity." }, { "input": "The gastric pathogen Helicobacter pylori produces large amounts of urease, whose enzyme activity enables the bacterium to survive in the stomach.", "output": "There is no related enetity." }, { "input": "We have previously shown that ureases display enzyme - independent effects in mammalian models, most through lipoxygenases - mediated pathways.", "output": "There is no related enetity." }, { "input": "Here, we evaluated potential pro - inflammatory properties of H. pylori urease ( HPU ).", "output": "There is no related enetity." }, { "input": "Mouse paw edema and activation of human neutrophils were tested using a purified, cell - free, recombinant HPU.", "output": "There is no related enetity." }, { "input": "rHPU induced paw edema with intense neutrophil infiltration.", "output": "There is no related enetity." }, { "input": "In vitro 100 nM rHPU was chemotactic to human neutrophils, inducing production of reactive oxygen species.", "output": "oxygen." }, { "input": "rHPU - activated neutrophils showed increased lifespan, with inhibition of apoptosis accompanied by alterations of Bcl - XL and Bad contents.", "output": "There is no related enetity." }, { "input": "These effects of rHPU persisted in the absence of enzyme activity.", "output": "There is no related enetity." }, { "input": "rHPU - induced paw edema, neutrophil chemotaxis and apoptosis inhibition reverted in the presence of the lipoxygenase inhibitors esculetin or AA861.", "output": "There is no related enetity." }, { "input": "Neutrophils exposed to rHPU showed increased content of lipoxygenase ( s ) and no alteration of cyclooxygenase ( s ).", "output": "There is no related enetity." }, { "input": "Altogether, our data indicate that HPU, besides allowing the bacterial survival in the stomach, could play an important role in the pathogenesis of the gastrointestinal inflammatory disease caused by H. pylori.", "output": "There is no related enetity." }, { "input": "Dietary Chlorella protects against heterocyclic amine - induced aberrant gene expression in the rat colon by increasing fecal excretion of unmetabolized PhIP.", "output": "heterocyclic amine, PhIP." }, { "input": "The food mutagen 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4, 5 - b ] pyridine ( PhIP ) is one of the most abundant heterocyclic amines formed by cooking meat and fish at high temperature.", "output": "2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine, PhIP, heterocyclic amines." }, { "input": "PhIP induces colorectal adenoma risk in male rats when administered orally.", "output": "PhIP." }, { "input": "This study used male Fisher 344 rats to investigate the impact of dietary Chlorella on PhIP metabolism and aberrant colonic gene expression following short - term PhIP treatment.", "output": "PhIP, PhIP." }, { "input": "High - performance liquid chromatography analysis revealed that fecal excretion of unmetabolized PhIP was significantly increased in rats whose diets were supplemented with Chlorella compared to rats in a PhIP - only group ( P < 0. 001 ).", "output": "PhIP, PhIP." }, { "input": "Quantitative realtime PCR confirmed that the increase in beta - catenin and cyclin D1 mRNA in the colon induced by PhIP was ameliorated in rats pre - fed with Chlorella ( P = 0. 052 for beta - catenin; P = 0. 005 for cyclin D1 ).", "output": "PhIP." }, { "input": "The increase in DNA shearing that is a hallmark of caspase - 8 - mediated apoptosis by PhIP was also significantly diminished in the colons of rats pre - fed Chlorella ( P = 0. 012 ).", "output": "PhIP." }, { "input": "These results suggested that administering dietary Chlorella with a Western - style diet concomitantly or immediately before mutagen exposure might be beneficial in blocking the absorption of food mutagens such as PhIP.", "output": "PhIP." }, { "input": "Occurrence of fumonisins in organic and conventional cereal - based products commercialized in France, Germany and Spain.", "output": "fumonisins." }, { "input": "A fast and effective method for quantitative determination of fumonisins B1 and B2 ( FB1 and FB2 ) in different cereal - based products was developed.", "output": "fumonisins B1 and B2, FB1, FB2." }, { "input": "Fumonisins were extracted combining a solid liquid extraction ( SLE ) pre - treatment and immunoaffinity columns ( IACs ), which were applied for an effective clean - up.", "output": "Fumonisins." }, { "input": "Consecutively, high pressure liquid chromatography ( HPLC ) coupled to hybrid triple quadrupole - linear ion trap mass spectrometer ( QTrap (R) ) was used for the separation, detection and quantification of targeted mycotoxins.", "output": "There is no related enetity." }, { "input": "The analytical method showed acceptable recoveries ranged from 89. 7 % to 99. 1 %, as well as a relative standard deviation ( %, RSD ) lower than 12 %.", "output": "There is no related enetity." }, { "input": "A total of 1250 samples from France, Germany and Spain were analysed.", "output": "There is no related enetity." }, { "input": "The incidence of fumonisin B1 and B2 in organic samples were 11. 4 % and 11. 3 %, respectively.", "output": "fumonisin B1 and B2." }, { "input": "By contrast, the occurrence of conventional samples was 3. 6 % of FB1 and 3. 5 % of FB2.", "output": "FB1, FB2." }, { "input": "The highest values were obtained in Spanish samples of flour, as an example toasted corn, called gofio that was contaminated with 1201. 7 and 1010. 5 mu gkg ( - 1 ) of FB1 and FB2, respectively.", "output": "FB1, FB2." }, { "input": "Oral l - glutamine increases active GLP - 1 ( 7 - 36 ) amide secretion and improves glycemic control in stretpozotocin - nicotinamide induced diabetic rats.", "output": "l - glutamine, amide, stretpozotocin, nicotinamide." }, { "input": "l - glutamine is a non - essential amino acid.", "output": "l - glutamine, amino acid." }, { "input": "It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients.", "output": "sugar." }, { "input": "The objective of the present investigation was to evaluate l - glutamine increases glucagon like peptide - 1 ( GLP - 1 ) ( 7 - 36 ) amide secretion in streptozotocin - nicotinamide ( STZ - NTM ) induced diabetic Sprague Dawley rats.", "output": "l - glutamine, amide, streptozotocin, nicotinamide, STZ, NTM." }, { "input": "Molecular docking study was performed to elucidate the molecular basis for GLP - 1 receptor agonistic activity.", "output": "There is no related enetity." }, { "input": "Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre - treated with nicotinamide ( 100mg / kg, i. p. ) followed by 20min after administration of streptozotocin ( 55mg / kg, i. p. ).", "output": "nicotinamide, streptozotocin." }, { "input": "The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin ( 5mg / kg, p. o. ), IV - l - glutamine ( 250mg / kg, p. o. ), V - l - glutamine ( 500mg / kg, p. o. ) and VI - l - glutamine ( 1000mg / kg, p. o. ).", "output": "sitagliptin, l - glutamine, l - glutamine, l - glutamine." }, { "input": "The l - glutamine and sitagliptin treatment was 8week.", "output": "l - glutamine, sitagliptin." }, { "input": "Plasma glucose was estimated every week.", "output": "glucose." }, { "input": "Body weight, food and water intake were recorded daily.", "output": "There is no related enetity." }, { "input": "Glycosylated haemoglobin, lipid profile, plasma and colonic active ( GLP - 1 ) ( 7 - 36 ) amide, mRNA expression of proglucagon GLP - 1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress ( superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase ) were measured after 8week.", "output": "amide, glutathione, malondialdehyde, glutathione, glutathione." }, { "input": "In acute study, the rats were divided into I - glucose ( 2. 5g / kg, p. o. ), II - sitagliptin ( 5mg / kg, p. o. ), III - l - glutamine ( 250mg / kg, p. o. ), IV - l - glutamine ( 500mg / kg, p. o. ) and V - l - glutamine ( 1000mg / kg, p. o. ).", "output": "glucose, sitagliptin, l - glutamine, l - glutamine, l - glutamine." }, { "input": "Plasma glucose, active GLP - 1 ( 7 - 36 ) amide concentration and insulin levels were measured after glucose loading.", "output": "glucose, amide, glucose." }, { "input": "The docking data indicated that l - glutamine bind to the GLP - 1 receptor.", "output": "l - glutamine." }, { "input": "l - glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP - 1 ( 7 - 36 ) amide secretion as well as decreased oxidative stress in streptozotocin - nicotinamide induced diabetic rats.", "output": "l - glutamine, glucose, amide, streptozotocin, nicotinamide." }, { "input": "Anti - diabetic effects of brown algae derived phlorotannins, marine polyphenols through diverse mechanisms.", "output": "phlorotannins, polyphenols." }, { "input": "Marine algae are popular and abundant food ingredients mainly in Asian countries, and also well known for their health beneficial effects due to the presence of biologically active components.", "output": "There is no related enetity." }, { "input": "The marine algae have been studied for biologically active components and phlorotannins, marine polyphenols are among them.", "output": "phlorotannins, polyphenols." }, { "input": "Among marine algae, brown algae have extensively studied for their potential anti - diabetic activities.", "output": "There is no related enetity." }, { "input": "Majority of the investigations on phlorotannins derived from brown algae have exhibited their various anti - diabetic mechanisms such as alpha - glucosidase and alpha - amylase inhibitory effect, glucose uptake effect in skeletal muscle, protein tyrosine phosphatase 1B ( PTP 1B ) enzyme inhibition, improvement of insulin sensitivity in type 2 diabetic db / db mice, and protective effect against diabetes complication.", "output": "phlorotannins, glucose, tyrosine." }, { "input": "In this review, we have made an attempt to discuss the various anti - diabetic mechanisms associated with phlorotannins from brown algae that are confined to in vitro and in vivo.", "output": "phlorotannins." }, { "input": "Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78 - kDa glucose - regulated protein, and CCAAT / enhancer - binding protein ( C / EBP ) homologous protein in adult mice.", "output": "choline, glucose." }, { "input": "RATIONALE: Social defeat stress induces physiological and behavioral symptoms, including anxiety, anhedonia, immune deficits, and altered expression of key brain genes.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: The present study investigated the effects of social defeat stress on the behaviors and expressions of Chat, Grp78, and chop in the brains of adult mice.", "output": "There is no related enetity." }, { "input": "METHODS: Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress.", "output": "There is no related enetity." }, { "input": "In experiment 1, behavioral tests were conducted, and brains were processed for Western blotting at day 27 after stress.", "output": "There is no related enetity." }, { "input": "In experiment 2, social avoidance tests were conducted, and brains were processed for Western blotting at day 12 after stress.", "output": "There is no related enetity." }, { "input": "RESULTS: The results indicate decreased and increased locomotion and anxiety behavior in all defeated mice.", "output": "There is no related enetity." }, { "input": "Decrease in social interaction, increased immobility, and impaired memory performance were only observed in susceptible mice.", "output": "There is no related enetity." }, { "input": "A decrease in the Chat level at days 12 and 27 was noted in the prefrontal cortex ( PFC ), amygdala ( Amyg ), and dorsal hippocampus ( HIP ) in defeated mice.", "output": "There is no related enetity." }, { "input": "The expression levels of Grp78 and chop measured on days 12 and 27 were significantly greater in the Amyg of susceptible mice.", "output": "There is no related enetity." }, { "input": "In the PFC and HIP, defeated mice displayed different patterns in the levels of Grp78 and chop expressions measured on days 12 and 27.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: The present study demonstrated that chronic social defeat stress in mice produces stress - related behaviors.", "output": "There is no related enetity." }, { "input": "Different response patterns were noted for Grp78 and chop expression among the groups in terms of brain regions and time - course effects.", "output": "There is no related enetity." }, { "input": "Sarothrin from Alkanna orientalis is an antimicrobial agent and efflux pump inhibitor.", "output": "Sarothrin." }, { "input": "An Alkanna orientalis leaf and flower extract inhibited the growth of Staphylococcus aureus, a pathogen that causes an estimated 478 000 hospitalizations in the US annually.", "output": "There is no related enetity." }, { "input": "Bioassay - guided fractionation of A. orientalis resulted in isolation of the flavonoid sarothrin ( 5, 7, 4 ' - trihydroxy - 3, 6, 8 - trimethoxyflavone ), which inhibited the growth of Mycobacterium smegmatis ( MIC 75 micro M ) and S. aureus ( MIC > 800 micro M ), and possessed efflux pump inhibitory activity.", "output": "flavonoid, sarothrin, 5 , 7 , 4 ' - trihydroxy - 3 , 6 , 8 - trimethoxyflavone." }, { "input": "This is the first report of antimicrobial or efflux pump inhibitory activity of sarothrin, and of its presence in A. orientalis.", "output": "sarothrin." }, { "input": "Our findings suggest that the effectiveness of A. orientalis extracts is due to a combination of multiple constituents, including sarothrin.", "output": "sarothrin." }, { "input": "Cell - Laden Hydrogels in Integrated Microfluidic Devices for Long - Term Cell Culture and Tubulogenesis Assays.", "output": "There is no related enetity." }, { "input": "A hydrogel biochip combining microfluidic mixing and orthogonal supplementation strategies is developed and validated to allow facile generation of libraries of optically transparent 3D culture microenvironments.", "output": "There is no related enetity." }, { "input": "Live, on - chip tracing of embryonic stem cell differentiation and endothelial cell tubulogenesis confirms that the platform can be used to both create communities of discrete 3D microenvironments as well as to locally monitor subsequent divergent responses at both single cell and multi - cell scales.", "output": "There is no related enetity." }, { "input": "The interaction of isopenicillin N synthase with homologated substrate analogues delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - Xaa characterised by protein crystallography.", "output": "isopenicillin N, delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - Xaa." }, { "input": "Isopenicillin N synthase ( IPNS ) converts the linear tripeptide delta - ( L - alpha - aminoadipoyl ) - L - cysteinyl - D - valine ( ACV ) into bicyclic isopenicillin N ( IPN ) in the central step in the biosynthesis of penicillin and cephalosporin antibiotics.", "output": "Isopenicillin N, delta - ( L - alpha - aminoadipoyl ) - L - cysteinyl - D - valine, ACV, isopenicillin N, IPN, penicillin, cephalosporin." }, { "input": "Solution - phase incubation experiments have shown that IPNS turns over analogues with a diverse range of side chains in the third ( valinyl ) position of the substrate, but copes less well with changes in the second ( cysteinyl ) residue.", "output": "valinyl, cysteinyl." }, { "input": "IPNS thus converts the homologated tripeptides delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - valine ( AhCV ) and delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - allylglycine ( AhCaG ) into monocyclic hydroxy - lactam products; this suggests that the additional methylene unit in these substrates induces conformational changes that preclude second ring closure after initial lactam formation.", "output": "delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - valine, AhCV, delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - allylglycine, AhCaG, monocyclic hydroxy - lactam, methylene, lactam." }, { "input": "To investigate this and solution - phase results with other tripeptides delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - Xaa, we have crystallised AhCV and delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - S - methylcysteine ( AhCmC ) with IPNS and solved crystal structures for the resulting complexes.", "output": "delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - Xaa, AhCV, delta - ( L - alpha - aminoadipoyl ) - L - homocysteinyl - D - S - methylcysteine, AhCmC." }, { "input": "The IPNS: Fe ( II ): AhCV complex shows diffuse electron density for several regions of the substrate, revealing considerable conformational freedom within the active site.", "output": "Fe ( II ), AhCV." }, { "input": "The substrate is more clearly resolved in the IPNS: Fe ( II ): AhCmC complex, by virtue of thioether coordination to iron.", "output": "Fe ( II ), AhCmC, thioether, iron." }, { "input": "AhCmC occupies two distinct conformations, both distorted relative to the natural substrate ACV, in order to accommodate the extra methylene group in the second residue.", "output": "AhCmC, ACV, methylene." }, { "input": "Attempts to turn these substrates over within crystalline IPNS using hyperbaric oxygenation give rise to product mixtures.", "output": "There is no related enetity." }, { "input": "8 - ( Tosylamino ) quinoline inhibits tumour progression through targeting phosphoinositide - 3 - kinase / Akt pathway.", "output": "8 - ( Tosylamino ) quinoline." }, { "input": "We examined whether 8 - ( tosylamino ) quinoline ( 8 - TQ ), a structural analogue of BAY 11 - 7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions.", "output": "8 - ( tosylamino ) quinoline, 8 - TQ, BAY 11 - 7082." }, { "input": "8 - TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA - MB - 231 cells with IC550 values ranging from 10 to 30 microM.", "output": "8 - TQ." }, { "input": "According to the analysis of level of active caspase - 3, and morphologies of C6, HeLa and MDA - MB - 231 cells, it was revealed that 8 - TQ is able to induce apoptosis.", "output": "8 - TQ." }, { "input": "Furthermore, this compound strongly diminished the invasion of MDA - MB - 231 cells, the migration of HeLa cells, and the new generation of blood vessels under non - toxic conditions.", "output": "There is no related enetity." }, { "input": "Reduction of the phospho - form levels of intracellular signalling enzymes by 8 - TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3 - kinase ( PI3K ) / phosphoinositide - dependent kinase - 1 ( PDK1 ) / Akt and extracellular - signal - regulated kinase ( ERK ) could be targeted by 8 - TQ treatment.", "output": "8 - TQ, 8 - TQ." }, { "input": "Indeed, the specific inhibitors ( LY294002 and U0126 ) of PI3K / PDK1 / Akt and ERK showed similar anti - cancer properties to 8 - TQ.", "output": "LY294002, U0126, 8 - TQ." }, { "input": "Finally, 8 - TQ intraperitoneally injected suppressed the increase of tumour volume up to 40 % compared to vehicle - treated control.", "output": "8 - TQ." }, { "input": "Taken together, our results clearly suggest that 8 - TQ might have applications as a novel anti - cancer drug or may be served as a lead compound to be further optimized.", "output": "8 - TQ." }, { "input": "Quinolines as chemotherapeutic agents for leishmaniasis.", "output": "Quinolines." }, { "input": "The development of leishmanicidal quinolines and their in vitro ( promastigote and amastigote ) and, where applicable, in vivo activities are reviewed.", "output": "quinolines." }, { "input": "This survey provides a direct comparison of bioactivity across different species ( e. g. L. donovani, L. amazonensis, L. chagasi, L infantum ), and in different animal models ( e. g. L. donovani Balb / c mice and L. donovani infected hamsters ).", "output": "There is no related enetity." }, { "input": "The progress of selected quinolines through pre - clinical development and phase I / II trials, and the lead quinoline drugs sitamaquinine and Imiquimod, are discussed in conjunction with delivery systems and combination therapies.", "output": "quinolines, quinoline, sitamaquinine, Imiquimod." }, { "input": "Identification of a RhoA - and SRF - Dependent Mechanism of Androgen Action that is Associated with Prostate Cancer Progression.", "output": "Androgen." }, { "input": "Androgen receptor ( AR ) action is critical for prostate cancer ( CaP ) progression, but is not inhibited fully by available androgen deprivation therapy ( ADT ).", "output": "Androgen, androgen." }, { "input": "One of the limitations to current ADT is that it targets all androgen action in CaP, and other, cells irrespective of clinical relevance.", "output": "There is no related enetity." }, { "input": "The resulting off - target effects are responsible for ADT associated side effects that affect negatively a patient ' s quality of life.", "output": "There is no related enetity." }, { "input": "Isolation of the AR - dependent events that drive CaP progression may lead to novel forms of ADT that are at least as effective but more selective.", "output": "There is no related enetity." }, { "input": "Here, an approach is described that starts from insights in the basic mechanism ( s ) by which AR regulates target gene expression to identify novel drugable targets downstream of AR.", "output": "There is no related enetity." }, { "input": "Exploration of the molecular events that underlie androgen regulation of the ARassociated coregulator FHL2 led to the isolation of a novel indirect mechanism of androgen action that is mediated by the secondary transcription factor Serum Response Factor ( SRF ).", "output": "androgen, androgen." }, { "input": "Using a combination of oligoarray and in silico analyses, an SRF - dependent fraction of AR action was identified that is enriched in CaP tissues, is able to discriminate between benign and malignant prostate, and correlates with aggressive disease and biochemical failure.", "output": "There is no related enetity." }, { "input": "The RhoA signaling axis, a well known upstream stimulator of SRF action that harbors drugable targets, conveyed androgen - responsiveness to SRF, and was activated in CaP where it correlates with increased CaP aggressiveness and poor outcome after surgery.", "output": "androgen." }, { "input": "A new tetracyclic triterpenoid compound from Mastich.", "output": "tetracyclic triterpenoid." }, { "input": "A new tetracyclic triterpenoid compound named as mastichinoic acid A ( 1 ) was isolated from Mastich.", "output": "tetracyclic triterpenoid, mastichinoic acid A." }, { "input": "The structure was established as 3, 7 - dioxo - 11 beta - hydroxy - 5 alpha - tirucalla - 8, 24 ( Z ) - dien - 26 - oic acid by various spectroscopic techniques including MS, 1D, and 2D NMR and HRTOFMS.", "output": "3 , 7 - dioxo - 11 beta - hydroxy - 5 alpha - tirucalla - 8 , 24 ( Z ) - dien - 26 - oic acid." }, { "input": "Cystatin C: an emerging biomarker in cardiovascular disease.", "output": "There is no related enetity." }, { "input": "Cystatin C ( cys - C ) is a small protein molecule ( 120 amino acid peptide chain, approximately 13kDa ) produced by virtually all nucleated cells in the human body.", "output": "amino acid." }, { "input": "It belongs to the family of papain - like cysteine proteases and its main biological role is the extracellular inhibition of cathepsins.", "output": "cysteine." }, { "input": "It ' s near constant production rate, the fact that it is freely filtered from the glomerular membrane and then completely reabsorbed without being secreted from the proximal tubular cells, made it an almost perfect candidate for estimating renal function.", "output": "There is no related enetity." }, { "input": "The strong correlation between chronic kidney disease ( CKD ) and cardiovascular disease ( CVD ) along with the growing understanding of the role of cysteinyl cathepsins in the pathophysiology of CVD inspired researchers to explore the potential association of cys - C with CVD.", "output": "cysteinyl." }, { "input": "Throughout the spectrum of CVD ( peripheral arterial disease, stroke, abdominal aortic aneurysm, heart failure, coronary artery disease ) adverse outcomes and risk stratification have been associated with high plasma levels of cys - C.", "output": "There is no related enetity." }, { "input": "The exact mechanisms behind the observed correlations have not been comprehensively clarified.", "output": "There is no related enetity." }, { "input": "Plausible links between high cys - C levels and poor cardiovascular outcome could be impaired renal function, atherogenesis and inflammatory mediators, remodeling of myocardial tissue and others ( genetic factors, aging and social habits ).", "output": "There is no related enetity." }, { "input": "The scope of the present article is to systematically review the current knowledge about cys - C biochemistry, metabolism, methods of detection and quantification and pathophysiological associations with different aspects of CVD.", "output": "There is no related enetity." }, { "input": "MicroRNAs and the Heart: Small Things Do Matter.", "output": "There is no related enetity." }, { "input": "MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells.", "output": "There is no related enetity." }, { "input": "Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront.", "output": "There is no related enetity." }, { "input": "MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease.", "output": "There is no related enetity." }, { "input": "In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets.", "output": "There is no related enetity." }, { "input": "Copeptin as a biomarker in cardiac disease.", "output": "There is no related enetity." }, { "input": "The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice - changing advancements in the way these patients are diagnosed and managed.", "output": "There is no related enetity." }, { "input": "Measurements of cardiac troponins or brain - type natriuretic peptide ( BNP ) and its precursor, N - terminal brain - type natriuretic peptide ( NT - proBNP ), have become indispensable in the evaluation of patients with acute coronary syndromes and heart failure, respectively, constituting an integral part of the diagnostic algorithm and risk stratification of these conditions.", "output": "N." }, { "input": "Copeptin, a glycopeptide, part of the prehormone molecule of the antidiuretic hormone - or arginine - vasopressin - has shown considerable promise in this field.", "output": "arginine." }, { "input": "There is evidence that copeptin might be useful as a diagnostic or prognostic biomarker and risk - stratifier in a range of cardiovascular disease conditions.", "output": "There is no related enetity." }, { "input": "The main clinical scenarios where copeptin has been studied as a biomarker are: early rule - out of myocardial infarction in patients with acute chest pain, diagnosis of heart failure in patients with acute dyspnea and determining the prognosis of destabilized or chronic stable heart failure.", "output": "There is no related enetity." }, { "input": "The present review is aimed at providing concise information about the molecular structure and biosynthesis of copeptin, the available medical chemistry methods of quantification, and the potential clinical uses of this molecule in patients with heart disease.", "output": "There is no related enetity." }, { "input": "High - Resolution Direct - Absorption Spectroscopy of Hydroxymethyl Radical in the CH Symmetric Stretching Region.", "output": "Hydroxymethyl, CH." }, { "input": "High - resolution, fully rotationally resolved direct absorption spectra of hydroxymethyl radical, CH2OH, are presented in the infrared CH stretching region.", "output": "hydroxymethyl, CH2OH, CH." }, { "input": "As a result of low rotational temperatures and sub - Doppler linewidths obtained in the slit supersonic expansion, the Ka = 0 <-- 0 band of the symmetric CH stretch for CH2OH has been unambiguously identified and analyzed.", "output": "CH, CH2OH." }, { "input": "By way of chemical confirmation, hydroxymethyl radical is generated via two different slit jet discharge syntheses: ( i ) direct dissociation of CH3OH to form CH2OH and ( ii ) dissociation of Cl2 followed by the radical H atom extraction reaction Cl + CH3OH --> HCl + CH2OH.", "output": "hydroxymethyl, CH3OH, CH2OH, Cl2, H, Cl, CH3OH, HCl, CH2OH." }, { "input": "The identified transitions are fit to a Watson A - reduced symmetric top Hamiltonian to yield first precision experimental values for the ground state rotational constants as well as improved values for the symmetric stretch rotational constants and vibrational band origin.", "output": "There is no related enetity." }, { "input": "The results both complement and substantially improve upon spectral efforts via previous double resonance ionization detected infrared methods by Feng et al.", "output": "There is no related enetity." }, { "input": "[ J. Phys. Chem. A, 2004, 108, 7093 ], as well as offer high - resolution predictions for laboratory and astronomical detection of hydroxymethyl radical in the millimeter - wave region.", "output": "hydroxymethyl." }, { "input": "Light reflection control in biogenic micro - mirror by diamagnetic orientation.", "output": "There is no related enetity." }, { "input": "As has become known, most materials, such as proteins and DNA, show orientation under strong magnetic fields.", "output": "There is no related enetity." }, { "input": "However, the critical threshold for the magnetic field of the magnetomechanical phenomena is still unknown.", "output": "There is no related enetity." }, { "input": "We demonstrate that a thin micro - mirror from a fish scale with high reflectivity exhibits a distinct magnetic response at 100 mT.", "output": "There is no related enetity." }, { "input": "A dramatic event under a magnetic field is the decrease of light scattering from guanine crystals as well as rapid rotation against the applied magnetic field.", "output": "guanine." }, { "input": "Enhancement of light scattering intensity is also observed when the three vectors of light incidence, magnetic field, and observation are orthogonally directed.", "output": "There is no related enetity." }, { "input": "The results indicate that biogenic guanine crystals have a large diamagnetic anisotropy along the surface parallel and normal directions.", "output": "guanine." }, { "input": "The micrometer to submicrometer scale of thin biogenic plates can act as a noninvasively, magnetically controlled micro - mirror for light irradiation control in the micrometer - scale region.", "output": "There is no related enetity." }, { "input": "Ideal redox behavior of the high - density self - assembled monolayer of a molecular tripod on a au ( 111 ) surface with a terminal ferrocene group.", "output": "au ( 111 ), ferrocene." }, { "input": "A dyad consisting of a tripod - shaped trithiol with an adamantane core and a terminal ferrocenyl group linked through ap - phenyleneethynylene bridge was synthesized.", "output": "trithiol, adamantane, ferrocenyl, phenyleneethynylene." }, { "input": "The trithiol formed a stable self - assembled monolayer ( SAM ) on Au ( 111 ), wherein each molecule is bound to the surface by three - point adsorption using all sulfur atoms, with confirmation by PM - IRRAS and XPS analyses.", "output": "trithiol, Au ( 111 ), sulfur." }, { "input": "Cyclic voltammetry of the SAM showed a line shape typical of an ideal adsorbed system, that is, a monolayer with negligible electrostatic interaction among the terminal ferrocenyl groups.", "output": "ferrocenyl." }, { "input": "Thus, a rare SAM was achieved, in which the component molecules were isolated from adjacent molecules without the coadsorption of nonelectroactive molecules.", "output": "There is no related enetity." }, { "input": "Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.", "output": "catecholamines." }, { "input": "Glutamatergic neurotransmission in the central nucleus of the amygdala ( CeA ) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses.", "output": "There is no related enetity." }, { "input": "While these behaviors can be modulated by corticotropin releasing factor ( CRF ) and catecholamine signaling, the mechanism ( s ) by which these signals modify CeA glutamatergic neurotransmission remains unclear.", "output": "catecholamine." }, { "input": "Utilizing whole - cell patch - clamp electrophysiology recordings from neurons in the lateral subdivision of the CeA ( CeAL ), we show that CRF, dopamine ( DA ) and the beta - adrenergic receptor agonist isoproterenol ( ISO ) all enhance the frequency of spontaneous excitatory postsynaptic currents ( sEPSC ) without altering sEPSC kinetics, suggesting they increase presynaptic glutamate release.", "output": "dopamine, isoproterenol, ISO, glutamate." }, { "input": "The effect of CRF on sEPSCs was mediated by a combination of CRFR1 and CRFR2 receptors.", "output": "There is no related enetity." }, { "input": "While previous work from our lab suggests that CRFRs mediate the effect of catecholamines on excitatory transmission in other subregions of the extended amygdala, blockade of CRFRs in the CeAL failed to significantly alter effects of DA and ISO on glutamatergic transmission.", "output": "catecholamines, ISO." }, { "input": "These findings suggest that catecholamine and CRF enhancement of glutamatergic transmission onto CeAL neurons occurs via distinct mechanisms.", "output": "catecholamine." }, { "input": "While CRF increased spontaneous glutamate release in the CeAL, CRF caused no significant changes to optogenetically evoked glutamate release in this region.", "output": "glutamate, glutamate." }, { "input": "The dissociable effects of CRF on different types of glutamatergic neurotransmission suggest that CRF may specifically regulate spontaneous excitatory transmission.", "output": "There is no related enetity." }, { "input": "Testing for departures from additivity in mixtures of perfluoroalkyl acids ( PFAAs ).", "output": "perfluoroalkyl acids, PFAAs." }, { "input": "This study is a follow - up to a paper by Carr et al. that determined a design structure to optimally test for departures from additivity in a fixed ratio mixture of four perfluoroalkyl acids ( PFAAs ) using an in vitro transiently - transfected COS - 1 PPAR alpha reporter model with a mixing ratio that is based on average serum levels in NHANES subjects.", "output": "perfluoroalkyl acids, PFAAs." }, { "input": "Availability of information regarding potential for additivity of PFAAs in mixtures is critically important for risk assessors who are concerned with the ability of the compounds to affect human health and impact ecological systems.", "output": "PFAAs." }, { "input": "It is clear that exposures are not to single compounds, but to mixtures of the PFAAs.", "output": "PFAAs." }, { "input": "This paper presents the results from the data collected using the design from Carr et al. along with subsequent analyses that were performed to classify the relationships among mixtures of PFAAs.", "output": "PFAAs." }, { "input": "A non - linear logistic additivity model was employed to predict relative luciferase units ( RLU ), an indicator of PPAR alpha activation.", "output": "There is no related enetity." }, { "input": "The results indicated a less than additive relationship among the four PFAAs.", "output": "PFAAs." }, { "input": "To determine if the possible \" antagonism \" is from the competition among or between carboxylates and sulfonates, four different binary mixtures were also studied.", "output": "carboxylates, sulfonates." }, { "input": "There was a less than additive relationship in all four binary mixtures.", "output": "There is no related enetity." }, { "input": "These findings are generally similar to two other reports of interfering interactions between PFAAs in mixtures.", "output": "PFAAs." }, { "input": "The most conservative interpretation for our data would be an assumption of additivity ( and lack of a greater than additive interaction ), with a potential for antagonistic interactions.", "output": "There is no related enetity." }, { "input": "Bioactivation of bisphenol A and its analogs ( BPF, BPAF, BPZ and DMBPA ) in human liver microsomes.", "output": "bisphenol A, BPF, BPAF, BPZ, DMBPA." }, { "input": "Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para - hydroxy group on both benzene rings.", "output": "Bisphenol A, diphenylmethanes, benzene, para - hydroxy, benzene." }, { "input": "Bisphenol A ( BPA ) can induce an uterotrophic response in immature CD - 1 mice and elicits estrogenic responses in many other experimental systems.", "output": "Bisphenol A, BPA." }, { "input": "Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and / or produce oxidative stress.", "output": "BPA." }, { "input": "We used a liquid chromatography with a triple quadrupole tandem mass spectrometry ( LC - MS / MS ) for the detection of metabolites and glutathione conjugates of BPA and its analogs ( BPF, BPAF, BPZ and DMBPA ) in human liver microsomes ( HLM ) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent.", "output": "glutathione, BPA, BPF, BPAF, BPZ, DMBPA, NADPH, GSH." }, { "input": "We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes.", "output": "BPA." }, { "input": "These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro.", "output": "BPA." }, { "input": "Human induced pluripotent stem cells and their use in drug discovery for toxicity testing.", "output": "There is no related enetity." }, { "input": "Predicting human safety risks of novel xenobiotics remains a major challenge, partly due to the limited availability of human cells to evaluate tissue - specific toxicity.", "output": "There is no related enetity." }, { "input": "Recent progress in the production of human induced pluripotent stem cells ( hiPSCs ) may fill this gap.", "output": "There is no related enetity." }, { "input": "hiPSCs can be continuously expanded in culture in an undifferentiated state and then differentiated to form most cell types.", "output": "There is no related enetity." }, { "input": "Thus, it is becoming technically feasible to generate large quantities of human cell types and, in combination with relatively new detection methods, to develop higher - throughput in vitro assays that quantify tissue - specific biological properties.", "output": "There is no related enetity." }, { "input": "Indeed, the first wave of large scale hiSC - differentiated cell types including patient - derived hiPSCS are now commercially available.", "output": "There is no related enetity." }, { "input": "However, significant improvements in hiPSC production and differentiation processes are required before cell - based toxicity assays that accurately reflect mature tissue phenotypes can be delivered and implemented in a cost - effective manner.", "output": "There is no related enetity." }, { "input": "In this review, we discuss the promising alignment of hiPSCs and recently emerging technologies to quantify tissue - specific functions.", "output": "There is no related enetity." }, { "input": "We emphasize liver, cardiovascular, and CNS safety risks and highlight limitations that must be overcome before routine screening for toxicity pathways in hiSC - derived cells can be established.", "output": "There is no related enetity." }, { "input": "Water deficit and heat affect the tolerance to high illumination in hibiscus plants.", "output": "There is no related enetity." }, { "input": "This work studies the effects of water deficit and heat, as well as the involvement of chlororespiration and the ferredoxin - mediated cyclic pathway, on the tolerance of photosynthesis to high light intensity in Hibiscus rosa - sinensis plants.", "output": "There is no related enetity." }, { "input": "Drought and heat resulted in the down - regulation of photosynthetic linear electron transport in the leaves, although only a slight decrease in variable fluorescence ( Fv ) / maximal fluorescence ( Fm ) was observed, indicating that the chloroplast was protected by mechanisms that dissipate excess excitation energy to prevent damage to the photosynthetic apparatus.", "output": "There is no related enetity." }, { "input": "The incubation of leaves from unstressed plants under high light intensity resulted in an increase of the activity of electron donation by nicotinamide adenine dinucleotide phosphate ( NADPH ) and ferredoxin to plastoquinone, but no increase was observed in plants exposed to water deficit, suggesting that cyclic electron transport was stimulated by high light only in control plants.", "output": "nicotinamide adenine dinucleotide phosphate, NADPH, plastoquinone." }, { "input": "In contrast, the activities of the chlororespiration enzymes ( NADH dehydrogenase ( NDH ) complex and plastid terminal oxidase ( PTOX ) ) increased after incubation under high light intensity in leaves of the water deficit plants, but not in control plants, suggesting that chlororespiration was stimulated in stressed plants.", "output": "NADH." }, { "input": "The results indicate that the relative importance of chlororespiration and the cyclic electron pathway in the tolerance of photosynthesis to high illumination differs under stress conditions.", "output": "There is no related enetity." }, { "input": "When plants were not subjected to stress, the contribution of chlororespiration to photosynthetic electron flow regulation was not relevant, and another pathway, such as the ferredoxin - mediated cyclic pathway, was more important.", "output": "There is no related enetity." }, { "input": "However, when plants were subjected to water deficit and heat, chlororespiration was probably essential.", "output": "There is no related enetity." }, { "input": "Controlled formation of mono - and dihydroxy - resolvins from EPA and DHA using soybean 15 - lipoxygenase.", "output": "mono - and dihydroxy - resolvins, EPA, DHA." }, { "input": "Resolvins and protectins are important anti - inflammatory and pro - resolution compounds derived from the enzymatic oxidation of omega - 3 fatty acids all - cis - 5, 8, 11, 14, 17 - eicosapentaenoic acid ( EPA ) and all - cis - 4, 7, 10, 13, 16, 19 - docosahexaenoic acid ( DHA ).", "output": "Resolvins, omega - 3 fatty acids, all - cis - 5 , 8 , 11 , 14 , 17 - eicosapentaenoic acid, EPA, all - cis - 4 , 7 , 10 , 13 , 16 , 19 - docosahexaenoic acid, DHA." }, { "input": "We have developed a simple, controlled method to synthesize an array of resolvin and protectin analogs from fatty acid starting materials using soybean 15 - lipoxygenase.", "output": "resolvin, fatty acid." }, { "input": "The conditions were optimized for the production of both mono - and dihydroxy derivatives, with enzyme concentration and pH found to have a significant effect on the reaction products.", "output": "mono - and dihydroxy." }, { "input": "The methods were applied to five biologically important omega - 3 and omega - 6 fatty acid substrates.", "output": "omega - 3 and omega - 6 fatty acid." }, { "input": "Mono - and dihydroxy compounds were successfully synthesized from all substrates and the products were characterized by normal phase ( NP ) HPLC, GC - MS, TOF - MS, UV - visible ( UV - vis ) spectroscopy, and NMR spectroscopy.", "output": "Mono - and dihydroxy." }, { "input": "The methods could be further applied to any polyunsaturated fatty acids containing the cis - 1, 4, 7, 10 - undecatetraene moiety to produce a range of novel compounds with potential biological activity.", "output": "polyunsaturated fatty acids, cis - 1 , 4 , 7 , 10 - undecatetraene." }, { "input": "Biomimetic metal oxides for the extraction of nanoparticles from water.", "output": "metal oxides." }, { "input": "Contamination of nanomaterials in the environment will pose significant health risks in the future.", "output": "There is no related enetity." }, { "input": "A viable purification method is necessary to address this problem.", "output": "There is no related enetity." }, { "input": "Here we report the synthesis and application of a series of metal oxides prepared using a biological template for the removal of nanoparticles from the aqueous environment.", "output": "metal oxides." }, { "input": "A simple synthesis of metal oxides such as ZnO, NiO, CuO, Co3O4 and CeO2 employing eggshell membrane ( ESM ) as a biotemplate is reported.", "output": "metal oxides, ZnO, NiO, CuO, Co3O4, CeO2." }, { "input": "The morphology of the metal oxide powders was characterized using electron microscopes and the lattice structure was established using X - ray diffraction methods.", "output": "metal oxide." }, { "input": "Extraction of nanoparticles from water was carried out to compare the efficiency of metal oxides.", "output": "metal oxides." }, { "input": "NiO showed good extraction efficiency in removing gold and silver nanoparticles from spiked water samples within an hour.", "output": "NiO, silver." }, { "input": "Easy access and enhanced stability of metal oxides makes them interesting candidates for applications in industrial effluent treatments and water purifications.", "output": "metal oxides." }, { "input": "Exendin - 4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome.", "output": "There is no related enetity." }, { "input": "Oxidative stress produced during pancreatic islet isolation leads to significant beta - cell damage.", "output": "There is no related enetity." }, { "input": "Homeostatic cytokines secreted subsequently to islet transplantation damage beta - cells by generating oxygen free radicals.", "output": "oxygen." }, { "input": "In this study, exendin - 4, a glucagon - like peptide - 1 analog improved islet transplantation outcome by increasing the survival of diabetic recipient mice from 58 % to 100 %.", "output": "There is no related enetity." }, { "input": "We hypothesized that this beneficial effect was due to the ability of exendin - 4 to reduce oxidative stress.", "output": "There is no related enetity." }, { "input": "Further experiments showed that it significantly reduced the apoptotic rate of cultured beta - cells subjected to hypoxia or to IL - 1 beta.", "output": "There is no related enetity." }, { "input": "Reduction of apoptotic events was confirmed in pancreatic islet grafts of exendin - 4 - treated mice.", "output": "There is no related enetity." }, { "input": "Exendin - 4 enhanced Akt phosphorylation of beta - cells and insulin released from them.", "output": "There is no related enetity." }, { "input": "It even augmented insulin secretion from islets cultivated at hypoxic conditions.", "output": "There is no related enetity." }, { "input": "Exposure to hypoxia led to a decrease in the activation of Akt, which was reversed when beta - cells were pretreated with exendin - 4.", "output": "There is no related enetity." }, { "input": "Moreover, exendin - 4 increased the activity of redox enzymes in a hypoxia - treated beta - cell line and reduced reactive oxygen species production in isolated pancreatic islets.", "output": "oxygen." }, { "input": "Recovery from diabetes in mice transplanted with hypoxic islets was more efficient when they received exendin - 4.", "output": "There is no related enetity." }, { "input": "In conclusion, exendin - 4 rescued islets from oxidative stress caused by hypoxia or due to cytokine exposure.", "output": "There is no related enetity." }, { "input": "It improved the outcome of syngenic and xenogenic islet transplantation.", "output": "There is no related enetity." }, { "input": "Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma.", "output": "quinolones." }, { "input": "PURPOSE: Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies.", "output": "There is no related enetity." }, { "input": "It is possible that phototoxic drugs promote the development of cutaneous melanoma ( CM ) by intensifying the effect of ultraviolet light on the skin.", "output": "There is no related enetity." }, { "input": "We investigated the association between the use of common systemic phototoxic drugs and development of CM.", "output": "There is no related enetity." }, { "input": "METHODS: This study was a case - control study in a Dutch population - based cohort.", "output": "There is no related enetity." }, { "input": "The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands.", "output": "There is no related enetity." }, { "input": "The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004.", "output": "There is no related enetity." }, { "input": "Controls were sampled from the PHARMO population.", "output": "There is no related enetity." }, { "input": "Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti - inflammatory drugs ( NSAIDs ).", "output": "There is no related enetity." }, { "input": "A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM.", "output": "There is no related enetity." }, { "input": "RESULTS: The study population included 1, 318 cases and 6, 786 controls.", "output": "There is no related enetity." }, { "input": "Any phototoxic drug during the study period was dispensed for 46 % of the cases and 43 % of the controls ( p = 0. 012 ).", "output": "There is no related enetity." }, { "input": "The use of quinolones [ odds ratio ( OR ) 1. 33, 95 % confidence interval ( CI ) 1. 01 - 1. 76 ] and propionic acid derivative NSAIDs ( OR 1. 33, 95 % CI 1. 14 - 1. 54 ) had a positive association with CM.", "output": "quinolones, propionic acid." }, { "input": "CONCLUSIONS: Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM.", "output": "There is no related enetity." }, { "input": "Even a short - term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM.", "output": "quinolones, propionic acid." }, { "input": "Patient education to promote sun - protective behaviour is essential to avoid immediate adverse effects and possible long - term effects of phototoxic drugs.", "output": "There is no related enetity." }, { "input": "A randomised trial of enteric - coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes.", "output": "There is no related enetity." }, { "input": "AIMS / HYPOTHESES: Glucagon - like peptide - 1 ( GLP - 1 ), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut.", "output": "There is no related enetity." }, { "input": "We aimed to determine whether enteric - coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP - 1.", "output": "lauric acid." }, { "input": "METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting.", "output": "metformin." }, { "input": "After an overnight fast, patients consumed 5 g active pellets ( 47 % lauric acid by weight ) or placebo with breakfast ( T = 0 min ) and lunch ( T = 240 min ), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers.", "output": "There is no related enetity." }, { "input": "Patients and investigators making measurements were blinded to the intervention.", "output": "There is no related enetity." }, { "input": "Blood was sampled frequently for blood glucose ( the primary outcome ) and hormone assays.", "output": "glucose." }, { "input": "RESULTS: Eight patients were randomised ( four to receive either intervention first ), and all completed the study without adverse effects.", "output": "There is no related enetity." }, { "input": "Blood glucose was lower after breakfast ( T = 0 - 240 min, area under the curve ( AUC ) 2, 075 +/- 368 vs 2, 216 +/- 163 mmol / l x min ) and lunch ( T = 240 - 480 min, AUC 1, 916 +/- 115 vs 2, 088 +/- 151 mmol / l x min ) ( p = 0. 02 for each ) after active pellets than after placebo.", "output": "glucose." }, { "input": "Plasma GLP - 1 concentrations were higher after breakfast ( p = 0. 08 ) and lunch ( p = 0. 04 ) for active pellets.", "output": "There is no related enetity." }, { "input": "While there were no differences in insulin or glucose - dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch ( p = 0. 002 for each ) for active pellets.", "output": "glucose." }, { "input": "CONCLUSIONS / INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP - 1 release and attenuate postprandial glycaemia.", "output": "There is no related enetity." }, { "input": "This novel approach has therapeutic potential in type 2 diabetes.", "output": "There is no related enetity." }, { "input": "TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842.", "output": "There is no related enetity." }, { "input": "FUNDING: The study was funded by Meyer Nutriceuticals.", "output": "There is no related enetity." }, { "input": "Interindividual variability of carboxymethylenebutenolidase homolog, a novel olmesartan medoxomil hydrolase, in the human liver and intestine.", "output": "olmesartan medoxomil." }, { "input": "Olmesartan medoxomil ( OM ) is a prodrug - type angiotensin II type 1 receptor antagonist.", "output": "Olmesartan medoxomil." }, { "input": "OM is rapidly converted into its active metabolite olmesartan by multiple hydrolases in humans, and we recently identified carboxymethylenebutenolidase homolog ( CMBL ) as one of the OM bioactivating hydrolases.", "output": "olmesartan." }, { "input": "In the present study, we further investigated the interindividual variability of mRNA and protein expression of CMBL and OM - hydrolase activity using 40 individual human liver and 30 intestinal specimens.", "output": "There is no related enetity." }, { "input": "In the intestinal samples, OM - hydrolase activity strongly correlated with the CMBL protein expression, clearly indicating that CMBL is a major contributor to the prodrug bioactivation in human intestine.", "output": "There is no related enetity." }, { "input": "The protein and activity were highly distributed in the proximal region ( duodenum and jejunum ) and decreased to the distal region of the intestine.", "output": "There is no related enetity." }, { "input": "Although there was high interindividual variability ( 16 - fold ) in both the protein and activity in the intestinal segments from the duodenum to colon, the interindividual variability in the duodenum and jejunum was relatively small ( 3. 0 - and 2. 4 - fold, respectively ).", "output": "There is no related enetity." }, { "input": "In the liver samples, the interindividual variability in the protein and activity was 4. 1 - and 6. 8 - fold, respectively.", "output": "There is no related enetity." }, { "input": "No sex differences in the protein and activity were shown in the human liver or intestine.", "output": "There is no related enetity." }, { "input": "A genetically engineered Y155C mutant of CMBL, which was caused by a single nucleotide polymorphism rs35489000, showed significantly lower OM - hydrolase activity than the wild - type protein although no minor allele was genotyped in the 40 individual liver specimens.", "output": "There is no related enetity." }, { "input": "Minireview: ubiquitination - regulated G protein - coupled receptor signaling and trafficking.", "output": "There is no related enetity." }, { "input": "G protein - coupled receptors ( GPCRs ) are the largest and most diverse superfamily of membrane proteins and mediate most cellular responses to hormones and neurotransmitters.", "output": "There is no related enetity." }, { "input": "Posttranslational modifications are considered the main regulators of all GPCRs.", "output": "There is no related enetity." }, { "input": "In addition to phosphorylation, glycosylation, and palmitoylation, increasing evidence as reviewed here reveals that ubiquitination also regulates the magnitude and temporospatial aspects of GPCR signaling.", "output": "There is no related enetity." }, { "input": "Posttranslational protein modification by ubiquitin is a key molecular mechanism governing proteins degradation.", "output": "There is no related enetity." }, { "input": "Ubiquitination mediates the covalent conjugation of ubiquitin, a highly conserved polypeptide of 76 amino acids, to protein substrates.", "output": "amino acids." }, { "input": "This process is catalyzed by 3 enzymes acting in tandem: an E1, ubiquitin - activating enzyme; an E2, ubiquitin - carrying enzyme; and an E3, ubiquitin ligase.", "output": "There is no related enetity." }, { "input": "Ubiquitination is counteracted by deubiquitinating enzymes that deconjugate ubiquitin - modified proteins and rescue the substrate from proteasomal degradation.", "output": "There is no related enetity." }, { "input": "Although ubiquitination is known to target many GPCRs for lysosomal or proteasomal degradation, emerging findings define novel roles for the basal status of ubiquitination and for rapid deubiquitination and transubiquitination controlling cell surface expression and cellular responsiveness of some GPCRs.", "output": "There is no related enetity." }, { "input": "In this review, we highlight the classical and novel roles of ubiquitin in the regulation of GPCR function, signaling, and trafficking.", "output": "There is no related enetity." }, { "input": "Synthesis of novel bis - anthraquinone derivatives and their biological evaluation as antitumor agents.", "output": "bis - anthraquinone." }, { "input": "Cancer has become a major worldwide problem and drug resistance now is one of the most important problems in treatment of cancer.", "output": "There is no related enetity." }, { "input": "Anthraquinone derivatives represent one of the most important drugs that can be used in treatment of many types of cancer.", "output": "Anthraquinone." }, { "input": "In this study two series of novel bis - anthraquinone derivatives have been synthesized.", "output": "bis - anthraquinone." }, { "input": "Five of these compounds were chosen to be evaluated for their antitumor activity against human cancer cell lines by the National Cancer Institute ( NCI, USA ).", "output": "There is no related enetity." }, { "input": "Marked activity was shown for the tested compounds ( 2 - 6 ).", "output": "There is no related enetity." }, { "input": "The most active one was compound 6 with mean value - 67. 00 against all cell lines.", "output": "There is no related enetity." }, { "input": "Compounds 7 and 8 were found inactive.", "output": "There is no related enetity." }, { "input": "Severe hypoglycemia from helicobacter pylori triple - drug therapy and insulin detemir drug interaction.", "output": "There is no related enetity." }, { "input": "Two drugs commonly used in triple - drug therapy for treatment of a Helicobacter pylori infection, clarithromycin and omeprazole, have rarely been associated with hypoglycemia when given alone.", "output": "clarithromycin, omeprazole." }, { "input": "No documented interactions between H. pylori treatment with clarithromycin, amoxicillin, and omeprazole and insulin detemir have been previously reported.", "output": "clarithromycin, amoxicillin, omeprazole." }, { "input": "This case report describes an 82 - year - old man with drug - controlled type 2 diabetes who experienced severe hypoglycemia during treatment for a H. pylori infection in an outpatient setting.", "output": "There is no related enetity." }, { "input": "His diabetes treatment included 32 units of insulin detemir once / day at bedtime and insulin aspart, determined by carbohydrate intake, 3 times / day with meals.", "output": "carbohydrate." }, { "input": "After 5 days of clarithromycin 500 mg twice / day, amoxicillin 500 mg twice / day, and omeprazole 20 mg twice / day for treatment of the H. pylori infection, the patient experienced hypoglycemia and self - discontinued clarithromycin.", "output": "clarithromycin, amoxicillin, omeprazole, clarithromycin." }, { "input": "Insulin detemir was decreased to 15 units and hypoglycemia reoccurred.", "output": "There is no related enetity." }, { "input": "Insulin detemir was further decreased to 10 units without further symptoms of hypoglycemia for the remainder of the H. pylori treatment.", "output": "There is no related enetity." }, { "input": "Once treatment was completed, the patient was instructed to resume taking 32 units of insulin detemir once / day.", "output": "There is no related enetity." }, { "input": "His blood glucose concentration returned to a baseline value, and he denied experiencing further hypoglycemic episodes.", "output": "glucose." }, { "input": "Health care practitioners should be aware of this possible drug interaction and anticipate that insulin detemir dosage adjustments may be required during treatment of H. pylori infection to avoid significant adverse events.", "output": "There is no related enetity." }, { "input": "An Intracellular Domain Fragment of the p75 Neurotrophin Receptor ( p75NTR ) Enhances Tropomyosin Receptor Kinase A ( TrkA ) Receptor Function.", "output": "There is no related enetity." }, { "input": "Facilitation of nerve growth factor ( NGF ) signaling by the p75 neurotrophin receptor ( p75 ( NTR ) ) is critical for neuronal survival and differentiation.", "output": "There is no related enetity." }, { "input": "However, the interaction between p75 ( NTR ) and TrkA receptors required for this activity is not understood.", "output": "There is no related enetity." }, { "input": "Here, we report that a specific 29 - amino acid peptide derived from the intracellular domain fragment of p75 ( NTR ) interacts with and potentiates binding of NGF to TrkA - expressing cells, leading to increased neurite outgrowth in sympathetic neurons as a result of enhanced Erk1 / 2 and Akt signaling.", "output": "amino acid." }, { "input": "An endogenous intracellular domain fragment of p75 ( NTR ) ( p75 ( ICD ) ) containing these 29 amino acids is produced by regulated proteolysis of the full - length receptor.", "output": "amino acids." }, { "input": "We demonstrate that generation of this fragment is a requirement for p75 ( NTR ) to facilitate TrkA signaling in neurons and propose that the juxtamembrane region of p75 ( ICD ) acts to cause a conformational change within the extracellular domain of TrkA.", "output": "There is no related enetity." }, { "input": "This finding provides new insight into the mechanism by which p75 ( NTR ) and TrkA interact to enhance neurotrophic signaling.", "output": "There is no related enetity." }, { "input": "H - H and Si - H Bond Addition to Fe = NNR2 Intermediates Derived from N2.", "output": "H - H, Si - H, Fe = NNR2, N2." }, { "input": "The synthesis and characterization of Fe - diphosphineborane complexes are described in the context of N2 functionalization chemistry.", "output": "Fe - diphosphineborane, N2." }, { "input": "Iron aminoimides can be generated at room temperature under 1 atm N2 and are shown to react with E - H bonds from PhSiH3 and H2.", "output": "Iron aminoimides, N2, E - H, PhSiH3, H2." }, { "input": "The resulting products derive from delivery of the E fragment to N alpha and the H atom to B.", "output": "H, B." }, { "input": "The flexibility and lability of the Fe - BPh interactions in these complexes engender this reactivity.", "output": "Fe - BPh." }, { "input": "Anion - Exchange Reactions on a Robust Phosphonium Photopolymer for the Controlled Deposition of Ionic Gold Nanoclusters.", "output": "There is no related enetity." }, { "input": "UV curing ( photopolymerization ) is ubiquitous in many facets of industry ranging from the application of paints, pigments, and barrier coatings all the way to fiber optic cable production.", "output": "There is no related enetity." }, { "input": "To date no reports have focused on polymerizable phosphonium salts under UV irradiation, and despite this dearth of examples, they potentially offer numerous substantial advantages to traditional UV formulation components.", "output": "There is no related enetity." }, { "input": "We have generated a highly novel coating based on UV - curable trialkylacryloylphosphonium salts that allow for the fast ( seconds ) and straightforward preparation of ion - exchange surfaces amenable to a roll - to - roll process.", "output": "trialkylacryloylphosphonium salts." }, { "input": "We have quantified the surface charges and exploited their accessibility by employing these surfaces in an anion exchange experiment by which [ Au25L18 ] ( - ) ( L = SCH2CH2Ph ) nanocrystals can be assembled into the solid state.", "output": "[ Au25L18 ] ( - ), SCH2CH2Ph." }, { "input": "This unprecedented application of such surfaces offers a paradigm shift in the emerging chemistry of Au25 research where the nanocrystals remain single and intact and where the integrity of the cluster and its solution photophysical properties are resilient in the solid state.", "output": "Au25." }, { "input": "The specific loading of [ Au25L18 ] ( - ) on the substrates has been determined and the completely reversible loading and unloading of intact nanocrystals to and from the surface has been established.", "output": "[ Au25L18 ] ( - )." }, { "input": "In the solid state, the assembly has an incredible mechanical resiliency, where the surface remains undamaged even when subjected to repeated Scotch tests.", "output": "There is no related enetity." }, { "input": "Bioactivity of tomato hybrid powder: antioxidant compounds and their biological activities.", "output": "There is no related enetity." }, { "input": "Abstract The antioxidant and cytotoxic activities and the polyphenolic and anthocyanin contents of tomato hybrid powders were studied.", "output": "polyphenolic, anthocyanin." }, { "input": "Tomato powders were obtained, starting from the fresh fruits that had undergone an industrial process of drying and pulverization at two different temperatures.", "output": "There is no related enetity." }, { "input": "Antioxidant activities were evaluated in different extracts by using spectrophotometric assays: 2, 2 ' - azino - bis - ( 3 - ethylbenzthiazoline - 6 - sulfonic acid and N, N - dimethyl - p - phenylenediamine dihydrochloride cation radical inhibition for lipophilic and hydrophilic extracts, respectively, and 2, 2 - diphenyl - 1 - picrylhydrazyl radical scavenging assay for polyphenolic extracts.", "output": "2 , 2 ' - azino - bis - ( 3 - ethylbenzthiazoline - 6 - sulfonic acid, N , N - dimethyl - p - phenylenediamine dihydrochloride, 2 , 2 - diphenyl - 1 - picrylhydrazyl, polyphenolic." }, { "input": "Moreover, polyphenolic and anthocyanin contents were also carried out to detect the presence of these bioactive compounds.", "output": "polyphenolic, anthocyanin." }, { "input": "The effect of cytotoxic activity in vitro of tomato hybrid powder extracts on T47D ( human breast carcinoma ) cells was also evaluated.", "output": "There is no related enetity." }, { "input": "Results showed good antioxidant activities in lipophilic, polyphenolic, and hydrophilic extracts of samples that were obtained at a lower temperature.", "output": "polyphenolic." }, { "input": "Extracts of the sample obtained at a higher temperature presented moderate antioxidant activity, lower than the extracts of other samples, which was probably due to the loss of labile antioxidant compounds during the industrial process.", "output": "There is no related enetity." }, { "input": "Very interesting was the presence of anthocyanins in both samples, even if in traces, and also a moderate cytotoxicity of a lipophilic extract on T47D cells.", "output": "anthocyanins." }, { "input": "Therefore, tomato hybrid powders, on the basis of their multifunctional properties, could have a biotechnological application in agri - food or cosmetic industries as an additive for improving nutritional and / or bioactive qualities of commercial products used in daily nutrition and cosmetics.", "output": "There is no related enetity." }, { "input": "Directing cluster formation of au nanoparticles from colloidal solution.", "output": "au." }, { "input": "Discrete clusters of closely spaced Au nanoparticles can be utilized in devices from photovoltaics to molecular sensors because of the formation of strong local electromagnetic field enhancements when illuminated near their plasmon resonance.", "output": "Au." }, { "input": "In this study, scalable, chemical self - organization methods are shown to produce Au nanoparticle clusters with uniform nanometer interparticle spacing.", "output": "Au." }, { "input": "The performance of two different methods, namely electrophoresis and diffusion, for driving the attachment of Au nanoparticles using a chemical cross - linker on chemically patterned domains of polystyrene - block - poly ( methyl methacrylate ) ( PS - b - PMMA ) thin films are evaluated.", "output": "Au, polystyrene, poly ( methyl methacrylate ), PMMA." }, { "input": "Significantly, electrophoresis is found to produce similar surface coverage as diffusion in 1 / 6th of the processing time with an ~ 2 - fold increase in the number of Au nanoparticles forming clusters.", "output": "Au." }, { "input": "Furthermore, average interparticle spacing within Au nanoparticle clusters was found to decrease from 2 - 7 nm for diffusion deposition to approximately 1 - 2 nm for electrophoresis deposition, and the latter method exhibited better uniformity with most clusters appearing to have about 1 nm spacing between nanoparticles.", "output": "Au." }, { "input": "The advantage of such fabrication capability is supported by calculations of local electric field enhancements using electromagnetic full - wave simulations from which we can estimate surface - enhanced Raman scattering ( SERS ) enhancements.", "output": "There is no related enetity." }, { "input": "In particular, full - wave results show that the maximum SERS enhancement, as estimated here as the fourth power of the local electric field, increases by a factor of 100 when the gap goes from 2 to 1 nm, reaching values as large as 10 ( 10 ), strengthening the usage of electrophoresis versus diffusion for the development of molecular sensors.", "output": "There is no related enetity." }, { "input": "Encapsulation of Hydrophobic Drugs in Pluronic F127 Micelles: Effects of Drug Hydrophobicity, Solution Temperature, and pH.", "output": "Pluronic F127." }, { "input": "Three drugs, ibuprofen, aspirin, and erythromycin, are encapsulated in spherical Pluronic F127 micelles.", "output": "ibuprofen, aspirin, erythromycin, Pluronic F127." }, { "input": "The shapes and the size distributions of the micelles in dilute, aqueous solutions, with and without drugs, are ascertained using cryo - scanning electron microscopy and dynamic light scattering ( DLS ) experiments, respectively.", "output": "There is no related enetity." }, { "input": "Uptake of drugs above a threshold concentration is seen to reduce the critical micellization temperature of the solution.", "output": "There is no related enetity." }, { "input": "The mean hydrodynamic radii and polydispersities of the micelles are found to increase with decrease in temperature and in the presence of drug molecules.", "output": "There is no related enetity." }, { "input": "The hydration of the micellar core at lower temperatures is verified using fluorescence measurements.", "output": "There is no related enetity." }, { "input": "Increasing solution pH leads to the ionization of the drugs incorporated in the micellar cores.", "output": "There is no related enetity." }, { "input": "This causes rupture of the micelles and release of the drugs into the solution at the highest solution pH value of 11. 36 investigated here and is studied using DLS and fluorescence spectrocopy.", "output": "There is no related enetity." }, { "input": "Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential.", "output": "indenoisoquinoline rexinoids." }, { "input": "Nuclear receptors, such as the retinoid X receptor ( RXR ), are proteins that regulate a myriad of cellular processes.", "output": "There is no related enetity." }, { "input": "Molecules that function as RXR agonists are of special interest for the prevention and control of carcinogenesis.", "output": "There is no related enetity." }, { "input": "The majority of these ligands possess an acidic moiety that is believed to be key for RXR activation.", "output": "There is no related enetity." }, { "input": "This communication presents the design, synthesis, and biological evaluation of both acidic and nonacidic indenoisoquinolines as new RXR ligands.", "output": "indenoisoquinolines." }, { "input": "In addition, a comprehensive structure - activity relationship study is presented that identifies the important features of the indenoisoquinoline rexinoids.", "output": "indenoisoquinoline rexinoids." }, { "input": "The ease of modification of the indenoisoquinoline core and the lack of the necessity of a carboxyl group for activity make them an attractive and unusual family of RXR agonists.", "output": "indenoisoquinoline, carboxyl." }, { "input": "This work establishes a structural foundation for the design of new and novel rexinoid cancer chemopreventive agents.", "output": "There is no related enetity." }, { "input": "Nanoparticle film assemblies as platforms for electrochemical biosensing - factors affecting the amperometric signal enhancement of hydrogen peroxide.", "output": "hydrogen peroxide." }, { "input": "Factors affecting the enhanced amperometric signal observed at electrodes modified with polyelectrolyte - gold nanoparticle ( Au - NP ) composite films, which are potential interfaces for first - generation biosensors, were systematically investigated and optimized for hydrogen peroxide ( H2O2 ) detection.", "output": "Au, hydrogen peroxide, H2O2." }, { "input": "Polyelectrolyte multilayer films embedded with citrate - stabilized gold nanoparticles exhibited high sensitivity toward the oxidation of H2O2.", "output": "citrate, H2O2." }, { "input": "From this Au - NP film assembly, the importance of Au - NP ligand protection, film permeability, the density of Au - NPs within the film, and electronic coupling between Au - NPs ( interparticle ) and between the film and the electrode ( interfacial ) were evaluated.", "output": "Au, Au, Au, Au." }, { "input": "Using alternative Au - NPs, including those stabilized with thiols, polymers, and bulky ligands, suggests that the amperometric enhancement of H2O2 is optimized at poly - l - lysine - linked film assemblies embedded with Au - NPs possessing small, charged, and conductive ( conjugated ) peripheral ligands.", "output": "Au, thiols, H2O2, poly - l - lysine, Au." }, { "input": "As a potential application of these Au - NP film assemblies, an enhanced amperometric signal for H2O2 oxidation was shown for modified \" needle \" electrodes.", "output": "Au, H2O2." }, { "input": "The overall aim of this research is to gain a greater understanding of designing electrochemical sensing strategies that incorporate Au - NPs and target specific analytes.", "output": "Au." }, { "input": "A new \" immunological \" role for adipocytes in obesity.", "output": "There is no related enetity." }, { "input": "Obesity - induced insulin resistance is associated with low - grade adipose tissue inflammation, but the mechanism driving this process remains unclear.", "output": "There is no related enetity." }, { "input": "In this issue of Cell Metabolism, a study by Deng et al.", "output": "There is no related enetity." }, { "input": "( 2013 ) demonstrates a direct immunological role of adipocytes in instigating adipose inflammation via a MHCII - dependent process.", "output": "There is no related enetity." }, { "input": "Iron and diabetes risk.", "output": "Iron." }, { "input": "Iron overload is a risk factor for diabetes.", "output": "Iron." }, { "input": "The link between iron and diabetes was first recognized in pathologic conditions - hereditary hemochromatosis and thalassemia - but high levels of dietary iron also impart diabetes risk.", "output": "iron, iron." }, { "input": "Iron plays a direct and causal role in diabetes pathogenesis mediated both by beta cell failure and insulin resistance.", "output": "Iron." }, { "input": "Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron - sensing role.", "output": "Iron, iron." }, { "input": "The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways.", "output": "There is no related enetity." }, { "input": "Identification of a SIRT1 mutation in a family with type 1 diabetes.", "output": "There is no related enetity." }, { "input": "Type 1 diabetes is caused by autoimmune - mediated beta cell destruction leading to insulin deficiency.", "output": "There is no related enetity." }, { "input": "The histone deacetylase SIRT1 plays an essential role in modulating several age - related diseases.", "output": "There is no related enetity." }, { "input": "Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis.", "output": "There is no related enetity." }, { "input": "Initially, a 26 - year - old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to beta cell antigens, and a rapid dependence on insulin.", "output": "There is no related enetity." }, { "input": "Direct and exome sequencing identified the presence of a T - to - C exchange in exon 1 of SIRT1, corresponding to a leucine - to - proline mutation at residue 107.", "output": "leucine, proline." }, { "input": "Expression of SIRT1 - L107P in insulin - producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines.", "output": "nitric oxide." }, { "input": "These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.", "output": "There is no related enetity." }, { "input": "Going where traditional markers have not gone before: utility of and promise for RAD sequencing in marine invertebrate phylogeography and population genomics.", "output": "There is no related enetity." }, { "input": "Characterization of large numbers of single - nucleotide polymorphisms ( SNPs ) throughout a genome has the power to refine the understanding of population demographic history and to identify genomic regions under selection in natural populations.", "output": "There is no related enetity." }, { "input": "To this end, population genomic approaches that harness the power of next - generation sequencing to understand the ecology and evolution of marine invertebrates represent a boon to test long - standing questions in marine biology and conservation.", "output": "There is no related enetity." }, { "input": "We employed restriction - site - associated DNA sequencing ( RAD - seq ) to identify SNPs in natural populations of the sea anemone Nematostella vectensis, an emerging cnidarian model with a broad geographic range in estuarine habitats in North and South America, and portions of England.", "output": "There is no related enetity." }, { "input": "We identified hundreds of SNP - containing tags in thousands of RAD loci from 30 barcoded individuals inhabiting four locations from Nova Scotia to South Carolina.", "output": "There is no related enetity." }, { "input": "Population genomic analyses using high - confidence SNPs resulted in a highly - resolved phylogeography, a result not achieved in previous studies using traditional markers.", "output": "There is no related enetity." }, { "input": "Plots of locus - specific FST against heterozygosity suggest that a majority of polymorphic sites are neutral, with a smaller proportion suggesting evidence for balancing selection.", "output": "There is no related enetity." }, { "input": "Loci inferred to be under balancing selection were mapped to the genome, where 90 % were located in gene bodies, indicating potential targets of selection.", "output": "There is no related enetity." }, { "input": "The results from analyses with and without a reference genome supported similar conclusions, further highlighting RAD - seq as a method that can be efficiently applied to species lacking existing genomic resources.", "output": "There is no related enetity." }, { "input": "We discuss the utility of RAD - seq approaches in burgeoning Nematostella research as well as in other cnidarian species, particularly corals and jellyfishes, to determine phylogeographic relationships of populations and identify regions of the genome undergoing selection.", "output": "There is no related enetity." }, { "input": "Engineered iron - oxide - based nanoparticles as enhanced t1 contrast agents for efficient tumor imaging.", "output": "iron - oxide." }, { "input": "We report the design and synthesis of small - sized zwitterion - coated gadolinium - embedded iron oxide ( GdIO ) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects.", "output": "gadolinium, iron oxide, GdIO." }, { "input": "The combination of spin - canting effects and the collection of gadolinium species within small - sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect.", "output": "gadolinium, GdIO." }, { "input": "For example, GdIO nanoparticles with a diameter of ~ 4. 8 nm exhibited a high r1 relaxivity of 7. 85 mM ( - 1 ). S ( - 1 ) and a low r2 / r1 ratio of 5. 24.", "output": "GdIO." }, { "input": "After being coated with zwitterionic dopamine sulfonate molecules, the 4. 8 nm GdIO nanoparticles showed a steady hydrodynamic diameter ( ~ 5. 2 nm ) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption.", "output": "dopamine sulfonate, GdIO." }, { "input": "This study provides a valuable strategy for the design of highly sensitive iron - oxide - based T1 contrast agents with relatively long circulation half - lives ( ~ 50 min ), efficient tumor passive targeting ( SKOV3, human ovarian cancer xenograft tumor as a model ), and the possibility of rapid renal clearance after tumor imaging.", "output": "iron - oxide." }, { "input": "Variations on glutamate binding in channel - gated receptors.", "output": "glutamate." }, { "input": "In this issue of Structure, Lomash and colleagues report on the crystal structure and ligand binding properties of a primitive eukaryote glutamate - gated ion channel: AvGluR1.", "output": "glutamate." }, { "input": "Degradation of MAC13243 and studies of the interaction of resulting thiourea compounds with the lipoprotein targeting chaperone LolA.", "output": "MAC13243, thiourea." }, { "input": "The discovery of novel small molecules that function as antibacterial agents or cellular probes of biology is hindered by our limited understanding of bacterial physiology and our ability to assign mechanism of action.", "output": "There is no related enetity." }, { "input": "We previously employed a chemical genomic strategy to identify a novel small molecule, MAC13243, as a likely inhibitor of the bacterial lipoprotein targeting chaperone, LolA.", "output": "MAC13243." }, { "input": "Here, we report on the degradation of MAC13243 into the active species, S - ( 4 - chlorobenzyl ) isothiourea.", "output": "MAC13243, S - ( 4 - chlorobenzyl ) isothiourea." }, { "input": "Analogs of this compound ( e. g., A22 ) have previously been characterized as inhibitors of the bacterial actin - like protein, MreB.", "output": "There is no related enetity." }, { "input": "Herein, we demonstrate that the antibacterial activity of MAC13243 and the thiourea compounds are similar; these activities are suppressed or sensitized in response to increases or decreases of LolA copy number, respectively.", "output": "MAC13243, thiourea." }, { "input": "We provide STD NMR data which confirms a physical interaction between LolA and the thiourea degradation product of MAC13243, with a Kd of ~ 150 mu M.", "output": "thiourea, MAC13243." }, { "input": "Taken together, we conclude that the thiourea series of compounds share a similar cellular mechanism that includes interaction with LolA in addition to the well - characterized target MreB.", "output": "thiourea." }, { "input": "Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo.", "output": "Hinokitiol." }, { "input": "Hinokitiol is a tropolone - related bioactive compound that has been used in hair tonics, cosmetics, and food as an antimicrobial agent.", "output": "Hinokitiol." }, { "input": "Recently, hinokitiol has attracted considerable interest because of its anticancer activities.", "output": "hinokitiol." }, { "input": "Platelet activation plays a crucial role in atherothrombotic processes.", "output": "There is no related enetity." }, { "input": "We examined the effects of hinokitiol treatment on platelet activation using human platelets.", "output": "hinokitiol." }, { "input": "In the present study, hinokitiol ( 1 and 2 mu M ) inhibited the collagen - induced aggregation of human platelets, but did not inhibit the activation of platelets by other agonists, including thrombin, arachidonic acid, and ADP.", "output": "hinokitiol, arachidonic acid, ADP." }, { "input": "Hinokitiol inhibited the phosphorylation of phospholipase C ( PLC ) gamma 2, protein kinase C ( PKC ), mitogen - activated protein kinases ( MAPKs ), and Akt in collagen - activated human platelets, and significantly reduced intracellular calcium mobilization and hydroxyl radical ( OH ) formation.", "output": "Hinokitiol, calcium, hydroxyl, OH." }, { "input": "Hinokitiol also reduced the PKC activation and platelet aggregation stimulated by PDBu.", "output": "Hinokitiol." }, { "input": "In addition, hinokitiol significantly prolonged thrombogenesis in mice.", "output": "hinokitiol." }, { "input": "Hinokitiol did not influence the binding of a fluorescent triflavin probe to the alpha IIb beta 3 integrin on platelet membrane, and neither ODQ nor SQ22536 significantly reversed the hinokitiol - mediated inhibition of platelet aggregation.", "output": "Hinokitiol, ODQ, SQ22536, hinokitiol." }, { "input": "In conclusion, hinokitiol may inhibit platelet activation by inhibiting the PLC gamma 2 - PKC cascade and hydroxyl radical formation, followed by suppressing the activation of MAPKs and Akt.", "output": "hinokitiol, hydroxyl." }, { "input": "Our study suggests that hinokitiol may represent a potential therapeutic agent for the prevention or treatment of thromboembolic disorders.", "output": "hinokitiol." }, { "input": "The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage - gated sodium channels.", "output": "There is no related enetity." }, { "input": "One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider Apomastus schlingeri.", "output": "There is no related enetity." }, { "input": "Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development.", "output": "There is no related enetity." }, { "input": "However, its disulfide - connectivity, three - dimensional structure, and mode of action have not been determined.", "output": "disulfide." }, { "input": "Here we show that recombinant Aps III ( rAps III ) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large beta hairpin loop that often houses the pharmacophore in this class of toxins.", "output": "disulfide, cystine, disulfide." }, { "input": "We demonstrate that the irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage - gated sodium channels.", "output": "sodium." }, { "input": "Channel block by rAps III is voltage - independent insofar as it occurs without significant alteration in the voltage - dependence of channel activation or steady - state inactivation.", "output": "There is no related enetity." }, { "input": "Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage - gated sodium channels.", "output": "sodium." }, { "input": "This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage - sensing domains of the channel.", "output": "sodium." }, { "input": "Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158N murine oligodendrocytes.", "output": "oxysterol, calcium." }, { "input": "There is some evidence that oxidized derivatives of cholesterol, 7 - ketocholesterol ( 7KC ) and 7 beta - hydroxycholesterol ( 7 beta OHC ), are increased in the plasma of patients with neurodegenerative diseases associated with demyelinization of the central nervous system ( CNS ).", "output": "cholesterol, 7 - ketocholesterol, 7KC, 7 beta - hydroxycholesterol, 7 beta OHC." }, { "input": "It was therefore of interest to investigate the effects of these oxysterols on oligodendrocytes, the myelin - forming cells in the CNS.", "output": "oxysterols." }, { "input": "To this end, 158N murine oligodendrocytes were treated with 7KC or 7 beta OHC inducing an apoptotic mode of cell death characterized by condensation / fragmentation of the nuclei, dephosphorylation of Akt and GSK3, mitochondrial depolarization involving Mcl - 1, and caspase - 3 activation.", "output": "7KC, 7 beta OHC." }, { "input": "In contrast, under treatment with 27 - hydroxycholesterol ( 27OHC ), no cell death was observed.", "output": "27 - hydroxycholesterol." }, { "input": "When the cells were stained with Fura - 2, no significant Ca ( 2 + ) rise was found with the different oxysterols, whereas strong signals were detected with ionomycin used as positive control.", "output": "Fura - 2, Ca ( 2 + ), oxysterols, ionomycin." }, { "input": "At concentrations which induced apoptosis, 7KC but not 7 beta OHC accumulated in lipid rafts.", "output": "7KC, 7 beta OHC." }, { "input": "Although not cytotoxic, 27OHC was mainly detected in lipid rafts.", "output": "27OHC." }, { "input": "It is noteworthy that alpha - tocopherol ( but not ellagic acid and resveratrol ) was able to counteract 7KC - and 7 beta OHC - induced apoptosis and to decrease the accumulation of 7KC and 27OHC in lipid rafts.", "output": "alpha - tocopherol, ellagic acid, resveratrol, 7KC, 7 beta OHC, 7KC, 27OHC." }, { "input": "Thus, in 158N cells, the ability of oxysterols to trigger a mode of cell death by apoptosis involving GSK - 3 and caspase - 3 activation is independent of the increase in the Ca ( 2 + ) level and of their accumulation in lipid raft microdomains.", "output": "oxysterols, Ca ( 2 + )." }, { "input": "Intact inhibitory control processes in abstinent drug abusers ( I ): A functional neuroimaging study in former cocaine addicts.", "output": "cocaine." }, { "input": "Neuroimaging studies in current cocaine dependent ( CD ) individuals consistently reveal cortical hypoactivity across regions of the response inhibition circuit ( RIC ).", "output": "cocaine." }, { "input": "Dysregulation of this critical executive network is hypothesized to account for the lack of inhibitory control that is a hallmark of the addictive phenotype, and chronic abuse is believed to compound the issue.", "output": "There is no related enetity." }, { "input": "A crucial question is whether deficits in this circuit persist after drug cessation, and whether recovery of this system will be seen after extended periods of abstinence, a question with implications for treatment course and outcome.", "output": "There is no related enetity." }, { "input": "Utilizing functional magnetic resonance imaging ( fMRI ), we examined activation in nodes of the RIC in abstinent CD individuals ( n = 27 ) and non - using controls ( n = 45 ) while they performed a motor response inhibition task.", "output": "There is no related enetity." }, { "input": "In contrast to current users, these abstinent individuals, despite extended histories of chronic cocaine - abuse ( average duration of use = 8. 2 years ), performed the task just as efficiently as non - users.", "output": "cocaine." }, { "input": "In line with these behavioral findings, no evidence for between - group differences in activation of the RIC was found and instead, robust activations were apparent in both groups within the well - characterized nodes of the RIC.", "output": "There is no related enetity." }, { "input": "Similarly, our complementary Electroencephalography ( EEG ) investigation also showed an absence of behavioral and electrophysiological deficits in abstinent drug abusers.", "output": "There is no related enetity." }, { "input": "These results are consistent with an amelioration of neurobiological deficits in inhibitory circuitry following drug cessation, and could help explain how long - term abstinence is maintained.", "output": "There is no related enetity." }, { "input": "Finally, regression analyses revealed a significant association between level of activation in the right insula with inhibition success and increased abstinence duration in the CD cohort suggesting that this region may be integral to successful recovery from cocaine addiction.", "output": "cocaine." }, { "input": "New plant sources of the anti - cancer alkaloid, camptothecine from the Icacinaceae taxa, India.", "output": "camptothecine." }, { "input": "In this study, the production of camptothecine and its derivatives, in thirteen species of the family Icacinaceae, namely, Apodytes dimidiata, Codiocarpus andamanicus, Gomphandra comosa, Gomphandra coriacea, Gomphandra polymorpha, Gomphandra tetrandra, Iodes cirrhosa, Iodes hookeriana, Miquelia dentata, Miquelia kleinii, Natsiatum herpeticum, Pyrenacantha volubilis and Sarcostigma kleinii is reported.", "output": "camptothecine." }, { "input": "Seeds of M. dentata were found to produce the highest content of camptothecine ( 1. 0 - 1. 4 % by dry weight of seeds ).", "output": "camptothecine." }, { "input": "Full scan LC - MS and ESI - MS / MS analysis of M. dentata revealed, besides camptothecine, a number of other derivatives, namely, 10 - hydroxycamptothecine, 9 - methoxycamptothecine, 20 - deoxycamptothecine.", "output": "camptothecine, 10 - hydroxycamptothecine, 9 - methoxycamptothecine, 20 - deoxycamptothecine." }, { "input": "Crude extract preparations of the seeds of M. dentata were effective against a breast cancer cell line ( IC50 = 3. 82 mu g / ml for MDA MB273 cell lines ) and two ovarian cancer cell lines ( IC50 = 2. 8 mu g / ml for NCI / ADR - RES and 4. 5 mu g / ml for SKOV ).", "output": "There is no related enetity." }, { "input": "These results are the first reports of camptothecine and its derivatives in these species and offer rich alternative plant sources for the anticancer compound, camptothecine.", "output": "camptothecine, camptothecine." }, { "input": "Continuous IV Crotalidae Polyvalent Immune Fab ( Ovine ) ( FabAV ) for selected North American Rattlesnake bite patients.", "output": "There is no related enetity." }, { "input": "BACKGROUND: In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab ( Ovine ) ( FabAV ), late hematologic abnormalities - persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT / INR, prolonged PTT, and / or thrombocytopenia beyond 48 h post - envenomation - are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality.", "output": "There is no related enetity." }, { "input": "The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined.", "output": "There is no related enetity." }, { "input": "The current FabAV treatment regimen is to give antivenom as a bolus dose over a one - hour period.", "output": "There is no related enetity." }, { "input": "We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and / or associated bleeding complications in rattlesnake envenomation.", "output": "There is no related enetity." }, { "input": "METHODS: This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and / or associated bleeding complications.", "output": "There is no related enetity." }, { "input": "Indications, dilution and infusion protocols, and duration of therapy were individualized.", "output": "There is no related enetity." }, { "input": "RESULTS: Five cases were identified between July 2010 and September 2011.", "output": "There is no related enetity." }, { "input": "All patients had profound late hematologic abnormalities and / or were associated with bleeding complications.", "output": "There is no related enetity." }, { "input": "Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response.", "output": "There is no related enetity." }, { "input": "All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities.", "output": "There is no related enetity." }, { "input": "Rates of infusion varied from 2 to 4 vials per 24 h ( mean = 3. 1 +/- 0. 4 vials / day ).", "output": "There is no related enetity." }, { "input": "The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation ( mean = 10 +/- 3 days ), after which hematologic values were normalized or were normalizing in all patients and continued to do so.", "output": "There is no related enetity." }, { "input": "DISCUSSION: The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and / or fibrinogen.", "output": "There is no related enetity." }, { "input": "This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe.", "output": "There is no related enetity." }, { "input": "Further assessments of the stability and sterility of the product during infusion are needed.", "output": "There is no related enetity." }, { "input": "The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications ( e. g. bleeding ) in this subset of patients.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6 - 14 days post - envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding.", "output": "There is no related enetity." }, { "input": "Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost - effective than observation without FabAV treatment or as - needed bolus dosing in selected patients with late hematologic abnormalities.", "output": "There is no related enetity." }, { "input": "In vitro interceptive and reparative effects of myo - inositol against copper - induced oxidative damage and antioxidant system disturbance in primary cultured fish enterocytes.", "output": "myo - inositol, copper." }, { "input": "Copper ( Cu ) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess.", "output": "Copper, Cu." }, { "input": "Our previous study reported that a nutrient antioxidant, myo - inositol ( MI ), can protect fish from Cu - induced oxidative injury; however, the mechanisms involved are not fully understood.", "output": "myo - inositol, Cu." }, { "input": "Therefore, the present study aimed to analyze potential pathways.", "output": "There is no related enetity." }, { "input": "First, to investigate the hypothesis that MI protects enterocytes against Cu toxicity via the intercept pathway, enterocytes were treated with different concentrations of MI ( 0 - 75mg / L medium ) in the presence of 6mg / L of Cu for 24h ( Experiment 1 ).", "output": "Cu, Cu." }, { "input": "Next, we investigated the potential reparative role of MI after a Cu challenge ( Experiment 2 ).", "output": "Cu." }, { "input": "The results of Experiment 1 indicated that cells exposed to Cu alone for 24h exhibited increases in lactate dehydrogenase release ( LDH ), malondialdehyde ( MDA ) formation and protein oxidation ( P < 0. 05 ).", "output": "Cu, lactate, malondialdehyde, MDA." }, { "input": "Notably, a dose - dependent inhibitory effect on LDH release was observed with all doses of MI.", "output": "There is no related enetity." }, { "input": "Moreover, co - treatment with MI completely inhibited Cu - induced protein carbonyl ( PC ) formation.", "output": "Cu, carbonyl." }, { "input": "However, Cu - induced lipid peroxidation was not altered by MI co - treatment.", "output": "Cu." }, { "input": "Additionally, Cu exposure suppressed total - superoxide dismutase ( T - SOD ), CuZnSOD and catalase ( CAT ) activities, and these changes were completely blocked by co - treatment with sufficient MI concentrations.", "output": "Cu, superoxide." }, { "input": "In contrast, cells exposed to Cu exhibited adaptive increases in reduced glutathione ( GSH ) content and the activities of anti - hydroxyl radical ( AHR ), glutathione peroxidase ( GPx ), glutathione - S - transferase ( GST ) and glutathione reductase ( GR ).", "output": "Cu, reduced glutathione, GSH, glutathione, glutathione, S, glutathione." }, { "input": "Interestingly, the Cu - stimulated increases in these antioxidants were blocked by co - treatment with sufficient MI concentrations.", "output": "Cu." }, { "input": "The results of Experiment 2 indicated that cell injury ( LDH release ), lipid peroxidation ( MDA formation ) and protein oxidation induced by Cu were reversed by subsequent MI treatment.", "output": "MDA, Cu." }, { "input": "Meanwhile, Cu - induced decreases in alkaline phosphatase ( AKP ), anti - superoxide anion ( ASA ), T - SOD and CuZnSOD activities were completely restored by subsequent MI treatment, while the reduced CAT activity was partially restored.", "output": "Cu, superoxide." }, { "input": "However, MI rescues partially restored the adaptive increase in GPx activity induced by Cu, whereas the adaptive increase in reduced GSH content was completely reversed by 75mg / L of MI.", "output": "Cu, reduced GSH." }, { "input": "However, subsequent MI treatments did not alter the induction of GST activity by Cu.", "output": "Cu." }, { "input": "In conclusion, we demonstrated for the first time that MI not only protected enterocytes from Cu - induced oxidative damage but also increased the repair activity in primary enterocytes after challenge with Cu.", "output": "Cu, Cu." }, { "input": "Moreover, MI - mediated increases in antioxidant enzyme activities contributed to lipid and protein oxidant repair.", "output": "There is no related enetity." }, { "input": "Effects of metal burden and food avoidance on the transfer of metals from naturally contaminated prey to a marine predator Nassarius siquijorensis.", "output": "There is no related enetity." }, { "input": "Nassarid snails are important opportunistic scavengers widely found in marine intertidal shores and trophic transfer is a predominant source of metal accumulation in these species, thus there is a significant need to understand the controls of metal trophic transfer.", "output": "There is no related enetity." }, { "input": "In the present study, we took advantage of a severely contaminated estuary and collected two prey organisms ( oysters Crassostrea angulata and barnacles Fistulobalanus albicostatus ) with different contamination histories.", "output": "There is no related enetity." }, { "input": "These naturally contaminated prey were fed to a marine neogastropod Nassarius siquijorensis for a period of up to 7 weeks.", "output": "There is no related enetity." }, { "input": "We then investigated the influences of prey type, metal burden, and subcellular distribution in the prey on the metal accumulation, trophic transfer, and potential toxicity on N. siquijorensis.", "output": "There is no related enetity." }, { "input": "We demonstrated an obvious negative relationship between the trophic transfer and the metal concentration in prey or the metal dosage.", "output": "There is no related enetity." }, { "input": "N. siquijorensis exhibited food avoidance behavior to the Cu contaminated food, which effectively reduced the metal ingestion and resulted in a decrease of trophic transfer, as well as a potential toxic effect from dietary exposure.", "output": "Cu." }, { "input": "On the other hand, our results also implied the metal - specific impact of subcellular metal distribution in prey on the trophic transfer to N. siquijorensis.", "output": "There is no related enetity." }, { "input": "Our study suggested that metal burden and feeding avoidance should be considered in studying the trophic transfer of metals in marine benthic food chain.", "output": "There is no related enetity." }, { "input": "Effects of salinity stress on Bufo balearicus and Bufo bufo tadpoles: Tolerance, morphological gill alterations and Na ( + ) / K ( + ) - ATPase localization.", "output": "Na ( + ), K ( + )." }, { "input": "Freshwater habitats are globally threatened by human - induced secondary salinization.", "output": "There is no related enetity." }, { "input": "Amphibians are generally poorly adapted to survive in saline environments.", "output": "There is no related enetity." }, { "input": "We experimentally investigated the effects of chronic exposure to various salinities ( 5 %, 10 %, 15 %, 20 %, 25 %, 30 % and 35 % seawater, SW ) on survival, larval growth and metamorphosis of tadpoles from two amphibian populations belonging to two species: the green toad Bufo balearicus and the common toad Bufo bufo.", "output": "There is no related enetity." }, { "input": "In addition, gill morphology of tadpoles of both species after acute exposure to hypertonic conditions ( 20 %, 25 %, and 30 % SW ) was examined by light and electron microscopy.", "output": "There is no related enetity." }, { "input": "Tadpoles experienced 100 % mortality above 20 % SW in B. balearicus while above 15 % SW in B. bufo.", "output": "There is no related enetity." }, { "input": "We detected also sublethal effects of salinity stress on growth and metamorphosis.", "output": "There is no related enetity." }, { "input": "B. bufo cannot withstand chronic exposure to salinity above 5 % SW, tadpoles grew slower and were significantly smaller than those in control at metamorphosis.", "output": "There is no related enetity." }, { "input": "B. balearicus tolerated salinity up to 20 % SW without apparent effects during larval development, but starting from 15 % SW tadpoles metamorphosed later and at a smaller size compared with control.", "output": "There is no related enetity." }, { "input": "We also revealed a negative relation between increasing salt concentration and gill integrity.", "output": "There is no related enetity." }, { "input": "The main modifications were increased mucous secretion, detachment of external layer, alteration of epithelial surface, degeneration phenomena, appearance of residual bodies, and macrophage immigration.", "output": "There is no related enetity." }, { "input": "These morphological alterations of gill epithelium can interfere with respiratory function and both osmotic and acid - base regulation.", "output": "There is no related enetity." }, { "input": "Significant variations in branchial Na ( + ) / K ( + ) - ATPase activity were also observed between two species; moreover an increase in enzyme activity was evident in response to SW exposure.", "output": "Na ( + ), K ( + )." }, { "input": "Epithelial responses to increasing salt concentration were different in the populations belonging to two species: the intensity of histological and ultrastructural pathology in B. bufo was greater and we noticed the appearance in exposed samples of the tubular vesicle cells ( TVCs ).", "output": "There is no related enetity." }, { "input": "Taken together, our results demonstrated that increased salinity of freshwater may give cause for concern and must be considered a stressor for amphibians as well as other pollutants.", "output": "There is no related enetity." }, { "input": "Evaluation of some selected blood parameters and histopathology of liver and kidney of rats fed protein - substituted mucuna flour and derived protein rich product.", "output": "There is no related enetity." }, { "input": "This comparative study reports the nutritional and toxicological characteristics of Mucuna pruriens flour and a protein - rich product developed from it.", "output": "There is no related enetity." }, { "input": "The protein - rich mucuna product ( PRMP ) was obtained by the three steps procedure: protein solubilization, heat - coagulation and sieving.", "output": "There is no related enetity." }, { "input": "Three weeks rats ( n = 6 per group ) were fed for 28days on standard protein - substituted rat feed with mucuna flour or PRMP.", "output": "There is no related enetity." }, { "input": "The experimental design was a factorial design with three mucuna accessions ( Velvet, Black and White ) and two treatments ( flour and PRMP ).", "output": "There is no related enetity." }, { "input": "The protein content ranged 27. 2 - 31. 5g / 100g for flour and 58. 8 - 61. 1 % for PRMP.", "output": "There is no related enetity." }, { "input": "Processing flour into PRMP led to a significant ( p < 0. 05 ) reduction of tannins ( 50 % ), total polyphenols ( 50 % ) and trypsin inhibitors ( 94 % ).", "output": "tannins, polyphenols." }, { "input": "The rats fed PMRP diets witnessed weight gain similar to casein, while those fed mucuna flour lost weight.", "output": "There is no related enetity." }, { "input": "The levels of total cholesterol, HDL - cholesterol and LDL - cholesterol observed in animals groups fed mucuna flour and PRMP were significantly lower ( p < 0. 05 ) than the control group.", "output": "cholesterol, cholesterol, cholesterol." }, { "input": "In addition lymphocytes, granulocytes, red blood cells, hemoglobin and hematocrit of rats fed mucuna flour were significantly ( p < 0. 05 ) lower than values in other rats groups.", "output": "There is no related enetity." }, { "input": "Kidneys glomerular sclerosis and high creatinine levels were observed in group fed mucuna flour.", "output": "creatinine." }, { "input": "PRMP then represents a good alternative of using mucuna proteins for human nutrition.", "output": "There is no related enetity." }, { "input": "Structure - property relationship for cellular accumulation of macrolones in human polymorphonuclear leukocytes ( PMNs ).", "output": "macrolones." }, { "input": "Macrolones are a new class of antimicrobial compounds consisting of a macrolide scaffold linked to a 4 - quinolone - 3 - carboxylic acid moiety via C ( 4 '' ) position of a macrolide.", "output": "Macrolones, macrolide, 4 - quinolone - 3 - carboxylic acid, C, macrolide." }, { "input": "As macrolides are known to possess favorable pharmacokinetic properties by accumulating in inflammatory cells, in this study we determined the intensity of accumulation in human polymorphonuclear leukocytes ( PMNs ) of 57 compounds of the macrolone class and analyzed the relationship between the molecular structure and this cellular pharmacokinetic property.", "output": "macrolides, macrolone." }, { "input": "Accumulation of macrolones ranged from 0 to 5. 5 - fold higher than the standard macrolide azithromycin.", "output": "macrolones, macrolide, azithromycin." }, { "input": "Distinct structural features in all three considered molecule parts: the macrolide scaffold, quinolone moiety and the linker, affect cellular accumulation.", "output": "macrolide, quinolone." }, { "input": "Interestingly, while the parent macrolide, azithromycin, accumulates approximately 3 - fold more than clarithromycin, among macrolones all clarithromycin derivatives accumulated in PMNs significantly more than their azithromycin counterparts.", "output": "macrolide, azithromycin, clarithromycin, macrolones, clarithromycin, azithromycin." }, { "input": "Modeling cellular accumulation of macrolones with simple molecular descriptors, as well as with the measured octanol - water distribution coefficient, revealed that the number of hydrogen bond donors and secondary amide groups negatively contribute to macrolone accumulation, while lipophilicity makes a positive contribution.", "output": "macrolones, octanol, hydrogen, secondary amide, macrolone." }, { "input": "Assessing vehicle effects on skin absorption using artificial membrane assays.", "output": "There is no related enetity." }, { "input": "A vast number of variations in drug / vehicle combinations may come into contact with skin.", "output": "There is no related enetity." }, { "input": "Evaluating the effect of potential drug, vehicle and skin interactions for all possible combinations is a daunting task.", "output": "There is no related enetity." }, { "input": "A practical solution is a rapid screening technique amenable to high throughput approaches ( e. g. 96 - well plates ).", "output": "There is no related enetity." }, { "input": "In this study, three artificial membranes ( isopropyl myristate ( IPM ), certramides and Strat - M (TM) ) were evaluated for their ability to predict the skin permeability of caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid and testosterone applied in propylene glycol, water and ethanol as unsaturated and saturated concentrations.", "output": "isopropyl myristate, IPM, certramides, caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid, testosterone, propylene glycol, ethanol." }, { "input": "Resultant absorption data was compared to porcine skin diffusion cell data.", "output": "There is no related enetity." }, { "input": "The correlations ( r ( 2 ) ) between membrane and diffusion cell data from saturated and unsaturated concentrations were 0. 38, 0. 47 and 0. 56 for the Strat - M (TM), certramide and IPM membranes, respectively.", "output": "certramide, IPM." }, { "input": "This relationship improved when only saturated concentrations were evaluated ( r ( 2 ) = 0. 60, 0. 63 and 0. 66 for the Strat - M (TM), certramide and IPM membranes, respectively ).", "output": "certramide, IPM." }, { "input": "A correlation between membrane retention and the amount remaining in skin had r ( 2 ) values of 0. 73 ( Strat - M (TM) ), 0. 67 ( certramides ), and 0. 67 ( IPM ).", "output": "certramides, IPM." }, { "input": "Quantitative structure - permeability relationship models for each membrane identified different physicochemical factors influencing the absorption process.", "output": "There is no related enetity." }, { "input": "Although further investigations exploring complex topical formulations are required, these results suggest potential use as an initial screening approach to assist in narrowing the selection of formulations to be evaluated with a more biologically intact model, thereby assisting in the development of new topical formulations.", "output": "There is no related enetity." }, { "input": "Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: Implications in the treatment of chronic obstructive airway pathologies.", "output": "simvastatin." }, { "input": "BACKGROUND: Chronic obstructive pulmonary disease ( COPD ) is characterised by mucus hyper - production.", "output": "There is no related enetity." }, { "input": "This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications.", "output": "There is no related enetity." }, { "input": "Newer therapeutic approaches are of increased interest, including the use of HMG - CoA reductase inhibitors.", "output": "HMG - CoA." }, { "input": "Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels.", "output": "statins." }, { "input": "These findings suggest statins may also provide a new therapeutic approach in COPD treatment.", "output": "statins." }, { "input": "PURPOSE: The aim of the present work was to study the transport of SV across Calu - 3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production.", "output": "There is no related enetity." }, { "input": "METHODS: Calu - 3 cells were grown under liquid covered culture ( LCC ) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer.", "output": "There is no related enetity." }, { "input": "For mucus detection, cells were grown under air interface culture ( AIC ) conditions.", "output": "There is no related enetity." }, { "input": "Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio.", "output": "alcian blue." }, { "input": "RESULTS: SV was transported through the cell monolayer and ' retained ' inside the Calu - 3 cells.", "output": "There is no related enetity." }, { "input": "Colour analysis of stained Calu - 3 monolayers microscope - images showed that chronic administration of SV for 14days caused a significant inhibition in mucus production.", "output": "There is no related enetity." }, { "input": "CONCLUSION: These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.", "output": "There is no related enetity." }, { "input": "Novel 5 - ( benzyloxy ) pyridin - 2 ( 1H ) - one derivatives as potent c - Met inhibitors.", "output": "5 - ( benzyloxy ) pyridin - 2 ( 1H ) - one." }, { "input": "A series of novel 5 - ( benzyloxy ) pyridin - 2 ( 1H ) - ones were designed, synthesized and biologically evaluated for c - Met inhibition.", "output": "5 - ( benzyloxy ) pyridin - 2 ( 1H ) - ones." }, { "input": "Various amides and benzoimidazoles at C - 3 position were investigated.", "output": "amides, benzoimidazoles." }, { "input": "A potent compound 12b with a c - Met IC50 of 12nM was identified.", "output": "There is no related enetity." }, { "input": "This compound exhibited potent inhibition of EBC - 1 cell associated with c - Met constitutive activation and showed high selectivity for c - Met than other tested 11 kinases.", "output": "There is no related enetity." }, { "input": "The binding model 12b with c - Met was disclosed by docking analysis.", "output": "There is no related enetity." }, { "input": "Transcriptional cooperation between p53 and NF - kappa B p65 regulates microRNA - 224 transcription in mouse ovarian granulosa cells.", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs ) have been indicated to play key roles in ovarian follicular development.", "output": "There is no related enetity." }, { "input": "However, little is known about how the miRNA gene expression itself is regulated in the mammalian ovary.", "output": "There is no related enetity." }, { "input": "We previously reported that miR - 224 is involved in TGF - beta 1 - mediated follicular granulosa cell ( GC ) growth and estradiol ( E2 ) production by targeting Smad4.", "output": "estradiol." }, { "input": "Here, the transcriptional regulation of miR - 224 expression in GCs was further investigated.", "output": "There is no related enetity." }, { "input": "Our results showed that both the tumor suppressor gene p53 and NF - kappa B p65 subunit suppressed the TGF - beta 1 - induced increase in pri - miR - 224 expression in GCs.", "output": "There is no related enetity." }, { "input": "ChIP assays demonstrated that TGF - beta 1 enhanced the binding of p53 and p65 to the proximal promoter region of GABAA receptor epsilon subunit ( miR - 224 host gene ).", "output": "There is no related enetity." }, { "input": "p53 and p65 transcriptionally cooperated to inactivate the GABAA receptor epsilon subunit promoter.", "output": "There is no related enetity." }, { "input": "In addition, p53 / p65 could up - regulate Smad4 expression by inhibiting its target miR - 224 in GCs which contributed, at least partially, to the effects of miR - 224 and Smad4 on GC proliferation and E2 release.", "output": "There is no related enetity." }, { "input": "Our results provide new data about the interplay between transcription factors involved in GC proliferation and function by cooperatively regulating miRNA expression.", "output": "There is no related enetity." }, { "input": "Inverted CdSe / CdS / ZnS quantum dot light emitting devices with titanium dioxide as an electron - injection contact.", "output": "CdSe, CdS, ZnS, titanium dioxide." }, { "input": "We demonstrated the fabrication of inverted CdSe / CdS / ZnS quantum dot light emitting devices ( QD - LEDs ) using titanium dioxide ( TiO2 ) as an electron - injection layer and investigated the operating mechanism by utilizing different hole - transport materials, 4, 4 - N, N - dicarbazole - biphenyl ( CBP ) and 4, 4 ', 4 ' ' - tris ( carbazol - 9 - yl ) - triphenylamine ( TCTA ).", "output": "CdSe, CdS, ZnS, titanium dioxide, TiO2, 4 , 4 - N , N - dicarbazole - biphenyl, CBP, 4 , 4 ' , 4 ' ' - tris ( carbazol - 9 - yl ) - triphenylamine, TCTA." }, { "input": "A more efficient device with CBP as the hole - transport layer ( HTL ) was obtained compared with the TCTA based device.", "output": "TCTA." }, { "input": "The peak efficiency of 6. 70 cd A ( - 1 ) for the CBP based device was found to be about 74. 5 % higher than the TCTA based device ( 3. 84 cd A ( - 1 ) ).", "output": "TCTA." }, { "input": "The studies on the time - resolved photoluminescence spectra of the QD - HTL composite structures showed that the energy transfer ( ET ) efficiencies from the two HTLs to the QD layer were similar and the charge separation between QDs and HTLs could be neglected.", "output": "There is no related enetity." }, { "input": "The enhancement in the performance of the CBP based device was attributed to the more efficient hole - injection from CBP to QDs.", "output": "There is no related enetity." }, { "input": "Nitrogen doped holey graphene as an efficient metal - free multifunctional electrochemical catalyst for hydrazine oxidation and oxygen reduction.", "output": "Nitrogen, graphene, hydrazine, oxygen." }, { "input": "Electrocatalysts for anode or cathode reactions are at the heart of electrochemical energy conversion and storage devices.", "output": "There is no related enetity." }, { "input": "Molecular design of carbon based nanomaterials may create the next generation electrochemical catalysts for broad applications.", "output": "carbon." }, { "input": "Herein, we present the synthesis of a three - dimensional ( 3D ) nanostructure with a large surface area ( 784 m ( 2 ) g ( - 1 ) ) composed of nitrogen doped ( up to 8. 6 at. % ) holey graphene.", "output": "nitrogen, graphene." }, { "input": "The holey structure of graphene sheets ( ~ 25 % of surface area is attributed to pores ) engenders more exposed catalytic active edge sites.", "output": "graphene." }, { "input": "Nitrogen doping further improves catalytic activity, while the formation of the 3D porous nanostructure significantly reduces graphene nanosheet stacking and facilitates the diffusion of reactants / electrolytes.", "output": "Nitrogen, graphene." }, { "input": "The three factors work together, leading to superb electrochemical catalytic activities for both hydrazine oxidation ( its current generation ability is comparable to that of 10 wt % Pt - C catalyst ) and oxygen reduction ( its limiting current is comparable to that of 20 wt % Pt - C catalyst ) with four - electron transfer processes and excellent durability.", "output": "hydrazine, Pt, C, oxygen, Pt, C." }, { "input": "Synthesis, in vitro antitumor evaluation and DNA - binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems.", "output": "tetrahydroquinolines." }, { "input": "The synthesis of some new tetrahydroquinolines, tetrahydropyrimido [ 4, 5 - b ] quinolines, and tetrahydropentaazacyclopenta [ a ] anthracenes structurally related to some DNA intercalators is described.", "output": "tetrahydroquinolines, tetrahydropyrimido [ 4 , 5 - b ] quinolines, tetrahydropentaazacyclopenta [ a ] anthracenes." }, { "input": "Fifteen compounds were evaluated for their antitumor activity by the National Cancer Institute ( NCI ), in vitro disease oriented antitumor screening.", "output": "There is no related enetity." }, { "input": "The most active tricyclic pyrimido [ 4, 5 - b ] quinolines 3b, 6b, 7b and 8b were further subjected to DNA - binding investigation in an attempt to rationalize their activity.", "output": "tricyclic pyrimido [ 4 , 5 - b ] quinolines." }, { "input": "Compound 8b proved to be the most active member in this study as evidenced from its remarkable growth inhibitory potential against some individual cell lines, and its broad spectrum of antitumor activity ( GI50, TGI and LC50 values 46. 9, 85. 3 and 97. 4, respectively ), together with a good DNA - binding affinity.", "output": "There is no related enetity." }, { "input": "Energetic contribution to hydration shells in one - dimensional aqueous electrolyte solution by anomalous hydrogen bonds.", "output": "hydrogen." }, { "input": "The hydration structure of NaCl aqueous solution was elucidated in carbon nanotubes ( CNTs ) on the basis of canonical ensemble Monte Carlo simulations.", "output": "NaCl, carbon." }, { "input": "Hydration shells were preferentially formed even in narrow CNTs to gain stabilization energy, whereas hydrogen bonding between water molecules in such CNTs was sacrificed.", "output": "hydrogen." }, { "input": "Nanoscale - confined aqueous electrolyte solutions therefore prioritize hydration shell formation between ions and water rather than hydrogen - bond formation between water molecules.", "output": "hydrogen." }, { "input": "Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.", "output": "There is no related enetity." }, { "input": "Background: New cosmetic applications and products based on the effects of botulinum toxin ( BTX ) treatment have stimulated demand for this class of natural compounds.", "output": "There is no related enetity." }, { "input": "This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Objectives: Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A ( BTX - A ) preparations on neuromuscular transmission through split - body test. Methods: The effectiveness was evaluated in terms of the compound muscle action potential ( CMAP ) and conduction velocity after BTX - A injection.", "output": "There is no related enetity." }, { "input": "We used a split - body method to compare two different BTX - As in the rat. Results: Based on the changes in the CMAP, the two different BTX - As induced paralytic effect on the rat tibialis anterior muscle.", "output": "There is no related enetity." }, { "input": "However, the two different BTX - A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. Conclusions: The new BTX - A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX - A. [ AQ: Please approve the edits made to the sentence \" The new BTX - A preparation ... \" ) We propose that a split - body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.", "output": "There is no related enetity." }, { "input": "Generation and characterization of fully human monoclonal antibodies against human orai1 for autoimmune disease.", "output": "There is no related enetity." }, { "input": "Calcium entry into T cells following antigen stimulation is crucial for nuclear factor of activated T cells ( NFAT ) - mediated T cell activation.", "output": "Calcium." }, { "input": "The movement of calcium is mediated by calcium release - activated calcium ( CRAC ) channels.", "output": "calcium, calcium, calcium." }, { "input": "There are two key components of this channel: Orai1 is the pore - forming subunit located in the plasma membrane, and stromal interaction molecule 1 ( STIM1 ) functions as a Ca ( 2 + ) sensor in the endoplasmic reticulum.", "output": "Ca ( 2 + )." }, { "input": "A subset of human patients carry mutations in either STIM1 or Orai1 that affect protein function or expression, resulting in defective store - operated Ca ( 2 + ) influx and CRAC channel function, and impaired T cell activation.", "output": "Ca ( 2 + )." }, { "input": "These patients suffer from a hereditary form of severe combined immune deficiency syndrome, highlighting the importance of the CRAC channel for T lymphocyte function in humans.", "output": "There is no related enetity." }, { "input": "Since autoreactive T cells play an important role in the development of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and organ transplantation, Orai1 becomes an attractive therapeutic target for ameliorating autoimmune disease.", "output": "There is no related enetity." }, { "input": "We developed a novel approach to inhibiting CRAC function by generating high - affinity fully human monoclonal antibodies to human Orai1.", "output": "There is no related enetity." }, { "input": "These antibodies inhibited ICRAC current, store - operated Ca ( 2 + ) influx, NFAT transcription, and cytokine release.", "output": "Ca ( 2 + )." }, { "input": "These fully human antibodies to human Orai1 may represent a novel therapeutic approach for the treatment of autoimmunity.", "output": "There is no related enetity." }, { "input": "Binding Preference of Carbon Nanotube Over Proline - Rich Motif Ligand on SH3 - Domain: A Comparison with Different Force Fields.", "output": "Carbon, Proline." }, { "input": "With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins.", "output": "carbon." }, { "input": "In molecular simulations of nanoparticle - protein interactions, the choice of empirical parameters ( force fields ) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications.", "output": "There is no related enetity." }, { "input": "Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube ( SWCNT ) with a native proline - rich motif ( PRM ) ligand on its target protein SH3 domain, a ubiquitous protein - protein interaction mediator involved in signaling and regulatory pathways.", "output": "proline." }, { "input": "We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference.", "output": "There is no related enetity." }, { "input": "The SWCNT prevents the ligand from reaching its native binding pocket by ( i ) occupying the binding pocket directly, and ( ii ) binding with the ligand itself and then being trapped together onto some off - sites.", "output": "There is no related enetity." }, { "input": "The pi - pi stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields.", "output": "There is no related enetity." }, { "input": "Further analyses show that even the SWCNT - ligand binding can also be relatively more stable than the native ligand - protein binding, indicating a serious potential disruption to the protein SH3 function.", "output": "There is no related enetity." }, { "input": "Follicular Variant of Papillary Thyroid Carcinoma is a Unique Clinical Entity: A Population - Based Study of 10, 740 Cases.", "output": "There is no related enetity." }, { "input": "Background: Follicular variant of papillary thyroid carcinoma ( FV - PTC ) has been increasingly diagnosed in recent years.", "output": "There is no related enetity." }, { "input": "However, little is known about its clinical behavior.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to determine the disease characteristics of FV - PTC, and to compare it with classical papillary thyroid carcinoma ( C - PTC ) and follicular thyroid carcinoma ( FTC ).", "output": "There is no related enetity." }, { "input": "Methods: All cases of C - PTC, FV - PTC and FTC larger than 1 cm in the Surveillance, Epidemiology and End Results ( SEER ) Cancer Database from 1988 to 2007 were identified.", "output": "There is no related enetity." }, { "input": "Tumor behavior and patient survival were compared among these three groups.", "output": "There is no related enetity." }, { "input": "Different risk factors for disease - specific mortality in each group were evaluated by multivariate analysis.", "output": "There is no related enetity." }, { "input": "Results: A total over 36, 000 surgical cases were identified including 21, 796 C - PTCs, 10, 740 FV - PTCs and 3, 958 FTCs.", "output": "There is no related enetity." }, { "input": "Extrathyroidal extension and lymph node metastases were more common in FV - PTC than in FTC, but significantly less common than in C - PTC ( p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Distant metastasis rate were present in 2 % of patients with FV - PTC, 1 % in C - PTC and 4 % in FTC ( p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "The 10 - year disease - specific survival for patients with FV - PTC was 98 %, similar to C - PTC ( 97 % ), but better than FTC ( 94 %, p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Age greater than 45 years remained a strong risk factor for disease - specific mortality in both FV - PTC and C - PTC, while the presence of extrathyroidal extension and distant metastases were stronger predictors of disease - specific mortality in FV - PTC than in C - PTC.", "output": "There is no related enetity." }, { "input": "Conclusions: FV - PTC is a common variant of PTC.", "output": "There is no related enetity." }, { "input": "Its clinical behavior is unique and represents an intermediate entity with clinical features that are between C - PTC and FTC.", "output": "There is no related enetity." }, { "input": "Interestingly, despite the variations in clinical behavior, the long - term outcome of these patients remains excellent and similar to C - PTC.", "output": "There is no related enetity." }, { "input": "Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin - 1 Analogues as Extremely Potent mu - Opioid Agonists.", "output": "Endomorphin - 1." }, { "input": "Recently we reported the synthesis and structure - activity study of endomorphin - 1 ( EM - 1 ) analogues containing novel, unnatural alpha - methylene - beta - aminopropanoic acids ( Map ).", "output": "endomorphin - 1, EM - 1, alpha - methylene - beta - aminopropanoic acids, Map." }, { "input": "In the present study, we describe new EM - 1 analogues containing Dmt ( 1 ), ( R / S ) - beta Pro ( 2 ), and ( ph ) Map ( 4 ) / ( 2 - furyl ) Map ( 4 ).", "output": "EM - 1, Dmt, ( R / S ) - beta Pro, ( ph ) Map, ( 2 - furyl ) Map." }, { "input": "All of the analogues showed a high affinity for the mu - opioid receptor ( MOR ) and increased stability in mouse brain homogenates.", "output": "There is no related enetity." }, { "input": "Of the new compounds, Dmt ( 1 ) - ( R ) - beta Pro ( 2 ) - Trp ( 3 ) - ( 2 - furyl ) Map ( 4 ) ( analogue 12 ) displayed the highest affinity toward MOR, in the picomolar range ( Ki ( mu ) = 3. 72 pM ).", "output": "Dmt, ( R ) - beta Pro, Trp, ( 2 - furyl ) Map." }, { "input": "Forskolin - induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range ( EC50 = 0. 0421 pM, Emax = 99. 5 % ).", "output": "Forskolin, cAMP." }, { "input": "This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail - flick test, which indicates that this analogue was able to cross the blood - brain barrier.", "output": "morphine." }, { "input": "Isocoumarin Derivatives and Benzofurans from a Sponge - Derived Penicillium sp.", "output": "Isocoumarin, Benzofurans." }, { "input": "Fungus.", "output": "There is no related enetity." }, { "input": "Ten new fungal metabolites, including three hydroisocoumarins, penicimarins A - C ( 1 - 3 ), three isocoumarins, penicimarins D - F ( 6 - 8 ), and four benzofurans, penicifurans A - D ( 11 - 14 ), together with four known isocoumarin derivatives ( 4, 5, 9, 10 ), were obtained from the sponge - derived fungus Penicillium sp.", "output": "hydroisocoumarins, penicimarins A - C, isocoumarins, penicimarins D - F, benzofurans, penicifurans A - D, isocoumarin." }, { "input": "MWZ14 - 4, collected from the South China Sea.", "output": "There is no related enetity." }, { "input": "Their planar structures and relative configurations were elucidated by detailed analysis of spectroscopic data and by comparison with related known compounds.", "output": "There is no related enetity." }, { "input": "The absolute configurations of 1 - 4 were assigned by the modified Mosher ' s method and TDDFT ECD calculations together with comparison of their CD spectra.", "output": "There is no related enetity." }, { "input": "Compound 1 represents a rare naturally occurring isocoumarin derivative with 4 - substitution, but no substituent at the 3 - position.", "output": "isocoumarin." }, { "input": "These compounds were evaluated for antibacterial activities and cytotoxic activities in vitro.", "output": "There is no related enetity." }, { "input": "Among them, penicifuran A ( 11 ) exhibited inhibitory activity against Staphylococcus albus with an MIC value of 3. 13 mu M.", "output": "penicifuran A." }, { "input": "Comparison of the inhibitory effect against copper ion - induced oxidation in rat plasma after oral administration of salvianolic acid B and its decocted solutions.", "output": "copper, salvianolic acid B." }, { "input": "The effects of salvianolic acid B ( Sal B ) decoction on antioxidative activities were evaluated.", "output": "salvianolic acid B, Sal B." }, { "input": "The 2, 2 - diphenyl - 1 - picrylhydrazyl ( DPPH ) radical - scavenging activity, Fe ( 2 + ) - chelating activity, reducing power, and total phenolic content of the Sal B - decocted solutions did not change significantly after decoction in an aqueous solution.", "output": "2 , 2 - diphenyl - 1 - picrylhydrazyl, DPPH, Fe ( 2 + ), phenolic, Sal B." }, { "input": "However, the formation of cholesteryl ester hydroperoxide ( CE - OOH ) in rat blood plasma containing the Sal B - decocted solutions was more effectively inhibited than that of plasma containing the Sal B solution, regardless of the decoction time.", "output": "cholesteryl ester hydroperoxide, CE - OOH, Sal B, Sal B." }, { "input": "In addition, the accumulation of CE - OOH in rat plasma after oral administration of the Sal B - decocted solutions was more effectively suppressed than when the Sal B solution was administered, considering the lag time.", "output": "CE - OOH, Sal B, Sal B." }, { "input": "It is likely that the decoction was partly responsible for the increased antioxidant activity in blood plasma.", "output": "There is no related enetity." }, { "input": "Therefore, the Sal B - decocted solution may contribute more to antioxidant defense in blood than a Sal B solution that is not decocted.", "output": "Sal B, Sal B." }, { "input": "Cucurbitacin I inhibits rac1 activation in breast cancer cells by a reactive oxygen species - mediated mechanism and independently of janus tyrosine kinase 2 and p - rex1.", "output": "Cucurbitacin I, oxygen, tyrosine." }, { "input": "The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis.", "output": "There is no related enetity." }, { "input": "Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac - guanine nucleotide exchange factor P - Rex1.", "output": "guanine nucleotide." }, { "input": "As the Janus tyrosine kinase 2 ( Jak2 ) / signal transducer and activator of transcription 3 ( Stat3 ) pathway has been shown to be functionally associated with ErbB receptors, we asked if this pathway could mediate P - Rex1 / Rac1 activation in response to ErbB ligands.", "output": "tyrosine." }, { "input": "Here we found that the anticancer agent cucurbitacin I, a Jak2 inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells.", "output": "cucurbitacin I." }, { "input": "However, Rac1 activation was not affected by Jak2 or Stat3 RNA interference, suggesting that the effect of cucurbitacin I occurs through a Jak2 - independent mechanism.", "output": "cucurbitacin I." }, { "input": "Cucurbitacin I also failed to affect the activation of P - Rex1 by heregulin.", "output": "Cucurbitacin I." }, { "input": "Subsequent analysis revealed that cucurbitacin I strongly activates RhoA and the Rho effector Rho kinase ( ROCK ) in breast cancer cells and induces the formation of stress fibers.", "output": "cucurbitacin I." }, { "input": "Interestingly, disruption of the RhoA - ROCK pathway prevented the inhibitory effect of cucurbitacin I on Rac1 activation by heregulin.", "output": "cucurbitacin I." }, { "input": "Lastly, we found that RhoA activation by cucurbitacin I is mediated by reactive oxygen species ( ROS ).", "output": "cucurbitacin I, oxygen." }, { "input": "The ROS scavenger N - acetyl l - cysteine and the mitochondrial antioxidant Mito - TEMPO rescued the inhibitory effect of cucurbitacin I on Rac1 activation.", "output": "N - acetyl l - cysteine, cucurbitacin I." }, { "input": "In conclusion, these results indicate that ErbB - driven Rac1 activation in breast cancer cells proceeds independently of the Jak2 pathway.", "output": "There is no related enetity." }, { "input": "Moreover, they established that the inhibitory effect of cucurbitacin I on Rac1 activity involves the alteration of the balance between Rho and Rac.", "output": "cucurbitacin I." }, { "input": "Synthesis and in - silico studies of some diaryltriazole derivatives as potential cyclooxygenase inhibitors.", "output": "diaryltriazole." }, { "input": "The synthesis of several 4 - phenyl - 5 - pyridin - 4 - yl - 2, 3 - dihydro - 3H - 1, 2, 4 - triazole - 3 - thiones possessing N - 2 Mannich bases or S - alkyl substituents, is reported.", "output": "4 - phenyl - 5 - pyridin - 4 - yl - 2 , 3 - dihydro - 3H - 1 , 2 , 4 - triazole - 3 - thiones, Mannich bases, S - alkyl." }, { "input": "Several of them exhibited a low nanomolar COX enzyme inhibition activity.", "output": "There is no related enetity." }, { "input": "Most of the compounds showed inhibition of edema was similar to that evoked by celocoxib in animal model.", "output": "celocoxib." }, { "input": "Molecular docking studies of the compounds into the binding sites of COX - 1 and COX - 2 allowed us to shed light on the binding mode of these novel COX inhibitors.", "output": "There is no related enetity." }, { "input": "Antibacterial substances from Albizia myriophylla wood against cariogenic Streptococcus mutans.", "output": "There is no related enetity." }, { "input": "Albizia myriophylla has been used for long by Thai traditional healers as an important ingredient herb in Thai herbal formulas for caries.", "output": "There is no related enetity." }, { "input": "In this study, three flavonoids lupinifolin ( 6 ), 8 - methoxy - 7, 3 ', 4 ' - trihydroxyflavone ( 7 ), and 7, 8, 3 ', 4 ' - tetrahydroxyflavone ( 8 ), a triterpenoid lupeol ( 3 ) as well as four sterols beta - sitosterone ( 1 ), stigmasta - 5, 22 - dien - 3 - one ( 2 ), beta - sitosterol ( 4 ), and stigmasterol ( 5 ) were isolated from A. myriophylla wood.", "output": "lupinifolin, 8 - methoxy - 7 , 3 ' , 4 ' - trihydroxyflavone, 7 , 8 , 3 ' , 4 ' - tetrahydroxyflavone, triterpenoid, lupeol, sterols, beta - sitosterone, stigmasta - 5 , 22 - dien - 3 - one, beta - sitosterol, stigmasterol." }, { "input": "The antibacterial activity of these compounds against Streptococcus mutans ATCC 25175 was performed using broth microdilution method.", "output": "There is no related enetity." }, { "input": "All compounds exhibited antibacterial activity against S. mutans with minimum inhibitory concentration ( MIC ) and minimum bactericidal concentration ( MBC ) ranging from 1 - 256 and 2 - 256 mu g / ml, respectively.", "output": "There is no related enetity." }, { "input": "Among the isolated compounds, lupinifolin ( 6 ) was found to be the most potent with MIC and MBC of 1 and 2 mu g / ml, respectively.", "output": "lupinifolin." }, { "input": "Lupinifolin ( 6 ) also showed a strong activity against ten clinical isolates of S. mutans with MIC and MBC ranging from 0. 25 - 2 and 0. 5 - 8 mu g / ml, respectively.", "output": "Lupinifolin." }, { "input": "These results reported the bioactive ingredients of A. myriophylla which support its ethnomedical claims as well.", "output": "There is no related enetity." }, { "input": "Lupinifolin ( 6 ) may have a potential to be a natural anticariogenic agent.", "output": "Lupinifolin." }, { "input": "Association of cadmium and lead with antioxidant status and incidence of benign prostatic hyperplasia in patients of Western India.", "output": "cadmium." }, { "input": "The association of cadmium ( Cd ) and lead ( Pb ) in the pathophysiology and progression of benign prostate hyperplasia ( BPH ) has been evaluated in an epidemiological study with 116 BPH patients of the western part of India.", "output": "cadmium, Cd, Pb." }, { "input": "The prostatic acid phosphatase activity, prostate - specific antigen, maximum urinary flow rate ( Q max ), and redox status of BPH patients were correlated with Cd and Pb contents.", "output": "Cd, Pb." }, { "input": "Additionally, patients were also separated on the basis of their age, genetic lineage, and additive habits and correlated with the Cd, Pb, and Q max levels.", "output": "Cd, Pb." }, { "input": "Our results suggest that the accumulation of toxic metals in prostate tissue has a significant positive correlation with the pathogenesis of BPH.", "output": "There is no related enetity." }, { "input": "Cd and Pb exert their effects through altered antioxidant defense mechanisms, ultimately leading to increased BPH severity.", "output": "Cd, Pb." }, { "input": "Progression of the pathogenesis also depends on other factors such as additive habits, genetic lineage, and age of the patients.", "output": "There is no related enetity." }, { "input": "[ 6 ] - gingerol: a novel AT 1 antagonist for the treatment of cardiovascular disease.", "output": "[ 6 ] - gingerol." }, { "input": "Considering the prevalence of cardiovascular disease in public health and the limited validated therapeutic options, this study aimed to find novel compounds targeting the angiotensin II type 1 receptor, accepted as a therapeutic target in cardiovascular disease.", "output": "There is no related enetity." }, { "input": "A small library consisting of 89 compounds from 39 Chinese herbs was profiled using a cell - based calcium mobilization assay which was developed and characterized for high - throughput screening.", "output": "There is no related enetity." }, { "input": "[ 6 ] - Gingerol derived from Zingiber officinale Roscoe ( ginger ) was identified as a novel angiotensin II type 1 receptor antagonist, with an IC50 value of 8. 173 micro M.", "output": "[ 6 ] - Gingerol." }, { "input": "The hit was further tested by a specificity assay indicating that it had no antagonistic effects on other evaluated GPCRs, such as endothelin receptors.", "output": "There is no related enetity." }, { "input": "The major ingredient of ginger, [ 6 ] - gingerol, could inhibit angiotensin II type 1 receptor activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system.", "output": "[ 6 ] - gingerol." }, { "input": "Peltogynoids and 2 - Phenoxychromones from Peltophorum pterocarpum and Evaluation of Their Estrogenic Activity.", "output": "Peltogynoids, 2 - Phenoxychromones." }, { "input": "Phytochemical investigation of the dichloromethane extract of the leaves of Peltophorum pterocarpum, a tropical ornamental tree, led to the isolation of twelve compounds ( 1 - 12 ).", "output": "dichloromethane." }, { "input": "One new derivative of peltogynoid ophioglonin ( 1 ) and a new 2 - phenoxychromone ( 2 ) with its 3 ' - O - beta - D - glucoside derivative ( 3 ) are described here for the first time.", "output": "ophioglonin, 2 - phenoxychromone, 3 ' - O - beta - D - glucoside." }, { "input": "In addition, nine flavonoid derivatives, including peltogynoid ophioglonin ( 4 ), were isolated for the first time from this plant.", "output": "ophioglonin." }, { "input": "The structures were determined by spectroscopic and chemical methods.", "output": "There is no related enetity." }, { "input": "Evaluation of the estrogenic activities of 1, 2, and 4 using different model cell systems revealed that 4 was estrogenic and that 2 was largely inactive.", "output": "There is no related enetity." }, { "input": "Interestingly, 1 was unable to stimulate the proliferation of breast and endometrial cancer cells but exhibited substantial estrogen receptor alpha - mediated activation of gene expression.", "output": "estrogen." }, { "input": "This observation indicates that 1 can be further evaluated for its cancer chemopreventive potential.", "output": "There is no related enetity." }, { "input": "First - Line Management of EGFR - Mutated Advanced Lung Adenocarcinoma: Recent Developments.", "output": "There is no related enetity." }, { "input": "Gefitinib and erlotinib are small - molecule reversible tyrosine kinase inhibitors ( TKIs ) of epidermal growth factor receptor ( EGFR ).", "output": "Gefitinib, erlotinib, tyrosine." }, { "input": "Objective responses have been observed frequently in patients with non - small cell lung cancer ( NSCLC ) harbouring activating EGFR mutations, the most common being deletions in exon 19 and the exon 21 L858R mutation.", "output": "There is no related enetity." }, { "input": "EGFR mutations are prevalent in female patients, those who have never smoked, those of Asian ethnicity and those who have adenocarcinoma histology.", "output": "There is no related enetity." }, { "input": "Given the efficacy of EGFR TKIs in advanced NSCLC in the salvage setting, and their favourable toxicity profile compared with conventional chemotherapy, there is considerable interest in evaluating their efficacy in the first - line treatment of advanced NSCLC.", "output": "There is no related enetity." }, { "input": "To date, there have been several phase II and phase III studies that have examined the efficacy of first - line single - agent EGFR TKIs in unselected, clinically selected or molecularly selected populations.", "output": "There is no related enetity." }, { "input": "Here we review and compare the differences in these phase III trials.", "output": "There is no related enetity." }, { "input": "Most phase III trials chose progression - free survival ( PFS ) rather than overall survival ( OS ) as their primary endpoint.", "output": "There is no related enetity." }, { "input": "PFS was prolonged but OS was not.", "output": "There is no related enetity." }, { "input": "The recent development of novel irreversible EGFR TKIs, such as afatinib and dacomitinib, is also reviewed.", "output": "afatinib, dacomitinib." }, { "input": "The 5 - hydroxytryptamine ( serotonin ) receptor 6 agonist EMD 386088 ameliorates ketamine - induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats.", "output": "5 - hydroxytryptamine, serotonin, EMD 386088, ketamine." }, { "input": "Preclinical data suggest that the 5 - hydroxytryptamine ( serotonin ) 6 ( 5 - HT6 ) receptor may be a potential target for the development of new therapies for treating cognitive dysfunctions in schizophrenia and other central nervous system disorders.", "output": "5 - hydroxytryptamine, serotonin." }, { "input": "Recent evidence indicates that not only blockade but also activation of 5 - HT6 receptors exerts procognitive effects.", "output": "There is no related enetity." }, { "input": "Nevertheless, little is known about the potential efficacy of 5 - HT6 receptor agonists in models of schizophrenia - like cognitive deficits.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to evaluate the effects of the 5 - HT6 receptor agonist, EMD 386088, on the ketamine - induced deficits in the attentional set - shifting task ( ASST ), novel object recognition ( NOR ) task and prepulse inhibition ( PPI ) task in rats.", "output": "EMD 386088, ketamine." }, { "input": "Acute administration of EMD 386088 ( 2. 5 and 5 mg / kg, intraperitoneally ) to Sprague - Dawley rats reversed the deficit in the ASST induced by repeated ketamine administration.", "output": "EMD 386088, ketamine." }, { "input": "Moreover, the ketamine - induced deficit in the NOR task was ameliorated by EMD 386088 at a dose of 5 mg / kg.", "output": "ketamine, EMD 386088." }, { "input": "However, in contrast to the antipsychotic drug clozapine, the 5 - HT6 agonist did not affect PPI disrupted by ketamine.", "output": "clozapine, ketamine." }, { "input": "The present study demonstrated the beneficial effects of the 5 - HT6 agonist in ameliorating some of the ketamine - induced deficits relevant to schizophrenia.", "output": "ketamine." }, { "input": "It thus seems likely that the 5 - HT6 receptor activation may represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder.", "output": "There is no related enetity." }, { "input": "Multilevel regulation of 2 - cys peroxiredoxin reaction cycle by s - nitrosylation.", "output": "cys." }, { "input": "S - Nitrosothiols ( SNOs ), formed by nitric oxide ( NO ) - mediated S - nitrosylation, and hydrogen peroxide ( H2O2 ), a prominent reactive oxygen species, are implicated in diverse physiological and pathological processes.", "output": "S - Nitrosothiols, SNOs, nitric oxide, NO, S, hydrogen peroxide, H2O2, oxygen." }, { "input": "Recent research has shown that the cellular action and metabolism of SNOs and H2O2 involve overlapping, thiol - based mechanisms, but how these reactive species may affect each other ' s fate and function is not well understood.", "output": "SNOs, H2O2, thiol." }, { "input": "In this study we investigated how NO / SNO may affect the redox cycle of mammalian peroxiredoxin - 1 ( Prx1 ), a representative of the 2 - Cys Prxs, a group of thioredoxin ( Trx ) - dependent peroxidases.", "output": "NO, SNO, Cys." }, { "input": "We found that, both in a cell - free system and in cells, NO / SNO donors such as S - nitrosocysteine and S - nitrosoglutathione readily induced the S - nitrosylation of Prx1, causing structural and functional alterations.", "output": "NO, SNO, S - nitrosocysteine, S - nitrosoglutathione, S." }, { "input": "In particular, nitrosylation promoted disulfide formation involving the pair of catalytic cysteines ( Cys - 52 and Cys - 173 ) and disrupted the oligomeric structure of Prx1, leading to loss of peroxidase activity.", "output": "disulfide, cysteines, Cys, Cys." }, { "input": "A highly potent inhibition of the peroxidase catalytic reaction by NO / SNO was seen in assays employing the coupled Prx - Trx system.", "output": "NO, SNO." }, { "input": "In this setting, S - nitrosocysteine ( 10 mu m ) effectively blocked the Trx - mediated regeneration of oxidized Prx1.", "output": "S - nitrosocysteine." }, { "input": "This effect appeared to be due to both competition between S - nitrosocysteine and Prx1 for the Trx system and direct modulation by S - nitrosocysteine of Trx reductase activity.", "output": "S - nitrosocysteine, S - nitrosocysteine." }, { "input": "Our findings that NO / SNO target both Prx and Trx reductase may have implications for understanding the impact of nitrosylation on cellular redox homeostasis.", "output": "NO, SNO." }, { "input": "Purification and sidewall functionalization of multiwalled carbon nanotubes and resulting bioactivity in two macrophage models.", "output": "carbon." }, { "input": "This study examined the consequences of surface carboxylation of multiwalled carbon nanotubes ( MWCNT ) on bioactivity.", "output": "carbon." }, { "input": "Since commercial raw MWCNT contain impurities that may affect their bioactivity, HCl refluxing was exploited to purify raw \" as - received \" MWCNT by removing the amorphous carbon layer on the MWCNT surface and reducing the metal impurities ( e. g. Ni ).", "output": "HCl, carbon, Ni." }, { "input": "The removal of amorphous carbon layer was confirmed by Raman spectroscopy and thermogravimetric analysis.", "output": "carbon." }, { "input": "Furthermore, the HCl - purified MWCNT provided more available reaction sites, leading to enhanced sidewall functionalization.", "output": "HCl." }, { "input": "The sidewall of HCl - purified MWCNT was further functionalized with the - COOH moiety by HNO ( 3 ) oxidation.", "output": "HCl, COOH, HNO ( 3 )." }, { "input": "This process resulted in four distinct MWCNT: raw, purified, - COOH - terminated raw MWCNT, and - COOH - terminated purified MWCNT.", "output": "COOH, COOH." }, { "input": "Freshly isolated alveolar macrophages from C57Bl / 6 mice were exposed to these nanomaterials to determine the effects of the surface chemistry on the bioactivity in terms of cell viability and inflammasome activation.", "output": "There is no related enetity." }, { "input": "Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase - 1.", "output": "There is no related enetity." }, { "input": "Purification reduced the cell toxicity and inflammasome activation slightly compared to raw MWCNT.", "output": "There is no related enetity." }, { "input": "In contrast, functionalization of MWCNT with the - COOH group dramatically reduced the cytotoxicity and inflammasome activation.", "output": "COOH." }, { "input": "Similar results were seen using THP - 1 cells supporting their potential use for high - throughput screening.", "output": "There is no related enetity." }, { "input": "This study demonstrated that the toxicity and bioactivity of MWCNT were diminished by removal of the Ni contamination and / or addition of - COOH groups to the sidewalls.", "output": "Ni, COOH." }, { "input": "Experimental and computational study of the interaction of novel colchicinoids with a recombinant human alpha I / beta I - tubulin heterodimer.", "output": "colchicinoids." }, { "input": "The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined.", "output": "colchicine, thiocolchicine." }, { "input": "Two methods were used for the determination of binding free energies.", "output": "There is no related enetity." }, { "input": "One is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations.", "output": "There is no related enetity." }, { "input": "The other method involved a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique.", "output": "There is no related enetity." }, { "input": "(c) 2013 John Wiley & Sons A / S.", "output": "There is no related enetity." }, { "input": "Polyallylamine functionalized palladium icosahedra: one - pot water - based synthesis and their superior electrocatalytic activity and ethanol tolerant ability in alkaline media.", "output": "Polyallylamine, palladium icosahedra, ethanol." }, { "input": "Polyallylamine ( PAH ) functionalized Pd icosahedra are synthesized through a simple, one - pot, seedless and hydrothermal growth method.", "output": "Polyallylamine, PAH, Pd icosahedra." }, { "input": "Herein, PAH is used efficiently as a complex - forming agent, capping agent, and facet - selective agent.", "output": "PAH." }, { "input": "The strong interaction between PAH and Pd atom sharply changes the electronic structure of Pd atom in the Pd icosahedra.", "output": "PAH, Pd, Pd, Pd icosahedra." }, { "input": "The protective function of PAH layers and enhanced antietching capability of Pd atom are responsible for the formation of the Pd icosahedra.", "output": "PAH, Pd, Pd icosahedra." }, { "input": "Very importantly, the as - prepared PAH functionalized Pd icosahedra exhibit superior electrocatalytic activity and ethanol tolerant ability toward the oxygen reduction reaction ( ORR ) compared to the commercially available Pt black in alkaline media.", "output": "PAH, Pd icosahedra, ethanol, oxygen, Pt black." }, { "input": "At 0. 95 V ( vs RHE ), the ORR specific kinetic current density at the Pd icosahedra is 4. 48 times higher than that at commercial Pt black.", "output": "Pd icosahedra, Pt black." }, { "input": "The fact demonstrates the appropriate surface modification of the Pd nanoparticles by nonmetallic molecules can be regarded as an effective way to enhance the electrocatalytic activity toward the ORR.", "output": "Pd." }, { "input": "Self - Assembling Multidomain Peptide Fibers with Aromatic Cores.", "output": "There is no related enetity." }, { "input": "Self - assembling multidomain peptides have been shown to have desirable properties, such as the ability to form hydrogels that rapidly recover following shear - thinning and the potential to be tailored by amino acid selection to vary their elasticity and encapsulate and deliver proteins and cells.", "output": "amino acid." }, { "input": "Here we describe the effects of substitution of aliphatic hydrophobic amino acids in the central domain of the peptide for the aromatic amino acids phenylalanine, tyrosine, and tryptophan.", "output": "amino acids, aromatic amino acids, phenylalanine, tyrosine, tryptophan." }, { "input": "While the basic nanofibrous morphology is retained in all cases, selection of the particular core residues results in switching from antiparallel hydrogen bonding to parallel hydrogen bonding in addition to changes in nanofiber morphology and in hydrogel rheological properties.", "output": "hydrogen, hydrogen." }, { "input": "Peptide nanofiber assemblies are investigated by circular dichroism polarimetry, infrared spectroscopy, atomic force microscopy, transmission and scanning electron microscopy, oscillatory rheology, and molecular dynamics simulations.", "output": "There is no related enetity." }, { "input": "Results from this study will aid in designing next generation cell scaffolding materials.", "output": "There is no related enetity." }, { "input": "Production and characterization of pellets using Avicel CL611 as spheronization aid.", "output": "There is no related enetity." }, { "input": "Abstract Purpose: The study looked into the feasibility of producing pellet using Avicel CL611 as spheronization aid by the extrusion / spheronization technique.", "output": "There is no related enetity." }, { "input": "Methods: Pellets were formulated to contain either 20 % or 40 % Avicel CL611 and lactose monohydrate as the other sole ingredient.", "output": "lactose monohydrate." }, { "input": "Water is used as liquid binder.", "output": "There is no related enetity." }, { "input": "Quality of pellets and extrudates were analyzed for size distribution, shape, surface tensile strength and disintegration profile.", "output": "There is no related enetity." }, { "input": "Results: More water was needed when higher Avicel CL611 fraction was used during the production of pellets.", "output": "There is no related enetity." }, { "input": "The pellets of larger size were obtained by increasing the water content.", "output": "There is no related enetity." }, { "input": "Pellets with aspect ratios of ~ 1. 1 were produced with high spheronization speed at short residence time.", "output": "There is no related enetity." }, { "input": "Higher tensile strength was achieved when increasing the water content and the fraction of Avicel CL611 during pellet production.", "output": "There is no related enetity." }, { "input": "These pellets also took longer time to disintegrate, nonetheless all the pellets disintegrated within 15 min.", "output": "There is no related enetity." }, { "input": "A positive linear relationship was obtained between the tensile strength and time for pellets to disintegrate.", "output": "There is no related enetity." }, { "input": "Conclusion: Strong but round pellets that disintegrate rapidly could be produced with Avicel CL611 as spheronization aid using moderately soluble compounds such as lactose.", "output": "lactose." }, { "input": "A Novel CUG ( exp ). MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1.", "output": "There is no related enetity." }, { "input": "Myotonic dystrophy type 1 ( DM1 ) is caused by an expanded CUG repeat ( CUG ( exp ) ) that sequesters muscleblind - like 1 protein ( MBNL1 ), a protein that regulates alternative splicing.", "output": "There is no related enetity." }, { "input": "CUG ( exp ) RNA is a validated drug target for this currently untreatable disease.", "output": "There is no related enetity." }, { "input": "Herein, we develop a bioactive small molecule ( 1 ) that targets CUG ( exp ) RNA and is able to inhibit the CUG ( exp ). MBNL1 interaction in cells that model DM1.", "output": "There is no related enetity." }, { "input": "The core of this small molecule is based on ligand 2, which was previously reported to be active in an in vitro assay.", "output": "There is no related enetity." }, { "input": "A polyamine - derivative side chain was conjugated to this core to make it aqueous - soluble and cell - penetrable.", "output": "polyamine." }, { "input": "In a DM1 cell model this conjugate was found to disperse CUG ( exp ) ribonuclear foci, release MBNL1, and partially reverse the mis - splicing of the insulin receptor pre - mRNA.", "output": "There is no related enetity." }, { "input": "Direct evidence for ribonuclear foci dispersion by this ligand was obtained in a live DM1 cell model using time - lapse confocal microscopy.", "output": "There is no related enetity." }, { "input": "Predicting ligand binding modes from neural networks trained on protein - ligand interaction fingerprints.", "output": "There is no related enetity." }, { "input": "We herewith present a novel approach to predict protein - ligand binding modes from the single two - dimensional structure of the ligand.", "output": "There is no related enetity." }, { "input": "Known protein - ligand X - ray structures were converted into binary bit strings encoding protein - ligand interactions.", "output": "There is no related enetity." }, { "input": "An artificial neural network was then set up to first learn and then predict protein - ligand interaction fingerprints from simple ligand descriptors.", "output": "There is no related enetity." }, { "input": "Specific models were constructed for three targets ( CDK2, p38 - alpha, HSP90 - alpha ) and 146 ligands for which protein - ligand X - ray structures are available.", "output": "There is no related enetity." }, { "input": "These models were able to predict protein - ligand interaction fingerprints and to discriminate important features from minor interactions.", "output": "There is no related enetity." }, { "input": "Predicted interaction fingerprints were successfully used as descriptors to discriminate true ligands from decoys by virtual screening.", "output": "There is no related enetity." }, { "input": "In some but not all cases, the predicted interaction fingerprints furthermore enable to efficiently rerank cross - docking poses and prioritize the best possible docking solutions.", "output": "There is no related enetity." }, { "input": "Are the intramolecular o - h... f and o - h... cl hydrogen bonds maintained in solution?", "output": "o - h, f, o - h, cl, hydrogen." }, { "input": "A theoretical study.", "output": "There is no related enetity." }, { "input": "The present case study aims at calculating the equilibrium conformer compositions for 2X - ethanol and 2X - phenol ( X = F, Cl ) in solution, and exploring the effect of the applied theoretical method and basis set on the obtained results, as well as considering the usefulness of the continuum solvent approach in comparison with the explicit solvent Monte Carlo model utilizing the free energy perturbation method.", "output": "ethanol, phenol, F, Cl." }, { "input": "Gas - phase optimizations at the DFT / B97D / aug - cc - pvtz and ab initio MP2 / aug - cc - pvtz levels predicted structures in good agreement with the available experimental data for three test molecules.", "output": "There is no related enetity." }, { "input": "Because in - solution geometries change only slightly according to the IEF - PCM continuum solvent calculations in carbon tetrachloride and water, the two theoretical levels were applied further on, and complete basis set ( CBS ) relative internal free energies were estimated for the conformers under study.", "output": "carbon tetrachloride." }, { "input": "The predicted OCCF gauche / trans ratio for 2F - ethanol was well reproduced in comparison with available experimental compositions.", "output": "OCCF, 2F - ethanol." }, { "input": "The predominant gauche structure maintains an intramolecular hydrogen bond in carbon tetrachloride ( HB structure ), whereas HB and NoHB gauche conformers appear in nearly the same fraction in aqueous solution.", "output": "hydrogen, carbon tetrachloride." }, { "input": "The internally hydrogen - bonded conformer is predominant also for 2X - phenol species, as calculated on the basis of relative CBS internal free energies and IEF - PCM and FEP / MC solvation free energies.", "output": "hydrogen, phenol." }, { "input": "Use of a trihydrate supermolecule model for 2F - ethanol conformers leads to the prediction of the aqueous - solution composition in contrast to the experiment.", "output": "trihydrate, 2F - ethanol." }, { "input": "Solution structure modeling predicts weak hydrogen - bond formation capacity for both the covalently bound F and Cl atoms, even in conformations where they are fully exposed to hydration.", "output": "hydrogen, F, Cl." }, { "input": "Effect of Solvent Polarity on the Vibrational Dephasing Dynamics of the Nitrosyl Stretch in an Fe ( II ) Complex Revealed by 2D IR Spectroscopy.", "output": "Nitrosyl, Fe ( II )." }, { "input": "The vibrational dephasing dynamics of the nitrosyl stretching vibration ( nu NO ) in sodium nitroprusside ( SNP, Na2 [ Fe ( CN ) 5NO ]. 2H2O ) are investigated using two - dimensional infrared ( 2D IR ) spectroscopy.", "output": "nitrosyl, NO, sodium nitroprusside, SNP, Na2 [ Fe ( CN ) 5NO ] . 2H2O." }, { "input": "The nu NO in SNP acts as a model system for the nitrosyl ligand found in metalloproteins which play an important role in the transportation and detection of nitric oxide ( NO ) in biological systems.", "output": "NO, SNP, nitrosyl, nitric oxide, NO." }, { "input": "We perform a 2D IR line shape study of the nu NO in the following solvents: water, deuterium oxide, methanol, ethanol, ethylene glycol, formamide, and dimethyl sulfoxide.", "output": "NO, deuterium oxide, methanol, ethanol, ethylene glycol, formamide, dimethyl sulfoxide." }, { "input": "The frequency of the nu NO exhibits a large vibrational solvatochromic shift of 52 cm ( - 1 ), ranging from 1884 cm ( - 1 ) in dimethyl sulfoxide to 1936 cm ( - 1 ) in water.", "output": "NO, dimethyl sulfoxide." }, { "input": "The vibrational anharmonicity of the nu NO varies from 21 to 28 cm ( - 1 ) in the solvents used in this study.", "output": "NO." }, { "input": "The frequency - frequency correlation functions ( FFCFs ) of the nu NO in SNP in each of the seven solvents are obtained by fitting the experimentally obtained 2D IR spectra using nonlinear response theory.", "output": "NO, SNP, 2D." }, { "input": "The fits to the 2D IR line shape reveal that the spectral diffusion time scale of the nu NO in SNP varies from 0. 8 to 4 ps and is negatively correlated with the empirical solvent polarity scales.", "output": "NO, SNP." }, { "input": "We compare our results with the experimentally determined FFCFs of other charged vibrational probes in polar solvents and in the active sites of heme proteins.", "output": "heme." }, { "input": "Our results suggest that the vibrational dephasing dynamics of the nu NO in SNP reflect the fluctuations of the nonhomogeneous electric field created by the polar solvents around the nitrosyl and cyanide ligands.", "output": "NO, SNP, nitrosyl, cyanide." }, { "input": "The solute solvent interactions occurring at the trans - CN ligand are sensed through the pi - back - bonding network along the Fe - NO bond in SNP.", "output": "trans - CN, Fe - NO, SNP." }, { "input": "Nicotinic acid conjugates of nonsteroidal anti - inflammatory drugs ( NSAID ' s ) and their anti - inflammatory properties.", "output": "Nicotinic acid." }, { "input": "A series of nicotinic acid conjugates with non - steroidal anti - inflammatory drugs ( NSAID ' s ) have been effectively synthesized using TBTU in high yield and purity.", "output": "nicotinic acid, TBTU." }, { "input": "All the synthesized conjugates were evaluated for their in vitro anti - inflammatory activity.", "output": "There is no related enetity." }, { "input": "Modulation of cellular insulin signaling and PTP1B effects by lipid metabolites in skeletal muscle cells.", "output": "There is no related enetity." }, { "input": "Normal glucose regulation is achieved by having adequate insulin secretion and effective glucose uptake / disposal.", "output": "glucose, glucose." }, { "input": "Excess lipids in peripheral tissues - skeletal muscle, liver and adipose tissue - may attenuate insulin signaling through the protein kinase B ( AKt ) pathway and up - regulate protein tyrosine phosphatase 1B ( PTP1B ), a negative regulator of insulin signaling.", "output": "tyrosine." }, { "input": "We studied accumulation of lipid metabolites [ triglycerides ( TAGs ), diglycerides ( DAGs ) ] and ceramides in relation to insulin signaling and expression and phosphorylation of PTP1B by preincubating rat skeletal muscle cells ( L6 myotubes ) with three saturated and three unsaturated free fatty acids ( FFAs ) ( 200 mu M ).", "output": "triglycerides, TAGs, diglycerides, DAGs, ceramides, fatty acids." }, { "input": "Cells were also evaluated in the presence of wortmannin, an inhibitor of phosphatidylinositol 3 - kinases and thus AKt ( 0 - 100 nM ).", "output": "wortmannin, phosphatidylinositol." }, { "input": "Unsaturated FFAs increased DAGs, TAGs and PTP1B expression significantly, but cells remained insulin sensitive as assessed by robust AKt and PTP1B phosphorylation at serine ( Ser ) 50, Ser 398 and tyrosine 152.", "output": "DAGs, TAGs, serine, Ser, Ser, tyrosine." }, { "input": "Saturated palmitic and stearic acids increased ceramides, up - regulated PTP1B, and had AKt and PTP1B phosphorylation at Ser 50 impaired.", "output": "palmitic and stearic acids, ceramides, Ser." }, { "input": "We show a significant correlation between phosphorylation levels of AKt and of PTP1B at Ser 50 ( R ( 2 ) = 0. 84, P <. 05 ).", "output": "There is no related enetity." }, { "input": "The same was observed with increasing wortmannin dose ( R ( 2 ) = 0. 73, P <. 05 ).", "output": "wortmannin." }, { "input": "Only FFAs that increased ceramides caused impairment of AKt and PTP1B phosphorylation at Ser 50.", "output": "ceramides, Ser." }, { "input": "PTP1B overexpression in the presence of excess lipids may not directly cause insulin resistance unless it is accompanied by decreased PTP1B phosphorylation.", "output": "There is no related enetity." }, { "input": "A clear relationship between PTP1B phosphorylation levels at Ser 50 and its negative effect on insulin signaling is shown.", "output": "Ser." }, { "input": "Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.", "output": "Aphanamgrandiol A, triterpenoid, carbon." }, { "input": "Aphanamgrandiol A ( 1 ), a novel triterpenoid with a bicyclo [ 3, 2, 1 ] octane ring skeleton produced by 2, 3 - ring opening and 2, 6 - ring closure, was isolated from the stems of Aphanamixis grandifolia.", "output": "Aphanamgrandiol A, triterpenoid, bicyclo [ 3 , 2 , 1 ] octane." }, { "input": "The structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and determined unambiguously by X - ray crystal diffraction.", "output": "There is no related enetity." }, { "input": "Aphanamgrandiol A showed moderate cytotoxicities against MCG - 803, SKOV - 3, HCT116 and HepG2 cell lines.", "output": "Aphanamgrandiol A." }, { "input": "N - substituted azaindoles as potent inhibitors of Cdc7 kinase.", "output": "N - substituted azaindoles." }, { "input": "Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy.", "output": "There is no related enetity." }, { "input": "We have identified a class of Cdc7 inhibitors based on a substituted indole core.", "output": "indole." }, { "input": "Synthesis of focused indole and azaindole analogs yielded potent and selective 5 - azaindole Cdc7 inhibitors with improved intrinsic metabolic stability ( ie 36 ).", "output": "indole, azaindole, 5 - azaindole." }, { "input": "In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co - crystallography data, and allowed the design of 7 - azaindole 37 as a second lead in this series.", "output": "7 - azaindole." }, { "input": "Helicusin E, Isochromophilone X and Isochromophilone XI: New Chloroazaphilones Produced by the Fungus Bartalinia robillardoides Strain LF550.", "output": "Helicusin E, Isochromophilone X, Isochromophilone XI, Chloroazaphilones." }, { "input": "Microbial studies of the Mediterranean sponge Tethya aurantium led to the isolation of the fungus Bartalinia robillardoides strain LF550.", "output": "There is no related enetity." }, { "input": "The strain produced a number of secondary metabolites belonging to the chloroazaphilones.", "output": "chloroazaphilones." }, { "input": "This is the first report on the isolation of chloroazaphilones of a fungal strain belonging to the genus Bartalinia.", "output": "chloroazaphilones." }, { "input": "Besides some known compounds ( helicusin A ( 1 ) and deacetylsclerotiorin ( 2 ) ), three new chloroazaphilones ( helicusin E ( 3 ); isochromophilone X ( 4 ) and isochromophilone XI ( 5 ) ) and one new pentaketide ( bartanolide ( 6 ) ) were isolated.", "output": "helicusin A, deacetylsclerotiorin, chloroazaphilones, helicusin E, isochromophilone X, isochromophilone XI, pentaketide, bartanolide." }, { "input": "The structure elucidations were based on spectroscopic analyses.", "output": "There is no related enetity." }, { "input": "All isolated compounds revealed different biological activity spectra against a test panel of four bacteria: three fungi; two tumor cell lines and two enzymes.", "output": "There is no related enetity." }, { "input": "Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene.", "output": "cadmium, phenanthrene." }, { "input": "Since the ' omics revolution ', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity.", "output": "There is no related enetity." }, { "input": "In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response.", "output": "cadmium, phenanthrene." }, { "input": "Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures.", "output": "There is no related enetity." }, { "input": "Subsequent transcriptional response analysis was done using five mixtures at the modeled 50 % effect level for reproduction.", "output": "There is no related enetity." }, { "input": "The transcription profiles of 86 high throughput RT - qPCR assays were studied by means of partial least squares regression analysis.", "output": "There is no related enetity." }, { "input": "The first and second principal components ( PCs ) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs.", "output": "cadmium, phenanthrene." }, { "input": "Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins.", "output": "There is no related enetity." }, { "input": "Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures.", "output": "phenanthrene." }, { "input": "Immune and inflammatory response assays did not correlate with any of the mixtures.", "output": "There is no related enetity." }, { "input": "These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures.", "output": "cadmium, phenanthrene." }, { "input": "The antagonism found for inhibition of reproduction may partially originate from these differences.", "output": "There is no related enetity." }, { "input": "Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real - world mixture exposures present in the field.", "output": "There is no related enetity." }, { "input": "High Purity Isolation and Quantification of Semiconducting Carbon Nanotubes via Column Chromatography.", "output": "Carbon." }, { "input": "The isolation of semiconducting carbon nanotubes ( CNTs ) to ultrahigh ( ppb ) purity is a prerequisite for their integration into high - performance electronic devices.", "output": "carbon." }, { "input": "Here, a method employing column chromatography is used to isolate semiconducting nanotubes to 99. 9 % purity.", "output": "There is no related enetity." }, { "input": "The study finds that by modifying the solution preparation step, both the metallic and semiconducting fraction are resolved and elute using a single surfactant system, allowing for multiple iterations.", "output": "There is no related enetity." }, { "input": "Iterative processing enables a far more rapid path to achieving the level of purities needed for high performance computing.", "output": "There is no related enetity." }, { "input": "After a single iteration, the metallic peak in the absorption spectra is completely attenuated.", "output": "There is no related enetity." }, { "input": "Although absorption spectroscopy is typically used to characterize CNT purity, it is found to be insufficient in quantifying solutions of high purity ( > 98 to 99 % ) due to low signal - to - noise in the metallic region of ultrahigh purity solutions.", "output": "There is no related enetity." }, { "input": "Therefore, a high throughput electrical testing method was developed to quantify the degree of separation by characterizing ~ 4000 field - effect transistors fabricated from the separated nanotubes after multiple iterations of the process.", "output": "There is no related enetity." }, { "input": "The separation and characterization methods described here provide a path to produce the ultrahigh purity semiconducting CNT solutions needed for high performance electronics.", "output": "There is no related enetity." }, { "input": "Influence of gas phase equilibria on the chemical vapor deposition of graphene.", "output": "graphene." }, { "input": "We have investigated the influence of gas phase chemistry on the chemical vapor deposition of graphene in a hot wall reactor.", "output": "graphene." }, { "input": "A new extended parameter space for graphene growth was defined through literature review and experimentation at low pressures ( >= 0. 001 mbar ).", "output": "graphene." }, { "input": "The deposited films were characterized by scanning electron microscopy, Raman spectroscopy, and dark field optical microscopy, with the latter showing promise as a rapid and nondestructive characterization technique for graphene films.", "output": "graphene." }, { "input": "The equilibrium gas compositions have been calculated across this parameter space.", "output": "There is no related enetity." }, { "input": "Correlations between the graphene films grown and prevalent species in the equilibrium gas phase revealed that deposition conditions associated with a high acetylene equilibrium concentration lead to good quality graphene deposition, and conditions that stabilize large hydrocarbon molecules in the gas phase result in films with multiple defects.", "output": "graphene, acetylene, graphene, hydrocarbon." }, { "input": "The transition between lobed and hexagonal graphene islands was found to be linked to the concentration of the monatomic hydrogen radical, with low concentrations associated with hexagonal islands.", "output": "graphene, hydrogen." }, { "input": "UVA Radiation Induced Ultrafast Electron Transfer from a Food Carcinogen Benzo [ a ] pyrene to Organic Molecules, Biological Macromolecules, and Inorganic Nano Structures.", "output": "Benzo [ a ] pyrene." }, { "input": "Reactions involving electron transfer ( ET ) and reactive oxygen species ( ROS ) play a pivotal role in carcinogenesis and cancer biochemistry.", "output": "oxygen." }, { "input": "Our present study emphasizes UVA radiation induced ET reaction as one of the key aspects of a potential carcinogen, benzo [ a ] pyrene ( BP ), in the presence of a wide variety of molecules covering organic p - benzoquinone ( BQ ), biological macromolecules like calf - thymus DNA ( CT - DNA ), human serum albumin ( HSA ) protein, and inorganic zinc oxide ( ZnO ) nanorods ( NRs ).", "output": "benzo [ a ] pyrene, p - benzoquinone, zinc oxide, ZnO." }, { "input": "Steady - state and picosecond - resolved fluorescence spectroscopy have been used to monitor such ET reactions.", "output": "There is no related enetity." }, { "input": "Physical consequences of BP association with CT - DNA have been investigated through temperature - dependent circular dichroism ( CD ) spectroscopy.", "output": "There is no related enetity." }, { "input": "The temperature - dependent steady - state, picosecond - resolved fluorescence lifetime and anisotropy studies reveal the effect of temperature on the perturbation of such ET reactions from BP to biological macromolecules, highlighting their temperature - dependent association.", "output": "There is no related enetity." }, { "input": "Furthermore, the electron - donating property of BP has been corroborated by measuring wavelength - dependent photocurrent in a BP - anchored ZnO NR - based photodevice, offering new physical insights for the carcinogenic study of BP.", "output": "ZnO." }, { "input": "Effect of sequence on the ionization behavior of a series of amphiphilic polypeptides.", "output": "There is no related enetity." }, { "input": "The behavior of five polypeptides made of hydrophilic and pH - responsive aspartic acid ( Asp ) and hydrophobic phenylalanine ( Phe ), which had been prepared by stitching together short well - defined sequences of Asp and Phe, was studied as a function of pH.", "output": "aspartic acid, Asp, phenylalanine, Phe, Asp, Phe." }, { "input": "The effect of pH on these polypeptides referred to as ( Asp3Phe1 ) n, ( Asp2Phe1 ) n, ( Asp1Phe1 ) n, ( Asp1Phe2 ) n, and ( Asp1Phe3 ) n varied dramatically depending on their constituting sequence.", "output": "There is no related enetity." }, { "input": "The more hydrophobic polypeptides ( Asp1Phe2 ) n and ( Asp1Phe3 ) n behaved as if the Asp ' s were isolated from each other and showed an apparent pKa ( pKa ( app ) ) that remained constant with level of ionization ( alpha = [ Asp ( - ) ] / [ Asp ] total ) and equaled 5. 4 and 6. 4, respectively.", "output": "Asp, Asp, Asp." }, { "input": "The more hydrophilic polypeptides ( Asp3Phe1 ) n and ( Asp2Phe1 ) n behaved like weak polyacids showing a linear increase in pKa ( app ) with increasing alpha.", "output": "There is no related enetity." }, { "input": "The pKa ( app ) of ( Asp1Phe1 ) n showed a trend as a function of alpha intermediate between the Asp - rich and Phe - rich polypeptides, behaving as if the Asp ' s were isolated at low alpha values ( < 0. 35 ) but acting as a weak polyacid for large alpha values ( > 0. 35 ).", "output": "Asp, Phe, Asp." }, { "input": "The effect that alpha, and thus the charge density of the polypeptides, had on the collapse and aggregation of the polypeptides was characterized by conducting static light scattering and fluorescence measurements.", "output": "There is no related enetity." }, { "input": "Static light scattering measurements demonstrated that all polypeptides precipitated and aggregated in solution at a critical charge density of 0. 2.", "output": "There is no related enetity." }, { "input": "Fluorescence measurements with pyrene indicated that this behavior was due to the formation of Phe aggregates in water.", "output": "pyrene, Phe." }, { "input": "Together, these experiments provide a complete description of how pH affects the behavior of a series of unique amphiphilic polypeptides designed with a well - defined sequence.", "output": "There is no related enetity." }, { "input": "Preferential adsorption and activity of monocomponent cellulases on lignocellulose thin films with varying lignin content.", "output": "There is no related enetity." }, { "input": "Understanding the enzymatic hydrolysis of cellulose and the influence of lignin in the process are critical for viable production of fuels and chemicals from lignocellulosic biomass.", "output": "There is no related enetity." }, { "input": "The interactions of monocomponent cellulases with cellulose and lignin substrates were investigated by using thin films supported on quartz crystal microgravimetry ( QCM ) resonators.", "output": "quartz." }, { "input": "Trichoderma reesei exoglucanase ( CBH - I ) and endoglucanase ( EG - I ) bound strongly to both cellulose and lignin but EG - I exhibited a distinctive higher affinity with lignin, causing a more extensive inhibition of the cellulolytic reactions.", "output": "There is no related enetity." }, { "input": "CBH - I was found to penetrate into the bulk of the cellulose substrate increasing the extent of hydrolysis and film deconstruction.", "output": "There is no related enetity." }, { "input": "In the absence of a cellulose binding domain ( CBD ) and a linker, the CBH - I core adsorbed slowly and was not able to penetrate into the film.", "output": "There is no related enetity." }, { "input": "Conversely to CBH - I, EG - I exhibited activity only on the surface of the lignocellulose substrate even when containing a CBD and a linker.", "output": "There is no related enetity." }, { "input": "Interestingly, EG - I displayed a clearly different interaction profile as a function of contact time registered by QCM.", "output": "There is no related enetity." }, { "input": "Conformation Guides Molecular Efficacy in Docking Screens of Activated beta - 2 Adrenergic G Protein Coupled Receptor.", "output": "There is no related enetity." }, { "input": "A prospective, large library virtual screen against an activated beta 2 - adrenergic receptor ( beta 2AR ) structure returned potent agonists to the exclusion of inverse - agonists, providing the first complement to the previous virtual screening campaigns against inverse - agonist - bound G protein coupled receptor ( GPCR ) structures, which predicted only inverse - agonists.", "output": "There is no related enetity." }, { "input": "In addition, two hits recapitulated the signaling profile of the co - crystal ligand with respect to the G protein and arrestin mediated signaling.", "output": "There is no related enetity." }, { "input": "This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable.", "output": "There is no related enetity." }, { "input": "However, the agonist - bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor ( DRD2 ) activated model templated on the activated beta 2AR structure returned few hits of only marginal potency.", "output": "dopamine." }, { "input": "Postsynthesis modification of a porous coordination polymer by LiCl To enhance H + transport.", "output": "LiCl, H +." }, { "input": "A Ca ( 2 + ) porous coordination polymer with 1D channels was functionalized by the postsynthesis addition of LiCl to enhance the H ( + ) conductivity.", "output": "Ca ( 2 + ), LiCl, H ( + )." }, { "input": "The compound showed over 10 ( - 2 ) S cm ( - 1 ) at 25 degrees C and 20 % relative humidity.", "output": "There is no related enetity." }, { "input": "Pulse - field gradient NMR elucidated that the fast H ( + ) conductivity was achieved by the support of Li ( + ) ion movements in the channel.", "output": "H ( + ), Li ( + )." }, { "input": "Hieranoid: Hierarchical Orthology Inference.", "output": "There is no related enetity." }, { "input": "An accurate inference of orthologs is essential in many research fields such as comparative genomics, molecular evolution, and genome annotation.", "output": "There is no related enetity." }, { "input": "Existing methods for genome - scale orthology inference are mostly based on all - versus - all similarity searches that scale quadratically with the number of species.", "output": "There is no related enetity." }, { "input": "This limits their application to the increasing number of available large - scale datasets.", "output": "There is no related enetity." }, { "input": "Here, we present Hieranoid, a new orthology inference method using a hierarchical approach.", "output": "There is no related enetity." }, { "input": "Hieranoid performs pairwise orthology analysis using InParanoid at each node in a guide tree as it progresses from its leaves to the root.", "output": "There is no related enetity." }, { "input": "This concept reduces the total runtime complexity from a quadratic to a linear function of the number of species.", "output": "There is no related enetity." }, { "input": "The tree hierarchy provides a natural structure in multi - species ortholog groups, and the aggregation of multiple sequences allows for multiple alignment similarity searching techniques, which can yield more accurate ortholog groups.", "output": "There is no related enetity." }, { "input": "Using the recently published orthobench benchmark, Hieranoid showed the overall best performance.", "output": "There is no related enetity." }, { "input": "Our progressive approach presents a new way to infer orthologs that combines efficient graph - based methodology with aspects of compute - intensive tree - based methods.", "output": "There is no related enetity." }, { "input": "The linear scaling with the number of species is a major advantage for large - scale applications and makes Hieranoid well suited to cope with vast amounts of sequenced genomes in the future.", "output": "There is no related enetity." }, { "input": "Hieranoid is an open source and can be downloaded at Hieranoid. sbc. su. se.", "output": "There is no related enetity." }, { "input": "Effect of iontophoresis on the in vitro trans - scleral transport of three single stranded oligonucleotides.", "output": "There is no related enetity." }, { "input": "Oligonucleotides represent a subject of clinical interest due to their potential ability to treat several diseases, including those affecting the posterior segment of the eye.", "output": "There is no related enetity." }, { "input": "Unfortunately, therapeutic oligonucleotides are currently administered by means of highly invasive approaches, such as intravitreal injections.", "output": "There is no related enetity." }, { "input": "The aim of the present work was to study in vitro, across isolated bovine sclera, the effect of iontophoresis on the transport of three single stranded oligonucleotides ( ssDNA ), 12 -, 24 - and 36 - mer, selected as reference compounds in view of a non - invasive drug delivery to the back of the eye.", "output": "There is no related enetity." }, { "input": "All the three sequences were able to cross bovine sclera in vitro without iontophoresis.", "output": "There is no related enetity." }, { "input": "When anodal iontophoresis was applied, no change in flux was observed, while in the presence of cathodal iontophoresis the permeability coefficients increased four - fold compared to passive conditions.", "output": "There is no related enetity." }, { "input": "This behavior can be ascribed to the electrorepulsive mechanism, due to the negative charge of the nucleic acid backbone.", "output": "There is no related enetity." }, { "input": "It was also observed that the molecular weights of the three sequences did not affect trans - scleral transport, neither in passive, nor in current assisted permeation.", "output": "There is no related enetity." }, { "input": "Furthermore, increasing the current intensity from 1. 75mA to 3mA, no effect on the trans - scleral transport of the 24 - mer was noticed.", "output": "There is no related enetity." }, { "input": "Although preliminary, the results demonstrate that cathodal iontophoresis enhances trans - scleral transport of single stranded oligonucleotides and suggest its use as a novel non - invasive approach for the treatment of diseases affecting the posterior segment of the eye.", "output": "There is no related enetity." }, { "input": "Activity - based assay for human mono - ADP - ribosyltransferases ARTD7 / PARP15 and ARTD10 / PARP10 aimed at screening and profiling inhibitors.", "output": "ADP." }, { "input": "Poly ( ADP - ribose ) polymerases ( PARPs ) or diphtheria toxin like ADP - ribosyl transferases ( ARTDs ) are enzymes that catalyze the covalent modification of proteins by attachment of ADP - ribose units to the target amino acid residues or to the growing chain of ADP - ribose.", "output": "Poly ( ADP - ribose ), ADP, ribosyl, ADP, ribose, amino acid, ADP, ribose." }, { "input": "A subclass of the ARTD superfamily consists of mono - ADP - ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP - ribose moiety to the target.", "output": "ADP, ribosyl, ADP, ribose." }, { "input": "Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme.", "output": "There is no related enetity." }, { "input": "Existing assays are not directly applicable for screening of inhibitors due to the different nature of the reaction and different target molecules.", "output": "There is no related enetity." }, { "input": "We modified and applied a fluorescence - based assay previously described for PARP1 / ARTD1 and tankyrase / ARTD5 for screening of PARP10 / ARTD10 and PARP15 / ARTD7 inhibitors.", "output": "There is no related enetity." }, { "input": "The assay measures the amount of NAD ( + ) present after chemically converting it to a fluorescent analog.", "output": "NAD ( + )." }, { "input": "We demonstrate that by using an excess of a recombinant acceptor protein the performance of the activity - based assay is excellent for screening of compound libraries.", "output": "There is no related enetity." }, { "input": "The assay is homogenous and cost effective, making it possible to test relatively large compound libraries.", "output": "There is no related enetity." }, { "input": "This method can be used to screen inhibitors of mono - ARTDs and profile inhibitors of the enzyme class.", "output": "There is no related enetity." }, { "input": "The assay was optimized for ARTD10 and ARTD7, but it can be directly applied to other mono - ARTDs of the ARTD superfamily.", "output": "There is no related enetity." }, { "input": "Profiling of known ARTD inhibitors against ARTD10 and ARTD7 in a validatory screening identified the best inhibitors with submicromolar potencies.", "output": "There is no related enetity." }, { "input": "Only few of the tested ARTD inhibitors were potent, implicating that there is a need to screen new compound scaffolds.", "output": "There is no related enetity." }, { "input": "This is needed to create small molecules that could serve as biological probes and potential starting points for drug discovery projects against mono - ARTDs.", "output": "There is no related enetity." }, { "input": "Multifunctional pH - sensitive superparamagnetic iron - oxide nanocomposites for targeted drug delivery and MR imaging.", "output": "iron - oxide." }, { "input": "A multifunctional pH - sensitive superparamagnetic iron - oxide ( SPIO ) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging ( MRI ) and therapy.", "output": "iron - oxide." }, { "input": "Small - size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin ( DOX ) and biocompatible poly ( ethylene glycol ) ( PEG ) through pH - sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH - sensitive properties.", "output": "doxorubicin, DOX, poly ( ethylene glycol ), PEG, acylhydrazone." }, { "input": "These DOX - conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations.", "output": "DOX." }, { "input": "Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH - sensitive acylhydrazone linkages.", "output": "DOX." }, { "input": "With the help of magnetic field, the DOX - conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property.", "output": "DOX." }, { "input": "Comparing to free DOX, the DOX - conjugated SPIO nanocomposites showed better antitumor effect under magnetic field.", "output": "DOX, DOX." }, { "input": "At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s ( - 1 ) mM ( - 1 ) Fe, leading to ~ 4 times enhancement compared to that of free SPIO nanoparticles.", "output": "Fe." }, { "input": "As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor - bearing mice.", "output": "There is no related enetity." }, { "input": "All of these results confirm that these pH - sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy.", "output": "There is no related enetity." }, { "input": "Effectiveness of albumin - conjugated gossypol as an immunogen to prevent gossypol - associated acute hepatotoxicity in rats.", "output": "gossypol, gossypol." }, { "input": "Gossypol is a highly reactive compound present in cotton ( Gossypium spp. ).", "output": "Gossypol." }, { "input": "The aim of this work was to determine whether the administration of gossypol conjugated to albumin can immunize rats and thereby prevent the acute hepatotoxicity associated with gossypol.", "output": "gossypol, gossypol." }, { "input": "The first experiment consisted of administering the immunogen gossypol - BSA, with or without the Freund ' s incomplete adjuvant, to rats.", "output": "gossypol." }, { "input": "The production of antibodies against gossypol was subsequently verified.", "output": "gossypol." }, { "input": "The second experiment comprised three groups of Wistar rats: VG, CG and CO.", "output": "There is no related enetity." }, { "input": "The rats from the VG cohort were injected with gossypol - BSA associated with Freund ' s incomplete adjuvant, and the animals from the CG and CO groups were injected with saline solution.", "output": "gossypol." }, { "input": "After 21days, the rats from the VG and CG cohorts were treated with 30mg / kg of gossypol by intraperitoneal injection, whereas the rats from the CO group received corn oil.", "output": "gossypol." }, { "input": "After 24h, the rats were evaluated for clinical signs of pathology, and their serum was biochemically analyzed.", "output": "There is no related enetity." }, { "input": "It was found that gossypol promoted hepatotoxic effects that were not prevented by the administration of gossypol - BSA.", "output": "gossypol, gossypol." }, { "input": "In conclusion, the administration of gossypol - BSA associated with Freund ' s incomplete adjuvant may be lightly to prevent the acute hepatotoxicity associated with gossypol.", "output": "gossypol, gossypol." }, { "input": "A Rice Immunophilin Gene, OsFKBP16 - 3, Confers Tolerance to Environmental Stress in Arabidopsis and Rice.", "output": "There is no related enetity." }, { "input": "The putative thylakoid lumen immunophilin, FKBP16 - 3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well - conserved CxxxC motif in photosynthetic organisms.", "output": "There is no related enetity." }, { "input": "Here, we characterized rice OsFKBP16 - 3 and examined the role of this gene in the regulation of abiotic stress in plants.", "output": "There is no related enetity." }, { "input": "FKBP16 - 3s are well conserved in eukaryotic photosynthetic organisms, including the presence of a unique disulfide - forming CxxxC motif in their N - terminal regions.", "output": "disulfide, N." }, { "input": "OsFKBP16 - 3 was mainly expressed in rice leaf tissues and was upregulated by various abiotic stresses, including salt, drought, high light, hydrogen peroxide, heat and methyl viologen.", "output": "hydrogen peroxide, methyl viologen." }, { "input": "The chloroplast localization of OsFKBP16 - 3 - GFP was confirmed through the transient expression of OsFKBP16 - 3 in Nicotiana benthamiana leaves.", "output": "There is no related enetity." }, { "input": "Transgenic Arabidopsis and transgenic rice plants that constitutively expressed OsFKBP16 - 3 exhibited increased tolerance to salinity, drought and oxidative stresses, but showed no change in growth or phenotype, compared with vector control plants, when grown under non - stressed conditions.", "output": "There is no related enetity." }, { "input": "This is the first report to demonstrate the potential role of FKBP16 - 3 in the environmental stress response, which may be regulated by a redox relay process in the thylakoid lumen, suggesting that artificial regulation of FKBP16 - 3 expression is a candidate for stress - tolerant crop breeding.", "output": "There is no related enetity." }, { "input": "Modeling distinct osteosarcoma subtypes in vivo using Cre: lox and lineage - restricted transgenic shRNA.", "output": "There is no related enetity." }, { "input": "Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents.", "output": "There is no related enetity." }, { "input": "Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes.", "output": "There is no related enetity." }, { "input": "We and others have previously described murine models of osteosarcoma based on osteoblast - restricted Cre: lox deletion of Trp53 ( p53 ) and Rb1 ( Rb ), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans.", "output": "Trp53." }, { "input": "We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype.", "output": "There is no related enetity." }, { "input": "In contrast to other osteosarcoma models that have used Cre: lox mediated gene deletion, this model was generated through shRNA - based knockdown of p53.", "output": "There is no related enetity." }, { "input": "As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre: lox approaches.", "output": "There is no related enetity." }, { "input": "Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre: lox and shRNA.", "output": "There is no related enetity." }, { "input": "This demonstrated that the effects of Cre: lox and shRNA mediated knock - down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma.", "output": "There is no related enetity." }, { "input": "Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer.", "output": "There is no related enetity." }, { "input": "Eliciting preferences for priority setting in genetic testing: a pilot study comparing best - worst scaling and discrete - choice experiments.", "output": "There is no related enetity." }, { "input": "Given the increasing number of genetic tests available, decisions have to be made on how to allocate limited health - care resources to them.", "output": "There is no related enetity." }, { "input": "Different criteria have been proposed to guide priority setting.", "output": "There is no related enetity." }, { "input": "However, their relative importance is unclear.", "output": "There is no related enetity." }, { "input": "Discrete - choice experiments ( DCEs ) and best - worst scaling experiments ( BWSs ) are methods used to identify and weight various criteria that influence orders of priority.", "output": "There is no related enetity." }, { "input": "This study tests whether these preference eliciting techniques can be used for prioritising genetic tests and compares the empirical findings resulting from these two approaches.", "output": "There is no related enetity." }, { "input": "Pilot DCE and BWS questionnaires were developed for the same criteria: prevalence, severity, clinical utility, alternatives to genetic testing available, infrastructure for testing and care established, and urgency of care.", "output": "There is no related enetity." }, { "input": "Interview - style experiments were carried out among different genetics professionals ( mainly clinical geneticists, researchers and biologists ).", "output": "There is no related enetity." }, { "input": "A total of 31 respondents completed the DCE and 26 completed the BWS experiment.", "output": "There is no related enetity." }, { "input": "Weights for the levels of the six attributes were estimated by conditional logit models.", "output": "There is no related enetity." }, { "input": "Although the results derived from the DCE and BWS experiments differed in detail, we found similar valuation patterns in the DCE and BWS experiments.", "output": "There is no related enetity." }, { "input": "The respondents attached greatest value to tests with high clinical utility ( defined by the availability of treatments that reduce mortality and morbidity ) and to testing for highly prevalent conditions.", "output": "There is no related enetity." }, { "input": "The findings from this study exemplify how decision makers can use quantitative preference eliciting methods to measure aggregated preferences in order to prioritise alternative clinical interventions.", "output": "There is no related enetity." }, { "input": "Further research is necessary to confirm the survey results. European Journal of Human Genetics advance online publication, 13 March 2013; doi: 10. 1038 / ejhg. 2013. 36.", "output": "There is no related enetity." }, { "input": "Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly.", "output": "There is no related enetity." }, { "input": "The method of window exchange umbrella sampling molecular dynamics ( WEUSMD ) with a pre - optimized parameter set was recently used to obtain the most probable conformations and the energetics of transmembrane ( TM ) helix assembly of a generic TM sequence.", "output": "There is no related enetity." }, { "input": "When applied to glycophorin A TM domain ( GpA - TM ) using the restraint potentials along the helix - helix distance, however, tight interfacial packing of GpA - TM resulted in insufficient conformational sampling at short helix - helix separation.", "output": "There is no related enetity." }, { "input": "This sampling issue is addressed by extending the WEUSMD into two dimensions with the restraint potentials along the helix - helix distance and crossing angle.", "output": "There is no related enetity." }, { "input": "The two - dimensional WEUSMD results demonstrate that the incomplete sampling in the one - dimensional WEUSMD arises from high barriers along the crossing angle between the GpA - TM helices.", "output": "There is no related enetity." }, { "input": "Together with the faster convergence in both the assembled conformations and the potential of mean force, the 2D - WEUSMD can be a general and efficient approach in computational studies of TM helix assembly.", "output": "There is no related enetity." }, { "input": "Rotational spectroscopy meets theory.", "output": "There is no related enetity." }, { "input": "Rotational spectroscopy is known to be a technique that is widely used to infer information on molecular structure and dynamics.", "output": "There is no related enetity." }, { "input": "In the last few decades, its role in the field of atmospheric and astrophysical investigations has rapidly grown.", "output": "There is no related enetity." }, { "input": "However, several are the challenging aspects in rotational spectroscopy, since the detection and analysis of spectra as well as interpretation of obtained results are not at all straightforward.", "output": "There is no related enetity." }, { "input": "Quantum chemistry has reached such an accuracy that can be used to disentangle these challenging situations by guiding the experimental investigation, assisting in the determination of the spectroscopic parameters, and extracting information of chemical interest.", "output": "There is no related enetity." }, { "input": "This perspective provides an overview of the theoretical background and computational requirements needed for the accurate evaluation of the spectroscopic parameters of relevance to rotational spectroscopy.", "output": "There is no related enetity." }, { "input": "The role of theory in guiding and supporting experiment is detailed through a few examples, and the interplay of experiment and theory is discussed in terms of the information of physical and chemical interest that can be derived.", "output": "There is no related enetity." }, { "input": "Effects of progesterone and medroxyprogesterone on actin remodeling and neuronal spine formation.", "output": "progesterone, medroxyprogesterone." }, { "input": "Sex steroids are important regulators of neuronal cell morphology, and this is critical for gender differences in brain function and dysfunction.", "output": "steroids." }, { "input": "Neuronal morphology is controlled by multiprotein complexes including moesin ( a member of the ezrin / radixin / moesin family ), focal adhesion kinase ( FAK ), or the Wiskott - Aldrich syndrome protein - family verprolin homologous ( WAVE1 ) protein, controlling dynamic remodeling of the cytoskeleton and cell membrane.", "output": "There is no related enetity." }, { "input": "We investigated the actions of natural progesterone ( P ) and of the synthetic progestin medroxyprogesterone acetate ( MPA ) on actin remodeling, focal adhesion complex formation, and actin branching in rat cortical neurons.", "output": "progesterone, progestin, medroxyprogesterone acetate, MPA." }, { "input": "Treatment with P and, to a lesser extent, MPA, increases the number and density of dendritic spines.", "output": "MPA." }, { "input": "P increases the phosphorylation of moesin, FAK, and WAVE1, and their redistribution toward cell membrane sites where spines are formed.", "output": "There is no related enetity." }, { "input": "Signaling to moesin is achieved by PR via a G alpha / G beta - dependent signaling to the small GTPase Ras homolog gene family, member A and its related kinase, Rho - associated kinase - 2.", "output": "There is no related enetity." }, { "input": "In parallel, WAVE1 recruitment is triggered by a G alpha i / G beta - dependent signaling of PR to c - Src, FAK, and Rac1 GTPase.", "output": "There is no related enetity." }, { "input": "Rac1 recruits cyclin - dependent kinase - 5, which phosphorylates WAVE1.", "output": "There is no related enetity." }, { "input": "Silencing of moesin, FAK, or WAVE1 abrogates the increase in dendritic spines induced by progesterone.", "output": "progesterone." }, { "input": "In all applications, MPA is found to act similar to P, albeit with a lower efficacy.", "output": "MPA." }, { "input": "In conclusion, our findings indicate that the control of actin polymerization and branching and focal adhesion complex formation via moesin, FAK, and WAVE1 is a key function of progesterone receptor in neurons, which may be relevant for the regulation of dendritic spine turnover and neuronal plasticity.", "output": "progesterone." }, { "input": "Gold nanoparticles on oxide - free silicon - molecule interface for single electron transport.", "output": "oxide, silicon." }, { "input": "Two different organic monolayers were prepared on silicon Si ( 111 ) and modified for attaching gold nanoparticles.", "output": "silicon, Si ( 111 )." }, { "input": "The molecules are covalently bound to silicon and form very ordered monolayers sometimes improperly called self - assembled monolayers ( SAM ).", "output": "silicon." }, { "input": "They are designed to be electrically insulating and to have very few electrical interface states.", "output": "There is no related enetity." }, { "input": "By positioning the tip of an STM above a nanoparticle, a double barrier tunnel junction ( DBTJ ) is created, and Coulomb blockade is demonstrated at 40 K.", "output": "There is no related enetity." }, { "input": "This is the first time Coulomb blockade is observed with an organic monolayer on oxide - free silicon.", "output": "silicon." }, { "input": "This work focuses on the fabrication and initial electrical characterization of this double barrier tunnel junction.", "output": "There is no related enetity." }, { "input": "The organic layers were prepared by thermal hydrosilylation of two different alkene molecules with either a long carbon chain ( C11 ) or a shorter one ( C7 ), and both were modified to be amine - terminated.", "output": "carbon, amine." }, { "input": "FTIR and XPS measurements confirm that the Si ( 111 ) substrate remains unoxidized during the whole chemical process.", "output": "Si ( 111 )." }, { "input": "Colloidal gold nanoparticles were prepared using two methods: either with citrate molecules ( Turkevich method ) or with ascorbic acid as the surfactant.", "output": "citrate, ascorbic acid." }, { "input": "In both cases AFM and STM images show a well - controlled deposition on the grafted organic monolayer.", "output": "There is no related enetity." }, { "input": "I - V curves obtained by scanning tunneling spectroscopy ( STS ) are presented on 8 nm diameter nanoparticles and exhibit the well - known Coulomb staircases at low temperature.", "output": "There is no related enetity." }, { "input": "The curves are discussed as a function of the organic layer thickness and silicon substrate doping.", "output": "There is no related enetity." }, { "input": "Nanodiamond nanofluids for enhanced thermal conductivity.", "output": "There is no related enetity." }, { "input": "Deaggregation of oxidized ultradispersed diamond ( UDD ) in dimethylsulfoxide followed by reaction with glycidol monomer, purification via aqueous dialysis, and dispersion in ethylene glycol ( EG ) base fluid affords nanodiamond ( ND ) - poly ( glycidol ) polymer brush: EG nanofluids exhibiting 12 % thermal conductivity enhancement at a ND loading of 0. 9 vol %.", "output": "diamond, dimethylsulfoxide, glycidol, ethylene glycol, poly ( glycidol )." }, { "input": "Deaggregation of UDD in the presence of oleic acid / octane followed by dispersion in light mineral oil and evaporative removal of octane gives ND. oleic acid: mineral oil dispersions exhibiting 11 % thermal conductivity enhancement at a ND loading of 1. 9 vol %.", "output": "oleic acid, octane, octane, oleic acid." }, { "input": "Average particle sizes of ND additives, determined by dynamic light scattering, are, respectively, ca.", "output": "There is no related enetity." }, { "input": "11 nm ( in H2O ) and 18 nm ( in toluene ).", "output": "H2O, toluene." }, { "input": "Observed thermal conductivity enhancements outperform enhancement effects calculated using Maxwell ' s effective medium approximation by 2 - to 4 - fold.", "output": "There is no related enetity." }, { "input": "Covalent ND surface modification gives 2 - fold greater thermal conductivity enhancement than ND surface modification via hydrogen - bonding interactions at similar concentrations.", "output": "hydrogen." }, { "input": "Stable, static ND: mineral oil dispersions are reported for the first time.", "output": "There is no related enetity." }, { "input": "Molecular dynamics simulation of nanosized water droplet spreading in an electric field.", "output": "There is no related enetity." }, { "input": "Molecular dynamics ( MD ) simulations are performed for the spreading of a nanosized water droplet on a solid substrate subject to a parallel electric field.", "output": "There is no related enetity." }, { "input": "A combined electrostatic and Lennard - Jones potential is employed to represent the intermolecular interactions.", "output": "There is no related enetity." }, { "input": "Results show that in response to the applied field, polar water molecules realign themselves and this microscopic reorientation of molecular dipoles combines with the intermolecular forces to produce a macroscopic deformation of a free spherical water droplet into an ellipsoid.", "output": "There is no related enetity." }, { "input": "The applied field has a strong effect on the spreading of the water droplet on a solid substrate.", "output": "There is no related enetity." }, { "input": "For a weaker parallel field, the droplet spreading is asymmetric with the leading contact angle being greater than the trailing contact angle.", "output": "There is no related enetity." }, { "input": "With an increase in field strength, this asymmetry continues to increase, culminates, and then decreases until it disappears.", "output": "There is no related enetity." }, { "input": "The symmetric spreading remains with a further increase in the field strength until the saturation point is reached.", "output": "There is no related enetity." }, { "input": "This transition from the asymmetric to symmetric spreading is a manifestation of the interaction of the electric field with polar water molecules and the intermolecular forces within the droplet and between the water and solid; the interaction also leads to a change in hydrogen bonds along the droplet surface.", "output": "hydrogen." }, { "input": "The dynamics of the droplet spreading is entailed by the electrically induced motion of molecules along the liquid surface toward the solid substrate and is controlled by a competing mechanism among the electric, water - water, and water - solid intermolecular forces.", "output": "There is no related enetity." }, { "input": "Enzymatic Conversion of 6 - Nitroquinoline to the Fluorophore 6 - Aminoquinoline Selectively under Hypoxic Conditions.", "output": "6 - Nitroquinoline, 6 - Aminoquinoline." }, { "input": "There is substantial interest in small molecules that can be used to detect or kill the hypoxic ( low oxygen ) cells found in solid tumors.", "output": "oxygen." }, { "input": "Nitroaryl moieties are useful components in the design of hypoxia - selective imaging agents and prodrugs because one - electron reductases can convert the nitroaryl group to nitroso, hydroxylamino, and amino metabolites selectively under low oxygen conditions.", "output": "Nitroaryl, nitroaryl, nitroso, hydroxylamino, amino, oxygen." }, { "input": "Here, we describe the in vitro, cell free metabolism of a pro - fluorescent substrate, 6 - nitroquinoline ( 1 ) under both aerobic and hypoxic conditions.", "output": "6 - nitroquinoline." }, { "input": "Both LC - MS and fluorescence spectroscopic analyses provided evidence that the one - electron reducing enzyme system, xanthine / xanthine oxidase, converted the nonfluorescent parent compound 1 to the known fluorophore 6 - aminoquinoline ( 2 ) selectively under hypoxic conditions.", "output": "xanthine, xanthine, 6 - aminoquinoline." }, { "input": "The presumed intermediate in this reduction process, 6 - hydroxylaminoquinoline ( 6 ), is fluorescent and can be efficiently converted by xanthine / xanthine oxidase to 2 only under hypoxic conditions.", "output": "6 - hydroxylaminoquinoline, xanthine, xanthine." }, { "input": "This finding provides evidence for multiple oxygen - sensitive steps in the enzymatic conversion of nitroaryl compounds to the corresponding amino derivatives.", "output": "oxygen, nitroaryl, amino." }, { "input": "In a side reaction that is separate from the bioreductive metabolism of 1, xanthine oxidase converted 1 to 6 - nitroquinolin - 2 ( 1H ) - one ( 5 ).", "output": "xanthine, 6 - nitroquinolin - 2 ( 1H ) - one." }, { "input": "These studies may enable the use of 1 as a fluorescent substrate for the detection and profiling of one - electron reductases in cell culture or biopsy samples.", "output": "There is no related enetity." }, { "input": "In addition, the compound may find use as a fluorogenic probe for the detection of hypoxia in tumor models.", "output": "There is no related enetity." }, { "input": "The occurrence of side products such as 5 in the enzymatic bioreduction of 1 underscores the importance of metabolite identification in the characterization of hypoxia - selective probes and drugs that employ nitroaryl units as oxygen sensors.", "output": "nitroaryl, oxygen." }, { "input": "Comparative antimalarial activities and ADME profiles of ozonides ( 1, 2, 4 - trioxolanes ) OZ277, OZ439, and their 1, 2 - dioxolane, 1, 2, 4 - trioxane, and 1, 2, 4, 5 - tetraoxane isosteres.", "output": "ozonides, 1 , 2 , 4 - trioxolanes, OZ277, OZ439, 1 , 2 - dioxolane, 1 , 2 , 4 - trioxane, 1 , 2 , 4 , 5 - tetraoxane." }, { "input": "To ascertain the structure - activity relationship of the core 1, 2, 4 - trioxolane substructure of dispiro ozonides OZ277 and OZ439, we compared the antimalarial activities and ADME profiles of the 1, 2 - dioxolane, 1, 2, 4 - trioxane, and 1, 2, 4, 5 - tetraoxane isosteres.", "output": "1 , 2 , 4 - trioxolane, dispiro ozonides, OZ277, OZ439, 1 , 2 - dioxolane, 1 , 2 , 4 - trioxane, 1 , 2 , 4 , 5 - tetraoxane." }, { "input": "Consistent with previous data, both dioxolanes had very weak antimalarial properties.", "output": "dioxolanes." }, { "input": "For the OZ277 series, the trioxane isostere had the best ADME profile, but its overall antimalarial efficacy was not superior to that of the trioxolane or tetraoxane isosteres.", "output": "OZ277, trioxane, trioxolane, tetraoxane." }, { "input": "For the OZ439 series, there was a good correlation between the antimalarial efficacy and ADME profiles in the rank order trioxolane > trioxane > tetraoxane.", "output": "OZ439, trioxolane, trioxane, tetraoxane." }, { "input": "As we have previously observed for OZ439 versus OZ277, the OZ439 series peroxides had superior exposure and efficacy in mice compared to the corresponding OZ277 series peroxides.", "output": "OZ439, OZ277, OZ439, peroxides, OZ277, peroxides." }, { "input": "Cardiovascular safety of the dipetidyl peptidase - 4 inhibitor alogliptin in type 2 diabetes mellitus ( + )", "output": "alogliptin." }, { "input": "AIM: As there have been concerns that some classes or agents for the treatment of type 2 diabetes may increase CV risk, we evaluated the cardiovascular profile of the dipeptidyl peptidase - 4 inhibitor alogliptin.", "output": "alogliptin." }, { "input": "METHODS: We evaluated the incidence of CV events in patients treated with alogliptin, placebo or comparator antihyperglycaemic drugs in the clinical trial database for alogliptin using the composite major adverse cardiovascular event ( MACE ) endpoints of CV death, non - fatal myocardial infarction and non - fatal stroke.", "output": "alogliptin, alogliptin." }, { "input": "RESULTS: The pooled analysis included 4168 patients exposed to alogliptin 12. 5 and 25 mg daily for 2023 patient - years compared to 691 patients treated with placebo for 263 patient - years and 1169 patients treated with other antidiabetic agents ( metformin, sulfonylureas and thiazolidinediones ) for 703 patient - years.", "output": "alogliptin, metformin, sulfonylureas, thiazolidinediones." }, { "input": "CV events were adjudicated by an expert endpoint committee blinded to treatment allocation.", "output": "There is no related enetity." }, { "input": "The incidence rates of the combined MACE were not significantly different between patients treated with alogliptin and comparator therapies ( hazard ratio = 0. 635, 95 % confidence interval, 0. 0, 1. 41 ).", "output": "alogliptin." }, { "input": "Additionally, other types of serious CV events were not significantly different between patients treated with alogliptin and comparator therapies.", "output": "alogliptin." }, { "input": "CONCLUSION: These analyses have not shown a signal of increased CV risk with alogliptin in patients with type 2 diabetes.", "output": "alogliptin." }, { "input": "Future results from the adequately powered EXAMINE trial will definitively assess the CV safety profile of aloglipin in patients with type 2 diabetes mellitus.", "output": "aloglipin." }, { "input": "Synthesis of ( R ) - norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa.", "output": "( R ) - norbgugaine." }, { "input": "( R ) - Bgugaine is a natural pyrrolidine alkaloid from Arisarum vulgare, which shows antifungal and antibacterial activity.", "output": "( R ) - Bgugaine, pyrrolidine alkaloid." }, { "input": "In this Letter, we have accomplished the simple synthesis of norbgugaine ( demethylated form of natural bgugaine ) employing Wittig olefination and cat. hydrogenation as the key steps and its biological studies are reported for the first time.", "output": "norbgugaine, bgugaine." }, { "input": "The synthesized norbgugaine was evaluated for inhibition of quorum sensing mediated virulence factors ( motility, biofilm formation, pyocyanin pigmentation, rhamnolipid production and LasA protease ) in Pseudomonas aeruginosa wherein swarming motility is reduced by 95 %, and biofilm formation by 83 %.", "output": "norbgugaine, pyocyanin." }, { "input": "Novel small molecules as apoptosis inducers: synthesis, preliminary structure - activity relationships, and in vitro biological evaluation.", "output": "There is no related enetity." }, { "input": "Inducing apoptosis is a promising therapeutic approach to overcome cancer.", "output": "There is no related enetity." }, { "input": "In this study, 30 compounds were synthesized and evaluated for their antiproliferative activity against three tumor cell lines in vitro: A875, H460 and Hela cancer cells by the MTT assay.", "output": "MTT." }, { "input": "The most potent analogue 7a, a novel compound was first reported by our group, inhibited the proliferation of A875 cells with an IC50 value of 98 nM.", "output": "There is no related enetity." }, { "input": "Flow cytometry analysis and morphological analysis suggested that compound 7a had potential anticancer efficacy via G2 / M cell cycle arrest, which could be attributed to its proliferation and apoptosis, and also in a concentration - dependent manner.", "output": "There is no related enetity." }, { "input": "The SAR analysis indicated that the substituents R ( 2 ) played a crucial role in the antiproliferation activity.", "output": "There is no related enetity." }, { "input": "N - ( Pyridin - 2 - yl ) arylsulfonamide inhibitors of 11 beta - hydroxysteroid dehydrogenase type 1: strategies to eliminate reactive metabolites.", "output": "N - ( Pyridin - 2 - yl ) arylsulfonamide, 11 beta - hydroxysteroid." }, { "input": "N - ( Pyridin - 2 - yl ) arylsulfonamides 1 and 2 ( PF - 915275 ) were identified as potent inhibitors of 11 beta - hydroxysteroid dehydrogenase type 1.", "output": "N - ( Pyridin - 2 - yl ) arylsulfonamides, PF - 915275, 11 beta - hydroxysteroid." }, { "input": "A screen for bioactivation revealed that these compounds formed glutathione conjugates.", "output": "glutathione." }, { "input": "This communication presents the results of a risk benefit analysis carried out to progress 2 ( PF - 915275 ) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors.", "output": "PF - 915275." }, { "input": "Based on the proposed mechanism of bioactivation and structure - activity relationships, design efforts led to N - ( pyridin - 2 - yl ) arylsulfonamides such as 18 and 20 that maintained potent 11 beta - hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.", "output": "N - ( pyridin - 2 - yl ) arylsulfonamides, 11 beta - hydroxysteroid." }, { "input": "Light at Night Alters Daily Patterns of Cortisol and Clock Proteins in Female Siberian Hamsters.", "output": "Cortisol." }, { "input": "Humans and other organisms have adapted to a 24 - h solar cycle in response to life on Earth.", "output": "There is no related enetity." }, { "input": "The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length.", "output": "There is no related enetity." }, { "input": "In order to successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm approximately 24 h in length.", "output": "There is no related enetity." }, { "input": "These rhythms arise from hierarchally - coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression.", "output": "There is no related enetity." }, { "input": "From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge.", "output": "There is no related enetity." }, { "input": "These circadian rhythms in physiology and behavior can be organized by a variety of cues, but they are most potently entrained by light.", "output": "There is no related enetity." }, { "input": "In recent history, there has been a major change from naturally occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting.", "output": "There is no related enetity." }, { "input": "Virtually every individual living in an industrialized country experiences light at night ( LAN ), but despite its prevalence, the biological effects of such unnatural lighting have not been fully considered.", "output": "There is no related enetity." }, { "input": "Using female Siberian hamsters ( Phodopus sungorus ), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations, and brain expression of circadian clock proteins ( i. e., PER1, PER2, BMAL1 ).", "output": "cortisol." }, { "input": "Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the SCN and hippocampus were altered.", "output": "cortisol." }, { "input": "These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology.", "output": "There is no related enetity." }, { "input": "(c) 2013 British Society for Neuroendocrinology.", "output": "There is no related enetity." }, { "input": "The effect of a unique halide - stabilizing residue on the catalytic properties of haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58.", "output": "halide, haloalkane." }, { "input": "Haloalkane dehalogenases catalyze the hydrolysis of carbon - halogen bonds in various chlorinated, brominated and iodinated compounds.", "output": "Haloalkane, carbon, halogen." }, { "input": "These enzymes have a conserved pair of halide - stabilizing residues that are important in substrate binding and stabilization of the transition state and the halide ion product via hydrogen bonding.", "output": "halide, halide, hydrogen." }, { "input": "In all previously known haloalkane dehalogenases, these residues are either a pair of tryptophans or a tryptophan - asparagine pair.", "output": "haloalkane, tryptophans, tryptophan, asparagine." }, { "input": "The newly - isolated haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58 ( EC 3. 8. 1. 5 ) possesses a unique halide - stabilizing tyrosine residue, Y109, in place of the conventional tryptophan.", "output": "haloalkane, halide, tyrosine, tryptophan." }, { "input": "A variant of DatA with the Y109W mutation was created and the effects of this mutation on the structure and catalytic properties of the enzyme were studied using spectroscopy and pre - steady - state kinetic experiments.", "output": "There is no related enetity." }, { "input": "Quantum mechanical and molecular dynamics calculations were used to obtain a detailed analysis of the hydrogen - bonding patterns within the active sites of the wild - type and the mutant, as well as of the stabilization of the ligands as the reaction proceeds.", "output": "hydrogen." }, { "input": "Fluorescence quenching experiments suggested that replacing the tyrosine with tryptophan improves halide binding by 3. 7 - fold, presumably as a result of the introduction of an additional hydrogen bond.", "output": "tyrosine, tryptophan, halide, hydrogen." }, { "input": "Kinetic analysis revealed that the mutation affected the substrate specificity of the enzyme and reduced its K0. 5 for selected halogenated substrates by a factor of 2 - 4, without impacting the rate - determining hydrolytic step.", "output": "There is no related enetity." }, { "input": "We conclude that DatA is the first natural haloalkane dehalogenase that stabilizes its substrate in the active site using only a single hydrogen bond, which is a new paradigm in catalysis by this enzyme family.", "output": "haloalkane, hydrogen." }, { "input": "Evidence that YycJ is a novel 5 ' - 3 ' double - stranded DNA exonuclease acting in Bacillus anthracis mismatch repair.", "output": "There is no related enetity." }, { "input": "The most important system for correcting replication errors that survive the built in editing system of DNA polymerase is the mismatch repair ( MMR ) system.", "output": "There is no related enetity." }, { "input": "We have identified a novel mutator strain yycJ in Bacillus anthracis.", "output": "There is no related enetity." }, { "input": "Mutations in the yycJ gene result in a spontaneous mutator phenotype with a mutational frequency and specificity comparable to that of MMR - deficient strains such as those with mutations in mutL or mutS.", "output": "There is no related enetity." }, { "input": "YycJ was annotated as a metallo - beta - lactamase ( M beta L ) super family member with unknown activity.", "output": "There is no related enetity." }, { "input": "In this study we carried out a biochemical characterization of YycJ and demonstrated that a recombinant YycJ protein possesses a 5 ' - 3 ' exonuclease activity at the 5 ' termini and at nicks of double - stranded DNA.", "output": "There is no related enetity." }, { "input": "This activity requires a divalent metal cofactor Mn ( 2 + ) and is stimulated by 5 ' - phosphate ends of duplex DNA.", "output": "Mn ( 2 + ), 5 ' - phosphate." }, { "input": "The mutagenesis of conserved amino acid residues revealed that in addition to the five M beta L family conserved motifs, YycJ appears to have its specific motifs that can be used to distinguish YycJ from other closely related M beta L family members.", "output": "amino acid." }, { "input": "A phylogenetic survey showed that putative YycJ homologs are present in several bacterial phyla as well as in members of the Methanomicrobiales and Thermoplasmales from Archaea.", "output": "There is no related enetity." }, { "input": "We propose that YycJ represents a new group of M beta L fold exonucleases, which is likely to act in the recognition of MMR entry point and subsequent removal of the mismatched base in certain MutH - less bacterial species.", "output": "There is no related enetity." }, { "input": "Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: I.", "output": "There is no related enetity." }, { "input": "Data Generation in a Small Fish Model.", "output": "There is no related enetity." }, { "input": "Adaptive or compensatory responses to chemical exposure can significantly influence in vivo concentration - duration - response relationships.", "output": "There is no related enetity." }, { "input": "This study provided data to support development of a computational dynamic model of the hypothalamic - pituitary - gonadal axis of a model vertebrate and its response to aromatase inhibitors as a class of endocrine active chemicals.", "output": "There is no related enetity." }, { "input": "Fathead minnows ( Pimephales promelas ) were either exposed to the aromatase inhibitor fadrozole ( 0. 5 or 30 mu g / l ) continuously for 1, 8, 12, 16, 20, 24, or 28 days or exposed for 8 days and then held in control water ( no fadrozole ) for an additional 4, 8, 12, 16, or 20 days.", "output": "fadrozole, fadrozole." }, { "input": "The time course of effects on ovarian steroid production, circulating 17 beta - estradiol ( E2 ) and vitellogenin ( VTG ) concentrations, and expression of steroidogenesis - related genes in the ovary was measured.", "output": "17 beta - estradiol, vitellogenin, VTG." }, { "input": "Exposure to 30 mu g fadrozole / l significantly reduced plasma E2 and VTG concentrations after just 1 day and those effects persisted throughout 28 days of exposure.", "output": "fadrozole, VTG." }, { "input": "In contrast, ex vivo E2 production was similar to that of controls on day 8 - 28 of exposure, whereas transcripts coding for aromatase and follicle - stimulating hormone receptor were elevated, suggesting a compensatory response.", "output": "There is no related enetity." }, { "input": "Following cessation of fadrozole exposure, ex vivo E2 and plasma E2 concentrations exceeded and then recovered to control levels, but plasma VTG concentrations did not, even after 20 days of depuration.", "output": "fadrozole, VTG." }, { "input": "Collectively these data provide several new insights into the nature and time course of adaptive responses to an aromatase inhibitor that support development of a computational model ( see companion article ).", "output": "There is no related enetity." }, { "input": "PDE3 and PDE4 isozyme selective inhibitors are both required for synergistic activation of brown adipose tissue.", "output": "There is no related enetity." }, { "input": "Brown adipose tissue ( BAT ) is a highly thermogenic organ that converts lipids and glucose into heat.", "output": "glucose." }, { "input": "Many of the metabolic and gene transcriptional hallmarks of BAT activation, namely increased lipolysis, uncoupling protein - 1 ( UCP1 ) mRNA, and glucose uptake are regulated by the adrenergic second messenger, adenosine - 3 ', 5 ' - cyclic monophosphate ( cAMP ).", "output": "glucose, adenosine - 3 ' , 5 ' - cyclic monophosphate, cAMP." }, { "input": "Cyclic nucleotide phosphodiesterases ( PDEs ) catalyze the breakdown of cAMP, thereby regulating the magnitude and duration of this signaling molecule.", "output": "nucleotide, cAMP." }, { "input": "In the absence of adrenergic stimulus, we found that it required a combination of a PDE3 and a PDE4 inhibitor to fully induce UCP1 mRNA and lipolysis in brown adipocytes, whereas neither PDE inhibitor alone had any substantial effect under basal conditions.", "output": "There is no related enetity." }, { "input": "Under submaximal beta - adrenoceptor stimulation of brown adipocytes, a PDE3 inhibitor alone could potentiate induction of UCP1 mRNA, while a PDE4 inhibitor alone could augment lipolysis, indicating differential roles for each of these two PDEs.", "output": "There is no related enetity." }, { "input": "Neither induction of UCP1 nor lipolysis was altered by inhibition of PDE1, PDE2 or PDE8A.", "output": "There is no related enetity." }, { "input": "Finally, when injected into mice, the combination of PDE3 and PDE4 inhibitors stimulated glucose uptake in BAT under thermoneutral and fasted conditions, a response that was further potentiated by the global ablation of PDE8A.", "output": "glucose." }, { "input": "Taken together, these data illustrate that multiple PDEs work in concert to regulate three of the important pathways leading to BAT activation, a finding that may provide an improved conceptual basis for the development of therapies for obesity - related diseases.", "output": "There is no related enetity." }, { "input": "Creb1 - Mecp2 - ( m ) CpG complex transactivates postnatal murine neuronal glucose transporter isoform 3 expression.", "output": "( m ) CpG, glucose." }, { "input": "The murine neuronal facilitative glucose transporter isoform 3 ( Glut3 ) is developmentally regulated, peaking in expression at postnatal day ( PN ) 14.", "output": "glucose." }, { "input": "In the present study, we characterized a canonical CpG island spanning the 5 ' - flanking region of the glut3 gene.", "output": "CpG." }, { "input": "Methylation - specific PCR and bisulfite sequencing identified methylation of this CpG ( ( m ) CpG ) island of the glut3 gene, frequency of methylation increasing 2. 5 - fold with a 1. 6 - fold increase in DNA methyl transferase 3a concentrations noted with advancing postnatal age ( PN14 vs PN3 ).", "output": "bisulfite, CpG, ( m ) CpG." }, { "input": "5 ' - flanking region of glut3 - luciferase reporter transient transfection in HT22 hippocampal neurons demonstrated that ( m ) CpGs inhibit glut3 transcription.", "output": "( m ) CpGs." }, { "input": "Contrary to this biological function, glut3 expression rises synchronously with ( m ) CpGs in PN14 vs PN3 neurons.", "output": "( m ) CpGs." }, { "input": "Chromatin immunoprecipitation ( IP ) revealed that methyl - CpG binding protein 2 ( Mecp2 ) bound the glut3 - ( m ) CpGs.", "output": "methyl, ( m ) CpGs." }, { "input": "Depending on association with specific coregulators, Mecp2, a dual regulator of gene transcription, may repress or activate a downstream gene.", "output": "There is no related enetity." }, { "input": "Sequential chromatin IP uncovered the glut3 - ( m ) CpGs to bind Mecp2 exponentially upon recruitment of Creb1 rather than histone deacetylase 1.", "output": "( m ) CpGs." }, { "input": "Co - IP and coimmunolocalization confirmed that Creb1 associated with Mecp2 and cotransfection with glut3 - ( m ) CpG in HT22 cells enhanced glut3 transcription.", "output": "( m ) CpG." }, { "input": "Separate 5 - aza - 2 ' - deoxycytidine pretreatment or in combination with trichostatin A reduced ( m ) CpG and specific small interference RNAs targeting Mecp2 and Creb1 separately or together depleting Mecp2 and / or Creb1 binding of glut3 - ( m ) CpGs reduced glut3 expression in HT22 cells.", "output": "5 - aza - 2 ' - deoxycytidine, trichostatin A, ( m ) CpG, ( m ) CpGs." }, { "input": "We conclude that Glut3 is a methylation - sensitive neuronal gene that recruits Mecp2.", "output": "There is no related enetity." }, { "input": "Recruitment of Creb1 - Mecp2 by glut3 - ( m ) CpG contributes towards transactivation, formulating an escape from ( m ) CpG - induced gene suppression, and thereby promoting developmental neuronal glut3 gene transcription and expression.", "output": "( m ) CpG, ( m ) CpG." }, { "input": "Development of N - Hydroxycinnamamide - Based Histone Deacetylase Inhibitors with Indole - Containing Cap Group.", "output": "N - Hydroxycinnamamide, Indole." }, { "input": "A novel series of histone deacetylase inhibitors combining N - hydroxycinnamamide bioactive fragment and indole bioactive fragment was designed and synthesized.", "output": "N - hydroxycinnamamide, indole." }, { "input": "Several compounds ( 17c, 17g, 17h, 17j and 17k ) exhibited comparable even superior total HDACs inhibitory activity and in vitro antiproliferative activities relative to the approved drug SAHA.", "output": "SAHA." }, { "input": "A representative compound 17a with moderate HDACs inhibition was progressed to isoform selectivity profile, western blot analysis and in vivo antitumor assay.", "output": "There is no related enetity." }, { "input": "Although HDACs isoform selectivity of 17a was similar to that of SAHA, our western blot results indicated that intracellular effects of 17a at 1 mu M were class I selective.", "output": "SAHA." }, { "input": "It was noteworthy that the effect on histone H4 acetylation of SAHA decreased with time while the effect on histone H4 acetylation of 17a maintained even increased.", "output": "SAHA." }, { "input": "Most importantly, compound 17a exhibited promising in vivo antitumor activity in a U937 xenograft model.", "output": "There is no related enetity." }, { "input": "Adipose Tissue Macrophages Function as Antigen Presenting Cells and Regulate Adipose Tissue CD4 + T Cells in Mice.", "output": "There is no related enetity." }, { "input": "The pro - inflammatory activation of leukocytes in adipose tissue contributes to metabolic disease.", "output": "There is no related enetity." }, { "input": "How crosstalk between immune cells initiates and sustains adipose tissue inflammation remains an unresolved question.", "output": "There is no related enetity." }, { "input": "We have examined the hypothesis that adipose tissue macrophages ( ATMs ) interact with and regulate the function of T cells.", "output": "There is no related enetity." }, { "input": "Dietary obesity was shown to activate the proliferation of effector memory CD4 ( + ) T cells in adipose tissue.", "output": "There is no related enetity." }, { "input": "Our studies further demonstrate that ATMs are functional antigen presenting cells that promote the proliferation of IFN - gamma producing CD4 ( + ) T cells in adipose tissue.", "output": "There is no related enetity." }, { "input": "ATMs from both lean and obese visceral fat process and present MHC class II - restricted antigens.", "output": "There is no related enetity." }, { "input": "ATMs were sufficient to promote proliferation and IFN - gamma production from antigen - specific CD4 ( + ) T cells in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Diet - induced obesity increased the expression of MHC II and T cell costimulatory molecules on ATMs in visceral fat, which correlated with an induction of T cell proliferation in that depot.", "output": "There is no related enetity." }, { "input": "Collectively, these data indicate that ATMs provide a functional link between the innate and adaptive immune systems within visceral fat in mice.", "output": "There is no related enetity." }, { "input": "Cytoplasmic - Nuclear Trafficking of G1 / S Cell Cycle Molecules and Adult Human Beta Cell Replication: A Revised Model of Human Beta Cell G1 / S Control.", "output": "There is no related enetity." }, { "input": "Harnessing control of human beta cell proliferation has proven frustratingly difficult.", "output": "There is no related enetity." }, { "input": "Most G1 / S control molecules, generally presumed to be nuclear proteins in the human beta cell, are in fact constrained to the cytoplasm.", "output": "There is no related enetity." }, { "input": "Here, we asked whether G1 / S molecules might traffic into and out of the cytoplasmic compartment in association with activation of cell cycle progression.", "output": "There is no related enetity." }, { "input": "Cdk6 and cyclin D3 were used to drive human beta cell proliferation, and promptly translocated into the nucleus in association with proliferation.", "output": "There is no related enetity." }, { "input": "In contrast, the cell cycle inhibitors p15, p18 and p19 did not alter their location, remaining cytoplasmic.", "output": "There is no related enetity." }, { "input": "Conversely, p16, p21, p27 all increased their nuclear frequency.", "output": "There is no related enetity." }, { "input": "In contrast once again, p57 decreased its nuclear frequency.", "output": "There is no related enetity." }, { "input": "While proliferating beta cells contained nuclear cyclin D3 and cdk6, proliferation generally did not occur in beta cells that contained nuclear cell cycle inhibitors, except p21.", "output": "There is no related enetity." }, { "input": "Dynamic cytoplasmic - nuclear trafficking of cdk6 was confirmed using GFP - tagged cdk6 and live - cell imaging.", "output": "There is no related enetity." }, { "input": "Thus, we provide novel working models describing the control of cell cycle progression in the human beta cell.", "output": "There is no related enetity." }, { "input": "In addition to known obstacles to beta cell proliferation, cytoplasmic - to - nuclear trafficking of G1 / S molecules may represent both an obstacle, as well as a therapeutic opportunity, for human beta cell expansion.", "output": "There is no related enetity." }, { "input": "Toxicological profiles of selected synthetic cannabinoids showing high binding affinities to the cannabinoid receptor subtype CB1.", "output": "cannabinoids, cannabinoid." }, { "input": "Products containing synthetic cannabinoids are consumed as a surrogate for marihuana due to their non - detectability with commonly used drug tests and their strong cannabimimetic effects.", "output": "cannabinoids." }, { "input": "Because data concerning their toxicological properties are scarce, the cytotoxic, genotoxic, immunomodulatory, and hormonal activities of four naphthoylindole compounds ( JWH - 018, JWH - 073, JWH - 122 and JWH - 210 ) and of one benzoylindole ( AM - 694 ) were studied in human cell lines and primary cells; tetrahydrocannabinol was included as the classical non - endogenous cannabinoid receptor ligand.", "output": "naphthoylindole, JWH - 018, JWH - 073, JWH - 122, JWH - 210, benzoylindole, AM - 694, tetrahydrocannabinol." }, { "input": "All compounds induced damage to the cell membranes of buccal ( TR146 ) and breast ( MCF - 7 ) derived cells at concentrations of >= 75 - 100 mu M.", "output": "There is no related enetity." }, { "input": "No cytotoxic responses were seen in other assays which reflect mitochondrial damage, protein synthesis, and lysosomal activities.", "output": "There is no related enetity." }, { "input": "JWH - 073 and JWH - 122 induced DNA migration in buccal and liver cells ( HepG2 ) in single cell gel electrophoresis assays, while JWH - 210 was only in the latter cell line active.", "output": "JWH - 073, JWH - 122, JWH - 210." }, { "input": "No estrogenic activities were detected in bone marrow cells ( U2 - OS ), but all compounds caused anti - estrogenic effects at levels between 2. 1 and 23. 0 mu M.", "output": "There is no related enetity." }, { "input": "Furthermore, no impact on cytokine release ( i. e., on IL - 10, IL - 6, IL - 12 / 23p40 and TNF alpha levels ) was seen in LPS - stimulated human PBMCs, except with JWH - 210 and JWH - 122 which caused a decrease of TNF alpha and IL - 12 / 23p40.", "output": "JWH - 210, JWH - 122." }, { "input": "All toxic effects were observed with concentrations higher than those expected in body fluids of users.", "output": "There is no related enetity." }, { "input": "Since genotoxic effects are in general linear over a wide concentration range and the exposure levels may be higher in epithelial cells or in serum, further experimental work is required to find out if DNA damage takes place in drug users.", "output": "There is no related enetity." }, { "input": "Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure.", "output": "There is no related enetity." }, { "input": "Brentuximab vedotin ( ADCETRIS ( (R) ) ) is an antibody - drug conjugate that is specifically targeted against CD30 - positive cancer cells such as those in Hodgkin lymphoma or systemic anaplastic large cell lymphoma ( ALCL ).", "output": "There is no related enetity." }, { "input": "Intravenous brentuximab vedotin was associated with an overall objective response rate ( primary endpoint ) of 75 % in 102 patients with Hodgkin lymphoma who had relapsed after high - dose chemotherapy and autologous haematopoietic stem cell transplantation, in a noncomparative, multicentre, phase II trial.", "output": "There is no related enetity." }, { "input": "In 58 patients with relapsed systemic ALCL after at least one prior treatment, intravenous brentuximab vedotin was associated with an overall objective response rate ( primary endpoint ) of 86 % in a noncomparative, multicentre, phase II trial.", "output": "There is no related enetity." }, { "input": "Tumour reductions were observed in 94 % of patients with Hodgkin lymphoma and 97 % of patients with systemic ALCL, and most tumours decreased in size by > 65 % and > 85 %, respectively.", "output": "There is no related enetity." }, { "input": "The estimated 12 - month survival rates were 89 % and 52 %, respectively.", "output": "There is no related enetity." }, { "input": "Brentuximab vedotin was generally well tolerated in these trials.", "output": "There is no related enetity." }, { "input": "The most common adverse event was peripheral neuropathy; approximately one - half of patients with this adverse event experienced complete resolution.", "output": "There is no related enetity." }, { "input": "Acute ketamine induces hippocampal synaptic depression and spatial memory impairment through dopamine D1 / D5 receptors.", "output": "ketamine, dopamine." }, { "input": "RATIONALE: Subanesthetic doses of ketamine have been reported to induce psychotic states that may mimic positive and negative symptoms as well as cognitive and memory deficits similar to those observed in schizophrenia.", "output": "ketamine." }, { "input": "The cognitive and memory deficits are persistent, and their underlying cellular mechanisms remain unclear.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We sought to investigate the roles of dopamine D1 / D5 receptors and alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazolepropionic acid ( AMPA ) receptors in hippocampal synaptic transmission and spatial memory impairment induced by ketamine.", "output": "dopamine, alpha - amino - 3 - hydroxy - 5 - methyl - 4 - isoxazolepropionic acid, AMPA, ketamine." }, { "input": "METHODS: We examined the effects of subanesthetic ketamine on hippocampal synaptic transmission in freely moving rats.", "output": "ketamine." }, { "input": "Spatial memory was tested with the Morris water maze.", "output": "There is no related enetity." }, { "input": "Pretreatment with the D1 / D5 receptors antagonist SCH23390 or the AMPA receptors endocytosis interfering peptide Tat - GluR23Y was conducted to examine their capacities to reverse ketamine - induced electrophysiological and behavioral alterations.", "output": "SCH23390, AMPA, ketamine." }, { "input": "A series of behavioral observations, including locomotion, prepulse inhibition, and social interaction, were also conducted after ketamine treatment.", "output": "ketamine." }, { "input": "RESULTS: Ketamine induced synaptic depression lasting at least 4 h at hippocampal Schaffer collateral - CA1 synapses in freely moving rats and long - term spatial memory impairment.", "output": "Ketamine." }, { "input": "Both the effects were blocked by either SCH23390 or Tat - GluR23Y.", "output": "SCH23390." }, { "input": "Ketamine also elicited transient behavioral changes lasting less than 90 min, such as hyperlocomotion and prepulse inhibition deficits.", "output": "Ketamine." }, { "input": "These changes were ameliorated by SCH23390 but not by Tat - GluR23Y.", "output": "SCH23390." }, { "input": "Rats treated with ketamine showed social withdrawal that was also attenuated by either SCH23390 or Tat - GluR23Y.", "output": "ketamine, SCH23390." }, { "input": "CONCLUSIONS: Our results indicate that hippocampal synaptic depression is involved in ketamine - induced memory impairment, and this is modulated by D1 / D5 receptors activation and AMPA receptors endocytosis.", "output": "ketamine, AMPA." }, { "input": "Effects of nitric oxide synthase inhibition in the dorsolateral periaqueductal gray matter on ethanol withdrawal - induced anxiety - like behavior in rats.", "output": "nitric oxide, ethanol." }, { "input": "RATIONALE: Nitric oxide ( NO ) - mediated transmission in the dorsolateral periaqueductal gray matter ( dlPAG ) has been involved in the expression of anxiety - like behaviors.", "output": "Nitric oxide, NO." }, { "input": "Ethanol withdrawal sensitizes the dlPAG and results in increased anxiety - like responses.", "output": "Ethanol." }, { "input": "OBJECTIVES: The objective of the study was to test the hypothesis that NO in the dlPAG is involved in the expression of ethanol withdrawal - induced anxiety.", "output": "NO, ethanol." }, { "input": "METHODS: Male Wistar rats were implanted with guide cannulae aimed at the dlPAG.", "output": "There is no related enetity." }, { "input": "The animals were forced to consume a liquid diet containing ethanol 6 - 8 % ( v / v ) for 15 days as their only source of diet.", "output": "ethanol." }, { "input": "Six days after surgery and 24 h after ethanol discontinuation, the animals received microinjections of the NO scavenger 2 - ( 4 - carboxyphenyl ) - 4, 4, 5, 5 - tetramethylimidazoline - 1 - oxyl - 3 - oxide ( carboxy - PTIO ), nonselective nitric oxide synthase inhibitor N ( G ) - nitro - L - arginine methyl ester ( L - NAME ), selective neuronal nitric oxide synthase inhibitor 1 - ( 2 - [ trifluoromethyl ] phenyl ) imidazole ( TRIM ), or selective inducible nitric oxide synthase ( iNOS ) inhibitor N - ( [ 3 - ( aminomethyl ) phenyl ] methyl ) ethanimidamide dihydrochloride ( 1400W ) into the dlPAG.", "output": "ethanol, NO, 2 - ( 4 - carboxyphenyl ) - 4 , 4 , 5 , 5 - tetramethylimidazoline - 1 - oxyl - 3 - oxide, carboxy - PTIO, nitric oxide, N ( G ) - nitro - L - arginine methyl ester, L - NAME, nitric oxide, 1 - ( 2 - [ trifluoromethyl ] phenyl ) imidazole, TRIM, nitric oxide, N - ( [ 3 - ( aminomethyl ) phenyl ] methyl ) ethanimidamide dihydrochloride, 1400W." }, { "input": "Ten minutes later, the animals were tested in the light / dark box.", "output": "There is no related enetity." }, { "input": "RESULTS: Carboxy - PTIO ( 1 nmol ), L - NAME ( 200 nmol ), TRIM ( 20 nmol ), and 1400W ( 0. 3 and 1 nmol ) decreased the anxiogenic - like effects of ethanol withdrawal in rats in the light / dark box test.", "output": "Carboxy - PTIO, L - NAME, TRIM, 1400W, ethanol." }, { "input": "The NO precursor L - arginine reversed the effects of L - NAME.", "output": "NO, L - arginine, L - NAME." }, { "input": "CONCLUSIONS: NO production in the dlPAG may play a role in the modulation of ethanol withdrawal - induced anxiety - like behavior in rats.", "output": "NO, ethanol." }, { "input": "Furthermore, iNOS - mediated NO synthesis in the dlPAG is predominantly involved in the behavioral expression of anxiety - like behavior during ethanol withdrawal.", "output": "NO, ethanol." }, { "input": "Ascorbigen Induces Dermal Papilla Cell Proliferation in Vitro, but Fails to Modulate Chemotherapy - Induced Alopecia in Vivo.", "output": "Ascorbigen." }, { "input": "Ascorbigen ( ABG ) is the predominant indole - derived compound from Brassica vegetables.", "output": "Ascorbigen, ABG, indole." }, { "input": "In this study, we attempted to evaluate the effects of ABG on hair growth.", "output": "ABG." }, { "input": "To this end, we examined the proliferation of isolated human dermal papilla ( DP ) cells and keratinocytes after incubation in various concentrations ( 0 - 1. 25 mM ) of ABG.", "output": "ABG." }, { "input": "Furthermore, hair shaft regrowth was monitored in a mouse model of chemotherapy - induced alopecia ( CIA ), and hematoxylin and eosin staining was performed for histological analyses.", "output": "hematoxylin, eosin." }, { "input": "We found that 1. 25 mM ABG induced a 1. 2 - fold increase in the growth of DP cells, but not keratinocytes.", "output": "ABG." }, { "input": "However, ABG did not exert significant protective effects against CIA in the mouse model.", "output": "ABG." }, { "input": "These findings suggest that ABG may not be able to counteract CIA and that further investigation of the therapeutic potential of ABG in disease models is required.", "output": "ABG, ABG." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Assessment of Cytotoxic Properties of Safranal and Nanoliposomal Safranal in Various Cancer Cell Lines.", "output": "Safranal, Safranal." }, { "input": "Saffron ( Crocus sativus ) is a widely used food additive used for its color and taste.", "output": "There is no related enetity." }, { "input": "It has been reported that saffron possesses significant in vivo and in vitro anti - tumor activity.", "output": "There is no related enetity." }, { "input": "In the present study, anti - tumor effects of safranal, the major aromatic compound in saffron, and its liposomal form were investigated.", "output": "safranal." }, { "input": "The role of apoptosis has also been explored in this toxicity.", "output": "There is no related enetity." }, { "input": "HeLa, MCF7 and L929 cell lines were cultured and exposed to safranal ( 0. 01 - 3 mM ) or liposomal safranal ( 0. 04 - 0. 32 mM ).", "output": "safranal, safranal." }, { "input": "3 - ( 4, 5 - Dimethylthiazol - 2 - yl ) - 2, 5 - diphenyl tetrazolium ( MTT ) assay was performed to assess cytotoxicity.", "output": "3 - ( 4 , 5 - Dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyl tetrazolium, MTT." }, { "input": "Apoptosis was evaluated by staining cells with propidium iodide and quantifying sub - Gl peak by flow cytometry.", "output": "propidium iodide." }, { "input": "MTT assay revealed a significant and concentration - dependent cytotoxic effect of safranal on HeLa and MCF7 cell lines.", "output": "MTT." }, { "input": "Liposomal safranal showed enhanced effect compared to the safranal solution, as compared by their IC50 concentrations.", "output": "safranal." }, { "input": "Flow cytometry results revealed induction of apoptosis by safranal.", "output": "safranal." }, { "input": "It might be concluded that safranal could be involved in saffron - induced cell death in HeLa and MCF7 cells.", "output": "safranal." }, { "input": "Liposome encapsulation improved anti - tumor effect of safranal.", "output": "safranal." }, { "input": "Safranal and particularly its liposomal form could be investigated as promising chemotherapeutic agents in cancer treatment.", "output": "Safranal." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Curcuminoids Modulate Pro - Oxidant - Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals.", "output": "Curcuminoids." }, { "input": "Curcuminoids have potentially important functional qualities including anti - inflammatory and antioxidant properties.", "output": "Curcuminoids." }, { "input": "In this randomized double - blind placebo - controlled cross - over trial, the effects of a curcuminoid supplement on serum pro - oxidant - antioxidant balance ( PAB ) and antibody titres to Hsp27 ( anti - Hsp27 ) and oxLDL ( anti - oxLDL ) were investigated.", "output": "curcuminoid." }, { "input": "Thirty obese individuals were randomized to receive either curcuminoids ( 1 g / day ) or placebo for a period of 30 days.", "output": "curcuminoids." }, { "input": "After a wash - out period of 2 weeks, subjects were crossed over to the alternate regimen for another 30 days.", "output": "There is no related enetity." }, { "input": "Serum PAB along with anti - Hsp27 and anti - oxLDL titres was measured at the beginning and at the end of each study period.", "output": "There is no related enetity." }, { "input": "There was no significant carry - over effect for any of the assessed parameters.", "output": "There is no related enetity." }, { "input": "Curcuminoid supplementation was associated with a significant decrease in PAB ( p = 0. 044 ).", "output": "Curcuminoid." }, { "input": "However, no significant change was observed in serum concentrations of anti - Hsp27 or anti - oxLDL ( p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "These findings suggest that oral curcuminoids supplementation ( 1g / day ) is effective in reducing oxidative stress burden, though this needs to be validated in larger study populations.", "output": "curcuminoids." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Spectroscopic Studies on Nicotine and Nornicotine in the UV Region.", "output": "Nicotine, Nornicotine." }, { "input": "The UV absorption and electronic circular dichroism ( ECD ) spectra of ( R ) - and ( S ) - nicotine and ( S ) - nornicotine in aqueous solution were measured to a significantly lower wavelength range than previously reported, allowing the identification of four previously unobserved electronic transitions.", "output": "( R ) - and ( S ) - nicotine, ( S ) - nornicotine." }, { "input": "The ECD spectra of the two enantiomers of nicotine were equal in magnitude and opposite in sign, while the UV absorption spectra were coincidental.", "output": "nicotine." }, { "input": "In line with previous observations, ( S ) - nicotine exhibited a negative cotton effect centered on 263 nm with vibronic structure ( pi - pi 1 * transition ) and a broad, positive ECD signal at around 240 nm associated with the n - pi 1 * transition.", "output": "( S ) - nicotine." }, { "input": "As expected this band disappeared when the pyridyl aromatic moiety was protonated.", "output": "pyridyl." }, { "input": "Four further electronic transitions are reported between 215 and 180 nm; it is proposed the negative maxima around 206 nm is either an n - sigma * transition or a charge transfer band resulting from the movement of charge from the pyrrolidyl N lone pair to the pyridyl pi * orbital.", "output": "pyrrolidyl, N, pyridyl." }, { "input": "The pyridyl pi - pi 2 * transition may be contained within the negative ECD signal envelope at around 200 nm.", "output": "pyridyl." }, { "input": "Another negative maximum at 188 nm is thought to be the pyridyl pi - pi 3 * transition, while the lowest wavelength end - absorption and positive ECD may be associated with the pi - pi 4 * transition.", "output": "pyridyl." }, { "input": "The UV absorption spectra of ( S ) - nornicotine was similar to that of ( S ) - nicotine in the range 280 - 220 nm and acidification of the aqueous solution enhanced the absorption.", "output": "( S ) - nornicotine, ( S ) - nicotine." }, { "input": "The ECD signals of ( S ) - nornicotine were considerably less intense compared to ( S ) - nicotine and declined further on acidification; in the far UV region the ECD spectra diverge considerably.", "output": "( S ) - nornicotine, ( S ) - nicotine." }, { "input": "Chirality 25: 288 - 293, 2013.", "output": "There is no related enetity." }, { "input": "(c) 2013 Wiley Periodicals, Inc.", "output": "There is no related enetity." }, { "input": "Oxygen Activation of Apo - obelin - Coelenterazine Complex.", "output": "Oxygen, Coelenterazine." }, { "input": "Ca ( 2 + ) - regulated photoproteins use a noncovalently bound 2 - hydroperoxycoelenterazine ligand to emit light in response to Ca ( 2 + ) binding.", "output": "Ca ( 2 + ), 2 - hydroperoxycoelenterazine, Ca ( 2 + )." }, { "input": "To better understand the mechanism of formation of active photoprotein from apoprotein, coelenterazine and molecular oxygen, we investigated the spectral properties of the anaerobic apo - obelin - coelenterazine complex and the kinetics of its conversion into active photoprotein after exposure to air.", "output": "coelenterazine, oxygen, coelenterazine." }, { "input": "Our studies suggest that coelenterazine bound within the anaerobic complex might be a mixture of N7 - protonated and C2 ( - ) anionic forms, and that oxygen shifts the equilibrium in favor of the C2 ( - ) anion as a result of peroxy anion formation.", "output": "coelenterazine, N7, C2 ( - ), oxygen, C2 ( - ), peroxy." }, { "input": "Proton removal from N7 and further protonation of peroxy anion and the resulting formation of 2 - hydroperoxycoelenterazine in obelin might occur with the assistance of His175.", "output": "N7, peroxy, 2 - hydroperoxycoelenterazine, His175." }, { "input": "It is proposed that this conserved His residue might play a key role both in formation of active photoprotein and in Ca ( 2 + ) - triggering of the bioluminescence reaction.", "output": "His, Ca ( 2 + )." }, { "input": "Prospects and challenges of graphene in biomedical applications.", "output": "graphene." }, { "input": "Graphene materials have entered a phase of maturity in their development that is characterized by their explorative utilization in various types of applications and fields from electronics to biomedicine.", "output": "Graphene." }, { "input": "Herein, we describe the recent advances made with graphene - related materials in the biomedical field and the challenges facing these exciting new tools both in terms of biological activity and toxicological profiling in vitro and in vivo.", "output": "graphene." }, { "input": "Graphene materials today have mainly been explored as components of biosensors and for construction of matrices in tissue engineering.", "output": "Graphene." }, { "input": "Their antimicrobial activity and their capacity to act as drug delivery platforms have also been reported, however, not as coherently.", "output": "There is no related enetity." }, { "input": "This report will attempt to offer some perspective as to which areas of biomedical applications can expect graphene - related materials to constitute a tool offering improved functionality and previously unavailable options.", "output": "graphene." }, { "input": "Raphanus sativus L. var niger as a source of Phytochemicals for the Prevention of Cholesterol Gallstones.", "output": "Cholesterol." }, { "input": "Raphanus sativus L. var niger ( black radish ) is a plant of the cruciferous family with important ethnobotanical uses for the treatment of gallstones in Mexican traditional medicine.", "output": "There is no related enetity." }, { "input": "It has been established that the juice of black radish decreases cholesterol levels in plasma and dissolves gallstones in mice.", "output": "cholesterol." }, { "input": "Glucosinolates, the main secondary metabolites of black radish, can hydrolyze into its respective isothiocyanates and have already demonstrated antioxidant properties as well as their ability to diminish hepatic cholesterol levels; such therapeutic effects can prevent the formation of cholesterol gallstones.", "output": "Glucosinolates, isothiocyanates, cholesterol, cholesterol." }, { "input": "This disease is considered a current problem of public health.", "output": "There is no related enetity." }, { "input": "In the present review, we analyze and discuss the therapeutic effects of the main glucosinolates of black radish, as well as the effects that this plant has on cholesterol gallstones disease.", "output": "glucosinolates, cholesterol." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "A cellular automata model of proton hopping down a channel.", "output": "There is no related enetity." }, { "input": "Proton hopping is the process where a H - atom on a hydronium ion forms a H - bond with the O - atom of a neighboring H ( 2 ) O molecule.", "output": "H, hydronium, H, O, H ( 2 ) O." }, { "input": "There is then an exchange of bonding forces when that covalent bond of the H - atom in the hydronium ion changes to a H - bond, and the previous H - bond changes to a covalent bond with the neighboring O - atom.", "output": "H, hydronium, H, H, O." }, { "input": "The neighboring molecule now becomes a hydronium ( H ( 3 ) O ( + ) ) ion.", "output": "hydronium, H ( 3 ) O ( + )." }, { "input": "This process repeats itself very rapidly among neighboring hydronium and H ( 2 ) O molecules.", "output": "hydronium, H ( 2 ) O." }, { "input": "There is a flow of protonic character through bulk H ( 2 ) O, referred to as proton hopping.", "output": "H ( 2 ) O." }, { "input": "This process carries information through living systems where H ( 2 ) O is present.", "output": "H ( 2 ) O." }, { "input": "A cellular automata model of proton hopping down a channel has been created and studied.", "output": "There is no related enetity." }, { "input": "Variations in the rate of proton entry into the channel and the effects of the polar character of the channel walls was studied using the model.", "output": "There is no related enetity." }, { "input": "The behavior of the models corresponds to experimental results.", "output": "There is no related enetity." }, { "input": "Two novel potent alpha - amylase inhibitors from the family of acarviostatins isolated from the culture of Streptomyces coelicoflavus ZG0656.", "output": "acarviostatins." }, { "input": "Two novel aminooligosaccharides were separated from the culture filtrate of Streptomyces coelicoflavus ZG0656.", "output": "There is no related enetity." }, { "input": "Their chemical structures were determined by acidic hydrolysis, electrospray - ionization tandem mass spectrometry ( ESI - MS / MS ), and NMR spectroscopy.", "output": "There is no related enetity." }, { "input": "The compounds were named acarviostatins III0 ( - 1 ) and III23 according to the nomenclature of this group of metabolites.", "output": "acarviostatins III0 ( - 1 ) and III23." }, { "input": "The two novel acarviostatins were both mixed noncompetitive inhibitors of porcine pancreatic alpha - amylase ( PPA ).", "output": "acarviostatins." }, { "input": "The inhibition constants ( K ( i ) ) for acarviostatins III0 ( - 1 ) and III23 were 0. 009 and 0. 026 mu M, respectively, 151 and 52 times more potent than acarbose.", "output": "acarviostatins III0 ( - 1 ) and III23." }, { "input": "Variability of n - alkanes and nonacosan - 10 - ol in natural populations of Picea omorika.", "output": "n - alkanes, nonacosan - 10 - ol." }, { "input": "This is the first report of population variability of the contents of n - alkanes and nonacosan - 10 - ol in the needle epicuticular waxes of Serbian spruce ( Picea omorika ).", "output": "n - alkanes, nonacosan - 10 - ol." }, { "input": "The hexane extracts of needle samples originated from three natural populations in Serbia ( Vranjak, Zmajeva c ki potok, and Mile s evka Canyon ) were investigated by GC and GC / MS analyses.", "output": "hexane." }, { "input": "The amount of nonacosan - 10 - ol varied individually from 50. 05 to 74. 42 % ( 65. 74 % in average ), but the differences between the three investigated populations were not statistically confirmed.", "output": "nonacosan - 10 - ol." }, { "input": "The results exhibited variability of the composition of n - alkanes in the epicuticular waxes with their size ranging from C ( 18 ) to C ( 35 ).", "output": "n - alkanes, C, C." }, { "input": "The most abundant n - alkanes were C ( 29 ), C ( 31 ), and C ( 27 ) ( 35. 22, 13. 77, and 12. 28 % in average, resp. ).", "output": "n - alkanes, C, C, C." }, { "input": "The carbon preference index of all the n - alkanes ( CPI ( total ) ) of the P. omorika populations ( average of populations I - III ) ranged from 3. 3 to 11. 5 ( mean of 5. 9 ), while the average chain length ( ACL ) ranged from 26. 6 to 29. 2.", "output": "carbon, n - alkanes." }, { "input": "The principal component and cluster analyses of the contents of nine n - alkanes showed the greatest difference for the population growing in the Mile s evka Canyon.", "output": "n - alkanes." }, { "input": "The obtained results were compared with previous literature data given for other Picea species, and this comparison was briefly discussed.", "output": "There is no related enetity." }, { "input": "Artemisinin - polypyrrole conjugates: synthesis, DNA binding studies and preliminary antiproliferative evaluation.", "output": "Artemisinin, polypyrrole." }, { "input": "Greater than the sum of its parts: Artemisinins are currently in phase I - II clinical trials against breast, colorectal and non - small - cell lung cancers.", "output": "Artemisinins." }, { "input": "In an attempt to offer increased specificity, a series of hybrid artemisinin - polypyrrole minor groove binder conjugates are described.", "output": "artemisinin, polypyrrole." }, { "input": "DNA binding / modelling studies and preliminary biological evaluation give insights into their mechanism of action and the potential of this strategy.", "output": "There is no related enetity." }, { "input": "Simulating adsorptive expansion of zeolites: application to biomass - derived solutions in contact with silicalite.", "output": "There is no related enetity." }, { "input": "We have constructed and applied an algorithm to simulate the behavior of zeolite frameworks during liquid adsorption.", "output": "There is no related enetity." }, { "input": "We applied this approach to compute the adsorption isotherms of furfural - water and hydroxymethyl furfural ( HMF ) - water mixtures adsorbing in silicalite zeolite at 300 K for comparison with experimental data.", "output": "furfural, hydroxymethyl furfural, HMF." }, { "input": "We modeled these adsorption processes under two different statistical mechanical ensembles: the grand canonical ( V - Nz - mu g - T or GC ) ensemble keeping volume fixed, and the P - Nz - mu g - T ( osmotic ) ensemble allowing volume to fluctuate.", "output": "There is no related enetity." }, { "input": "To optimize accuracy and efficiency, we compared pure Monte Carlo ( MC ) sampling to hybrid MC - molecular dynamics ( MD ) simulations.", "output": "There is no related enetity." }, { "input": "For the external furfural - water and HMF - water phases, we assumed the ideal solution approximation and employed a combination of tabulated data and extended ensemble simulations for computing solvation free energies.", "output": "HMF." }, { "input": "We found that MC sampling in the V - Nz - mu g - T ensemble ( i. e., standard GCMC ) does a poor job of reproducing both the Henry ' s law regime and the saturation loadings of these systems.", "output": "There is no related enetity." }, { "input": "Hybrid MC - MD sampling of the V - Nz - mu g - T ensemble, which includes framework vibrations at fixed total volume, provides better results in the Henry ' s law region, but this approach still does not reproduce experimental saturation loadings.", "output": "There is no related enetity." }, { "input": "Pure MC sampling of the osmotic ensemble was found to approach experimental saturation loadings more closely, whereas hybrid MC - MD sampling of the osmotic ensemble quantitatively reproduces such loadings because the MC - MD approach naturally allows for locally anisotropic volume changes wherein some pores expand whereas others contract.", "output": "There is no related enetity." }, { "input": "Photoelectric energy conversion of plasmon - generated hot carriers in metal - insulator - semiconductor structures.", "output": "There is no related enetity." }, { "input": "Plasmonic excitation in metals has received great attention for light localization and control of light - matter interactions at the nanoscale with a plethora of applications in absorption enhancement, surface - enhanced Raman scattering, or biosensing.", "output": "There is no related enetity." }, { "input": "Electrically active plasmonic devices, which had remained underexplored, have recently become a growing field of interest.", "output": "There is no related enetity." }, { "input": "In this report we introduce a metal - insulator - semiconductor heterostructure for plasmo - electric energy conversion, a novel architecture to harvest hot - electrons derived from plasmonic excitations.", "output": "There is no related enetity." }, { "input": "We demonstrate external quantum efficiency ( EQE ) of 4 % at 460 nm using a Ag nanostructured electrode and EQE of 1. 3 % at 550 nm employing a Au nanostructured electrode.", "output": "Ag, Au." }, { "input": "The insulator interfacial layer has been found to play a crucial role in interface passivation, a requisite in photovoltaic applications to achieving both high open - circuit voltages ( 0. 5 V ) and fill - factors ( 0. 5 ), but its introduction simultaneously modifies hot - electron injection and transport.", "output": "There is no related enetity." }, { "input": "We investigate the influence passivation has on these processes for different material configurations, and characterize different types of transport depending on the initial plasmon energy band, reporting power conversion efficiencies of 0. 03 % for nanopatterned silver electrodes.", "output": "silver." }, { "input": "Chromium supplementation in overweight and obesity: a systematic review and meta - analysis of randomized clinical trials.", "output": "Chromium." }, { "input": "The increased prevalence of obesity has made the use of dietary supplements as weight reducing agents highly popular, but their efficacy has not been proven.", "output": "There is no related enetity." }, { "input": "One such supplement is chromium.", "output": "chromium." }, { "input": "The purpose of this review was to evaluate the evidence for or against the efficacy of chromium supplementation in overweight and obese individuals.", "output": "chromium." }, { "input": "Electronic searches were conducted in Medline, Embase, Amed and The Cochrane Library.", "output": "There is no related enetity." }, { "input": "The bibliographies of located articles were also searched.", "output": "There is no related enetity." }, { "input": "No age, gender or language restrictions were imposed.", "output": "There is no related enetity." }, { "input": "The reporting quality of identified randomized clinical trials ( RCTs ) was assessed using a methodological checklist adapted from the Consolidated Standard of Reporting Trials Statement and Preferred Reporting Items for Systematic Reviews and Meta - Analyses guidelines.", "output": "There is no related enetity." }, { "input": "Thirty - nine trials were identified and 20 were included.", "output": "There is no related enetity." }, { "input": "There were variations in reporting quality of included studies.", "output": "There is no related enetity." }, { "input": "A meta - analysis of 11 studies showed a statistically significant difference in weight loss favouring chromium over placebo ( mean difference ( MD ): - 0. 50 kg; 95 % confidence interval ( CI ): - 0. 97, - 0. 03 ).", "output": "chromium." }, { "input": "There was a high statistical heterogeneity.", "output": "There is no related enetity." }, { "input": "Adverse events included watery stools, vertigo, headaches and urticaria.", "output": "There is no related enetity." }, { "input": "The evidence from available RCTs shows that chromium supplementation generates statistically significant reductions in body weight.", "output": "chromium." }, { "input": "The magnitude of the effect is small, and the clinical relevance is uncertain.", "output": "There is no related enetity." }, { "input": "Future trials should last at least 16 weeks and greater uniformity in the measuring and assessment tools for body composition is recommended.", "output": "There is no related enetity." }, { "input": "Obstructed Diffusion in Silica Colloidal Crystals.", "output": "There is no related enetity." }, { "input": "The hindered diffusion in silica colloidal crystals was studied experimentally, both by fluorescence recovery after photobleaching and by measurement of ionic conductivity.", "output": "There is no related enetity." }, { "input": "Particle size was varied to include 120, 220, 470, and 1300 nm, and the porosities were determined by flow measurements.", "output": "There is no related enetity." }, { "input": "For fluorescein, the results showed that the obstruction factor, which is the ratio of the diffusion coefficients inside the media and in open solution, is equal to the porosity within experimental error.", "output": "fluorescein." }, { "input": "For proteins, the same conclusion is made after correction for size exclusion of the pores.", "output": "There is no related enetity." }, { "input": "The obstruction factors for these media are 2 - fold lower than those measured for chromatographic media, 60 % higher than theoretical predictions, and equal to what is assumed for electrophoretic sieving in random fibers.", "output": "There is no related enetity." }, { "input": "Probing the Electronic Properties of W3Ox ( - / 0 ) ( x = 0 - 2 ) and W3 ( 2 - ) Clusters: The Aromaticity of W3 and W3 ( 2 - ).", "output": "W3Ox ( - / 0 ), W3 ( 2 - ), W3, W3 ( 2 - )." }, { "input": "Density functional theory ( DFT ) calculations are employed to investigate the structural and electronic properties of bare tritungsten clusters ( W3, W3 ( - ), W3 ( 2 - ) ) and tritungsten oxide clusters W3Ox ( - / 0 ) ( x = 1, 2 ).", "output": "tritungsten, W3, W3 ( - ), W3 ( 2 - ), tritungsten oxide, W3Ox ( - / 0 )." }, { "input": "Generalized Koopmans ' theorem is applied to predict the vertical detachment energies and simulate the photoelectron spectra ( PES ) for W3Ox ( - ) ( x = 0 - 2 ) clusters.", "output": "W3Ox ( - )." }, { "input": "Extensive DFT calculations are performed in search of the lowest energy structures for both the anions and the neutrals.", "output": "There is no related enetity." }, { "input": "The bare tritungsten clusters are predicted to be triangular structures with D3h ( ( 3 ) A1 ' ), C2v ( ( 2 ) A1 ) and D3h ( ( 1 ) A1 ' ) symmetry for W3, W3 ( - ) and W3 ( 2 - ), respectively.", "output": "tritungsten, W3, W3 ( - ), W3 ( 2 - )." }, { "input": "For W3O ( - ) and W3O clusters, the oxygen atom occupies the terminal site, while the next added oxygen atom is found to be a bridging one in both W3O2 ( - ) and W3O2 clusters.", "output": "W3O ( - ), W3O, oxygen, oxygen, W3O2 ( - ), W3O2." }, { "input": "Molecular orbital analyses are carried out to elucidate the chemical bonding of these clusters and provide insights into the sequential oxidation from W3 ( - ) to W3O2 ( - ).", "output": "W3 ( - ), W3O2 ( - )." }, { "input": "Partial sigma - and delta - aromaticity are revealed in the neutral W3 ( D3h, ( 3 ) A1 ' ), while the anion W3 ( 2 - ) ( D3h, ( 1 ) A1 ' ) possesses only delta - aromaticity.", "output": "W3, W3 ( 2 - )." }, { "input": "Formation of Aragonitic Layered Structures from Kaolinite and Amorphous Calcium Carbonate Precursors.", "output": "Kaolinite, Calcium Carbonate." }, { "input": "Clay materials have been an ever - present accoutrement of modern civilization; improvements to process these materials have quickened their utilization for use in complex multiaxial load - bearing structures.", "output": "There is no related enetity." }, { "input": "Specifically, with better methods to organize the constituent metal oxide components in clay, the distribution of characteristic nematic and smectic phases can be controlled.", "output": "metal oxide." }, { "input": "In this work, we utilize the interactions of an amorphous calcium carbonate phase with kaolinite to form a complex composite that can be organized into distinct hierarchical structures.", "output": "calcium carbonate, kaolinite." }, { "input": "We demonstrate that these ACC - kaolinite composites can maintain characteristic long - range - ordered layer - by - layer structures across many length scales, from nano - to millimeter, through convenient and economical processing at room temperature.", "output": "kaolinite." }, { "input": "Synthesis and in vitro evaluation of N - Aryl pyrido - quinazolines derivatives as potent EGFR inhibitors.", "output": "N - Aryl pyrido - quinazolines." }, { "input": "A series of pyrido - quinazolines have been synthesised, characterised and tested for their in vitro EGFR tyrosine kinase inhibitory activity.", "output": "pyrido - quinazolines, tyrosine." }, { "input": "The compounds were prepared from Alkylideno / arylideno - bis - ureas.", "output": "Alkylideno / arylideno - bis - ureas." }, { "input": "Their final structure of the compounds were elucidated on the basis of spectral studies ( IR., 1H NMR, FT - IR and EI - MS ).", "output": "1H." }, { "input": "The cellular EGFR internalization response of selected compounds was evaluated using HeLa cells.", "output": "There is no related enetity." }, { "input": "Most of the synthesized compounds displayed potent EGFR - TK inhibitory activity and structurally halogenated derivatives had a pronounced effect in inhibiting EGFR internalization.", "output": "There is no related enetity." }, { "input": "(c) 2013 John Wiley & Sons A / S.", "output": "There is no related enetity." }, { "input": "Pigment production by a new thermotolerant microalga Coelastrella sp.", "output": "There is no related enetity." }, { "input": "F50.", "output": "There is no related enetity." }, { "input": "Microalgae are good crops to produce natural pigments because of their high growth rates.", "output": "There is no related enetity." }, { "input": "Tropical zones are better locations than temperate areas for microalgal cultivation because they have longer duration of daylight and more stable temperatures throughout the year, but the high temperatures pose a challenge to microalgal cultivation.", "output": "There is no related enetity." }, { "input": "A newly isolated thermotolerant microalga produces reddish pigments under environmental stress.", "output": "There is no related enetity." }, { "input": "Morphological and molecular evidence including meridional ribs on the cell wall, pigment production, and its 18S rDNA sequence suggests that this microalga belongs to the genus Coelastrella.", "output": "There is no related enetity." }, { "input": "Salt stress and high light intensity accelerated biosynthesis of the pigments, and significant quantities of oil accumulated as the cells experienced stress due to nutrient deficiency.", "output": "There is no related enetity." }, { "input": "This microalga could withstand temperature of 50 degrees C for more than 8h, which is a necessary trait for outdoor cultivation in tropical areas.", "output": "There is no related enetity." }, { "input": "The pigments contain astaxanthin, lutein, canthaxanthin, and beta - carotene as analysed by using HPLC.", "output": "astaxanthin, lutein, canthaxanthin, beta - carotene." }, { "input": "Morphology and structural properties of high - amylose rice starch residues hydrolysed by amyloglucosidase.", "output": "There is no related enetity." }, { "input": "High - amylose starches are attracting considerable attention because of their potential health benefits and industrial uses.", "output": "There is no related enetity." }, { "input": "Enzyme hydrolysis of starch is involved in many biological and industrial processes.", "output": "There is no related enetity." }, { "input": "In this paper, starches were isolated from high - amylose transgenic rice ( TRS ) and its wild type rice, Te - qing ( TQ ).", "output": "There is no related enetity." }, { "input": "The morphological and structural changes of starch residues following Aspergillus niger amyloglucosidase ( AAG ) hydrolysis were investigated.", "output": "There is no related enetity." }, { "input": "AAG hydrolysed TQ starch from the granule surface, and TRS starch from the granule interior.", "output": "There is no related enetity." }, { "input": "During AAG hydrolysis, the content of amorphous structure increased, the contents of ordered structure and single helix decreased, and gelatinisation enthalpy decreased in TQ and TRS starch residues.", "output": "There is no related enetity." }, { "input": "The A - type polymorph of TRS C - type starch was hydrolysed faster than the B - type polymorph.", "output": "There is no related enetity." }, { "input": "The short - range ordered structure and B - type polymorph in the peripheral region of the subgranule and the surrounding band of TRS starch increased the resistance of TRS starch to AAG hydrolysis.", "output": "There is no related enetity." }, { "input": "Determination of chemical variability of phenolic and monoterpene glycosides in the seeds of Paeonia species using HPLC and profiling analysis.", "output": "phenolic and monoterpene glycosides." }, { "input": "A rapid, sensitive, and accurate HPLC - DAD method was developed and validated for simultaneous determination of one phenolic glycoside and seven monoterpene glycosides, including 1 - O - beta - d - ( 4 - hydroxybenzoyl ) glucose ( 1 ), pyridylpaeoniflorin ( 2 ), ( 8R ) - piperitone - 4 - en - 9 - O - beta - d - glucopyranoside ( 3 ), oxypaeoniflorin ( 4 ), 6 ' - O - beta - glucopyranosylalbiflorin ( 5 ), albiflorin ( 6 ), beta - gentiobiosylpaeoniflorin ( 7 ), and paeoniflorin ( 8 ), in 44 batches of peony seeds from nine Paeonia species collected from different areas.", "output": "phenolic glycoside, monoterpene glycosides, 1 - O - beta - d - ( 4 - hydroxybenzoyl ) glucose, pyridylpaeoniflorin, ( 8R ) - piperitone - 4 - en - 9 - O - beta - d - glucopyranoside, oxypaeoniflorin, 6 ' - O - beta - glucopyranosylalbiflorin, albiflorin, beta - gentiobiosylpaeoniflorin, paeoniflorin." }, { "input": "Using the optimised method, separations were conducted with a YMC - pack ODS - A column with water / formic acid and methanol as the mobile phase.", "output": "formic acid, methanol." }, { "input": "All eight analytes demonstrated good linearity ( r ( 2 ) > 0. 9993 ).", "output": "There is no related enetity." }, { "input": "The recoveries, measured at three concentration levels, varied from 98. 20 % to 103. 81 %.", "output": "There is no related enetity." }, { "input": "Six compounds including 1 and 4 - 8 occur ubiquitously in all the seeds of nine Paeonia species, and compounds 2 and 3 showed undetectable levels or very low content in several samples.", "output": "There is no related enetity." }, { "input": "The seed samples were classified into several groups, which coincide with the taxonomy of Paeonia at the section level.", "output": "There is no related enetity." }, { "input": "Peony seed might be a useful resource in developing new herbal or food products.", "output": "There is no related enetity." }, { "input": "Application of response surface methodology to optimise extraction of flavonoids from fructus sophorae.", "output": "flavonoids." }, { "input": "Response surface methodology ( RSM ) based on a central composite design ( CCD ) was applied to optimise the extraction conditions for flavonoids from fructus sophorae with advantages in terms of resisting flavonoids during the whole process and maximising of extraction yield.", "output": "flavonoids, flavonoids." }, { "input": "Three aglycon forms of the flavonoids, namely, quercetin, kaempferol and isorhamnetin were quantified by high - performance liquid chromatography with ultraviolet detection ( HPLC - UV ) to estimate extraction yield.", "output": "flavonoids, quercetin, kaempferol, isorhamnetin." }, { "input": "The combined effects of independent variables were studied and the optimal extraction conditions were obtained as ethanol concentration, 74. 47 %; solid - liquid ratio, 17. 99 ml / g; temperature, 89. 13 degrees C; and extraction time, 2. 10h.", "output": "ethanol." }, { "input": "The reliability of the method was confirmed by recovery experiments, performed under optimal conditions.", "output": "There is no related enetity." }, { "input": "Recoveries indicated that flavonoids resisted the extraction conditions.", "output": "flavonoids." }, { "input": "The experimental extraction yield under optimal conditions was found to be 10. 459 %, which was well matched with the predicted values of 10. 461 %.", "output": "There is no related enetity." }, { "input": "AKT signalling and mitochondrial pathways are involved in mushroom polysaccharide - induced apoptosis and G1 or S phase arrest in human hepatoma cells.", "output": "There is no related enetity." }, { "input": "This study describes molecular mechanisms for inhibiting tumour cell proliferation using polysaccharides from medicinal mushrooms in human hepatoma cells.", "output": "There is no related enetity." }, { "input": "The results show that regarding cell cycle - related proteins, three types of polysaccharides significantly enhance the expression of p27 ( Kip ) in HepG2 and Bel - 7404 cells, while suppressing the activity of cyclin D1 / CDK4 and / or cyclin E / CDK2.", "output": "There is no related enetity." }, { "input": "Considering apoptosis - related factors, the polysaccharides suppressed AKT activity through the inhibition of AKT phosphorylation at Thr ( 308 ) and / or Ser ( 473 ).", "output": "Thr, Ser." }, { "input": "The growth of HepG2 and Bel - 7404 cells was suppressed by the up - regulation of a subunit of PI3K and phospho - PTEN, which are modulators of AKT activity.", "output": "There is no related enetity." }, { "input": "The polysaccharides also activated the mitochondria - mediated apoptosis pathway by stimulating the activation of Bcl - 2 family proteins to release cytochrome c and Smac and cleave caspase - 9 and caspase - 3 in HepG2 and Bel - 7404 cells.", "output": "There is no related enetity." }, { "input": "These factors have a potent effect on cell cycle arrest in G ( 1 ) and / or S phase and induce apoptosis in HepG2 and Bel - 7404 cells.", "output": "There is no related enetity." }, { "input": "Mild Fe - deficiency improves biomass production and quality of hydroponic - cultivated spinach plants ( Spinacia oleracea L. ).", "output": "Fe." }, { "input": "It is of great practical importance to improve yield and quality of vegetables in soilless cultures.", "output": "There is no related enetity." }, { "input": "This study investigated the effects of iron - nutrition management on yield and quality of hydroponic - cultivated spinach ( Spinacia oleracea L. ).", "output": "iron." }, { "input": "The results showed that mild Fe - deficient treatment ( 1 mu M FeEDTA ) yielded a greater biomass of edible parts than Fe - omitted treatment ( 0 mu M FeEDTA ) or Fe - sufficient treatments ( 10 and 50 mu M FeEDTA ).", "output": "Fe, FeEDTA, Fe, FeEDTA, Fe, FeEDTA." }, { "input": "Conversely, mild Fe - deficient treatment had the lowest nitrate concentration in the edible parts out of all the Fe treatments.", "output": "Fe, nitrate, Fe." }, { "input": "Interestingly, all the concentrations of soluble sugar, soluble protein and ascorbate in mild Fe - deficient treatments were higher than Fe - sufficient treatments.", "output": "ascorbate, Fe, Fe." }, { "input": "In addition, both phenolic concentration and DPPH scavenging activity in mild Fe - deficient treatments were comparable with those in Fe - sufficient treatments, but were higher than those in Fe - omitted treatments.", "output": "DPPH, Fe, Fe, Fe." }, { "input": "Therefore, we concluded that using a mild Fe - deficient nutrition solution to cultivate spinach not only would increase yield, but also would improve quality.", "output": "Fe." }, { "input": "Application of reduced graphene oxide and carbon nanotube modified electrodes for measuring the enzymatic activity of alcohol dehydrogenase.", "output": "graphene oxide, carbon, alcohol." }, { "input": "An electrochemical method was developed to measure the enzymatic activity of alcohol dehydrogenase ( ADH ) by monitoring the amount of reduced nicotinamide adenine dinucleotide ( NADH ) generated in the catalysed oxidation of ethanol by ADH.", "output": "alcohol, reduced nicotinamide adenine dinucleotide, NADH, ethanol." }, { "input": "The concentration of NADH was determined by amperometric measurements, which recorded the oxidation current of NADH versus time on reduced graphene oxide and functionalised multi - walled carbon nanotube modified electrodes.", "output": "NADH, NADH, graphene oxide, carbon." }, { "input": "The initial reaction rates and the apparent Michaelis constants of the enzymatic reaction were obtained in the absence and presence of Al ( 3 + ) and nanometre - sized tridecameric aluminium polycationic ( nano - Al ( 13 ) ) species.", "output": "Al ( 3 + ), tridecameric aluminium, Al ( 13 )." }, { "input": "The results showed that Al ( 3 + ) and nano - Al ( 13 ) exhibited inhibitory effect on the enzymatic activity of ADH.", "output": "Al ( 3 + ), Al ( 13 )." }, { "input": "Fluorescence and circular dichroism spectra indicated the inhibitory effect was likely caused by the conformational changes of ADH and / or NADH induced by Al ( 3 + ) and nano - Al ( 13 ).", "output": "NADH, Al ( 3 + ), Al ( 13 )." }, { "input": "The influence of Goishi tea on adipocytokines in obese mice.", "output": "There is no related enetity." }, { "input": "This study investigated the influence of Goishi - tea on visceral fat weight in induced obese mice.", "output": "There is no related enetity." }, { "input": "Mice were divided into two main groups, normal and obesity.", "output": "There is no related enetity." }, { "input": "In obesity group, mice were fed with high - fat diet.", "output": "There is no related enetity." }, { "input": "Goishi - tea including its fractions ( ethyl - acetate layer and water layer ) was administrated in normal and obesity three sub - groups.", "output": "ethyl - acetate." }, { "input": "Results showed no influence of Goishi - tea in normal group.", "output": "There is no related enetity." }, { "input": "However, visceral fat weight, size of adipose cell and cholesterol level were significantly decreased in obesity group fed Goishi - tea compared to control group.", "output": "cholesterol." }, { "input": "Moreover, adiponectin levels tended to increase and adipocytokines has significant values lower in obesity group fed Goishi - tea compared to control group.", "output": "There is no related enetity." }, { "input": "Interestingly, Goishi tea involved in the high - fat diet induced - obese mice can inhibit fat accumulation and maintain adiponectins without increasing tumor necrosis factor - alpha and interleukin - 6.", "output": "There is no related enetity." }, { "input": "It would be beneficial for the prevention of metabolic syndrome and obesity - related disorder.", "output": "There is no related enetity." }, { "input": "Physicochemical characterisation of dietary fibre components and their ability to bind some process - induced mutagenic heterocyclic amines, Trp - P - 1, Trp - P - 2, A alpha C and MeA alpha C.", "output": "Trp - P - 1, Trp - P - 2, A alpha C, MeA alpha C." }, { "input": "The physicochemical properties of potato fibre, wheat bran and oat samples were investigated, along with their binding capability to heterocyclic amines ( HCAs ).", "output": "There is no related enetity." }, { "input": "Potato fibre displayed highest total dietary fibre content ( 71. 8 / 100g dry weight basis, dwb ), followed by wheat bran ( 57. 2 / 100 g dwb ) and oat sample 2 ( 53. 0 / 100 g dwb ).", "output": "There is no related enetity." }, { "input": "Oat samples 1, 3 and 4 displayed considerably lower dietary fibre content ( 20. 5 - 28. 8 / 100g, dwb ).", "output": "There is no related enetity." }, { "input": "Oat samples 3 and 4 displayed highest soluble fibre content ( 70 - 83 % ), and oat sample 3 also displayed highest swelling and water retention capacity ( WRC ).", "output": "There is no related enetity." }, { "input": "Dietary fibre samples, except samples 3 and 4, displayed improved binding to HCAs as sample weight increased.", "output": "There is no related enetity." }, { "input": "The behaviour of wheat bran and potato fibre was similar to oat samples 1 and 2.", "output": "There is no related enetity." }, { "input": "Binding of MeA alpha C was comparatively greater than that of other HCAs.", "output": "MeA alpha C." }, { "input": "Dietary fibre fractions with high insoluble fibre and functional groups of HCAs may significantly contribute to the binding capacity.", "output": "HCAs." }, { "input": "Evaluation of sequential inoculation of Saccharomyces cerevisiae and Oenococcus oeni strains on the chemical and aromatic profiles of cherry wines.", "output": "There is no related enetity." }, { "input": "The current study was carried out to elucidate the effect of sequential inoculation of Saccharomyces cerevisiae ( RC212, D254 ) and Oenococcus oeni ( SG26, Lalvin 31 and Uvaferm Alpha ) on the production of cherry wines, especially on the chemical and aromatic characteristics.", "output": "There is no related enetity." }, { "input": "SI - D culture required the shortest period ( 23 d ) to complete the fermentation, while other inoculations needed longer time.", "output": "There is no related enetity." }, { "input": "Analysis from chemical composition showed that titratable acidity and content of l - malic acid exhibited evident differences among the samples after MLF.", "output": "l - malic acid." }, { "input": "For volatile compounds, 49 major components were identified, mostly comprising of alcohols, acids and esters.", "output": "alcohols, esters." }, { "input": "Cherry wines obtained from SI - B and SI - C showed higher contents of total volatile alcohols, and SI - D wines produced the greatest amount of volatile acids.", "output": "alcohols." }, { "input": "According to the odour active value ( OAV ), 9 out of 49 studied volatile components had OAV > 1 in all the analyzed wines, while six volatile components showed OAV > 1 only for some of them.", "output": "There is no related enetity." }, { "input": "Furthermore, a sensory analysis was performed to compare the sensory profile of these cherry wines, and results evidenced that wines resulting from different inoculations presented diverse sensory profiles.", "output": "There is no related enetity." }, { "input": "These findings suggest that sequential inoculations posed a great potential in affecting and modulating the aromatic profile of cherry wines.", "output": "There is no related enetity." }, { "input": "Structural characterisation of polysaccharides from Tricholoma matsutake and their antioxidant and antitumour activities.", "output": "There is no related enetity." }, { "input": "In this study, polysaccharides from Tricholoma matsutake ( TM - P ) were purified using a DEAE - Sepharose fast flow column and three polysaccharide fractions ( TM - P1, TM - P2 and TM - P3 ) were obtained.", "output": "DEAE." }, { "input": "The chemical composition and structural characteristics of TM - P2 were quite different from those of TM - P1 and TM - P3.", "output": "There is no related enetity." }, { "input": "TM - P2 consisted of glucose, galactose and mannose with a molar ratio of 5. 9: 1. 1: 1. 0.", "output": "glucose, galactose, mannose." }, { "input": "The glycosidic linkages were mainly composed of 1, 6 - and 1 - linked glucose.", "output": "glucose." }, { "input": "Furthermore, TM - P2 showed the strongest in vitro antioxidant and antitumour activities.", "output": "There is no related enetity." }, { "input": "The oxygen radical absorbance capacity ( ORAC ) of TM - P2 was 2100. 44 mu mol Trolox / g.", "output": "oxygen, Trolox." }, { "input": "The antiproliferative activities of TM - P2 ( 4. 0mg / ml ) on the growth of HepG2 and A549 cells were 67. 98 % and 59. 04 %, respectively.", "output": "There is no related enetity." }, { "input": "Kinetics of protein physicochemical changes induced by heating in meat using mimetic models: ( 2 ) effects of fibre type, peroxides and antioxidants.", "output": "peroxides." }, { "input": "Heating - induced changes in meat proteins were investigated using models made of aqueous suspensions of myofibrils according to muscle fibre types and cellular compounds ( oxidants and antioxidants ).", "output": "There is no related enetity." }, { "input": "These changes were evaluated by measurements of carbonyl groups and protein surface hydrophobicity.", "output": "carbonyl." }, { "input": "Model results were compared to trial results obtained on pork meat ( M. Longissimus dorsi ) heated under the same conditions ( 45 and 75 degrees C, from 5 to 120 min ).", "output": "There is no related enetity." }, { "input": "Myofibrillar proteins from alpha - white fibres were more sensitive to oxidation and thermal denaturation than those from beta - red fibres.", "output": "There is no related enetity." }, { "input": "At 45 degrees C, there were negligible differences due to peroxide or antioxidant types.", "output": "peroxide." }, { "input": "At 75 degrees C, organic peroxides ( ROOH ) were less oxidative than hydrogen peroxide ( H2O2 ), and antioxidant enzymes were less efficient than vitamin E and carnosine at protecting proteins against oxidation.", "output": "organic peroxides, ROOH, hydrogen peroxide, H2O2, vitamin E, carnosine." }, { "input": "Protein oxidation observed in meat is lower than in the mimetic models and the increase in hydrophobicity remained limited in meat.", "output": "There is no related enetity." }, { "input": "High pressure homogenization increases antioxidant capacity and short - chain fatty acid yield of polysaccharide from seeds of Plantago asiatica L.", "output": "short - chain fatty acid." }, { "input": "Physiological properties of homogenized and non - homogenized polysaccharide from the seeds of Plantago asiatica L., including antioxidant capacity and short - chain fatty acid ( SCFA ) production, were compared in this study.", "output": "short - chain fatty acid, SCFA." }, { "input": "High pressure homogenization decreased particle size of the polysaccharide, and changed the surface topography from large flake - like structure to smaller porous chips.", "output": "There is no related enetity." }, { "input": "FT - IR showed that high pressure homogenization did not alter the primary structure of the polysaccharide.", "output": "There is no related enetity." }, { "input": "However, high pressure homogenization increased antioxidant capacity of the polysaccharide, evaluated by 4 antioxidant capacity assays ( hydroxyl radical - scavenging, superoxide radical - scavenging, 1, 1 - diphenyl - 2 - picryl - hydrazyl radical ( DPPH ) - scavenging and lipid peroxidation inhibition ).", "output": "hydroxyl, superoxide, 1 , 1 - diphenyl - 2 - picryl - hydrazyl." }, { "input": "Additionally, the production of total SCFA, propionic acid and n - butyric acid in ceca and colons of mice significantly increased after dieting supplementation with homogenized polysaccharide.", "output": "SCFA, propionic acid, n - butyric acid." }, { "input": "These results showed that high pressure homogenization treatment could be a promising approach for the production of value - added polysaccharides in the food industry.", "output": "There is no related enetity." }, { "input": "Inhibition of citral degradation in an acidic aqueous environment by polyoxyethylene alkylether surfactants.", "output": "citral, polyoxyethylene alkylether." }, { "input": "Citral is a flavour component widely used in food and cosmetic industries, but is chemically unstable and degrades over time in aqueous solutions due to acid - catalysed and oxidative reactions leading to loss of desirable flavour.", "output": "Citral." }, { "input": "The present study reveals the effect of non - ionic micellar solutions of Brij30 and Brij35 on the extent of solubilisation and stabilisation of citral.", "output": "citral." }, { "input": "The rate of chemical degradation of citral in acidic aqueous solutions was found to be highest, which was subsequently reduced significantly within these studied surfactant systems, suggesting protection of citral from an acidic environment once it is incorporated into the micelles.", "output": "citral, citral." }, { "input": "The work concludes that polyoxyethylene alkylether surfactants with lower HLB value, less dense hydrophilic corona and more hydrophobic core volume are efficient in solubilising and stabilising citral against an acidic environment.", "output": "polyoxyethylene alkylether, citral." }, { "input": "Stability of sunflower 2S albumins and LTP to physiologically relevant in vitro gastrointestinal digestion.", "output": "There is no related enetity." }, { "input": "In order for a protein to elicit a systemic allergic response it must reach the circulatory system through the intestinal mucosa as a sufficiently large fragment with adequate structural integrity.", "output": "There is no related enetity." }, { "input": "Sunflower LTP and 2S albumins ( SFA8 and three mixed fractions of Alb1 and Alb2 ) were digested in simulated gastric fluid ( SGF ) for 2h and the conditions were then changed to mimic the intestinal environment for a further 2h digestion.", "output": "There is no related enetity." }, { "input": "The effects of phosphatidylcholine ( PC ) and emulsification on the digestibility of the proteins were investigated.", "output": "phosphatidylcholine." }, { "input": "PC protected all of the proteins studied against both gastric and intestinal digestive enzymes but to different extents.", "output": "There is no related enetity." }, { "input": "Emulsification of SFA8 resulted in strong protection against digestion, which was further enhanced by the presence of PC in the SGF.", "output": "There is no related enetity." }, { "input": "These results highlight the importance of considering real food structures such as emulsified systems and also the gastrointestinal environment that proteins are exposed to once consumed when assessing allergenicity.", "output": "There is no related enetity." }, { "input": "Wine bottle colour and oxidative spoilage: whole bottle light exposure experiments under controlled and uncontrolled temperature conditions.", "output": "There is no related enetity." }, { "input": "Exposure of a Chardonnay wine to light from a mercury vapour lamp under controlled temperature conditions showed that colour enhancement was dependent on bottle colour.", "output": "mercury." }, { "input": "The increase in colouration was Antique Green < French Green < Arctic Blue < Flint, in agreement with the transmission characteristics of each bottle type.", "output": "There is no related enetity." }, { "input": "Xanthylium pigments were identified as one component contributing to the observed enhancement of colour.", "output": "There is no related enetity." }, { "input": "The presence of oxygen was shown to be a critical factor to initiate the formation of these xanthylium pigments during light exposure.", "output": "There is no related enetity." }, { "input": "Without temperature control, wine colour development was highest in Antique Green and lowest in Flint.", "output": "There is no related enetity." }, { "input": "This alternate order reflects the ability of the darker bottles to retain heat longer than lighter coloured ones as confirmed by surface temperature decay rates.", "output": "There is no related enetity." }, { "input": "Specific pigments contributing to the wine colour enhancement in uncontrolled temperature / light exposure experiments could not be identified, although tentative evidence was obtained for the presence of flavan - 3 - ol based compounds.", "output": "There is no related enetity." }, { "input": "The different bottle glass surfaces did not influence the rate of loss of dissolved oxygen or oxidation of ascorbic acid.", "output": "There is no related enetity." }, { "input": "The potential to develop the results obtained in this study to identify markers for light and / or temperature exposure of white wines is discussed.", "output": "There is no related enetity." }, { "input": "Discovery of new potential hits of Plasmodium falciparum enoyl - ACP reductase through ligand - and structure - based drug design approaches.", "output": "enoyl." }, { "input": "We here report the discovery of novel Plasmodium falciparum enoyl - ACP reductase ( PfENR ) inhibitors as new antimalarial hits through ligand - and structure - based drug design approaches.", "output": "enoyl." }, { "input": "We performed 2D and 3D QSAR studies on a set of rhodanine analogues using hologram QSAR ( HQSAR ), comparative molecular field analysis ( CoMFA ) and comparative molecular similarity indices analysis ( CoMSIA ) techniques.", "output": "rhodanine." }, { "input": "Statistical and satisfactory results were obtained for the best HQSAR ( r ( 2 ) of 0. 968 and qLOO ( 2 ) of 0. 751 ), CoMFA ( r ( 2 ) of 0. 955 and qLOO ( 2 ) of 0. 806 ) and CoMSIA ( r ( 2 ) of 0. 965 and qLOO ( 2 ) of 0. 659 ) models.", "output": "There is no related enetity." }, { "input": "The information gathered from the QSAR models guided us to design new PfENR inhibitors.", "output": "There is no related enetity." }, { "input": "Three new hits were predicted with potency in the submicromolar range and presented drug - like properties.", "output": "There is no related enetity." }, { "input": "Exploring the UDP pocket of LpxC through amino acid analogs.", "output": "UDP, amino acid." }, { "input": "Lipopolysaccharide ( LPS ) biosynthesis is an attractive antibacterial target as it is both conserved and essential for the survival of key pathogenic bacteria.", "output": "There is no related enetity." }, { "input": "Lipid A is the hydrophobic anchor for LPS and a key structural component of the outer membrane of Gram - negative bacteria.", "output": "There is no related enetity." }, { "input": "Lipid A biosynthesis is performed in part by a unique zinc dependent metalloamidase, LpxC ( UDP - 3 - O - ( R - 3 - hydroxymyristoyl ) - N - acetylglucosamine deacetylase ), which catalyzes the first non - reversible step in lipid A biosynthesis.", "output": "zinc, UDP - 3 - O - ( R - 3 - hydroxymyristoyl ) - N - acetylglucosamine." }, { "input": "The UDP portion of the LpxC substrate - binding pocket has been relatively unexplored.", "output": "UDP." }, { "input": "We have designed and evaluated a series of hydroxamate based inhibitors which explore the SAR of substitutions directed into the UDP pocket with a range of substituted alpha - amino acid based linkers.", "output": "hydroxamate, UDP, alpha - amino acid." }, { "input": "We also provide the first wild type structure of Pseudomonas aeruginosa LpxC which was utilized in the design of many of these analogs.", "output": "There is no related enetity." }, { "input": "EBF2 Determines and Maintains Brown Adipocyte Identity.", "output": "There is no related enetity." }, { "input": "The master transcription factor Ppar gamma regulates the general differentiation program of both brown and white adipocytes.", "output": "There is no related enetity." }, { "input": "However, it has been unclear whether Ppar gamma also controls fat lineage - specific characteristics.", "output": "There is no related enetity." }, { "input": "Here, we show that early B cell factor - 2 ( Ebf2 ) regulates Ppar gamma binding activity to determine brown versus white adipocyte identity.", "output": "There is no related enetity." }, { "input": "The Ebf DNA - binding motif was highly enriched within brown adipose - specific Ppar gamma binding sites that we identified by genome - wide ChIP - Seq.", "output": "There is no related enetity." }, { "input": "Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose - specific Ppar gamma target genes.", "output": "There is no related enetity." }, { "input": "When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppar gamma to its brown - selective binding sites and reprogrammed cells to a brown fat fate.", "output": "There is no related enetity." }, { "input": "Brown adipose cells and tissue from Ebf2 - deficient mice displayed a loss of brown - specific characteristics and thermogenic capacity.", "output": "There is no related enetity." }, { "input": "Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function.", "output": "There is no related enetity." }, { "input": "Phylogeny and phylogeography of Mantophryne ( Anura: Microhylidae ) reveals cryptic diversity in New Guinea.", "output": "There is no related enetity." }, { "input": "New Guinea is one of five high biodiversity wilderness areas, and frog diversity is exceptionally large, with more than 400 species described to date.", "output": "There is no related enetity." }, { "input": "The microhylid frog genus Mantophryne is endemic to New Guinea and consists of four species, three of which have narrow geographic distributions and a fourth, M. lateralis, with a broad range that spans the eastern half of the island.", "output": "There is no related enetity." }, { "input": "Here, we sequence 104 Mantophryne samples for three mitochondrial and three nuclear loci to reconstruct the first phylogeny of the genus and to examine spatial patterns of diversity within M. lateralis.", "output": "There is no related enetity." }, { "input": "Results indicate that the wide - ranging M. lateralis is composed of at least nine geographically separated and well - supported lineages that represent putative species.", "output": "There is no related enetity." }, { "input": "Biogeographic analysis suggests that Mantophryne evolved on the eastern Papuan peninsula with subsequent dispersal westward, as well as overwater dispersal events to the Louisiade and D ' Entrecasteaux archipelagos.", "output": "There is no related enetity." }, { "input": "Levomilnacipran ( F2695 ), a norepinephrine - preferring SNRI: Profile in vitro and in models of depression and anxiety.", "output": "Levomilnacipran, F2695, norepinephrine." }, { "input": "Levomilnacipran ( LVM; F2695 ) is the more active enantiomer of the serotonin / norepinephrine ( 5 - HT / NE ) reuptake inhibitor ( SNRI ) milnacipran and is currently under development for the treatment of major depressive disorder.", "output": "Levomilnacipran, LVM, F2695, serotonin, norepinephrine, 5 - HT, milnacipran." }, { "input": "LVM was benchmarked against two other SNRIs, duloxetine and venlafaxine, in biochemical, neurochemical and pharmacological assays.", "output": "LVM, duloxetine, venlafaxine." }, { "input": "LVM exhibited high affinity for human NE ( Ki = 92. 2 nM ) and 5 - HT ( 11. 2 nM ) transporters, and potently inhibited NE ( IC50 = 10. 5 nM ) and 5 - HT ( 19. 0 nM ) reuptake ( human transporter ) in vitro.", "output": "LVM, 5 - HT, 5 - HT." }, { "input": "LVM had 2 - fold greater potency for norepinephrine relative to serotonin reuptake inhibition ( i. e. NE / 5 - HT potency ratio: 0. 6 ) and 17 and 27 times higher selectivity for NE reuptake inhibition compared with venlafaxine and duloxetine, respectively.", "output": "LVM, norepinephrine, serotonin, 5 - HT, venlafaxine, duloxetine." }, { "input": "LVM did not exhibit affinity for 23 off - target receptors.", "output": "LVM." }, { "input": "LVM ( i. p. ) increased cortical extracellular levels of 5 - HT, and NE ( minimal effective doses: MEDs = 20 and 10 mg / kg, respectively ).", "output": "LVM, 5 - HT." }, { "input": "In anti - depressive / anti - stress models, i. p.", "output": "There is no related enetity." }, { "input": "LVM diminished immobility time in the mouse forced swim ( MED = 20 mg / kg ) and tail suspension ( MED = 2. 5 mg / kg ) tests, and reduced shock - induced ultrasonic vocalizations in rats ( MED = 5 mg / kg ).", "output": "LVM." }, { "input": "Duloxetine and venlafaxine were less potent ( MEDs >= 10 mg / kg ).", "output": "Duloxetine, venlafaxine." }, { "input": "At doses active in these three therapeutically - relevant models, LVM ( i. p. ) did not significantly affect spontaneous locomotor activity.", "output": "LVM." }, { "input": "In summary, LVM is a potent, selective inhibitor of NE and 5 - HT transporters with preferential activity at the former.", "output": "LVM, 5 - HT." }, { "input": "It is efficacious in models of anti - depressive / anti - stress activity, with minimal potential for locomotor side effects.", "output": "There is no related enetity." }, { "input": "Effect of UDP - glucuronosyltransferase 1A8 polymorphism on raloxifene glucuronidation.", "output": "UDP, raloxifene." }, { "input": "Raloxifene is an antiestrogen marketed for the treatment of osteoporosis.", "output": "Raloxifene." }, { "input": "The major metabolic pathway of raloxifene is glucuronidation at 6 - and / or 4 ' - positions, which is mainly catalyzed by UDP - glucuronosyltransferase 1A8 ( UGT1A8 ) expressed in extrahepatic tissues such as the small intestine and colon.", "output": "raloxifene, UDP." }, { "input": "Two non - synonymous allelic variants, termed UGT1A8 * 2 ( 518C > G, A173G ) and UGT1A8 * 3 ( 830G > A, C277Y ), have been found in Caucasian, African - American and Asian populations.", "output": "There is no related enetity." }, { "input": "In this study, the effect of amino acid substitutions in UGT1A8 on raloxifene glucuronidation was studied using recombinant UGT1A8 enzymes of wild - type ( UGT1A8. 1 ) and variant UGT1A8 ( UGT1A8. 2 and UGT1A8. 3 ) expressed in Sf9 cells.", "output": "amino acid, raloxifene." }, { "input": "Raloxifene 6 - and 4 ' - glucuronidation by UGT1A8. 1 exhibited negative allosteric kinetics.", "output": "Raloxifene." }, { "input": "The Km and Vmax values of UGT1A8. 1 were 15. 0 mu M and 111pmol / min / mg protein for 6 - glucuronidation, and 9. 35 mu M and 232pmol / min / mg protein for 4 ' - glucuronidation, respectively.", "output": "There is no related enetity." }, { "input": "The kinetics of raloxifene 6 - glucuronidation by UGT1A8. 2 was positive allosteric, whereas the kinetics of raloxifene 4 ' - glucuronidation was negative allosteric.", "output": "raloxifene, raloxifene." }, { "input": "The S50 value of raloxifene 6 - glucuronidation was markedly low ( 1. 2 % ) compared with the Km value of UGT1A8. 1, and the Km value for raloxifene 4 ' - glucuronidation was 29 % that of UGT1A8. 1.", "output": "raloxifene, raloxifene." }, { "input": "The Vmax value for raloxifene 6 - glucuronidation by UGT1A8. 2 was comparable to that of UGT1A8. 1, whereas the Vmax value for raloxifene 4 ' - glucuronidation was significantly lower ( 54 % ) than that of UGT1A8. 1.", "output": "raloxifene, raloxifene." }, { "input": "The activities of raloxifene 6 - and 4 ' - glucuronidation in UGT1A8. 3 were markedly lower than those of UGT1A8. 1.", "output": "raloxifene." }, { "input": "In mycophenolic acid glucuronidation, the kinetics by wild - type and variant UGT1A8s fitted the Michaelis - Menten model.", "output": "mycophenolic acid." }, { "input": "The Km and Vmax values of UGT1A8. 1 were 123 mu M and 4820pmol / min / mg protein, respectively.", "output": "There is no related enetity." }, { "input": "The Km and Vmax values of UGT1A8. 2 were comparable to those of UGT1A8. 1.", "output": "There is no related enetity." }, { "input": "The Km value of UGT1A8. 3 was similar to that of UGT1A8. 1, whereas the Vmax value was reduced to 2. 4 % of UGT1A8. 1.", "output": "There is no related enetity." }, { "input": "These findings suggest that A173G and C277Y substitutions of UGT1A8 change the metabolic ability toward raloxifene, and that the polymorphic alleles of UGT1A8 may influence the clinical response and bioavailability of medicines metabolized mainly by UGT1A8.", "output": "raloxifene." }, { "input": "Synthesis and molecular modeling of ( 4 ' R ) - and ( 4 ' S ) - 4 ' - substituted 2 ' - { [ ( E ) - androst - 5 - en - 17 - ylidene ] - methyl } oxazolines.", "output": "( 4 ' R ) - and ( 4 ' S ) - 4 ' - substituted 2 ' - { [ ( E ) - androst - 5 - en - 17 - ylidene ] - methyl } oxazolines." }, { "input": "Synthesis of four novel ( 4 ' R ) - and ( 4 ' S ) - 2 ' - { [ ( E ) - 3 beta - hydroxyandrost - 5 - en - 17 - ylidene ] - methyl } oxazolines, comprising 4 ' - hydroxymethyl ( 1 and 2 ) and 4 ' - methoxycarbonyl ( 3 and 4 ) substituents is presented.", "output": "( 4 ' R ) - and ( 4 ' S ) - 2 ' - { [ ( E ) - 3 beta - hydroxyandrost - 5 - en - 17 - ylidene ] - methyl } oxazolines, 4 ' - hydroxymethyl, 4 ' - methoxycarbonyl." }, { "input": "Reaction of 17 alpha - bromo - 21 - iodo - 3 beta - acetoxypregn - 5 - en - 20 - one with either ( L ) - serine methyl ester, or ( D ) - serine methyl ester resulted in methyl N - [ 3 beta - acetoxy - 21 - oxopregna - 5, 17 ( 20 ) - dien - 21 - yl ] - ( L ) - serinate and methyl N - [ 3 beta - acetoxy - 21 - oxopregna - 5, 17 ( 20 ) - dien - 21 - yl ] - ( D ) - serinate ( as mixtures of related [ 17 ( 20 ) E ] - and [ 17 ( 20 ) Z ] - isomers ).", "output": "17 alpha - bromo - 21 - iodo - 3 beta - acetoxypregn - 5 - en - 20 - one, ( L ) - serine methyl ester, ( D ) - serine methyl ester, methyl N - [ 3 beta - acetoxy - 21 - oxopregna - 5 , 17 ( 20 ) - dien - 21 - yl ] - ( L ) - serinate, methyl N - [ 3 beta - acetoxy - 21 - oxopregna - 5 , 17 ( 20 ) - dien - 21 - yl ] - ( D ) - serinate." }, { "input": "Cyclization of obtained amides led to methyl 2 ' - { [ ( E ) - 3 beta - acetoxyandrost - 5 - en - 17 - ylidene ] methyl } - ( 4 ' S ) - 4 ', 5 ' - dihydro - 1 ', 3 ' - oxazole - 4 ' - carboxylate and methyl 2 ' - { [ ( E ) - 3 beta - acetoxyandrost - 5 - en - 17 - ylidene ] methyl } - ( 4 ' R ) - 4 ', 5 ' - dihydro - 1 ', 3 ' - oxazole - 4 ' - carboxylate which were transformed to titled compounds 1 - 4.", "output": "amides, methyl 2 ' - { [ ( E ) - 3 beta - acetoxyandrost - 5 - en - 17 - ylidene ] methyl } - ( 4 ' S ) - 4 ' , 5 ' - dihydro - 1 ' , 3 ' - oxazole - 4 ' - carboxylate, methyl 2 ' - { [ ( E ) - 3 beta - acetoxyandrost - 5 - en - 17 - ylidene ] methyl } - ( 4 ' R ) - 4 ' , 5 ' - dihydro - 1 ' , 3 ' - oxazole - 4 ' - carboxylate." }, { "input": "The molecular docking of compounds 1 - 4 to ligand binding site of nuclear receptor LXR beta revealed significant differences due to stereochemical configuration of 4 ' atom and structure of 4 ' - substituent.", "output": "There is no related enetity." }, { "input": "The importance of early bedside echocardiography in children with scorpion envenomation.", "output": "There is no related enetity." }, { "input": "Scorpion sting may cause myocardial injury and heart failure ( HF ).", "output": "There is no related enetity." }, { "input": "Clinical signs of failure may develop several hours or even days after the sting, while electrocardiography ( ECG ) and blood examination soon after the sting may be normal.", "output": "There is no related enetity." }, { "input": "We sought to examine whether normal echocardiographic ( echo ) examination performed shortly after hospital arrival would exclude subsequent HF.", "output": "There is no related enetity." }, { "input": "We also sought to check if blood troponin and natriuretic peptide values measured shortly after arrival may predict or exclude subsequent HF.", "output": "There is no related enetity." }, { "input": "Natriuretic peptide activities have not been measured in scorpion sting victims.", "output": "There is no related enetity." }, { "input": "We also wanted to check if HF occurs in envenomated young infants.", "output": "There is no related enetity." }, { "input": "In a 3 - year prospective study we looked at the demographic, clinical, laboratory, ECG, and echo data of all patients with general envenomation who arrived at the emergency department ( ED ) after scorpion sting.", "output": "There is no related enetity." }, { "input": "Clinical, laboratory, ECG, and echo results on arrival and 24 h after arrival were checked and compared between groups of patients with normal and abnormal echo on arrival.", "output": "There is no related enetity." }, { "input": "We then looked for differences in clinical course, therapy, and outcome between groups.", "output": "There is no related enetity." }, { "input": "The study included 98 children aged 80 days to 19 years ( median 53. 1 months ), 25 were below the age of 2 years.", "output": "There is no related enetity." }, { "input": "Envenomation by the \" yellow scorpion \" Leiurus quinquestriatus was suspected in 74 cases.", "output": "There is no related enetity." }, { "input": "Median time between sting and ED arrival was 80 min.", "output": "There is no related enetity." }, { "input": "Echo was performed on arrival in 93 of the 98 patients, ( in 5 occasions it was not performed or not recorded ) 74 were normal and 19 were abnormal.", "output": "There is no related enetity." }, { "input": "Abnormal echo included hypokinesia and low fractional shortening and ejection fraction of the left ventricle.", "output": "There is no related enetity." }, { "input": "Clinical signs, abnormal ECG, and laboratory results were not discriminative between groups on arrival.", "output": "There is no related enetity." }, { "input": "Mean troponin T was higher in patients with abnormal echo, but within normal range in 13 of the 19 patients with abnormal echo and above normal in 2 of the 74 patients with normal echo - missing sensitivity and specificity.", "output": "There is no related enetity." }, { "input": "Mean N - terminal pro B - type natriuretic peptide was above normal in both groups but within normal range in 5 patients with abnormal echo and above normal range in 24 patients with normal echo - missing sensitivity and specificity.", "output": "N." }, { "input": "None of the patients with normal echo had subsequent HF and none of the children younger than 2 years of age had HF.", "output": "There is no related enetity." }, { "input": "All patients survived the intoxication and were discharged home without sequel.", "output": "There is no related enetity." }, { "input": "We conclude that early echo examination is an important procedure.", "output": "There is no related enetity." }, { "input": "In our study, normal examination excluded subsequent HF.", "output": "There is no related enetity." }, { "input": "Abnormal examination accelerated cardiac therapy which might have contributed to our favorable outcome.", "output": "There is no related enetity." }, { "input": "HF did not occur in infants younger than two years of age.", "output": "There is no related enetity." }, { "input": "Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor.", "output": "There is no related enetity." }, { "input": "The glucocorticoid receptor regulates transcriptional output through complex interactions with the genome.", "output": "There is no related enetity." }, { "input": "These events require continuous remodeling of chromatin, interactions of the glucocorticoid receptor with chaperones and other accessory factors, and recycling of the receptor by the proteasome.", "output": "There is no related enetity." }, { "input": "Therefore, the cohort of factors expressed in a particular cell type can determine the physiological outcome upon treatment with glucocorticoid hormones.", "output": "There is no related enetity." }, { "input": "In addition, circadian and ultradian cycling of hormones can also affect GR response.", "output": "There is no related enetity." }, { "input": "Here we will discuss revision of the classical static model of GR binding to response elements to incorporate recent findings from single cell and genome - wide analyses of GR regulation.", "output": "There is no related enetity." }, { "input": "We will highlight how these studies have changed our views on the dynamics of GR recruitment and its modulation of gene expression.", "output": "There is no related enetity." }, { "input": "Anti - apoptotic cardioprotective effects of SHP - 1 gene silencing against ischemia - reperfusion injury: Use of deoxycholic acid - modified low molecular weight polyethyleneimine as a cardiac siRNA - carrier.", "output": "deoxycholic acid, polyethyleneimine." }, { "input": "The cardiomyocyte apoptosis plays a critical role in the development of myocardial injury after ischemia and reperfusion.", "output": "There is no related enetity." }, { "input": "Thus, alteration of the major apoptosis - regulatory factors during myocardial ischemia - reperfusion is expected to have favorable cardioprotective effects.", "output": "There is no related enetity." }, { "input": "Herein, we report ischemic - reperfused myocardial infarction ( MI ) repair with siRNA against Src homology region 2 domain - containing tyrosine phosphatase - 1 ( SHP - 1 ), which is known as a key factor involved in regulating the progress of apoptosis in many cell types.", "output": "tyrosine." }, { "input": "A low molecular weight polyethyleneimine modified with deoxycholic acid ( PEI1. 8 - DA ) - based delivery strategy was suggested for the cardiac application of SHP - 1 siRNA to overcome the poor gene delivery efficiency to myocardium due to the highly charged structures of the compact cardiac muscles.", "output": "polyethyleneimine, deoxycholic acid." }, { "input": "The PEI1. 8 - DA conjugates formed stable nanocomplexes with SHP - 1 siRNA via electrostatic and hydrophobic interactions.", "output": "There is no related enetity." }, { "input": "The PEI1. 8 - DA / SHP - 1 siRNA polyplexes effectively silenced SHP - 1 gene expression in cardiomyocytes, leading to a significant inhibition of cardiomyocyte apoptosis under hypoxia.", "output": "There is no related enetity." }, { "input": "In comparison to conventional gene carriers, relatively large amounts of siRNA molecules remained after treatment with the PEI1. 8 - DA / SHP - 1 siRNA polyplexes.", "output": "There is no related enetity." }, { "input": "Cardiac administration of the PEI1. 8 - DA / SHP - 1 siRNA polyplexes resulted in substantial improvement in SHP - 1 gene silencing, which can be explained by the enhancement of cardiac delivery efficiency of the PEI1. 8 - DA conjugates.", "output": "There is no related enetity." }, { "input": "In addition, in vivo treatment with the PEI1. 8 - DA / SHP - 1 siRNA polyplexes induced a highly significant reduction in myocardial apoptosis and infarct size in rat MI models.", "output": "There is no related enetity." }, { "input": "These results demonstrate that the PEI1. 8 - DA / SHP - 1 siRNA polyplex formulation is a useful system for efficient gene delivery into the compact myocardium that provides a fundamental advantage in treating ischemic - reperfused MI.", "output": "There is no related enetity." }, { "input": "The interaction of a polymeric persimmon proanthocyanidin fraction with Chinese cobra PLA2 and BSA.", "output": "proanthocyanidin." }, { "input": "To elucidate the anti - venom mechanism of persimmon tannin, the interaction between a polymeric persimmon proanthocyanidin fraction ( PT40 ) and phospholipase A2 ( PLA2 ) or bovine serum albumin ( BSA ) were studied using a competitive binding assay and spectroscopic methods including Fourier transform infrared spectroscopy ( FT - IR ), circular dichroism ( CD ), and resonance light scattering ( RLS ) spectroscopy.", "output": "proanthocyanidin." }, { "input": "The results revealed that PT40 has a higher affinity for PLA2 than for BSA at physiological pH and induced greater conformational changes in PLA2 than in BSA.", "output": "There is no related enetity." }, { "input": "PT40 covalently bound to PLA2 in a reaction probably involving Lys residues.", "output": "Lys." }, { "input": "We propose that the high affinity of PT40 for PLA2 and the covalent modification of PLA2 by PT40 may be responsible for the ability of the tannin to irreversibly inhibit PLA2 catalytic activity, to prevent edema, and to neutralize the lethality of Chinese cobra PLA2in vivo.", "output": "There is no related enetity." }, { "input": "Characterization and skin permeation of ketoprofen loaded vesicular systems.", "output": "ketoprofen." }, { "input": "PURPOSE: To determine the effect of elasticity on the skin permeation of ketoprofen from surfactant - based vesicular formulations and elastic liposomes.", "output": "ketoprofen." }, { "input": "METHODS: Ketoprofen loaded surfactant - based vesicles and elastic liposomes were prepared by sonication.", "output": "Ketoprofen." }, { "input": "Citric buffer ( at pH 3. 0 ) was used as rehydration buffer.", "output": "There is no related enetity." }, { "input": "Characterization studies of the prepared liposomal formulations were performed by dynamic light scattering, extrusion, and ( 1 ) H and ( 31 ) P - nuclear magnetic resonance ( NMR ) spectroscopy.", "output": "( 1 ) H, ( 31 ) P." }, { "input": "Ketoprofen transport studies across human skin were performed for all formulations.", "output": "Ketoprofen." }, { "input": "RESULTS: Stable ketoprofen loaded formulations were prepared.", "output": "ketoprofen." }, { "input": "Addition of an edge activator, in the absence of the drug, increased the elasticity of the vesicles and liposomes.", "output": "There is no related enetity." }, { "input": "Ketoprofen loading reduced the elasticity of the liposomes and surfactant - based - vesicles.", "output": "Ketoprofen." }, { "input": "However, at saturation the elasticity was still higher than that in the absence of the edge activator and ketoprofen, except for ketoprofen loaded liposomes with Span 80.", "output": "ketoprofen, ketoprofen." }, { "input": "NMR studies revealed that the ketoprofen molecules were entrapped in a vesicle bilayer in all vesicular formulations, and that the ketoprofen molecules affected the phosphate mobility in the liposomal formulations.", "output": "ketoprofen, ketoprofen, phosphate." }, { "input": "Ketoprofen transport studies across human skin clearly showed that the surfactant - based vesicular formulations were superior to the elastic liposomal formulations.", "output": "Ketoprofen." }, { "input": "CONCLUSION: Surfactant - based vesicles enhance ketoprofen transport across human skin, while no enhancement of ketoprofen was observed when loaded in elastic liposomes.", "output": "ketoprofen, ketoprofen." }, { "input": "Sphaerospora sensu stricto: Taxonomy, diversity and evolution of a unique lineage of myxosporeans ( Myxozoa ).", "output": "There is no related enetity." }, { "input": "Myxosporeans ( Myxozoa ) are eukaryotic parasites, primarily of fish, whose classification is in a state of flux as taxonomists attempt to synthesize the traditional morphology - based system with emerging DNA sequence - based phylogenies.", "output": "There is no related enetity." }, { "input": "The genus Sphaerospora Th e lohan, 1892, which includes pathogenic species that cause significant impacts on fisheries and aquaculture, is one of the most polyphyletic taxa and exemplifies the current challenges facing myxozoan taxonomists.", "output": "There is no related enetity." }, { "input": "The type species, S. elegans, clusters within the Sphaerospora sensu stricto clade, members of which share similar tissue tropism and long insertions in their variable rRNA gene regions.", "output": "There is no related enetity." }, { "input": "However, other morphologically similar sphaerosporids lie in different branches of myxozoan phylogenetic trees.", "output": "There is no related enetity." }, { "input": "Herein, we significantly extend taxonomic sampling of sphaerosporids with SSU + LSU rDNA and EF - 2 sequence data for 12 taxa including three representatives of the morphologically similar genus Polysporoplasma Sitj a - Bobadilla et A lvarez - Pellitero, 1995.", "output": "There is no related enetity." }, { "input": "These taxa were sampled from different vertebrate host groups, biogeographic realms and environments.", "output": "There is no related enetity." }, { "input": "Our phylogenetic analyses and statistical tests of single and concatenated datasets revealed Sphaerospora s.", "output": "There is no related enetity." }, { "input": "s. as a strongly supported monophyletic lineage, that clustered sister to the whole myxosporean clade ( freshwater + marine lineages ).", "output": "There is no related enetity." }, { "input": "Generally, Sphaerospora s.", "output": "There is no related enetity." }, { "input": "s.", "output": "There is no related enetity." }, { "input": "rDNA sequences ( up to 3. 7kb ) are the longest of all myxozoans and indeed metazoans.", "output": "There is no related enetity." }, { "input": "The sphaerosporid clade has two lineages, which have specific morphological, biological and sequence traits.", "output": "There is no related enetity." }, { "input": "Lineage A taxa ( marine Sphaerospora spp. ) have a single binucleate sporoplasm and shorter AT - rich rDNA inserts.", "output": "There is no related enetity." }, { "input": "Lineage B taxa ( freshwater / brackish Sphaerospora spp. + marine / brackish Polysporoplasma spp. ) have 2 - 12 uninucleate sporoplasms and longer GC - rich rDNA inserts.", "output": "There is no related enetity." }, { "input": "Lineage B has four subclades that correlate with host group and habitat; all Polysporoplasma species, including the type species, cluster together in one of these subclades.", "output": "There is no related enetity." }, { "input": "We thus suppress the genus Polysporoplasma and the family Polysporoplasmidae and emend the generic diagnosis of the genus Sphaerospora.", "output": "There is no related enetity." }, { "input": "The combination of morphological, biological and DNA sequence data applied in this study helped to elucidate an important part of the taxonomic puzzle within the phylum Myxozoa.", "output": "There is no related enetity." }, { "input": "Sex specific impact of perinatal bisphenol A ( BPA ) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation.", "output": "bisphenol A, BPA." }, { "input": "Bisphenol A ( BPA ) is a high volume production chemical used in polycarbonate plastics, epoxy resins, thermal paper receipts, and other household products.", "output": "Bisphenol A, BPA, polycarbonate, epoxy." }, { "input": "The neural effects of early life BPA exposure, particularly to low doses administered orally, remain unclear.", "output": "BPA." }, { "input": "Thus, to better characterize the dose range over which BPA alters sex specific neuroanatomy, we examined the impact of perinatal BPA exposure on two sexually dimorphic regions in the anterior hypothalamus, the sexually dimorphic nucleus of the preoptic area ( SDN - POA ) and the anterioventral periventricular ( AVPV ) nucleus.", "output": "BPA, BPA." }, { "input": "Both are sexually differentiated by estradiol and play a role in sex specific reproductive physiology and behavior.", "output": "estradiol." }, { "input": "Long Evans rats were prenatally exposed to 10, 100, 1000, 10, 000 mu g / kg bw / day BPA through daily, non - invasive oral administration of dosed - cookies to the dams.", "output": "BPA." }, { "input": "Offspring were reared to adulthood.", "output": "There is no related enetity." }, { "input": "Their brains were collected and immunolabeled for tyrosine hydroxylase ( TH ) in the AVPV and calbindin ( CALB ) in the SDN - POA.", "output": "tyrosine." }, { "input": "We observed decreased TH - ir cell numbers in the female AVPV across all exposure groups, an effect indicative of masculinization.", "output": "There is no related enetity." }, { "input": "In males, AVPV TH - ir cell numbers were significantly reduced in only the BPA 10 and BPA 10, 000 groups.", "output": "BPA, BPA." }, { "input": "SDN - POA endpoints were unaltered in females but in males SDN - POA volume was significantly lower in all BPA exposure groups.", "output": "BPA." }, { "input": "CALB - ir was significantly lower in all but the BPA 1000 group.", "output": "BPA." }, { "input": "These effects are consistent with demasculinization.", "output": "There is no related enetity." }, { "input": "Collectively these data demonstrate that early life oral exposure to BPA at levels well below the current No Observed Adverse Effect Level ( NOAEL ) of 50mg / kg / day can alter sex specific hypothalamic morphology in the rat.", "output": "BPA." }, { "input": "Synthesis of C17 - OH - north unit of ritterazine G via \" Red - Ox \" modifications of hecogenin acetate.", "output": "OH, ritterazine G, hecogenin acetate." }, { "input": "The C17 - OH - north unit of ritterazine G was prepared in 13 steps from hecogenin acetate.", "output": "OH, ritterazine G, hecogenin acetate." }, { "input": "This synthesis features a highly efficient and stereoselective introduction of the C17 - OH via E - ring cleavage / F - ring formation, D - ring oxidation, and F - ring cleavage / E - ring formation.", "output": "OH." }, { "input": "Oxyphytosterol formation in humans: Identification of high vs. low oxidizers.", "output": "Oxyphytosterol." }, { "input": "Animal studies suggest that oxyphytosterols are atherogenic.", "output": "oxyphytosterols." }, { "input": "However, we have previously shown that plasma oxyphytosterol concentrations did not increase after consuming a diet enriched in plant sterol esters ( 3g / day ), while minor reductions were seen after consuming a plant stanol ester - enriched diet.", "output": "oxyphytosterol, sterol esters, stanol ester." }, { "input": "Large variations in oxyphytosterol concentrations between individuals however existed.", "output": "oxyphytosterol." }, { "input": "The aim of this study was to identify factors that may explain inter - individual differences in plasma oxyphytosterol concentrations.", "output": "oxyphytosterol." }, { "input": "For this, 43 subjects consumed for 4 weeks in random order a plant sterol, stanol and control margarine.", "output": "sterol, stanol." }, { "input": "Plasma oxyphytosterol concentrations were determined in butylated hydroxytoluene ( BHT ) - enriched EDTA plasma via GC - MS and serum oxidized low - density lipoprotein ( oxLDL ) concentrations were analyzed via ELISA.", "output": "oxyphytosterol, butylated hydroxytoluene, BHT, EDTA." }, { "input": "Trolox equivalent antioxidant capacity ( TEAC ) values, alpha - tocopherol concentrations and iron / copper status were determined to assess plasma oxidative and anti - oxidative capacity.", "output": "Trolox, alpha - tocopherol, iron, copper." }, { "input": "Serum ( non - oxidized ) sitosterol and campesterol concentrations did not correlate with plasma oxysitosterol and oxycampesterol concentrations during any of the three dietary interventions.", "output": "sitosterol, campesterol, oxysitosterol, oxycampesterol." }, { "input": "Moreover, plasma oxyphytosterol concentrations remained relatively stable over time.", "output": "oxyphytosterol." }, { "input": "Six subjects could be arbitrarily classified as having consistent low or high plasma oxyphytosterol concentrations, which was also reflected in oxLDL concentrations.", "output": "oxyphytosterol." }, { "input": "However, oxidative and anti - oxidative capacity markers, such as iron / copper status, alpha - tocopherol concentrations and TEAC values, could not explain these differences.", "output": "iron, copper, alpha - tocopherol." }, { "input": "In conclusion, subjects seem to have consistent plasma oxyphytosterol concentrations, which resulted in the identification of ' low and high oxidizers '.", "output": "oxyphytosterol." }, { "input": "Differences, however, could not be attributed to the oxidative and anti - oxidative capacity markers analyzed.", "output": "There is no related enetity." }, { "input": "HDL particle functionality as a primary pharmacological target for HDL - based therapies.", "output": "There is no related enetity." }, { "input": "Despite all existing pharmaceuticals aiming at effectively reducing LDL cholesterol, the steadily increasing prevalence of coronary heart disease ( CHD ) worldwide shifted focus on HDL as an alternative therapeutic target for the treatment of CHD.", "output": "cholesterol." }, { "input": "Indeed, based on the results from epidemiological studies, high HDL cholesterol ( HDL - C ) levels have been traditionally associated to atheroprotection.", "output": "cholesterol." }, { "input": "Therefore, current drug design considers plasma HDL - C levels as a primary pharmacological target for combating CHD.", "output": "There is no related enetity." }, { "input": "However, this approach does not take into consideration the fact that HDL is a rather heterogeneous mixture of lipoprotein particles with distinct apolipoprotein and lipid composition that dictate their atheroprotective or proatherogenic function.", "output": "There is no related enetity." }, { "input": "This may explain why simply raising HDL - C levels by pharmacological means has yet to yield the expected atheroprotection in recent clinical trials.", "output": "There is no related enetity." }, { "input": "In this review we argue that HDL particle functionality rather than HDL - C levels should be the primary target in the rational design of new HDL - based pharmaceuticals aiming at successfully treating CHD.", "output": "There is no related enetity." }, { "input": "Current perspectives on parathyroid hormone ( PTH ) and PTH - related protein ( PTHrP ) as bone anabolic therapies.", "output": "There is no related enetity." }, { "input": "Osteoporosis is characterized by low bone mineral density and / or poor bone microarchitecture leading to an increased risk of fractures.", "output": "There is no related enetity." }, { "input": "The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption.", "output": "There is no related enetity." }, { "input": "Osteoporosis therapies have mostly relied on antiresorptive drugs.", "output": "There is no related enetity." }, { "input": "An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone ( PTH ).", "output": "There is no related enetity." }, { "input": "Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival.", "output": "There is no related enetity." }, { "input": "PTH and PTH - related protein ( PTHrP ) - an abundant local factor in bone - interact with the common PTH type 1 receptor with similar affinities in osteoblasts.", "output": "There is no related enetity." }, { "input": "Studies mainly in osteoporosis rodent models and limited data in postmenopausal women suggest that N - terminal PTHrP peptides might be considered a promising bone anabolic therapy.", "output": "N." }, { "input": "In addition, putative osteogenic actions of PTHrP might be ascribed not only to its N - terminal domain but also to its PTH - unrelated C - terminal region.", "output": "N, C." }, { "input": "In this review, we discuss the underlying cellular and molecular mechanisms of the anabolic actions of PTH and the similar potential of PTH - related protein ( PTHrP ) to increase bone mass and improve bone regeneration.", "output": "There is no related enetity." }, { "input": "Pharmacokinetics and the drug - target residence time concept.", "output": "There is no related enetity." }, { "input": "The concept of drug - target residence time has been in focus in recent drug discovery literature.", "output": "There is no related enetity." }, { "input": "However, few studies consider the combined effect of pharmacokinetics ( PK ) and binding kinetics ( BK ) on the duration of effect of a drug.", "output": "There is no related enetity." }, { "input": "Using a simple model that takes both PK and BK into account, we found that prolongation of binding owing to a long drug - target residence time can only occur when the binding dissociation is slower than the PK elimination.", "output": "There is no related enetity." }, { "input": "Data for several drugs and / or drug candidates in the literature indicate that the opposite is observed, that is, they have a slower elimination compared with dissociation.", "output": "There is no related enetity." }, { "input": "These observations greatly reduce the usability of drug - target residence times for estimating the duration of effect of a drug in vivo.", "output": "There is no related enetity." }, { "input": "Astaxanthin ameliorates lung fibrosis in vivo and in vitro by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.", "output": "Astaxanthin." }, { "input": "Astaxanthin, a member of the carotenoid family, is the only known ketocarotenoid transported into the brain by transcytosis through the blood - brain barrier.", "output": "Astaxanthin." }, { "input": "However, whether astaxanthin has antifibrotic functions is unknown.", "output": "astaxanthin." }, { "input": "In this study, we investigated the effects of astaxanthin on transforming growth factor beta 1 - mediated and bleomycin - induced pulmonary fibrosis in vitro and in vivo.", "output": "astaxanthin, bleomycin." }, { "input": "The results showed that astaxanthin significantly improved the structure of the alveoli and alleviated collagen deposition in vivo.", "output": "astaxanthin." }, { "input": "Compared with the control group, the astaxanthin - treated groups exhibited downregulated protein expressions of alpha - smooth muscle actin, vimentin, hydroxyproline, and B cell lymphoma / leukemia - 2 as well as upregulated protein expressions of E - cadherin and p53 in vitro and in vivo.", "output": "astaxanthin, hydroxyproline." }, { "input": "Astaxanthin also inhibited the proliferation of activated A549 and MRC - 5 cells at median inhibitory concentrations of 40 and 30 mu M, respectively.", "output": "Astaxanthin." }, { "input": "In conclusion, astaxanthin could relieve the symptoms and halt the progression of pulmonary fibrosis, partly by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.", "output": "astaxanthin." }, { "input": "Interactions between the Fusarium toxin deoxynivalenol and lipopolysaccharides on the in vivo protein synthesis of acute phase proteins, cytokines and metabolic activity of peripheral blood mononuclear cells in pigs.", "output": "deoxynivalenol." }, { "input": "The in vivo effects of the Fusarium toxin deoxynivalenol ( DON ) on albumin and fibrinogen synthesis in pigs and metabolic activity of porcine peripheral blood mononuclear cells ( PBMCs ) were studied alone or in combination with lipopolysaccharides ( LPSs ) in order to examine proposed synergistic effects of both substances.", "output": "deoxynivalenol, DON." }, { "input": "A total of 36 male castrated pigs ( initial weight of 26kg ) were used.", "output": "There is no related enetity." }, { "input": "Uncontaminated ( Control ) and naturally DON - contaminated ( chronic oral DON, 3. 1mg / kg diet ) wheat was fed for 37days.", "output": "DON, DON." }, { "input": "On the day of protein synthesis measurement, pigs recruited from the Control group were treated once intravenously with ( iv ) DON ( 100 mu g / kg live weight ( LW ) / h ), iv LPS ( 7. 5 mu g / kgLW / h ) or a combination of both substances, and six pigs from the chronic oral group were treated once with iv LPS.", "output": "DON." }, { "input": "A treatment with DON alone exhibited no alterations of acute phase protein synthesis and metabolic activity of PBMC.", "output": "DON." }, { "input": "There was no evidence that the chosen dosing regimen of DON had influences on the induced sub - acute stage of sepsis, as the LPS challenge, irrespective of DON co - exposure, mediated an acute phase reaction with a typical decrease of albumin synthesis, as well as changes in cytokine concentration and a loss of metabolic activity in PBMC.", "output": "DON, DON." }, { "input": "Activation of ALDH2 with ethanol attenuates diabetes induced myocardial injury in rats.", "output": "ethanol." }, { "input": "This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with ALDH2 activator ethanol ( EtOH ).", "output": "ethanol, EtOH." }, { "input": "The rats were divided into six groups: control, EtOH control, diabetic rat at 4th week ( DM4W ), 8th week ( DM8W ), 12th week ( DM12W ) and EtOH + DM8W groups.", "output": "EtOH, EtOH." }, { "input": "Compared with control group, fasting blood glucose ( FBG ) and glycosylated hemoglobin ( HbA1c ) levels were increased in DM groups.", "output": "glucose." }, { "input": "HbA1c level in DM12W group was higher than in DM4W group, HbA1c level in EtOH + DM8W group was lower than in DM8W group.", "output": "EtOH." }, { "input": "Compared with control group, there were no changes of LVDP, HR and +/- dp / dtmax in DM4W group, but there were decreased in DM8W and DM12W groups, and increased in the EtOH + DM8W group.", "output": "EtOH." }, { "input": "In DM groups, SOD activity, ALDH2 mRNA and protein levels were reduced, MDA content was increased compared with control group; which decreased further as diabetes progressed.", "output": "MDA." }, { "input": "Compared with DM8W group, SOD and ALDH2 in EtOH + DM8W group was increased, MDA was decreased.", "output": "EtOH, MDA." }, { "input": "Our results indicated with the development of diabetes, myocardial ALDH2 expression was further decreased accompanying decreased ventricular function.", "output": "There is no related enetity." }, { "input": "However, activation of ALDH2 can decrease diabetes induced myocardial injury.", "output": "There is no related enetity." }, { "input": "ALDH2 may be one key endogenous cardiac protective factor in diabetic individuals.", "output": "There is no related enetity." }, { "input": "Protective effects of a compound isolated from Alnus japonica on oxidative stress - induced death in transformed retinal ganglion cells.", "output": "There is no related enetity." }, { "input": "Here, we investigated whether hirsutenone, a compound isolated from Alnus japonica, was able to attenuate oxidative stress - induced death in transformed retinal ganglion ( RGC - 5 ) cells.", "output": "hirsutenone." }, { "input": "Hirsutenone effectively protected RGC - 5 cells from oxidative insult induced by, l - buthionine - ( S, R ) - sulfoximine ( BSO ) plus glutamate in a concentration - dependent manner, as demonstrated by propidium iodide ( PI ) / Hoechst 33342 double staining, flow cytometry, and MTT assays.", "output": "l - buthionine - ( S , R ) - sulfoximine, BSO, glutamate, propidium iodide, MTT." }, { "input": "Moreover, hirsutenone inhibited the increase in apoptotic protein expression resulting from BSO plus glutamate.", "output": "hirsutenone, BSO." }, { "input": "Hirsutenone also effectively inhibited sodium nitroprusside ( SNP ) - induced lipid peroxidation in rat brain homogenates.", "output": "Hirsutenone, sodium nitroprusside, SNP." }, { "input": "To investigate the effects of hirsutenone in vivo, we used N - methyl - d - aspartate ( NMDA ) as a negative insult on the retinas of rats.", "output": "hirsutenone, N - methyl - d - aspartate, NMDA." }, { "input": "NMDA affects the thinning of the inner plexiform layer ( IPL ) and causes an increase in the number of terminal deoxynucleotidyl transferase - mediated dUTP nick - end labeling ( TUNEL ) - positive ganglion cells in the ganglion cell layer ( GCL ).", "output": "NMDA, dUTP." }, { "input": "Hirsutenone treatment led to a reduction in NMDA - induced IPL and TUNEL staining of the GCL.", "output": "Hirsutenone, NMDA." }, { "input": "In conclusion, hirsutenone isolated from A. japonica may act as neuroprotective agent for conditions such as glaucoma.", "output": "hirsutenone." }, { "input": "Synthesis and anticancer activity of novel 2 - pyridyl hexahyrocyclooctathieno [ 2, 3 - d ] pyrimidine derivatives.", "output": "2 - pyridyl hexahyrocyclooctathieno [ 2 , 3 - d ] pyrimidine." }, { "input": "A series of new 2 - pyridyl hexahydrocycloocta [ 4, 5 ] thieno [ 2, 3 - d ] pyrimidines with different substituents as C - 4 position was synthesized.", "output": "2 - pyridyl hexahydrocycloocta [ 4 , 5 ] thieno [ 2 , 3 - d ] pyrimidines." }, { "input": "The anticancer activity of the newly synthesized compounds was tested in vitro using a two - stage process utilizing 60 different human tumor cell lines representing leukemia, melanoma and cancers of lung, colon, central nervous system, ovary, kidney, prostate as well as breast.", "output": "There is no related enetity." }, { "input": "Compounds 4a, 6a, 7a, 7d and 7g showed potent anticancer activity at low concentrations against most of the used human tumor cell lines comparable with doxorubicin as standard potent anticancer drug ( average log10 GI50 over all cell lines = - 6. 85 ).", "output": "doxorubicin." }, { "input": "Also, compound 4b was selective against SNB - 75 ( CNS cancer ) log10 GI50 = - 5. 57.", "output": "There is no related enetity." }, { "input": "Interestingly, compound 7e exhibited promising selectivity against 13 tumor cell lines showing growth inhibition percentages between 54. 05 and 89. 23.", "output": "There is no related enetity." }, { "input": "Synthesis and antibacterial evaluation of novel pleuromutilin derivatives.", "output": "pleuromutilin." }, { "input": "A series of novel pleuromutilin derivatives possessing thioether moiety has been synthesized via acylation reaction under mild conditions.", "output": "pleuromutilin." }, { "input": "Their in vitro antibacterial activity against methicillin - resistant Staphylococcus aureus, methicillin - resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by agar dilution method and Oxford cup assay.", "output": "methicillin, methicillin." }, { "input": "Among the 17 compounds screened, 14 - O - [ ( 4 - methoxybenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin 4i, 14 - O - [ ( 2 - aminobenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin 5a and 14 - O - [ ( 4 - aminobenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin 5c were resulted as most active antibacterial agents.", "output": "14 - O - [ ( 4 - methoxybenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin, 14 - O - [ ( 2 - aminobenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin, 14 - O - [ ( 4 - aminobenzamide - 2 - methylpropane - 2 - yl ) thioacetate ] mutilin." }, { "input": "Associations of ABCB1, NFKB1, CYP3A, and NR1I2 polymorphisms with cyclosporine trough concentrations in Chinese renal transplant recipients.", "output": "cyclosporine." }, { "input": "Aim: Cyclosporine requires close therapeutic drug monitoring because of its narrow therapeutic index and marked inter - individual pharmacokinetic variation.", "output": "Cyclosporine." }, { "input": "In this study, we investigated the associations of CYP3A4, CYP3A5, ABCB1, NFKB1, and NR1I2 polymorphisms with cyclosporine concentrations in Chinese renal transplant recipients in the early period after renal transplantation. Methods: A total of 101 renal transplant recipients receiving cyclosporine were genotyped for CYP3A4 ( * ) 1G, CYP3A5 ( * ) 3, ABCB1 C1236T, G2677T / A, C3435T, NFKB1 - 94 ins / del ATTG, and NR1I2 polymorphisms.", "output": "cyclosporine, cyclosporine." }, { "input": "Cyclosporine whole blood levels were measured by a fluorescence polarization immunoassay.", "output": "Cyclosporine." }, { "input": "Trough concentrations of cyclosporine were determined for days 7 - 18 following transplantation. Results: The dose - adjusted trough concentration ( C0 ) of cyclosporine in ABCB1 2677 TT carriers was significantly higher than that in GG carriers together with GT carriers [ 90. 4 +/- 24. 5 vs 67. 8 +/- 26. 8 ( ng / mL ) / ( mg / kg ), P = 0. 001 ].", "output": "cyclosporine, cyclosporine." }, { "input": "ABCB1 3435 TT carriers had a significantly higher dose - adjusted C0 of cyclosporine than CC carriers together with CT carriers [ 92. 0 +/- 24. 0 vs 68. 4 +/- 26. 5 ( ng / mL ) / ( mg / kg ), P = 0. 002 ].", "output": "cyclosporine." }, { "input": "Carriers of the ABCB1 1236TT - 2677TT - 3435TT haplotype had a considerably higher CsA C0 / D than carriers of other genotypes [ 97. 2 +/- 21. 8 vs 68. 7 +/- 26. 9 ( ng / mL ) / ( mg / kg ), P = 0. 001 ].", "output": "There is no related enetity." }, { "input": "Among non - carriers of the ABCB1 2677 TT and 3435 TT genotypes, patients with the NFKB1 - 94 ATTG ins / ins genotype had a significantly higher dose - adjusted C0 than those with the - 94 ATTG del / del genotype [ 75. 9 +/- 32. 9 vs 55. 1 +/- 15. 1 ( ng / mL ) / ( mg / kg ), P = 0. 026 ]. Conclusion: These results illustrate that the ABCB1 and NFKB1 genotypes are closely correlated with cyclosporine trough concentrations, suggesting that these SNPs are useful for determining the appropriate dose of cyclosporine.", "output": "cyclosporine, cyclosporine." }, { "input": "The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway.", "output": "There is no related enetity." }, { "input": "The final step of cytoplasmic mRNA degradation proceeds in either a 5 ' - 3 ' direction catalysed by Xrn1 or in a 3 ' - 5 ' direction catalysed by the exosome.", "output": "There is no related enetity." }, { "input": "Dis3 / Rrp44, an RNase II family protein, is the catalytic subunit of the exosome.", "output": "There is no related enetity." }, { "input": "In humans, there are three paralogues of this enzyme: DIS3, DIS3L, and DIS3L2.", "output": "There is no related enetity." }, { "input": "In this work, we identified a novel Schizosaccharomyces pombe exonuclease belonging to the conserved family of human DIS3L2 and plant SOV.", "output": "There is no related enetity." }, { "input": "Dis3L2 does not interact with the exosome components and localizes in the cytoplasm and in cytoplasmic foci, which are docked to P - bodies.", "output": "There is no related enetity." }, { "input": "Deletion of dis3l2 ( + ) is synthetically lethal with xrn1 Delta, while deletion of dis3l2 ( + ) in an lsm1 Delta background results in the accumulation of transcripts and slower mRNA degradation rates.", "output": "There is no related enetity." }, { "input": "Accumulated transcripts show enhanced uridylation and in vitro Dis3L2 displays a preference for uridylated substrates.", "output": "There is no related enetity." }, { "input": "Altogether, our results suggest that in S. pombe, and possibly in most other eukaryotes, Dis3L2 is an important factor in mRNA degradation.", "output": "There is no related enetity." }, { "input": "Therefore, this novel 3 ' - 5 ' RNA decay pathway represents an alternative to degradation by Xrn1 and the exosome.", "output": "There is no related enetity." }, { "input": "Composite dissolving microneedles for coordinated control of antigen and adjuvant delivery kinetics in transcutaneous vaccination.", "output": "There is no related enetity." }, { "input": "Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained / controlled drug release.", "output": "There is no related enetity." }, { "input": "To this end, we demonstrate a microneedle materials platform for rapid implantation of controlled - release polymer depots into the cutaneous tissue.", "output": "There is no related enetity." }, { "input": "Arrays of microneedles comprised of drug - loaded poly ( lactide - co - glycolide ) ( PLGA ) microparticles or solid PLGA tips were prepared with a supporting and rapidly water - soluble poly ( acrylic acid ) ( PAA ) matrix.", "output": "poly ( lactide - co - glycolide ), PLGA, PLGA, poly ( acrylic acid ), PAA." }, { "input": "Upon application of microneedle patches to the skin of mice, the microneedles perforated the stratum corneum and epidermis.", "output": "There is no related enetity." }, { "input": "Penetration of the outer skin layers was followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which were retained following patch removal.", "output": "PAA." }, { "input": "These polymer depots remained in the skin for weeks following application and sustained the release of encapsulated cargos for systemic delivery.", "output": "There is no related enetity." }, { "input": "To show the utility of this approach we demonstrated the ability of these composite microneedle arrays to deliver a subunit vaccine formulation.", "output": "There is no related enetity." }, { "input": "In comparison to traditional needle - based vaccination, microneedle delivery gave improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery.", "output": "There is no related enetity." }, { "input": "However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.", "output": "There is no related enetity." }, { "input": "Impact of long - range van der Waals forces on chiral recognition in a Cinchona alkaloid chiral selector system.", "output": "There is no related enetity." }, { "input": "Singly - charged complexes of ( 8S, 9R ) - tert - butylcarbamoylquinine ( tBuCQN ), N - 3, 5 - dinitrobenzoyl - ( S, R ) - leucine ( DNB - S / R - leucine ), and alkali metal counter ions ( Li ( + ), Na ( + ), K ( + ) ) were investigated by density - functional theory.", "output": "( 8S , 9R ) - tert - butylcarbamoylquinine, tBuCQN, N - 3 , 5 - dinitrobenzoyl - ( S , R ) - leucine, DNB, S / R - leucine, Li ( + ), Na ( + ), K ( + )." }, { "input": "It is shown that the cations prefer formation of an ionic pair with the carboxylate group of DNB - Leu over the formation of a cation - pi interaction.", "output": "carboxylate, DNB, Leu." }, { "input": "The [ tBuCQN. DNB - S / R - Leu. Na ] ( + ) complex is bound by a coulombic attraction, a hydrogen bond, a pi - pi interaction and van der Waals forces.", "output": "[ tBuCQN . DNB - S / R - Leu . Na ] ( + )." }, { "input": "The tBuCQN chiral selector preferentially complexes with the DNB - S - Leu enantiomer, because the favourable stereochemistry allows the stabilization of the complex by at least one binding mode more compared to the complex containing the DNB - R - Leu molecule.", "output": "tBuCQN, DNB, S - Leu, DNB, R - Leu." }, { "input": "Weakening of the binding modes is observed using the lithium counter ion compared to the sodium one.", "output": "lithium, sodium." }, { "input": "The weakening is more pronounced in [ tBuCQN. DNB - R - Leu. Li ] ( + ) than in [ tBuCQN. DNB - S - Leu. Li ] ( + ).", "output": "[ tBuCQN . DNB - R - Leu . Li ] ( + ), [ tBuCQN . DNB - S - Leu . Li ] ( + )." }, { "input": "The exact opposite effect is observed using the potassium counter ion.", "output": "potassium." }, { "input": "Hence, the lithium counter ion enhances the enantioselectivity of tBuCQN while the potassium counter ion reduces the enantioselectivity of tBuCQN.", "output": "lithium, tBuCQN, potassium, tBuCQN." }, { "input": "Synthesis of new 1, 3, 4 - benzotriazepin - 5 - one derivatives and their biological evaluation as antitumor agents.", "output": "1 , 3 , 4 - benzotriazepin - 5 - one." }, { "input": "New derivatives of 1, 3, 4 - benzotriazepin - 5 - one were designed and synthesized as structural analogues to the antitumor agents devazepide and asperlicin.", "output": "1 , 3 , 4 - benzotriazepin - 5 - one, devazepide, asperlicin." }, { "input": "An efficient and novel approach to the synthesis of 2 - amino - 1, 3, 4 - benzotriazepin - 5 - one 2 was developed and its structure was confirmed.", "output": "2 - amino - 1 , 3 , 4 - benzotriazepin - 5 - one." }, { "input": "The newly synthesized derivatives were evaluated for their in vitro antitumor activity on 60 different cell lines.", "output": "There is no related enetity." }, { "input": "Compounds 8 and 9 displayed the most potent antitumor activity against several cell lines specifically ovarian cancer, renal cancer and prostate cancer, while compounds 5, 10 and 12 showed significant activities against UO - 31 renal cancer cell line.", "output": "There is no related enetity." }, { "input": "Pharmacotherapy for the core symptoms in autistic disorder: current status of the research.", "output": "There is no related enetity." }, { "input": "The current review covers extant literature on pharmacotherapy for core symptoms of autism.", "output": "There is no related enetity." }, { "input": "The core symptoms of autism include impairments in social interaction and communication, as well as the presence of restricted and repetitive behaviors.", "output": "There is no related enetity." }, { "input": "There are no known efficacious treatments for the core social symptoms, although effects on repetitive behaviors are indicated with some data.", "output": "There is no related enetity." }, { "input": "While studies of fenfluramine, secretin, opiates, and mood stabilizers generally find no effect, mixed results suggest more research is needed on antidepressants and atypical antipsychotics.", "output": "fenfluramine." }, { "input": "Newer lines of research, including cholinergic and glutamatergic agents and oxytocin, will be of considerable interest in the future.", "output": "oxytocin." }, { "input": "However, research on the treatment of core symptoms is plagued by limitations in study design, statistical power, and other issues inherent to the study of treatments for autism ( e. g., heterogeneity of the disorder ) that continue to prevent the elucidation of efficacious treatments.", "output": "There is no related enetity." }, { "input": "Solar - Powered Nanomechanical Transduction from Crystalline Molecular Rotors.", "output": "There is no related enetity." }, { "input": "A photoinduced solid - state SO2 isomerism drives a larger mechanical change ( benzene - ring rotation ) in a neighbouring ion ( i. e., the system acts as a solar - powered molecular transducer ).", "output": "SO2, benzene." }, { "input": "The ring rotation and SO2 photoisomerisation are observed using in situ X - ray crystallography and are controllable, reproducible, and metastable at low temperatures.", "output": "SO2." }, { "input": "This discovery presents a new range of materials for solar - energy - based molecular transduction.", "output": "There is no related enetity." }, { "input": "Inhibitory Effect of Ketoconazole on the Pharmacokinetics of a Multireceptor Tyrosine Kinase Inhibitor BMS - 690514 in Healthy Participants: Assessing the Mechanism of the Interaction With Physiologically - Based Pharmacokinetic Simulations.", "output": "Ketoconazole, Tyrosine, BMS - 690514." }, { "input": "BMS - 690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development.", "output": "BMS - 690514." }, { "input": "The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction ( 34 % ) of metabolism.", "output": "There is no related enetity." }, { "input": "It is also a substrate of P - glycoprotein ( P - gp ) in vitro.", "output": "There is no related enetity." }, { "input": "To assess the effect of ketoconazole on BMS - 690514 pharmacokinetics, 17 healthy volunteers received 200 mg BMS - 690514 alone followed by 100 mg BMS - 690514 with ketoconazole ( 400 mg once daily for 4 days ).", "output": "ketoconazole, BMS - 690514, BMS - 690514, BMS - 690514, ketoconazole." }, { "input": "The AUC infinity of 100 mg BMS - 690514 concomitantly administered with ketoconazole was similar to that of 200 mg BMS - 690514 alone.", "output": "BMS - 690514, ketoconazole, BMS - 690514." }, { "input": "The dose - normalized Cmax and AUC infinity of BMS - 690514 from the 100 - mg BMS - 690514 / 400 - mg ketoconazole treatment increased by 55 % and 127 %, respectively, relative to those from 200 mg BMS - 690514 alone.", "output": "BMS - 690514, BMS - 690514, ketoconazole, BMS - 690514." }, { "input": "Prediction of the drug - drug interaction ( DDI ) using a population - based simulator ( Simcyp ) indicated that, in addition to CYP3A4 inhibition, the inhibition of P - gp by ketoconazole in the intestine, liver, and kidneys must be invoked to fully account for the DDI observed.", "output": "ketoconazole." }, { "input": "This finding suggests that the inhibition of P - gp by ketoconazole, along with its effect on CYP3A4, needs to be considered when designing a DDI study of ketoconazole with a victim drug that is a dual substrate.", "output": "ketoconazole, ketoconazole." }, { "input": "A Stochastic Simulator of Birth - Death Master Equations with Application to Phylodynamics.", "output": "There is no related enetity." }, { "input": "In this article, we present a versatile new software tool for the simulation and analysis of stochastic models of population phylodynamics and chemical kinetics.", "output": "There is no related enetity." }, { "input": "Models are specified via an expressive and human - readable XML format and can be used as the basis for generating either single population histories or large ensembles of such histories.", "output": "There is no related enetity." }, { "input": "Importantly, phylogenetic trees or networks can be generated alongside the histories they correspond to, enabling investigations into the interplay between genealogies and population dynamics.", "output": "There is no related enetity." }, { "input": "Summary statistics such as means and variances can be recorded in place of the full ensemble, allowing for a reduction in the amount of memory used - an important consideration for models including large numbers of individual subpopulations or demes.", "output": "There is no related enetity." }, { "input": "In the case of population size histories, the resulting simulation output is written to disk in the flexible JSON format, which is easily read into numerical analysis environments such as R for visualization or further processing.", "output": "There is no related enetity." }, { "input": "Simulated phylogenetic trees can be recorded using the standard Newick or NEXUS formats, with extensions to these formats used for non - tree - like inheritance relationships.", "output": "There is no related enetity." }, { "input": "A Comparative Study of Baby Immature and Adult Shoots of Aloe Vera on UVB - Induced Skin Photoaging in vitro.", "output": "There is no related enetity." }, { "input": "Ultraviolet ( UV ) irradiation induces photo - damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure.", "output": "There is no related enetity." }, { "input": "Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase ( MMP ) expression.", "output": "There is no related enetity." }, { "input": "The production of type I procollagen is regulated by transforming growth factor - beta 1 ( TGF - beta 1 ) expression; the activation of MMP is also correlated with an increase of interleukin - 6 ( IL - 6 ).", "output": "There is no related enetity." }, { "input": "Aloe barbadensis M.", "output": "There is no related enetity." }, { "input": "( Aloe vera ) is widely used in cosmetic and pharmaceutical products.", "output": "There is no related enetity." }, { "input": "In this study, we examined whether baby aloe shoot extract ( BAE, immature aloe extract ), which is from the one - month - old shoots of Aloe vera, and adult aloe shoot extract ( AE ), which is from the four - month - old shoots of Aloe vera, have a protective effect on UVB - induced skin photoaging in normal human dermal fibroblasts ( NHDFs ).", "output": "There is no related enetity." }, { "input": "The effects of BAE and AE on UVB - induced photoaging were tested by measuring the levels of reactive oxygen species, MMP - 1, MMP - 3, IL - 6, type I procollagen, and TGF - beta 1 after UVB irradiation.", "output": "oxygen." }, { "input": "We found that NHDF cells treated with BAE after UVB - irradiation suppressed MMP - 1, MMP - 3, and IL - 6 levels compared to the AE - treated cells.", "output": "There is no related enetity." }, { "input": "Furthermore, BAE treatment elevated type I procollagen and TGF - beta 1 levels.", "output": "There is no related enetity." }, { "input": "Our results suggest that BAE may potentially protect the skin from UVB - induced damage more than AE.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Diverse effects of macromolecular crowding on the sequential glycan - processing pathway involved in glycoprotein quality control.", "output": "There is no related enetity." }, { "input": "Compared with in vitro conditions, the intracellular environment is highly crowded with biomolecules; this has numerous effects on protein functions, including enzymatic activity.", "output": "There is no related enetity." }, { "input": "We examined the effects of macromolecular crowding on glycan processing of N - glycoprotein in the endoplasmic reticulum as a model sequential metabolic pathway.", "output": "N." }, { "input": "Experiments with synthetic substrates of physiological glycan structure clearly showed that the first half of the pathway ( glucose trimming ) was accelerated, whereas the second ( mannose trimming ) was decelerated under molecular crowding conditions.", "output": "glucose, mannose." }, { "input": "Furthermore, calreticulin, a lectin - like molecular chaperone, bound more strongly to a glycan - processing intermediate under these conditions.", "output": "There is no related enetity." }, { "input": "This study demonstrates the diverse effects of molecular crowding on sequential enzymatic processing, and the importance of the effects of macromolecular crowding on in vitro assays for understanding sequential metabolic pathways.", "output": "There is no related enetity." }, { "input": "A computational study of water and CO migration sites and channels inside myoglobin.", "output": "CO." }, { "input": "Pathways are computed for transport of H2O and CO in myoglobin ( Mb ), using the single sweep and zero - temperature string methods in a fully atomistic, explicitly solvated model system.", "output": "H2O, CO." }, { "input": "Our predictions of sites and barriers in the pathways for CO transport agree with previous studies.", "output": "CO." }, { "input": "For H2O, we predict a binding site in the distal pocket ( DP ), in agreement with crystallographic observations, and another one close to Leu 29 which explains the importance of this residue in controlling the pocket ' s hydrophobicity, as well as disordered minima in the largely apolar xenon cavities.", "output": "H2O, Leu, xenon." }, { "input": "In particular, H2O can occupy and transition among the xenon cavities, Xe4, Xe2, and Xe3.", "output": "H2O, xenon, Xe4, Xe2, Xe3." }, { "input": "Our results support the hypothesis that the thermodynamically most favorable entry / exit portal for H2O is the so - called histidine gate ( HG ), the same as for CO.", "output": "H2O, histidine, CO." }, { "input": "This result, along with the observation of water occupation of both DP and apolar Xe cavities, suggest that water and small gas molecules like CO compete for access to the protein interior, and therefore models of gas molecule transport within proteins should also explicitly consider water transport.", "output": "Xe, CO." }, { "input": "Detection of Nanosized Ordered Domains in DOPC / DPPC and DOPC / Ch Binary Lipid Mixture Systems of Large Unilamellar Vesicles Using a TEMPO Quenching Method.", "output": "DOPC, DPPC, DOPC." }, { "input": "Nanosized ordered domains formed in 1, 2 - dioleoyl - sn - glycero - 3 - phosphocholine / 1, 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine ( DOPC / DPPC ) and DOPC / cholesterol ( Ch ) liposomes were characterized using a newly developed ( 2, 2, 6, 6 - tetramethylpiperidin - 1 - yl ) oxyl ( TEMPO ) quenching method.", "output": "1 , 2 - dioleoyl - sn - glycero - 3 - phosphocholine, 1 , 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine, DOPC, DPPC, DOPC, cholesterol, ( 2 , 2 , 6 , 6 - tetramethylpiperidin - 1 - yl ) oxyl, TEMPO." }, { "input": "The membrane fluidity of the DOPC / DPPC liposomes, evaluated by the use of 1, 6 - diphenyl - 1, 3, 5 - hexatriene ( DPH ), increased significantly above their phase - transition temperature.", "output": "DOPC, DPPC, 1 , 6 - diphenyl - 1 , 3 , 5 - hexatriene, DPH." }, { "input": "The fluorescence spectra of 6 - lauroyl - 2 - dimethylamino naphthalene ( Laurdan ) indicated the formation of an immiscible ordered phase in the DOPC / DPPC ( 50 / 50 ) liposomal membrane at 30 degrees C.", "output": "6 - lauroyl - 2 - dimethylamino naphthalene, Laurdan, DOPC, DPPC." }, { "input": "The analysis of the membrane polarity indicated that the surface of the liquid - disordered phase was hydrated whereas that of the ordered phase was dehydrated.", "output": "There is no related enetity." }, { "input": "DOPC / DPPC and DOPC / Ch ( 70 / 30 ) liposomes exhibited heterogeneous membranes, indicating that nanosized ordered domains formed on the surface of the DOPC / DPPC liposomes.", "output": "DOPC, DPPC, DOPC, DOPC, DPPC." }, { "input": "The size of these nanosized ordered domains was estimated using the TEMPO quenching method.", "output": "TEMPO." }, { "input": "Because TEMPO can quench DPH distributed in the disordered phases, the remaining fluorescence from DPH is proportional to the size of the ordered domain.", "output": "TEMPO, DPH, DPH." }, { "input": "The domain sizes calculated for DOPC / DPPC ( 50 / 50 ), DOPC / DPPC ( 25 / 75 ), DOPC / Ch ( 70 / 30 ), and DOPC / DPPC / Ch ( 40 / 40 / 20 ) were 13. 9, 36. 2, 13. 2, and 35. 5 A, respectively.", "output": "DOPC, DPPC, DOPC, DPPC, DOPC, DOPC, DPPC." }, { "input": "Novel regulatory system nemRA - gloA for electrophile reduction in Escherichia coli K - 12.", "output": "There is no related enetity." }, { "input": "Electrophilic compounds such as glyoxals, which are toxic due to their reactive carbonyl group, are generated in vivo through various pathways.", "output": "glyoxals, carbonyl." }, { "input": "In this study, we obtained evidence indicating that the nemRA operon, previously reported to encode a repressor and the N - ethylmaleimide reductase, respectively, is co - transcribed with the 3 ' - proximal gloA gene encoding glyoxalase I.", "output": "N - ethylmaleimide." }, { "input": "The operon is not only involved in cytosolic detoxification but is also regulated by electrophiles such as quinones and glyoxals.", "output": "quinones, glyoxals." }, { "input": "A gel mobility shift assay revealed that purified NemR repressor bound to DNA was dissociated upon interaction with quinones and glyoxals, while their reduced forms were ineffective.", "output": "quinones, glyoxals." }, { "input": "The cysteines of NemR at 21 and 116 were essential in sensing electrophiles in vivo and in vitro.", "output": "There is no related enetity." }, { "input": "Reversible intermolecular disulphide bonds were observed with a reducing agent as well as with electrophiles.", "output": "disulphide." }, { "input": "DNA binding affinity reduced by glyoxal was also increased with a reducing agent.", "output": "glyoxal." }, { "input": "The NemA reductase, an FMN - containing enzyme, exhibited catalytic activity toward various electrophiles including quinones, while GloA played a major role in glyoxal detoxification.", "output": "FMN, quinones, glyoxal." }, { "input": "Therefore, we propose that cells have a cytosolic system consisting of the nemRA - gloA operon for the reduction of electrophiles, especially quinones and glyoxals, to maintain an appropriate intracellular redox balance.", "output": "quinones, glyoxals." }, { "input": "Interfacial rheology of asphaltenes at oil - water interfaces and interpretation of the equation of state.", "output": "There is no related enetity." }, { "input": "In an earlier study, ( 1 ) oil - water interfacial tension was measured by the pendant drop technique for a range of oil - phase asphaltene concentrations and viscosities.", "output": "There is no related enetity." }, { "input": "The interfacial tension was found to be related to the relative surface coverage during droplet expansion.", "output": "There is no related enetity." }, { "input": "The relationship was independent of aging time and bulk asphaltenes concentration, suggesting that cross - linking did not occur at the interface and that only asphaltene monomers were adsorbed.", "output": "There is no related enetity." }, { "input": "The present study extends this work to measurements of interfacial rheology with the same fluids.", "output": "There is no related enetity." }, { "input": "Dilatation moduli have been measured using the pulsating droplet technique at different frequencies, different concentrations ( below and above CNAC ), and different aging times.", "output": "There is no related enetity." }, { "input": "Care was taken to apply the technique in conditions where viscous and inertial effects are small.", "output": "There is no related enetity." }, { "input": "The elastic modulus increases with frequency and then plateaus to an asymptotic value.", "output": "There is no related enetity." }, { "input": "The asymptotic or instantaneous elasticity has been plotted against the interfacial tension, indicating the existence of a unique relationship, between them, independent of adsorption conditions.", "output": "There is no related enetity." }, { "input": "The relationship between interfacial tension and surface coverage is analyzed with a Langmuir equation of state.", "output": "There is no related enetity." }, { "input": "The equation of state also enabled the prediction of the observed relationship between the instantaneous elasticity and interfacial tension.", "output": "There is no related enetity." }, { "input": "The fit by a simple Langmuir equation of state ( EOS ) suggests minimal effects of aging and of nanoaggregates or gel formation at the interface.", "output": "There is no related enetity." }, { "input": "Only one parameter is involved in the fit, which is the surface excess coverage Gamma infinity = 3. 2 molecules / nm ( 2 ) ( 31. 25 A ( 2 ) / molecule ).", "output": "There is no related enetity." }, { "input": "This value appears to agree with flat - on adsorption ( 2 ) of monomeric asphaltene structures consisting of aromatic cores composed of an average of six fused rings and supports the hypothesis that nanoaggregates do not adsorb on the interface.", "output": "There is no related enetity." }, { "input": "The observed interfacial effects of the adsorbed asphaltenes, correlated by the Langmuir EOS, are consistent with the asphaltene aggregation behavior in the bulk fluid expected from the Yen - Mullins model.", "output": "There is no related enetity." }, { "input": "( 3, 4 ).", "output": "There is no related enetity." }, { "input": "The heart in sepsis: from basic mechanisms to clinical management.", "output": "There is no related enetity." }, { "input": "Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production.", "output": "There is no related enetity." }, { "input": "In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated.", "output": "There is no related enetity." }, { "input": "As a result, cells and organs may survive in a non - functioning hibernation - like condition.", "output": "There is no related enetity." }, { "input": "Sepsis - induced cardiac dysfunction may represent an example of such functional shutdown.", "output": "There is no related enetity." }, { "input": "Sepsis - induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors.", "output": "There is no related enetity." }, { "input": "Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins.", "output": "calcium, calcium." }, { "input": "All these changes are mediated by cytokines.", "output": "There is no related enetity." }, { "input": "Treatment includes preload optimization with sufficient fluids.", "output": "There is no related enetity." }, { "input": "However, excessive volume loading is harmful.", "output": "There is no related enetity." }, { "input": "The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines.", "output": "norepinephrine, catecholamines." }, { "input": "During early sepsis, cardiac output can be increased by dobutamine.", "output": "dobutamine." }, { "input": "While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful.", "output": "catecholamines." }, { "input": "Novel therapies for sepsis - induced cardiac dysfunction are discussed in this article.", "output": "There is no related enetity." }, { "input": "Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands.", "output": "levosimendan, istaroxime, omecamtiv mecarbil, oxygen." }, { "input": "Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling.", "output": "ivabradine, oxygen." }, { "input": "Beta - blockers additionally reduce local and systemic inflammation.", "output": "There is no related enetity." }, { "input": "Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions.", "output": "pyruvate, succinate." }, { "input": "All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.", "output": "There is no related enetity." }, { "input": "BACE2 as a new diabetes target: a patent review ( 2010 - 2012 ).", "output": "There is no related enetity." }, { "input": "Introduction: When two novel aspartyl proteases were published in 1999 and 2000, beta - site APP - cleaving enzyme 1 ( BACE1 ) was confirmed as the long sought after beta - secretase and Alzheimer ' s disease drug target.", "output": "There is no related enetity." }, { "input": "However, the role of its paralogue, BACE2, proved elusive until a 2011 publication implicated it as a Collectrin ( TMEM27 ) secretase controlling pancreatic beta - cell proliferation and a new therapeutic intervention for diabetes.", "output": "There is no related enetity." }, { "input": "Areas covered: This review, using SureChemOpen, encompasses early validation compounds and small - molecule BACE2 inhibitors for diabetes.", "output": "There is no related enetity." }, { "input": "Since 2010, one assay patent and several chemical series have been published by Roche but these were followed by filings from Novartis and Schering in 2012.", "output": "There is no related enetity." }, { "input": "The patents from these three companies include BACE2 - only filings but also some specifying both BACE1 and BACE2 inhibitors.", "output": "There is no related enetity." }, { "input": "Expert opinion: Roche ' s early collaborative target validation has given them a lead in BACE2 medicinal chemistry.", "output": "There is no related enetity." }, { "input": "However, the extensive data output for BACE1 in patents and papers over the last decade, plus liganded crystal structures for both proteases, should expedite the design of BACE2 inhibitors by other organisations.", "output": "There is no related enetity." }, { "input": "This may also shorten the development time for clinical candidates that, unlike those now entering Phase I trials for BACE1, would not need to be brain - penetrant.", "output": "There is no related enetity." }, { "input": "A novel benzo [ d ] imidazole derivate prevents the development of dextran sulfate sodium - induced murine experimental colitis via inhibition of NLRP3 inflammasome.", "output": "benzo [ d ] imidazole, sodium." }, { "input": "NLRP3 inflammasome has been reported to be associated with various kinds of immunological diseases including colitis.", "output": "There is no related enetity." }, { "input": "However, there are few drug candidates targeting inflammasomes for the treatment of colitis.", "output": "There is no related enetity." }, { "input": "In the present study, we aimed at examining the effect of 1 - ethyl - 5 - methyl - 2 - phenyl - 1H - benzo [ d ] imidazole, a synthetic small molecular compound also named Fc11a - 2, for the treatment of dextran sulfate sodium ( DSS ) - induced experimental colitis in mice via targeting NLRP3 inflammasome.", "output": "1 - ethyl - 5 - methyl - 2 - phenyl - 1H - benzo [ d ] imidazole, Fc11a - 2, sulfate, sodium." }, { "input": "Treatment with Fc11a - 2 dose - dependently attenuated the loss of body weight and shortening of colon length induced by DSS.", "output": "There is no related enetity." }, { "input": "In addition, the disease activity index, histopathologic scores and myeloperoxidase activity were also significantly reduced by Fc11a - 2 treatment.", "output": "Fc11a - 2." }, { "input": "Moreover, protein and mRNA levels of DSS - induced proinflammatory cytokines in colon, including TNF - alpha, IL - 1 beta, IL - 18, IL - 17A and IFN - gamma, were markedly suppressed by Fc11a - 2.", "output": "Fc11a - 2." }, { "input": "Furthermore, a decreased CD11c ( + ) macrophage infiltration in colons and inactivation of caspase - 1 in peritoneal macrophages were detected in Fc11a - 2 - treated mice.", "output": "Fc11a." }, { "input": "The mechanism of action of Fc11a - 2 was related to the inhibition of the cleavage of pro - caspase - 1, pro - IL - 1 beta and pro - IL - 18 which in turn suppressed the activation of NLRP3 inflammasome.", "output": "Fc11a - 2." }, { "input": "Taken together, our results demonstrate the ability of Fc11a - 2 to inhibit NLRP3 inflammasome activation and its potential use in the treatment of inflammatory bowel diseases.", "output": "Fc11a - 2." }, { "input": "Intact inhibitory control processes in abstinent drug abusers ( II ): A high - density electrical mapping study in former cocaine and heroin addicts.", "output": "cocaine, heroin." }, { "input": "Response inhibition deficits are well - documented in drug users, and are related to the impulsive tendencies characteristic of the addictive phenotype.", "output": "There is no related enetity." }, { "input": "Addicts also show significant motivational issues that may accentuate these inhibitory deficits.", "output": "There is no related enetity." }, { "input": "We investigated the extent to which these inhibitory deficits are present in abstinence.", "output": "There is no related enetity." }, { "input": "Salience of the task stimuli was also manipulated on the premise that emotionally - valenced inputs might impact inhibitory efficacy by overcoming the blunted responses to everyday environmental inputs characteristic of this population.", "output": "There is no related enetity." }, { "input": "Participants performed response inhibition tasks consisting of both neutral and emotionally valenced stimuli while high - density event - related potentials ( ERPs ) were recorded.", "output": "There is no related enetity." }, { "input": "Electrophysiological responses ( N2 / P3 components ) to successful inhibitions in abstinent abusers ( N = 20 ) and non - using participants ( N = 21 ) were compared.", "output": "There is no related enetity." }, { "input": "In contrast to previous work in current users, our abstinent cohort showed no detectable behavioral or electrophysiological differences in their inhibitory responses, and no differences on self - reports of impulsivity, despite their long histories of chronic use ( mean = 10. 3 years ).", "output": "There is no related enetity." }, { "input": "The current findings are consistent with a recovery of inhibitory control processes as a function of abstinence.", "output": "There is no related enetity." }, { "input": "Abstinent former users, however, did show a reduced modulation, relative to controls, of their ERPs to valenced input while performing successful inhibitions, although contrary to our hypothesis, the use of valenced inputs had no impact on inhibitory performance.", "output": "There is no related enetity." }, { "input": "Reduced ERP modulation to emotionally valenced inputs may have implications for relapse in emotional contexts outside the treatment center.", "output": "There is no related enetity." }, { "input": "Minireview: Nuclear Insulin and Insulin - like Growth Factor - 1 Receptors: A Novel Paradigm in Signal Transduction.", "output": "There is no related enetity." }, { "input": "The specificity of the insulin receptor ( InsR ) and insulin - like growth factor - 1 receptor ( IGF1R ) signaling pathways has been the focus of significant debate over the past few years.", "output": "There is no related enetity." }, { "input": "Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog.", "output": "There is no related enetity." }, { "input": "Hence, in addition to the classical roles associated with cell - surface receptors ( eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 ( IRS - 1 ) and additional substrates, protein - protein interactions with membrane and cytoplasm components ), new data are consistent with nuclear ( genomic ) role ( s ) for both InsR and IGF1R.", "output": "tyrosine." }, { "input": "The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation ( ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors ).", "output": "There is no related enetity." }, { "input": "The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction.", "output": "There is no related enetity." }, { "input": "Although research on the role of nuclear InsR / IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer.", "output": "There is no related enetity." }, { "input": "Loss of an ig kappa gene enhancer in mature B cells results in rapid gene silencing and partial reversible dedifferentiation.", "output": "There is no related enetity." }, { "input": "We address here whether there is cellular memory of a transcriptional enhancer once it has served its purpose to establish an active chromatin state.", "output": "There is no related enetity." }, { "input": "We have previously shown that the mouse Ig kappa gene ' s downstream enhancers, E3 ' and Ed, are essential but play redundant roles for establishing transcriptional activity in the locus during B cell development.", "output": "There is no related enetity." }, { "input": "To determine whether these enhancers are also necessary for the maintenance of transcriptional activity, we conditionally deleted E3 ' in mature B cells that possessed Ed ( - / - ) alleles.", "output": "There is no related enetity." }, { "input": "Upon E3 ' deletion, the locus became rapidly silenced and lost positive histone epigenetic marks, and the mature B cells partially dedifferentiated, induced RAG - 1 and - 2 along with certain other pro - B cell makers, and then redifferentiated after triggering Ig lambda gene rearrangements.", "output": "There is no related enetity." }, { "input": "We conclude that the Ig kappa gene ' s downstream enhancers are essential for both the establishment and maintenance of transcriptional activity and that there is no cellular memory of previous transcriptional activity in this locus.", "output": "There is no related enetity." }, { "input": "Furthermore, upon enhancer loss, the mature B cells unexpectedly underwent reversible retrograde differentiation.", "output": "There is no related enetity." }, { "input": "This result establishes that receptor editing can occur in mature B cells and raises the possibility that this may provide a tolerance mechanism for eliminating autoreactive B cells in the periphery.", "output": "There is no related enetity." }, { "input": "Multiple functional polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels.", "output": "glucose." }, { "input": "AIMS / HYPOTHESIS: We previously identified the G6PC2 locus as a strong determinant of fasting plasma glucose ( FPG ) and showed that a common G6PC2 intronic single nucleotide polymorphism ( SNP ) ( rs560887 ) and two common G6PC2 promoter SNPs ( rs573225 and rs13431652 ) are highly associated with FPG.", "output": "glucose." }, { "input": "However, these promoter SNPs have complex effects on G6PC2 fusion gene expression, and our data suggested that only rs13431652 is a potentially causative SNP.", "output": "There is no related enetity." }, { "input": "Here we examine the effect of rs560887 on G6PC2 pre - mRNA splicing and the contribution of an additional common G6PC2 promoter SNP, rs2232316, to the association signal.", "output": "There is no related enetity." }, { "input": "METHODS: Minigene analyses were used to characterise the effect of rs560887 on G6PC2 pre - mRNA splicing.", "output": "There is no related enetity." }, { "input": "Fusion gene and gel retardation analyses characterised the effect of rs2232316 on G6PC2 promoter activity and transcription factor binding.", "output": "There is no related enetity." }, { "input": "The genetic association of rs2232316 with FPG variation was assessed using regression adjusted for age, sex and BMI in 4, 220 Europeans with normal FPG.", "output": "There is no related enetity." }, { "input": "RESULTS: The rs560887 - G allele was shown to enhance G6PC2 pre - mRNA splicing, whereas the rs2232316 - A allele enhanced G6PC2 transcription by promoting Foxa2 binding.", "output": "There is no related enetity." }, { "input": "Genetic analyses provide evidence for association of the rs2232316 - A allele with increased FPG ( beta = 0. 04 mmol / l; p = 4. 3 x 10 ( - 3 ) ) as part of the same signal as rs560887, rs573225 and rs13431652.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS / INTERPRETATION: As with rs13431652, the in situ functional data with rs560887 and rs2232316 are in accord with the putative function of G6PC2 in pancreatic islets, and suggest that all three are potentially causative SNPs that contribute to the association between G6PC2 and FPG.", "output": "There is no related enetity." }, { "input": "DNA Methylation and Cancer Development: Molecular Mechanism.", "output": "There is no related enetity." }, { "input": "DNA methylation is a significant regulator of gene expression, and its role in carcinogenesis recently has been a subject of remarkable interest.", "output": "There is no related enetity." }, { "input": "The aim of this review is to analyze the mechanism and cell regulatory effects of both hypo - and hyper - DNA methylation on cancer.", "output": "There is no related enetity." }, { "input": "In this review, we report new developments and their implications regarding the effects of DNA methylation on cancer development.", "output": "There is no related enetity." }, { "input": "Indeed, alteration of the pattern of DNA methylation has been a constant finding in cancer cells of the same type and differences in the pattern of DNA methylation not only occur in a variety of tumor types, but also in developmental processes Furthermore, the pattern of histone modification appears to be a predicator of the risk of recurrence of human cancers.", "output": "There is no related enetity." }, { "input": "It is well known that hypermethylation represses transcription of the promoter sections of tumor - suppressor genes leading to gene silencing.", "output": "There is no related enetity." }, { "input": "However, hypomethylation also has been identified as a cause of oncogenesis.", "output": "There is no related enetity." }, { "input": "Furthermore, experiments concerning the mechanism of methylation and its control have led to the discovery of many regulatory enzymes and proteins.", "output": "There is no related enetity." }, { "input": "This review reports on methods developed for the detection of 5 - hydroxymethylcytosine methylation at the 5 - methylcytosine of protein domains in the CpG context compared to non - methylated DNA, histone modification, and microRNA change.", "output": "5 - hydroxymethylcytosine, 5 - methylcytosine." }, { "input": "Agonist - induced Down - regulation of Endogenous Protein Kinase C alpha through an Endolysosomal Mechanism.", "output": "There is no related enetity." }, { "input": "Protein kinase C ( PKC ) isozymes undergo down - regulation upon sustained stimulation.", "output": "There is no related enetity." }, { "input": "Previous studies have pointed to the existence of both proteasome - dependent and - independent pathways of PKC alpha processing.", "output": "There is no related enetity." }, { "input": "Here we demonstrate that these down - regulation pathways are engaged in different subcellular compartments; proteasomal degradation occurs mainly at the plasma membrane, whereas non - proteasomal processing occurs in the perinuclear region.", "output": "There is no related enetity." }, { "input": "Using cholesterol depletion, pharmacological inhibitors, RNA interference, and dominant - negative mutants, we define the mechanisms involved in perinuclear accumulation of PKC alpha and identify the non - proteasomal mechanism mediating its degradation.", "output": "cholesterol." }, { "input": "We show that intracellular accumulation of PKC alpha involves at least two clathrin - independent, cholesterol / lipid raft - mediated pathways that do not require ubiquitination of the protein; one is dynamin - dependent and likely involves caveolae, whereas the other is dynamin - and small GTPase - independent.", "output": "cholesterol." }, { "input": "Internalized PKC alpha traffics through endosomes and is delivered to the lysosome for degradation.", "output": "There is no related enetity." }, { "input": "Supportive evidence includes ( a ) detection of the enzyme in EEA1 - positive early endosomes, Rab7 - positive late endosomes / multivesicular bodies, and LAMP1 - positive lysosomes and ( b ) inhibition of its down - regulation by lysosome - disrupting agents and leupeptin.", "output": "leupeptin." }, { "input": "Only limited dephosphorylation of PKC alpha occurs during trafficking, with fully mature enzyme being the main target for lysosomal degradation.", "output": "There is no related enetity." }, { "input": "These studies define a novel and widespread mechanism of desensitization of PKC alpha signaling that involves endocytic trafficking and lysosome - mediated degradation of the mature, fully phosphorylated protein.", "output": "There is no related enetity." }, { "input": "2 - aminothiazoles with improved pharmacotherapeutic properties for treatment of prion disease.", "output": "2 - aminothiazoles." }, { "input": "Recently, we described the aminothiazole lead ( 4 - biphenyl - 4 - ylthiazol - 2 - yl ) - ( 6 - methylpyridin - 2 - yl ) - amine ( 1 ), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ~ 40 %, and high exposure in the brains of mice.", "output": "aminothiazole, ( 4 - biphenyl - 4 - ylthiazol - 2 - yl ) - ( 6 - methylpyridin - 2 - yl ) - amine." }, { "input": "Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease - causing prion protein PrP ( Sc ).", "output": "There is no related enetity." }, { "input": "Accordingly, we sought to identify analogues of 1 with improved antiprion potency in ScN2a - cl3 cells while retaining similar or superior properties.", "output": "There is no related enetity." }, { "input": "Herein we report the discovery of improved lead compounds such as ( 6 - methylpyridin - 2 - yl ) - [ 4 - ( 4 - pyridin - 3 - yl - phenyl ) thiazol - 2 - yl ] amine and cyclopropanecarboxylic acid ( 4 - biphenylthiazol - 2 - yl ) amide, which exhibit brain exposure / EC50 ratios at least tenfold greater than that of compound 1.", "output": "( 6 - methylpyridin - 2 - yl ) - [ 4 - ( 4 - pyridin - 3 - yl - phenyl ) thiazol - 2 - yl ] amine, cyclopropanecarboxylic acid ( 4 - biphenylthiazol - 2 - yl ) amide." }, { "input": "Enhanced Catalytic Four - Electron Dioxygen ( O2 ) and Two - Electron Hydrogen Peroxide ( H2O2 ) Reduction with a Copper ( II ) Complex Possessing a Pendant Ligand Pivalamido Group.", "output": "Dioxygen, O2, Hydrogen Peroxide, H2O2, Copper ( II )." }, { "input": "A copper complex, [ ( PV - tmpa ) Cu ( II ) ] ( ClO4 ) 2 ( 1 ) [ PV - tmpa = bis ( pyrid - 2 - ylmethyl ) { [ 6 - ( pivalamido ) pyrid - 2 - yl ] methyl } amine ], acts as a more efficient catalyst for the four - electron reduction of O2 by decamethylferrocene ( Fc * ) in the presence of trifluoroacetic acid ( CF3COOH ) in acetone as compared with the corresponding copper complex without a pivalamido group, [ ( tmpa ) Cu ( II ) ] ( ClO4 ) 2 ( 2 ) ( tmpa = tris ( 2 - pyridylmethyl ) amine ).", "output": "copper, [ ( PV - tmpa ) Cu ( II ) ] ( ClO4 ) 2, PV - tmpa, bis ( pyrid - 2 - ylmethyl ) { [ 6 - ( pivalamido ) pyrid - 2 - yl ] methyl } amine, O2, decamethylferrocene, trifluoroacetic acid, CF3COOH, acetone, copper, pivalamido, [ ( tmpa ) Cu ( II ) ] ( ClO4 ) 2, tmpa, tris ( 2 - pyridylmethyl ) amine." }, { "input": "The rate constant ( kobs ) of formation of decamethylferrocenium ion ( Fc * ( + ) ) in the catalytic four - electron reduction of O2 by Fc * in the presence of a large excess CF3COOH and O2 obeyed first - order kinetics.", "output": "decamethylferrocenium, O2, CF3COOH, O2." }, { "input": "The kobs value was proportional to the concentration of catalyst 1 or 2, whereas the kobs value remained constant irrespective of the concentration of CF3COOH or O2.", "output": "CF3COOH, O2." }, { "input": "This indicates that electron transfer from Fc * to 1 or 2 is the rate - determining step in the catalytic cycle of the four - electron reduction of O2 by Fc * in the presence of CF3COOH.", "output": "O2, CF3COOH." }, { "input": "The second - order catalytic rate constant ( kcat ) for 1 is 4 times larger than the corresponding value determined for 2.", "output": "There is no related enetity." }, { "input": "With the pivalamido group in 1 compared to 2, the Cu ( II ) / Cu ( I ) potentials are - 0. 23 and - 0. 05 V vs SCE, respectively.", "output": "pivalamido, Cu ( II ), Cu ( I )." }, { "input": "However, during catalytic turnover, the CF3COO ( - ) anion present readily binds to 2 shifting the resulting complex ' s redox potential to - 0. 35 V.", "output": "CF3COO ( - )." }, { "input": "The pivalamido group in 1 is found to inhibit anion binding.", "output": "pivalamido." }, { "input": "The overall effect is to make 1 easier to reduce ( relative to 2 ) during catalysis, accounting for the relative kcat values observed.", "output": "There is no related enetity." }, { "input": "1 is also an excellent catalyst for the two - electron two - proton reduction of H2O2 to water and is also more efficient than is 2.", "output": "H2O2." }, { "input": "For both complexes, reaction rates are greater than for the overall four - electron O2 - reduction to water, an important asset in the design of catalysts for the latter.", "output": "O2." }, { "input": "Structure - Based Design of beta - Site APP Cleaving Enzyme 1 ( BACE1 ) Inhibitors for the Treatment of Alzheimer ' s Disease.", "output": "There is no related enetity." }, { "input": "The amyloid hypothesis asserts that excess production or reduced clearance of the amyloid - beta ( A beta ) peptides in the brain initiates a sequence of events that ultimately lead to Alzheimer ' s disease and dementia.", "output": "There is no related enetity." }, { "input": "The A beta hypothesis has identified BACE1 as a therapeutic target to treat Alzheimer ' s and led to medicinal chemistry efforts to design its inhibitors both in the pharmaceutical industry and in academia.", "output": "There is no related enetity." }, { "input": "This review summarizes two distinct categories of inhibitors designed based on conformational states of \" closed \" and \" open \" forms of the enzyme.", "output": "There is no related enetity." }, { "input": "In each category the inhibitors are classified based on the core catalytic interaction group or the aspartyl binding motif ( ABM ).", "output": "aspartyl." }, { "input": "This review covers the description of inhibitors in each ABM class with X - ray crystal structures of key compounds, their binding modes, related structure - activity data highlighting potency advances, and additional properties such as selectivity profile, P - gp efflux, pharmacokinetic, and pharmacodynamic data.", "output": "There is no related enetity." }, { "input": "Mechanism of One - Way Traffic of Hexameric Phi29 DNA Packaging Motor with Four Electropositive Relaying Layers Facilitating Antiparallel Revolution.", "output": "There is no related enetity." }, { "input": "The importance of nanomotors in nanotechnology is akin to that of mechanical engines to daily life.", "output": "There is no related enetity." }, { "input": "The AAA + superfamily is a class of nanomotors performing various functions.", "output": "There is no related enetity." }, { "input": "Their hexagonal arrangement facilitates bottom - up assembly for stable structures.", "output": "There is no related enetity." }, { "input": "The bacteriophage phi29 DNA translocation motor contains three coaxial rings: a dodecamer channel, a hexameric ATPase ring, and a hexameric pRNA ring.", "output": "There is no related enetity." }, { "input": "The viral DNA packaging motor has been believed to be a rotational machine.", "output": "There is no related enetity." }, { "input": "However, we discovered a revolution mechanism without rotation.", "output": "There is no related enetity." }, { "input": "By analogy, the earth revolves around the sun while rotating on its own axis.", "output": "There is no related enetity." }, { "input": "One - way traffic of dsDNA translocation is facilitated by five factors: ( 1 ) ATPase changes its conformation to revolve dsDNA within a hexameric channel in one direction; ( 2 ) the 30 degrees tilt of the channel subunits causes an antiparallel arrangement between two helices of dsDNA and channel wall to advance one - way translocation; ( 3 ) unidirectional flow property of the internal channel loops serves as a ratchet valve to prevent reversal; ( 4 ) 5 ' - 3 ' single - direction movement of one DNA strand along the channel wall ensures single direction; and ( 5 ) four electropositive layers interact with one strand of the electronegative dsDNA phosphate backbone, resulting in four relaying transitional pauses during translocation.", "output": "phosphate." }, { "input": "The discovery of a riding system along one strand provides a motion nanosystem for cargo transportation and a tool for studying force generation without coiling, friction, and torque.", "output": "There is no related enetity." }, { "input": "The revolution of dsDNA among 12 subunits offers a series of recognition sites on the DNA backbone to provide additional spatial variables for nucleotide discrimination for sensing applications.", "output": "nucleotide." }, { "input": "Mechanical Regulation of Cellular Adhesion onto Honeycomb - Patterned Porous Scaffolds by Altering the Elasticity of Material Surfaces.", "output": "There is no related enetity." }, { "input": "In this report, we show the preparation of honeycomb scaffolds for cell culturing by using \" breath figure \" method, and we found that their mechanical and topographical properties strongly affect the adhesion of fibroblasts.", "output": "There is no related enetity." }, { "input": "By photo - cross - linking of the poly ( 1, 2 - butadiene ), the hardness of the honeycomb scaffold can be successfully controlled without any surface chemical changes, and detail modulus values of scaffolds were measured by atomic force microscopy.", "output": "poly ( 1 , 2 - butadiene )." }, { "input": "We found that only small numbers of the cells adhered on the softer honeycomb scaffolds, which has even higher modulus value than conventional gels, comparing with flat films and a hard honeycomb scaffold.", "output": "There is no related enetity." }, { "input": "These results indicate that the elastomeric honeycomb substrates are useful for evaluating the effect of the mechanical signal - derived geometry on the transduction system of cells.", "output": "There is no related enetity." }, { "input": "Synthesis of a DOTA ( Gd ( 3 + ) ) - conjugate of proton - pump inhibitor pantoprazole for gastric wall imaging studies.", "output": "DOTA, Gd ( 3 + ), pantoprazole." }, { "input": "Magnetic resonance imaging ( MRI ) is used to evaluate gastrointestinal ( GI ) structure and functions in humans.", "output": "There is no related enetity." }, { "input": "Despite filling the viscus lumen with a contrast agent, visualization of the viscus wall is limited.", "output": "There is no related enetity." }, { "input": "To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd - based MRI contrast agent, encaged with a chelating agent ( DOTA ), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon.", "output": "Gd, DOTA, pantoprazole." }, { "input": "The DOTA linkage was installed at a mechanism - based strategic location in the pantoprazole molecule to minimize a possible negative effect of the structural modification on the drug.", "output": "DOTA, pantoprazole." }, { "input": "It is anticipated that by defining the wall of the stomach and colon, this compound will facilitate functional MRI of the GI tract in humans.", "output": "There is no related enetity." }, { "input": "Evaluation of anti - HCV activity and SAR study of ( + ) - lycoricidine through targeting of host heat - stress cognate 70 ( Hsc70 ).", "output": "( + ) - lycoricidine." }, { "input": "The anti hepatitis C virus ( HCV ) activity of ( + ) - lycoricidine ( 1 ) was evaluated for the first time in this letter, yielding an EC50 value of 0. 55nmol / mL and an selection index ( SI ) value of 12. 72.", "output": "( + ) - lycoricidine." }, { "input": "Further studies indicated that 1 induced this effect by down - regulating host heat - stress cognate 70 ( Hsc70 ) expression.", "output": "There is no related enetity." }, { "input": "In addition, 20 derivatives were designed and synthesised to investigate the basic structure - activity relationship ( SAR ) of the title compound.", "output": "There is no related enetity." }, { "input": "Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 ( EC50 = 0. 68nmol / mL, SI = 33. 86 ), compound 2d ( EC50 = 15nmol / mL, SI = 12 ) and compound 5 ( EC50 = 33nmol / mL, SI > 10. 91 ).", "output": "There is no related enetity." }, { "input": "Meanwhile, the experimental data suggest that the modification of certain groups of ( + ) - lycoricidine can reduce the cytotoxicity of the compounds.", "output": "( + ) - lycoricidine." }, { "input": "Photosensitized protein damage by dimethoxyphosphorus ( V ) tetraphenylporphyrin.", "output": "dimethoxyphosphorus ( V ) tetraphenylporphyrin." }, { "input": "For the purpose of the basic study of photodynamic therapy, the activity of the water - soluble P ( V ) porphyrin, dimethoxyP ( V ) tetraphenylporphyrin chloride ( DMP ( V ) TPP ), on photosensitized protein damage was examined.", "output": "P ( V ) porphyrin, dimethoxyP ( V ) tetraphenylporphyrin chloride, DMP ( V ) TPP." }, { "input": "The quantum yield of singlet oxygen generation by DMP ( V ) TPP ( 0. 64 ) was comparable with that of typical porphyrin photosensitizers.", "output": "oxygen, DMP ( V ) TPP, porphyrin." }, { "input": "Absorption spectrum measurement demonstrated the binding interaction between DMP ( V ) TPP and human serum albumin, a water - soluble protein.", "output": "DMP ( V ) TPP." }, { "input": "Photo - irradiated DMP ( V ) TPP damaged the amino acid residue of human serum albumin, resulting in the decrease of the fluorescence intensity from the tryptophan residue of human serum albumin.", "output": "DMP ( V ) TPP, amino acid, tryptophan." }, { "input": "A singlet oxygen quencher, sodium azide, could not completely inhibit the damage of human serum albumin, suggesting that the electron transfer mechanism contributes to protein damage as does singlet oxygen generation.", "output": "oxygen, sodium azide, oxygen." }, { "input": "The decrease of the fluorescence lifetime of DMP ( V ) TPP by human serum albumin supported the electron transfer mechanism.", "output": "DMP ( V ) TPP." }, { "input": "The estimated contribution of the electron transfer mechanism is 0. 64.", "output": "There is no related enetity." }, { "input": "These results suggest that the activity of DMP ( V ) TPP can be preserved under lower oxygen concentration condition such as tumor.", "output": "DMP ( V ) TPP, oxygen." }, { "input": "Evaluation of an alternative in vitro test battery for detecting reproductive toxicants.", "output": "There is no related enetity." }, { "input": "The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved.", "output": "There is no related enetity." }, { "input": "A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays.", "output": "There is no related enetity." }, { "input": "We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays.", "output": "There is no related enetity." }, { "input": "The battery correctly detected 11 / 12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery.", "output": "There is no related enetity." }, { "input": "Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data.", "output": "There is no related enetity." }, { "input": "This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays.", "output": "There is no related enetity." }, { "input": "Derivatives of Dictyostelium discoideum differentiation - inducing factor - 3 suppress the activities of Trypanosoma cruzi in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Chagas disease ( human American trypanosomiasis ), which is caused by the protozoan parasite Trypanosoma cruzi, is responsible for numerous deaths each year; however, established treatments for the disease are limited.", "output": "There is no related enetity." }, { "input": "Differentiation - inducing factor - 1 ( DIF - 1 ) and DIF - 3 are chlorinated alkylphenones originally found in the cellular slime mold Dictyostelium discoideum that have been shown to possess pharmacological activities.", "output": "alkylphenones." }, { "input": "Here, we investigated the effects of DIF - 3 derivatives on the infection rate and growth of T. cruzi by using an in vitro assay system utilizing host human fibrosarcoma HT1080 cells.", "output": "There is no related enetity." }, { "input": "Certain DIF - 3 derivatives, such as butoxy - DIF - 3 ( Bu - DIF - 3 ), at micro - molar levels strongly suppressed both the infection rate and growth of T. cruzi in HT1080 cells and exhibited little toxicity for HT1080 cells.", "output": "butoxy." }, { "input": "For example, the IC50 of DIF - 3 and Bu - DIF - 3 versus the growth of T. cruzi in HT1080 cells were 3. 95 and 0. 72 mu M, respectively, and the LD50 of the two compounds versus HT1080 cells were both greater than 100 mu M.", "output": "There is no related enetity." }, { "input": "We also examined the effects of DIF - 3 and Bu - DIF - 3 on T. cruzi activity in C57BL / 6 mice.", "output": "There is no related enetity." }, { "input": "Intraperitoneally administered Bu - DIF - 3 ( 50mg / kg ) significantly suppressed the number of trypomastigotes in blood with no apparent adverse effects.", "output": "There is no related enetity." }, { "input": "These results strongly suggest that DIF - 3 derivatives could be new lead compounds in the development of anti - trypanosomiasis drugs.", "output": "There is no related enetity." }, { "input": "Acetylcholinesterase inhibition reveals endogenous nicotinic modulation of glutamate inputs to CA1 stratum radiatum interneurons in hippocampal slices.", "output": "glutamate." }, { "input": "The involvement of brain nicotinic acetylcholine receptors ( nAChRs ) in the neurotoxicological effects of soman, a potent acetylcholinesterase ( AChE ) inhibitor and a chemical warfare agent, is not clear.", "output": "acetylcholine." }, { "input": "This is partly due to a poor understanding of the role of AChE in brain nAChR - mediated functions.", "output": "There is no related enetity." }, { "input": "To test the hypothesis that AChE inhibition builds sufficient acetylcholine ( ACh ) in the brain and facilitates nAChR - dependent glutamate transmission, we used whole - cell patch - clamp technique to record spontaneous glutamate excitatory postsynaptic currents ( EPSCs ) from CA1 stratum radiatum interneurons ( SRI ) in hippocampal slices.", "output": "acetylcholine, glutamate, glutamate." }, { "input": "First, the frequency, amplitude and kinetics of EPSCs recorded from slices of control guinea pigs were compared to those recorded from slices of guinea pigs after a single injection of the irreversible AChE inhibitor soman ( 25. 2 mu g / kg, s. c. ).", "output": "There is no related enetity." }, { "input": "Second, EPSCs were recorded from rat hippocampal slices before and after their superfusion with the reversible AChE inhibitor donepezil ( 100nM ).", "output": "donepezil." }, { "input": "The frequency of EPSCs was significantly higher in slices taken from guinea pigs 24h but not 7 days after the soman injection than in slices from control animals.", "output": "There is no related enetity." }, { "input": "In 52 % of the rat hippocampal slices tested, bath application of donepezil increased the frequency of EPSCs.", "output": "donepezil." }, { "input": "Further, exposure to donepezil increased both burst - like and large - amplitude EPSCs, and increased the proportion of short ( 20 - 100ms ) inter - event intervals.", "output": "donepezil." }, { "input": "Donepezil ' s effects were suppressed significantly in presence of 10 mu M mecamylamine or 10nM methyllycaconitine.", "output": "Donepezil, mecamylamine, methyllycaconitine." }, { "input": "These results support the concept that AChE inhibition is able to recruit nAChR - dependent glutamate transmission in the hippocampus and such a mechanism can contribute to the acute neurotoxicological actions of soman.", "output": "glutamate." }, { "input": "SEVERE HYPOGLYCEMIC EPISODES: A PERSISTENT THREAT FOR CHILDREN WITH TYPE 1 DIABETES MELLITUS AND THEIR FAMILIES.", "output": "There is no related enetity." }, { "input": "Background: As lowering HbA1c levels is still the main goal of insulin treatment, severe hypoglycaemia ( SH ) remains a common experience in children with type 1 diabetes mellitus ( T1DM ) and their families.", "output": "There is no related enetity." }, { "input": "Aim: This study aims to evaluate the incidence and the clinical features of SH episodes in our Centre in the last 20 years.", "output": "There is no related enetity." }, { "input": "Subjects and Methods: We analysed SH incidence in 269 patients diagnosed from 1990 to 2010 ( total follow - up 2212. 9 patient - years ).", "output": "There is no related enetity." }, { "input": "Inclusion criteria: at least 3 visits / year and 1 year of follow - up.", "output": "There is no related enetity." }, { "input": "SH episode was defined as any condition of low blood glucose requiring third - party assistance.", "output": "glucose." }, { "input": "Results: 50. 2 % of patients experienced at least 1 SH episode for a total of 345 episodes.", "output": "There is no related enetity." }, { "input": "Whole incidence was 15. 6 / 100 pts / yr, slightly different between first and second decade ( 12. 6 vs 16. 5, p = 0. 047 ).", "output": "There is no related enetity." }, { "input": "HbA1c at the time of SH was lower in the non - BB group ( 7. 4 +/- 1. 3 vs 8. 2 +/- 1. 4; p = 0. 0001 ) and worsened 3 months later ( p = 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Impaired awareness was the main or only symptom in 43. 5 %.", "output": "There is no related enetity." }, { "input": "SH occurred at night in 32 % of patients and they were significantly younger than those with SH at other times.", "output": "There is no related enetity." }, { "input": "5 SH episodes or more occurred in 8. 1 % of patients who presented a lower HbA1c, a younger age and shorter disease duration than the other patients.", "output": "There is no related enetity." }, { "input": "HbA1c at first SH was negatively correlated with number of SH ( r = - 0. 20; p = 0. 05 ).", "output": "There is no related enetity." }, { "input": "Conclusions: Despite the advent of new insulin regimens, we confirm that SH still represents a relevant risk and a current threat for patients with T1DM and their families.", "output": "There is no related enetity." }, { "input": "Effectiveness of in - patient rehabilitation in obesity - related orthopedic conditions.", "output": "There is no related enetity." }, { "input": "Background: The aim of the present paper is to provide initial evidence that in - patient multidisciplinary rehabilitation is effective in minimizing the obesity - related disability and enhancing functional capacities in obese patients with motor disability.", "output": "There is no related enetity." }, { "input": "Subjects: 464 obese patients with orthopedic conditions admitted to our Rehabilitation Unit for multidisciplinary rehabilitation were enrolled in this study.", "output": "There is no related enetity." }, { "input": "Methods: At admission and discharge ( after 4 weeks ), the following outcome measures were computed: body weight ( BW; Kg ), body mass index ( BMI; Kg / m2 ), Functional Independence Measure ( FIM ) motor and cognitive, Obesity - related disability test ( TSD - OC ), Visual Analogue Score ( VAS ) for functioning, Timed - Up - Go ( TUG ).", "output": "There is no related enetity." }, { "input": "Intensive rehabilitation addressed to obese patients with orthopedic conditions and motor difficulties consisted of a 4 - week and 3 - hour daily multidisciplinary program covering nutritional, motor and psychological aspects.", "output": "There is no related enetity." }, { "input": "Results: All of the outcomes measured, except the FIM cognitive score, improved significantly after in - patient rehabilitation.", "output": "There is no related enetity." }, { "input": "The obesity - specific disability scale appears sensitive to changes among groups with different grades of disability and the percentage of change does not differ among groups.", "output": "There is no related enetity." }, { "input": "Younger obese individuals generally showed to benefit more from rehabilitation interventions than the older ones.", "output": "There is no related enetity." }, { "input": "Conclusions: In - patient rehabilitation interventions appear effective in reducing both mild and severe disabilities related to obesity with orthopedic co - morbidities.", "output": "There is no related enetity." }, { "input": "This paper provides initial evidence that in - patient multidisciplinary intensive rehabilitation is effective in minimizing the obesity - related disability and initial support to the indications of the Italian Ministry of Health for such rehabilitation pathway.", "output": "There is no related enetity." }, { "input": "The disability grading could help the decision making of allocating patients to appropriate rehabilitation settings.", "output": "There is no related enetity." }, { "input": "Patterning of controllable surface wettability for printing techniques.", "output": "There is no related enetity." }, { "input": "Patterning of controllable surface wettability has attracted wide scientific attention due to its importance in both fundamental research and practical applications.", "output": "There is no related enetity." }, { "input": "In particular, it is crucial to form clear image areas and non - image areas in printing techniques based on wetting and dewetting.", "output": "There is no related enetity." }, { "input": "This review summarizes the recent research on and applications of patterning of controllable surface wettability for printing techniques, with a focus on the design and fabrication of the precise surface wettability patterning by enhancing the contrast of hydrophilicity and hydrophobicity, such as superhydrophilicity and superhydrophobicity.", "output": "There is no related enetity." }, { "input": "The selected topics mainly include patterned surface wettability for lithographic printing with different plate - making techniques, patterned surface wettability for microcontact printing with a patterned wetting stamp and special wettability mediated patterning microtransfer printing, patterned surface wettability for inkjet printing with controllable surface wettability of the substrate and printing head to ink, and patterned surface wettability by a combination of different printing techniques.", "output": "There is no related enetity." }, { "input": "A personal perspective on the future development and remaining challenges of this research is also briefly discussed.", "output": "There is no related enetity." }, { "input": "A Nanogram Dose of the CYP3A Probe Substrate Midazolam to Evaluate Drug Interactions.", "output": "Midazolam." }, { "input": "The objective of the study was to establish an in vivo method for assessing cytochrome P450 3A ( CYP3A ) activity using therapeutically inert nanogram doses of midazolam.", "output": "midazolam." }, { "input": "We administered four escalating single doses of oral midazolam ( 0. 0001 - 3 mg ) to 12 healthy participants, stratified according to CYP3A5 carrier status, to assess pharmacokinetics linearity.", "output": "midazolam." }, { "input": "We then evaluated the interactions with the CYP3A inhibitor ketoconazole ( 400 mg q. d. ) after nanogram and regular doses of midazolam.", "output": "ketoconazole, midazolam." }, { "input": "Area under the plasma concentration - time curve ( AUC ) and peak plasma concentration ( Cmax ) were linear over the entire range of doses.", "output": "There is no related enetity." }, { "input": "Ketoconazole reduced midazolam oral clearance by 92. 8 %.", "output": "Ketoconazole, midazolam." }, { "input": "AUC and Cmax increased by 1, 540 and 363 %, respectively.", "output": "There is no related enetity." }, { "input": "CYP3A5 carrier status had no influence on midazolam oral clearance or its inhibition by ketoconazole.", "output": "midazolam, ketoconazole." }, { "input": "This is the first study showing that midazolam pharmacokinetics is linear in a 30, 000 - fold concentration range, and therefore that nano - and microgram doses of midazolam can reliably predict the pharmacokinetics of midazolam in therapeutic doses and can be used to assess CYP3A activity even in the presence of strong CYP3A inhibitors. Clinical Pharmacology & Therapeutics ( 2013 ); advance online publication 20 March 2013. doi: 10. 1038 / clpt. 2013. 27.", "output": "midazolam, midazolam, midazolam." }, { "input": "PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine.", "output": "PEG." }, { "input": "Neisseria meningitidis is a life - threatening pathogen that causes meningitis and other clinical manifestations.", "output": "There is no related enetity." }, { "input": "As a key virulence determinant, meningococcal capsular polysaccharide ( PS ) can be used to prevent meningococcal diseases.", "output": "There is no related enetity." }, { "input": "Conjugation of PS to carrier protein can significantly improve the immunogenicity of PS and induce memory response in infants and young children.", "output": "There is no related enetity." }, { "input": "However, the conjugate vaccine may suffer from steric shielding of antigenic PS epitopes by carrier protein.", "output": "There is no related enetity." }, { "input": "Here, a heterobifunctional polyethylene glycol ( PEG ) was used as a spacer arm to conjugate meningococcal group Y capsular PS with tetanus toxoid ( TT ).", "output": "polyethylene glycol, PEG." }, { "input": "PEG can avoid self - crosslink of PS and increase the PS / TT ratio of the vaccine.", "output": "PEG." }, { "input": "Significant structural change in TT and PS was not observed upon conjugation.", "output": "There is no related enetity." }, { "input": "As compared to the vaccine without PEG, immunization with the vaccine using PEG as the spacer arm led to 3. 0 - fold increase in the PS - specific IgG titers and a prolonged immune persistence.", "output": "PEG, PEG." }, { "input": "Paradoxically, PEG, a non - immunogenic hydrophilic polymer has been widely used to couple therapeutic protein for increasing its circulatory time and decreasing its immunogenicity.", "output": "PEG." }, { "input": "Presumably, PEG can fully decrease the steric shielding effect of TT on antigenic epitopes of PS and suppress the immunogenicity of TT.", "output": "PEG." }, { "input": "In addition, PEG can prolong the immune persistence of the conjugate vaccine and improve its ability to elicit cellular immunity.", "output": "PEG." }, { "input": "Thus, PEG can be used as a spacer arm to develop more effective PS conjugate vaccine for prevention of bacterial infection.", "output": "PEG." }, { "input": "It is important research, but why is it necessary?", "output": "There is no related enetity." }, { "input": "The findings regarding cardiovascular actions of dietary supplements labeled as \" ephedra free \" reported by Foster et al. in the March issue reaffirm decades of research that began in the 1920s with K. K.", "output": "There is no related enetity." }, { "input": "Chen ' s study of naturally occurring adrenergic chemicals.", "output": "There is no related enetity." }, { "input": "Although the study by Foster et al. provides scientifically sound data needed by the US Food and Drug Administration ( FDA ) as it evaluates the safety of these products, we should ask, \" Why was it necessary that these chemicals be studied again for their cardiovascular actions in humans? \"", "output": "There is no related enetity." }, { "input": "Model - based drug development in oncology: what ' s next?", "output": "There is no related enetity." }, { "input": "Model - based estimates of tumor growth inhibition ( TGI ) metrics have the potential to enhance learning in early ( phase II ) clinical studies.", "output": "There is no related enetity." }, { "input": "They can be used as end points and biomarkers to predict treatment effect on clinical outcome measures - e. g., overall survival ( OS ) - and support phase II study design, end - of - phase II decisions, and phase III planning and execution.", "output": "There is no related enetity." }, { "input": "Efforts should be made to assess models in simulating independent studies with treatments of varying mechanisms of action.", "output": "There is no related enetity." }, { "input": "The rough endoplasmatic reticulum is a central nucleation site of siRNA - mediated RNA silencing.", "output": "There is no related enetity." }, { "input": "Despite progress in mechanistic understanding of the RNA interference ( RNAi ) pathways, the subcellular sites of RNA silencing remain under debate.", "output": "There is no related enetity." }, { "input": "Here we show that loading of lipid - transfected siRNAs and endogenous microRNAs ( miRNA ) into RISC ( RNA - induced silencing complexes ), encounter of the target mRNA, and Ago2 - mediated mRNA slicing in mammalian cells are nucleated at the rough endoplasmic reticulum ( rER ).", "output": "There is no related enetity." }, { "input": "Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA - and siRNA - loaded Ago2 populations co - sediment almost exclusively with the rER membranes, together with the RISC loading complex ( RLC ) factors Dicer, TAR RNA binding protein ( TRBP ) and protein activator of the interferon - induced protein kinase ( PACT ).", "output": "There is no related enetity." }, { "input": "Fractionation and membrane co - immune precipitations further confirm that siRNA - loaded Ago2 physically associates with the cytosolic side of the rER membrane.", "output": "There is no related enetity." }, { "input": "Additionally, RLC - associated double - stranded siRNA, diagnostic of RISC loading, and RISC - mediated mRNA cleavage products exclusively co - sediment with rER.", "output": "There is no related enetity." }, { "input": "Finally, we identify TRBP and PACT as key factors anchoring RISC to ER membranes in an RNA - independent manner.", "output": "There is no related enetity." }, { "input": "Together, our findings demonstrate that the outer rER membrane is a central nucleation site of siRNA - mediated RNA silencing.", "output": "There is no related enetity." }, { "input": "Extending the range of FRET - the Monte Carlo study of the antenna effect.", "output": "There is no related enetity." }, { "input": "The problem of extending the utilizable range of F o rster resonance energy transfer ( FRET ) is of great current interest, due to the demand of conformation studies of larger biological structures at distances exceeding typical limiting distance of 100 A.", "output": "There is no related enetity." }, { "input": "One of the ways to address this issue is the use of so - called antenna effect.", "output": "There is no related enetity." }, { "input": "In the present work, the influence of the antenna effect on the FRET efficiency is investigated by the Monte Carlo analysis.", "output": "There is no related enetity." }, { "input": "The previously published results Bojarski et al.", "output": "There is no related enetity." }, { "input": "( J Phys Chem B 115: 10120 - 10125, 2011 ) indicate that using a simple model of donor linked with a protein labeled with multiple acceptors, significantly increases the transfer efficiency in comparison with donor - single acceptor system.", "output": "There is no related enetity." }, { "input": "The effect is stronger if the transition moments of acceptors are mutually parallel.", "output": "There is no related enetity." }, { "input": "In this work, to extend the scope of possible biological systems to be analyzed, different distributions of donor - acceptors distance are analyzed, as well as the size and shape of the attached molecule.", "output": "There is no related enetity." }, { "input": "Self - Assembled PAA - Based Nanoparticles as Potential Gene and Protein Delivery Systems.", "output": "PAA." }, { "input": "A series of nanoparticles is prepared via layer - by - layer assembly of oppositely charged, synthetic biocompatible polyamidoamine polymers as potential carriers.", "output": "polyamidoamine." }, { "input": "Particle size, surface charge and internal chain mobility are quantified as a function of the polymer type and number of layers.", "output": "There is no related enetity." }, { "input": "The effect of addition of surfactant is examined to simulate the effects of nanoparticle dissolution.", "output": "There is no related enetity." }, { "input": "The cyctotoxicity of these particles ( in epithelia and murine cell lines ) are orders of magnitude lower than polyethyleneimine controls.", "output": "polyethyleneimine." }, { "input": "Stable nanoparticles may be prepared from mixtures of strongly, oppositely charged polymers, but less successfully from weakly charged polymers, and, given their acceptable toxicity characteristics, such modularly designed constructs show promise for drug and gene delivery.", "output": "There is no related enetity." }, { "input": "Impact of DNA Sequence and Oligonucleotide Length on a Polythiophene - Based Fluorescent DNA Biosensor.", "output": "Polythiophene." }, { "input": "DNA hybridization is a universal and specific mechanism for the recognition of biological targets.", "output": "There is no related enetity." }, { "input": "Some cationic polythiophene transducers sensitive to DNA structure have been previously utilized to detect such biomolecules.", "output": "polythiophene." }, { "input": "Further characterization of these systems indicates that both DNA sequence composition and length modulate the biosensor performance.", "output": "There is no related enetity." }, { "input": "It appears that different repeated sequence patterns cause different conformational changes of the polythiophene, from a more relaxed form to an extremely rigid one.", "output": "polythiophene." }, { "input": "A length difference between the DNA oligonucleotide probe and target has a detrimental effect on the fluorescent signal, but it can be attenuated by changing the sequence composition of the protruding target sequence.", "output": "There is no related enetity." }, { "input": "This demonstrates that the nature of DNA can be critical for hybridization - based detection systems.", "output": "There is no related enetity." }, { "input": "Pesticide tolerant and phosphorus solubilizing Pseudomonas sp. strain SGRAJ09 isolated from pesticides treated Achillea clavennae rhizosphere soil.", "output": "phosphorus." }, { "input": "In this study, an attempt was made to identify an effective phosphate solubilizing bacteria from pesticide polluted field soil.", "output": "phosphate." }, { "input": "Based on the formation of solubilization halo on Pikovskaya ' s agar, six isolates were selected and screened for pesticide tolerance and phosphate ( P ) solubilization ability through liquid assay.", "output": "phosphate." }, { "input": "The results showed that only one strain ( SGRAJ09 ) obtained from Achillea clavennae was found to tolerate maximum level of the pesticides tested and it was phylogenetically identified as Pseudomonas sp.", "output": "There is no related enetity." }, { "input": "It possessed a wide range of pesticide tolerance, ranging from 117 mu g mL ( - 1 ) for alphamethrin to 2, 600 mu g mL ( - 1 ) for endosulfan.", "output": "alphamethrin, endosulfan." }, { "input": "The available P concentrations increased with the maximum and double the maximum dose of monocrotophos and imidacloprid, respectively.", "output": "monocrotophos, imidacloprid." }, { "input": "On subjected to FT - IR and HPLC analysis, the presence of organic acids functional group in the culture broth and the production of gluconic acid as dominant acid aiding the P solubilization were identified.", "output": "gluconic acid." }, { "input": "On comparison with control broth, monocrotophos and imidacloprid added culture broth showed quantitatively high organic acids production.", "output": "monocrotophos, imidacloprid." }, { "input": "In addition to gluconic acid production, citric and acetic acids were also observed in the pesticide amended broth.", "output": "gluconic acid, citric and acetic acids." }, { "input": "Furthermore, the Pseudomonas sp. strain SGRAJ09 possessed all the plant growth promoting traits tested.", "output": "There is no related enetity." }, { "input": "In presence of monocrotophos and imidacloprid, its plant growth promoting activities were lower than that of the pesticides unamended treatment.", "output": "monocrotophos, imidacloprid." }, { "input": "Effect of the Potent Antiviral 1 - Cinnamoyl - 3, 11 - Dihydroxymeliacarpin on Cytokine Production by Murine Macrophages Stimulated with HSV - 2.", "output": "1 - Cinnamoyl - 3 , 11 - Dihydroxymeliacarpin." }, { "input": "The limonoid 1 - cinnamoyl - 3, 11 - dihydroxymeliacarpin ( CDM ) isolated from leaf extracts of Melia azedarach L, has potent antiherpetic effect in epithelial cells.", "output": "1 - cinnamoyl - 3 , 11 - dihydroxymeliacarpin, CDM." }, { "input": "Since Meliacine, the partially purified extract source of CDM, has therapeutic effect on murine genital herpes, the potential use of CDM as microbicide against herpetic infections was studied here.", "output": "CDM, CDM." }, { "input": "To determine the cytotoxic effect of CDM, the MTT assay and acridine orange staining of living cells were performed.", "output": "CDM, MTT." }, { "input": "The antiherpetic action of CDM was measured by plaque reduction assay, and the immunomodulatory effect was determined by measuring the cytokine production using a bioassay and ELISA method.", "output": "CDM." }, { "input": "The results presented here showed that CDM inhibited Herpes Simplex Virus type 2 ( HSV - 2 ) multiplication in Vero cells but did not affect its replication in macrophages which were not permissive to HSV infection.", "output": "CDM." }, { "input": "In macrophages, levels of TNF - alpha, IFN - gamma, NO, IL - 6 and IL - 10 were increased by CDM used alone or in combination with HSV - 2.", "output": "CDM." }, { "input": "Besides, CDM not only synergized TNF - alpha production combined with IFN - gamma, but also prolonged its expression in time.", "output": "CDM." }, { "input": "Results indicate that CDM inhibits HSV - 2 multiplication in epithelial cells and also increases cytokine production in macrophages, both important actions to the clearance of infecting virus in the mouse vagina.", "output": "CDM." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Recruiting the Host ' s Immune System to Target Helicobacter pylori ' s Surface Glycans.", "output": "There is no related enetity." }, { "input": "Due to the increased prevalence of bacterial strains that are resistant to existing antibiotics, there is an urgent need for new antibacterial strategies.", "output": "There is no related enetity." }, { "input": "Bacterial glycans are an attractive target for new treatments, as they are frequently linked to pathogenesis and contain distinctive structures that are absent in humans.", "output": "There is no related enetity." }, { "input": "We set out to develop a novel targeting strategy based on surface glycans present on the gastric pathogen Helicobacter pylori ( Hp ).", "output": "There is no related enetity." }, { "input": "In this study, metabolic labeling of bacterial glycans with an azide - containing sugar allowed selective delivery of immune stimulants to azide - covered Hp.", "output": "azide, azide." }, { "input": "We established that Hp ' s surface glycans are labeled by treatment with the metabolic substrate peracetylated N - azidoacetylglucosamine ( Ac4 GlcNAz ).", "output": "peracetylated N - azidoacetylglucosamine, Ac4 GlcNAz." }, { "input": "By contrast, mammalian cells treated with Ac4 GlcNAz exhibited no incorporation of the chemical label within extracellular glycans.", "output": "Ac4 GlcNAz." }, { "input": "We further demonstrated that the Staudinger ligation between azides and phosphines proceeds under acidic conditions with only a small loss of efficiency.", "output": "azides, phosphines." }, { "input": "We then targeted azide - covered Hp with phosphines conjugated to the immune stimulant 2, 4 - dinitrophenyl ( DNP ), a compound capable of directing a host immune response against these cells.", "output": "azide, phosphines, 2 , 4 - dinitrophenyl, DNP." }, { "input": "Finally, we report that immune effector cells catalyze selective damage in vitro to DNP - covered Hp in the presence of anti - DNP antibodies.", "output": "DNP, DNP." }, { "input": "The technology reported herein represents a novel strategy to target Hp based on its glycans.", "output": "There is no related enetity." }, { "input": "Fluorescent Polymeric Micelles with Aggregation - Induced Emission Properties for Monitoring the Encapsulation of Doxorubicin.", "output": "Doxorubicin." }, { "input": "A new type of fluorescent polymeric micelles is developed by self - assembly from a series of amphiphilic block copolymers, poly ( ethylene glycol ) - b - poly [ styrene - co - ( 2 - ( 1, 2, 3, 4, 5 - pentaphenyl - 1H - silol - 1 - yloxy ) ethyl methacrylate ) ] [ PEG - b - P ( S - co - PPSEMA ) ].", "output": "poly ( ethylene glycol ) - b - poly [ styrene - co - ( 2 - ( 1 , 2 , 3 , 4 , 5 - pentaphenyl - 1H - silol - 1 - yloxy ) ethyl methacrylate ) ], PEG - b - P ( S - co - PPSEMA )." }, { "input": "Their capability of loading doxorubicin ( DOX ) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles.", "output": "doxorubicin, DOX." }, { "input": "F o rster resonance energy transfer from PPSEMA to DOX is observed in DOX - loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles.", "output": "PPSEMA, DOX, DOX, DOX." }, { "input": "The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX - loaded micelles.", "output": "DOX." }, { "input": "Nonviral Gene Delivery to Neural Stem Cells with Minicircles by Microporation.", "output": "There is no related enetity." }, { "input": "The main purpose of this work was to evaluate the transfection of novel DNA vectors, minicircles ( mC ), on embryonic stem cell - derived neural stem cells ( NSC ).", "output": "There is no related enetity." }, { "input": "We demonstrated that by combining microporation with mC, 75 % of NSC expressing a transgene is achieved without compromising cell survival, morphology, and differentiation potential.", "output": "There is no related enetity." }, { "input": "When comparing mC with their plasmid DNA ( pDNA ) counterparts, both gave rise to similar transfection levels but cells harboring mC showed 10 % higher cell viability, maintaining 90 % of survival at least for 10 days.", "output": "There is no related enetity." }, { "input": "Long - term analysis showed that NSC harbor a higher number of mC copies and consequently exhibit higher transgene expression when compared to their pDNA counterpart.", "output": "There is no related enetity." }, { "input": "Taken together, our results offer the first insights on the use of mC as a novel and safe strategy to genetically engineer NSC envisaging their use as biopharmaceuticals in clinical settings for the treatment of neurodegenerative or neurological diseases.", "output": "There is no related enetity." }, { "input": "The role of platelet / lymphocyte serotonin transporter in depression and beyond.", "output": "serotonin." }, { "input": "A large amount of the data gathered in the last 50 years support the hypothesis that alterations of the serotonin ( 5 - HT ) neurotransmission play a crucial role in the pathophysiology of not only major depression ( MD ), but also of different neuropsychiatric disorders.", "output": "serotonin, 5 - HT." }, { "input": "Research in this field has been substantially promoted by the evidence that the reuptake protein ( SERT ), present in presynaptic neurons, is a key element in terminating the activity of the neurotransmitter in the synaptic cleft.", "output": "There is no related enetity." }, { "input": "For this reason, it was specifically targeted for the development of second - generation antidepressants, in particular of selective 5 - HT reuptake inhibitors ( SSRIs ), with the aim of increasing the intrasynaptic 5 - HT concentrations.", "output": "5 - HT, 5 - HT." }, { "input": "Moreover, since a lot of studies showed that circulating platelets and, more recently, lymphocytes possess functional SERT proteins, they have been widely used as peripheral mirrors of the same structures located in the central nervous system.", "output": "There is no related enetity." }, { "input": "The presence of functional SERT in blood cells suggests strict relationships between the nervous and the immune system that need to be better clarified in MD, as well as the possibility of reciprocal modulation of the two systems by different drugs.", "output": "There is no related enetity." }, { "input": "This paper aims to review briefly the literature on the 5 - HT hypothesis of depression with a major focus on the possible role of SERT in this disorder, while highlighting how recent data are more oriented on dimensional rather than nosological involvement of this structure in different conditions spanning from normality to pathology.", "output": "5 - HT." }, { "input": "GC - Targeted C8 - Linked Pyrrolobenzodiazepine - Biaryl Conjugates with Femtomolar in Vitro Cytotoxicity and in Vivo Antitumor Activity in Mouse Models.", "output": "Pyrrolobenzodiazepine, Biaryl." }, { "input": "DNA binding 4 - ( 1 - methyl - 1H - pyrrol - 3 - yl ) benzenamine ( MPB ) building blocks have been developed that span two DNA base pairs with a strong preference for GC - rich DNA.", "output": "4 - ( 1 - methyl - 1H - pyrrol - 3 - yl ) benzenamine, MPB." }, { "input": "They have been conjugated to a pyrrolo [ 2, 1 - c ] [ 1, 4 ] benzodiazepine ( PBD ) molecule to produce C8 - linked PBD - MPB hybrids that can stabilize GC - rich DNA by up to 13 - fold compared to AT - rich DNA.", "output": "pyrrolo [ 2 , 1 - c ] [ 1 , 4 ] benzodiazepine, PBD, PBD - MPB." }, { "input": "Some have subpicomolar IC50 values in human tumor cell lines and in primary chronic lymphocytic leukemia cells, while being up to 6 orders less cytotoxic in the non - tumor cell line WI38, suggesting that key DNA sequences may be relevant targets in these ultrasensitive cancer cell lines.", "output": "There is no related enetity." }, { "input": "One conjugate, 7h ( KMR - 28 - 39 ), which has femtomolar activity in the breast cancer cell line MDA - MB - 231, has significant dose - dependent antitumor activity in MDA - MB - 231 ( breast ) and MIA PaCa - 2 ( pancreatic ) human tumor xenograft mouse models with insignificant toxicity at therapeutic doses.", "output": "KMR - 28 - 39." }, { "input": "Preliminary studies suggest that 7h may sterically inhibit interaction of the transcription factor NF - kappa B with its cognate DNA binding sequence.", "output": "There is no related enetity." }, { "input": "Hyaluronic Acid nanoparticles titrate the viscoelastic properties of viscosupplements.", "output": "There is no related enetity." }, { "input": "Hyaluronic acid ( HA ) is a glycosaminoglycan with diverse biomedical applications including viscosupplementation of synovial fluid for the treatment osteoarthritis.", "output": "There is no related enetity." }, { "input": "Current HA viscosupplements such as Synvisc, Orthovisc, and Hyalgan have shown positive effects of reducing pain and improving joint function.", "output": "There is no related enetity." }, { "input": "The therapeutic efficacy, however, is highly transient, and these viscous fluids suffer from poor injectability.", "output": "There is no related enetity." }, { "input": "HA nanoparticles were found to modify the rheological properties of a model of the HA viscosupplement Orthovisc.", "output": "There is no related enetity." }, { "input": "Nanoparticles were successfully synthesized from 17 and 1500 kDa HA.", "output": "There is no related enetity." }, { "input": "Nanoparticle suspensions of HA were studied at different concentrations and in blends with the model viscosupplement.", "output": "There is no related enetity." }, { "input": "Nanoparticles made from 1500 kDa HA reduced the viscosupplement viscosity and elasticity to a much greater degree than nanoparticles made from 17 kDa HA.", "output": "There is no related enetity." }, { "input": "The difference in the nanoparticle effect on viscoelasticity suggested that nanoparticles made from 17 kDa HA may have dangling surface polymers that facilitated interactions with HA in solution.", "output": "There is no related enetity." }, { "input": "This hypothesis was supported by the greater compressibility of 17 kDa nanoparticles as determined by ultrasonic vibrational spectroscopy.", "output": "There is no related enetity." }, { "input": "Rheological investigations showed that the viscoelasticity of viscosupplements could be discretely titrated by modulating the concentration and type of HA nanoparticle additive ( hard sphere or hairy ).", "output": "There is no related enetity." }, { "input": "Thus, the injectability of viscosupplements may be enhanced while maintaining high elasticity.", "output": "There is no related enetity." }, { "input": "Functional Diversity of HDL Cargo.", "output": "There is no related enetity." }, { "input": "For decades high - density lipoproteins ( HDL ) and HDL - cholesterol ( HDL - C ) levels were viewed as synonymous and modulation of HDL - C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease.", "output": "cholesterol." }, { "input": "Nevertheless, recent failures of drugs that raise HDL - C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL.", "output": "There is no related enetity." }, { "input": "As such, the focus of HDL has now started to shift away from a cholesterol centric view towards HDL particle number, subclasses, and other alternative metrics of HDL.", "output": "cholesterol." }, { "input": "Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux, but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids.", "output": "cholesterol." }, { "input": "Based on the ability of HDL to interact with almost all cells and transport and deliver fat - soluble cargo, HDL has the remarkable capacity to affect a wide - variety of endocrine - like systems.", "output": "There is no related enetity." }, { "input": "Here in this review, we characterize the unique cargo on HDL and address the functional relevance and consequences of HDL transport and delivery of non - cholesterol molecules to recipient cells and tissues.", "output": "cholesterol." }, { "input": "Evaluation of estrogenic effects of polychlorinated biphenyls and organochlorinated pesticides using immature rat uterotrophic assay.", "output": "polychlorinated biphenyls, organochlorinated." }, { "input": "In this study, we investigated the effects of polychlorinated biphenyls ( PCBs ) and organochlorinated pesticides on the serum levels of luteinising hormone ( LH ), follicle stimulating hormone ( FSH ) and weights and histomorphometry of uterine tissue in immature female rats using uterotrophic assay.", "output": "polychlorinated biphenyls, PCBs, organochlorinated." }, { "input": "A total of 36 rats were randomly divided into six groups ( n = 6 per group ) as control, oestradiol ( E2, 100 mu g / kg ), PCB 180, Aroclor 1221, endosulfan and mirex at 10 mg / kg dosage.", "output": "oestradiol, PCB 180, Aroclor 1221, endosulfan, mirex." }, { "input": "After 3 days of injections ( subcutaneous ), animals were decapitated and blood samples were collected.", "output": "There is no related enetity." }, { "input": "Uteri were dissected, weighed out and then fixed in 10 % formaldehyde.", "output": "formaldehyde." }, { "input": "They were processed for histomorphometry.", "output": "There is no related enetity." }, { "input": "The serum levels of LH and FSH were determined by enzyme immunoassay. Uterine weight was significantly increased by E2 and reduced by mirex ( p < 0. 001 and p < 0. 05, respectively ).", "output": "mirex." }, { "input": "Total volume of uterus was significantly raised by E2, Aroclor 1221 and endosulfan compared with that of the control group ( p < 0. 01 ).", "output": "Aroclor 1221, endosulfan." }, { "input": "The ratio of epithelium was significantly increased by E2, PCBs and pesticides ( p < 0. 01 ).", "output": "PCBs." }, { "input": "The uterine cavity ratio was decreased by aroclor ( p < 0. 01 ), PCB 180 and mirex ( p < 0. 05 ).", "output": "PCB 180, mirex." }, { "input": "The serum levels of LH did not significantly differ among the groups but the levels of FSH were decreased by PCB 180 and endosulfan ( p < 0. 05 and p < 0. 01, respectively ).", "output": "PCB 180, endosulfan." }, { "input": "These findings suggest that PCB 180, Aroclor 1221 and endosulfan may be estrogenic in immature uterotrophic assay.", "output": "PCB 180, Aroclor 1221, endosulfan." }, { "input": "Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH - expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.", "output": "escitalopram." }, { "input": "RATIONALE: Selective rapid eye movement sleep ( REMS ) deprivation using the platform - on - water ( \" flower pot \" ) method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin - concentrating hormone ( MCH ) expressing neurons in the hypothalamus.", "output": "There is no related enetity." }, { "input": "MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH - containing neurons.", "output": "serotonin, escitalopram." }, { "input": "METHODS: Escitalopram or vehicle ( 10 mg / kg, intraperitoneally ) was administered to REMS - deprived ( 72 h ) or home cage male Wistar rats.", "output": "Escitalopram." }, { "input": "During the 3 - h - long \" rebound sleep \", electroencephalography was recorded, followed by an MCH / Fos double immunohistochemistry.", "output": "There is no related enetity." }, { "input": "RESULTS: During REMS rebound, the time spent in REMS and the number of MCH / Fos double - labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease.", "output": "There is no related enetity." }, { "input": "All these effects of REMS deprivation were significantly attenuated by escitalopram treatment.", "output": "escitalopram." }, { "input": "Besides the REMS - suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound.", "output": "escitalopram." }, { "input": "CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH - containing neurons, in parallel.", "output": "escitalopram." }, { "input": "Escitalopram caused a shift from REMS to slow wave sleep during the rebound.", "output": "Escitalopram." }, { "input": "Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders.", "output": "There is no related enetity." }, { "input": "Mechanisms involved in the antinociceptive effects of orally administered oleanolic acid in the mouse.", "output": "oleanolic acid." }, { "input": "The antinociceptive effects of oleanolic acid were examined in ICR mice.", "output": "oleanolic acid." }, { "input": "Oleanolic acid administered orally ( 1, 5 and 10 mg / kg ) showed an antinociceptive effect in a dose - dependent manner as measured in the acetic acid - induced writhing test.", "output": "Oleanolic acid, acetic acid." }, { "input": "In the time - course study, duration of antinociceptive action of oleanolic acid maintained at least for 60 min.", "output": "oleanolic acid." }, { "input": "In addition, the cumulative nociceptive response time for intraplantar formalin injection ( 2nd phase ), intrathecal injection of substance P ( 0. 7 mu g ) or glutamate ( 20 mu g ) was diminished by oleanolic acid.", "output": "glutamate, oleanolic acid." }, { "input": "Intraperitoneal ( i. p. ) pretreatment with naloxone ( opioid receptor antagonist ) or methysergide ( 5 - HT serotonergic receptor antagonist ) attenuated antinociceptive effect induced by oleanolic acid in the writhing test.", "output": "naloxone, methysergide, 5 - HT, oleanolic acid." }, { "input": "However, yohimbine ( adrenergic receptor antagonist ) did not affect antinociception induced by oleanolic acid.", "output": "yohimbine, oleanolic acid." }, { "input": "The results indicate that oleanolic acid shows an antinociceptive property in various pain models such as writhing, formalin, substance P and glutamate pain tests.", "output": "oleanolic acid, formalin, glutamate." }, { "input": "Furthermore, this antinociceptive effect of oleanolic acid may be mediated by opioidergic and serotonergic receptors, but not adrenergic receptors.", "output": "oleanolic acid." }, { "input": "Multifocal motor neuropathy: current therapies and novel strategies.", "output": "There is no related enetity." }, { "input": "Multifocal motor neuropathy ( MMN ) is a purely motor mononeuritis multiplex characterized by the presence of conduction block on motor but not on sensory nerves and by the presence of high titers of anti - GM1 antibodies.", "output": "There is no related enetity." }, { "input": "Several data point to a pathogenetic role of the immune system in this neuropathy, although this has not yet been proved.", "output": "There is no related enetity." }, { "input": "Several uncontrolled studies and randomized controlled trials have demonstrated the efficacy of therapy with high - dose intravenous immunoglobulin ( IVIg ) in MMN.", "output": "There is no related enetity." }, { "input": "However, this therapy has a short - lasting effect that needs to be maintained with periodic infusions.", "output": "There is no related enetity." }, { "input": "This can be partly overcome by the use of subcutaneous immunoglobulin ( SCIg ) at the same dose.", "output": "There is no related enetity." }, { "input": "The high cost and need for repeated infusions have led to the search for other immune therapies, the efficacy of which have not yet been confirmed in randomized trials.", "output": "There is no related enetity." }, { "input": "In addition, some therapies, including corticosteroids and plasma exchange, are not only ineffective but have been associated with clinical worsening.", "output": "There is no related enetity." }, { "input": "More recently, a number of novel therapies have been investigated in MMN, including interferon - beta 1a, the anti - CD20 monoclonal antibody rituximab and the complement inhibitor eculizumab.", "output": "There is no related enetity." }, { "input": "Preliminary data from open - label uncontrolled studies show that some patients improve after these therapies; however, randomized controlled trials are needed to confirm efficacy.", "output": "There is no related enetity." }, { "input": "Until then, IVIg ( and SCIg ) remains the mainstay of treatment in MMN, and the use of other immune therapies should only be considered for patients not responding to, or becoming resistant to, IVIg.", "output": "There is no related enetity." }, { "input": "Surface topography effects in protein adsorption on nanostructured carbon allotropes.", "output": "carbon." }, { "input": "We report a molecular dynamics ( MD ) simulation study of protein adsorption on the surface of nanosized carbon allotropes, namely single - walled carbon nanotubes ( SWNT ) considering both the convex outer surface and the concave inner surface, together with a graphene sheet for comparison.", "output": "carbon, carbon, graphene." }, { "input": "These systems are chosen to investigate the effect of the surface curvature on protein adsorption at the same surface chemistry, given by sp ( 2 ) carbon atoms in all cases.", "output": "carbon." }, { "input": "The simulations show that proteins do favorably interact with these hydrophobic surfaces, as previously found on graphite which has the same chemical nature.", "output": "graphite." }, { "input": "However, the main finding of the present study is that the adsorption strength does depend on the surface topography: in particular, it is slightly weaker on the outer convex surfaces of SWNT and is conversely enhanced on the inner concave SWNT surface, being therefore intermediate for flat graphene.", "output": "graphene." }, { "input": "We additionally find that oligopeptides may enter the cavity of common SWNT, provided their size is small enough and the tube diameter is large enough for both entropic and energetic reasons.", "output": "There is no related enetity." }, { "input": "Therefore, we suggest that proteins can effectively be used to solubilize in water single - walled ( and by analogy also multiwalled ) carbon nanotubes through adsorption on the outer surface, as indeed experimentally found, and to functionalize them after insertion of oligopeptides within the cavity of nanotubes of appropriate size.", "output": "carbon." }, { "input": "Nanofiber near - field light - matter interactions for enhanced detection of molecular level displacements and dynamics.", "output": "There is no related enetity." }, { "input": "We experimentally demonstrate that plasmonic nanoparticles embedded in the evanescent field of subwavelength optical waveguides ( WGs ) are highly sensitive to distances normal to the propagation of light, showing an ~ 10 x increase in spatial resolution compared to the optical field decay of the WG.", "output": "There is no related enetity." }, { "input": "The scattering cross - section of the Au nanoparticle is increased by the plasmon - dielectric coupling interaction when the nanoparticle is placed near the dielectric surface of the WG, and the decay of the scattering signal is enhanced, showing angstrom level distance sensitivity within 10 nm from the WG.", "output": "Au." }, { "input": "Numerical studies with the finite - difference time - domain ( FDTD ) method correlate well with the experimental results.", "output": "There is no related enetity." }, { "input": "To demonstrate real - time monitoring of a single molecule stretching in the evanescent field, we linked individual single - stranded DNA molecules between the WG and plasmonic nanoparticles and pushed on the nanoparticles with fluidic forces.", "output": "There is no related enetity." }, { "input": "The simple design and ease of obtaining optical feedback on molecular displacements makes our approach ideal for new in situ force sensing devices, imaging technologies, and high - throughput molecular analysis.", "output": "There is no related enetity." }, { "input": "Biophysical Fragment Screening of the beta 1 - Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure - Based Drug Design.", "output": "Arylpiperazine." }, { "input": "Biophysical fragment screening of a thermostabilized beta 1 - adrenergic receptor ( beta 1AR ) using surface plasmon resonance ( SPR ) enabled the identification of moderate affinity, high ligand efficiency ( LE ) arylpiperazine hits 7 and 8.", "output": "arylpiperazine." }, { "input": "Subsequent hit to lead follow - up confirmed the activity of the chemotype, and a structure - based design approach using protein - ligand crystal structures of the beta 1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20.", "output": "indole, quinoline." }, { "input": "In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized beta 1AR complexed with 19 and 20 were determined at resolutions of 2. 8 and 2. 7 A, respectively.", "output": "There is no related enetity." }, { "input": "Genomics - Guided Discovery of Thailanstatins A, B, and C As Pre - mRNA Splicing Inhibitors and Antiproliferative Agents from Burkholderia thailandensis MSMB43.", "output": "Thailanstatins A , B , and C." }, { "input": "Mining the genome sequence of Burkholderia thailandensis MSMB43 revealed a cryptic biosynthetic gene cluster resembling that of FR901464 ( 4 ), a prototype spliceosome inhibitor produced by Pseudomonas sp.", "output": "FR901464." }, { "input": "No. 2663.", "output": "There is no related enetity." }, { "input": "Transcriptional analysis revealed a cultivation condition in which a regulatory gene of the cryptic gene cluster is adequately expressed.", "output": "There is no related enetity." }, { "input": "Consequently, three new compounds, named thailanstatins A ( 1 ), B ( 2 ), and C ( 3 ), were isolated from the fermentation broth of B. thailandensis MSMB43.", "output": "thailanstatins." }, { "input": "Thailanstatins are proposed to be biosynthesized by a hybrid polyketide synthase - nonribosomal peptide synthetase pathway.", "output": "Thailanstatins." }, { "input": "They differ from 4 by lacking an unstable hydroxyl group and by having an extra carboxyl moiety; those differences endow thailanstatins with a significantly greater stability than 4 as tested in phosphate buffer at pH 7. 4.", "output": "hydroxyl, carboxyl, thailanstatins, phosphate." }, { "input": "In vitro assays showed that thailanstatins inhibit pre - mRNA splicing as potently as 4, with half - maximal inhibitory concentrations in the single to sub - mu M range.", "output": "thailanstatins." }, { "input": "Cell culture assays indicated that thailanstatins also possess potent antiproliferative activities in representative human cancer cell lines, with half - maximal growth inhibitory concentrations in the single nM range.", "output": "thailanstatins." }, { "input": "This work provides new chemical entities for research and development and new structure - activity information for chemical optimization of related spliceosome inhibitors.", "output": "There is no related enetity." }, { "input": "Growth Inhibition of Human Colon Carcinoma Cells by Sesquiterpenoids and Tetralones of Zygogynum calothyrsum.", "output": "Sesquiterpenoids, Tetralones." }, { "input": "Bioassay - guided phytochemical investigation of Zygogynum calothyrsum using the human colon carcinoma cell lines COLO205 and KM12 led to the isolation of three new drimane - type sesquiterpenoids, 1 beta - p - hydroxy - E - cinnamoyldrimeninol ( 1 ), 1 beta - p - hydroxy - E - cinnamoyl - 5 alpha - hydroxydrimeninol ( 2 ), and methyl ether of 1 beta - p - hydroxy - E - cinnamoyl - 12 alpha - methoxydrimeninol ( 3 ).", "output": "sesquiterpenoids, 1 beta - p - hydroxy - E - cinnamoyldrimeninol, 1 beta - p - hydroxy - E - cinnamoyl - 5 alpha - hydroxydrimeninol, methyl ether of 1 beta - p - hydroxy - E - cinnamoyl - 12 alpha - methoxydrimeninol." }, { "input": "Also isolated was the known 1 beta - p - coumaroyloxypolygodial ( 4 ) together with two new tetralones, 3 ' - deoxyisozygolone A ( 5 ) and calothyrlone A ( 9 ), three known tetralones, isozygolone A ( 6 ), zygolone A ( 7 ), and 4 ' - O - methylzygolone A ( 8 ), and a known cinnamolide ( 10 ).", "output": "1 beta - p - coumaroyloxypolygodial, tetralones, 3 ' - deoxyisozygolone A, calothyrlone A, isozygolone A, zygolone A, 4 ' - O - methylzygolone A, cinnamolide." }, { "input": "Compounds 1, 7, and 8 demonstrated higher cytotoxicity against COLO205 ( GI50 18, 17, and 11 mu M, respectively ) and KM12 ( GI50 14, 14, and 17 mu M, respectively ) than the other compounds.", "output": "There is no related enetity." }, { "input": "Anti - inflammatory Lanostanoids and Lactone Derivatives from Antrodia camphorata.", "output": "Lanostanoids, Lactone." }, { "input": "Four new lanostanoids, ethyl lucidenate A ( 1 ), ethyl lucidenate F ( 2 ), 15 - O - acetylganolucidate A ( 3 ), and 3, 11, 15, 23 - tetraoxo - 27 xi - lanosta - 8, 16 - dien - 26 - oic acid ( 4 ), and two new lactone derivatives, 5 - hydroxy - 5 - ( methoxymethyl ) - 4 - methylfuran - 2 ( 5H ) - one ( 5 ) and 3 - ( 4 - methoxy - 2 - oxo - 2H - pyran - 6 - yl ) propanoic acid ( 6 ), together with four known compounds, 11 alpha - hydroxy - 3, 7 - dioxolanost - 8, 24 ( E ) - dien - 26 - oic acid ( 7 ), 3, 7, 11 - trioxo - 5 alpha - lanosta - 8, 24 ( E ) - dien - 26 - oic acid ( 8 ), methyl 3, 7, 11, 12, 15, 23 - hexaoxo - 5 alpha - lanost - 8 - en - 26 - oate ( 9 ), and ethyl 3, 7, 11, 12, 15, 23 - hexaoxo - 5 alpha - lanost - 8 - en - 26 - oate ( 10 ), were characterized from Antrodia camphorata.", "output": "lanostanoids, ethyl lucidenate A, ethyl lucidenate F, 15 - O - acetylganolucidate A, 3 , 11 , 15 , 23 - tetraoxo - 27 xi - lanosta - 8 , 16 - dien - 26 - oic acid, lactone, 5 - hydroxy - 5 - ( methoxymethyl ) - 4 - methylfuran - 2 ( 5H ) - one, 3 - ( 4 - methoxy - 2 - oxo - 2H - pyran - 6 - yl ) propanoic acid, 11 alpha - hydroxy - 3 , 7 - dioxolanost - 8 , 24 ( E ) - dien - 26 - oic acid, 3 , 7 , 11 - trioxo - 5 alpha - lanosta - 8 , 24 ( E ) - dien - 26 - oic acid, methyl 3 , 7 , 11 , 12 , 15 , 23 - hexaoxo - 5 alpha - lanost - 8 - en - 26 - oate, ethyl 3 , 7 , 11 , 12 , 15 , 23 - hexaoxo - 5 alpha - lanost - 8 - en - 26 - oate." }, { "input": "The structures of these new compounds were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments.", "output": "There is no related enetity." }, { "input": "Ten components were evaluated for anti - inflammatory activity by examining their effect on LPS - iNOS - dependent NO production in murine macrophage ( RAW 264. 7 ) cells.", "output": "NO." }, { "input": "Among them, compounds 1, 3, 7, 8, 9, and 10 significantly suppressed the NO concentration in LPS - treated RAW 264. 7 cells with IC50 values <= 10 mu M.", "output": "NO." }, { "input": "Generating Long Supramolecular Pathways with a Continuous Density of States by Physically Linking Conjugated Molecules via Their End Groups.", "output": "There is no related enetity." }, { "input": "Self - assembly of conjugated 2, 5 - dialkoxy - phenylene - thienylene - based oligomers on epitaxial monolayer graphene was studied in ultrahigh vacuum by low - temperature scanning tunneling microscopy ( STM ).", "output": "2 , 5 - dialkoxy - phenylene - thienylene, graphene." }, { "input": "The formation of long one - dimensional ( 1D ) supramolecular chain - like structures has been observed, associated to a physical linking of their ends which involved the rotation of the end thiophene rings in order to allow pi - pi stacking of these end - groups.", "output": "thiophene." }, { "input": "dI / dV maps taken at an energy corresponding to the excited states showed a continuous electronic density of states, which tentatively suggests that within such molecular chains conjugation of electrons is preserved even across physically linked molecules.", "output": "There is no related enetity." }, { "input": "Thus, in a self - organization process conjugation may be extended by appropriately adapting conformations of neighboring molecules.", "output": "There is no related enetity." }, { "input": "Our STM results on such self - organized end - linked molecules potentially represent a direct visualization of J - aggregates.", "output": "There is no related enetity." }, { "input": "Light - Triggered Cross - Linking of Alginates with Caged Ca ( 2 + )", "output": "Ca ( 2 + )." }, { "input": "A strategy to light - trigger ionic cross - linking of alginates by incorporating a photosensitive Ca ( 2 + ) cage ( nitr - T ) is presented.", "output": "Ca ( 2 + )." }, { "input": "Upon irradiation, free Ca ( 2 + ) was released, and this caused gelation of the alginate solution.", "output": "Ca ( 2 + )." }, { "input": "Addition of Ca ( 2 + ) \" on - demand \" allowed us to obtain homogeneous alginate ( ALG ) gels using concentrated initial ALG solutions ( 10 % ), not possible with other ionic gelation approaches.", "output": "Ca ( 2 + )." }, { "input": "The cross - linking degree and derived mechanical properties of the hydrogel were modulated by the exposure dose.", "output": "There is no related enetity." }, { "input": "The light - mediated cross - linked alginate hydrogel displayed a significant improvement in the mechanical properties and homogeneity when compared to mixtures of alginate and soluble Ca ( 2 + ) at comparable concentrations.", "output": "Ca ( 2 + )." }, { "input": "Cations Bind Only Weakly to Amides in Aqueous Solutions.", "output": "Amides." }, { "input": "We investigated salt interactions with butyramide as a simple mimic of cation interactions with protein backbones.", "output": "butyramide." }, { "input": "The experiments were performed in aqueous metal chloride solutions using two spectroscopic techniques.", "output": "chloride." }, { "input": "In the first, which provided information about contact pair formation, the response of the amide I band to the nature and concentration of salt was monitored in bulk aqueous solutions via attenuated total reflection Fourier transform infrared spectroscopy.", "output": "amide." }, { "input": "It was found that molar concentrations of well - hydrated metal cations ( Ca ( 2 + ), Mg ( 2 + ), Li ( + ) ) led to the rise of a peak assigned to metal cation - bound amides ( 1645 cm ( - 1 ) ) and a decrease in the peak associated with purely water - bound amides ( 1620 cm ( - 1 ) ).", "output": "Ca ( 2 + ), Mg ( 2 + ), Li ( + ), amides, amides." }, { "input": "In a complementary set of experiments, the effect of cation identity and concentration was investigated at the air / butyramide / water interface via vibrational sum frequency spectroscopy.", "output": "butyramide." }, { "input": "In these studies, metal ion - amide binding led to the ordering of the adjacent water layer.", "output": "amide." }, { "input": "Such experiments were sensitive to the interfacial partitioning of cations in either a contact pair with the amide or as a solvent separated pair.", "output": "amide." }, { "input": "In both experiments, the ordering of the interactions of the cations was: Ca ( 2 + ) > Mg ( 2 + ) > Li ( + ) > Na ( + ) =~ K ( + ).", "output": "Ca ( 2 + ), Mg ( 2 + ), Li ( + ), Na ( + ), K ( + )." }, { "input": "This is a direct cationic Hofmeister series.", "output": "There is no related enetity." }, { "input": "Even for Ca ( 2 + ), however, the apparent equilibrium dissociation constant of the cation with the amide carbonyl oxygen was no tighter than ~ 8. 5 M.", "output": "Ca ( 2 + ), amide carbonyl oxygen." }, { "input": "For Na ( + ) and K ( + ), no evidence was found for any binding.", "output": "Na ( + ), K ( + )." }, { "input": "As such, the interactions of metal cations with amides are far weaker than the analogous binding of weakly hydrated anions.", "output": "amides." }, { "input": "Comparative pharmacokinetics of N ( omega ) - hydroxy - nor - L - arginine, an arginase inhibitor, after single - dose intravenous, intraperitoneal and intratracheal administration to brown Norway rats.", "output": "N ( omega ) - hydroxy - nor - L - arginine." }, { "input": "Abstract 1. Rodent studies have documented that N ( omega ) - hydroxy - nor - L - arginine ( nor - NOHA ), an arginase inhibitor, has therapeutic potential in the treatment of cardiovascular and obstructive airway diseases.", "output": "N ( omega ) - hydroxy - nor - L - arginine, nor - NOHA." }, { "input": "However, its bioavailability and pharmacokinetics have not been described so far.", "output": "There is no related enetity." }, { "input": "2. Anesthetized brown Norway rats were administered single doses of nor - NOHA ( 10, 30 or 90 mg / kg ) intravenously ( i. v. ), intraperitonealy ( i. p. ) or via intratracheal ( i. t. ) instillation of aerosol.", "output": "nor - NOHA." }, { "input": "Plasma nor - NOHA was assayed using a validated HPLC method.", "output": "nor - NOHA." }, { "input": "3. Upon i. v. administration, the mean concentration showed a biphasic decline and its value dropped below 10 % of the maximum after 20 min.", "output": "There is no related enetity." }, { "input": "The pharmacokinetics were linear with the total and inter - compartmental clearances of 33 and 17 mL / min / kg, central and peripheral volumes of distribution of 0. 19 and 0. 43 L / kg and terminal half - life of 30 min.", "output": "There is no related enetity." }, { "input": "4. The average absolute bioavailability of nor - NOHA after i. p. and i. t. delivery was 98 % and 53 %, respectively.", "output": "nor - NOHA." }, { "input": "The absorption from the airways was rate - limiting and its extent decreased with the dose.", "output": "There is no related enetity." }, { "input": "5. In conclusion, nor - NOHA is rapidly cleared from the plasma in concordance with the short time window of its in vivo inhibitory activity reported in the literature.", "output": "nor - NOHA." }, { "input": "I. t. instillation of aerosol for topical effects of nor - NOHA in the airways is characterized with significant systemic availability.", "output": "nor - NOHA." }, { "input": "All Zinc - Blende GaAs / ( Ga, Mn ) As Core - Shell Nanowires with Ferromagnetic Ordering.", "output": "Zinc - Blende, GaAs, ( Ga , Mn ) As." }, { "input": "Combining self - catalyzed vapor - liquid - solid growth of GaAs nanowires and low - temperature molecular - beam epitaxy of ( Ga, Mn ) As, we successfully synthesized all zinc - blende ( ZB ) GaAs / ( Ga, Mn ) As core - shell nanowires on Si ( 111 ) substrates.", "output": "GaAs, ( Ga , Mn ) As, zinc - blende, GaAs, ( Ga , Mn ) As, Si." }, { "input": "The ZB GaAs nanowire cores are first fabricated at high temperature by utilizing the Ga droplets as the catalyst and controlling the triple phase line nucleation, then the ( Ga, Mn ) As shells are epitaxially grown on the side facets of the GaAs core at low temperature.", "output": "GaAs, Ga, ( Ga , Mn ) As, GaAs." }, { "input": "The growth window for the pure phase GaAs / ( Ga, Mn ) As core - shell nanowires is found to be very narrow.", "output": "GaAs, ( Ga , Mn ) As." }, { "input": "Both high - resolution transmission electron microscopy and scanning electron microscopy observations confirm that all - ZB GaAs / ( Ga, Mn ) As core - shell nanowires with smooth side surface are obtained when the Mn concentration is not more than 2 % and the growth temperature is 245 degrees C or below.", "output": "GaAs, ( Ga , Mn ) As, Mn." }, { "input": "Magnetic measurements with different applied field directions provide strong evidence for ferromagnetic ordering in the all - ZB GaAs / ( Ga, Mn ) As nanowires.", "output": "GaAs, ( Ga , Mn ) As." }, { "input": "The hybrid nanowires offer an attractive platform to explore spin transport and device concepts in fully epitaxial all - semiconductor nanospintronic structures.", "output": "There is no related enetity." }, { "input": "N - Methyldihydroquinazolinone Derivatives of Retro - 2 with Enhanced Efficacy against Shiga Toxin.", "output": "N - Methyldihydroquinazolinone." }, { "input": "The Retro - 2 molecule protects cells against Shiga toxins by specifically blocking retrograde transport from early endosomes to the trans - Golgi network.", "output": "There is no related enetity." }, { "input": "A SAR study has been carried out to identify more potent compounds.", "output": "There is no related enetity." }, { "input": "Cyclization and modifications of Retro - 2 led to a compound with roughly 100 - fold improvement of the EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.", "output": "There is no related enetity." }, { "input": "We also demonstrated that only one enantiomer of the dihydroquinazolinone reported herein is bioactive.", "output": "dihydroquinazolinone." }, { "input": "Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells.", "output": "Nitroxide, TEMPO." }, { "input": "2, 2, 6, 6 - Tetramethylpiperidine - 1 - oxyl ( TEMPO ) is a low molecular weight nitroxide and stable free radical.", "output": "2 , 2 , 6 , 6 - Tetramethylpiperidine - 1 - oxyl, TEMPO." }, { "input": "In this study, we investigated the cytotoxicity and genotoxicity of TEMPO in mammalian cells using the mouse lymphoma assay ( MLA ) and in vitro micronucleus assay.", "output": "TEMPO." }, { "input": "In the absence of metabolic activation ( S9 ), 3mM TEMPO produced significant cytotoxicity and marginal mutagenicity in the MLA; in the presence of S9, treatment of mouse lymphoma cells with 1 - 2mM TEMPO resulted in dose - dependent decreases of the relative total growth and increases in mutant frequency.", "output": "TEMPO, TEMPO." }, { "input": "Treatment of TK6 human lymphoblastoid cells with 0. 9 - 2. 3mM TEMPO increased the frequency of both micronuclei ( a marker for clastogenicity ) and hypodiploid nuclei ( a marker of aneugenicity ) in a dose - dependent manner; greater responses were produced in the presence of S9.", "output": "TEMPO." }, { "input": "Within the dose range tested, TEMPO induced reactive oxygen species and decreased glutathione levels in mouse lymphoma cells.", "output": "TEMPO, oxygen, glutathione." }, { "input": "In addition, the majority of TEMPO - induced mutants had loss of heterozygosity at the Tk locus, with allele loss of >= 34Mbp.", "output": "TEMPO." }, { "input": "These results indicate that TEMPO is mutagenic in the MLA and induces micronuclei and hypodiploid nuclei in TK6 cells.", "output": "TEMPO." }, { "input": "Oxidative stress may account for part of the genotoxicity induced by TEMPO in both cell lines.", "output": "TEMPO." }, { "input": "Testosterone exposure in childhood: discerning pathology from physiology.", "output": "Testosterone." }, { "input": "Introduction: Testosterone ( T ) drives normal male sexual development both in utero and at puberty.", "output": "Testosterone." }, { "input": "Aberrant T exposure manifests as virilization of a female fetus, contrasexual precocity in girls, and isosexual precocity in boys.", "output": "There is no related enetity." }, { "input": "Evidence of pathologic T exposure warrants a prompt evaluation.", "output": "There is no related enetity." }, { "input": "Areas covered: The authors introduce the topic of T exposure in children by reviewing its physiology in the fetus and during childhood and adolescence.", "output": "There is no related enetity." }, { "input": "Pathologic conditions leading to virilization of a female fetus as well as androgen - mediated gonadotropin - independent precocious puberty in both genders are then discussed.", "output": "androgen." }, { "input": "The authors finish by noting exogenous T exposure in children and adolescents, focusing specifically on secondary exposure to topical T preparations.", "output": "There is no related enetity." }, { "input": "Expert opinion: Contrasexual precocity in a girl or sexual precocity in a boy should prompt evaluation for causes of gonadotropin - independent pubertal changes.", "output": "There is no related enetity." }, { "input": "Initial biochemical evaluation includes a bone age, T, 17 - hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulfate ( DHEA - S ) and high sensitivity gonadotropin levels.", "output": "17 - hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulfate, DHEA - S." }, { "input": "The provider must query exposure to topical androgen - containing preparations as unintentional secondary exposure to topical T must be considered.", "output": "androgen." }, { "input": "Hyperandrogenism is temporally related to exposure of topical T and removal of exposure results in a marked decrease in serum T as well as resolution or stabilization of the signs and symptoms.", "output": "There is no related enetity." }, { "input": "Efficient induction of apoptosis in HeLa cells by a novel cationic porphycene photosensitizer.", "output": "porphycene." }, { "input": "In the present study we analyze the photobiological properties of 2, 7, 12 - tris ( alpha - pyridinio - p - tolyl ) - 17 - ( p - ( methoxymethyl ) phenyl ) porphycene ( Py3MeO - TBPo ) in Hela cells, in order to assess its potential as a new photosensitizer for photodynamic therapy of cultured tumor cells.", "output": "2 , 7 , 12 - tris ( alpha - pyridinio - p - tolyl ) - 17 - ( p - ( methoxymethyl ) phenyl ) porphycene, Py3MeO - TBPo." }, { "input": "Using 0. 5 mu M Py3MeO - TBPo, flow cytometry studies demonstrated an increase of intracellular drug levels related to the incubation time, reaching a maximum at 18 h.", "output": "Py3MeO - TBPo." }, { "input": "LysoTracker ( (R) ) Green ( LTG ) and MitoTracker ( (R) ) Green ( MTG ) probes were used to identify the subcellular localization.", "output": "There is no related enetity." }, { "input": "Upon exposure to ultraviolet excitation, red porphycene fluorescence was detected as red granules in the cytoplasm that colocalized with LTG.", "output": "porphycene." }, { "input": "No significant toxic effects were detected for Py3MeO - TBPo in the dark at concentrations below 1 mu M.", "output": "Py3MeO - TBPo." }, { "input": "In contrast, Py3MeO - TBPo combined with red - light irradiation induced concentration - and fluence - dependent HeLa cells inactivation.", "output": "Py3MeO - TBPo." }, { "input": "Besides, all photodynamic protocols assayed induced a clear effect of cell detachment inhibition after trypsin treatment.", "output": "There is no related enetity." }, { "input": "Both apoptotic and necrotic cell death mechanisms can occur in HeLa cells depending on the experimental protocol.", "output": "There is no related enetity." }, { "input": "After 18 h incubation with 0. 5 mu M Py3MeO - TBPo and subsequent red light irradiation ( 3. 6 J / cm ( 2 ) ), a high number of cells die by apoptosis, as evaluated by morphological alterations, immunofluorescent relocalization of Bax from cytosol to mitochondria, and TUNEL assay.", "output": "Py3MeO - TBPo." }, { "input": "Likewise, immunofluorescence techniques showed that cytochrome c is released from mitochondria into cytosol in cells undergoing apoptosis, which occurs immediately after relocation of Bax in mitochondria.", "output": "There is no related enetity." }, { "input": "The highest amount of apoptosis appeared 24 h after treatment ( 70 % ) and this cell death occurred without cell detachment to the substrate.", "output": "There is no related enetity." }, { "input": "In contrast, with 0. 75 mu M Py3MeO - TBPo and 3. 6 J / cm ( 2 ) irradiation, morphological changes showed a preferential necrotic cell death.", "output": "Py3MeO - TBPo." }, { "input": "Singlet oxygen was identified as the cytotoxic agent involved in cell photoinactivation.", "output": "oxygen." }, { "input": "Moreover, cell cultures pre - exposed to the singlet oxygen scavenger sodium azide showed pronounced protection against the loss of viability induced by Py3MeO - TBPo and light.", "output": "oxygen, sodium azide, Py3MeO - TBPo." }, { "input": "Different changes in distribution and organization of cytoskeletal elements ( microtubules and actin microfilaments ) as well as the protein vinculin, after apoptotic and necrotic photodynamic treatments have been analyzed.", "output": "There is no related enetity." }, { "input": "Neither of these two cell death mechanisms ( apoptosis or necrosis ) induced cell detachment.", "output": "There is no related enetity." }, { "input": "In summary, Py3MeO - TBPo appears to meet the requirements for further scrutiny as a very good photosensitizer for photodynamic therapy: it is water soluble, has a high absorption in the red spectral region ( where light penetration in tissue is higher ), and is able to induce effective high apoptotic rate ( 70 % ) related to the more widely studied photosensitizers.", "output": "Py3MeO - TBPo." }, { "input": "The life history of a botulinum toxin molecule.", "output": "There is no related enetity." }, { "input": "There is an emerging literature describing the absorption, distribution, metabolism and elimination of botulinum toxin.", "output": "There is no related enetity." }, { "input": "This work reveals that the toxin can be absorbed by both the oral and inhalation routes.", "output": "There is no related enetity." }, { "input": "The primary mechanism for absorption is binding and transport across epithelial cells.", "output": "There is no related enetity." }, { "input": "Toxin that enters the body undergoes a distribution phase, which is quite short, and an elimination phase, which is comparatively long.", "output": "There is no related enetity." }, { "input": "During the distribution phase, botulinum toxin migrates to the peri - neuronal microcompartment in the vicinity of vulnerable cells, such as cholinergic nerve endings.", "output": "There is no related enetity." }, { "input": "Only these cells have the ability to selectively accumulate the molecule.", "output": "There is no related enetity." }, { "input": "When the toxin moves from the cell membrane to the cell interior, it undergoes programmed death.", "output": "There is no related enetity." }, { "input": "This is coincident with release of the catalytically active light chain that paralyzes transmission.", "output": "There is no related enetity." }, { "input": "Intraneuronal metabolism of light chain is via the ubiquitination - proteasome pathway.", "output": "There is no related enetity." }, { "input": "Systemic metabolism and elimination is assumed to be via the liver.", "output": "There is no related enetity." }, { "input": "The analysis of absorption, distribution, metabolism and elimination of the toxin helps to create a life history of the molecule in the body.", "output": "There is no related enetity." }, { "input": "This has many benefits, including: a ) clarifying the mechanisms that underlie the disease botulism, b ) providing insights for development of medical countermeasures against the toxin, and c ) helping to explain the meaning of a lethal dose of toxin.", "output": "There is no related enetity." }, { "input": "It is likely that work intended to enhance understanding of the fate of botulinum toxin in the body will intensify.", "output": "There is no related enetity." }, { "input": "These efforts will include new and powerful analytic tools, such as single molecule - single cell analyses in vitro and real time, 3 - dimensional pharmacokinetic studies in vivo.", "output": "There is no related enetity." }, { "input": "A novel GIP - oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP - 1 receptors exhibits weight reducing and anti - diabetic properties.", "output": "There is no related enetity." }, { "input": "Oxyntomodulin ( Oxm ) is a 37 - amino acid peptide linked to alleviation of obesity - diabetes through a dual mode of action mediated at both glucagon and GLP - 1 receptors.", "output": "There is no related enetity." }, { "input": "GIP is the principle physiological regulator of postprandial insulin secretion.", "output": "There is no related enetity." }, { "input": "Therefore, the primary aim was to design a novel GIP - Oxm peptide incorporating the actions of GIP, GLP - 1 and glucagon in a single molecule.", "output": "There is no related enetity." }, { "input": "The first 11 N - terminal residues of Oxm were substituted with the sequence of stable dA ( 2 ) GIP molecule to generate a novel GIP - Oxm peptide ( dA ( 2 ) GIP - Oxm ).", "output": "N." }, { "input": "dA ( 2 ) GIP - Oxm was resistant to DPP - IV and significantly stimulated in vitro insulin release.", "output": "There is no related enetity." }, { "input": "dA ( 2 ) GIP - Oxm stimulated cAMP production in GIP - R, glucagon - R and GLP - 1 - R transfected cells by up to 95 %, 83 % and 77 % of that elicited by respective native ligands.", "output": "cAMP." }, { "input": "Acute administration of dA ( 2 ) GIP - Oxm to HFF mice resulted in reduced plasma glucose ( 45 % reduction ) and increased insulin concentrations ( 1. 7 - fold increase ).", "output": "glucose." }, { "input": "Furthermore, dA ( 2 ) GIP - Oxm lowered plasma glucose ( 42 % reduction ) and increased plasma insulin ( 1. 6 - fold increase ) when administered to HFF mice four hours prior to a glucose load.", "output": "glucose, glucose." }, { "input": "Once - daily administration of dA ( 2 ) GIP - Oxm for 15 days in HFF mice lowered body weight ( 13 % reduction ), reduced plasma glucose ( 40 % reduction ) and increased plasma insulin ( 1. 7 - fold increase ).", "output": "glucose." }, { "input": "Furthermore, glycemic responses were improved ( 38 % reduction ) and glucose - mediated plasma insulin concentrations enhanced ( 2 - fold increase ).", "output": "glucose." }, { "input": "These improvements in metabolic control were independent of changes in food intake and insulin sensitivity.", "output": "There is no related enetity." }, { "input": "dA ( 2 ) GIP - Oxm exerts positive beneficial actions on glucose homeostasis, beta - cell insulin secretion and body weight, mediated through GIP, glucagon and GLP - 1 receptors.", "output": "glucose." }, { "input": "Such multiple - acting peptides may hold promise as novel therapies for obesity - diabetes.", "output": "There is no related enetity." }, { "input": "Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils.", "output": "Acetaminophen." }, { "input": "Acetaminophen is a frequently prescribed over - the - counter drug to reduce fever and pain in the event of inflammatory process.", "output": "Acetaminophen." }, { "input": "As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance.", "output": "acetaminophen." }, { "input": "The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils ' oxidative burst and lifespan in vitro.", "output": "acetaminophen." }, { "input": "The obtained results demonstrate that acetaminophen efficiently modulates neutrophils ' oxidative burst in phorbol myristate acetate - activated neutrophils, in a concentration - dependent manner, at in vivo relevant concentrations.", "output": "acetaminophen, phorbol myristate acetate." }, { "input": "It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils.", "output": "acetaminophen, HOCl, H2O2." }, { "input": "Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate.", "output": "Acetaminophen, glutathione." }, { "input": "Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils - mediated apoptosis.", "output": "acetaminophen." }, { "input": "Overall, our data suggested that acetaminophen has considerable potential to be included in anti - inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation.", "output": "acetaminophen." }, { "input": "Estrogenic and androgenic effects in mosquitofish ( Gambusia affinis ) from streams contaminated by municipal effluent in Guangzhou, China.", "output": "There is no related enetity." }, { "input": "The study reported in this paper used mosquitofish to investigate the estrogenic and androgenic effects of municipal wastewater contamination on the stream system in Guangzhou, China.", "output": "There is no related enetity." }, { "input": "Western mosquitofish collected from a reference site and five study sites in streams forming part of the Pearl River network were dissected and analyzed for their morphological characteristics ( anal fin and hemal spine characteristics ) and target mRNA expression of genes ( VTG alpha and ER alpha mRNA expression ).", "output": "There is no related enetity." }, { "input": "Increased VTG alpha mRNA expression in males and decreased VTG alpha mRNA expression in females were observed in samples taken from four of the five study sites, with no such observations being made at the reference site.", "output": "There is no related enetity." }, { "input": "Correlation analysis indicated a significant correlation between the hemal spine morphology index and the gene transcription relative to the reference site.", "output": "There is no related enetity." }, { "input": "The multiple index also indicated that both male and female mosquitofish in contaminated streams were altered by discharged wastewater, as reflected in their morphological changes and relative induction of mRNA expression of genes in comparison to fish collected from the reference site.", "output": "There is no related enetity." }, { "input": "Effects of rare - earth co - doping on the local structure of rare - earth phosphate glasses using high and low energy X - ray diffraction.", "output": "rare - earth phosphate." }, { "input": "Rare - earth co - doping in inorganic materials has a long - held tradition of facilitating highly desirable optoelectronic properties for their application to the laser industry.", "output": "Rare - earth." }, { "input": "This study concentrates specifically on rare - earth phosphate glasses, ( R2O3 ) x ( R ' 2O3 ) y ( P2O5 ) 1 - ( x + y ), where ( R, R ' ) denotes ( Ce, Er ) or ( La, Nd ) co - doping and the total rare - earth composition corresponds to a range between metaphosphate, RP3O9, and ultraphosphate, RP5O14.", "output": "rare - earth phosphate, ( R2O3 ) x ( R ' 2O3 ) y ( P2O5 ) 1 - ( x + y ), Ce, Er, La, Nd, rare - earth, metaphosphate, RP3O9, ultraphosphate, RP5O14." }, { "input": "Thereupon, the effects of rare - earth co - doping on the local structure are assessed at the atomic level.", "output": "rare - earth." }, { "input": "Pair - distribution function analysis of high - energy X - ray diffraction data ( Qmax = 28 A ( - 1 ) ) is employed to make this assessment.", "output": "There is no related enetity." }, { "input": "Results reveal a stark structural invariance to rare - earth co - doping which bears testament to the open - framework and rigid nature of these glasses.", "output": "rare - earth." }, { "input": "A range of desirable attributes of these glasses unfold from this finding; in particular, a structural simplicity that will enable facile molecular engineering of rare - earth phosphate glasses with ' dial - up ' lasing properties.", "output": "rare - earth phosphate." }, { "input": "When considered together with other factors, this finding also demonstrates additional prospects for these co - doped rare - earth phosphate glasses in nuclear waste storage applications.", "output": "rare - earth phosphate." }, { "input": "This study also reveals, for the first time, the ability to distinguish between P - O and P [ double bond, length as m - dash ] O bonding in these rare - earth phosphate glasses from X - ray diffraction data in a fully quantitative manner.", "output": "P - O, P, O, rare - earth phosphate." }, { "input": "Complementary analysis of high - energy X - ray diffraction data on single rare - earth phosphate glasses of similar rare - earth composition to the co - doped materials is also presented in this context.", "output": "rare - earth phosphate." }, { "input": "In a technical sense, all high - energy X - ray diffraction data on these glasses are compared with analogous low - energy diffraction data; their salient differences reveal distinct advantages of high - energy X - ray diffraction data for the study of amorphous materials.", "output": "There is no related enetity." }, { "input": "Non - bonding interactions and internal dynamics in CH2F2H2CO: a rotational and model calculations study.", "output": "CH2F2H2CO." }, { "input": "The rotational spectra of three isotopologues of the 1: 1 complex between difluoromethane and formaldehyde have been observed and assigned using pulsed jet Fourier transform microwave spectroscopy.", "output": "difluoromethane, formaldehyde." }, { "input": "The formaldehyde lies in the FCF plane of difluoromethane, linked through a C - HF and a bifurcated CH2O weak hydrogen bonds.", "output": "formaldehyde, FCF, difluoromethane, C - HF, CH2O, hydrogen." }, { "input": "The rotational transitions are split into two component lines with a relative intensity ratio of 1: 3, due to the internal rotation of the formaldehyde moiety along its symmetry axis.", "output": "formaldehyde." }, { "input": "The barrier to this motion has been estimated by using a flexible model to be V2 = 180 ( 10 ) cm ( - 1 ).", "output": "There is no related enetity." }, { "input": "An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice.", "output": "There is no related enetity." }, { "input": "Testis size and sperm production are directly correlated to the total number of adult Sertoli cells ( SCs ).", "output": "There is no related enetity." }, { "input": "Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete.", "output": "There is no related enetity." }, { "input": "To investigate whether the IGF system is required for germ cell ( GC ) and SC development and function, we inactivated the insulin receptor ( Insr ), the IGF1 receptor ( Igf1r ), or both receptors specifically in the GC lineage or in SCs.", "output": "There is no related enetity." }, { "input": "Whereas ablation of insulin / IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs ( SC - Insr; Igf1r ) displayed a 75 % reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period.", "output": "There is no related enetity." }, { "input": "In addition, in vivo analyses revealed that FSH requires the insulin / IGF signaling pathway to mediate its proliferative effects on immature SCs.", "output": "There is no related enetity." }, { "input": "Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output.", "output": "There is no related enetity." }, { "input": "They also indicate that the insulin / IGF signaling pathway is required for FSH - mediated SC proliferation.", "output": "There is no related enetity." }, { "input": "Tuning the electronic and photophysical properties of heteroleptic iridium ( iii ) phosphorescent emitters through ancillary ligand substitution: a theoretical perspective.", "output": "iridium ( iii )." }, { "input": "The development and application of phosphorescent emitters in organic light - emitting diodes ( OLEDs ) have played a critical role in the push to commercialization of OLED - based display and lighting technologies.", "output": "There is no related enetity." }, { "input": "Here, we use density functional theory methods to study how modifying the ancillary ligand influences the electronic and photophysical properties of heteroleptic bis ( 4, 6 - difluorophenyl ) pyridinato - N, C [ dfppy ] iridium ( iii ) complexes.", "output": "bis ( 4 , 6 - difluorophenyl ) pyridinato - N , C [ dfppy ] iridium ( iii )." }, { "input": "We examine three families of bidentate ancillary ligands based on acetylacetonate, picolinate, and pyridylpyrazolate.", "output": "acetylacetonate, picolinate, pyridylpyrazolate." }, { "input": "It is found that the frontier molecular orbitals of the heteroleptic complexes can be substantially modulated both as a function of the bidentate ligand family and of the substitution patterns within a family.", "output": "There is no related enetity." }, { "input": "As a consequence, considerable control over the first absorption and phosphorescence emission transitions, both of which are dominated by one - electron transitions between the HOMO and LUMO, is obtained.", "output": "There is no related enetity." }, { "input": "Tuning the nature of the ancillary ligand, therefore, can be used to readily modulate the photophysical properties of the emitters, providing a powerful tool in the design of the emitter architecture.", "output": "There is no related enetity." }, { "input": "The early molecular processes underlying the neurological manifestations of an animal model of Wilson ' s disease.", "output": "There is no related enetity." }, { "input": "The Long - Evans Cinnamon ( LEC ) rat shows age - dependent hepatic manifestations that are similar to those of Wilson ' s disease ( WD ).", "output": "There is no related enetity." }, { "input": "The pathogenic process in the brain has, however, not been evaluated in detail due to the rarity of the neurological symptoms.", "output": "There is no related enetity." }, { "input": "However, copper accumulation is noted in LEC rat brain tissue from 24 weeks of age, which results in oxidative injuries.", "output": "copper." }, { "input": "The current study investigated the gene expression profiles of LEC rat brains at 24 weeks of age in order to identify the important early molecular changes that underlie the development of neurological symptoms in WD.", "output": "There is no related enetity." }, { "input": "Biological ontology - based analysis revealed diverse altered expressions of the genes related to copper accumulation.", "output": "copper." }, { "input": "Of particular interest, we found altered expression of genes connected to mitochondrial respiration ( Sdhaf2 and Ndufb7 ), calcineurin - mediated cellular processes ( Ppp3ca, Ppp3cb, and Camk2a ), amyloid precursor protein ( Anks1b and A2m ) and alpha - synuclein ( Snca ).", "output": "There is no related enetity." }, { "input": "In addition to copper - related changes, compensatory upregulations of Cp and Hamp reflect iron - mediated neurotoxicity.", "output": "copper, iron." }, { "input": "Of note, reciprocal expression of Asmt and Bhmt is an important clue that altered S - adenosylhomocysteine metabolism underlies brain injury in WD, which is directly correlated to the decreased expression of S - adenosylhomocysteine hydrolase in hepatic tissue in LEC rats.", "output": "S - adenosylhomocysteine, S - adenosylhomocysteine." }, { "input": "In conclusion, our study indicates that diverse molecular changes, both variable and complex, underlie the development of neurological manifestations in WD.", "output": "There is no related enetity." }, { "input": "Copper - related injuries were found to be the principal pathogenic process, but Fe - or adenosylhomocysteine - related injuries were also implicated.", "output": "Copper, Fe, adenosylhomocysteine." }, { "input": "Investigations using other animal models or accessible human samples will be required to confirm our observations.", "output": "There is no related enetity." }, { "input": "Opposite modulation of cell migration by distinct subregions of urokinase connecting Peptide.", "output": "There is no related enetity." }, { "input": "Functional analysis of isolated protein domains may uncover cryptic activities otherwise missed.", "output": "There is no related enetity." }, { "input": "The serine protease urokinase ( uPA ) has a clear - cut motogen activity that is catalytically independent and resides in its amino - terminal growth factor domain ( GFD, residues 1 - 49 ) and connecting peptide region ( CP, residues 132 - 158 ).", "output": "serine, amino." }, { "input": "To functionally dissect the CP region, we analysed the biological activity of two synthetic peptides corresponding to the N - terminal [ uPA - ( 135 - 143 ), residues 135 - 143 ] and C - terminal [ uPA - ( 144 - 158 ), residues 144 - 158 ] CP subregions.", "output": "N, C." }, { "input": "Most of the chemotactic activity of connecting peptide - derived peptide ( CPp, [ uPA - ( 135 - 158 ) ] ) for embryonic kidney HEK293 / uPAR - 25 cells is retained by uPA - ( 144 - 158 ) at nanomolar concentrations.", "output": "There is no related enetity." }, { "input": "In contrast, uPA - ( 135 - 143 ) inhibits basal, CPp -, vitronectin - and fibronectin - induced cell migration.", "output": "There is no related enetity." }, { "input": "Radioreceptor binding assays on intact HEK293 cells revealed that uPA - ( 135 - 143 ) and uPA - ( 144 - 158 ) are both able to compete with [ ( 125 ) I ] - CPp, albeit with different binding affinities.", "output": "( 125 ) I." }, { "input": "The consequences of phospho - mimicking, S138E substitution, were studied using [ 138E ] uPA - ( 135 - 158 ) and [ 138E ] uPA - ( 135 - 143 ) peptides.", "output": "phospho." }, { "input": "Unlike CPp, [ 138E ] uPA - ( 135 - 158 ) and [ 138E ] uPA - ( 135 - 143 ) exhibit remarkable inhibitory properties.", "output": "There is no related enetity." }, { "input": "Finally, analysis of the conformational preferences of the peptides allowed to identify secondary structure elements exclusively characterising the stimulatory CPp and uPA - ( 144 - 158 ) versus the inhibitory uPA - ( 135 - 143 ), [ 138E ] uPA - ( 135 - 158 ) and [ 138E ] uPA - ( 135 - 143 ) peptides.", "output": "There is no related enetity." }, { "input": "In conclusion, these data shed light on the cryptic activities of uPA connecting peptide, revealing the occurrence of two adjacent regions, both competing for binding to cell surface but conveying opposite signalling on cell migration.", "output": "There is no related enetity." }, { "input": "Effects of Prior Intensive versus Conventional Therapy and History of Glycemia on Cardiac Function in Type 1 Diabetes in the DCCT / EDIC.", "output": "There is no related enetity." }, { "input": "Intensive diabetes therapy reduces the prevalence of coronary calcification and progression of atherosclerosis, and the risk of cardiovascular disease events in the DCCT / EDIC study.", "output": "There is no related enetity." }, { "input": "The effects of intensive therapy on measures of cardiac function and structure and their association with glycemia have not been explored in type 1 diabetes ( T1DM ).", "output": "There is no related enetity." }, { "input": "We assess whether intensive treatment compared to conventional treatment during the DCCT led to differences in these parameters during EDIC.", "output": "There is no related enetity." }, { "input": "After 6. 5 years of intensive versus conventional therapy in the DCCT, and 15 years additional follow - up in EDIC, left ventricular indices were measured by cardiac magnetic resonance ( CMR ) imaging in 1017 of the 1371 members of the DCCT cohort.", "output": "There is no related enetity." }, { "input": "There were no differences between the DCCT intensive versus conventional treatment in end diastolic volume, end systolic volume, stroke volume, cardiac output, left ventricular mass, ejection fraction, LV mass / EDV, nor aortic distensibility.", "output": "There is no related enetity." }, { "input": "Mean DCCT / EDIC HbA1c over time was associated with EDV, SV, CO, LVmass, LVmass / EDV, and AD.", "output": "There is no related enetity." }, { "input": "These associations persisted after adjustment for CVD risk factors.", "output": "There is no related enetity." }, { "input": "Cardiac function and remodeling in T1DM assessed by CMR in the EDIC cohort was associated with prior glycemic exposure, but there was no effect of intensive versus conventional treatment during the DCCT on cardiac parameters.", "output": "There is no related enetity." }, { "input": "Barriers to superfast water transport in carbon nanotube membranes.", "output": "carbon." }, { "input": "Carbon nanotube ( CNT ) membranes hold the promise of extraordinary fast water transport for applications such as energy efficient filtration and molecular level drug delivery.", "output": "Carbon." }, { "input": "However, experiments and computations have reported flow rate enhancements over continuum hydrodynamics that contradict each other by orders of magnitude.", "output": "There is no related enetity." }, { "input": "We perform large scale molecular dynamics simulations emulating for the first time the micrometer thick CNTs membranes used in experiments.", "output": "There is no related enetity." }, { "input": "We find transport enhancement rates that are length dependent due to entrance and exit losses but asymptote to 2 orders of magnitude over the continuum predictions.", "output": "There is no related enetity." }, { "input": "These rates are far below those reported experimentally.", "output": "There is no related enetity." }, { "input": "The results suggest that the reported superfast water transport rates cannot be attributed to interactions of water with pristine CNTs alone.", "output": "There is no related enetity." }, { "input": "Bioassay - guided isolation and identification of antitermitic active compound from the leaf of Chinese cedar ( Cryptomeria fortunei Hooibrenk ).", "output": "There is no related enetity." }, { "input": "The persistent use of synthetic termiticides is at present of environmental concern and has resulted in the need to search for plant - derived compounds as an alternative for termite control.", "output": "There is no related enetity." }, { "input": "Antitermitic activity of Chinese cedar ( Cryptomeria fortunei Hooibrenk ) against Reticulitermes chinensis was demonstrated in laboratory tests.", "output": "There is no related enetity." }, { "input": "Bioactivity tests against the termite R. chinensis demonstrate that the lethal concentration ( LC50 ) value of leaf essential oil is 2. 80 mg / mL.", "output": "There is no related enetity." }, { "input": "Furthermore, alpha - terpineol, which was responsible for the antitermitic property and isolated from Chinese cedar that exhibited very strong antitermitic activity, was found to be significantly effective against R. chinensis with median LC50 values of 0. 86 mg / mL.", "output": "alpha - terpineol." }, { "input": "The findings suggested that the essential oil from Chinese cedar leaf and alpha - terpineol might be considered as a potent source for the production of effective, environmentally friendly and safe termiticides.", "output": "alpha - terpineol." }, { "input": "New methylated flavonol glucosides from Fumana montana Pomel.", "output": "methylated flavonol glucosides." }, { "input": "Three new methylated flavonol glucosides: 3 - methoxy - 7 - O - beta - ( 6 '' - galloylgluco - pyranoside ) quercetin ( 1 ), 3, 4 ' - dimethoxy - 7 - O - beta - ( 6 '' - galloyl - glucopyranoside ) quercetin ( 2 ) and 3 - methoxy - 7 - O - beta - ( 6 '' - galloylgluco - pyranoside ) kaempferol ( 3 ), in addition to six known flavonols, were isolated from the ethyl acetate extract of Fumana montana Pomel.", "output": "methylated flavonol glucosides, 3 - methoxy - 7 - O - beta - ( 6 '' - galloylgluco - pyranoside ) quercetin, 3 , 4 ' - dimethoxy - 7 - O - beta - ( 6 '' - galloyl - glucopyranoside ) quercetin, 3 - methoxy - 7 - O - beta - ( 6 '' - galloylgluco - pyranoside ) kaempferol, flavonols, ethyl acetate." }, { "input": "Their structures were assigned by spectroscopic methods.", "output": "There is no related enetity." }, { "input": "Phase diagram of solvophilic nanodiscs in a polymer solution: depletion attraction.", "output": "There is no related enetity." }, { "input": "Entropic attraction between anisotropic nanoparticles in nonadsorbing polymer solutions is significantly greater than that between nanospheres.", "output": "There is no related enetity." }, { "input": "In this study, depletion attraction between two solvophilic nanodiscs and the aggregation behavior of a nanodisc suspension are explored by dissipative particle dynamics.", "output": "There is no related enetity." }, { "input": "The depletion force due to polymer addition is proportional to the product of the osmotic pressure and the area of the nanodisc, even for concentrated polymer solutions.", "output": "There is no related enetity." }, { "input": "For a suspension of nanodiscs, three possible equilibrium states are observed upon polymer addition: dispersion, pretransition, and phase separation.", "output": "There is no related enetity." }, { "input": "By varying nanodisc concentration ( phi D ) and polymer concentration ( phi P ), the phase diagram is obtained.", "output": "There is no related enetity." }, { "input": "Dispersion exists for small phi D and phi P.", "output": "There is no related enetity." }, { "input": "As phi D exceeds critical aggregation concentration, finite sized clusters are mainly formed with columnar structure in the pretransition regime, similar to micellization associated with typical surfactants.", "output": "There is no related enetity." }, { "input": "The mean size of columnar clusters seems to grow with phi D ( 1 / 2 ) and phi P.", "output": "There is no related enetity." }, { "input": "For high enough phi D and phi P, finite sized clusters vanish and phase separation appears.", "output": "There is no related enetity." }, { "input": "The nanodisc - rich phase is formed by a bundle of columns or a pack of columns owing to face - to - side and side - to - side depletion attractions.", "output": "There is no related enetity." }, { "input": "Molecular Dynamics Simulations of DPPC Bilayers Using \" LIME \", a New Coarse - Grained Model.", "output": "DPPC." }, { "input": "A new intermediate resolution model for phospholipids, LIME, designed for use with discontinuous molecular dynamics ( DMD ) simulations is presented.", "output": "There is no related enetity." }, { "input": "The implicit - solvent model was developed using a multiscale modeling approach in which the geometric and energetic parameters are obtained by collecting data from atomistic simulations of a system composed of 1, 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine ( DPPC ) molecules and explicit water.", "output": "1 , 2 - dipalmitoyl - sn - glycero - 3 - phosphocholine, DPPC." }, { "input": "In the model, 14 coarse - grained sites that are classified as 1 of 6 types represent DPPC.", "output": "DPPC." }, { "input": "DMD simulations performed on a random solution of DPPC resulted in the formation of a defect - free bilayer in less than 4 h.", "output": "DPPC." }, { "input": "The bilayer formed quantitatively reproduces the main structural properties ( e. g., area per lipid, bilayer thickness, bond order parameters ) that are observed experimentally.", "output": "There is no related enetity." }, { "input": "In addition, the bilayer transitions from a liquid - crystalline phase to a tilted gel phase when the temperature is reduced.", "output": "There is no related enetity." }, { "input": "Transbilayer movement of a lipid from the bottom leaflet to the top leaflet is observed when the temperature is increased.", "output": "There is no related enetity." }, { "input": "Dose - ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus.", "output": "AZD1656." }, { "input": "AIM: To assess the glucose - lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus.", "output": "AZD1656." }, { "input": "METHODS: This was a randomized, double - blind, placebo - controlled study performed in Japan ( NCT01152385 ).", "output": "There is no related enetity." }, { "input": "Patients ( n = 224 ) were randomized to AZD1656 ( 40 - 200, 20 - 140 or 10 - 80 mg titrated doses ) or placebo.", "output": "AZD1656." }, { "input": "The primary variable was the placebo - corrected change from baseline to 4 months in glycated haemoglobin ( HbA1c ).", "output": "There is no related enetity." }, { "input": "Effects on fasting plasma glucose ( FPG ) and safety were also assessed.", "output": "glucose." }, { "input": "RESULTS: HbA1c was reduced numerically from baseline by 0. 3 - 0. 8 % with AZD1656 and by 0. 1 % with placebo over the first 2 months of treatment, after which effects of AZD1656 started to decline.", "output": "AZD1656, AZD1656." }, { "input": "The changes from baseline to 4 months in HbA1c were not significant for the AZD1656 40 - 200 mg group versus placebo [ mean ( 95 % CI ) placebo - corrected change: - 0. 22 ( - 0. 65, 0. 20 ) %; p = 0. 30 ].", "output": "AZD1656." }, { "input": "Formal significance testing was not carried out for the other two AZD1656 dose groups.", "output": "AZD1656." }, { "input": "A higher percentage of patients on AZD1656 achieved HbA1c <= 7 % after 4 months versus placebo, but responder rates were low.", "output": "AZD1656." }, { "input": "Results for FPG reflected those for HbA1c.", "output": "There is no related enetity." }, { "input": "Cases of hypoglycaemia were rare with AZD1656 ( one patient ) and no safety concerns were raised.", "output": "AZD1656." }, { "input": "CONCLUSIONS: Although initially favourable plasma glucose reductions were observed, there was a loss of effect over time with sustained AZD1656 treatment.", "output": "glucose, AZD1656." }, { "input": "The study design did not allow an evaluation of the reasons for this lack of long - term efficacy.", "output": "There is no related enetity." }, { "input": "Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled - coil domain regulates 6 - helical bundle formation.", "output": "There is no related enetity." }, { "input": "HIV entry is mediated by the envelope glycoproteins gp120 and gp41.", "output": "There is no related enetity." }, { "input": "The gp41 subunit contains several functional domains: the N - terminal heptad repeat ( NHR ) domains fold a triple stranded coiled - coil forming a meta - stable prefusion intermediate.", "output": "N." }, { "input": "C - terminal heptad repeat ( CHR ) subsequently folds onto the hydrophobic grooves of the NHR coiled - coil to form a stable 6 - helix bundle, which juxtaposes the viral and cellular membranes for fusion.", "output": "C." }, { "input": "The C34 which has 34 amino acid residues is known as the core structure in CHR.", "output": "amino acid." }, { "input": "A highly anti - HIV peptide inhibitor derived from C34 was designed.", "output": "There is no related enetity." }, { "input": "An artificial salt bridge was added in the 6 - helical bundle by substitution of lysine for Ile646.", "output": "lysine, Ile646." }, { "input": "With a cholesterol modification at C - terminal, the inhibitor containing I646K mutation represented higher anti - viral activity than C34 - cholesterol combination without mutation.", "output": "cholesterol, C, cholesterol." }, { "input": "Cu ( OTf ) 2 catalyzed three component reaction: Efficient synthesis of spiro [ indoline - 3, 4 ' - pyrano [ 3, 2 - b ] pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines.", "output": "Cu ( OTf ) 2, spiro [ indoline - 3 , 4 ' - pyrano [ 3 , 2 - b ] pyran." }, { "input": "Cu ( OTf ) 2 catalyzed efficient synthesis of spiropyrano [ 3, 2 - b ] pyran - 4 ( 8H ) - ones is accomplished via one - pot three component reaction between isatin, kojic acid and active methylenes.", "output": "Cu ( OTf ) 2, spiropyrano [ 3 , 2 - b ] pyran - 4 ( 8H ) - ones, isatin, kojic acid, methylenes." }, { "input": "This synthetic protocol is operationally simple and affords product with good to excellent yields at a short reaction time.", "output": "There is no related enetity." }, { "input": "The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human lung cancer cell line ( A549 ) and found that 13 compounds exhibited moderate to good anticancer potency.", "output": "There is no related enetity." }, { "input": "Molecular docking studies were performed for all the synthesized compounds and the results showed that compound 4e showed greater affinity for anaplastic lymphoma kinase ( ALK ) receptor.", "output": "There is no related enetity." }, { "input": "Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC - 3 prostate cancer cells.", "output": "Ginkgetin." }, { "input": "Ginkgetin is a natural biflavonoid isolated from leaves of Ginkgo biloba L.", "output": "Ginkgetin, biflavonoid." }, { "input": "Though it was known to have anti - inflammatory, anti - influenza virus, anti - fungal activity, osteoblast differentiation stimulating activity and neuro - protective effects, the underlying antitumor mechanism of ginkgetin still remains unclear.", "output": "ginkgetin." }, { "input": "Thus, in the present study, anti - cancer mechanism of ginkgetin was elucidated in human prostate cancer PC - 3 cells.", "output": "ginkgetin." }, { "input": "Ginkgetin suppressed the viability of PC - 3 cells in a concentration - dependent manner and also significantly increased the sub - G1 DNA contents of cell cycle in PC - 3 cells.", "output": "Ginkgetin." }, { "input": "Ginkgetin activated caspase - 3 and attenuated the expression of survival genes such as Bcl - 2, Bcl - xL, survivin and Cyclin D1 at protein and mRNA levels.", "output": "Ginkgetin." }, { "input": "Consistently, pan - caspase inhibitor Z - DEVD - fmk blocked sub G1 accumulation and cleavages of PRAP and caspase 3 induced by ginkgetin in PC - 3 cells.", "output": "Z - DEVD - fmk, ginkgetin." }, { "input": "Overall, these findings suggest that ginkgetin induces apoptosis in PC - 3 cells via activation of caspase 3 and inhibition of survival genes as a potent chemotherapeutic agent for prostate cancer treatment.", "output": "ginkgetin." }, { "input": "In vivo effect of Schisandrin B on cytochrome P450 enzyme activity.", "output": "Schisandrin B." }, { "input": "To investigate the possible drug interaction, this study is designed to evaluate the ability of Schisandrin B ( Sch B ) to modulate cytochrome P450 3A activity ( CYP3A ) in vivo and to alter the pharmacokinetic profiles of CYP3A substrate ( midazolam ) in treated rats.", "output": "Schisandrin B, Sch B, midazolam." }, { "input": "Rats were repeated administered with physiological saline ( negative control group ), ketoconazole ( 75mg / kg, positive control group ) or varied doses of Sch B ( experimental groups ) for three consecutive days.", "output": "ketoconazole, Sch B." }, { "input": "Subsequently, changes in hepatic microsomal CYP3A activity and the pharmacokinetic profiles of midazolam and 1 ' - hydroxy midazolam in plasma were studied to evaluate CYP3A activity.", "output": "midazolam, 1 ' - hydroxy midazolam." }, { "input": "The results indicated that Sch B significantly dose - dependently inhibited rat hepatic microsomal CYP3A activity with Ki value of 16. 64mg / kg and showed the characteristic of a noncompetitive inhibitor.", "output": "Sch B." }, { "input": "Oral administration of Sch B for 3 days in rats produced significant effect on the pharmacokinetics of oral midazolam.", "output": "Sch B, midazolam." }, { "input": "Sch B resulted in a significant, dose - dependent increase in midazolam AUC0 - infinity except at the dose of 2mg / kg, while AUC0 - infinity increased by 26. 1 % ( 8mg / kg ) and 60. 6 % ( 16mg / kg ), respectively.", "output": "Sch B, midazolam." }, { "input": "In the pharmacokinetic profiles of 1 ' - hydroxy midazolam, the significant, dose - dependent decrease in AUC0 - infinity was observed except at the dose of 2mg / kg, while AUC0 - infinity reduced by 44. 5 % ( 8mg / kg ) and 49. 2 % ( 16mg / kg ), respectively.", "output": "1 ' - hydroxy midazolam." }, { "input": "These results suggested that 3 - day treatment of Sch B could increase concentration and oral bioavailability of drug metabolized by CYP3A.", "output": "Sch B." }, { "input": "When the drug, consisting of Sch B, is used in the clinic for more than 3 days, the possible drug - drug interactions should be taken into consideration.", "output": "Sch B." }, { "input": "A Mammalian Pre - mRNA 5 ' End Capping Quality Control Mechanism and an Unexpected Link of Capping to Pre - mRNA Processing.", "output": "There is no related enetity." }, { "input": "Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5 ' end - capped messenger RNAs ( mRNAs ).", "output": "There is no related enetity." }, { "input": "Here, we report that their mammalian homolog, Dom3Z ( referred to as DXO ), possesses pyrophosphohydrolase, decapping, and 5 ' - to - 3 ' exoribonuclease activities.", "output": "There is no related enetity." }, { "input": "Surprisingly, we found that DXO preferentially degrades defectively capped pre - mRNAs in cells.", "output": "There is no related enetity." }, { "input": "Additional studies show that incompletely capped pre - mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation.", "output": "There is no related enetity." }, { "input": "Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1. 5 A provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities.", "output": "There is no related enetity." }, { "input": "Our data reveal a pre - mRNA 5 ' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5 ' end capping and subsequent pre - mRNA processing.", "output": "There is no related enetity." }, { "input": "Lipidic spherulites: Formulation optimisation by paired optical and cryoelectron microscopy.", "output": "There is no related enetity." }, { "input": "Objective of this study was to assess the various steps leading to spherulite obtention by means of optical and cryoelectron microscopy.", "output": "There is no related enetity." }, { "input": "The formulation, resting and hydration steps were optimised.", "output": "There is no related enetity." }, { "input": "Green - based process and organic - based process were compared.", "output": "There is no related enetity." }, { "input": "It was found that spherulites could be obtained only when two key steps were followed: a prior resting phase of excipients and the shearing stress of the hydrated excipients.", "output": "There is no related enetity." }, { "input": "Moreover, the new formulation under study formed spherulites in the 100 - 200nm range, which is smaller than previously reported spherulites.", "output": "There is no related enetity." }, { "input": "Such laboratory scale optimised process led the integration of spherulites in a larger number of prospective studies.", "output": "There is no related enetity." }, { "input": "Indeed, we finally showed that the encapsulated payload of a hydrophobic compound, such as the anti - angiogenic agent fisetin, was increased to a much higher degree than with a liposomal encapsulation.", "output": "There is no related enetity." }, { "input": "Pharmacokinetic evaluation in mice of amorphous itraconazole - based dry powder formulations for inhalation with high bioavailability and extended lung retention.", "output": "itraconazole." }, { "input": "Three Itraconazole ( ITZ ) dry powders for inhalation ( DPI ) were prepared by spray - drying a mannitol solution in which the ITZ was in suspension ( F1 ) or was in solution without ( F2 ) or with phospholipid ( PL ) ( F3 ).", "output": "Itraconazole, ITZ, mannitol, ITZ." }, { "input": "These powders were endotracheally insufflated in vivo at a single dose of 0. 5mg / kg for pharmacokinetic profile ( lung and plasma concentration ) determination in ICR CD - 1 mice.", "output": "There is no related enetity." }, { "input": "ITZ was crystalline in F1 and assumed to be amorphous in the F2 and F3 formulations.", "output": "ITZ." }, { "input": "The amorphous nature of ITZ in F2 and F3 formulations allowed the in vitro formation of an ITZ supersaturated solution with a maximum solubility of 450 +/- 124ng / ml ( F2 ) and 498 +/- 44ng / ml ( F3 ), in contrast to formulation F1 ( < 10ng / ml ).", "output": "ITZ, ITZ." }, { "input": "As a result of these higher solubilities, absorption into the systemic compartment after endotracheal administration was faster for formulations F2 and F3 ( shorter tmax ) and in larger quantities compared to the F1 formulation ( plasmatic AUC0 - 24h of 182ngh / ml, 491. 5ngh / ml and 376. 8ngh / ml, and tmax of 60min, 30min and 5min for F1, F2 and F3, respectively ).", "output": "There is no related enetity." }, { "input": "PL increased the systemic bioavailability of ITZ ( determined by the AUCplasma to AUClung ratio ) as a consequence of their wetting and absorption enhancement effect.", "output": "ITZ." }, { "input": "ITZ lung concentrations after pulmonary administration remained higher than the targeted dose, based on the minimal inhibitory concentrations for Aspergillus Fumigatus ( 2 mu g / gwetlung ), 24h post - administration for both F1 and F2 formulations.", "output": "ITZ." }, { "input": "However, this was not the case for formulation F3, which exhibited a faster elimination rate from the lung, with an elimination half - life of 4. 1h vs. 6. 5h and 14. 7h for F1 and F2, respectively.", "output": "There is no related enetity." }, { "input": "Antagonism of the transient receptor potential ankyrin 1 ( TRPA1 ) attenuates hyperalgesia and urinary bladder overactivity in cyclophosphamide - induced haemorrhagic cystitis.", "output": "cyclophosphamide." }, { "input": "The aim of this study was to investigate the involvement of the transient receptor potential ankyrin 1 ( TRPA1 ) in haemorrhagic cystitis, the main side effect of cyclophosphamide - based chemotherapy.", "output": "cyclophosphamide." }, { "input": "Hannover female rats received intraperitoneal ( i. p. ) injection of cyclophosphamide ( three doses of 100mg / kg, every other day, in a total of five days ).", "output": "cyclophosphamide." }, { "input": "This treatment was followed by the treatment with TRPA1 antagonist HC 030031 ( 50mg / kg, p. o. ).", "output": "HC 030031." }, { "input": "The threshold for hindpaw withdrawal or abdominal retraction to von Frey Hair and the locomotor activity were measured.", "output": "There is no related enetity." }, { "input": "The treatment with the TRPA1 antagonist HC 030031 significantly decreased mechanical hyperalgesia induced by cyclophosphamide without interfere with locomotor activity.", "output": "HC 030031, cyclophosphamide." }, { "input": "Urodynamic parameters were performed by cystometry 24h after a single treatment with cyclophosphamide ( 200mg / kg, i. p. ) in control and HC 030031 treated rats.", "output": "cyclophosphamide, HC 030031." }, { "input": "Analyses of the urodynamic parameters showed that a single dose of cyclophosphamide was enough to significantly increase the number and amplitude of non - voiding contractions and to decrease the voided volume and voiding efficiency, without significantly altering basal, threshold or maximum pressure.", "output": "cyclophosphamide." }, { "input": "The treatment with HC 030031 either before ( 100mg / kg, p. o. ) or after ( 30mg / kg, i. v. ) cyclophosphamide inhibited the non - voiding contractions but failed to counteract the loss in voiding efficiency.", "output": "HC 030031, cyclophosphamide." }, { "input": "Our data demonstrates that nociceptive symptoms and urinary bladder overactivity caused by cyclophosphamide, in part, are dependent upon the activation of TRPA1.", "output": "cyclophosphamide." }, { "input": "In this context, the antagonism of the receptor may be an alternative to minimise the urotoxic symptoms caused by this chemotherapeutic agent.", "output": "There is no related enetity." }, { "input": "Differential responses to omega - agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.", "output": "There is no related enetity." }, { "input": "omega - Agatoxin - IVA is a well known P / Q - type Ca ( 2 + ) channel blocker and has been shown to affect presynaptic Ca ( 2 + ) currents as well postsynaptic potentials.", "output": "Ca ( 2 + ), Ca ( 2 + )." }, { "input": "P / Q - type voltage gated Ca ( 2 + ) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation.", "output": "Ca ( 2 + )." }, { "input": "Monitoring spontaneous activity of neuronal networks on microelectrode arrays ( MEAs ) provides an important tool for examining this neurotoxin.", "output": "There is no related enetity." }, { "input": "Changes in extracellular action potentials are readily observed and are dependent on synaptic function.", "output": "There is no related enetity." }, { "input": "Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of omega - agatoxin on spontaneous action potential firing within these networks.", "output": "There is no related enetity." }, { "input": "We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50nM was required to alter activity in frontal cortex networks.", "output": "There is no related enetity." }, { "input": "Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed.", "output": "There is no related enetity." }, { "input": "These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters.", "output": "There is no related enetity." }, { "input": "Administration of bicuculline, a GABAA inhibitor, isolated a single response to omega - agatoxin, which was characterized by a reduction in network activity.", "output": "bicuculline." }, { "input": "These data support the notion that the two clusters detected with omega - agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations.", "output": "There is no related enetity." }, { "input": "Pharmacokinetic, neurochemical, stereological and neuropathological studies on the potential effects of paraquat in the substantia nigra pars compacta and striatum of male C57BL / 6J mice.", "output": "paraquat." }, { "input": "The pharmacokinetics and neurotoxicity of paraquat dichloride ( PQ ) were assessed following once weekly administration to C57BL / 6J male mice by intraperitoneal injection for 1, 2 or 3 weeks at doses of 10, 15 or 25mg / kg / week.", "output": "paraquat dichloride." }, { "input": "Approximately 0. 3 % of the administered dose was taken up by the brain and was slowly eliminated, with a half - life of approximately 3 weeks.", "output": "There is no related enetity." }, { "input": "PQ did not alter the concentration of dopamine ( DA ), homovanillic acid ( HVA ) or 3, 4 - dihydroxyphenylacetic acid ( DOPAC ), or increase dopamine turnover in the striatum.", "output": "dopamine, homovanillic acid, HVA, 3 , 4 - dihydroxyphenylacetic acid, DOPAC, dopamine." }, { "input": "There was inconsistent stereological evidence of a loss of DA neurons, as identified by chromogenic or fluorescent - tagged antibodies to tyrosine hydroxylase in the substantia nigra pars compacta ( SNpc ).", "output": "tyrosine." }, { "input": "There was no evidence that PQ induced neuronal degeneration in the SNpc or degenerating neuronal processes in the striatum, as indicated by the absence of uptake of silver stain or reduced immunolabeling of tyrosine - hydroxylase - positive ( TH ( + ) ) neurons.", "output": "silver, tyrosine." }, { "input": "There was no evidence of apoptotic cell death, which was evaluated using TUNEL or caspase 3 assays.", "output": "There is no related enetity." }, { "input": "Microglia ( IBA - 1 immunoreactivity ) and astrocytes ( GFAP immunoreactivity ) were not activated in PQ - treated mice 4, 8, 16, 24, 48, 96 or 168h after 1, 2 or 3 doses of PQ.", "output": "There is no related enetity." }, { "input": "In contrast, mice dosed with the positive control substance, 1 - methyl - 4 - phenyl - 1, 2, 3, 6 - tetrahydropyridine ( MPTP; 10mg / kg / dose x 4 doses, 2h apart ), displayed significantly reduced DA and DOPAC concentrations and increased DA turnover in the striatum 7 days after dosing.", "output": "1 - methyl - 4 - phenyl - 1 , 2 , 3 , 6 - tetrahydropyridine, MPTP, DOPAC." }, { "input": "The number of TH ( + ) neurons in the SNpc was reduced, and there were increased numbers of degenerating neurons and neuronal processes in the SNpc and striatum.", "output": "There is no related enetity." }, { "input": "MPTP - mediated cell death was not attributed to apoptosis.", "output": "MPTP." }, { "input": "MPTP activated microglia and astrocytes within 4h of the last dose, reaching a peak within 48h.", "output": "MPTP." }, { "input": "The microglial response ended by 96h in the SNpc, but the astrocytic response continued through 168h in the striatum.", "output": "There is no related enetity." }, { "input": "These results bring into question previous published stereological studies that report loss of TH ( + ) neurons in the SNpc of PQ - treated mice.", "output": "There is no related enetity." }, { "input": "This study also suggests that even if the reduction in TH ( + ) neurons reported by others occurs in PQ - treated mice, this apparent phenotypic change is unaccompanied by neuronal cell death or by modification of dopamine levels in the striatum.", "output": "dopamine." }, { "input": "Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF - kappa B dependant TGF - beta activation: A biphasic experimental study.", "output": "Berberine, bleomycin." }, { "input": "Idiopathic pulmonary fibrosis ( IPF ) is a progressive, debilitating and fatal lung disorder with high mortality rate.", "output": "There is no related enetity." }, { "input": "Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure.", "output": "There is no related enetity." }, { "input": "Thus, it becomes great interest to find novel agents to treat IPF.", "output": "There is no related enetity." }, { "input": "Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases.", "output": "Berberine." }, { "input": "This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin - induced lung injury and fibrosis, a tentative animal model.", "output": "berberine, bleomycin." }, { "input": "Male wistar rats were subjected to single intratracheal instillation of 2. 5U / kg of bleomycin on day 0.", "output": "bleomycin." }, { "input": "Berberine treatments were either provided in preventive or therapeutic mode respectively.", "output": "Berberine." }, { "input": "Berberine administration significantly ameliorated the bleomycin mediated histological alterations and reduced the inflammatory cell infiltrate in BALF.", "output": "Berberine, bleomycin." }, { "input": "Berberine significantly blocked collagen accumulations with parallel reduction in the hydroxyproline level.", "output": "Berberine, hydroxyproline." }, { "input": "The immunological sign of bleomycin stimulated mast cell deposition and histamine release were considerably reduced by berberine.", "output": "bleomycin, histamine, berberine." }, { "input": "Berberine enhanced the antioxidant status, through upregulating the redox sensing transcription factor nuclear factor E2 - related factor 2 ( Nrf2 ).", "output": "Berberine." }, { "input": "Berberine inhibited the bleomycin mediated activation of inflammatory mediator nuclear factor kappa B ( NF - kappa B ) and suppressed its downstream target inducible nitric oxide synthase ( iNOS ).", "output": "Berberine, bleomycin, nitric oxide." }, { "input": "Strikingly, berberine exhibited target attenuation of tumor necrosis factor alpha ( TNF - alpha ) and key pro - fibrotic mediator, transforming growth factor beta 1 ( TGF - beta 1 ).", "output": "berberine." }, { "input": "Taken together, this study reveals the beneficial effects of berberine against bleomycin mediated fibrotic challenge through activating Nrf2 and suppressing NF - kappa B dependent inflammatory and TGF - beta 1 mediated fibrotic events.", "output": "berberine, bleomycin." }, { "input": "Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure.", "output": "crocin, diazinon." }, { "input": "This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L.", "output": "crocin." }, { "input": "( Saffron ) against subchronic diazinon ( DZN ) induced cardiotoxicity in rats.", "output": "diazinon, DZN." }, { "input": "METHODS: Rats were divided into 7 groups; control ( corn oil, gavage ), DZN ( 15mg / kg / day, gavage, ), crocin ( 12. 5, 25 or 50mg / kg / day, i. p ) plus DZN, vitamin E ( 200IU / kg, i. p, three times per week ) plus DZN and crocin ( 50mg / kg / day, i. p ) groups.", "output": "crocin, DZN, vitamin E, DZN, crocin." }, { "input": "Treatments were continued for 4weeks.", "output": "There is no related enetity." }, { "input": "Creatine phosphokinase MB ( CK - MB ), malondealdehyde ( MDA ) and glutathione ( GSH ) levels were evaluated in heart tissue at the end of treatments.", "output": "Creatine, malondealdehyde, MDA, glutathione, GSH." }, { "input": "Levels of apoptotic proteins ( Bax, Bcl2, caspase 3 ) and cytosolic cytochrome c were analyzed by Western blotting.", "output": "There is no related enetity." }, { "input": "Transcript levels of Bax and Bcl2 were also determined using qRT PCR.", "output": "There is no related enetity." }, { "input": "RESULTS: DZN induced histophatological damages and elevated the level of cardiac marker CK - MB.", "output": "DZN." }, { "input": "These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax / Bcl2 ratio ( both protein and mRNA levels ), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue.", "output": "MDA, GSH." }, { "input": "Crocin ( 25 and 50mg / kg ) or vitamin E improved histopathological damages, decreased MDA and CK - MB, increased GSH content and attenuated the increase of Bax / Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN.", "output": "Crocin, vitamin E, MDA, GSH, DZN." }, { "input": "In summary, DZN induced mitochondrial - mediated apoptosis in heart tissue of rat following subchronic exposure.", "output": "DZN." }, { "input": "Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.", "output": "Crocin, DZN." }, { "input": "Effect of naloxone on ischemic acute kidney injury in the mouse.", "output": "naloxone." }, { "input": "Renal ischemia produces sympathoexcitation, which is responsible for the development of ischemic acute kidney injury.", "output": "There is no related enetity." }, { "input": "Stimulation of central opioid receptors activates the renal sympathetic nerve.", "output": "There is no related enetity." }, { "input": "The present study examined the effect of an opioid receptor antagonist naloxone on the ischemia / reperfusion - induced renal dysfunction in mice.", "output": "naloxone." }, { "input": "Blood urea nitrogen ( BUN ) and plasma creatinine increased 24 h after the renal ischemia / reperfusion.", "output": "urea, nitrogen, creatinine." }, { "input": "Intraperitoneal or intracerebroventricular, but not intrathecal, pretreatment with naloxone suppressed the renal ischemia / reperfusion - induced increases in BUN and plasma creatinine.", "output": "naloxone, creatinine." }, { "input": "This effect of naloxone was reversed by subcutaneous pretreatment with morphine.", "output": "naloxone, morphine." }, { "input": "Selective MOP receptor antagonist beta - funaltrexamine ( FNA ) also suppressed the renal ischemia / reperfusion - induced increases in BUN and plasma creatinine.", "output": "beta - funaltrexamine, FNA, creatinine." }, { "input": "Moreover, tyrosine hydroxylase expression in the renal tissue increased 24 h after renal ischemia / reperfusion, which was abolished by intraperitoneal or intracerebroventricular pretreatment with naloxone and FNA.", "output": "tyrosine, naloxone, FNA." }, { "input": "Immunohistochemical experiments revealed a significant increase in the number of the Fos family proteins ( c - Fos, FosB, Fra - 1, and Fra - 2 ) positive cells in the paraventricular nucleus of hypothalamus and supraoptic nucleus 24 h after the renal ischemia / reperfusion.", "output": "There is no related enetity." }, { "input": "Intracerebroventricular pretreatment with naloxone attenuated the renal ischemia / reperfusion - induced increase in the number of the Fos family proteins positive cells in these areas.", "output": "naloxone." }, { "input": "Finally, we observed that i. c. v. pretreatment with antiserum against beta - endorphin also suppressed the increased blood urea and plasma creatinine.", "output": "urea, creatinine." }, { "input": "These results suggest that the blockade of central opioid receptors can attenuate the ischemic acute kidney injury through the inhibition of renal sympathoexcitation.", "output": "There is no related enetity." }, { "input": "The central opioid receptors may thus be a new target for the treatment of ischemic organ failures.", "output": "There is no related enetity." }, { "input": "Clinical toxinology specialty training.", "output": "There is no related enetity." }, { "input": "Clinical toxinology is the medical discipline dealing with the diagnosis, treatment and prevention of toxin diseases caused by exposure to venomous animals and poisonous animals, plants and mushrooms.", "output": "There is no related enetity." }, { "input": "Currently there is no national or international organisation accrediting or training doctors in this discipline, but the role of the IST in this area is the subject of a recently approved revised Constitution.", "output": "There is no related enetity." }, { "input": "A few courses covering some aspects of clinical toxinology exist, either with limited curricula, or with only a minor clinical focus, or with a very regional, non - global focus.", "output": "There is no related enetity." }, { "input": "The only comprehensive clinical toxinology course is the one provided in Adelaide, Australia, running regularly since 1997.", "output": "There is no related enetity." }, { "input": "This course may form the nucleus from which IST can develop a global accredited training scheme in clinical toxinology.", "output": "There is no related enetity." }, { "input": "Such a scheme will require input from diverse global regions and will be far more comprehensive and over a much longer time than the current Short Course, though may incorporate the Short Course in some way, or a derivative of it.", "output": "There is no related enetity." }, { "input": "Accreditation of medical expertise in clinical toxinology will be required at the national level and this might be accomplished by the IST working with existing national medical specialty organisations and governments, with the IST supervising the training and accreditation requirements and the national organisations providing the framework for registration of medical expertise at the local level.", "output": "There is no related enetity." }, { "input": "Synthesis and biological evaluation of novel pyrrolidine - 2, 5 - dione derivatives as potential antidepressant agents.", "output": "pyrrolidine - 2 , 5 - dione." }, { "input": "Part 1.", "output": "There is no related enetity." }, { "input": "A series of 3 - ( 1H - indol - 3 - yl ) pyrrolidine - 2, 5 - dione derivatives was synthesized and their biological activity was evaluated.", "output": "3 - ( 1H - indol - 3 - yl ) pyrrolidine - 2 , 5 - dione." }, { "input": "The chemical structures of the newly prepared compounds were confirmed by ( 1 ) H NMR, ( 13 ) C NMR and ESI - HRMS spectra data.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "All tested compounds proved to be potent 5 - HT1A receptor and serotonin transporter protein ( SERT ) ligands.", "output": "serotonin." }, { "input": "Among them, compounds 15, 18, 19 and 30 showed significant affinity for 5 - HT1A and SERT.", "output": "There is no related enetity." }, { "input": "Computer docking simulations carried out for compounds 15, 31 and 32 to models of 5 - HT1A receptor and SERT confirm the results of biological tests.", "output": "There is no related enetity." }, { "input": "Due to high affinity for the 5 - HT1A receptor and moderate affinity for SERT, compounds 31, 32, 35, and 37 were evaluated for their affinity for D2L, 5 - HT6, 5 - HT7 and 5 - HT2A receptors.", "output": "There is no related enetity." }, { "input": "In vivo tests, in turn, resulted in determining the functional activity of compounds 15, 18, 19 and 30 to the 5 - HT1A receptor.", "output": "There is no related enetity." }, { "input": "The results of these tests indicate that all of the ligands possess properties characteristic of 5 - HT1A receptor agonists.", "output": "There is no related enetity." }, { "input": "Mild hyperthermia triggered doxorubicin release from optimized stealth thermosensitive liposomes improves intratumoral drug delivery and efficacy.", "output": "doxorubicin." }, { "input": "Liposome mediated anticancer drug delivery has the advantage of reducing cytotoxicity in healthy tissues.", "output": "There is no related enetity." }, { "input": "However, undesired slow drug release impedes the therapeutic efficacy of clinically applied PEG - liposomal doxorubicin ( Dox ).", "output": "PEG, doxorubicin, Dox." }, { "input": "The aim of this study is to combine stealth thermosensitive liposomes ( TSL ) and local mild hyperthermia ( HT ) to increase bioavailable Dox levels in tumors.", "output": "Dox." }, { "input": "Dox was encapsulated in stealth TSL ( ~ 80nm ) with optimized PEG concentration in the membrane, and compared with lysolipid - based Dox - LTSL for in vitro stability, release kinetics, and in vivo tumor growth control.", "output": "Dox, PEG, Dox." }, { "input": "In vitro cytotoxicity of Dox - TSL against murine BFS - 1 sarcoma and, human BLM melanoma cell lines and Human Umbilical Vein Endothelial Cells ( HUVEC ) under normothermia ( 37 degrees C ) and HT ( 42 degrees C ) was compared with non - encapsulated Dox.", "output": "Dox, Dox." }, { "input": "In vitro Dox uptake in nuclei was imaged in BLM and HUVEC.", "output": "Dox." }, { "input": "In vivo intravascular Dox release from TSL in BFS - 1 tumors under local mild HT in dorsal skin flap window chamber models was captured by intravital confocal microscopy.", "output": "Dox." }, { "input": "Intravascular Dox - TSL release kinetics, penetration depth and interstitial Dox density were subjected to quantitative image analysis.", "output": "Dox, Dox." }, { "input": "Systemic Dox - TSL administration in combination with local mild HT on subcutaneous tumor growth control was compared to Dox - LTSL plus local mild HT.", "output": "Dox, Dox." }, { "input": "Dox - TSL was stable at 37 degrees C, while released over 95 % Dox within 1min in 90 % serum at 42 degrees C.", "output": "Dox, Dox." }, { "input": "Dox - TSL demonstrated efficient in vivo intratumoral Dox release under local mild HT, followed by significant Dox uptake by tumor and tumor vascular endothelial cells.", "output": "Dox, Dox, Dox." }, { "input": "Dox - TSL plus mild HT showed improved tumor growth control over Dox - LTSL plus mild HT.", "output": "Dox, Dox." }, { "input": "Survival after a single treatment of Dox - TSL plus mild HT was 67 %, while survival after Dox - LTSL plus mild HT was 22 %.", "output": "Dox, Dox." }, { "input": "This combination of Dox - TSL and local mild HT offers promising clinical opportunities to improve liposomal Dox delivery to solid tumors.", "output": "Dox, Dox." }, { "input": "Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: Effective photoinduced in vitro killing of osteosarcoma.", "output": "porphyrin." }, { "input": "Mesenchymal stem cells ( MSC ) have the unique ability to home and engraft in tumor stroma.", "output": "There is no related enetity." }, { "input": "These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma.", "output": "There is no related enetity." }, { "input": "In the present study, we investigate whether fluorescent core - shell PMMA nanoparticles ( FNPs ) post - loaded with a photosensitizer, namely meso - tetrakis ( 4 - sulfonatophenyl ) porphyrin ( TPPS ) and uploaded by MSC could trigger osteosarcoma ( OS ) cell death in vitro upon specific photoactivation.", "output": "meso - tetrakis ( 4 - sulfonatophenyl ) porphyrin, TPPS." }, { "input": "In co - culture studies we demonstrate using laser confocal microscopy and time lapse imaging, that only after laser irradiation MSC loaded with photosensitizer - coated fluorescent NPs ( TPPS @ FNPs ) undergo cell death and release reactive oxygen species ( ROS ) which are sufficient to trigger cell death of all OS cells in the culture.", "output": "TPPS, oxygen." }, { "input": "These results encourage further studies aimed at proving the efficacy of this novel tri - component system for PDT applications.", "output": "There is no related enetity." }, { "input": "Compound promiscuity: what can we learn from current data?", "output": "There is no related enetity." }, { "input": "The specificity paradigm that assigns central relevance to achieving target specificity of drug candidates has recently been revisited.", "output": "There is no related enetity." }, { "input": "Evidence is mounting that polypharmacological drug behavior is often responsible for therapeutic efficacy suggesting the consideration of new drug development strategies.", "output": "There is no related enetity." }, { "input": "Target promiscuity of compounds is at the origin of polypharmacology.", "output": "There is no related enetity." }, { "input": "For many bioactive compounds, multiple target annotations are available indicating that compound promiscuity is a general phenomenon.", "output": "There is no related enetity." }, { "input": "However, careful analysis of compound activity data reveals that the degree of apparent promiscuity is strongly influenced by data selection criteria and the type of activity measurements that are considered.", "output": "There is no related enetity." }, { "input": "Furthermore, promiscuity involving unrelated targets is less common.", "output": "There is no related enetity." }, { "input": "Apparent target promiscuity might often better be interpreted as activity promiscuity in different assays.", "output": "There is no related enetity." }, { "input": "Cosmetics Europe multi - laboratory pre - validation of the SkinEthic (TM) reconstituted human corneal epithelium test method for the prediction of eye irritation.", "output": "There is no related enetity." }, { "input": "Cosmetics Europe, The Personal Care Association, known as Colipa before 2012, conducted a program of technology transfer and assessment of Within / Between Laboratory ( WLV / BLV ) reproducibility of the SkinEthic (TM) Reconstituted Human Corneal Epithelium ( HCE ) as one of two human reconstructed tissue eye irritation test methods.", "output": "There is no related enetity." }, { "input": "The SkinEthic (TM) HCE test method involves two exposure time treatment procedures - one for short time exposure ( 10min - SE ) and the other for long time exposure ( 60min - LE ) of tissues to test substance.", "output": "There is no related enetity." }, { "input": "This paper describes pre - validation studies of the SkinEthic (TM) HCE test method ( SE and LE protocols ) as well as the Eye Peptide Reactivity Assay ( EPRA ).", "output": "There is no related enetity." }, { "input": "In the SE WLV study, 30 substances were evaluated.", "output": "There is no related enetity." }, { "input": "A consistent outcome with respect to viability measurement across all runs was observed with all substances showing an SD of less than 18 %.", "output": "There is no related enetity." }, { "input": "In the LE WLV study, 44 out of 45 substances were consistently classified.", "output": "There is no related enetity." }, { "input": "These data demonstrated a high level of reproducibility within laboratory for both the SE and LE treatment procedures.", "output": "There is no related enetity." }, { "input": "For the LE BLV, 19 out of 20 substances were consistently classified between the three laboratories, again demonstrating a high level of reproducibility between laboratories.", "output": "There is no related enetity." }, { "input": "The results for EPRA WLV and BLV studies demonstrated that all substances analysed were categorised similarly and that the method is reproducible.", "output": "There is no related enetity." }, { "input": "The SkinEthic (TM) HCE test method entered into the experimental phase of a formal ECVAM validation program in 2010.", "output": "There is no related enetity." }, { "input": "Mechanochemical activation of vincamine mediated by linear polymers: Assessment of some \" critical \" steps.", "output": "vincamine." }, { "input": "The aim of the research was to investigate three \" critical steps \" that deserve particular attention during the mechanochemical activation of vincamine.", "output": "vincamine." }, { "input": "The first step consisted in the selection of the best polymeric carrier / most affine stabiliser between linear PVP and NaCMC by using the GRID and the GRID based AutoDock software packages which permit to calculate their surface features and interactions.", "output": "PVP." }, { "input": "Moreover, the calculation of the partial and total solubility parameters supported the results obtained by GRID and AutoDock software.", "output": "There is no related enetity." }, { "input": "Then, after the selection of linear PVP - K30 as the suitable carrier, the influence of process and formulation variables on the amorphisation degree and solubility enhancement was studied, to select the most suitable process conditions and formulation parameters.", "output": "PVP - K30." }, { "input": "Subsequently, the best performing samples were widely characterised using XRPD, TEM and SSNMR ( including the proton relaxation ( ( 1 ) H T1 NMR ) time ) techniques.", "output": "( 1 ) H." }, { "input": "These studies highlighted that all the coground samples were nanocrystalline solid dispersions indicating a dramatic difference between the amorphisation capacities of linear PVP - K30 and cross - linked PVP, used in previous analogous experiences.", "output": "PVP - K30, PVP." }, { "input": "In particular, ( 13 ) C, ( 15 ) N and ( 1 ) H T1 NMR data point to a description of the system as a dispersion of nanocrystals in the polymer.", "output": "( 13 ) C, ( 15 ) N, ( 1 ) H." }, { "input": "In these dispersions vincamine is in a disordered crystalline state due to extensive interactions and contacts with PVP - K30 but the main hydrogen bonding motif characterising its packing remains.", "output": "vincamine, PVP - K30, hydrogen." }, { "input": "Again, differently from cross - linked PVP, dissolution studies revealed that linear PVP - K30 was able to promote a complete in vitro solubilisation of vincamine in some coground samples.", "output": "PVP, PVP - K30, vincamine." }, { "input": "What is more important, by using a linear polymer, drug - to - polymer and milling time variables appeared less influent on the solid state and in vitro properties of the composites.", "output": "There is no related enetity." }, { "input": "Finally, stability studies conducted for a period of 1year highlighted the high physical stability of the selected samples.", "output": "There is no related enetity." }, { "input": "Binding pattern and toxicological effects of lectins from genus Canavalia on bovine sperm.", "output": "There is no related enetity." }, { "input": "The aim of this study was to determine the binding patterns of Canavalia ensiformis ( ConA ), Canavalia boliviana ( ConBol ) and Canavalia brasiliensis ( ConBr ) lectins to bovine sperm and their effects on sperm motility, viability, lipid peroxidation, reactive oxygen species production and fertilization ability.", "output": "oxygen." }, { "input": "ConA bound to whole spermatozoa, with the exception of the equatorial segment, ConBol did not interact with the acrosome region and ConBr exhibited a fragmented binding pattern.", "output": "There is no related enetity." }, { "input": "The three lectins decreased sperm motility but did not affect cell viability or lipid peroxidation.", "output": "There is no related enetity." }, { "input": "Nevertheless, ROS production was increased in comparison to controls and a reduction in the cleavage and blastocyst ratio was induced in comparison to controls.", "output": "There is no related enetity." }, { "input": "In conclusion, this study determined that structurally similar lectins interact differently with bovine sperm and affect sperm motility, viability, lipid peroxidation, ROS production and fertilization ability in various ways.", "output": "There is no related enetity." }, { "input": "Selective class IIa histone deacetylase inhibition via a nonchelating zinc - binding group.", "output": "zinc." }, { "input": "In contrast to studies on class I histone deacetylase ( HDAC ) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs ( HDAC4, HDAC5, HDAC7 and HDAC9 ) is impaired by the lack of potent and selective chemical probes.", "output": "There is no related enetity." }, { "input": "Here we report the discovery of inhibitors that fill this void with an unprecedented metal - binding group, trifluoromethyloxadiazole ( TFMO ), which circumvents the selectivity and pharmacologic liabilities of hydroxamates.", "output": "trifluoromethyloxadiazole, TFMO, hydroxamates." }, { "input": "We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate - substituted analog.", "output": "TFMO, TFMO, hydroxamate." }, { "input": "We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs.", "output": "There is no related enetity." }, { "input": "The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal - binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors.", "output": "There is no related enetity." }, { "input": "A 3D - RISM - SCF method with dual solvent boxes for a highly polarized system: application to 1, 6 - anhydrosugar formation reaction of phenyl alpha - and beta - d - glucosides under basic conditions.", "output": "1 , 6 - anhydrosugar, phenyl alpha - and beta - d - glucosides." }, { "input": "One of the difficulties in application of the usual reference interaction site model self - consistent field ( RISM - SCF ) method to a highly polarized and bulky system arises from the approximate evaluation of electrostatic potential ( ESP ) with pure point charges.", "output": "There is no related enetity." }, { "input": "To improve this ESP evaluation, the ESP near a solute is directly calculated with a solute electronic wavefunction, that distant from a solute is approximately calculated with solute point charges, and they are connected with a switching function.", "output": "There is no related enetity." }, { "input": "To evaluate the fine solvation structure near the solute by incorporating the long - range solute - solvent Coulombic interaction with low computational cost, we introduced the dual solvent box protocol; one small box with the fine spacing is employed for the first and the second solvation shells and the other large box with the normal spacing is employed for long - range solute - solvent interaction.", "output": "There is no related enetity." }, { "input": "The levoglucosan formation from phenyl alpha - and beta - d - glucosides under basic conditions is successfully inspected by this 3D - RISM - SCF method at the MP2 and SCS - MP2 levels, though the 1D - RISM - SCF could not be applied to this reaction due to the presence of highly polarized and bulky species.", "output": "levoglucosan, phenyl alpha - and beta - d - glucosides." }, { "input": "This 3D - RISM - SCF calculation reproduces the experimentally reported higher reactivity of the beta - anomer.", "output": "There is no related enetity." }, { "input": "The 3D - RISM - SCF - calculated activation free energy for the beta - anomer is closer to the experimental value than the PCM - calculated one.", "output": "There is no related enetity." }, { "input": "Interestingly, the solvation effect increases the difference in reactivity between these two anomers.", "output": "There is no related enetity." }, { "input": "The reason is successfully elucidated with 3D - RISM - SCF - calculated microscopic solvation structure and decomposition analysis of solute - solvent interaction.", "output": "There is no related enetity." }, { "input": "Nuclear Factor kappa B Mediates Suppression of Canonical Transient Receptor Potential 6 Expression by Reactive Oxygen Species and Protein Kinase C in Kidney Cells.", "output": "Oxygen." }, { "input": "This study was carried out to explore the molecular mechanism for down - regulation of TRPC6 expression in the reactive oxygen species ( ROS ) / PKC signaling in kidney cells.", "output": "oxygen." }, { "input": "In cultured human mesangial cells, H2O2 and TNF - alpha inhibited TRPC6 mRNA expression in a time - dependent manner.", "output": "H2O2." }, { "input": "Inhibition of NF - kappa B reversed both H2O2 - and phorbol 12 - myristate 13 - acetate ( PMA ) - induced decrease in TRPC6 protein expression.", "output": "H2O2, phorbol 12 - myristate 13 - acetate, PMA." }, { "input": "Activation of NF - kappa B by knocking down I kappa B alpha using siRNA could mimic the suppressive effect of ROS / PKC on TRPC6.", "output": "There is no related enetity." }, { "input": "a Ca ( 2 + ) imaging study showed that activation and inhibition of NF - kappa B significantly decreased and increased the TRPC6 - mediated Ca ( 2 + ) entry, respectively.", "output": "Ca ( 2 + ), Ca ( 2 + )." }, { "input": "Further experiments showed that PMA, but not its inactive analog 4 alpha - phorbol 12, 13 - didecanoate ( 4 alpha - PDD ), caused phosphorylation of I kappa B alpha and stimulated the nuclear translocation of NF - kappa B p50 and p65 subunits.", "output": "PMA, 4 alpha - phorbol 12 , 13 - didecanoate, 4 alpha - PDD." }, { "input": "The PMA - dependent I kappa B alpha phosphorylation was significantly inhibited by G o 6976.", "output": "PMA, G o 6976." }, { "input": "Electrophoretic mobility shift assay revealed that PMA stimulated DNA binding activity of NF - kappa B.", "output": "PMA." }, { "input": "Furthermore, specific knockdown of p65, but not p50, prevented an H2O2 inhibitory effect on TRPC6 protein expression, suggesting p65 as a predominant NF - kappa B subunit repressing TRPC6.", "output": "H2O2." }, { "input": "In agreement with a major role of p65, chromatin immunoprecipitation assays showed that PMA treatment induced p65 binding to the TRPC6 promoter.", "output": "PMA." }, { "input": "Moreover, PMA treatment increased the association of p65 with histone deacetylase ( HDAC ) and decreased histone acetylation at the TRPC6 promoter.", "output": "PMA." }, { "input": "Consistently, knockdown of HDAC2 by siRNA or inhibition of HDAC with trichostatin A prevented a H2O2 - induced decrease in TRPC6 mRNA and protein expressions, respectively.", "output": "trichostatin A, H2O2." }, { "input": "Taken together, our findings imply an important role of NF - kappa B in a negative regulation of TRPC6 expression at the gene transcription level in kidney cells.", "output": "There is no related enetity." }, { "input": "Single - molecule surface - enhanced Raman spectroscopy: a perspective on the current status.", "output": "There is no related enetity." }, { "input": "This perspective presents an overview of single - molecule surface - enhanced Raman scattering ( sm - SERS ).", "output": "There is no related enetity." }, { "input": "Our overview is organized as a brief theoretical background, discussion of the factors that enhance SERS, various experimental preparations for inserting a single molecule in a hot spot, recent sm - SERS experiments, and a perspective.", "output": "There is no related enetity." }, { "input": "Although, there have been numerous review papers on sm - SERS, we mainly concentrated on the logical development of sm - SERS on the basis of the fundamental concepts and their physical significance, so that readers outside this field can understand the motivation and the underlying physics when describing current sm - SERS measurements.", "output": "There is no related enetity." }, { "input": "Indeed, understanding such current sm - SERS experiments conducted by representative groups would be very helpful for readers to answer for themselves the fundamental and practical questions surrounding sm - SERS: ( 1 ) what information can sm - SERS provide?", "output": "There is no related enetity." }, { "input": "( 2 ) Which factors based on the SERS mechanism should be considered to significantly amplify the SERS signal?", "output": "There is no related enetity." }, { "input": "( 3 ) What kinds of related microscopy techniques could be combined with sm - SERS to attain more meaningful results?", "output": "There is no related enetity." }, { "input": "( 4 ) Which statistical approaches can be used and how they can be applied to properly analyze sm - SERS data?", "output": "There is no related enetity." }, { "input": "We hope that this review article can help readers answer these questions.", "output": "There is no related enetity." }, { "input": "NMR characterisation of dynamics in solvates and desolvates of formoterol fumarate.", "output": "formoterol fumarate." }, { "input": "Solid - state NMR is used to characterise dynamics in the ethanol solvate of the pharmaceutical material formoterol fumarate and its associated desolvate.", "output": "ethanol, formoterol fumarate." }, { "input": "Jump rates and activation barriers for dynamic processes such as phenyl ring rotation and methyl group rotational diffusion are derived from 1D - EXSY and ( 13 ) C spin - lattice relaxation times respectively.", "output": "phenyl, methyl, ( 13 ) C." }, { "input": "( 2 ) H and ( 13 ) C spin - lattice relaxation times measured under magic - angle spinning conditions are used to show that the fumarate ion in the desolvate is undergoing small - amplitude motion on a frequency scale of 100s of MHz at ambient temperature with an activation parameter of about 32 kJ mol ( - 1 ).", "output": "( 2 ) H, ( 13 ) C, fumarate." }, { "input": "Exact calculations of relaxation times under MAS provide a simple and robust means to test motional models in cases where relaxation rate maxima are observed, including for systems where the crystal structure of the material is unknown.", "output": "There is no related enetity." }, { "input": "Two populations of glucocorticoid receptor - binding sites in the male rat hippocampal genome.", "output": "There is no related enetity." }, { "input": "In the present study, genomic binding sites of glucocorticoid receptors ( GR ) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next - generation sequencing.", "output": "There is no related enetity." }, { "input": "We identified 2470 significant GR - binding sites ( GBS ) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values.", "output": "There is no related enetity." }, { "input": "Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS.", "output": "There is no related enetity." }, { "input": "Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS.", "output": "There is no related enetity." }, { "input": "Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone ( CORT ) ranging from 3 to 3000 mu g / kg, resulting in clear differences in the GR - binding profile to individual GBS.", "output": "corticosterone, CORT." }, { "input": "Two groups of GBS could be distinguished: a low - CORT group that displayed GR binding across the full range of CORT concentrations, and a second high - CORT group that displayed significant GR binding only after administering the highest concentration of CORT.", "output": "CORT, CORT, CORT, CORT." }, { "input": "All validated GBS, in both the low - CORT and high - CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 mu g / kg CORT upward.", "output": "CORT, CORT, CORT." }, { "input": "Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature.", "output": "There is no related enetity." }, { "input": "In addition, motifs corresponding with new potential GR - interacting proteins were identified, such as zinc finger and BTB domain containing 3 ( Zbtb3 ) and CUP ( CG11181 gene product from transcript CG11181 - RB ), which may be involved in GR - dependent transactivation and transrepression, respectively.", "output": "zinc." }, { "input": "In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.", "output": "There is no related enetity." }, { "input": "State - Dependent Etomidate Occupancy of its Allosteric Agonist Sites Measured in a Cysteine - Substituted GABAA Receptor.", "output": "Cysteine." }, { "input": "A central axiom of ligand - receptor theory is that agonists bind more tightly to active than to inactive receptors.", "output": "There is no related enetity." }, { "input": "However, measuring agonist affinity in inactive receptors is confounded by concomitant activation.", "output": "There is no related enetity." }, { "input": "We identified a cysteine substituted mutant GABAA receptor with unique characteristics allowing determination of allosteric agonist site occupancy in both inactive and active receptors.", "output": "cysteine." }, { "input": "Etomidate, the allosteric agonist, is an anesthetic that activates / modulates alpha 1 beta 2 gamma 2L GABAA receptors via transmembrane sites near beta 2M286 residues in M3 domains.", "output": "Etomidate." }, { "input": "Voltage - clamp electrophysiology studies of alpha 1 beta 2M286C gamma 2L receptors show that GABA is an efficacious agonist, and etomidate modulates GABA - activated activity, but direct etomidate agonism is absent.", "output": "GABA, etomidate, GABA, etomidate." }, { "input": "Quantitative analysis of mutant activity using an established Monod - Wyman - Changeux ( MWC ) allosteric model indicates that the intrinsic efficacy of etomidate, defined as its relative affinity for active vs. inactive receptors, is lower than in wild - type receptors.", "output": "etomidate." }, { "input": "Para - chloromercuribenzene sulfonate ( pCMBS ) covalently modifies beta 2M286C sidechain sulfhydryls, irreversibly altering GABA - induced currents.", "output": "Para - chloromercuribenzene sulfonate, pCMBS, sulfhydryls, GABA." }, { "input": "Etomidate concentration - dependently reduces the apparent rate of beta 2M286C - pCMBS bond formation, tracked electrophysiologically.", "output": "Etomidate." }, { "input": "High etomidate concentrations completely protect the beta 2M286C suflhydryl from covalent modification, suggesting close steric interactions.", "output": "etomidate, suflhydryl." }, { "input": "The 50 % protective etomidate concentration ( PC50 ) is 14 mu M in inactive receptors and 1. 1 to 2. 2 mu M during GABA - activation, experimentally demonstrating that activated receptors bind etomidate more avidly than inactive receptors.", "output": "etomidate, GABA, etomidate." }, { "input": "The experimental PC50 values are remarkably close to, and therefore validate MWC model predictions for etomidate dissociation constants in both inactive and active receptors.", "output": "etomidate." }, { "input": "Our results support MWC models as valid frameworks for understanding agonism, co - agonism, and modulation of ligand - gated ion channels.", "output": "There is no related enetity." }, { "input": "The nuclear receptors COUP - TF: a long - lasting experience in forebrain assembly.", "output": "There is no related enetity." }, { "input": "Chicken ovalbumin upstream promoter transcription factors ( COUP - TFs ) are nuclear receptors belonging to the superfamily of the steroid / thyroid hormone receptors.", "output": "steroid." }, { "input": "Members of this family are internalized to the nucleus both in a ligand - dependent or - independent manner and act as strong transcriptional regulators by binding to the DNA of their target genes.", "output": "There is no related enetity." }, { "input": "COUP - TFs are defined as orphan receptors, since ligands regulating their activity have not so far been identified.", "output": "There is no related enetity." }, { "input": "From the very beginning of metazoan evolution, these molecules have been involved in various key events during embryonic development and organogenesis.", "output": "There is no related enetity." }, { "input": "In this review, we will mainly focus on their function during development and maturation of the central nervous system, which has been well characterized in various animal classes ranging from ctenophores to mammals.", "output": "There is no related enetity." }, { "input": "We will start by introducing the current knowledge on COUP - TF mechanisms of action and then focus our discussion on the crucial processes underlying forebrain ontogenesis, with special emphasis on mammalian development.", "output": "There is no related enetity." }, { "input": "Finally, the conserved roles of COUP - TFs along phylogenesis will be highlighted, and some hypotheses, worth exploring in future years to gain more insight into the mechanisms controlled by these factors, will be proposed.", "output": "There is no related enetity." }, { "input": "Cavitation during tensile deformation of isothermally crystallized polypropylene and high - density polyethylene.", "output": "polypropylene, polyethylene." }, { "input": "The cavitation phenomenon was studied in isothermally and non - isothermally crystallized polypropylene and high - density polyethylene.", "output": "polypropylene, polyethylene." }, { "input": "It was found that nano - voids were not present in the crystallized samples, but were formed during their tensile deformation.", "output": "There is no related enetity." }, { "input": "The process of cavitation was initiated before reaching the yield point.", "output": "There is no related enetity." }, { "input": "The ellipsoidal voids were initially elongated perpendicularly to the deformation direction, but if the polymer ( i. e., high - density polyethylene ) was able to deform beyond the yield, then the reorientation of voids into the deformation direction was observed at local strains of 100 - 200 %.", "output": "polyethylene." }, { "input": "This behavior was similar to that observed previously in the samples crystallized without an exact control of solidification conditions.", "output": "There is no related enetity." }, { "input": "The calculations of Guinier ' s radius showed that voids in deformed polypropylene samples were characterized by the gyration radii of 28 - 50 nm.", "output": "polypropylene." }, { "input": "Smaller voids were observed in polyethylene.", "output": "polyethylene." }, { "input": "The scale of cavitation during deformation, studied on the example of polyethylene, depended on the preceding crystallization process and was most intensive for the specimens crystallized at the highest temperature of 125 degrees C.", "output": "polyethylene." }, { "input": "Combinatorial Design of Hydrolytically Degradable, Bone - like Biocomposites Based on PHEMA and Hydroxyapatite.", "output": "PHEMA, Hydroxyapatite." }, { "input": "With advantages such as design flexibility in modifying degradation, surface chemistry, and topography, synthetic bone - graft substitutes are increasingly demanded in orthopedic tissue engineering to meet various requirements in the growing numbers of cases of skeletal impairment worldwide.", "output": "There is no related enetity." }, { "input": "Using a combinatorial approach, we developed a series of biocompatible, hydrolytically degradable, elastomeric, bone - like biocomposites, comprising 60 wt % poly ( 2 - hydroxyethyl methacrylate - co - methacrylic acid ), poly ( HEMA - co - MA ), and 40 wt % bioceramic hydroxyapatite ( HA ).", "output": "poly ( 2 - hydroxyethyl methacrylate - co - methacrylic acid ), poly ( HEMA - co - MA ), hydroxyapatite." }, { "input": "Hydrolytic degradation of the biocomposites is rendered by a degradable macromer / crosslinker, dimethacrylated poly ( lactide - b - ethylene glycol - b - lactide ), which first degrades to break up 3 - D hydrogel networks, followed by dissolution of linear pHEMA macromolecules and bioceramic particles.", "output": "dimethacrylated poly ( lactide - b - ethylene glycol - b - lactide ), pHEMA." }, { "input": "Swelling and degradation were examined at Hank ' s balanced salt solution at 37 degrees C in a 12 - week period of time.", "output": "There is no related enetity." }, { "input": "The degradation is strongly modulated by altering the concentration of the co - monomer of methacrylic acid and of the macromer, and chain length / molecular weight of the macromer.", "output": "methacrylic acid." }, { "input": "95 % weight loss in mass is achieved after degradation for 12 weeks in a composition consisting of HEMA / MA / Macromer = 0 / 60 / 40, while 90 % weight loss is seen after degradation only for 4 weeks in a composition composed of HEMA / MA / Macromer = 27 / 13 / 60 using a longer chain macromer.", "output": "HEMA, HEMA." }, { "input": "For compositions without a co - monomer, only about 14 % is achieved in weight loss after 12 - week degradation.", "output": "There is no related enetity." }, { "input": "These novel biomaterials offer numerous possibilities as drug delivery carriers and bone grafts particularly for low and medium load - bearing applications.", "output": "There is no related enetity." }, { "input": "Chemical genetic analyses of quantitative changes in Cdk1 activity during the human cell cycle.", "output": "There is no related enetity." }, { "input": "Cyclin - dependent kinase 1 ( Cdk1 ) controls cell proliferation and is inhibited by promising anticancer agents, but its mode of action and the consequences of its inhibition are incompletely understood.", "output": "There is no related enetity." }, { "input": "Cdk1 promotes S - and M - phases during the cell - cycle but also suppresses endoreduplication, which is associated with polyploidy and genome instability.", "output": "There is no related enetity." }, { "input": "The complexity of Cdk1 regulation has made it difficult to determine whether these different roles require different thresholds of kinase activity and whether the surge of activity as inhibitory phosphates are removed at mitotic onset is essential for cell proliferation.", "output": "phosphates." }, { "input": "Here, we have used chemical genetics in a human cell line to address these issues.", "output": "There is no related enetity." }, { "input": "We rescued cells lethally depleted of endogenous Cdk1 with an exogenous Cdk1 conferring sensitivity to one ATP analogue inhibitor ( 1NMPP1 ) and resistance to another ( RO3306 ).", "output": "ATP, 1NMPP1, RO3306." }, { "input": "At no 1NMPP1 concentration was mitosis in rescued clones prevented without also inducing endoreduplication, suggesting that these two key roles for Cdk1 are not simply controlled by different Cdk1 activity thresholds.", "output": "1NMPP1." }, { "input": "We also rescued RO3306 - resistant clones using exogenous Cdk1 without inhibitory phosphorylation sites, indicating that the mitotic surge of Cdk1 activity is dispensable for cell proliferation.", "output": "RO3306." }, { "input": "These results suggest that the basic mammalian cycle requires at least some qualitative changes in Cdk1 activity and that quantitative increases in activity need not be rapid.", "output": "There is no related enetity." }, { "input": "Furthermore, the viability of cells that are unable to undergo rapid Cdk1 activation, and the strong association between endoreduplication and impaired proliferation, may place restrictions on the therapeutic use of a Cdk1 inhibitors.", "output": "There is no related enetity." }, { "input": "Serum trace elements levels in preeclampsia and eclampsia: correlation with the pregnancy disorder.", "output": "There is no related enetity." }, { "input": "Preeclampsia and eclampsia are fatal medical complications of pregnancy accounting for 20 - 80 % of increased maternal death in developing countries.", "output": "There is no related enetity." }, { "input": "Their aetiologies are still under investigation.", "output": "There is no related enetity." }, { "input": "Serum trace elements have been suggested to be involved in the pathogenesis of preeclampsia.", "output": "There is no related enetity." }, { "input": "Aim of this study was to address the correlation of serum trace elements with preeclampsia and eclampsia.", "output": "There is no related enetity." }, { "input": "It was a comparative cross - sectional study conducted on conveniently recruited 44 preeclampsia, 33 eclampsia and 27 normotensive pregnant patients.", "output": "There is no related enetity." }, { "input": "Atomic absorption spectrometry was employed to analyse serum concentrations of Ca, Mg, Cu, Zn and Fe.", "output": "Ca, Mg, Cu, Zn, Fe." }, { "input": "Data were analysed by Student ' s t test, one - way analysis of variance and multinomial logistic and binary regression analyses.", "output": "There is no related enetity." }, { "input": "p < 0. 05 was considered as a level of significance.", "output": "There is no related enetity." }, { "input": "In preeclampsia, the serum Ca and Mg were significantly lower than those in eclampsia, while Cu and Zn values were higher.", "output": "Ca, Mg, Cu, Zn." }, { "input": "Significant changes of Ca, Mg and Cu were noted among preeclampsia, eclampsia and pregnant control.", "output": "Ca, Mg, Cu." }, { "input": "Serum Ca and Mg indicated a positive association, and Cu gave a negative association in preeclampsia.", "output": "Ca, Mg, Cu." }, { "input": "Cu / Fe ratio was high in eclampsia.", "output": "Cu, Fe." }, { "input": "Significant correlations of Mg with Zn in eclampsia and Mg with Fe in preeclampsia and eclampsia were predicted.", "output": "Mg, Zn, Mg, Fe." }, { "input": "Significant changes in serum trace element levels were present in preeclampsia and eclampsia that may have a link with the pathogenesis of pregnancy disorder.", "output": "There is no related enetity." }, { "input": "Blood Flow of the Acral Finger Arterioles in Patients With Type 2 Diabetes by Quality Doppler Profiles.", "output": "There is no related enetity." }, { "input": "Patients with diabetes mellitus exhibit peripheral arterioles lesions that is associated with reduced blood flow.", "output": "There is no related enetity." }, { "input": "Here, we intended to assess the acral arterioles lesion in patients with type 2 diabetes based on the rate of blood flow by multigate spectral Doppler ultrasonography.", "output": "There is no related enetity." }, { "input": "Fifty - two patients with type 2 DM were divided into two groups.", "output": "There is no related enetity." }, { "input": "Group 1 included 13 men and 12 women with an average age of 60. 60 +/- 14. 03 years and a duration of type 2 diabetes for 2. 44 +/- 1. 50 years.", "output": "There is no related enetity." }, { "input": "Group 2 included 17 men and 11 women with an average age of 64. 25 +/- 10. 84 years and type 2 diabetes for 12. 57 +/- 6. 26 years.", "output": "There is no related enetity." }, { "input": "Age - matched control subjects ( n = 52 ) were recruited ( 30 men and 22 woman, mean age of 61. 19 +/- 10. 38 years ).", "output": "There is no related enetity." }, { "input": "A multigate spectral Doppler algorithm was applied to the acral finger of the thumb of the right hand to test the arteriole diameter and hemodynamic parameters, including diameter of the acral finger arterioles ( D ), area of the blood flow profile of the acral finger arterioles ( A max ) and hemodynamic parameters.", "output": "There is no related enetity." }, { "input": "Patients with diabetes exhibited a significant reduction in the arteriole diameter ( 1. 63 +/- 0. 18 and 1. 57 +/- 0. 22 mm, respectively, P < 0. 001 for both ) compared to control subjects ( 2. 09 +/- 0. 17 mm ).", "output": "There is no related enetity." }, { "input": "A max were significantly reduced in patients with diabetes ( 61. 35 +/- 10. 66 mm ( 2 ) / s for group 1 and 46. 50 +/- 6. 59 mm ( 2 ) / s for group 2, P < 0. 001 for both ) compared to that in control subjects ( 77. 93 +/- 12. 37 mm ( 2 ) / s ).", "output": "There is no related enetity." }, { "input": "Furthermore, a significant difference in Amax was found between group 1 and group 2 ( P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "The vascular resistance index ( RI ) was significantly higher in both patient groups 0. 58 +/- 0. 06 for group 1 ( P < 0. 001 ) and 0. 64 +/- 0. 07 for group 2 ( P < 0. 001 ) than that in control subjects ( 0. 48 +/- 0. 04 ).", "output": "There is no related enetity." }, { "input": "The RI value of the acral finger arterioles differed significantly between group 1 and group 2 ( P < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Diabetic patients exhibited a weak blood flow in the acral finger arterioles.", "output": "There is no related enetity." }, { "input": "The multigate spectral Doppler technology can be used to test blood flow in the acral finger arterioles and provide hemodynamic data for systematic analyses of the peripheral arteriole lesions in diabetes.", "output": "There is no related enetity." }, { "input": "Alkaloids from Lycoris caldwellii and their particular cytotoxicities against the astrocytoma and glioma cell lines.", "output": "There is no related enetity." }, { "input": "Phytochemical investigation of the ethanol extract of the bulbs of Lycoris caldwellii afforded four new alkaloids, ( + ) - N - methoxylcarbonyl - nandigerine ( 1 ), ( + ) - N - methoxycarbonyl - lindcarpine ( 2 ), ( + ) - 10 - O - methylhernovine N - oxide ( 3 ), and ( + ) - 3 - hydroxy - anhydrolycorine N - oxide ( 4 ).", "output": "ethanol, ( + ) - N - methoxylcarbonyl - nandigerine, ( + ) - N - methoxycarbonyl - lindcarpine, ( + ) - 10 - O - methylhernovine N - oxide, ( + ) - 3 - hydroxy - anhydrolycorine N - oxide." }, { "input": "Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ( ( 1 ) H - ( 1 ) H COSY, HMQC, and HMBC ) NMR spectroscopy, in addition to high resolution mass spectrometry.", "output": "( 1 ) H, ( 1 ) H." }, { "input": "All the alkaloids were in vitro evaluated for their cytotoxic activities against eight tumor cell lines ( BEN - MEN - 1, CCF - STTG1, CHG - 5, SHG - 44, U251, BGC - 823, HepG2, and SK - OV - 3 ).", "output": "There is no related enetity." }, { "input": "Alkaloids 1 and 2 exhibited particular cytotoxic activities against astrocytoma and glioma cell lines with IC50 of 9. 2 - 11. 3 mu M and 10. 4 - 12. 2 mu M respectively.", "output": "There is no related enetity." }, { "input": "Discovery of a Series of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion.", "output": "Thiazole." }, { "input": "Effective inhibitors of cancer cell migration and invasion can potentially lead to clinical applications as therapy to block tumor metastasis, the primary cause of death in cancer patients.", "output": "There is no related enetity." }, { "input": "To this end we have designed and synthesized a series of thiazole derivatives that showed potent efficacy against cell migration and invasion in metastatic cancer cells.", "output": "thiazole." }, { "input": "The most effective compound, 5k, was found to have an IC50 value of 176 nM in the dose - dependent transwell migration assays in MDA - MB - 231cells.", "output": "There is no related enetity." }, { "input": "At the dose of 10 mu M, 5k also blocked about 80 % of migration in HeLa and A549 cells and 60 % of invasion of MDA - MB - 231 cells.", "output": "There is no related enetity." }, { "input": "Importantly, the majority of the derivatives exhibited no apparent cytotoxicity in the clonogenic assays.", "output": "There is no related enetity." }, { "input": "The low to negligible inhibition of cell proliferation is a desirable property of these anti - migration derivatives because they hold promise of low toxicity to healthy cells as potential therapeutic agents.", "output": "There is no related enetity." }, { "input": "Mechanistic studies analyzing the actin cytoskeleton by microscopy demonstrate that compound 5k substantially reduced cellular f - actin, and prevented localization of fascin to actin - rich membrane protrusions.", "output": "There is no related enetity." }, { "input": "These results suggest that the anti - migration activity may result from impaired actin structures in protrusions that are necessary to drive migration.", "output": "There is no related enetity." }, { "input": "Recent Advances in Metal - Organic Framework - Based Mixed Matrix Membranes.", "output": "There is no related enetity." }, { "input": "Mixed matrix membranes ( MMMs ) combine easy processability and low cost of polymers with the high selectivity of nanoporous filler particles.", "output": "There is no related enetity." }, { "input": "These membranes represent an important avenue for enhancing the performance of polymeric membranes in gas separations.", "output": "There is no related enetity." }, { "input": "Recently, a new group of nanoporous materials called metal - organic frameworks ( MOFs ) have been used as filler particles in MMM applications, and significant improvements in gas selectivity and permeability have been reported for these MOF - based membranes.", "output": "There is no related enetity." }, { "input": "We discuss the recent developments in MOF - based MMMs by reviewing both the experimental studies and computational modeling methods that can accelerate selection of MOF / polymer combinations for high - performance gas separations.", "output": "There is no related enetity." }, { "input": "Acute Kidney Injury During Vancomycin Therapy in Critically Ill Children.", "output": "Vancomycin." }, { "input": "STUDY OBJECTIVE: To determine the rate, risk factors, and outcome of vancomycin - associated acute kidney injury ( AKI ) in critically ill children.", "output": "vancomycin." }, { "input": "DESIGN: Retrospective cohort study.", "output": "There is no related enetity." }, { "input": "SETTING: Tertiary care children ' s hospital.", "output": "There is no related enetity." }, { "input": "PATIENTS: We reviewed the charts of children admitted to the pediatric intensive care unit during a 2 - year period who were treated with vancomycin.", "output": "vancomycin." }, { "input": "Courses of vancomycin interrupted by 3 days or more were counted separately.", "output": "vancomycin." }, { "input": "Patients were excluded if they received vancomycin treatment for fewer than 3 days, had preexisting renal failure, or had incomplete serum creatinine ( Scr ) data.", "output": "vancomycin, creatinine." }, { "input": "MEASUREMENTS AND MAIN RESULTS: Demographic and laboratory data; vancomycin dose, duration, and concentrations; and concurrent use of nephrotoxic drugs were recorded.", "output": "vancomycin." }, { "input": "Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50 % or more from the beginning of vancomycin therapy.", "output": "vancomycin." }, { "input": "Descriptive statistics, step - wise logistic regression, and repeated measures ANOVA were used to analyze the data.", "output": "There is no related enetity." }, { "input": "A total of 284 patients were included, for a total of 391 courses of vancomycin ( 272 children and 119 infants ).", "output": "vancomycin." }, { "input": "The mean duration of vancomycin therapy was 6. 9 +/- 4. 5 days.", "output": "vancomycin." }, { "input": "Forty nine ( 17. 2 % ) patients developed AKI during 61 ( 15. 6 % ) courses.", "output": "There is no related enetity." }, { "input": "Elevated Scr concentrations returned to baseline after stopping vancomycin in 53 ( 87 % ) courses.", "output": "vancomycin." }, { "input": "Mortality was higher in children who developed AKI ( p < 0. 001; Fisher ' s exact test ).", "output": "There is no related enetity." }, { "input": "Administration of nephrotoxic drugs ( odds ratio 2. 23, Confidence Interval 1. 27 - 3. 93 ) and presence of high blood urea nitrogen ( BUN ): Scr ratio before vancomycin therapy ( p < 0. 05 ) were associated with AKI.", "output": "urea, nitrogen, vancomycin." }, { "input": "The BUN and Scr concentrations significantly increased during vancomycin therapy and decreased after vancomycin was discontinued ( p < 0. 05 ).", "output": "vancomycin, vancomycin." }, { "input": "CONCLUSIONS: In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio.", "output": "vancomycin." }, { "input": "The Mechanisms of Radical SAM / Cobalamin Methylations: An Evolving Working Hypothesis.", "output": "Cobalamin." }, { "input": "All about Me: Pierre and co - workers have revealed mechanistic details of a tryptophan methyltransferase ( TsrM ) involved in the biosynthesis of the thiopeptide antibiotic, thiostrepton.", "output": "tryptophan, thiostrepton." }, { "input": "Utilising cobalamin and a [ 4Fe - 4S ] cluster to generate 2 - methyltryptophan from tryptophan, a key difference between this enzyme and other radical SAM methyltransferases is that the reaction is not initiated by a single - electron reduction of SAM to generate 5 ' - dA..", "output": "cobalamin, 4Fe - 4S, 2 - methyltryptophan, tryptophan." }, { "input": "tert - Butylcarbamate - Containing Histone Deacetylase Inhibitors: Apoptosis Induction, Cytodifferentiation, and Antiproliferative Activities in Cancer Cells.", "output": "tert - Butylcarbamate." }, { "input": "Herein we report novel pyrrole - and benzene - based hydroxamates ( 8, 10 ) and 2 ' - aminoanilides ( 9, 11 ) bearing the tert - butylcarbamate group at the CAP moiety as histone deacetylase ( HDAC ) inhibitors.", "output": "pyrrole, benzene, hydroxamates, 2 ' - aminoanilides, tert - butylcarbamate." }, { "input": "Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl - alpha - tubulin levels in human acute myeloid leukemia U937 cells.", "output": "hydroxamates." }, { "input": "In the same cell line, compounds 8 b and 10 c elicited 18. 4 and 21. 4 % apoptosis, respectively ( SAHA: 16. 9 % ), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect ( 90. 9 % ).", "output": "SAHA, pyrrole anilide." }, { "input": "In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub - micromolar ( neuroblastoma LAN - 5 and SH - SY5Y cells, chronic myeloid leukemia K562 cells ) to low - micromolar ( lung H1299 and A549, colon HCT116 and HT29 cancer cells ) concentrations.", "output": "There is no related enetity." }, { "input": "In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony - forming potential of the cancer cells by up to 60 %.", "output": "There is no related enetity." }, { "input": "Phospholipid / Carbocyanine Dye - Shelled Microbubbles as Ultrasound - Modulated Fluorescent Contrast Agents.", "output": "Carbocyanine." }, { "input": "Fluorescent microbubbles have been fabricated with the capacity to have their emission modulated by ultrasound.", "output": "There is no related enetity." }, { "input": "These contrast agent particles could potentially be used in the future to extract fluorescence modulation from a strong light background to increase imaging depth and resolution in scattering media.", "output": "There is no related enetity." }, { "input": "Fluorescence intensity modulation was demonstrated at the ultrasound driving frequency.", "output": "There is no related enetity." }, { "input": "Exploring the effect of N - substitution in nor - lobelane on the interaction with VMAT2: discovery of a potential clinical candidate for treatment of methamphetamine abuse.", "output": "N, nor - lobelane, methamphetamine." }, { "input": "A series of N - substituted lobelane analogues was synthesized and evaluated for their [ ( 3 ) H ] dihydrotetrabenazine binding affinity at the vesicular monoamine transporter and for their inhibition of vesicular [ ( 3 ) H ] dopamine uptake.", "output": "N, lobelane, [ ( 3 ) H ] dihydrotetrabenazine, monoamine, [ ( 3 ) H ] dopamine." }, { "input": "Compound 19a, which contains an N - 1, 2 ( R ) - dihydroxypropyl group, had been identified as a potential clinical candidate for the treatment of methamphetamine abuse.", "output": "N - 1 , 2 ( R ) - dihydroxypropyl, methamphetamine." }, { "input": "Using Supramolecular Binding Motifs To Provide Precise Control over the Ratio and Distribution of Species in Multiple Component Films Grafted on Surfaces: Demonstration Using Electrochemical Assembly from Aryl Diazonium Salts.", "output": "Aryl Diazonium." }, { "input": "Supramolecular interactions between two surface modification species are explored to control the ratio and distribution of these species on the resultant surface.", "output": "There is no related enetity." }, { "input": "A binary mixture of aryl diazonium salts bearing oppositely charged para - substituents ( either - SO3 ( - ) or - N ( + ) ( Me ) 3 ), which also reduce at different potentials, has been examined on glassy carbon surfaces using cyclic voltammetry and X - ray photoelectron spectroscopy ( XPS ).", "output": "aryl diazonium, SO3 ( - ), N ( + ) ( Me ) 3, glassy carbon." }, { "input": "Striking features were observed: ( 1 ) the two aryl diazonium salts in the mixed solution undergo reductive adsorption at the same potential which is distinctively less negative than the potential required for the reduction of either of the two aryl diazonium salts alone; ( 2 ) the surface ratio of the two phenyl derivatives is consistently 1: 1 regardless of the ratio of the two aryl diazonium salts in the modification solutions.", "output": "aryl diazonium, aryl diazonium, aryl diazonium." }, { "input": "Homogeneous distribution of the two oppositely charged phenyl species on the modified surface has also been suggested by XPS survey spectra.", "output": "phenyl." }, { "input": "Diffusion coefficient measurements by DOSY NMR and DFT based computation have indicated the association of the two aryl diazonium species in the solution, which has led to changes in the molecular orbital energies of the two species.", "output": "aryl diazonium." }, { "input": "This study highlights the potential of using intermolecular interactions to control the assembly of multicomponent thin layers.", "output": "There is no related enetity." }, { "input": "Does Dietary Copper Supplementation Enhance or Diminish PCB126 Toxicity in the Rodent Liver?", "output": "Copper." }, { "input": "Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins.", "output": "Copper." }, { "input": "However, in its free form copper can participate in Fenton - like reactions that produce reactive hydroxyl radicals.", "output": "copper, hydroxyl." }, { "input": "Aryl - hydrocarbon receptor ( AhR ) agonists, including the most potent polychlorinated biphenyl ( PCB ) congener, 3, 3 ', 4, 4 ', 5 - pentachlorobiphenyl ( PCB126 ), increase copper levels in rodent livers.", "output": "Aryl - hydrocarbon, polychlorinated biphenyl, PCB, 3 , 3 ' , 4 , 4 ' , 5 - pentachlorobiphenyl, PCB126, copper." }, { "input": "This is accompanied by biochemical and toxic changes.", "output": "There is no related enetity." }, { "input": "To assess the involvement of copper in PCB toxicity, male Sprague - Dawley rats were fed an AIN - 93G diet with differing dietary copper levels: low ( 2 ppm ), adequate ( 6 ppm ), and high ( 10 ppm ).", "output": "PCB, copper." }, { "input": "After three weeks, rats from each group were given a single ip injection of corn oil ( control ), 1, or 5 mu mol / kg body weight PCB126.", "output": "PCB126." }, { "input": "Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated.", "output": "There is no related enetity." }, { "input": "Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin.", "output": "copper, copper." }, { "input": "In the livers of PCB126 - treated rats, the hallmark signs of AhR activation were present, including increased cytochrome P450 and lipid levels and decreased glutathione.", "output": "PCB126, glutathione." }, { "input": "In addition, a doubling of hepatic copper levels was seen, and overall metal homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc, and iron.", "output": "copper, selenium, manganese, zinc, iron." }, { "input": "Expression of key metalloproteins was either decreased ( cytochrome c oxidase ), unchanged ( ceruloplasmin and CuZnSOD ), or increased ( tyrosinase and metallothioneins 1 and 2 ) with exposure to PCB126.", "output": "PCB126." }, { "input": "Increases in metallothionein may contribute / reflect the increased copper seen.", "output": "copper." }, { "input": "Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126.", "output": "copper, PCB126." }, { "input": "PCB126 toxicity, i. e., oxidative stress and steatosis, is clearly associated with disturbed metal homeostasis.", "output": "PCB126." }, { "input": "Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists.", "output": "There is no related enetity." }, { "input": "Novel Cellulose Polyampholyte - Gold Nanoparticle - Based Colorimetric Competition Assay for the Detection of Cysteine and Mercury ( II ).", "output": "Cysteine, Mercury ( II )." }, { "input": "We provide a highly sensitive and selective assay to detect cysteine ( Cys ) and Hg ( 2 + ) in aqueous solutions using Au nanoparticles ( NPs ) stabilized by carboxylethyl quaternized cellulose ( CEQC ).", "output": "cysteine, Cys, Hg ( 2 + ), Au, carboxylethyl." }, { "input": "This method is based on the thiophilicity of Hg ( 2 + ) and Au NPs as well as the unique optical properties of CEQC - stabilized Au NPs.", "output": "Hg ( 2 + ), Au, Au." }, { "input": "CEQC chains are good stabilizing agents for Au NPs even in a high - salt solution.", "output": "Au." }, { "input": "The addition of Cys results in the aggregation of CEQC - stabilized Au NPs, which induces the visible color change and obvious redshift in UV - visible absorption spectra.", "output": "Cys, Au." }, { "input": "On the other hand, Hg ( 2 + ) is more apt to interact with thiols than Au NPs; thus, it can remove the Cys and trigger Au NP aggregate redispersion again.", "output": "Hg ( 2 + ), thiols, Au, Cys, Au." }, { "input": "By taking advantage of this mechanism, a novel off - on colorimetric sensor has been established for Cys and Hg ( 2 + ) detection.", "output": "Cys, Hg ( 2 + )." }, { "input": "This new assay could selectively detect Cys and Hg ( 2 + ) with the detection limits as low as 20 and 40 nM in aqueous solutions, respectively.", "output": "Cys, Hg ( 2 + )." }, { "input": "Nanopore - spanning lipid bilayers on silicon nitride membranes that seal and selectively transport ions.", "output": "silicon nitride." }, { "input": "We report the formation of POPC lipid bilayers that span 130 nm pores in a freestanding silicon nitride film supported on a silicon substrate.", "output": "POPC, silicon nitride, silicon." }, { "input": "These solvent - free lipid membranes self - assemble on organosilane - treated Si3N4 via the fusion of 200 nm unilamellar vesicles.", "output": "organosilane, Si3N4." }, { "input": "Membrane fluidity is verified by fluorescence recovery after photobleaching ( FRAP ), and membrane resistance in excess of 1 G Omega is demonstrated using electrical impedance spectroscopy ( EIS ).", "output": "There is no related enetity." }, { "input": "An array of 40 000 membranes maintained high impedance over 72 h, followed by rupture of most of the membranes by 82 h.", "output": "There is no related enetity." }, { "input": "Membrane incorporation of gramicidin, a model ion channel, resulted in increased membrane conductance.", "output": "There is no related enetity." }, { "input": "This membrane conductance was diminished when the gramicidin channels were blocked with CaCl2, indicating that the change in membrane conductance results from gramicidin - mediated ion transport.", "output": "CaCl2." }, { "input": "These very stable, biologically functional pore - spanning membranes open many possibilities for silicon - based ion - channel devices for applications such as biosensors and high - throughput drug screening.", "output": "silicon." }, { "input": "Cross - talk between constitutive androstane receptor and hypoxia - inducible factor in the regulation of gene expression.", "output": "androstane." }, { "input": "Hypoxia inducible factor ( HIF ) and 5 ' - AMP - activated protein kinase are often activated under similar physiological conditions.", "output": "5 ' - AMP." }, { "input": "Constitutive androstane receptor ( CAR ) translocates into the nucleus in accordance with 5 ' - AMP - activated protein kinase and thus confers transactivation.", "output": "androstane, 5 ' - AMP." }, { "input": "The aim of the present study was to investigate a possible link between CAR and HIF alpha.", "output": "There is no related enetity." }, { "input": "Phenobarbital ( PB ), a typical CAR activator, increased the gene expression of HIF - target genes in the livers of mice, including erythropoietin, heme oxygenase - 1 and vascular endothelial growth factor - a.", "output": "Phenobarbital." }, { "input": "PB induced an accumulation of nuclear HIF - 1 alpha and an increase in the HIF - responsive element - mediated transactivation in HepG2 cells.", "output": "There is no related enetity." }, { "input": "Cobalt chloride, a typical HIF activator, induced the gene expression of CAR - target genes, including cyp2b9 and cyp2b10, an accumulation of nuclear CAR and an increase in the PB - responsive enhancer module - mediated transactivation in the mouse liver.", "output": "Cobalt chloride." }, { "input": "Immunoprecipitation - immunoblot and chromatin immunoprecipitation analyses suggest that CAR binds to the PB - responsive enhancer module with HIF - 1 alpha in the liver of untreated mice and that the complex dissociates upon PB treatment.", "output": "There is no related enetity." }, { "input": "Taken together these results suggest that CAR and HIF - alpha interact and reciprocally modulate the functions of each other.", "output": "There is no related enetity." }, { "input": "Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A.", "output": "androgen, bisphenol A." }, { "input": "To investigate the effects of a low bisphenol A ( BPA ) concentration on male reproduction, adult rats were administered a concentration of BPA that was less than the no observable adverse effect level ( 0. 0005 - 5mg / kg / bw ) for 8 weeks.", "output": "bisphenol A, BPA, BPA." }, { "input": "General toxicity, reproductive hormones, and spermatogenesis were then determined.", "output": "There is no related enetity." }, { "input": "The expression of genes related to hormone synthesis and spermatogenesis was also analyzed.", "output": "There is no related enetity." }, { "input": "These BPA concentrations generated no general toxicity and no significant changes on serum hormones.", "output": "BPA." }, { "input": "However, the testicular testosterone, hormone synthesis - related genes StAR and Cyp450scc increased, whereas 3 beta - HSD, 17 beta - HSD, and Cyp450arom decreased.", "output": "testosterone." }, { "input": "Additionally, BPA significantly decreased the epithelial height and round spermatids in seminiferous tubules, sperm count, androgen receptor expression, and the expression of the spermatogenesis - related genes outer dense fiber protein 1 ( ODF1 ) and transition protein 1.", "output": "BPA, androgen." }, { "input": "Our results indicate that a low BPA concentration can induce spermatogenesis disorders mainly through decreasing androgen receptor expression.", "output": "BPA, androgen." }, { "input": "The present results may bring attention to the risk of environmental BPA exposure.", "output": "BPA." }, { "input": "Design and synthesis of 2 - substituted benzoxazoles as novel PTP1B inhibitors.", "output": "2 - substituted benzoxazoles." }, { "input": "A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition.", "output": "benzoxazole, oxamic acid." }, { "input": "Compound 31d showed best biochemical potency ( Ki ) of 6. 7 mu M.", "output": "There is no related enetity." }, { "input": "Structure - activity relationship were explained with the help of molecular modeling approach.", "output": "There is no related enetity." }, { "input": "Antibacterial action of quinolones: From target to network.", "output": "quinolones." }, { "input": "Quinolones are widely used broad - spectrum antibacterials with incomplete elucidated mechanism of action.", "output": "Quinolones." }, { "input": "Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated.", "output": "quinolones." }, { "input": "Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug - enzyme - DNA cleavage complexes, resulting in bacteriostasis.", "output": "Quinolones." }, { "input": "Cell death arises from chromosome fragmentation in protein synthesis - dependent or - independent pathways according to distinguished quinolone structures.", "output": "quinolone." }, { "input": "In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually.", "output": "oxygen." }, { "input": "Toxin - antitoxin mazEF is triggered as an additional lethal action.", "output": "There is no related enetity." }, { "input": "Bacteria survive and develop resistance by SOS and other stress responses.", "output": "There is no related enetity." }, { "input": "Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance.", "output": "quinolone." }, { "input": "Epidermal growth factor receptor inhibitor PKI - 166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5 / 6 nephrectomised rats.", "output": "PKI - 166." }, { "input": "Transactivation of epidermal growth factor receptor ( EGFR ) signaling by G - protein - coupled receptors has been implicated in several cardiovascular ( CV ) conditions, including hypertension, heart failure, cardiac and vascular hypertrophy.", "output": "There is no related enetity." }, { "input": "However, the therapeutic potential of EGFR inhibition in these conditions is currently unknown.", "output": "There is no related enetity." }, { "input": "Main objective of the present study was to investigate cardiac, vascular and renal effects of EGFR inhibition by PKI - 166 in the hypertensive chronic kidney disease ( CKD ) model.", "output": "PKI - 166." }, { "input": "Rats underwent 5 / 6 nephrectomy ( 5 / 6Nx ) and were treated with PKI - 166 or lisinopril or vehicle from week 6 after disease induction until week 12.", "output": "PKI - 166, lisinopril." }, { "input": "Sham animals received either PKI - 166 or vehicle.", "output": "PKI - 166." }, { "input": "Treatment with PKI - 166 did not affect the development of the characteristic renal features in 5 / 6Nx including proteinuria, diminished creatinine clearance and increased glomerulosclerosis, whereas these were attenuated by lisinopril.", "output": "PKI - 166, creatinine, lisinopril." }, { "input": "Despite absence of effects on progressive renal damage, PKI - 166 attenuated the progression of hypertension and maintained cardiac function ( LVEDP ) to a similar extent as lisinopril.", "output": "PKI - 166." }, { "input": "Also, PKI - 166 attenuated the increase in phosphorylated EGFR in heart as induced by 5 / 6Nx.", "output": "PKI - 166." }, { "input": "Moreover, PKI - 166 and lisinopril restored the impaired contraction of isolated thoracic aortic rings to phenylephrine and angiotensin II and impaired myogenic constriction of small mesenteric arteries in 5 / 6Nx rats.", "output": "PKI - 166, lisinopril, phenylephrine." }, { "input": "Blockade of the EGFR displays a CV benefit independently of limiting the progression of renal injury.", "output": "There is no related enetity." }, { "input": "Our findings extend the evidence on EGFR signaling as a target in CV disorders.", "output": "There is no related enetity." }, { "input": "Recent progress in nanosensors for sensitive detection of biomolecules.", "output": "There is no related enetity." }, { "input": "Developing sensitive, rapid, and cost - effective methods for detection of biomolecules is important for both clinical and numerous non - clinical applications.", "output": "There is no related enetity." }, { "input": "During the last two decades, functional nanomaterials with unique physical and chemical properties have provided significant advantages for biological detection.", "output": "There is no related enetity." }, { "input": "In this feature article, we introduce recent progress in nanobiosensor development by exploiting the optical, electrical and catalytic properties of a range of nanomaterials, with a focus on gold nanoparticles, carbon nanotubes, graphene and carbon dots.", "output": "carbon, graphene, carbon." }, { "input": "In addition, the perspectives on future opportunities and unsolved challenges are also discussed.", "output": "There is no related enetity." }, { "input": "Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.", "output": "There is no related enetity." }, { "input": "The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist.", "output": "There is no related enetity." }, { "input": "The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia.", "output": "There is no related enetity." }, { "input": "Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age - matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment ( HOMA ) - insulin resistance index, beta cell function measured by HOMA - beta index, leptin and adiponectin levels.", "output": "glucose." }, { "input": "Plasma insulin levels and HOMA indexes ( both insulin resistance and beta indexes ) were significantly higher in hyperprolactinemic women.", "output": "There is no related enetity." }, { "input": "The other parameters were similar between both groups.", "output": "There is no related enetity." }, { "input": "There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women.", "output": "glucose." }, { "input": "The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women.", "output": "There is no related enetity." }, { "input": "This effect seems to be independent of body weight, leptin and adiponectin levels.", "output": "There is no related enetity." }, { "input": "High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole - body insulin resistance.", "output": "There is no related enetity." }, { "input": "RANKL subcellular trafficking and regulatory mechanisms in osteocytes.", "output": "There is no related enetity." }, { "input": "The receptor activator of the NF - kappa B ligand ( RANKL ) is the central player in the regulation of osteoclastogenesis and the quantity of RANKL presented to osteoclast precursors is an important factor determining the magnitude of osteoclast formation.", "output": "There is no related enetity." }, { "input": "Since osteoblastic cells are thought to be a major source of RANKL, the regulatory mechanisms of RANKL subcellular trafficking have been studied in osteoblastic cells.", "output": "There is no related enetity." }, { "input": "However, recent reports showed that osteocytes are a major source of RANKL presentation to osteoclast precursors, prompting a need to reinvestigate RANKL subcellular trafficking in osteocytes.", "output": "There is no related enetity." }, { "input": "Investigation of molecular mechanisms in detail needs well - designed in vitro experimental systems.", "output": "There is no related enetity." }, { "input": "Thus, we developed a novel co - culture system of osteoclast precursors and osteocytes embedded in collagen gel.", "output": "There is no related enetity." }, { "input": "Experiments using this model revealed that osteocytic RANKL is provided as a membrane - bound form to osteoclast precursors through osteocyte dendritic processes and that the contribution of soluble RANKL to the osteoclastogenesis supported by osteocytes is minor.", "output": "There is no related enetity." }, { "input": "Moreover, the regulation of RANKL subcellular trafficking, such as OPG - mediated transport of newly synthesized RANKL molecules to lysosomal storage compartments, and the release of RANKL to the cell surface upon stimulation with RANK, are confirmed to be functional in osteocytes.", "output": "There is no related enetity." }, { "input": "These results provide a novel understanding of the regulation of osteoclastogenesis.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Biomimetic Synthesis and Studies Toward Enantioselective Synthesis of Flindersial Alkaloids.", "output": "There is no related enetity." }, { "input": "A strategy allowing both stereocontrol and control over structural isomer formation has been defined for the antimalarial flindersial alkaloids.", "output": "There is no related enetity." }, { "input": "The recently reported flinderoles were demonstrated to be derived from the natural product borrerine.", "output": "flinderoles, borrerine." }, { "input": "The structural isomers of flinderoles, the borreverines, were also produced in vitro along with the flinderoles through the dimerization of borrerine in acidic conditions.", "output": "flinderoles, borreverines, flinderoles, borrerine." }, { "input": "This result is thought to replicate the biosynthesis of these compounds.", "output": "There is no related enetity." }, { "input": "Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine can each be synthesized in three steps from tryptamine.", "output": "Flinderoles A , B , and C, isoborreverine, dimethylisoborreverine, tryptamine." }, { "input": "Furthermore, progress toward a concise enantioselective synthesis of flinderoles A, B, and C is described.", "output": "flinderoles A , B , and C." }, { "input": "This work includes enantioselective conjugate addition to an unprotected indole - appended enone.", "output": "indole, enone." }, { "input": "Chirality 00: 000 - 000, 2013.", "output": "There is no related enetity." }, { "input": "(c) 2013 Wiley Periodicals, Inc.", "output": "There is no related enetity." }, { "input": "Multifunctional Hybrid Materials From Poly ( 3 - Hydroxybutyrate ), TiO2 Nanoparticles, and Chitosan Oligomers by Combining Electrospinning / Electrospraying and Impregnation.", "output": "Poly ( 3 - Hydroxybutyrate ), TiO2." }, { "input": "Several types of fibrous material containing poly ( 3 - hydroxybutyrate ) ( PHB ), nanosized TiO2 - anatase ( nanoTiO2 ), and chitosan oligomers are prepared by combining the electrospinning, electrospraying, and impregnation techniques.", "output": "poly ( 3 - hydroxybutyrate ), PHB, TiO2, nanoTiO2." }, { "input": "Simultaneous electrospinning / electrospraying provides uniform distribution of electrosprayed nanoTiO2 along the PHB fibers and throughout the mat.", "output": "nanoTiO2, PHB." }, { "input": "Hybrid materials of different design manifest excellent photocatalytic activity, even after repeated use.", "output": "There is no related enetity." }, { "input": "They exhibit high bactericidal activity against Escherichia coli.", "output": "There is no related enetity." }, { "input": "In addition, the fibrous scaffolds are compatible with human mesenchymal stem cells and provide a favorable environment for their development.", "output": "There is no related enetity." }, { "input": "Mimicking Nanofibrous Hybrid Bone Substitute for Mesenchymal Stem Cells Differentiation into Osteogenesis.", "output": "There is no related enetity." }, { "input": "Mimicking hybrid extracellular matrix is one of the main challenges for bone tissue engineering ( BTE ).", "output": "There is no related enetity." }, { "input": "Biocompatible polycaprolactone / poly ( alpha, beta ) - DL - aspartic acid / collagen nanofibrous scaffolds were fabricated by electrospinning and nanohydroxyapatite ( n - HA ) was deposited by calcium phosphate dipping method for BTE.", "output": "polycaprolactone, poly ( alpha , beta ) - DL - aspartic acid." }, { "input": "Human mesenchymal stem cells ( hMSCs ) were cultured on these hybrid scaffolds to investigate the cell proliferation, osteogenic differentiation by alkaline phosphatase activity, mineralization, double immunofluorescent staining using CD90 and expression of osteocalcin.", "output": "There is no related enetity." }, { "input": "The present study indicated that the PCL / PAA / collagen / n - HA scaffolds promoted greater osteogenic differentiation of hMSCs, proving to be a potential hybrid scaffolds for BTE.", "output": "PCL, PAA." }, { "input": "Metabolic Effects of Chronic Cannabis Smoking.", "output": "There is no related enetity." }, { "input": "OBJECTIVEWe examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced beta - cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODSIn a cross - sectional, case - control study, we studied cannabis smokers ( n = 30; women, 12; men, 18; 27 +/- 8 years ) and control subjects ( n = 30 ) matched for age, sex, ethnicity, and BMI ( 27 +/- 6 ).", "output": "There is no related enetity." }, { "input": "Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively.", "output": "There is no related enetity." }, { "input": "Insulin - sensitivity indices and various aspects of beta - cell function were derived from oral glucose tolerance tests ( OGTT ). RESULTSSelf - reported cannabis use was: 9. 5 ( 2 - 38 ) years; joints / day: 6 ( 3 - 30 ) [ median ( range ) ].", "output": "glucose." }, { "input": "Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers.", "output": "Carbohydrate, carbohydrates." }, { "input": "There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat ( 18 +/- 9 vs. 12 +/- 5 %; P = 0. 004 ).", "output": "There is no related enetity." }, { "input": "Cannabis smokers had lower plasma HDL cholesterol ( 49 +/- 14 vs. 55 +/- 13 mg / dL; P = 0. 02 ), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids ( FFA ) were not different.", "output": "cholesterol, glucose, cholesterol, cholesterol, triglycerides, fatty acids." }, { "input": "Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower ( P < 0. 05 ) in cannabis smokers.", "output": "There is no related enetity." }, { "input": "However, oral glucose insulin sensitivity index, measures of beta - cell function, or incretin concentrations did not differ between the groups. CONCLUSIONSChronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic beta - cell function, or glucose intolerance.", "output": "glucose, glucose." }, { "input": "Chalcogenopyrylium Dyes as Differential Modulators of Organic Anion Transport by MRP1, MRP2 and MRP4.", "output": "Chalcogenopyrylium." }, { "input": "Multidrug resistance proteins ( MRPs ) mediate the ATP - dependent efflux of structurally diverse compounds, including anticancer drugs and physiological organic anions.", "output": "ATP." }, { "input": "Five classes of chalcogenopyrylium dyes ( CGPs ) were examined for their ability to modulate transport of [ ( 3 ) H ] estradiol glucuronide ( E217 beta G ) ( a prototypical MRP substrate ) into MRP - enriched inside - out membrane vesicles.", "output": "chalcogenopyrylium, CGPs, [ ( 3 ) H ] estradiol glucuronide, E217 beta G." }, { "input": "Additionally, some CGPs were tested in intact transfected cells using a calcein efflux assay.", "output": "CGPs, calcein." }, { "input": "Sixteen of 34 CGPs inhibited MRP1 - mediated E217 beta G uptake by > 50 % ( IC50 ' s 0. 7 - 7. 6 mu M ).", "output": "CGPs, E217 beta G." }, { "input": "Of 9 CGPs with IC50 ' s <= 2 mu M, two belonged to Class I, two to Class III and five to Class V. When tested in the intact cells, only 4 of 16 CGPs ( at 10 mu M ) inhibited MRP1 - mediated calcein efflux by > 50 % ( III - 1, V - 3, - 4, - 6 ) while a fifth ( I - 5 ) inhibited efflux by just 23 %.", "output": "CGPs, CGPs, calcein." }, { "input": "These five CGPs also inhibited [ ( 3 ) H ] E217 beta G uptake by MRP4.", "output": "CGPs, [ ( 3 ) H ] E217 beta G." }, { "input": "In contrast, their effects on MRP2 varied with two ( V - 4, V - 6 ) inhibiting E217 beta G transport ( IC50 ' s 2. 0, 9. 2 mu M ), two ( V - 3, III - 1 ) stimulating transport ( > 2 - fold ), while CGP I - 5 had no effect.", "output": "E217 beta G, CGP." }, { "input": "Strikingly, although V - 3 and V - 4 had opposite effects on MRP2 activity, they are structurally identical except for their chalcogen atom ( Se versus Te ).", "output": "chalcogen, Se, Te." }, { "input": "This study is the first to identify Class V CGPs with their distinctive methine or trimethine linkage between two disubstituted pyrylium moieties as a particularly potent class of MRP modulators and also show that within this core structure, differences in the electronegativity associated with a chalcogen atom can be the sole determinant of whether a compound will stimulate or inhibit MRP2.", "output": "methine, trimethine, pyrylium, chalcogen." }, { "input": "Nicotine Kinetics in Zebra Finches in vivo and in vitro.", "output": "Nicotine." }, { "input": "Nicotine enhances cognitive performance, and in the zebra finch ( Taeniopygia guttata ), which is a well - established model of cognition, the effect of nicotine on song production has been reported.", "output": "Nicotine, nicotine." }, { "input": "Nicotine and cotinine plasma levels were assessed in vivo after s. c. injection of 0. 18 mg / kg nicotine, a dose that elicits changes in song production.", "output": "Nicotine, cotinine, nicotine." }, { "input": "The half - life of nicotine elimination was 33 min, and levels were undetectable by 4h.", "output": "nicotine." }, { "input": "Average plasma nicotine over 2 hours was 32 ng / ml, similar to levels seen in human smokers and rat models of nicotine behavior.", "output": "nicotine, nicotine." }, { "input": "Nicotine brain levels were 30 and 14 ng / g at 1 and 2 h after treatment.", "output": "Nicotine." }, { "input": "To understand the potential for drug interactions and regulation of nicotine metabolism in zebra finches, we characterized in vitro nicotine metabolism and the hepatic enzyme involved.", "output": "nicotine, nicotine." }, { "input": "In humans, cytochrome P450 ( CYP ) 2A6 metabolizes nicotine to cotinine, and CYP2A - like activity and protein have been reported in some birds.", "output": "nicotine, cotinine." }, { "input": "Zebra finch liver microsomes metabolized nicotine and bupropion ( CYP2B substrate ) but not coumarin ( CYP2A substrate ).", "output": "nicotine, bupropion, coumarin." }, { "input": "Nicotine was metabolized to cotinine with a Km of 96 mu M and Vmax of 56 pmol / min / mg.", "output": "Nicotine, cotinine." }, { "input": "Nicotine and bupropion metabolism were inhibited by C - 8 - xanthate ( specific CYP2B inhibitor ) but not CYP2A - specific inhibitors, and hepatic levels of CYP2B - like but not CYP2A - like proteins correlated with nicotine ( r = 0. 52, p = 0. 04 ) and bupropion metabolism ( r = 0. 81, p < 0. 001 ), suggesting CYP2B - mediation of nicotine metabolism as seen in rats.", "output": "Nicotine, bupropion, C - 8 - xanthate, nicotine, bupropion, nicotine." }, { "input": "These results will facilitate further investigation of nicotine ' s effects in zebra finches.", "output": "nicotine." }, { "input": "Prilocaine - and Lidocaine - induced Methemoglobinemia is Caused by Human Carboxylesterase -, CYP2E1 - and CYP3A4 - mediated Metabolic Activation.", "output": "Prilocaine, Lidocaine." }, { "input": "Prilocaine and lidocaine are classified as amide - type local anesthetics whose serious adverse effects include methemoglobinemia.", "output": "Prilocaine, lidocaine, amide." }, { "input": "Although the hydrolyzed metabolites of prilocaine ( o - toluidine ) and lidocaine ( 2, 6 - xylidine ) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized.", "output": "prilocaine, o - toluidine, lidocaine, 2 , 6 - xylidine." }, { "input": "In the present study, we aimed to identify the human enzymes that are responsible for prilocaine - and lidocaine - induced methemoglobinemia.", "output": "prilocaine, lidocaine." }, { "input": "Our experiments revealed that prilocaine was hydrolyzed by recombinant human carboxylesterase ( CES ) 1A and CES2, whereas lidocaine was hydrolyzed only by human CES1A.", "output": "prilocaine, lidocaine." }, { "input": "When the parent compounds ( prilocaine and lidocaine ) were incubated with HLM, Met - Hb formation was lower than when the hydrolyzed metabolites were incubated with HLM.", "output": "prilocaine, lidocaine." }, { "input": "In addition, Met - Hb formation when prilocaine and o - toluidine were incubated with HLM was higher than that when lidocaine and 2, 6 - xylidine were incubated with HLM.", "output": "prilocaine, o - toluidine, lidocaine, 2 , 6 - xylidine." }, { "input": "Incubation with diisopropyl fluorophosphate and bis - ( 4 - nitrophenyl ) phosphate, which are general inhibitors of CES, significantly decreased Met - Hb formation when prilocaine and lidocaine were incubated with HLM.", "output": "diisopropyl fluorophosphate, bis - ( 4 - nitrophenyl ) phosphate, prilocaine, lidocaine." }, { "input": "An anti - CYP3A4 antibody further decreased the residual formation of Met - Hb.", "output": "There is no related enetity." }, { "input": "Met - Hb formation following the incubation of o - toluidine and 2, 6 - xylidine with HLM was only markedly decreased by incubation with an anti - CYP2E1 antibody.", "output": "o - toluidine, 2 , 6 - xylidine." }, { "input": "o - Toluidine and 2, 6 - xylidine were further metabolized by CYP2E1 to 4 - and 6 - hydroxy - o - toluidine and 4 - hydroxy - 2, 6 - xylidine, respectively, and these metabolites were shown to more efficiently induce Met - Hb formation than the parent compounds.", "output": "o - Toluidine, 2 , 6 - xylidine, 4 - and 6 - hydroxy - o - toluidine, 4 - hydroxy - 2 , 6 - xylidine." }, { "input": "Collectively, we found that the metabolites produced by human CES -, CYP2E1 - and CYP3A4 - mediated metabolism were involved in prilocaine - and lidocaine - induced methemoglobinemia.", "output": "prilocaine, lidocaine." }, { "input": "The Hyaluronan Receptor for Endocytosis ( HARE ) activates NF - kappa B mediated gene expression in response to 40 - 400 kDa, but not smaller or larger, hyaluronan.", "output": "There is no related enetity." }, { "input": "The Hyaluronan ( HA ) Receptor for Endocytosis ( HARE ) binds and clears 14 different ligands, including HA and heparin, via clathrin - mediated endocytosis.", "output": "There is no related enetity." }, { "input": "HA binding to HARE stimulates ERK1 / 2 activation ( Kyosseva et al. J. Biol. Chem. 283, 15047, 2008 ).", "output": "There is no related enetity." }, { "input": "To assess a possible HA size - dependence for signaling, we tested purified HA fractions of different weight - average molar mass ( Mw ) and with narrow size distributions and Select - HA for stimulation of HARE - mediated gene expression using an NF - kappa B promoter - driven luciferase reporter system.", "output": "There is no related enetity." }, { "input": "Human HARE - mediated gene expression was stimulated in a dose - dependent manner with small HA ( SHA ) > 40 kDa and intermediate HA ( IHA ) < 400 kDa.", "output": "There is no related enetity." }, { "input": "The hyperbolic dose - response saturated at 20 - 50 nM with an apparent Km ~ 10 nM, identical to the Kd for HA - HARE binding.", "output": "There is no related enetity." }, { "input": "Activation was not detected with oligomeric HA ( OHA ), SHA < 40 kDa, IHA > 400 kDa or large HA ( LHA ).", "output": "There is no related enetity." }, { "input": "Similar responses occurred with rat HARE.", "output": "There is no related enetity." }, { "input": "Activation by SHA - IHA was blocked by excess nonsignaling SHA, IHA or LHA, deletion of the HA - binding LINK domain, or HA - blocking antibody.", "output": "There is no related enetity." }, { "input": "Endogenous NF - kappa B activation also occurred in the absence of luciferase plasmids, as assessed by degradation of I kappa B - alpha.", "output": "There is no related enetity." }, { "input": "ERK1 / 2 activation was also HA - size dependent.", "output": "There is no related enetity." }, { "input": "The results show that HA - HARE interactions stimulate NF - kappa B activated gene expression and that HARE senses a narrow size - range of HA degradation products.", "output": "There is no related enetity." }, { "input": "We propose a model in which optimal length HA binds multiple HARE proteins to allow cytoplasmic domain interactions that stimulate intracellular signaling.", "output": "There is no related enetity." }, { "input": "This HARE signaling system during continuous HA clearance could monitor the homeostasis of tissue biomatrix turnover throughout the body.", "output": "There is no related enetity." }, { "input": "Discoidin Domain Receptor 1 is a novel modulator of megakaryocyte - collagen interactions.", "output": "There is no related enetity." }, { "input": "Growing evidence demonstrates that extracellular matrices ( ECMs ) regulate many aspects of megakaryocyte ( MK ) development; however, among the different ECM receptors, integrin alpha2beta1 and GPVI are the only collagen receptors studied in platelets and MKs.", "output": "There is no related enetity." }, { "input": "In this study, we demonstrate the expression of the novel collagen receptor Discoidin Domain Receptor 1 ( DDR1 ) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and Syk tyrosine kinase.", "output": "tyrosine." }, { "input": "Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, GPVI, alpha2beta1 and LAIR - 1 determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk.", "output": "There is no related enetity." }, { "input": "Consistently, inhibition of Syk activity restored MK migration on type I collagen.", "output": "There is no related enetity." }, { "input": "In conclusion, we report the expression and function of a novel collagen receptor on human MKs and we point out that increasing level of complexity is necessary to better understand MK - collagen interactions in the bone marrow environment.", "output": "There is no related enetity." }, { "input": "Maternal adiposity as an independent risk factor for pre - eclampsia: a meta - analysis of prospective cohort studies.", "output": "There is no related enetity." }, { "input": "Studies investigating the association between maternal adiposity and risk of pre - eclampsia showed contradictory results.", "output": "There is no related enetity." }, { "input": "Therefore, we performed a meta - analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre - eclampsia.", "output": "There is no related enetity." }, { "input": "We reviewed 1, 286 abstracts and finally included 29 prospective cohort studies with 1, 980, 761 participants and 67, 075 pre - eclampsia events.", "output": "There is no related enetity." }, { "input": "We pooled data with a random - effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal - weight ( reference ), overweight, obese and severely obese.", "output": "There is no related enetity." }, { "input": "In the cohort studies that unadjusted for pre - eclampsia risk factors, the pooled unadjusted relative risks ( RR ) with 95 % confidence intervals ( 95 % CI ) for pre - eclampsia of overweight, obese and severely obese women were 1. 58 ( 95 % CI 1. 44 - 1. 72, P < 0. 001 ), 2. 68 ( 95 % CI 2. 39 - 3. 01, P < 0. 001 ) and 3. 12 ( 95 % CI 2. 24 - 4. 36, P < 0. 001 ), respectively.", "output": "There is no related enetity." }, { "input": "In those cohorts that adjusted for pre - eclampsia risk factors, the pooled unadjusted RRs for pre - eclampsia of overweight, obese and severely obese women were 1. 70 ( 95 % CI 1. 60 - 1. 81, P < 0. 001 ), 2. 93 ( 95 % CI 2. 58 - 3. 33, P < 0. 001 ) and 4. 14 ( 95 % CI 3. 61 - 4. 75, P < 0. 001 ), respectively.", "output": "There is no related enetity." }, { "input": "Sensitivity analysis showed maternal adiposity was associated with increased risk of pre - eclampsia in both nulliparous and multiparas women.", "output": "There is no related enetity." }, { "input": "In conclusion, overweight or obese pregnant women have a substantially increased risk of pre - eclampsia, and maternal adiposity is an independent risk factor of pre - eclampsia.", "output": "There is no related enetity." }, { "input": "Electron Paramagnetic Resonance Spectroscopic Study of Copper Hopping in Doped Bis ( l - histidinato ) cadmium Dihydrate.", "output": "Copper, Bis ( l - histidinato ) cadmium Dihydrate." }, { "input": "Electron paramagnetic resonance ( EPR ) spectroscopy was used to study Cu ( II ) dynamic behavior in a doped biological model crystal, bis ( l - histidinato ) cadmium dihydrate, in order to gain better insight into copper site stability in metalloproteins.", "output": "Cu ( II ), bis ( l - histidinato ) cadmium dihydrate, copper." }, { "input": "Temperature - dependent changes in the low temperature X - band EPR spectra became visible around 100 K and continued up to room temperature.", "output": "There is no related enetity." }, { "input": "The measured 298 K g - tensor ( principal values: 2. 17, 2. 16, 2. 07 ) and copper hyperfine coupling tensor ( principal values: - 260, - 190, - 37 MHz ) were similar to the average of the 77 K tensor values pertaining to two neighboring histidine binding sites.", "output": "copper, histidine." }, { "input": "The observed temperature dependence was interpreted using Anderson ' s theory of motional narrowing, where the magnetic parameters for the different states are averaged as the copper rapidly hops between sites.", "output": "copper." }, { "input": "The EPR pattern was also found to undergo a sharp sigmoidal - shaped, temperature - dependent conversion between two species with a critical temperature Tc =~ 160 K.", "output": "There is no related enetity." }, { "input": "The species below Tc hops between the two low temperature site patterns, and the one above Tc represents an average of the molecular spin Hamiltonian coupling tensors of the two 77 K sites.", "output": "There is no related enetity." }, { "input": "In addition, the low and high temperature species hop between one another, contributing to the dynamic averaging.", "output": "There is no related enetity." }, { "input": "Spectral simulations using this 4 - state model determined a hop rate between the two low temperature sites nu h4 = 4. 5 x 10 ( 8 ) s ( - 1 ) and between the low and high temperature states nu h2 = 1. 7 x 10 ( 8 ) s ( - 1 ) at 160 K.", "output": "There is no related enetity." }, { "input": "An Arrhenius relationship of hop rate and temperature gave energy barriers of Delta E4 = 389 cm ( - 1 ) and Delta E2 = 656 cm ( - 1 ) between the two low temperature sites and between the low and high temperature states, respectively.", "output": "There is no related enetity." }, { "input": "Preventing Interfacial Recombination in Colloidal Quantum Dot Solar Cells by Doping the Metal Oxide.", "output": "Metal Oxide." }, { "input": "Recent research has pushed the efficiency of colloidal quantum dot solar cells toward a level that spurs commercial interest.", "output": "There is no related enetity." }, { "input": "Quantum dot / metal oxide bilayers form the most efficient colloidal quantum dot solar cells, and most studies have advanced the understanding of the quantum dot component.", "output": "metal oxide." }, { "input": "We study the interfacial recombination process in depleted heterojunction colloidal quantum dot ( QD ) solar cells formed with ZnO as the oxide by varying ( i ) the carrier concentration of the ZnO layer and ( ii ) the density of intragap recombination sites in the QD layer.", "output": "ZnO, oxide, ZnO." }, { "input": "We find that the open - circuit voltage and efficiency of PbS QD / ZnO devices can be improved by 50 % upon doping of the ZnO with nitrogen to reduce its carrier concentration.", "output": "PbS, ZnO, ZnO, nitrogen." }, { "input": "In contrast, doping the ZnO did not change the performance of PbSe QD / ZnO solar cells.", "output": "ZnO, PbSe, ZnO." }, { "input": "We use X - ray photoemission spectroscopy, ultraviolet photoemission spectroscopy, transient photovoltage decay measurements, transient absorption spectroscopy, and intensity - dependent photocurrent measurements to investigate the origin of this effect.", "output": "There is no related enetity." }, { "input": "We find a significant density of intragap states within the band gap of the PbS quantum dots.", "output": "PbS." }, { "input": "These states facilitate recombination at the PbS / ZnO interface, which can be suppressed by reducing the density of occupied states in the ZnO.", "output": "PbS, ZnO, ZnO." }, { "input": "For the PbSe QD / ZnO solar cells, where fewer intragap states are observed in the quantum dots, the interfacial recombination channel does not limit device performance.", "output": "PbSe, ZnO." }, { "input": "Our study sheds light on the mechanisms of interfacial recombination in colloidal quantum dot solar cells and emphasizes the influence of quantum dot intragap states and metal oxide properties on this loss pathway.", "output": "metal oxide." }, { "input": "Low - temperature NMR studies on the geometry of base pairs involving 5 - substituted uracil derivatives.", "output": "5 - substituted uracil." }, { "input": "Uridine ( U ) imino proton chemical shifts, measured in the slow hydrogen - bond exchange regime at low temperatures in a freonic solution, show that electron - withdrawing 5 - bromo and 5 - fluoro substituents on the uracil base strengthen NHN hydrogen bonds in ( X ) U. A base pairs formed by the free nucleosides.", "output": "Uridine, hydrogen, 5 - bromo, 5 - fluoro, uracil, NHN, hydrogen, nucleosides." }, { "input": "Whereas the halogens do not alter the preferential formation of Watson - Crick geometries, self - associates of the halouracils point to a more favorable engagement of the 2 - carbonyl as proton acceptor in the cyclic hydrogen bonds, suggesting increased formation of reverse geometries and wobble base pairs with guanine when compared to the thymine base.", "output": "halogens, halouracils, 2 - carbonyl, hydrogen, guanine, thymine." }, { "input": "Employing ( 15 ) N - labeled 5 - bromouridine, no noticeable population of minor enol tautomers is found in the freonic mixture at 113 K.", "output": "( 15 ) N, 5 - bromouridine, enol." }, { "input": "Inflammation, serotonin and major depression.", "output": "serotonin." }, { "input": "The understanding of the neurobiological processes leading to major depressive disorder ( MDD ) is an active field of research in the scientific community.", "output": "There is no related enetity." }, { "input": "For years, the alteration of monoamine neurotransmission, in particular serotonin ( 5 - HT ), has been considered the most significant pathophysiological mechanism of the disorder.", "output": "monoamine, serotonin, 5 - HT." }, { "input": "However, biological data supporting the postulated MDD - related monoamine alterations have been inconclusive, and the use of monoaminergic antidepressants has not yielded the expected results.", "output": "There is no related enetity." }, { "input": "In the last few years, it has been demonstrated that inflammatory pathways have a significant role in the pathophysiology of MDD.", "output": "There is no related enetity." }, { "input": "According to the cytokine hypothesis, the disorder would be due to a stress - related increased production of cytokines, including interleukins, tumor necrosis factor - alpha and interferon - alpha and gamma.", "output": "There is no related enetity." }, { "input": "These, in turns, would cause the activation of the indoleamine 2, 3 dioxygenase ( IDO ), with subsequent production of tryptophan ( TRP ) catabolites along the IDO pathway ( TRYCATs ) and decreased availability of TRP and 5 - HT.", "output": "indoleamine, tryptophan, TRP, TRP, 5 - HT." }, { "input": "Besides monoamines, other molecular mechanisms, as those within the inflammatory pathways, should be taken into account in the attempt to clarify the pathophysiology of MDD and to improve its treatment.", "output": "monoamines." }, { "input": "Study on medicinal chemistry of k203 in wistar rats and beagle dogs.", "output": "There is no related enetity." }, { "input": "K203 is an experimental bis - pyridinium mono - aldoxime type cholinesterase reactivator of potential use in organophosphate / organophosphonate poisoning.", "output": "bis - pyridinium mono - aldoxime, organophosphate, organophosphonate." }, { "input": "Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion - pair HPLC.", "output": "There is no related enetity." }, { "input": "Serum and cerebrospinal fluid concentrations of K203 were determined using ion - pair reversedphase chromatography on octadecyl silica column.", "output": "octadecyl silica." }, { "input": "HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0. 1 mu g / mL while its low concentrations in cerebrospinal fluid required electrochemical detection ( 0. 015 through 4 mu g / mL range ).", "output": "There is no related enetity." }, { "input": "In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration.", "output": "There is no related enetity." }, { "input": "Zero order pharmacokinetics was also observed in beagle dogs after low dose ( 15 mu mol / kg ) of K203 administration.", "output": "There is no related enetity." }, { "input": "High dose administration ( 250 mu mol / kg ) led to subsequent hindered elimination from both cerebrospinal fluid and serum.", "output": "There is no related enetity." }, { "input": "Transgenerational, dynamic methylation of stomata genes in response to low relative humidity.", "output": "There is no related enetity." }, { "input": "Transgenerational inheritance of abiotic stress - induced epigenetic modifications in plants has potential adaptive significance and might condition the offspring to improve the response to the same stress, but this is at least partly dependent on the potency, penetrance and persistence of the transmitted epigenetic marks.", "output": "There is no related enetity." }, { "input": "We examined transgenerational inheritance of low Relative Humidity - induced DNA methylation for two gene loci in the stomatal developmental pathway in Arabidopsis thaliana and the abundance of associated short - interfering RNAs ( siRNAs ).", "output": "There is no related enetity." }, { "input": "Heritability of low humidity - induced methylation was more predictable and penetrative at one locus ( SPEECHLESS, entropy <= 0. 02; chi 2 < 0. 001 ) than the other ( FAMA, entropy <= 0. 17; chi 2 ns ).", "output": "There is no related enetity." }, { "input": "Methylation at SPEECHLESS correlated positively with the continued presence of local siRNAs ( r2 = 0. 87; p = 0. 013 ) which, however, could be disrupted globally in the progeny under repeated stress.", "output": "There is no related enetity." }, { "input": "Transgenerational methylation and a parental low humidity - induced stomatal phenotype were heritable, but this was reversed in the progeny under repeated treatment in a previously unsuspected manner.", "output": "There is no related enetity." }, { "input": "Transfer of highly porous nanoparticle layers to various substrates through mechanical compression.", "output": "There is no related enetity." }, { "input": "A new two - step layer transfer process is introduced that is capable of fabricating mechanically stabilized highly porous nanoparticle layers on various substrates.", "output": "There is no related enetity." }, { "input": "In a first step titanium dioxide nanoparticles were synthesized with Flame - Spray - Pyrolysis and accumulated on a filter paper in the gas phase.", "output": "titanium dioxide." }, { "input": "In a second step this highly porous filter cake is subsequently transferred to a final substrate via low pressure lamination at room temperature.", "output": "There is no related enetity." }, { "input": "This leads to mechanical restructuring and stabilization of the porous layer.", "output": "There is no related enetity." }, { "input": "Pore size analysis indicates homogenization of the layers through rearrangement of the aggregates inside the layers that increases with applied pressure.", "output": "There is no related enetity." }, { "input": "Additionally, the Young ' s moduli of the layers were quantified through Colloidal - Probe - Technique indentation measurements with an Atomic - Force - Microscope.", "output": "There is no related enetity." }, { "input": "The highest lamination pressure of 2. 5 MPa resulted in triplication of the Young ' s modulus.", "output": "There is no related enetity." }, { "input": "The results show that our novel two - step layer transfer process leads to mechanically stabilized layers that preserve their high porosity.", "output": "There is no related enetity." }, { "input": "Through the decoupling of the high temperature nanoparticle synthesis and the final substrate the process also enables the possibility to apply temperature sensitive substrates such as polypropylene foil.", "output": "polypropylene." }, { "input": "Structural and Functional Aspects of Hetero - oligomers Formed by the Small Heat - Shock Proteins alpha B crystallin and HSP27.", "output": "There is no related enetity." }, { "input": "Small heat shock proteins ( sHSPs ) exist as large polydisperse species in which there is constant dynamic subunit exchange between oligomeric and dissociated forms.", "output": "There is no related enetity." }, { "input": "Their primary role in vivo is to bind destabilized proteins and prevent their misfolding and aggregating.", "output": "There is no related enetity." }, { "input": "alpha B Crystallin ( alpha B ) and HSP27 are the two most widely distributed and most studied sHSPs in the human body.", "output": "There is no related enetity." }, { "input": "They are co - expressed in different tissues where they are known to associate with each other and form hetero - oligomeric complexes.", "output": "There is no related enetity." }, { "input": "This study aimed to determine how these two sHSPs interact to form hetero - oligomers in vitro and whether, by doing so, there is an increase in their chaperone activity and stability compared to their homo - oligomeric forms.", "output": "There is no related enetity." }, { "input": "Results demonstrate that HSP27 and alpha B form polydisperse hetero - oligomers in vitro which have an average molecular mass higher than each of the homo - oligomers and are more thermostable than alpha B, but less so than HSP27.", "output": "There is no related enetity." }, { "input": "The hetero - oligomer chaperone function was found to be equivalent to that of alpha B, with each being significantly better at preventing the amorphous aggregation of alpha - lactalbumin and the amyloid fibril formation of alpha - synuclein in comparison to HSP27.", "output": "There is no related enetity." }, { "input": "Using mass spectrometry to monitor subunit exchange over time it was found that HSP27 and alpha B exchange subunits 23 % faster than the reported rate for HSP27 / alpha A, and almost twice that of alpha A / alpha B.", "output": "There is no related enetity." }, { "input": "This represents the first quantitative evaluation of HSP27 / alpha B subunit exchange and the results are discussed in the broader context of regulation of function and cellular proteostasis.", "output": "There is no related enetity." }, { "input": "Impact of the Proline Residue on Ligand Binding of Neurotensin Receptor 2 ( NTS2 ) - Selective Peptide - Peptoid Hybrids.", "output": "Proline." }, { "input": "To investigate the binding mode and structure - activity relationships ( SARs ) of selective neurotensin receptor 2 ( NTS2 ) ligands, novel peptide - peptoid hybrids that simulate the function of the endogenous ligand were developed.", "output": "There is no related enetity." }, { "input": "Starting from our recently described NTS2 ligands of type 1, structural variants of type 2 and the metabolically stable analogues 3 a, b were developed.", "output": "There is no related enetity." }, { "input": "Replacement of the proline unit by a collection of structural surrogates and evaluation of the respective molecular probes for NTS2 affinity and selectivity indicated similar SARs as described for NT ( 8 - 13 ) derivatives bound to the subtype NTS1.", "output": "proline." }, { "input": "Peptide - peptoid hybrids 2 d, 3 a, b showed substantial NTS2 binding affinity ( Ki = 8. 1 - 16 nM ) and 2400 - 8600 - fold selectivity over NTS1.", "output": "There is no related enetity." }, { "input": "The thiazolidine derivative 3 b showed metabolic stability over 32 h in a serum degradation assay.", "output": "thiazolidine." }, { "input": "In an inositol phosphate accumulation assay, the neurotensin mimetics 3 a and 3 b displayed an inhibition of constitutive activity exceeding 1. 7 - 2. 0 times the activity of NT ( 8 - 13 ).", "output": "inositol phosphate." }, { "input": "The fluorinated derivative 3 a could afford attractive opportunities to detect NTS2 by ( 19 ) F magnetic resonance imaging.", "output": "There is no related enetity." }, { "input": "Enhanced Striatal beta 1 - Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats.", "output": "There is no related enetity." }, { "input": "After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function.", "output": "There is no related enetity." }, { "input": "The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood.", "output": "There is no related enetity." }, { "input": "To investigate this, we measured changes in gene expression the dorsal striatum, where 17 beta - estradiol modulates catecholamine signaling.", "output": "17 beta - estradiol, catecholamine." }, { "input": "In human caudate, quantitative PCR determined a significant elevation in beta 1 - adrenergic receptor ( beta 1AR ) expression in menopausal females when compared with similarly aged males.", "output": "There is no related enetity." }, { "input": "No differences were detected in beta 2 - adrenergic and D1 - and D2 - dopamine receptor expression.", "output": "dopamine." }, { "input": "Consistent with humans, adult ovariectomized female rats exhibited a similar increase in beta 1AR expression when compared with gonadectomized males.", "output": "There is no related enetity." }, { "input": "No sex difference in beta 1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy.", "output": "There is no related enetity." }, { "input": "Additionally, increased beta 1AR expression in adult ovariectomized females was not observed if animals were masculinized / defeminized with testosterone injections as neonates.", "output": "testosterone." }, { "input": "To generate a model system for assessing functional impact, increased beta 1AR expression was induced in female - derived cultured striatal neurons via exposure to and then removal of hormone - containing serum.", "output": "There is no related enetity." }, { "input": "Increased beta 1AR action on cAMP formation, cAMP response element - binding protein phosphorylation and gene expression was observed.", "output": "cAMP, cAMP." }, { "input": "This up - regulation of beta 1AR action was eliminated with 17 beta - estradiol addition to the media, directly implicating this hormone as a regulator of beta 1AR expression.", "output": "17 beta - estradiol." }, { "input": "Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence.", "output": "There is no related enetity." }, { "input": "Antithrombotic activity of a newly synthesized coumarin derivative 3 - ( 5 - hydroxy - 2, 2 - dimethyl - chroman - 6 - yl ) - N - { 2 - [ 3 - ( 5 - hydroxy - 2, 2 - dimethyl - chroman - 6 - yl ) - propionylamino ] - ethyl } - propionamide.", "output": "coumarin, 3 - ( 5 - hydroxy - 2 , 2 - dimethyl - chroman - 6 - yl ) - N - { 2 - [ 3 - ( 5 - hydroxy - 2 , 2 - dimethyl - chroman - 6 - yl ) - propionylamino ] - ethyl } - propionamide." }, { "input": "Anti - platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions.", "output": "There is no related enetity." }, { "input": "This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis.", "output": "seselin." }, { "input": "Administration of C3 ( 16 mg / kg ) offered 70 % protection against collagen - and epinephrine - induced pulmonary thromboembolism and 30 % protection against arachidonic acid - induced death in mice, without adversely affecting bleeding time.", "output": "epinephrine, arachidonic acid." }, { "input": "No significant difference was observed by C3 in ferric chloride - induced arterial thrombosis in rats.", "output": "ferric chloride." }, { "input": "Significant reduction in thrombus weight was observed in arteriovenous shunt model.", "output": "There is no related enetity." }, { "input": "In rat PRP, C3 reduced ADP and collagen - induced platelet aggregation.", "output": "ADP." }, { "input": "In chronic hamster model of dyslipidemia, administration of C3 ( 16 mg / kg p. o. for 90 days ) had no effect on plasma lipids, vasoreactivity and platelet adhesion.", "output": "There is no related enetity." }, { "input": "C3 fed hamsters showed reduced whole - blood aggregation response to ADP and collagen compared to HC - fed hamsters.", "output": "ADP." }, { "input": "In addition, C3 augmented thrombin time; however, time to occlusion was not increased.", "output": "There is no related enetity." }, { "input": "These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time.", "output": "There is no related enetity." }, { "input": "The high benefit / risk ratio of this compound makes it a suitable candidate for future valid studies.", "output": "There is no related enetity." }, { "input": "Virtual and in vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against xanthine oxidase and cyclooxygenase - 2 for gout treatment.", "output": "flavonoids, isoflavones, xanthine." }, { "input": "Synthetic drugs such as allopurinol and benzbromarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid.", "output": "allopurinol, benzbromarone, uric acid." }, { "input": "We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase and cyclooxygenase - 2 enzymes.", "output": "xanthine." }, { "input": "In this study, we report the screening of nine compounds of flavonoids from the ZINC and PubChem databases ( containing 2092 flavonoids ) using the IGEMDOCK software tool against the xanthine oxidase and cyclooxygenase - 2 3D protein structures.", "output": "flavonoids, flavonoids, xanthine." }, { "input": "Each compound was also evaluated by an in vitro bioassay testing the inhibition of xanthine oxidase and cyclooxygenase - 2.", "output": "xanthine." }, { "input": "Myricetin and luteolin were found to be the potential dual inhibitors of xanthine oxidase and cyclooxygenase - 2 as demonstrated by IC ( 50 ): 62. 7 and 3. 29 mu g / mL ( xanthine oxidase ) / 70. 8 and 16. 38 mu g / mL ( cyclooxygenase - 2 ), respectively.", "output": "Myricetin, luteolin, xanthine, xanthine." }, { "input": "In addition, structure - activity relationships and other important factors of the flavonoids binding to the active site of xanthine oxidase and cyclooxygenase - 2 were discussed, which is expected for further rational drug design.", "output": "flavonoids, xanthine." }, { "input": "Bioinformatics and Molecular Dynamics Simulation Study of L1 Stalk Non - Canonical rRNA Elements: Kink - Turns, Loops, and Tetraloops.", "output": "There is no related enetity." }, { "input": "The L1 stalk is a prominent mobile element of the large ribosomal subunit.", "output": "There is no related enetity." }, { "input": "We explore the structure and dynamics of its non - canonical rRNA elements, which include two kink - turns, an internal loop, and a tetraloop.", "output": "There is no related enetity." }, { "input": "We use bioinformatics to identify the L1 stalk RNA conservation patterns and carry out over 11. 5 mu s of MD simulations for a set of systems ranging from isolated RNA building blocks up to complexes of L1 stalk rRNA with the L1 protein and tRNA fragment.", "output": "There is no related enetity." }, { "input": "We show that the L1 stalk tetraloop has an unusual GNNA or UNNG conservation pattern deviating from major GNRA and YNMG RNA tetraloop families.", "output": "There is no related enetity." }, { "input": "We suggest that this deviation is related to a highly conserved tertiary contact within the L1 stalk.", "output": "There is no related enetity." }, { "input": "The available X - ray structures contain only UCCG tetraloops which in addition differ in orientation ( anti vs syn ) of the guanine.", "output": "guanine." }, { "input": "Our analysis suggests that the anti orientation might be a mis - refinement, although even the anti interaction would be compatible with the sequence pattern and observed tertiary interaction.", "output": "There is no related enetity." }, { "input": "Alternatively, the anti conformation may be a real substate whose population could be pH - dependent, since the guanine syn orientation requires protonation of cytosine in the tertiary contact.", "output": "guanine, cytosine." }, { "input": "In absence of structural data, we use molecular modeling to explore the GCCA tetraloop that is dominant in bacteria and suggest that the GCCA tetraloop is structurally similar to the YNMG tetraloop.", "output": "There is no related enetity." }, { "input": "Kink - turn Kt - 77 is unusual due to its 11 - nucleotide bulge.", "output": "nucleotide." }, { "input": "The simulations indicate that the long bulge is a stalk - specific eight - nucleotide insertion into consensual kink - turn only subtly modifying its structural dynamics.", "output": "nucleotide." }, { "input": "We discuss a possible evolutionary role of helix H78 and a mechanism of L1 stalk interaction with tRNA.", "output": "There is no related enetity." }, { "input": "We also assess the simulation methodology.", "output": "There is no related enetity." }, { "input": "The simulations provide a good description of the studied systems with the latest bsc0 chi OL3 force field showing improved performance.", "output": "There is no related enetity." }, { "input": "Still, even bsc0 chi OL3 is unable to fully stabilize an essential sugar - edge H - bond between the bulge and non - canonical stem of the kink - turn.", "output": "sugar, H." }, { "input": "Inclusion of Mg ( 2 + ) ions may deteriorate the simulations.", "output": "Mg ( 2 + )." }, { "input": "On the other hand, monovalent ions can in simulations readily occupy experimental Mg ( 2 + ) binding sites.", "output": "Mg ( 2 + )." }, { "input": "Novel analgesic / anti - inflammatory agents: 1, 5 - diarylpyrrole nitrooxyalkyl ethers and related compounds as cyclooxygenase - 2 inhibiting nitric oxide donors.", "output": "1 , 5 - diarylpyrrole nitrooxyalkyl ethers, nitric oxide." }, { "input": "A series of 3 - substituted 1, 5 - diarylpyrroles bearing a nitrooxyalkyl side chain linked to different spacers were designed.", "output": "3 - substituted 1 , 5 - diarylpyrroles, nitrooxyalkyl." }, { "input": "New classes of pyrrole - derived nitrooxyalkyl inverse esters, carbonates, and ethers ( 7 - 10 ) as COX - 2 selective inhibitors and NO donors were synthesized and are herein reported.", "output": "pyrrole, nitrooxyalkyl, esters, carbonates, ethers, NO." }, { "input": "By taking into account the metabolic conversion of nitrooxyalkyl ethers ( 9, 10 ) into corresponding alcohols, derivatives 17 and 18 were also studied.", "output": "nitrooxyalkyl ethers, alcohols." }, { "input": "Nitrooxy derivatives showed NO - dependent vasorelaxing properties, while most of the compounds proved to be very potent and selective COX - 2 inhibitors in in vitro experimental models.", "output": "Nitrooxy, NO." }, { "input": "Further in vivo studies on compounds 9a, c and 17a highlighted good anti - inflammatory and antinociceptive activities.", "output": "There is no related enetity." }, { "input": "Compound 9c was able to inhibit glycosaminoglycan ( GAG ) release induced by interleukin - 1 beta ( IL - 1 beta ), showing cartilage protective properties.", "output": "There is no related enetity." }, { "input": "Finally, molecular modeling and ( 1 ) H - and ( 13 ) C - NMR studies performed on compounds 6c, d, 9c, and 10b allowed the right conformation of nitrooxyalkyl ester and ether side chain of these molecules within the COX - 2 active site to be assessed.", "output": "( 1 ) H, ( 13 ) C, nitrooxyalkyl ester and ether." }, { "input": "Electrohydrodynamic Bubbling: An Alternative Route to Fabricate Porous Structures of Silk Fibroin Based Materials.", "output": "There is no related enetity." }, { "input": "Conventional fabrication techniques and structures employed in the design of silk fibroin ( SF ) based porous materials provide only limited control over pore size and require several processing stages.", "output": "There is no related enetity." }, { "input": "In this study, it is shown that, by utilizing electrohydrodynamic bubbling, not only can new hollow spherical structures of SF be formed in a single step by means of bubbles, but the resulting bubbles can serve as pore generators when dehydrated.", "output": "There is no related enetity." }, { "input": "The bubble characteristics can be controlled through simple adjustments to the processing parameters.", "output": "There is no related enetity." }, { "input": "Bubbles with diameters in the range of 240 - 1000 mu m were fabricated in controlled fashion.", "output": "There is no related enetity." }, { "input": "FT - IR characterization confirmed that the rate of air infused during processing enhanced beta - sheet packing in SF at higher flow rates.", "output": "There is no related enetity." }, { "input": "Dynamic mechanical analysis also demonstrated a correlation between air flow rate and film tensile strength.", "output": "There is no related enetity." }, { "input": "Results indicate that electrohydrodynamically generated SF and their composite bubbles can be employed as new tools to generate porous structures in a controlled manner with a range of potential applications in biocoatings and tissue engineering scaffolds.", "output": "There is no related enetity." }, { "input": "Generalized structural description of calcium - sodium aluminosilicate hydrate gels: the cross - linked substituted tobermorite model.", "output": "calcium - sodium aluminosilicate hydrate, tobermorite." }, { "input": "Structural models for the primary strength and durability - giving reaction product in modern cements, a calcium ( alumino ) silicate hydrate gel, have previously been based solely on non - cross - linked tobermorite structures.", "output": "calcium ( alumino ) silicate, tobermorite." }, { "input": "However, recent experimental studies of laboratory - synthesized and alkali - activated slag ( AAS ) binders have indicated that the calcium - sodium aluminosilicate hydrate [ C - ( N ) - A - S - H ] gel formed in these systems can be significantly cross - linked.", "output": "calcium - sodium aluminosilicate hydrate, C - ( N ) - A - S - H." }, { "input": "Here, we propose a model that describes the C - ( N ) - A - S - H gel as a mixture of cross - linked and non - cross - linked tobermorite - based structures ( the cross - linked substituted tobermorite model, CSTM ), which can more appropriately describe the spectroscopic and density information available for this material.", "output": "C - ( N ) - A - S - H, tobermorite, tobermorite." }, { "input": "Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite - type C - ( N ) - A - S - H gel, due to the structural constraints of the gel.", "output": "tobermorite, C - ( N ) - A - S - H." }, { "input": "Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four - coordinated silicate and aluminate species.", "output": "silicate, aluminate." }, { "input": "The CSTM therefore provides a more advanced description of the chemistry and structure of calcium - sodium aluminosilicate gel structures than that previously established in the literature.", "output": "calcium - sodium aluminosilicate." }, { "input": "Methionine salvage and S - adenosylmethionine: essential links between sulfur, ethylene and polyamine biosynthesis.", "output": "Methionine, S - adenosylmethionine, sulfur, ethylene." }, { "input": "Both Met ( methionine ) and SAM ( S - adenosylmethionine ), the activated form of Met, participate in a number of essential metabolic pathways in plants.", "output": "Met, methionine, SAM, S - adenosylmethionine, Met." }, { "input": "The subcellular compartmentalization of Met fluxes will be discussed in the present review with respect to regulation and communication with the sulfur assimilation pathway, the network of the aspartate - derived amino acids and the demand for production of SAM.", "output": "Met, sulfur, aspartate, amino acids, SAM." }, { "input": "SAM enters the ethylene, nicotianamine and polyamine biosynthetic pathways and provides the methyl group for the majority of methylation reactions required for plant growth and development.", "output": "SAM, ethylene, nicotianamine, methyl." }, { "input": "The multiple essential roles of SAM require regulation of its synthesis, recycling and distribution to sustain these different pathways.", "output": "SAM." }, { "input": "A particular focus of the present review will be on the function of recently identified genes of the Met salvage cycle or Yang cycle and the importance of the Met salvage cycle in the metabolism of MTA ( 5 ' - methylthioadenosine ).", "output": "Met, Met, MTA, 5 ' - methylthioadenosine." }, { "input": "MTA has the potential for product inhibition of ethylene, nicotianamine and polyamine biosynthesis which provides an additional link between these pathways.", "output": "MTA, ethylene, nicotianamine." }, { "input": "Interestingly, regulation of Met cycle genes was found to differ between plant species as shown for Arabidopsis thaliana and Oryza sativa.", "output": "Met." }, { "input": "Galangin attenuates mast cell - mediated allergic inflammation.", "output": "Galangin." }, { "input": "A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis.", "output": "There is no related enetity." }, { "input": "Therefore discovery of drugs for the treatment of these diseases is an important subject in human health.", "output": "There is no related enetity." }, { "input": "In this study, we investigated anti - allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models.", "output": "galangin." }, { "input": "Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12 - mystate 13 - acetate plus calcium ionophore A23187 - stimulated human mast cells ( HMC - 1 ).", "output": "Galangin, histamine, calcium, phorbol 12 - mystate 13 - acetate, calcium." }, { "input": "Galangin decreased expression of pro - inflammatory cytokines, such as tumor necrosis factor ( TNF ) - alpha, interleukin ( IL ) - 6, IL - 1 beta, and IL - 8.", "output": "Galangin." }, { "input": "The inhibitory effect of galangin on theses pro - inflammatory cytokines was related with c - Jun N - terminal kinases, and p38 mitogen - activated protein kinase, nuclear factor - kappa B, and caspase - 1.", "output": "galangin, N." }, { "input": "Furthermore, galangin attenuated IgE - mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue.", "output": "galangin, histamine." }, { "input": "The inhibitory effects of galangin were more potent than cromolyn, a known anti - allergic drug.", "output": "galangin, cromolyn." }, { "input": "Our results showed that galangin down - regulates mast cell - derived allergic inflammatory reactions by blocking histamine release and expression of pro - inflammatory cytokines.", "output": "galangin, histamine." }, { "input": "In light of in vitro and in vivo anti - allergic inflammatory effects, galangin could be a beneficial anti - allergic inflammatory agent.", "output": "galangin." }, { "input": "Scoparone attenuates d - galactosamine / lipopolysaccharide - induced fulminant hepatic failure through inhibition of toll - like receptor 4 signaling in mice.", "output": "Scoparone, d - galactosamine." }, { "input": "The purpose of this study was to investigate the protective effects and molecular mechanisms of scoparone on d - galactosamine ( d - GalN ) / lipopolysaccharide ( LPS ) - induced fulminant hepatic failure ( FHF ) in mice.", "output": "scoparone, d - galactosamine, d - GalN." }, { "input": "FHF was induced in mice by intraperitoneal injection of d - GalN ( 800mg / kg ) / LPS ( 40 mu g / kg ).", "output": "d - GalN." }, { "input": "Mice were treated intraperitoneally with scoparone 1h before d - GalN / LPS treatment.", "output": "scoparone, d - GalN." }, { "input": "Treatment with d - GalN / LPS markedly increased mortality, serum aminotransferase activity, and tolllike receptor 4 ( TLR4 ) protein expression, and these increases were attenuated by scoparone.", "output": "d - GalN, scoparone." }, { "input": "Treatment with d - GalN / LPS markedly increased myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal - regulated kinase and c - Jun N - terminal kinase, nuclear protein expression of nuclear factor kappa B and phosphorylated c - Jun, and levels of serum tumor necrosis factor - alpha and interleukin - 6 and these increases were attenuated by scoparone.", "output": "d - GalN, N, scoparone." }, { "input": "In addition, increased levels of toll - receptor - associated activator of interferon protein expression, phosphorylation of interferon ( IFN ) regulatory factor 3, and serum IFN - beta level in d - GalN / LPS - treated mice were attenuated by scoparone.", "output": "d - GalN, scoparone." }, { "input": "Our results suggest that scoparone attenuates d - GalN / LPSinduced liver damage by inhibition of the TLR - mediated inflammatory pathway.", "output": "scoparone, d - GalN." }, { "input": "Aberrant activation of M phase proteins by cell proliferation - evoking carcinogens after 28 - day administration in rats.", "output": "There is no related enetity." }, { "input": "We have previously reported that hepatocarcinogens increase liver cells expressing p21 ( Cip1 ), a G1 checkpoint protein and M phase proteins after 28 - day treatment in rats.", "output": "There is no related enetity." }, { "input": "This study aimed to identify early prediction markers of carcinogens available in many target organs after 28 - day treatment in rats.", "output": "There is no related enetity." }, { "input": "Immunohistochemical analysis was performed on Ki - 67, p21 ( Cip1 ) and M phase proteins [ nuclear Cdc2, phospho - Histone H3 ( p - Histone H3 ), Aurora B and heterochromatin protein 1 alpha ( HP1 alpha ) ] with carcinogens targeting different organs.", "output": "There is no related enetity." }, { "input": "Carcinogens targeting thyroid ( sulfadimethoxine; SDM ), urinary bladder ( phenylethyl isothiocyanate ), forestomach ( butylated hydroxyanisole; BHA ), glandular stomach ( catechol; CC ), and colon ( 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4, 5 - b ] pyridine and chenodeoxycholic acid ) were examined using a non - carcinogenic toxicant ( caprolactam ) and carcinogens targeting other organs as negative controls.", "output": "sulfadimethoxine, SDM, phenylethyl isothiocyanate, butylated hydroxyanisole, BHA, catechol, 2 - amino - 1 - methyl - 6 - phenylimidazo [ 4 , 5 - b ] pyridine, chenodeoxycholic acid, caprolactam." }, { "input": "All carcinogens increased Ki - 67 ( + ), nuclear Cdc2 ( + ), p - Histone H3 ( + ) or Aurora B ( + ) carcinogenic target cells, except for both colon carcinogens, which did not increase cell proliferation.", "output": "There is no related enetity." }, { "input": "On the other hand, p21 ( Cip1 + ) cells increased with SDM and CC.", "output": "There is no related enetity." }, { "input": "HP1 alpha responded only to BHA.", "output": "BHA." }, { "input": "Results revealed carcinogens evoking cell proliferation concurrently induced cell cycle arrest at M phase or showing chromosomal instability reflecting aberration in cell cycle regulation, irrespective of target organs, after 28 - day treatment.", "output": "There is no related enetity." }, { "input": "Therefore, M phase proteins may be early prediction markers of carcinogens evoking cell proliferation in many target organs.", "output": "There is no related enetity." }, { "input": "Potent naphthoquinones against antimony - sensitive and - resistant Leishmania parasites: Synthesis of novel alpha - and nor - alpha - lapachone - based 1, 2, 3 - triazoles by copper - catalyzed azide - alkyne cycloaddition.", "output": "naphthoquinones, alpha - and nor - alpha - lapachone, 1 , 2 , 3 - triazoles, copper, azide, alkyne." }, { "input": "Continuing our screening program for novel anti - parasite compounds, we synthesized seven 1, 4 - naphthoquinones coupled to 1, 2, 3 - triazoles, five nor - beta - lapachone - based 1, 2, 3 - triazoles and ten alpha - lapachone - based 1, 2, 3 - triazoles.", "output": "1 , 4 - naphthoquinones, 1 , 2 , 3 - triazoles, nor - beta - lapachone, 1 , 2 , 3 - triazoles, alpha - lapachone, 1 , 2 , 3 - triazoles." }, { "input": "These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony - sensitive and - resistant strains of Leishmania infantum ( syn. Leishmania chagasi ) and Leishmania amazonensis.", "output": "There is no related enetity." }, { "input": "The toxicity of these compounds to mammalian cells was also examined.", "output": "There is no related enetity." }, { "input": "The substances were more potent than an antimonial drug, with IC50 values ranging from 1. 0 to 50. 7 mu M.", "output": "There is no related enetity." }, { "input": "Nor - alpha - lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10 - 15.", "output": "Nor - alpha - lapachone." }, { "input": "These compounds emerged as important leads for further investigation as antileishmanial agents.", "output": "There is no related enetity." }, { "input": "Additionally, one of these compounds exhibited cross - resistance in Sb - resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites.", "output": "There is no related enetity." }, { "input": "Heterocyclic bismuth carboxylates based on a diphenyl sulfone scaffold: Synthesis and antifungal activity against Saccharomycescerevisiae.", "output": "Heterocyclic bismuth carboxylates, diphenyl sulfone." }, { "input": "A series of heterocyclic organobismuth ( III ) carboxylates 4 and 5 [ RCO2Bi ( C6H4 - 2 - SO2C6H4 - 1 ' - ) ] derived from diphenyl sulfone was synthesized to determine the influence of the carboxylate ligand structure on the lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae.", "output": "heterocyclic organobismuth ( III ) carboxylates, RCO2Bi ( C6H4 - 2 - SO2C6H4 - 1 ' - ), diphenyl sulfone, carboxylate." }, { "input": "In contrast to the clear structure - activity relationship between the size of the inhibition zone and the value of ClogP for specific substitution on diphenyl sulfone scaffold 1 [ ClBi ( 5 - RC6H3 - 2 - SO2C6H4 - 1 ' - ) ], scaffolds 4 and 5 showed similar inhibition activities irrespective of the ClogP value.", "output": "diphenyl sulfone, ClBi ( 5 - RC6H3 - 2 - SO2C6H4 - 1 ' - )." }, { "input": "This suggests that these molecules function inside the yeast cell by separating into the cationic heterocyclic bismuth scaffold and the anionic carboxylate moiety, and that the bismuth scaffold plays an important role in the inhibition activity.", "output": "bismuth, carboxylate, bismuth." }, { "input": "Novel and highly potent histamine H3 receptor ligands.", "output": "histamine." }, { "input": "Part 3: An alcohol function to improve the pharmacokinetic profile.", "output": "alcohol." }, { "input": "Synthesis and biological evaluation of potent histamine H3 receptor antagonists incorporating a hydroxyl function are described.", "output": "histamine, hydroxyl." }, { "input": "Compounds in this series exhibited nanomolar binding affinities for human receptor, illustrating a new possible component for the H3 pharmacophore.", "output": "There is no related enetity." }, { "input": "As demonstrated with compound BP1. 4160 ( cyclohexanol 19 ), the introduction of an alcohol function counter - intuitively allowed to reach high in vivo efficiency and favorable pharmacokinetic profile with reduced half - life.", "output": "BP1 . 4160, cyclohexanol, alcohol." }, { "input": "Impact of cell wall composition on maize resistance to pests and diseases.", "output": "There is no related enetity." }, { "input": "In cereals, the primary cell wall is built of a skeleton of cellulosic microfibrils embedded in a matrix of hemicelluloses and smaller amounts of pectins, glycoproteins and hydroxycinnamates.", "output": "hydroxycinnamates." }, { "input": "Later, during secondary wall development, p - coumaryl, coniferyl and sinapyl alcohols are copolymerized to form mixed lignins.", "output": "p - coumaryl , coniferyl and sinapyl alcohols." }, { "input": "Several of these cell wall components show a determinative role in maize resistance to pest and diseases.", "output": "There is no related enetity." }, { "input": "However, defense mechanisms are very complex and vary among the same plant species, different tissues or even the same tissue at different developmental stages.", "output": "There is no related enetity." }, { "input": "Thus, it is important to highlight that the role of the cell wall components needs to be tested in diverse genotypes and specific tissues where the feeding or attacking by the pathogen takes place.", "output": "There is no related enetity." }, { "input": "Understanding the role of cell wall constituents as defense mechanisms may allow modifications of crops to withstand pests and diseases.", "output": "There is no related enetity." }, { "input": "Management of schizophrenia: clinical experience with asenapine.", "output": "asenapine." }, { "input": "Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms ( particularly depression and anxiety ).", "output": "There is no related enetity." }, { "input": "The management of schizophrenia requires effective short - and long - term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term.", "output": "There is no related enetity." }, { "input": "Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults.", "output": "Asenapine." }, { "input": "It has a unique receptor - binding profile and a broad range of therapeutic effects.", "output": "There is no related enetity." }, { "input": "Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent ' s efficacy and tolerability under ' real - world ' clinical practice conditions is also required.", "output": "There is no related enetity." }, { "input": "As in clinical trials, real - life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention.", "output": "asenapine." }, { "input": "It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia.", "output": "There is no related enetity." }, { "input": "Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters.", "output": "Asenapine." }, { "input": "As such, asenapine is valuable option for the treatment of schizophrenia in adults.", "output": "asenapine." }, { "input": "Reactivity of Chemical Sensitizers Toward Amino Acids In Cellulo Plays a Role in the Activation of the Nrf2 - ARE Pathway in Human Monocyte Dendritic Cells and the THP - 1 Cell Line.", "output": "Amino Acids." }, { "input": "Allergic contact dermatitis resulting from skin sensitization is an inflammatory skin disease linked to the use of chemicals termed haptens.", "output": "There is no related enetity." }, { "input": "Chemical reactivity is necessary for a chemical to be a sensitizer, allowing both covalent binding to proteins and maturation of dendritic cells ( DCs ) by mimicking \" danger signals. \" The aim of this study was to evaluate how the reactivity of chemical sensitizers toward amino acids translates into a biological response using the activation of the nuclear factor - erythroid 2 - related factor 2 ( Nrf2 ) pathway, which was assessed by the induction of three Nrf2 target genes ( ho - 1, nqo1, and il - 8 ) and Nrf2 protein accumulation.", "output": "amino acids." }, { "input": "Nrf2 activation is known to play a role in numerous detoxification mechanisms that could regulate danger signal outcomes in myeloid cells.", "output": "There is no related enetity." }, { "input": "Monocyte - derived DCs and THP - 1 cells were exposed to ( a ) haptens with cysteine, lysine, or cysteine / lysine reactivity, ( b ) pro - / prehaptens, and ( c ) nonsensitizing molecules with reducing or oxidative properties ( 17 molecules in total ).", "output": "cysteine, lysine, cysteine, lysine." }, { "input": "Chemicals were classified as \" Nrf2 pathway activators \" when at least two Nrf2 target genes associated with Nrf2 protein expression were induced.", "output": "There is no related enetity." }, { "input": "Results showed that most chemical sensitizers having cysteine and cysteine / lysine affinities were inducers of the Nrf2 pathway in both cell models, whereas lysine - reactive chemicals were less efficient.", "output": "cysteine, cysteine, lysine, lysine." }, { "input": "In THP - 1 cells, the Nrf2 pathway was also activated by pro - / prehaptens.", "output": "There is no related enetity." }, { "input": "Regression analysis revealed that ho - 1 and nqo1 expressions were found to be associated with chemical sensitizer reactivity to cysteine, providing evidence of the importance of chemical reactivity, as a part of danger signals, in DC biology.", "output": "cysteine." }, { "input": "An overview on the marine neurotoxin, saxitoxin: genetics, molecular targets, methods of detection and ecological functions.", "output": "saxitoxin." }, { "input": "Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish.", "output": "There is no related enetity." }, { "input": "These compounds interact with voltage - gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types.", "output": "sodium, potassium, calcium." }, { "input": "This review provides a summary of marine neurotoxins, including their structures, molecular targets and pharmacologies.", "output": "There is no related enetity." }, { "input": "Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins ( PSTs ), are unique among neurotoxins in that they are found in both marine and freshwater environments by organisms inhabiting two kingdoms of life.", "output": "Saxitoxin." }, { "input": "Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters.", "output": "There is no related enetity." }, { "input": "Bioaccumulation by filter - feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning.", "output": "saxitoxin." }, { "input": "These illnesses are a result of saxitoxin ' s ability to bind to the voltage - gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis.", "output": "saxitoxin, sodium." }, { "input": "Recent advances in saxitoxin research are discussed, including the molecular biology of toxin synthesis, new protein targets, association with metal - binding motifs and methods of detection.", "output": "saxitoxin." }, { "input": "The eco - evolutionary role ( s ) PSTs may serve for phytoplankton species that produce them are also discussed.", "output": "There is no related enetity." }, { "input": "Modulation of the JAK / ERK / STAT signaling in melanocortin - induced inhibition of local and systemic responses to myocardial ischemia / reperfusion.", "output": "There is no related enetity." }, { "input": "The janus kinases ( JAK ), extracellular signal - regulated kinases ( ERK ) and signal transducers and activators of transcription ( STAT ) pathways have been shown to play a cardioprotective role.", "output": "There is no related enetity." }, { "input": "We previously gave evidence that melanocortins afford cardioprotection in conditions of myocardial ischemia / reperfusion.", "output": "There is no related enetity." }, { "input": "Here we aimed to investigate the influence of melanocortins on the JAK / ERK / STAT signaling in cardiac and systemic responses to prolonged myocardial ischemia / reperfusion.", "output": "There is no related enetity." }, { "input": "Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30min.", "output": "There is no related enetity." }, { "input": "At the end of the 2 - h reperfusion, western blot analysis of the cardioprotective transcription factors pJAK2, pERK1 / 2, pTyr - STAT3 and pSer - STAT3, the inflammatory mediator tumor necrosis factor - alpha ( TNF - alpha ), the pro - apoptotic factors BAX and c - jun N - terminal kinases ( pJNK ), the anti - apoptotic protein Bcl - XL, as well as of the cardioprotective enzyme heme oxygenase - 1 ( HO - 1 ), was performed in the left ventricle and spleen.", "output": "N." }, { "input": "Intravenous treatment, during coronary artery occlusion, with the melanocortin analogs [ Nle ( 4 ), D - Phe ( 7 ) ] alpha - melanocyte - stimulating hormone ( NDP - alpha - MSH ) and adrenocorticotropic hormone 1 - 24 [ ACTH - ( 1 - 24 ) ], induced a left ventricle up - regulation of pJAK2, pERK1 / 2 and pTyr - STAT3 ( JAK - dependent ), and a reduction in pJNK and TNF - alpha levels; these effects of NDP - alpha - MSH and ACTH - ( 1 - 24 ) were associated with over - expression of the pro - survival proteins HO - 1 and Bcl - XL, and marked decrease of the myocardial infarct size.", "output": "Nle, D - Phe." }, { "input": "Melanocortin treatment did not affect left ventricle pSer - STAT3 ( ERK1 / 2 - dependent ) and BAX levels.", "output": "There is no related enetity." }, { "input": "In the spleen, NDP - alpha - MSH and ACTH - ( 1 - 24 ) induced similar effects on the expression of the above transcription factors / proteins, except for pERK1 / 2 ( down - regulated ) and HO - 1 ( unaffected ).", "output": "There is no related enetity." }, { "input": "Blockade of JAK and ERK pathways with AG490 and U0126, respectively, abrogated the myocardial infarct size reduction by NDP - alpha - MSH.", "output": "AG490, U0126." }, { "input": "These results indicate that melanocortins inhibit local and systemic inflammatory and apoptotic cascades triggered by prolonged myocardial ischemia / reperfusion, with consequent reduction in myocardium infarct size, seemingly via activation of the JAK / STAT signaling and with modulation of an ERK ( STAT unrelated ) signaling pathway.", "output": "There is no related enetity." }, { "input": "Global increases in both common and rare copy number load associated with autism.", "output": "There is no related enetity." }, { "input": "Children with autism have an elevated frequency of large, rare copy number variants ( CNVs ).", "output": "There is no related enetity." }, { "input": "However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented.", "output": "There is no related enetity." }, { "input": "We examined CNV data from 516 individuals with autism or typical development from the population - based Childhood Autism Risks from Genetics and Environment ( CHARGE ) study.", "output": "There is no related enetity." }, { "input": "We interrogated 120 regions flanked by segmental duplications ( genomic hotspots ) for events > 50 kbp and the entire genomic backbone for variants > 300 kbp using a custom targeted DNA microarray.", "output": "There is no related enetity." }, { "input": "This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform ( > 1 kbp ) in 142 children matched for gender and ethnicity.", "output": "There is no related enetity." }, { "input": "In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism.", "output": "There is no related enetity." }, { "input": "Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events.", "output": "There is no related enetity." }, { "input": "Further, the entire CNV load detected with the finely tiled array was contributed by common variants.", "output": "There is no related enetity." }, { "input": "The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load.", "output": "There is no related enetity." }, { "input": "The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated ( Spearman ' s r = - 0. 13, P = 0. 034 ) with the duplication CNV load for the affected children; the strongest association was found for communication ( P = 0. 048 ) and socialization ( P = 0. 022 ) scores.", "output": "There is no related enetity." }, { "input": "We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism.", "output": "There is no related enetity." }, { "input": "Controlling potassium selectivity and proton blocking in a hybrid biological / solid - state polymer nanoporous membrane.", "output": "potassium." }, { "input": "Specific separations of protons and cations are usually performed by electromembrane processes, which require external electric energy.", "output": "There is no related enetity." }, { "input": "An easier process would be using a membrane able to separate both entities by passive diffusion.", "output": "There is no related enetity." }, { "input": "Presently, such synthetic nanoporous membranes do not exist.", "output": "There is no related enetity." }, { "input": "Here, we report the production of a robust hybrid biological / artificial solid - state membrane, which allows selective permeation of alkali metal cations without competing or concurrent permeation of protons.", "output": "There is no related enetity." }, { "input": "This membrane is simple to prepare and is based on the hydrophobic nature of the polymeric pore walls, and the confined gramicidin A molecules within.", "output": "There is no related enetity." }, { "input": "This work opens a new route for separation in the domain of nanobiofiltration, especially for tunable nanodevices based on differential ion conduction, with a fundamental understanding of the confinement mechanism.", "output": "There is no related enetity." }, { "input": "Comparing the sensitivity of geographically distinct Lemna minor populations to atrazine.", "output": "atrazine." }, { "input": "The objectives of this study were to compare the sensitivities of field populations and a laboratory culture of a duckweed species ( Lemna minor ) to the herbicide atrazine using three different endpoints and to determine whether sensitivity to atrazine was affected by past exposure to the herbicide.", "output": "atrazine, atrazine." }, { "input": "L. minor cultures were purchased commercially or collected from field sites within an agricultural watershed and exposed to atrazine for 7 days under greenhouse conditions.", "output": "atrazine." }, { "input": "Populations differed significantly in their sensitivity to atrazine.", "output": "atrazine." }, { "input": "Biomass was more sensitive than frond number, while chlorophyll fluorescence was not a sensitive endpoint.", "output": "There is no related enetity." }, { "input": "Overall, the sensitivity of the various populations to atrazine was not strongly related to measures of past exposure to agriculture stressors.", "output": "atrazine." }, { "input": "Positive correlations between biomass twenty - five percent inhibition concentrations ( IC25s ), biomass estimated marginal means and in - stream atrazine concentrations were observed, providing evidence that atrazine exposure is linked to a decrease in sensitivity to atrazine.", "output": "atrazine, atrazine, atrazine." }, { "input": "However, IC25s generated for each population were similar, ranging from 19 to 40 and 57 to 92 mu g / L atrazine for biomass and frond data respectively, and likely do not represent biologically significant differences in atrazine sensitivity.", "output": "atrazine, atrazine." }, { "input": "Given the small range in sensitivity observed between populations, commercial laboratory cultures appear to provide a good estimate of the sensitivity of field populations of L. minor to atrazine and should continue to be used in regulatory phytotoxicity testing.", "output": "atrazine." }, { "input": "Challenges and approaches for the development of safer immunomodulatory biologics.", "output": "There is no related enetity." }, { "input": "Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases.", "output": "There is no related enetity." }, { "input": "However, unwanted adverse reactions - - including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity - - pose a challenge to the development of new ( and safer ) immunomodulatory biologics.", "output": "There is no related enetity." }, { "input": "In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use.", "output": "There is no related enetity." }, { "input": "We also outline how these approaches can inform the development of safer immunomodulatory biologics.", "output": "There is no related enetity." }, { "input": "beta - Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway.", "output": "beta - Ionone." }, { "input": "beta - Ionone is an end ring analog of beta - carotenoid which has been shown to possess potent anti - proliferative activity both in vitro and in vivo.", "output": "beta - Ionone." }, { "input": "To investigate the possible inhibitory effects of beta - ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen - activated protein kinases ( MAPKs ) pathways in the human gastric adenocarcinoma cancer cell line ( SGC - 7901 ).", "output": "beta - ionone." }, { "input": "Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0 / G1 phase in a dose - dependent manner in cells treated with beta - ionone ( 25, 50, 100 and 200 mu mol / L ) for 24 h.", "output": "beta - ionone." }, { "input": "We found that the beta - ionone significantly decreased the extracellular signal - regulated kinase protein expression and significantly increased the levels of p38 and Jun - amino - terminal kinase protein expression ( P < 0. 01 ).", "output": "beta - ionone, amino." }, { "input": "beta - Ionone also inhibited cell cycle - related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC - 7901 cells.", "output": "beta - Ionone." }, { "input": "These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down - regulation of cell cycle proteins.", "output": "There is no related enetity." }, { "input": "These results demonstrate potent ability of beta - ionone to arrest cell cycle of SGC - 7901 cells and decrease proliferation.", "output": "beta - ionone." }, { "input": "Regulation of neutrophil extracellular trap formation by anti - inflammatory drugs.", "output": "There is no related enetity." }, { "input": "The formation of neutrophil extracellular traps ( NETs ) is a newly described phenomenon that increases the bacteria killing ability and the inflammatory response of neutrophils.", "output": "There is no related enetity." }, { "input": "Because NET generation occurs in an inflammatory microenvironment, we examined its regulation by anti - inflammatory drugs.", "output": "There is no related enetity." }, { "input": "Treatment of neutrophils with dexamethasone had no effect while acetylsalicylic acid ( ASA ) treatment prevented NET formation.", "output": "dexamethasone, acetylsalicylic acid, ASA." }, { "input": "NETosis was also abrogated by the presence of BAY 11 - 7082 and Ro 106 - 9920, two structurally unrelated NF - kappa B inhibitors.", "output": "BAY 11 - 7082, Ro 106 - 9920." }, { "input": "The decrease in NET formation mediated by ASA, BAY - 11 - 7082 and Ro 106 - 9920 was correlated with a significant reduction in the phosphorylation of NF - kappa B p65 subunit, indicating that the activation of this transcription factor is a relevant signaling pathway involved in the generation of DNA traps.", "output": "ASA, BAY - 11 - 7082, Ro 106 - 9920." }, { "input": "The inhibitory effect of these drugs was also observed when NET generation was induced under acidic or hyperthermic conditions, two stress signals of the inflammatory microenvironment.", "output": "There is no related enetity." }, { "input": "In a mouse peritonitis model, while pretreatment of animals with ASA or BAY 11 - 7082 resulted in a marked suppression of NET formation along with increased bacteremia, dexamethasone had no effect.", "output": "ASA, BAY 11 - 7082, dexamethasone." }, { "input": "Our results show that NETs have an important role in the local control of infection and that ASA and NF - kappa B blockade could be useful therapies to avoid undesired effect of persistent neutrophil activation.", "output": "ASA." }, { "input": "Fasting Plasma Glucose at 24 - 28 Weeks to Screen for Gestational Diabetes Mellitus: New evidence from China.", "output": "Glucose." }, { "input": "OBJECTIVETo evaluate the usefulness of a fasting plasma glucose ( FPG ) at 24 - 28 weeks ' gestation to screen for gestational diabetes mellitus ( GDM ). RESEARCH DESIGN AND METHODSThe medical records and results of a 75 - g 2 - h oral glucose tolerance test ( OGTT ) of 24, 854 pregnant women without known pre - GDM attending prenatal clinics in 15 hospitals in China were examined. RESULTSFPG cutoff value of 5. 1 mmol / L identified 3, 149 ( 12. 1 % ) pregnant women with GDM.", "output": "glucose, glucose." }, { "input": "FPG cutoff value of 4. 4 mmol / L ruled out GDM in 15, 369 ( 38. 2 % ) women.", "output": "There is no related enetity." }, { "input": "With use of this cutoff point, 12. 2 % of patients with mild GDM will be missed.", "output": "There is no related enetity." }, { "input": "The positive predictive value is 0. 322, and the negative predictive value is 0. 928. CONCLUSIONSFPG at 24 - 28 weeks ' gestation could be used as a screening test to identify GDM patients in low - resource regions.", "output": "There is no related enetity." }, { "input": "Women with an FPG between >= 4. 4 and <= 5. 0 mmol / L would require a 75 - g OGTT to diagnose GDM.", "output": "There is no related enetity." }, { "input": "This would help to avoid approximately one - half ( 50. 3 % ) of the formal 75 - g OGTTs in China.", "output": "There is no related enetity." }, { "input": "Efficacy and Safety of Lixisenatide Once - Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin ( GetGoal - M ).", "output": "Metformin." }, { "input": "OBJECTIVEExamine the efficacy and safety of lixisenatide ( 20 mu g once daily, administered before the morning or evening meal ) as add - on therapy in type 2 diabetes patients insufficiently controlled with metformin alone. RESEARCH DESIGN AND METHODSA 24 - week, randomized, double - blind, placebo - controlled study in 680 patients with inadequately controlled type 2 diabetes ( HbA1c 7 - 10 % [ 53 - 86 mmol / mol ] ).", "output": "metformin." }, { "input": "Patients were randomized to lixisenatide morning ( n = 255 ), lixisenatide evening ( n = 255 ), placebo morning ( n = 85 ), or placebo evening ( n = 85 ) injections. RESULTSLixisenatide morning injection significantly reduced mean HbA1c versus combined placebo ( mean change - 0. 9 % [ 9. 8 mmol / mol ] vs. - 0. 4 % [ 4. 4 mmol / mol ]; least squares [ LS ] mean difference vs. placebo - 0. 5 % [ 5. 5 mmol / mol ], P < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "HbA1c was significantly reduced by lixisenatide evening injection ( mean change - 0. 8 % [ 8. 7 mmol / mol ] vs. - 0. 4 % [ 4. 4 mmol / mol ]; LS mean difference - 0. 4 % [ 4. 4 mmol / mol ], P < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Lixisenatide morning injection significantly reduced 2 - h postprandial glucose versus morning placebo ( mean change - 5. 9 vs. - 1. 4 mmol / L; LS mean difference - 4. 5 mmol / L, P < 0. 0001 ).", "output": "glucose." }, { "input": "LS mean difference in fasting plasma glucose was significant in both morning ( - 0. 9 mmol / L, P < 0. 0001 ) and evening ( - 0. 6 mmol / L, P = 0. 0046 ) groups versus placebo.", "output": "glucose." }, { "input": "Mean body weight decreased to a similar extent in all groups.", "output": "There is no related enetity." }, { "input": "Rates of adverse events were 69. 4 % in both lixisenatide groups and 60. 0 % in the placebo group.", "output": "There is no related enetity." }, { "input": "Rates for nausea and vomiting were 22. 7 and 9. 4 % for lixisenatide morning and 21. 2 and 13. 3 % for lixisenatide evening versus 7. 6 and 2. 9 % for placebo, respectively.", "output": "There is no related enetity." }, { "input": "Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes. CONCLUSIONSIn patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 mu g once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated.", "output": "metformin." }, { "input": "Tumor Suppressor Protein p53 Negatively Regulates Human Pregnane X Receptor Activity.", "output": "Pregnane." }, { "input": "The human pregnane X receptor ( PXR ) regulates genes involved in drug metabolism and disposition.", "output": "There is no related enetity." }, { "input": "PXR associates with multiple corepressors that attenuate, and coactivators that enhance its activity.", "output": "There is no related enetity." }, { "input": "PXR plays a vital role in the drug metabolism pathway, and a comprehensive examination of PXR - associated proteins will provide greater insight into the regulation of the receptor and possible therapeutic implications.", "output": "There is no related enetity." }, { "input": "We performed a mass spectrometric screen to identify PXR - associated proteins.", "output": "There is no related enetity." }, { "input": "Here we report that the tumor suppressor protein p53 can associate with PXR and downregulate its activity.", "output": "There is no related enetity." }, { "input": "A loss - of - function p53 mutant ( R175H ) interacts with PXR but does not repress its activity.", "output": "There is no related enetity." }, { "input": "Mutant p53 can relieve the suppressive effect of wild - type p53 by competing with its interaction with PXR, suggesting that protein - protein interaction is required but not sufficient for p53 to repress PXR activity.", "output": "There is no related enetity." }, { "input": "Interestingly, a PXR variant with a naturally occurring deletion of a conserved, unique sequence in the ligand binding domain ( PXR174 - 210 ) did not interact with p53, indicating that the PXR - p53 interaction is specific.", "output": "There is no related enetity." }, { "input": "Using a chromatin immunoprecipitation assay, we showed that p53 inhibits the binding of PXR to the CYP3A4 promoter.", "output": "There is no related enetity." }, { "input": "The loss of p53 function in tumor cells leads to aberrant cell proliferation, apoptosis, carcinogenesis, and altered sensitivity to chemotherapeutic drugs, while PXR contributes to chemoresistance in many cancer cells.", "output": "There is no related enetity." }, { "input": "Our findings show for the first time that wild - type p53 can negatively regulate PXR by physically associating with it.", "output": "There is no related enetity." }, { "input": "Thus, PXR and p53 appear to play important yet opposing roles in the sensitivity of tumor cells to chemotherapy.", "output": "There is no related enetity." }, { "input": "Efficient anodic allylation and benzylation of carbons using allyl and benzyl trimethylsilanes.", "output": "carbons, allyl, benzyl, trimethylsilanes." }, { "input": "An easy process for allylation and benzylation of different carbon materials, primarily of glassy carbon, in acetonitrile solutions containing tetraalkyammonium salts is described.", "output": "carbon, glassy carbon, acetonitrile, tetraalkyammonium." }, { "input": "The method relies on the capability of C ( sp ( 2 ) ) zones of glassy carbon ( graphite and fullerene - like inclusions ) to be anodically charged at potentials > 1. 5 V versus Ag / AgCl to form electrophilic centers reacting with substituted trimethylsilanes RSiMe3.", "output": "C, glassy carbon, graphite, fullerene, Ag, AgCl, trimethylsilanes, RSiMe3." }, { "input": "Great propensity of the trimethylsilyl group ( TMS ( + ) ) to act as a cationic leaving group facilitates electrophilic reactions of the charged anodic surface with R - carrying silylated precursors, permitting efficient grafting of a large variety of R groups.", "output": "trimethylsilyl, TMS ( + )." }, { "input": "The present preliminary work focuses only on the efficient grafting of benzyl and allyl moieties.", "output": "benzyl, allyl." }, { "input": "Hydrocarbon - soluble nanocatalysts with no bulk phase: coplanar, two - coordinate arrays of the base metals.", "output": "Hydrocarbon." }, { "input": "A structurally unique class of hydrocarbon - soluble, ancillary - ligand - free, tetrametallic Co ( I ) and Ni ( I ) clusters is reported.", "output": "hydrocarbon, Co ( I ), Ni ( I )." }, { "input": "The highly unsaturated complexes are supported by simple, sterically bulky phosphoranimide ligands, one per metal.", "output": "phosphoranimide." }, { "input": "The electron - rich nitrogen centers are strongly bridging but sterically limited to bimetallic interactions.", "output": "nitrogen." }, { "input": "The hydrocarbon - soluble clusters consist of four coplanar metal centers, mutually bridged by single nitrogen atoms.", "output": "hydrocarbon, nitrogen." }, { "input": "Each metal center is monovalent, rigorously linear, and two - coordinate.", "output": "There is no related enetity." }, { "input": "The clusters are in essence two - dimensional atomic - scale \" molecular squares, \" a structural motif adapted from supramolecular chemistry.", "output": "There is no related enetity." }, { "input": "Both clusters exhibit high solution - phase magnetic susceptibility at room temperature, suggesting the potential for applications in molecular electronics.", "output": "There is no related enetity." }, { "input": "Designed to be catalyst precursors, both clusters exhibit high activity for catalytic hydrogenation of unsaturated hydrocarbons at low pressure and temperature.", "output": "unsaturated hydrocarbons." }, { "input": "Spray drying method for large - scale and high - performance silicon negative electrodes in li - ion batteries.", "output": "silicon, li." }, { "input": "Nanostructured silicon electrodes have shown great potential as lithium ion battery anodes because they can address capacity fading mechanisms originating from large volume changes of silicon alloys while delivering extraordinarily large gravimetric capacities.", "output": "silicon, lithium, silicon." }, { "input": "Nonetheless, synthesis of well - defined silicon nanostructures in an industrially adaptable scale still remains as a challenge.", "output": "silicon." }, { "input": "Herein, we adopt an industrially established spray drying process to enable scalable synthesis of silicon - carbon composite particles in which silicon nanoparticles are embedded in porous carbon particles.", "output": "silicon, carbon, silicon, carbon." }, { "input": "The void space existing in the porous carbon accommodates the volume expansion of silicon and thus addresses the chronic fading mechanisms of silicon anodes.", "output": "carbon, silicon, silicon." }, { "input": "The composite electrodes exhibit excellent electrochemical performance, such as 1956 mAh / g at 0. 05C rate and 91 % capacity retention after 150 cycles.", "output": "There is no related enetity." }, { "input": "Moreover, the spray drying method requires only 2 s for the formation of each particle and allows a production capability of ~ 10 g / h even with an ultrasonic - based lab - scale equipment.", "output": "There is no related enetity." }, { "input": "This investigation suggests that established industrial processes could be adaptable to the production of battery active materials that require sophisticated nanostructures as well as large quantity syntheses.", "output": "There is no related enetity." }, { "input": "Enantioselective Iron - Catalyzed Azidation of beta - Keto Esters and Oxindoles.", "output": "Iron, beta - Keto Esters, Oxindoles." }, { "input": "The first example of Fe - catalyzed enantioselective azidations of beta - keto esters and oxindoles using a readily available N3 - transfer reagent is reported.", "output": "Fe, beta - keto esters, oxindoles." }, { "input": "A number of alpha - azido - beta - keto esters were obtained with up to 93 % ee, and this methodology also generates 3 - substitued 3 - azidooxindoles with high enantioselectivities ( up to 94 % ).", "output": "alpha - azido - beta - keto esters, 3 - substitued 3 - azidooxindoles." }, { "input": "Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: A new strategy for anticancer therapy.", "output": "There is no related enetity." }, { "input": "The aim of this study was to develop clickable prodrugs bearing a tunable pH responsive linker designed for acidic pH - mediated release of histone deacetylase inhibitors.", "output": "There is no related enetity." }, { "input": "HDACi are an important class of molecules belonging to the epigenetic modulators used for innovative cancer strategies.", "output": "There is no related enetity." }, { "input": "The behavior of these prodrugs was determined by a bioluminescence resonance energy transfer assay in living tumor cells.", "output": "There is no related enetity." }, { "input": "This work demonstrated that this innovative type of clickable prodrugs entered cancer cells and showed restored anti proliferative properties attributed to the effective release of the HDAC inhibitors.", "output": "There is no related enetity." }, { "input": "A correlation between kinetic studies, dose responses, and biological activities was obtained, making such clickable prodrugs good candidates for new strategies in epigenetic - oriented anticancer therapies.", "output": "There is no related enetity." }, { "input": "Antioxidant and micronutrient - rich milk formula reduces lead poisoning and related oxidative damage in lead - exposed mice.", "output": "There is no related enetity." }, { "input": "Lead poisoning is a global environmental disease that induces lifelong adverse health effects.", "output": "There is no related enetity." }, { "input": "The effect of a milk formula consisting of antioxidant of bamboo leaves ( AOB ), vitamin C ( Vc ), calcium lactate ( CaLac ), ferrous sulfate ( FeSO4 ) and zinc sulfate ( ZnSO4 ) on the reduction of lead and lead - induced oxidative damage in lead - exposed mice was studied.", "output": "vitamin C, calcium lactate, CaLac, ferrous sulfate, FeSO4, zinc sulfate, ZnSO4." }, { "input": "The lead - reducing effect of milk formula was investigated via a 7 - week toxicokinetics study and a tissue distribution level examination.", "output": "There is no related enetity." }, { "input": "The ameliorating effect of milk formula on lead - induced oxidative damage was investigated.", "output": "There is no related enetity." }, { "input": "Results demonstrated current milk formula could effectively reduce blood lead levels ( BLLs ) and lead distribution levels of liver, kidneys, thighbones and brain in mice based on metal ion - mediated antagonism and chelation mechanisms.", "output": "There is no related enetity." }, { "input": "This milk formula could not only protect lead - susceptible tissues against lead poisoning, but also maintain normal absorption and distribution of essential elements in vivo.", "output": "There is no related enetity." }, { "input": "Meanwhile, current milk formula could prevent the reduction of delta - aminolevulinic acid dehydratase ( delta - ALAD ) activity and enhancement of free erythrocyte protoporphyrins ( FEP ) levels in blood erythrocytes of mice.", "output": "delta - aminolevulinic acid, protoporphyrins." }, { "input": "Also, this formula could indirectly protect blood cell membranes against lead - induced lipid peroxidation.", "output": "There is no related enetity." }, { "input": "We conclude that current optimized milk formula effectively reduces lead poisoning and lead - induced in vivo oxidative damage in lead - exposed mice.", "output": "There is no related enetity." }, { "input": "Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.", "output": "There is no related enetity." }, { "input": "The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits ( 4months - old ).", "output": "turinabol, methanabol." }, { "input": "The experimental scheme consisted of two oral administration periods, lasting 1month each, interrupted by 1 - month wash - out period.", "output": "There is no related enetity." }, { "input": "Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals.", "output": "There is no related enetity." }, { "input": "Oxidative stress markers have also been monitored at the end of each administration period.", "output": "There is no related enetity." }, { "input": "Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period.", "output": "There is no related enetity." }, { "input": "Re - administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction.", "output": "There is no related enetity." }, { "input": "A dose - dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed.", "output": "There is no related enetity." }, { "input": "The adverse effects were more pronounced in the methanabol group.", "output": "methanabol." }, { "input": "For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment.", "output": "There is no related enetity." }, { "input": "In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects.", "output": "There is no related enetity." }, { "input": "Effects of lactational and / or in utero exposure to environmental contaminants on the glucocorticoid stress - response and DNA methylation of the glucocorticoid receptor promoter in male rats.", "output": "There is no related enetity." }, { "input": "Perinatal events can reprogram the hypothalamo - pituitary - adrenal axis for the entire lifespan leading to abnormal glucocorticoid stress - response ( GSR ) in adulthood: a phenomenon reported to be mediated by changes in DNA methylation of the glucocorticoid receptor ( GR ) gene promoter.", "output": "There is no related enetity." }, { "input": "We examined whether in utero and / or lactational exposure to mixtures of environmental contaminants can also induce abnormal GSR during adulthood.", "output": "There is no related enetity." }, { "input": "The experiment included nine treatment groups.", "output": "There is no related enetity." }, { "input": "From gestation day ( GD ) 0 until postnatal day ( PND ) 20, dams were fed daily with a cookie laced with corn oil ( control ) or a chemical mixture ( M ) [ polychlorinated biphenyls ( PCBs ), organochlorine pesticides, and methylmercury ] at 0. 5 or 1. 0mg / kg / day ( 0. 5M, and M ).", "output": "polychlorinated biphenyls, PCBs, organochlorine, methylmercury." }, { "input": "At birth, some control ( C ) and M litters were cross - fostered to create four groups with the following in utero / postnatal exposure: C / C, M / C, C / M, M / M.", "output": "There is no related enetity." }, { "input": "Other dams received 1. 8ng / kg / day of a mixture of aryl hydrocarbon receptor ( AhR ) agonists ( non - ortho PCBs, PC - dibenzodioxins and PC - dibenzofurans ) without or with 0. 5M ( 0. 5MAhR ).", "output": "hydrocarbon, non - ortho PCBs, PC - dibenzodioxins, PC - dibenzofurans." }, { "input": "In adult male offspring the abundance of GR in treated groups was not different from the control, but the AhR and M groups were significantly different from each other with opposite effects in the hippocampus and liver.", "output": "There is no related enetity." }, { "input": "There was no change in DNA methylation of the GR promoter ( exon - 17 and - 110 ).", "output": "There is no related enetity." }, { "input": "Abnormal GSRs were detected in the AhR, 0. 5MAhR, CM, and MM groups.", "output": "There is no related enetity." }, { "input": "The literature associates abnormal GSR with metabolic and mental health impairments, thus these results support further investigation of the influence of developmental exposure to environmental contaminants and predisposition to stress - induced diseases.", "output": "There is no related enetity." }, { "input": "Similar pyruvate kinase modifications in glioblastoma cells by 7 beta - hydroxycholesterol and glutamine withdrawal.", "output": "pyruvate, 7 beta - hydroxycholesterol, glutamine." }, { "input": "Oxysterols possess anti - proliferative properties that may be used with much effect in the treatment of cancer.", "output": "Oxysterols." }, { "input": "We have demonstrated previously that 7 beta - hydroxycholesterol ( 7b - HC ) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells.", "output": "7 beta - hydroxycholesterol, 7b - HC." }, { "input": "These observations suggested that glycolysis might have been changed.", "output": "There is no related enetity." }, { "input": "Here we will show that 7b - HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate.", "output": "7b - HC, pyruvate, phosphoenol pyruvate." }, { "input": "The latter effect is mimicked by glutamine withdrawal.", "output": "glutamine." }, { "input": "Nobiletin attenuates metastasis via both ERK and PI3K / Akt pathways in HGF - treated liver cancer HepG2 cells.", "output": "Nobiletin." }, { "input": "Hepatocyte growth factor ( HGF ), and its receptor, c - Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells.", "output": "There is no related enetity." }, { "input": "We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF / c - Met - mediated tumor invasion and metastasis.", "output": "apigenin, tricetin, tangeretin, nobiletin." }, { "input": "Among them, nobiletin markedly inhibited HGF - induced the abilities of the adhesion, invasion, and migration by cell - matrix adhesion assay and transwell - chamber invasion / migration assay under non - cytotoxic concentrations.", "output": "nobiletin." }, { "input": "Data also showed nobiletin inhibited HGF - induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia.", "output": "nobiletin." }, { "input": "Furthermore, nobiletin could inhibit HGF - induced the membrane localization of phosphorylated c - Met, ERK2, and Akt, but not phosphorylated JNK1 / 2 and p38.", "output": "nobiletin." }, { "input": "Next, nobiletin significantly decreased the levels of phospho - ERK2 and phospho - Akt in ERK2 or Akt siRNA - transfected cells concomitantly with a marked reduction on cell invasion and migration.", "output": "nobiletin, phospho, phospho." }, { "input": "In conclusion, nobiletin attenuates HGF - induced HepG2 cells metastasis involving both ERK and PI3K / Akt pathways and are potentially useful as anti - metastatic agents for the treatment of hepatoma.", "output": "nobiletin." }, { "input": "Synergistic antibacterial effect of curcumin against methicillin - resistant Staphylococcus aureus.", "output": "curcumin, methicillin." }, { "input": "Methicillin - resistant Staphylococcus aureus ( MRSA ) are spread among infected patients, with infection rates increasing at an alarming rate.", "output": "Methicillin." }, { "input": "Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of infectious diseases worldwide.", "output": "There is no related enetity." }, { "input": "Under the selection pressure of exposure to antibiotics, microorganisms evolve to survive against the new conditions imposed by therapy.", "output": "There is no related enetity." }, { "input": "Therefore, there exists a need to develop alternative natural or combination drug therapies.", "output": "There is no related enetity." }, { "input": "Curcumin ( CCM ), a natural polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa Linn e., has been found to possess many beneficial biological activities.", "output": "Curcumin, CCM, polyphenolic flavonoid." }, { "input": "The aim of this study was to investigate the synergistic effect of curcumin and antibiotics as well as to determine the antibacterial activity of CCM against specific MRSA strains.", "output": "curcumin, CCM." }, { "input": "The antibacterial activity of CCM was assessed by the broth microdilution method ( by calculating the minimal inhibitory concentration [ MIC ] ), checkerboard dilution test, and time - kill assay.", "output": "CCM." }, { "input": "Antimicrobial activity of CCM was observed against all tested strains.", "output": "CCM." }, { "input": "The MICs of CCM against 10 strains of S. aureus ranged from 125 to 250 mu g / ml.", "output": "CCM." }, { "input": "In the checkerboard test, CCM markedly reduced the MICs of the antibiotics oxacillin ( OXI ), ampicillin ( AMP ), ciprofloxacin ( CIP ), and norfloxacin ( NOR ) used against MRSA.", "output": "CCM, oxacillin, OXI, ampicillin, AMP, ciprofloxacin, CIP, norfloxacin, NOR." }, { "input": "The time - kill curves showed that a combined CCM and OXI treatment reduced the bacterial counts below the lowest detectable limit after 24h.", "output": "CCM, OXI." }, { "input": "This study suggested that CCM reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and NOR, and that CCM in combination with antibiotics could lead to the development of new combination of antibiotics against MRSA infection.", "output": "CCM, OXI, AMP, CIP, NOR, CCM." }, { "input": "The birth and early years of INA, the International Neurotoxicology Association.", "output": "There is no related enetity." }, { "input": "The International Neurotoxicology Association ( INA ) is a scientific society whose members have interest and expertise in the discipline of neurotoxicology.", "output": "There is no related enetity." }, { "input": "The idea of forming INA was born in 1984, as a follow - up to a NATO - sponsored meeting on Toxicology of the Nervous System.", "output": "There is no related enetity." }, { "input": "INA held its first meeting in the Netherlands in 1987 and has had continuous meetings every other year since then.", "output": "There is no related enetity." }, { "input": "INA is registered as a scientific society in the Netherlands, and is an affiliated society of IUTOX.", "output": "There is no related enetity." }, { "input": "This paper presents a personal account of the events that led to the birth of INA, and of the first fifteen years of this association.", "output": "There is no related enetity." }, { "input": "Anticancer activity of novel hybrid molecules containing 5 - benzylidene thiazolidine - 2, 4 - dione.", "output": "5 - benzylidene thiazolidine - 2 , 4 - dione." }, { "input": "Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer.", "output": "There is no related enetity." }, { "input": "Molecules bearing a thiazolidine - 2, 4 - dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines.", "output": "thiazolidine - 2 , 4 - dione." }, { "input": "In this manuscript we have described the synthesis and biological evaluation of two series of N - 3 - substituted - 5 - arylidene thiazolidine - 2, 4 - diones, bearing the alpha - bromoacryloylamido moiety at the para - or meta - position on the phenyl of the arylidene portion.", "output": "N - 3 - substituted - 5 - arylidene thiazolidine - 2 , 4 - diones, alpha - bromoacryloylamido, phenyl, arylidene." }, { "input": "We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL - 60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well - known features of apoptosis.", "output": "There is no related enetity." }, { "input": "Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria.", "output": "There is no related enetity." }, { "input": "Genetic diversity revealed by single nucleotide polymorphism markers in a worldwide germplasm collection of durum wheat.", "output": "There is no related enetity." }, { "input": "Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources.", "output": "There is no related enetity." }, { "input": "Newly developed single nucleotide polymorphism ( SNP ) markers are effective in detecting genetic diversity.", "output": "There is no related enetity." }, { "input": "In the present study, a worldwide durum wheat collection consisting of 150 accessions was used.", "output": "There is no related enetity." }, { "input": "Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat.", "output": "There is no related enetity." }, { "input": "Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities.", "output": "There is no related enetity." }, { "input": "A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution.", "output": "There is no related enetity." }, { "input": "Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity.", "output": "There is no related enetity." }, { "input": "Transcriptional Analysis of Drought - Induced Genes in the Roots of a Tolerant Genotype of the Common Bean ( Phaseolus vulgaris L. ).", "output": "There is no related enetity." }, { "input": "In Brazil, common bean ( Phaseolus vulgaris L. ) productivity is severely affected by drought stress due to low technology cultivation systems.", "output": "There is no related enetity." }, { "input": "Our purpose was to identify differentially expressed genes in roots of a genotype tolerant to water deficit ( BAT 477 ) when submitted to an interruption of irrigation during its development.", "output": "There is no related enetity." }, { "input": "A SSH library was constructed taking as \" driver \" the genotype Carioca 80SH ( susceptible to drought ).", "output": "There is no related enetity." }, { "input": "After clustering and data mining, 1572 valid reads were obtained, resulting in 1120 ESTs ( expressed sequence tags ).", "output": "There is no related enetity." }, { "input": "We found sequences for transcription factors, carbohydrates metabolism, proline - rich proteins, aquaporins, chaperones and ubiquitins, all of them organized according to their biological processes.", "output": "carbohydrates, proline." }, { "input": "Our suppressive subtractive hybridization ( SSH ) library was validated through RT - qPCR experiment by assessing the expression patterns of 10 selected genes in both genotypes under stressed and control conditions.", "output": "There is no related enetity." }, { "input": "Finally, the expression patterns of 31 ESTs, putatively related to drought responses, were analyzed in a time - course experiment.", "output": "There is no related enetity." }, { "input": "Our results confirmed that such genes are more expressed in the tolerant genotype during stress; however, they are not exclusive, since different levels of these transcripts were also detected in the susceptible genotype.", "output": "There is no related enetity." }, { "input": "In addition, we observed a fluctuation in gene regulation over time for both the genotypes, which seem to adopt and adapt different strategies in order to develop tolerance against this stress.", "output": "There is no related enetity." }, { "input": "Diketopiperazine Derivatives from the Marine - Derived Actinomycete Streptomyces sp.", "output": "Diketopiperazine." }, { "input": "FXJ7. 328.", "output": "There is no related enetity." }, { "input": "Five new diketopiperazine derivatives, ( 3Z, 6E ) - 1 - N - methyl - 3 - benzy lidene - 6 - ( 2S - methyl - 3 - hydroxypropylidene ) piperazine - 2, 5 - dione ( 1 ), ( 3Z, 6E ) - 1 - N - methyl - 3 - benzylidene - 6 - ( 2R - methyl - 3 - hydroxypropylidene ) piperazine - 2, 5 - dione ( 2 ), ( 3Z, 6Z ) - 3 - ( 4 - hydroxybenzylidene ) - 6 - isobutylidenepiperazine - 2, 5 - dione ( 3 ), ( 3Z, 6Z ) - 3 - ( ( 1H - imidazol - 5 - yl ) - methylene ) - 6 - isobutylidenepiperazine - 2, 5 - dione ( 4 ), and ( 3Z, 6S ) - 3 - benzylidene - 6 - ( 2S - but - 2 - yl ) piperazine - 2, 5 - dione ( 5 ), were isolated from the marine - derived actinomycete Streptomyces sp.", "output": "diketopiperazine, ( 3Z , 6E ) - 1 - N - methyl - 3 - benzy lidene - 6 - ( 2S - methyl - 3 - hydroxypropylidene ) piperazine - 2 , 5 - dione, ( 3Z , 6E ) - 1 - N - methyl - 3 - benzylidene - 6 - ( 2R - methyl - 3 - hydroxypropylidene ) piperazine - 2 , 5 - dione, ( 3Z , 6Z ) - 3 - ( 4 - hydroxybenzylidene ) - 6 - isobutylidenepiperazine - 2 , 5 - dione, ( 3Z , 6Z ) - 3 - ( ( 1H - imidazol - 5 - yl ) - methylene ) - 6 - isobutylidenepiperazine - 2 , 5 - dione, ( 3Z , 6S ) - 3 - benzylidene - 6 - ( 2S - but - 2 - yl ) piperazine - 2 , 5 - dione." }, { "input": "FXJ7. 328.", "output": "There is no related enetity." }, { "input": "The structures of 1 - 5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher ' s, Marfey ' s and the C3 Marfey ' s methods.", "output": "There is no related enetity." }, { "input": "Compound 3 showed modest antivirus activity against influenza A ( H1N1 ) virus with an IC50 value of 41. 5 +/- 4. 5 mu M.", "output": "There is no related enetity." }, { "input": "In addition, compound 6 and 7 displayed potent anti - H1N1 activity with IC50 value of 28. 9 +/- 2. 2 and 6. 8 +/- 1. 5 mu M, respectively.", "output": "There is no related enetity." }, { "input": "Due to the lack of corresponding data in the literature, the 13C NMR data of ( 3Z, 6S ) - 3 - benzylidene - 6 - isobutylpiperazine - 2, 5 - dione ( 6 ) were also reported here for the first time.", "output": "13C, ( 3Z , 6S ) - 3 - benzylidene - 6 - isobutylpiperazine - 2 , 5 - dione." }, { "input": "Sponge - Derived Kocuria and Micrococcus spp. as Sources of the New Thiazolyl Peptide Antibiotic Kocurin.", "output": "Thiazolyl, Kocurin." }, { "input": "Forty four marine actinomycetes of the family Microccocaceae isolated from sponges collected primarily in Florida Keys ( USA ) were selected from our strain collection to be studied as new sources for the production of bioactive natural products.", "output": "There is no related enetity." }, { "input": "A 16S rRNA gene based phylogenetic analysis showed that the strains are members of the genera Kocuria and Micrococcus.", "output": "There is no related enetity." }, { "input": "To assess their biosynthetic potential, the strains were PCR screened for the presence of secondary metabolite genes encoding nonribosomal synthetase ( NRPS ) and polyketide synthases ( PKS ).", "output": "There is no related enetity." }, { "input": "A small extract collection of 528 crude extracts generated from nutritional microfermentation arrays was tested for the production of bioactive secondary metabolites against clinically relevant strains ( Bacillus subtilis, methicillin - resistant Staphylococcus aureus ( MRSA ), Acinetobacter baumannii and Candida albicans ).", "output": "methicillin." }, { "input": "Three independent isolates were shown to produce a new anti - MRSA bioactive compound that was identified as kocurin, a new member of the thiazolyl peptide family of antibiotics emphasizing the role of this family as a prolific resource for novel drugs.", "output": "kocurin, thiazolyl." }, { "input": "A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay.", "output": "There is no related enetity." }, { "input": "In this work, a simple and versatile microfluidic cell density gradient generator was successfully developed for cytotoxicity of quantum dots ( QDs ) assay.", "output": "There is no related enetity." }, { "input": "The microfluidic cell density gradient generator is composed of eight parallel channels which are respectively surrounded by 1 - 8 microwells with optimized length and width.", "output": "There is no related enetity." }, { "input": "The cells fall into microwells by gravity and the cell densities are obviously dependent of microwell number.", "output": "There is no related enetity." }, { "input": "In a case study, HepG2 and MCF - 7 cells were successfully utilized for generating cell density gradients on the microfluidic chip.", "output": "There is no related enetity." }, { "input": "The microfluidic cell density gradient generator was proved to be easily handled, cell - friendly and could be used to conduct the subsequent cell - based assay.", "output": "There is no related enetity." }, { "input": "As a proof - of - concept, QD cytotoxicity was evaluated and the results exhibited obvious cell density - dependence.", "output": "There is no related enetity." }, { "input": "For comparison, QD cytotoxicity was also investigated with a series of cell densities infused by pipette tips.", "output": "There is no related enetity." }, { "input": "Higher reproducibility was observed on the microfluidic cell density gradient generator and cell density was demonstrated to be a vital factor in cytotoxic study.", "output": "There is no related enetity." }, { "input": "With higher efficiency, controllability and reproducibility, the microfluidic cell density gradient generator could be integrated into microfluidic analysis systems to promote chip - based biological assay.", "output": "There is no related enetity." }, { "input": "Antidiabetic attributes of desert and steppic plants: a review.", "output": "There is no related enetity." }, { "input": "The rapidly increasing incidence of diabetes mellitus is becoming a serious threat to mankind ' s health in all parts of the world.", "output": "There is no related enetity." }, { "input": "In fact, known cases reflect only part of the problem, as many diabetics, especially with type 2 diabetes, are unaware of their disease, which initially shows no definitive symptoms.", "output": "There is no related enetity." }, { "input": "Despite the great efforts invested in diabetes research, its prevalence continues to grow, while current medications do not cover all of the symptoms and complications of the disease.", "output": "There is no related enetity." }, { "input": "The present review highlights a plethora of studies focusing on the antidiabetic properties of desert and semidesert ( steppic ) plants, many of them being used for centuries in traditional medicine by Bedouins living in the arid zones of the Middle East and also by ethnic groups in other arid and semiarid parts of the world.", "output": "There is no related enetity." }, { "input": "The review concludes in summarizing the work done on the subject and also in pointing to the yet existing gaps in diabetes research of desert and steppic plants, and suggests directions for future exploration.", "output": "There is no related enetity." }, { "input": "Cardiac natriuretic Peptide gene expression and plasma concentrations during the first 72 hours of life in piglets.", "output": "There is no related enetity." }, { "input": "Plasma measurement of cardiac natriuretic peptides constitutes promising markers of congenital heart disease.", "output": "There is no related enetity." }, { "input": "However, concentrations change rapidly and dramatically during the first days after delivery even in healthy neonates, which complicates clinical interpretation.", "output": "There is no related enetity." }, { "input": "It is unknown whether these changes in plasma concentrations are explained by corresponding changes in the cardiac gene expression.", "output": "There is no related enetity." }, { "input": "We quantified the chamber - specific mRNA levels of ANP ( A - type natriuretic peptide ) and BNP ( B - type natriuretic peptide ) and plasma pro - ANP and BNP - 32 concentrations in healthy piglets during the first 72 hours of life ( from 2 litters, n = 44 ).", "output": "There is no related enetity." }, { "input": "Chamber - specific ANP and BNP mRNA levels reflected hemodynamic neonate changes at birth but did not correlate with circulating natriuretic peptide concentrations.", "output": "There is no related enetity." }, { "input": "However, plasma pro - ANP and creatinine concentrations were closely correlated ( P <. 0001; r = 0. 73 ).", "output": "creatinine." }, { "input": "Plasma pro - ANP levels were highest on the day of delivery ( 5580 pmol / L [ 4320 - 6786 ] decreasing to 2484 pmol / L [ 1602 - 2898 ] after 72 hours, P <. 0001 ).", "output": "There is no related enetity." }, { "input": "During the 72 hours, gel chromatography suggested that the translational products in circulation and in atrial tissue were immature, ie, unprocessed pro - ANP.", "output": "There is no related enetity." }, { "input": "In contrast to pro - ANP, BNP - 32 plasma concentrations were low at delivery and peaked after 48 hours ( 12 [ 10. 5 - 20. 6 ] vs. 88. 8 [ 71. 7 - 101. 4 ] pmol / L, P <. 0001 ).", "output": "There is no related enetity." }, { "input": "To conclude, ANP and BNP gene expression differs considerably between cardiac chambers in the first 72 hours of life in healthy piglets, resembling the transition from fetal to neonate circulation.", "output": "There is no related enetity." }, { "input": "However, the cardiac gene expression does not explain plasma concentrations.", "output": "There is no related enetity." }, { "input": "Use of human in vitro skin models for accurate and ethical risk assessment: metabolic considerations.", "output": "There is no related enetity." }, { "input": "Several human skin models employing primary cells and immortalised cell lines, used as monocultures or combined to produce reconstituted 3D skin constructs, have been developed.", "output": "There is no related enetity." }, { "input": "Furthermore, these models have been included in European genotoxicity and sensitization / irritation assay validation projects.", "output": "There is no related enetity." }, { "input": "In order to help interpret data, Cosmetics Europe ( formerly COLIPA ) facilitated research projects that measured a variety of defined phase 1 and 2 enzyme activities and created a complete proteomic profile of xenobiotic metabolising enzymes ( XMEs ) in native human skin and compared them with data obtained from a number of in vitro models of human skin.", "output": "There is no related enetity." }, { "input": "Here, we have summarised our findings on the current knowledge of the metabolic capacity of native human skin and in vitro models, and make an overall assessment of the metabolic capacity from gene expression, proteomic expression and substrate metabolism data.", "output": "There is no related enetity." }, { "input": "The known low expression and function of phase 1 enzymes in native whole skin was reflected in the in vitro models.", "output": "There is no related enetity." }, { "input": "Some XMEs in whole skin were not detected in in vitro models and vice versa, and some major hepatic XMEs such as cytochrome P450 - monooxygenases were absent or measured only at very low levels in the skin.", "output": "There is no related enetity." }, { "input": "Conversely, despite varying mRNA and protein levels of phase 2 enzymes, functional activity of glutathione S - transferases, N - acetyltransferase 1, and UDP - glucuronosyltransferases were all readily measurable in whole skin and in vitro skin models at activity levels similar to those measured in the liver.", "output": "glutathione, S, N, UDP." }, { "input": "These projects have enabled a better understanding of the contribution of XMEs to toxicity endpoints.", "output": "There is no related enetity." }, { "input": "Full central neurokinin - 1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies.", "output": "orvepitant." }, { "input": "Full, persistent blockade of central neurokinin - 1 ( NK1 ) receptors may be a potential antidepressant mechanism.", "output": "There is no related enetity." }, { "input": "The selective NK1 antagonist orvepitant ( GW823296 ) was used to test this hypothesis.", "output": "orvepitant, GW823296." }, { "input": "A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder ( MDD ).", "output": "There is no related enetity." }, { "input": "Displacement of central [ ( 11 ) C ] GR205171 binding indicated that oral orvepitant doses of 30 - 60 mg / day provided > 99 % receptor occupancy for >= 24 h.", "output": "[ ( 11 ) C ] GR205171, orvepitant." }, { "input": "Studies 733 and 833 randomized patients with MDD and 17 - item Hamilton Depression Rating Scale ( HAM - D ) >= 22 to double - blind treatment with orvepitant 30 mg / day, orvepitant 60 mg / day or placebo ( 1: 1: 1 ).", "output": "orvepitant, orvepitant." }, { "input": "Primary outcome measure was change from baseline in 17 - item HAM - D total score at Week 6 analyzed using mixed models repeated measures.", "output": "There is no related enetity." }, { "input": "Study 733 ( n = 328 ) demonstrated efficacy on the primary endpoint ( estimated drug - placebo differences of 30 mg: - 2. 41, 95 % confidence interval ( CI ) ( - 4. 50 to - 0. 31 ) p = 0. 0245; 60 mg: - 2. 86, 95 % CI ( - 4. 97 to - 0. 75 ) p = 0. 0082 ).", "output": "There is no related enetity." }, { "input": "Study 833 ( n = 345 ) did not show significance ( estimated drug - placebo differences of 30 mg: - 1. 67, 95 % CI ( - 3. 73 to 0. 39 ) p = 0. 1122; 60 mg: - 0. 76, 95 % CI ( - 2. 85 to 1. 32 ) p = 0. 4713 ).", "output": "There is no related enetity." }, { "input": "The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD.", "output": "There is no related enetity." }, { "input": "Heart failure therapy in patients with coronary artery disease.", "output": "There is no related enetity." }, { "input": "Heart failure and coronary artery disease share many risk factors.", "output": "There is no related enetity." }, { "input": "Coronary artery disease often pre - dates the development of heart failure with reduced ejection fraction.", "output": "There is no related enetity." }, { "input": "A diagnosis of heart failure should be considered in any patient with a history of coronary artery disease who presents with breathlessness, ankle oedema or fatigue.", "output": "There is no related enetity." }, { "input": "Several therapies, such as renin - angiotensin antagonists and B blockers, have been proven to improve survival in patients with heart failure with reduced ejection fraction but evidence for effectiveness in heart failure with preserved ejection fraction is lacking.", "output": "There is no related enetity." }, { "input": "The management of heart failure and coronary artery disease overlaps considerably but can also be conflicting.", "output": "There is no related enetity." }, { "input": "Optimal risk factor management is key to preventing progression to heart failure in patients with coronary artery disease.", "output": "There is no related enetity." }, { "input": "Interleukin - 23: a promising therapeutic target in seronegative spondyloarthropathy.", "output": "There is no related enetity." }, { "input": "Particular therapeutic challenges are raised by the spondyloarthropathies which represent a key area of unmet medical need.", "output": "There is no related enetity." }, { "input": "Recent investigations have shown that these conditions are characterised both by altered responsiveness to interleukin ( IL ) - 23 and expansion of IL - 23 responsive cells as well as increased production of IL - 23.", "output": "There is no related enetity." }, { "input": "The gut in particular has emerged as a key site of IL - 23 production, and gut inflammation is known to be strongly clinically associated with these conditions.", "output": "There is no related enetity." }, { "input": "Moreover, HLA - B27, which is strongly associated with spondyloarthropathy, has also been shown to stimulate IL - 23 production.", "output": "There is no related enetity." }, { "input": "The view is thus emerging that dysregulation of IL - 23 biology is a unifying feature of spondyloarthropathy, suggesting that treatments targeting this cytokine are likely to be highly efficacious.", "output": "There is no related enetity." }, { "input": "Molar Mass, Entanglement, and Associations of the Biofilm Polysaccharide of Staphylococcus epidermidis.", "output": "There is no related enetity." }, { "input": "Biofilms are microbial communities that are characterized by the presence of a viscoelastic extracellular polymeric substance ( EPS ).", "output": "There is no related enetity." }, { "input": "Studies have shown that polysaccharides, along with proteins and DNA, are a major constituent of the EPS and play a dominant role in mediating its microstructure and rheological properties.", "output": "There is no related enetity." }, { "input": "Here, we investigate the possibility of entanglements and associative complexes in solutions of extracellular polysaccharide intercellular adhesin ( PIA ) extracted from Staphylococcus epidermidis biofilms.", "output": "There is no related enetity." }, { "input": "We report that the weight average molar mass and radius of gyration of PIA isolates are 2. 01 x 10 ( 5 ) +/- 1200 g / mol and 29. 2 +/- 1. 2 nm, respectively.", "output": "There is no related enetity." }, { "input": "The coil overlap concentration, c *, was thus determined to be ( 32 +/- 4 ) x 10 ( - 4 ) g / mL.", "output": "There is no related enetity." }, { "input": "Measurements of the in situ concentration of PIA ( cPIA, biofilm ) was found to be ( 10 +/- 2 ) x 10 ( - 4 ) g / mL.", "output": "There is no related enetity." }, { "input": "Thus, cPIA, biofilm < c * and the amount of PIA in the biofilm is too low to cause polymer chain entanglements.", "output": "There is no related enetity." }, { "input": "In the pH range 3. 0 - 5. 5, PIA was found to both self - associate and to form complexes with bovine serum albumin ( BSA ).", "output": "There is no related enetity." }, { "input": "By static light scattering, both self - association and complex formation with 0. 5 % ( w / v ) BSA were found to occur at PIA concentrations of 0. 30 x 10 ( - 4 ) g / mL and greater, which is about 30 times lower than the measured cPIA, biofilm.", "output": "There is no related enetity." }, { "input": "These results suggest that the microscopic origin of EPS viscoelasticity is unlikely to be due to polysaccharide entanglements.", "output": "There is no related enetity." }, { "input": "Furthermore, the onset of self - association and protein complexation of PIA occurs at concentrations far lower than the native PIA concentration in biofilms.", "output": "There is no related enetity." }, { "input": "This finding therefore suggests a critical role for those two association mechanisms in mediating biofilm viscoelasticity.", "output": "There is no related enetity." }, { "input": "The Arabidopsis Nucleosome Remodeler DDM1 Allows DNA Methyltransferases to Access H1 - Containing Heterochromatin.", "output": "There is no related enetity." }, { "input": "Nucleosome remodelers of the DDM1 / Lsh family are required for DNA methylation of transposable elements, but the reason for this is unknown.", "output": "There is no related enetity." }, { "input": "How DDM1 interacts with other methylation pathways, such as small - RNA - directed DNA methylation ( RdDM ), which is thought to mediate plant asymmetric methylation through DRM enzymes, is also unclear.", "output": "There is no related enetity." }, { "input": "Here, we show that most asymmetric methylation is facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from RdDM.", "output": "There is no related enetity." }, { "input": "We find that heterochromatic sequences preferentially require DDM1 for DNA methylation and that this preference depends on linker histone H1.", "output": "There is no related enetity." }, { "input": "RdDM is instead inhibited by heterochromatin and absolutely requires the nucleosome remodeler DRD1.", "output": "There is no related enetity." }, { "input": "Together, DDM1 and RdDM mediate nearly all transposon methylation and collaborate to repress transposition and regulate the methylation and expression of genes.", "output": "There is no related enetity." }, { "input": "Our results indicate that DDM1 provides DNA methyltransferases access to H1 - containing heterochromatin to allow stable silencing of transposable elements in cooperation with the RdDM pathway.", "output": "There is no related enetity." }, { "input": "Asymmetric Collapse in Biomimetic Complex Coacervates Revealed by Local Polymer and Water Dynamics.", "output": "There is no related enetity." }, { "input": "Complex coacervation is a phenomenon characterized by the association of oppositely charged polyelectrolytes into micrometer - scale liquid condensates.", "output": "There is no related enetity." }, { "input": "This process is the purported first step in the formation of underwater adhesives by sessile marine organisms, as well as the process harnessed for the formation of new synthetic and protein - based contemporary materials.", "output": "There is no related enetity." }, { "input": "Efforts to understand the physical nature of complex coacervates are important for developing robust adhesives, injectable materials, or novel drug delivery vehicles for biomedical applications; however, their internal fluidity necessitates the use of in situ characterization strategies of their local dynamic properties, capabilities not offered by conventional techniques such as X - ray scattering, microscopy, or bulk rheological measurements.", "output": "There is no related enetity." }, { "input": "Herein, we employ the novel magnetic resonance technique Overhauser dynamic nuclear polarization enhanced nuclear magnetic resonance ( DNP ), together with electron paramagnetic resonance ( EPR ) line shape analysis, to concurrently quantify local molecular and hydration dynamics, with species - and site - specificity.", "output": "There is no related enetity." }, { "input": "We observe striking differences in the structure and dynamics of the protein - based biomimetic complex coacervates from their synthetic analogues, which is an asymmetric collapse of the polyelectrolyte constituents.", "output": "There is no related enetity." }, { "input": "From this study we suggest charge heterogeneity within a given polyelectrolyte chain to be an important parameter by which the internal structure of complex coacervates may be tuned.", "output": "There is no related enetity." }, { "input": "Acquiring molecular - level insight to the internal structure and dynamics of dynamic polymer complexes in water through the in situ characterization of site - and species - specific local polymer and hydration dynamics should be a promising general approach that has not been widely employed for materials characterization.", "output": "There is no related enetity." }, { "input": "Biocompatible Polylactide - block - Polypeptide - block - Polylactide Nanocarrier.", "output": "Polylactide, Polylactide." }, { "input": "Polypeptides are successfully incorporated into poly ( l - lactide ) ( PLLA ) chains in a ring - opening polymerization ( ROP ) of l - lactide by using them as initiators.", "output": "poly ( l - lactide ), PLLA, l - lactide." }, { "input": "The resulting ABA triblock copolymers possess molecular weights up to 11000 g. mol ( - 1 ) and polydispersities as low as 1. 13, indicating the living character of the polymerization process.", "output": "There is no related enetity." }, { "input": "In a nonaqueous emulsion, peptide - initiated polymerization of l - lactide leads to well - defined nanoparticles, consisting of PLLA - block - peptide - block - PLLA copolymer.", "output": "l - lactide, PLLA, PLLA." }, { "input": "These nanoparticles are easily loaded by dye - encapsulation and transferred into aqueous media without aggregation ( average diameter of 100 nm ) or significant dye leakage.", "output": "There is no related enetity." }, { "input": "Finally, internalization of PLLA - block - peptide - block - PLLA nanoparticles by HeLa cells is demonstrated by a combination of coherent anti - Stokes Raman spectroscopy ( CARS ) and fluorescence microscopy.", "output": "PLLA, PLLA." }, { "input": "This demonstrates the promise of their utilization as cargo delivery vehicles.", "output": "There is no related enetity." }, { "input": "A Coffee Ring Biosensor for Rapid Protein Detection.", "output": "There is no related enetity." }, { "input": "We introduce a new biosensing platform for rapid protein detection that combines one of the simplest methods for biomolecular concentration, coffee ring formation, with a sensitive aptamer - based optical detection scheme.", "output": "There is no related enetity." }, { "input": "In this approach, aptamer beacons are utilized for signal transduction where a fluorescence signal is emitted in the presence of the target molecule.", "output": "There is no related enetity." }, { "input": "Signal amplification is achieved by concentrating aptamer - target complexes within liquid droplets, resulting in the formation of coffee ring \" spots \".", "output": "There is no related enetity." }, { "input": "Surfaces with various chemical coatings were utilized to investigate the correlation between surface hydrophobicity, concentration efficiency and signal amplification.", "output": "There is no related enetity." }, { "input": "Based on our results, we found that the increase in coffee ring diameter with larger droplet volumes is independent of surface hydrophobicity.", "output": "There is no related enetity." }, { "input": "Furthermore, we show that highly hydrophobic surfaces produce enhanced particle concentration, via coffee ring formation, resulting in signal intensities 6 - fold greater than those on hydrophilic surfaces.", "output": "There is no related enetity." }, { "input": "To validate this biosensing platform for the detection of clinical samples, we detected alpha - thrombin in human serum and 4x diluted whole blood.", "output": "There is no related enetity." }, { "input": "Based on our results, coffee ring spots produced detection signals 40x larger than samples in liquid droplets.", "output": "There is no related enetity." }, { "input": "Additionally, this biosensor exhibits a lower limit of detection of 2 ng / mL ( 54 pM ) in serum, and 4 ng / mL ( 105 pM ) in blood.", "output": "There is no related enetity." }, { "input": "Based on its simplicity and high performance, this platform demonstrates immense potential as an inexpensive diagnostic tool for the detection of disease biomarkers, particularly for use in developing countries that lack the resources and facilities required for conventional biodetection practices.", "output": "There is no related enetity." }, { "input": "Androgen deprivation from pre - puberty to peripuberty interferes in proteins expression in pubertal and adult rat epididymis.", "output": "Androgen." }, { "input": "Few studies have focused on experimental testosterone deprivation in immature animals.", "output": "testosterone." }, { "input": "Therefore, this study used sexually immature rats aiming to evaluate the testes and epididymis histology and proteins expression in these organs on PND50 and 75, after premature antiandrogen exposure, from PND21 to 44.", "output": "There is no related enetity." }, { "input": "Although the androgen deprivation from pre - puberty up to peripuberty did not alter the histological organization of the testes and epididymis either at puberty or at adulthood, the treatment impaired the expression of specific proteins in epididymal tissue at puberty and adulthood ( androgen receptor, calmodulin, Rab11A ).", "output": "androgen, androgen." }, { "input": "These changes may be related to impaired epididymal function, sperm quality and fertility capacity as observed in a previous study.", "output": "There is no related enetity." }, { "input": "Further studies are necessary to better investigate the molecular mechanisms involved in the impairment on reproductive competence of male rats after precocious hormonal injury.", "output": "There is no related enetity." }, { "input": "Anti - inflammatory effect of essential oil and its constituents from fingered citron ( Citrus medica L. var. sarcodactylis ) through blocking JNK, ERK and NF - kappa B signaling pathways in LPS - activated RAW 264. 7 cells.", "output": "There is no related enetity." }, { "input": "We investigated the composition of essential oil from fingered citron ( Citrus medica L. var. sarcodactylis ) ( FCEO ) peels by GC - MS and its anti - inflammatory effects on lipopolysaccharide ( LPS ) - stimulated mouse macrophage ( RAW 264. 7 ) cells.", "output": "There is no related enetity." }, { "input": "Fifteen compounds, representing 98. 97 % of the essential oil, were tentatively identified; the main constituents were limonene ( 52. 44 % ) and gamma - terpinene ( 28. 41 % ).", "output": "limonene, gamma - terpinene." }, { "input": "FCEO significantly inhibited nitric oxide ( NO ) and prostaglandin E2 ( PGE2 ) by suppressing the protein expression of inducible nitric oxide synthase ( iNOS ) and cyclooxygenase ( COX ) - 2, respectively.", "output": "nitric oxide, NO, prostaglandin E2, PGE2, nitric oxide." }, { "input": "Additionally, FCEO suppressed the production of tumor necrosis factor - alpha ( TNF - alpha ), interleukin ( IL ) - 1 beta, and IL - 6.", "output": "There is no related enetity." }, { "input": "FCEO attenuated LPS - induced nuclear factor - kappa B ( NF - kappa B ) activation via inhibition of inhibitor kappa B - alpha phosphorylation.", "output": "There is no related enetity." }, { "input": "Furthermore, FCEO blocked activation of c - Jun N - terminal kinase ( JNK ) and extracellular signal - regulated kinase ( ERK ) but not that of p38 mitogen - activated protein kinase.", "output": "There is no related enetity." }, { "input": "These results indicate that FCEO inhibits LPS - stimulated inflammation by blocking the NF - kappa B, JNK, and ERK pathways in macrophages, and demonstrate that FCEO possesses anti - inflammatory properties.", "output": "There is no related enetity." }, { "input": "Aldosterone - induced ENaC and basal Na ( + ) / K ( + ) - ATPase trafficking via protein kinase D1 - phosphatidylinositol 4 - kinaseIII beta trans Golgi signalling in M1 cortical collecting duct cells.", "output": "Aldosterone, Na ( + ), K ( + ), phosphatidylinositol." }, { "input": "Aldosterone regulates Na ( + ) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel ( ENaC ) and Na ( + ) / K ( + ) - ATPase subunits.", "output": "Aldosterone, Na ( + ), Na ( + ), K ( + )." }, { "input": "Aldosterone also induces the rapid phosphorylation of Protein Kinase D1 ( PKD1 ).", "output": "Aldosterone." }, { "input": "PKD isoforms regulate protein trafficking, by the control of vesicle fission from the trans Golgi network ( TGN ) through activation of phosphatidylinositol 4 - kinaseIII beta ( PI4KIII beta ).", "output": "phosphatidylinositol." }, { "input": "We report rapid ENaC gamma translocation to the plasma membrane after 30min aldosterone treatment in polarized M1 cortical collecting duct cells, which was significantly impaired in PKD1 shRNA - mediated knockdown cells.", "output": "There is no related enetity." }, { "input": "In PKD1 - deficient cells, the ouabain - sensitive current was significantly reduced and Na ( + ) / K ( + ) - ATPase alpha and beta subunits showed aberrant localization.", "output": "ouabain, Na ( + ), K ( + )." }, { "input": "PKD1 and PI4KIII beta localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIII beta following aldosterone treatment.", "output": "aldosterone, aldosterone." }, { "input": "This study reveals a novel mechanism for rapid regulation of ENaC and the Na ( + ) / K ( + ) - ATPase, via directed trafficking through PKD1 - PI4KIII beta signalling at the level of the TGN.", "output": "Na ( + ), K ( + )." }, { "input": "Glycyrrhetinic acid and its analogs: A new class of antifilarial agents.", "output": "Glycyrrhetinic acid." }, { "input": "Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance.", "output": "There is no related enetity." }, { "input": "As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid ( GA, 1a ) effective against microfilariae ( mf ) in vitro ( LC100: 12. 5 mu M; IC50: 1. 20 mu M ), but was inactive against adult worms.", "output": "glycyrrhetinic acid." }, { "input": "Further, GA ( 1a ) was converted into six analogs ( 2a - 7a ) and their antifilarial potential was evaluated by studying in vitro motility and MTT reduction assays employing mf and adult worms of Brugia malayi.", "output": "MTT." }, { "input": "The results showed that out of six GA analogs, the benzyl amide analog ( 6a ) killed adults and mf at 25 and 50 mu M concentration, respectively, and inhibited 49 % MTT reduction potential of the adult parasites.", "output": "benzyl amide, MTT." }, { "input": "The IC50 values were found to be 8. 8 and 2. 2 mu M for adults and mf, respectively.", "output": "There is no related enetity." }, { "input": "The SI of the compound was > 60.", "output": "There is no related enetity." }, { "input": "On the other hand the octylamide analog ( 7a ) required much higher concentration to adversely affect the parasites.", "output": "octylamide." }, { "input": "Finally, both active amide analogs ( 6a and 7a ) were in vivo evaluated using B. malayi - jird model, which showed that analog 6a possesses promising macrofilaricidal activity at 100mg / kg, s. c.", "output": "amide." }, { "input": "x 5days and around 40 % of the treated animals showed calcified masses of worm fragments in peritoneal cavity of the animals.", "output": "There is no related enetity." }, { "input": "To the best of our knowledge this is the first ever report on the antifilarial potential of GA analogs.", "output": "There is no related enetity." }, { "input": "Further work on optimization of the antifilarial lead is under progress.", "output": "There is no related enetity." }, { "input": "Discovery of a series of novel 5H - pyrrolo [ 2, 3 - b ] pyrazine - 2 - phenyl ethers, as potent JAK3 kinase inhibitors.", "output": "5H - pyrrolo [ 2 , 3 - b ] pyrazine - 2 - phenyl ethers." }, { "input": "We report the discovery of a novel series of ATP - competitive Janus kinase 3 ( JAK3 ) inhibitors based on the 5H - pyrrolo [ 2, 3 - b ] pyrazine scaffold.", "output": "ATP, 5H - pyrrolo [ 2 , 3 - b ] pyrazine." }, { "input": "The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family.", "output": "There is no related enetity." }, { "input": "Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity.", "output": "There is no related enetity." }, { "input": "Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity.", "output": "There is no related enetity." }, { "input": "The Decapping Scavenger Enzyme DCS - 1 Controls MicroRNA Levels in Caenorhabditis elegans.", "output": "There is no related enetity." }, { "input": "In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation.", "output": "There is no related enetity." }, { "input": "MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation.", "output": "There is no related enetity." }, { "input": "However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA.", "output": "There is no related enetity." }, { "input": "Here, we uncover the implication of the decapping scavenger protein DCS - 1 in the control of microRNA turnover.", "output": "There is no related enetity." }, { "input": "In Caenorhabditis elegans, mutations in dcs - 1 increase the levels of functional microRNAs.", "output": "There is no related enetity." }, { "input": "We demonstrate that DCS - 1 interacts with the exonuclease XRN - 1 to promote microRNA degradation in an independent manner from its known decapping scavenger activity, establishing two molecular functions for DCS - 1.", "output": "There is no related enetity." }, { "input": "Our findings thus indicate that DCS - 1 is part of a degradation complex that performs microRNA turnover in animals.", "output": "There is no related enetity." }, { "input": "Two antagonistic clock - regulated histidine kinases time the activation of circadian gene expression.", "output": "histidine." }, { "input": "The cyanobacterial circadian pacemaker consists of a three - protein clock - KaiA, KaiB, and KaiC - that generates oscillations in the phosphorylation state of KaiC.", "output": "There is no related enetity." }, { "input": "Here we investigate how temporal information encoded in KaiC phosphorylation is transduced to RpaA, a transcription factor required for circadian gene expression.", "output": "There is no related enetity." }, { "input": "We show that phosphorylation of RpaA is regulated by two antagonistic histidine kinases, SasA and CikA, which are sequentially activated at distinct times by the Kai clock complex.", "output": "There is no related enetity." }, { "input": "SasA acts as a kinase toward RpaA, whereas CikA, previously implicated in clock input, acts as a phosphatase that dephosphorylates RpaA.", "output": "There is no related enetity." }, { "input": "CikA and SasA cooperate to generate an oscillation of RpaA activity that is distinct from that generated by either enzyme alone and offset from the rhythm of KaiC phosphorylation.", "output": "There is no related enetity." }, { "input": "Our observations reveal how circadian clocks can precisely control the timing of output pathways via the concerted action of two oppositely acting enzymes.", "output": "There is no related enetity." }, { "input": "Signaling pathways mediating the effects of insulin - like growth factor - I in bovine muscle satellite cells.", "output": "There is no related enetity." }, { "input": "The objective of this study was to identify the signaling pathways mediating the effects of IGF - I on muscle cell proliferation, protein synthesis, and protein degradation in a physiologically more relevant muscle cell model.", "output": "There is no related enetity." }, { "input": "We isolated muscle satellite cells from adult cattle and expanded them as myoblasts or induced them to form myotubes in culture.", "output": "There is no related enetity." }, { "input": "We determined the effects of IGF - I on proliferation of myoblasts and protein synthesis and degradation in myotubes in the presence or absence of specific signaling inhibitors.", "output": "There is no related enetity." }, { "input": "Our data suggest that both the MEK / ERK and PI3K / AKT pathways mediate the stimulatory effect of IGF - I on myoblast proliferation and that the PI3K / AKT pathway mediates this effect through cyclin D2.", "output": "There is no related enetity." }, { "input": "Our data also suggest that both the MEK / ERK and PI3K / AKT pathways mediate the stimulatory effect of IGF - I on protein synthesis through p70S6K and that the PI3K / AKT pathway mediates the inhibitory effect of IGF - I on protein degradation through FoxO3a.", "output": "There is no related enetity." }, { "input": "The effects of RFRP - 3, the mammalian ortholog of GnIH, on the female pig reproductive axis in vitro.", "output": "RFRP - 3." }, { "input": "RFamide - related peptide - 3 ( RFRP - 3 ) has been proposed as a key inhibitory regulator of mammalian reproduction.", "output": "RFamide - related peptide - 3, RFRP - 3." }, { "input": "To further determine the potential mechanisms and sites of action of RFRP - 3, we systematically investigated the direct effect of RFRP - 3 on the female pig reproductive axis in vitro.", "output": "RFRP - 3, RFRP - 3." }, { "input": "Initially, we confirmed that G protein - coupled receptor 147 ( GPR147 ) was distributed in isolated hypothalamic, anterior pituitary and ovarian granulosa cells, suggesting that RFRP - 3 could act on these cells in vitro.", "output": "RFRP - 3." }, { "input": "Subsequently, the direct effects of RFRP - 3 on hormone and steroid secretion, the synthesis of subunit genes and the expression of proteins related to proliferation in the hypothalamus, pituitary and ovary were evaluated.", "output": "RFRP - 3, steroid." }, { "input": "Our results demonstrate that different doses of RFRP - 3 inhibited the release and synthesis of gonadotrophin releasing hormone, gonadotrophin and steroid hormones and impacted the relative gene expression of KISS1 and GnRHR and the protein expression of cyclin B1, PCNA and ERK 1 / 2.", "output": "RFRP - 3, steroid." }, { "input": "Genome - wide association studies on serum sex steroid levels.", "output": "steroid." }, { "input": "Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown.", "output": "steroid." }, { "input": "With the advent of genome - wide association studies ( GWAS ), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone - binding globulin.", "output": "dehydroepiandrosterone sulfate, testosterone." }, { "input": "The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone - sensitive cancers.", "output": "steroid." }, { "input": "This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.", "output": "steroid." }, { "input": "Steric Complementarity in the Decoding Center Is Important for tRNA Selection by the Ribosome.", "output": "There is no related enetity." }, { "input": "Accurate tRNA selection by the ribosome is essential for the synthesis of functional proteins.", "output": "There is no related enetity." }, { "input": "Previous structural studies indicated that the ribosome distinguishes between cognate and near - cognate tRNAs by monitoring the geometry of the codon - anticodon helix in the decoding center using the universally conserved 16S ribosomal RNA bases G530, A1492 and A1493.", "output": "There is no related enetity." }, { "input": "These bases form hydrogen bonds with the 2 ' - hydroxyl groups of the codon - anticodon helix, which are expected to be disrupted with a near - cognate codon - anticodon helix.", "output": "hydrogen, 2 ' - hydroxyl." }, { "input": "However, a recent structural study showed that G530, A1492 and A1493 form hydrogen bonds in a manner identical with that of both cognate and near - cognate codon - anticodon helices.", "output": "hydrogen." }, { "input": "To understand how the ribosome discriminates between cognate and near - cognate tRNAs, we made 2 ' - deoxynucleotide and 2 ' - fluoro substituted mRNAs, which disrupt the hydrogen bonds between the A site codon and G530, A1492 and A1493.", "output": "2 ' - fluoro, hydrogen." }, { "input": "Our results show that multiple 2 ' - deoxynucleotide substitutions in the mRNA substantially inhibit tRNA selection, whereas multiple 2 ' - fluoro substitutions in the mRNA have only modest effects on tRNA selection.", "output": "2 ' - fluoro." }, { "input": "Furthermore, the miscoding antibiotics paromomycin and streptomycin rescue the defects in tRNA selection with the multiple 2 ' - deoxynucleotide substituted mRNA.", "output": "There is no related enetity." }, { "input": "These results suggest that steric complementarity in the decoding center is more important than the hydrogen bonds between the A site codon and G530, A1492 and A1493 for tRNA selection.", "output": "hydrogen." }, { "input": "The in vitro cytotoxicity and genotoxicity of cigarette smoke particulate matter with reduced toxicant yields.", "output": "There is no related enetity." }, { "input": "Tobacco smoke contains more than 5600 constituents, of which approximately 150 are toxicants.", "output": "There is no related enetity." }, { "input": "This paper describes the activities in the Neutral Red uptake ( NRU ) assay, the Salmonella mutagenicity test ( SAL ), the mouse lymphoma mammalian cell mutation assay ( MLA ) and the in vitro micronucleus test ( IVMNT ) of Particulate Matter ( PM ) obtained from experimental cigarettes ( ECs ), designed to produce reduced levels of toxicants.", "output": "Neutral Red." }, { "input": "The designs included tobacco substitute sheet ( TSS ) containing glycerol, which dilutes toxicants in smoke, or the incorporation of blend - treated ( BT ) tobacco to reduce the levels of nitrogenous toxicant precursors and some polyphenols.", "output": "glycerol, polyphenols." }, { "input": "All samples were cytotoxic in the NRU, however TSS reduced PM cytotoxicity in this assay.", "output": "There is no related enetity." }, { "input": "All PMs were mutagenic in the SAL, MLA and IVMNT.", "output": "There is no related enetity." }, { "input": "Reductions in bacterial mutagenicity were observed in the SAL, for cigarettes with BT tobacco, compared with their respective controls.", "output": "There is no related enetity." }, { "input": "The quantitative changes in bacterial mutagenicity could be explained by analytical chemistry data on smoke generated from the ECs used in the study.", "output": "There is no related enetity." }, { "input": "These observations, and the absence of consistent qualitative differences in the activities of the experimental, control and reference cigarettes, suggest that reduced toxicity cigarettes, as measured by the tests described in this paper, may be developed without introducing any additional cytotoxic or genotoxic hazards, but the impact of this on human health risks remains unknown.", "output": "There is no related enetity." }, { "input": "In vivo and in vitro anti - inflammatory activity of Lentinus polychrous extract.", "output": "There is no related enetity." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Lentinus polychrous is a Thai local edible mushroom, traditionally used for the treatments of fever and inflammation due to snake or scorpion envenomation.", "output": "There is no related enetity." }, { "input": "AIM OF STUDY: The present study aimed to investigate an anti - inflammatory effect of Lentinus polychrous mycelial extract ( LPME ) both in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: The cytotoxicity and suppressive effects of LPME on nitric oxide production, intracellular O2 ( - ) production, pro - inflammatory mediator expression, TNF - alpha production were determined by using LPS - activated RAW 264. 7 cells.", "output": "nitric oxide, O2 ( - )." }, { "input": "In addition, Anti - inflammatory effect of LPME was evaluated by using carageenan - induced paw edema in rats.", "output": "There is no related enetity." }, { "input": "RESULTS: The LPME exhibited cytotoxicity with 50 % inhibitory concentration ( IC50 ) of 280. 25 +/- 10. 10 mu g / ml and significantly suppressed the productions of NO and intracellular O2 ( - ) with dose - dependent manner.", "output": "NO, O2 ( - )." }, { "input": "LPME decreased the expressions of iNOS, IL - 1 beta, IL - 6, TNF - alpha and COX - 2 and significantly decreased the TNF - alpha production in LPS - activated macrophage with dose - dependent manners.", "output": "There is no related enetity." }, { "input": "Moreover, LPME showed significant suppressive effect on paw edema in rats.", "output": "There is no related enetity." }, { "input": "CONCLUSION: The results clearly revealed that the LPME inhibited NO and pro - inflammatory productions by down - regulating the gene expressions of pro - inflammatory mediators leading to the decrease paw edema in rat which support the traditional use.", "output": "NO." }, { "input": "Oxidative status in ICU patients with septic shock.", "output": "There is no related enetity." }, { "input": "The aim of this pilot study was to investigate variability of oxidative stress during sepsis evolution.", "output": "There is no related enetity." }, { "input": "ICU patients with the diagnosis of septic shock were included.", "output": "There is no related enetity." }, { "input": "Thiobarbituric - acid reactive substances, total antioxidant capacity, protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8thday after sepsis appearance.", "output": "Thiobarbituric - acid, carbonyls, glutathione." }, { "input": "A total of 17 patients were divided in two groups: survivors ( n = 7 ) and non - survivors ( n = 10 ).", "output": "There is no related enetity." }, { "input": "APACHE II was 11. 5 +/- 5. 4 and 19. 9 +/- 4. 97 in survivors and non - survivors respectively ( p = 0. 005 ), while mean age and SOFA score at sepsis diagnosis, were similar between the two groups.", "output": "There is no related enetity." }, { "input": "GSH levels, catalase activity and protein carbonyls presented significant different course in time between survivors and non - survivors ( p < 0. 05 ).", "output": "GSH, carbonyls." }, { "input": "Catalase activity was significantly higher in survivors ( 238. 8 +/- 51. 5 ) than non - survivors ( 166. 4 +/- 40. 2; p = 0. 005 ), while protein carbonyls levels were significantly lower in survivors ( 0. 32 +/- 0. 09 ) than non - survivors ( 0. 48 +/- 0. 16; p = 0. 036 ) on the 1stday.", "output": "carbonyls." }, { "input": "Yet, non - survivors exhibited a declining course in GSH levels during time, while GSH levels were maintained in survivors.", "output": "GSH, GSH." }, { "input": "Conclusively, a longstanding antioxidant deficiency in non - surviving patients was noted.", "output": "There is no related enetity." }, { "input": "This phenomenon was clearly prominent in patients ' erythrocytes.", "output": "There is no related enetity." }, { "input": "SPIO - PICsome: Development of a highly sensitive and stealth - capable MRI nano - agent for tumor detection using SPIO - loaded unilamellar polyion complex vesicles ( PICsomes ).", "output": "There is no related enetity." }, { "input": "Size controllable polyion complex vesicles ( PICsomes ), composed of biocompatible poly ( ethylene glycol ) ( PEG ) and poly ( amino acid ) s, have an extremely prolonged lifetime in the bloodstream that enables them to accumulate effectively in tumors via the enhanced permeability and retention ( EPR ) effect.", "output": "poly ( ethylene glycol ), PEG, poly ( amino acid ) s." }, { "input": "The purpose of this study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for more precise tumor detection.", "output": "There is no related enetity." }, { "input": "We synthesized SPIO - Cy5 - PICsomes ( superparamagnetic iron oxide nanoparticle - loaded Cy5 - cross - linked Nano - PICsomes ) and characterized them using dynamic light scattering and transmission electron microscopy in vitro and evaluated their ability to detect subcutaneously grafted tumors in vivo with MRI.", "output": "iron oxide." }, { "input": "The transverse relaxivity ( r2 ) of the SPIO - Cy5 - PICsomes ( r2 = 663 +/- 28mM ( - 1 ) s ( - 1 ) ) was 2. 54 times higher than that of bare clinically - used SPIO.", "output": "There is no related enetity." }, { "input": "In in vivo MRI experiments on mice subcutaneously grafted with colon - 26 tumor cells, the tumor signal was significantly altered at 3h after SPIO - Cy5 - PICsome administration and persisted for at least 24h.", "output": "There is no related enetity." }, { "input": "Small and early - stage in vivo tumors ( 3days after grafting, approximately 4mm ( 3 ) ) were also clearly detected with MRI.", "output": "There is no related enetity." }, { "input": "SPIO - loaded PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier to detect small tumors for early diagnosis.", "output": "There is no related enetity." }, { "input": "Sensitization of restraint - induced corticosterone secretion after chronic restraint in rats: Involvement of 5 - HT7 receptors.", "output": "corticosterone." }, { "input": "Serotonin ( 5 - HT ) modulates the hypothalamic - pituitary - adrenal ( HPA ) axis response to stress.", "output": "Serotonin, 5 - HT." }, { "input": "We examined the effect of chronic restraint stress ( CRS; 20 min / day ) as compared to control ( CTRL ) conditions for 14 days, on: 1 ) restraint - induced ACTH and corticosterone ( CORT ) secretion in rats pretreated with vehicle or SB - 656104 ( a 5 - HT7 receptor antagonist ); 2 ) 5 - HT7 receptor - like immunoreactivity ( 5 - HT7 - LI ) and protein in the hypothalamic paraventricular nucleus ( PVN ) and adrenal glands ( AG ); 3 ) baseline levels of 5 - HT and 5 - hydroxyindolacetic acid ( 5 - HIAA ), and 5 - HIAA / 5 - HT ratio in PVN and AG; and 4 ) 5 - HT - like immunoreactivity ( 5 - HT - LI ) in AG and tryptophan hydroxylase ( TPH ) protein in PVN and AG.", "output": "corticosterone, CORT, SB - 656104, 5 - HT, 5 - hydroxyindolacetic acid, 5 - HIAA, 5 - HIAA, 5 - HT, 5 - HT, 5 - HT, tryptophan." }, { "input": "On day 15, animals were subdivided into Treatment and No treatment groups.", "output": "There is no related enetity." }, { "input": "Treatment animals received an i. p. injection of vehicle or SB - 656104; No Treatment animals received no injection.", "output": "SB - 656104." }, { "input": "Sixty min later, Treatment animals were either decapitated with no further stress ( 0 min ) or submitted to acute restraint ( 10, 30, 60 or 120 min ); hormone serum levels were measured.", "output": "There is no related enetity." }, { "input": "No Treatment animals were employed for the rest of measurements.", "output": "There is no related enetity." }, { "input": "CRS decreased body weight gain and increased adrenal weight.", "output": "There is no related enetity." }, { "input": "In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint - dependent manner; both responses were inhibited by SB - 656104.", "output": "CORT, SB - 656104." }, { "input": "Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB - 656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses.", "output": "CORT, SB - 656104, CORT." }, { "input": "In CTRL animals, 5 - HT7 - LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex.", "output": "There is no related enetity." }, { "input": "Exposure to CRS decreased 5 - HT7 - LI and protein in the PVN, but increased 5 - HT7 - LI in the adrenal cortex and protein in whole AG.", "output": "There is no related enetity." }, { "input": "Higher 5 - HT and 5 - HIAA levels were detected in PVN and AG from CRS animals but 5 - HIAA / 5 - HT ratio increased in AG only.", "output": "5 - HT, 5 - HIAA, 5 - HIAA, 5 - HT." }, { "input": "Finally, whereas 5 - HT - LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals.", "output": "5 - HT." }, { "input": "No TPH protein was detected in AG from both animal groups.", "output": "There is no related enetity." }, { "input": "Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint.", "output": "CORT." }, { "input": "This phenomenon may be associated with increased function and expression of 5 - HT7 receptors as well as 5 - HT turnover in AG.", "output": "5 - HT." }, { "input": "5 - Hydroxy - 3, 6, 7, 8, 3 ' 4 ' - hexamethoxyflavone inhibits nitric oxide production in lipopolysaccharide - stimulated BV2 microglia via NF - kappa B suppression and Nrf - 2 - dependent heme oxygenase - 1 induction.", "output": "5 - Hydroxy - 3 , 6 , 7 , 8 , 3 ' 4 ' - hexamethoxyflavone, nitric oxide." }, { "input": "In this study, we found that 5 - hydroxy - 3, 6, 7, 8, 3 ' 4 ' - hexamethoxyflavone ( 5HHMF ) from Hizikia fusiforme considerably inhibits lipopolysaccharide ( LPS ) - stimulated NO production by suppressing the expression of inducible NO synthase ( iNOS ) in BV2 microglia.", "output": "5 - hydroxy - 3 , 6 , 7 , 8 , 3 ' 4 ' - hexamethoxyflavone, 5HHMF, NO, NO." }, { "input": "In addition, 5HHMF blocked LPS - induced phosphorylation of I kappa B, resulting in suppression of the nuclear translocation of nuclear factor - kappa B ( NF - kappa B ) subunits, namely p65 and p50, which are important molecules involved in the regulation of iNOS expression.", "output": "5HHMF." }, { "input": "Pyrrolidine dithiocarbamate ( PDTC ), a specific NF - kappa B inhibitor, along with 20S proteasome inhibitor ( PSI ) significantly inhibited LPS - induced iNOS expression, which indirectly suggested that 5HHMF downregulated iNOS expression by suppressing NF - kappa B activity.", "output": "Pyrrolidine dithiocarbamate, PDTC, 5HHMF." }, { "input": "Thus, we found that 5HHMF enhances heme oxygenase - 1 ( HO - 1 ) expression via nuclear factor - erythroid 2 - related factor 2 ( Nrf2 ) activation.", "output": "5HHMF." }, { "input": "In addition, cobalt protoporphyrin ( CoPP ), a specific HO - 1 inducer, predominantly suppressed LPS - induced NO production.", "output": "cobalt protoporphyrin, CoPP, NO." }, { "input": "In contrast, zinc protoporphyrin ( ZnPP ), a specific HO - 1 inhibitor, showed a partial suppressive effect of 5HHMF on LPS - induced NO production.", "output": "zinc protoporphyrin, ZnPP, 5HHMF, NO." }, { "input": "Further, 5HHMF increased specific DNA - binding activity of Nrf2, and transient knockdown with Nrf2 siRNA subsequently reversed 5HHMF - induced NO inhibition, which was followed by suppression of HO - 1 activity.", "output": "5HHMF, 5HHMF, NO." }, { "input": "Taken together, our findings indicate that 5HHMF suppresses NO production through modulation of iNOS, consequently suppressing NF - kappa B activity and induction of Nrf2 - dependent HO - 1 activity.", "output": "5HHMF, NO." }, { "input": "Pulmonary DWCNT exposure causes sustained local and low - level systemic inflammatory changes in mice.", "output": "There is no related enetity." }, { "input": "Carbon nanotubes ( CNTs ) represent promising vectors to facilitate cellular drug delivery and to overcome biological barriers, but some types may also elicit persistent pulmonary inflammation based on their fibre characteristics.", "output": "Carbon." }, { "input": "Here, we show the pulmonary response to aqueous suspensions of block copolymer dispersed, double - walled carbon nanotubes ( DWCNT, length 1 - 10 mu m ) in mice by bronchoalveolar lavage ( BAL ) analysis, and BAL and blood cytokine and lung antioxidant profiling.", "output": "carbon." }, { "input": "The intratracheally instilled dose of 50 mu g DWCNT caused significant pulmonary inflammation that was not resolved during a 7 - day observation period.", "output": "There is no related enetity." }, { "input": "Light microscopy investigation of the uptake of DWCNT agglomerates revealed no particle ingestion for granulocytes, but only for macrophages.", "output": "There is no related enetity." }, { "input": "Accumulating macrophage, multinucleated macrophage and lymphocyte numbers in the alveolar region further indicated ineffective resolution with chronification of the inflammation.", "output": "There is no related enetity." }, { "input": "The local inflammatory impairment of the lung was accompanied by pulmonary antioxidant depletion and haematological signs of systemic inflammation.", "output": "There is no related enetity." }, { "input": "While the observed inflammation during its acute phase was dominated by neutrophils and neutrophil recruiting cytokines, the contribution of macrophages and lymphocytes with related cytokines became more significant after day 3 of exposure.", "output": "There is no related enetity." }, { "input": "This study confirms that acute pulmonary toxicity can occur on exposure of high doses of DWCNT agglomerates and offers further insight for improved nanotube design parameters to avoid potential long - term toxicity.", "output": "There is no related enetity." }, { "input": "The effects of 17 - alpha - ethinylestradiol ( EE2 ) on molecular signaling cascades in mummichog ( Fundulus heteroclitus ).", "output": "17 - alpha - ethinylestradiol, EE2." }, { "input": "Exposures to <= 10ng / L of 17 - alpha - ethinylestradiol ( EE2 ) will reduce or shut down egg production in freshwater fish models, while mummichog ( Fundulus heteroclitus ), an estuarine species, are able to produce eggs at EE2 concentrations > 3000ng / L.", "output": "17 - alpha - ethinylestradiol, EE2, EE2." }, { "input": "The objective of this study was to gain mechanistic insight into how mummichog are able to produce eggs during exposures to high EE2.", "output": "EE2." }, { "input": "Mummichog were exposed to 0, 50 or 250ng / L of EE2 for 14d.", "output": "EE2." }, { "input": "There were no changes in gonadosomatic index, liversomatic index, gonad development, or plasma estradiol levels after exposure to EE2.", "output": "estradiol, EE2." }, { "input": "However, testosterone significantly decreased with EE2 exposures ( 50, 250ng / L ).", "output": "EE2." }, { "input": "Microarray analysis in the liver revealed that cell processes associated with lipids were affected by EE2 at the transcriptome level.", "output": "EE2." }, { "input": "Based on the transcriptomics data, we hypothesize that mummichog are able to maintain lipid transport and uptake into the ovary and this may be associated with apolipoproteins, facilitating normal oocyte development.", "output": "There is no related enetity." }, { "input": "Novel gene regulatory networks for protein modification targets were also constructed to learn more about the potential roles of estrogens in the teleost liver.", "output": "estrogens." }, { "input": "Although post - translational modifications ( PTMs ) are important regulatory mechanisms, the roles of PTMs in protein regulation in fish and the susceptibility of PTMs to aquatic pollutants are largely unexplored and may offer novel insight into mechanisms of endocrine disruption.", "output": "There is no related enetity." }, { "input": "Leptin as regulator of pulmonary immune responses: Involvement in respiratory diseases.", "output": "There is no related enetity." }, { "input": "Leptin is an adipocyte - derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor ( Ob - Rb ) in the hypothalamus.", "output": "There is no related enetity." }, { "input": "Structurally, leptin belongs to the long - chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity.", "output": "There is no related enetity." }, { "input": "The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases.", "output": "There is no related enetity." }, { "input": "The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease ( COPD ), asthma, and pneumonia.", "output": "There is no related enetity." }, { "input": "Commentary to Gebel 2012: a quantitative review should apply meta - analytical methods.", "output": "There is no related enetity." }, { "input": "Gebel ( 2012 ) performed a quantitative review of inhalation rat studies on the association of granular biopersistent dust exposures and lung cancer risk.", "output": "There is no related enetity." }, { "input": "The analytical methods applied are unreliable because they do not fulfil the requirements of current meta - analytical methods.", "output": "There is no related enetity." }, { "input": "RNAi silencing of three homologues of S - adenosylmethionine decarboxylase gene in tapetal tissue of tomato results in male sterility.", "output": "S - adenosylmethionine." }, { "input": "Polyamines play very important role in various cellular metabolic functions, including floral induction, floral differentiation and fertility regulation.", "output": "Polyamines." }, { "input": "In the present study, S - adenosylmethionine decarboxylase ( SAMDC ), a key gene involved in polyamine biosynthesis, has been targeted in tapetal tissue of tomato using RNAi to examine its effect on tapetum development and pollen viability.", "output": "S - adenosylmethionine, polyamine." }, { "input": "The target SAMDC gene fragments of three homologues were cloned in a hairpin RNA construct under the control of tapetal - specific A9 promoter, which was used to generate several RNAi tomato plants.", "output": "There is no related enetity." }, { "input": "These RNAi lines expressed the intended small interfering RNAs in the anther and showed the aborted and sterile pollen exhibiting shrunken and distorted morphology.", "output": "There is no related enetity." }, { "input": "These RNAi tomato plants having sterile pollen, failed to set fruits but female fertility of the plants remained unaffected as cross pollination resulted in fruit setting.", "output": "There is no related enetity." }, { "input": "Expression profiling of SAMDC genes showed considerable decrease in transcripts of SAMDC1 ( 5 - 8 fold ) and SAMDC2 and SAMDC3 ( 2 - 3 fold ) in the anthers of RNAi plants.", "output": "There is no related enetity." }, { "input": "The other polyamine biosynthesis genes, ADC and SPDSYN exhibited ~ 1. 5 fold decrease in their transcript levels.", "output": "polyamine." }, { "input": "Presence of siRNA molecules specific to SAMDC homologues in anther and tapetal - specific activity of A9 promoter as shown with GUS reporter system of RNAi plants suggested down - regulation of the target genes in tapetum by RNAi.", "output": "There is no related enetity." }, { "input": "These observations indicate the importance of SAMDC, in turn polyamines in pollen development, and thus tapetum - specific down - regulation of SAMDC genes using RNAi can be used for developing male sterile plants.", "output": "polyamines." }, { "input": "A Re - evaluation of the Role of hCTR1, the Human High Affinity Cu Transporter in Pt - Drug Entry into Human Cells.", "output": "Cu, Pt." }, { "input": "Cisplatin ( cDDP ) is an anti - cancer drug used in a number of malignancies including testicular, ovarian, cervical, bladder, lung, head, and neck cancers.", "output": "Cisplatin, cDDP." }, { "input": "Its use is limited by the development of resistance, often rationalized via effects on cellular uptake.", "output": "There is no related enetity." }, { "input": "It has been claimed that hCTR1, the human high affinity copper transporter, is the major entry pathway for cDDP and related drugs via a mechanism that mimics copper.", "output": "copper, cDDP." }, { "input": "This is an unexpected property of hCTR1, a highly selective copper ( I ) transporter.", "output": "There is no related enetity." }, { "input": "We compared the uptake rates of copper with cDDP ( and several analogs ) into HEK293 cells over - expressing wild - type or mutant hCTR1, mouse embryonic fibroblasts ( mefs ) that do or do not express CTR1, and human ovarian tumor cells, sensitive or resistant to cDDP.", "output": "cDDP." }, { "input": "We have also compared the effects of extracellular copper, which causes regulatory endocytosis of hCTR1, to those of cDDP.", "output": "copper, cDDP." }, { "input": "We confirm the correlation between higher hCTR1 levels and higher Pt - drug uptake in tumor cells sensitive to the drug.", "output": "Pt." }, { "input": "However, we show that hCTR1 is not the major entry route of platinum - drugs and that the copper transporter is not internalized in response to extracellular drug.", "output": "platinum, copper." }, { "input": "Our data suggest the major entry pathway for platinum - drugs is not saturable at relevant concentrations and not protein - mediated.", "output": "platinum." }, { "input": "Clinical trials have been initiated that depend upon regulating membrane levels of hCTR1.", "output": "There is no related enetity." }, { "input": "If reduced drug uptake is a major factor in resistance, hCTR1 is unlikely to be a productive target in attempts to enhance efficacy, although the proteins involved in copper homeostasis may play a role.", "output": "copper." }, { "input": "Radioiodide induces apoptosis in human thyroid tissue in culture.", "output": "Radioiodide." }, { "input": "Radioiodide ( ( 131 ) I ) is routinely used for the treatment of toxic adenoma, Graves ' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer.", "output": "Radioiodide, ( 131 ) I." }, { "input": "The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and / or apoptotic process.", "output": "There is no related enetity." }, { "input": "The involvement of apoptosis in radiation - induced cell death in the thyrocytes has been questioned.", "output": "There is no related enetity." }, { "input": "The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest ( 131 ) I dose.", "output": "( 131 ) I." }, { "input": "We developed a method to study the effects of ( 131 ) I in human thyroid tissue in culture, by which we demonstrated that ( 131 ) I induces thyroid cell apoptosis.", "output": "( 131 ) I, ( 131 ) I." }, { "input": "Human thyroid tissues of about 1 mm ( 3 ) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay.", "output": "MTT." }, { "input": "Radioiodide added to the culture medium was actively taken up by the tissues.", "output": "Radioiodide." }, { "input": "The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase - cleavage fragment of cytokeratin 18 ( M30 ) by an enzyme - linked immunoassay.", "output": "There is no related enetity." }, { "input": "Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture.", "output": "There is no related enetity." }, { "input": "( 131 ) I added to the culture medium induced a dose - dependent and a time - dependent generation of M30 fragment.", "output": "( 131 ) I." }, { "input": "The apoptotic process was confirmed by the generation of caspase - 3 and PARP cleavage products.", "output": "There is no related enetity." }, { "input": "These results demonstrate that ( 131 ) I induces apoptosis in human thyrocytes.", "output": "( 131 ) I." }, { "input": "Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by ( 131 ) I.", "output": "( 131 ) I." }, { "input": "Aqua Mediated Synthesis of Bio - active Compounds.", "output": "There is no related enetity." }, { "input": "Recently the aqueous medium has attracted the interest of organic chemists, and many.", "output": "There is no related enetity." }, { "input": "Moreover, in the past 20 years, the drug - discovery process has undergone extraordinary changes, and high - throughput biological screening of potential drug candidates has led to an ever - increasing demand for novel drug - like compounds.", "output": "There is no related enetity." }, { "input": "Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance.", "output": "There is no related enetity." }, { "input": "The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium.", "output": "There is no related enetity." }, { "input": "This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio - active compounds possessing various biological properties.", "output": "There is no related enetity." }, { "input": "Self - Assembling Behavior of Cellulose Nanoparticles during Freeze - Drying: Effect of Suspension Concentration, Particle Size, Crystal Structure, and Surface Charge.", "output": "There is no related enetity." }, { "input": "Cellulose nanocrystals and cellulose nanofibers with I and II crystalline allomorphs ( designated as CNC I, CNC II, CNF I, and CNF II ) were isolated from bleached wood fibers by alkaline pretreatment and acid hydrolysis.", "output": "There is no related enetity." }, { "input": "The effects of concentration, particle size, surface charge, and crystal structure on the lyophilization - induced self - assembly of cellulose particles in aqueous suspensions were studied.", "output": "There is no related enetity." }, { "input": "Within the concentration range of 0. 5 to 1. 0 wt %, cellulose particles self - organized into lamellar structured foam composed of aligned membrane layers with widths between 0. 5 and 3 mu m.", "output": "There is no related enetity." }, { "input": "At 0. 05 wt %, CNC I, CNF I, CNC II, and CNF II self - assembled into oriented ultrafine fibers with mean diameters of 0. 57, 1. 02, 1. 50, and 1. 00 mu m, respectively.", "output": "There is no related enetity." }, { "input": "The size of self - assembled fibers became larger when more hydroxyl groups and fewer sulfates ( weaker electrostatic repulsion ) were on cellulose surfaces.", "output": "hydroxyl, sulfates." }, { "input": "Possible formation mechanism was inferred from ice growth and interaction between cellulose nanoparticles in liquid - crystalline suspensions.", "output": "There is no related enetity." }, { "input": "Theoretical Strategy to Build Structural Models of Microhydrated Inorganic Systems for the Knowledge of Their Vibrational Properties: The Case of the Hydrated Nitrate Aerosols.", "output": "Hydrated Nitrate." }, { "input": "This study provides theoretical anharmonic calculations for microhydrated NaNO3 - labeled ( NaNO3, nH2O ) x with a water - to - solute ratio ( n ) ranging from 1 to 3.", "output": "NaNO3, ( NaNO3 , nH2O ) x." }, { "input": "A representative geometrical model of these forms was first investigated by simulating the molecular clusters as ( NaNO3, 1H2O ) x with x = 1 to 4.", "output": "( NaNO3 , 1H2O ) x." }, { "input": "The comparison between the calculated time independent anharmonic frequencies using the B3LYP - D / 6 - 311 + G ( d, p ) method and their experimental counterparts led to the choice of a supercluster model.", "output": "There is no related enetity." }, { "input": "The most probable structures of ( NaNO3, nH2O ) 3 molecular system were investigated by using our global search algorithm we developed recently ( GSAM code ) both at the B3LYP / 6 - 311 + G ( d, p ) and the B3LYP - D / 6 - 311 + G ( d, p ) levels of theory.", "output": "( NaNO3 , nH2O ) 3." }, { "input": "The quality of the structural model is illustrated by comparing the B3LYP / 6 - 311 + G ( d, p ) and B3LYP - D / 6 - 311 + G ( d, p ) anharmonic vibrational signatures with those obtained from IR experiments.", "output": "There is no related enetity." }, { "input": "While an average deviation of 16 cm ( - 1 ) is observed in the case of the B3LYP computations, the deviation is reduced to 7 cm ( - 1 ) for the B3LYP - D computations.", "output": "There is no related enetity." }, { "input": "Abdominal adiposity through adipocyte secretion products, a risk factor for endometrial cancer.", "output": "There is no related enetity." }, { "input": "Abstract Background and aim: The adipose cell has been considered an inert cell from a secretory point of view.", "output": "There is no related enetity." }, { "input": "Studies over the past years have confirmed the capacity of the adipocyte to synthesize many substances including: adiponectin, leptin, which integrate multiple metabolic and endocrine signals.", "output": "There is no related enetity." }, { "input": "In the context of endometrial cancer, abdominal obesity as a risk factor is associated with a chronic inflammatory process, confirmed by the increase of inflammatory markers.", "output": "There is no related enetity." }, { "input": "The study aimed to identify a correlation between abdominal obesity, plasma adipokine levels and endometrial cancer.", "output": "There is no related enetity." }, { "input": "Material and method: Two groups of patients were included in the study: group I - 44 patients diagnosed with endometrial cancer, group II - 44 patients without gynecological pathology or inflammatory disorders.", "output": "There is no related enetity." }, { "input": "After the performance of clinical examination and anthropometric measurements, abdominal fat was determined by dual X - ray absorptiometry and plasma adiponectin and leptin levels were measured.", "output": "There is no related enetity." }, { "input": "Results: A significantly higher abdominal fat and leptin value was found in the group of patients in with endometrial cancer ( p < 0. 0001 ), while the plasma adiponectin level was significantly lower, compared to the control group ( p < 0. 0001 ).", "output": "There is no related enetity." }, { "input": "Abdominal fat was in a negative linear correlation with the plasma adiponectin level and in a positive linear correlation with the plasma leptin level.", "output": "There is no related enetity." }, { "input": "Conclusions: The measurement of adiponectin and leptin levels associated with the determination of abdominal adipose tissue can be a useful predictor factor for endometrial cancer.", "output": "There is no related enetity." }, { "input": "Symptomatic Amyloid Goiters: Report of 5 Cases.", "output": "There is no related enetity." }, { "input": "Background: Massive amyloid deposition in the thyroid to the point of goiter formation is rare.", "output": "There is no related enetity." }, { "input": "Here we describe the clinical presentation and outcomes of 5 patients with amyloid goiter ( radiographically confirmed goiter in the context of tissue - proven thyroid amyloidosis ) encountered in the past 23 years at our institution.", "output": "There is no related enetity." }, { "input": "Methods: Mayo Clinic archives were searched between 1987 and 2010 for diagnosis \" thyroid amyloidosis, \" \" amyloid deposits, \" \" amyloid deposition, \" or \" liquid chromatography consistent with amyloid. \" Inclusion criteria were symptomatic thyromegaly; tissue confirmation of thyroid enlarged by amyloid deposits; and radiologic confirmation of thyroid enlargement.", "output": "There is no related enetity." }, { "input": "Results: Five patients were identified who met all inclusion criteria.", "output": "There is no related enetity." }, { "input": "Amyloid goiter etiology included both primary and secondary amyloidosis, and the goiters ranged from 50 to 130 g each.", "output": "There is no related enetity." }, { "input": "Diagnosis was made by fine - needle aspiration biopsy with Congo red staining and, if needed, spectrophotometry.", "output": "There is no related enetity." }, { "input": "All 5 patients had histories of persistent hoarseness for several years prior to presentation with compressive symptoms referable to their enlarging thyroids, and all had some degree of thyroid dysfunction ( both hypothyroidism and hyperthyroidism ) by the end of our follow - up period, which ranged from 5 months to 13 years.", "output": "There is no related enetity." }, { "input": "Two patients underwent surgical intervention ( s ), 2 were managed conservatively, and in 1, the goiter shrank following systemic therapy for amyloidosis.", "output": "There is no related enetity." }, { "input": "Conclusions: Our clinical observations suggest slower goiter progression and a higher prevalence of thyroid dysfunction than previously thought.", "output": "There is no related enetity." }, { "input": "Ultralow friction induced by tribochemical reactions: a novel mechanism of lubrication on steel surfaces.", "output": "steel." }, { "input": "The tribological properties of two steel surfaces rubbing against each other are measured while they are in contact with 1, 3 - diketones of varying structure.", "output": "steel, 1 , 3 - diketones." }, { "input": "Such systems show after a short running - in period ultralow friction properties with a coefficient of friction of as low as mu = 0. 005.", "output": "There is no related enetity." }, { "input": "It is suggested that the extremely favorable friction properties are caused by a tribochemical reaction between the 1, 3 - diketones and the steel surfaces, leading to formation of a chelated iron - diketo complex.", "output": "1 , 3 - diketones, iron, diketo." }, { "input": "The influence of temperature and the molecular structure of the 1, 3 diketo - lubricants onto the friction properties of the system is elucidated under both static and dynamic conditions.", "output": "1 , 3 diketo." }, { "input": "With progression of the tribochemical reaction, the sliding surfaces become very conformal and smooth, so that the pressure is greatly reduced and further wear is strongly reduced.", "output": "There is no related enetity." }, { "input": "All iron particles potentially generated by wear during the initial running - in period are completely dissolved through complex formation.", "output": "iron." }, { "input": "It is proposed that the tribochemical polishing reaction causes a transition from boundary lubrication to fluid lubrication.", "output": "There is no related enetity." }, { "input": "Discovery of a novel series of non - nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.", "output": "nucleoside." }, { "input": "A novel series of non - nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment - based approach using information from X - ray crystallographic analysis of NS5B - inhibitor complexes and iterative rounds of parallel synthesis.", "output": "nucleoside." }, { "input": "Structure - based drug design strategies led to the discovery of potent sub - micromolar inhibitors 11a - c and 12a - c from a weak - binding fragment - like structure 1 as a starting point.", "output": "There is no related enetity." }, { "input": "Acetaminophen reduces lipopolysaccharide - induced fever by inhibiting cyclooxygenase - 2.", "output": "Acetaminophen." }, { "input": "Acetaminophen is one of the world ' s most commonly used drugs to treat fever and pain, yet its mechanism of action has remained unclear.", "output": "Acetaminophen." }, { "input": "Here we tested the hypothesis that acetaminophen blocks fever through inhibition of cyclooxygenase - 2 ( Cox - 2 ), by monitoring lipopolysaccharide induced fever in mice with genetic manipulations of enzymes in the prostaglandin cascade.", "output": "acetaminophen, prostaglandin." }, { "input": "We exploited the fact that lowered levels of a specific enzyme make the system more sensitive to any further inhibition of the same enzyme.", "output": "There is no related enetity." }, { "input": "Mice were immune challenged by an intraperitoneal injection of bacterial wall lipopolysaccharide and their body temperature recorded by telemetry.", "output": "There is no related enetity." }, { "input": "We found that mice heterozygous for Cox - 2, but not for microsomal prostaglandin E synthase - 1 ( mPGES - 1 ), displayed attenuated fever, indicating a rate limiting role of Cox - 2.", "output": "prostaglandin E." }, { "input": "We then titrated a dose of acetaminophen that did not inhibit the lipopolysaccharide - induced fever in wild - type mice.", "output": "acetaminophen." }, { "input": "However, when the same dose of acetaminophen was given to Cox - 2 heterozygous mice, the febrile response to lipopolysaccharide was strongly attenuated, resulting in an almost normalized temperature curve, whereas no difference was seen between wild - type and heterozygous mPGES - 1 mice.", "output": "acetaminophen." }, { "input": "Furthermore, the fever to intracerebrally injected prostaglandin E2 was unaffected by acetaminophen treatment.", "output": "prostaglandin E2, acetaminophen." }, { "input": "These findings reveal that acetaminophen, similar to aspirin and other non - steroidal anti - inflammatory drugs, is antipyretic by inhibiting cyclooxygenase - 2, and not by inhibiting mPGES - 1 or signaling cascades downstream of prostaglandin E2.", "output": "acetaminophen, aspirin, prostaglandin E2." }, { "input": "Species differences in the neuromuscular activity of post - synaptic neurotoxins from two Australian black snakes ( Pseudechis porphyriacus and Pseudechis colletti ).", "output": "There is no related enetity." }, { "input": "Bites by Australian black snakes ( Pseudechis spp. ) do not cause neurotoxicity in human envenoming.", "output": "There is no related enetity." }, { "input": "This is unusual as in vitro neurotoxicity has been reported for all Pseudechis spp. venoms.", "output": "There is no related enetity." }, { "input": "The present study aimed to identify, isolate and characterise neurotoxins from the venoms of Pseudechis porphyriacus and Pseudechis colletti to elucidate the reason for the lack of neurotoxicity in humans.", "output": "There is no related enetity." }, { "input": "alpha - Elapitoxin - Ppr1 and alpha - elapitoxin - Pc1 were isolated from P. porphyriacus and P. colletti, respectively, using reverse - phase high performance liquid chromatography.", "output": "There is no related enetity." }, { "input": "Each toxin consisted of 62 amino acids with molecular weights of 6746. 5Da and 6759. 6Da, respectively.", "output": "There is no related enetity." }, { "input": "alpha - Elapitoxin - Ppr1 and alpha - elapitoxin - Pc1 caused concentration - dependent ( 0. 1 - 0. 3 mu M ) inhibition of indirect twitches in the chick biventer cervicis nerve - muscle preparation.", "output": "There is no related enetity." }, { "input": "Both toxins inhibited contractile responses to exogenous ACh and CCh, but not KCl, suggesting a post - synaptic mode of action at the nicotinic acetylcholine receptor ( nAChR ).", "output": "ACh, KCl, acetylcholine." }, { "input": "CCh concentration - response curves obtained in the presence or absence of alpha - elapitoxin - Ppr1 or alpha - elapitoxin - Pc1 indicated pA2 values of 6. 97 +/- 0. 03 and 7. 04 +/- 0. 07, respectively.", "output": "There is no related enetity." }, { "input": "Neither alpha - elapitoxin - Ppr1 ( 0. 1 mu M ) nor alpha - elapitoxin - Pc1 ( 0. 1 mu M ) had a significant effect on the electrically - induced twitches of the rat isolated phrenic nerve - diaphragm preparation.", "output": "There is no related enetity." }, { "input": "When the venom with the toxin removed ( 10 mu g / ml ) was added to both the rat and chick preparations, the inhibition was significantly less than that caused by the intact whole venoms ( 10 mu g / ml ).", "output": "There is no related enetity." }, { "input": "The current study shows that alpha - elapitoxin - Ppr1 and alpha - elapitoxin - Pc1 act as pseudo - irreversible antagonists at the nAChR of the skeletal neuromuscular junction and that the avian preparation is more sensitive to the neurotoxic effects of these toxins than the mammalian preparation.", "output": "There is no related enetity." }, { "input": "Total saponins of Panax notoginseng enhance VEGF and relative receptors signals and promote angiogenesis derived from rat bone marrow mesenchymal stem cells.", "output": "saponins." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Total saponins of Panax notoginseng ( tPNS ), main constituents extracted from Panax Notoginseng, a highly valued traditional Chinese medicine, has been shown to increase protein expression and the secretion of vascular endothelial growth factor ( VEGF ) in human umbilical vein endothelial cells.", "output": "There is no related enetity." }, { "input": "AIMS OF THE STUDY: The effects of tPNS on angiogenesis were studied in rat bone marrow mesenchymal stem cells ( rBMSCs ).", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: rBMSCs were stimulated by tPNS of 48h.", "output": "There is no related enetity." }, { "input": "The mRNA expression levels of VEGF - A, Flt - 1 and Kdr in rBMSCs were determined by quantitative real time PCR ( qRT - PCR ).", "output": "There is no related enetity." }, { "input": "rBMSCs were induced to differentiate into endothelial - like cells and the effects of tPNS on the angiogenesis ability of rBMSCs and rBMSCs after endothelial differentiation were assayed by a Matrigel model in vivo and in vitro.", "output": "There is no related enetity." }, { "input": "RESULTS: tPNS ( 100 mu g / ml ) significantly enhanced the mRNA expression level of VEGF - A and Kdr compared to the control group, while they had no obvious effect on the expression of Flt - 1.", "output": "There is no related enetity." }, { "input": "tPNS ( 1 mu g / ml and 100 mu g / ml ) significantly increased capillary network forming of rBMSCs after endothelial differentiation in Matrigel in vitro.", "output": "There is no related enetity." }, { "input": "tPNS ( 50 mu g / kg, 100 mu g / kg and 150 mu g / kg ) also significantly increased angiogenesis induced by the combination with implantation of rBMSCs and Matrigel in vivo.", "output": "There is no related enetity." }, { "input": "CONCLUSION: tPNS up - regulate VEGF - A and Kdr expression, and promote angiogenesis in rat bone marrow mesenchymal stem cells.", "output": "There is no related enetity." }, { "input": "In Vitro Metabolism and Kinetics Studies on Methylone.", "output": "Methylone." }, { "input": "Abuse of the stimulant designer drug methylone ( methylenedioxymethcathinone ) has been documented in most parts of the world.", "output": "methylone, methylenedioxymethcathinone." }, { "input": "As with many of the new designer drugs that continuously appear in the illicit drug market, little is known about the pharmacokinetics of methylone.", "output": "methylone." }, { "input": "Using in vitro studies, CYP2D6 was determined to be the primary enzyme that metabolizes methylone, with minor contributions from CYP1A2, CYP2B6, and CYP2C19.", "output": "methylone." }, { "input": "The major metabolite was identified as dihydroxymethcathinone, and the minor metabolites were N - hydroxy - methylone, nor - methylone, and dihydro - methylone.", "output": "dihydroxymethcathinone, N - hydroxy - methylone, dihydro - methylone." }, { "input": "Measuring the formation of the major metabolite, biphasic Michaelis - Menten kinetic parameters were determined: Vmax, 1 = 0. 046 +/- 0. 005 ( S. E. ) nmol / min / mg protein, Km, 1 = 19. 0 +/- 4. 2 mu M, Vmax, 2 = 0. 22 +/- 0. 04 nmol / min / mg protein, and Km, 2 = 1953 +/- 761 mu M; the low - capacity and high - affinity contribution was assigned to the activity of CYP2D6.", "output": "There is no related enetity." }, { "input": "Additionally, a time - dependent loss of CYP2D6 activity was observed when the enzyme was preincubated with methylone, reaching a maximum rate of inactivation at high methylone concentrations, indicating that methylone is a mechanism - based inhibitor of CYP2D6.", "output": "methylone, methylone." }, { "input": "The inactivation parameters were determined to be KI = 15. 1 +/- 3. 4 ( S. E ) mu M and kinact = 0. 075 +/- 0. 005 min ( - 1 ).", "output": "There is no related enetity." }, { "input": "Determination of the mutagenic and genotoxic potential of simulated leachate from an automobile workshop soil on eukaryotic system.", "output": "There is no related enetity." }, { "input": "Contamination of soil and water bodies with spent engine oil and petroleum products is a serious ecological problem, primarily in the automobile workshops and garages.", "output": "There is no related enetity." }, { "input": "This has potential short and chronic adverse health risks.", "output": "There is no related enetity." }, { "input": "Information is currently scarce on the potential mutagenicity and genotoxicity of such wastes.", "output": "There is no related enetity." }, { "input": "In this study, the potential mutagenic and genotoxic effects of simulated leachate from automobile workshop soil in Sagamu, Ogun state, Nigeria, were investigated.", "output": "There is no related enetity." }, { "input": "The assays utilized were bone marrow micronucleus ( MN ) and chromosome aberration ( CA ), sperm morphology and sperm count in mice.", "output": "There is no related enetity." }, { "input": "The physicochemical analysis of the leachate was also carried out.", "output": "There is no related enetity." }, { "input": "Experiments were carried out at concentrations of 1, 5, 10, 25, 50, 75 and 100 % ( volume per volume; leachate: distilled water ) of the leachate sample.", "output": "There is no related enetity." }, { "input": "MN analysis showed a concentration - dependent induction of micronucleated polychromatic erythrocytes across the treatment groups.", "output": "There is no related enetity." }, { "input": "In the CA test, there was concentration - dependent significant reduction in mitotic index and induction of different types of CAs.", "output": "There is no related enetity." }, { "input": "Assessment of sperm shape showed a significant increase in sperm abnormalities with significant decrease in mean sperm count in treated groups.", "output": "There is no related enetity." }, { "input": "Heavy metals analyzed in the tested sample are believed to contribute significantly to the observed genetic damage.", "output": "There is no related enetity." }, { "input": "This indicates that automobile workshop soil - simulated leachate contains potential genotoxic agents and constitutes a genetic risk in exposed human population.", "output": "There is no related enetity." }, { "input": "Isolation of Five New Flavonoids from Melicope triphylla.", "output": "Flavonoids." }, { "input": "Five new flavonoids, 5, 8 - dihydroxy - 3, 7 - dimethoxy - 3 ', 4 ' - methylenedioxyflavone ( 1 ), 7 - hydroxy - 3, 5 - dimethoxy - 3 ', 4 ' - methylenedioxyflavone ( 2 ), 7 - ( 2, 3 - dihydroxy - 3 - methylbutoxy ) - 3, 5 - dimethoxy - 3 ', 4 ' - methylenedioxyflavone ( 3 ), 7 - ( 2, 3 - dihydroxy - 3 - methylbutoxy ) - 3, 3 ', 4 ', 5 - tetramethoxyflavone ( 4 ), and 7 - ( 2, 3 - dihydroxy - 3 - methylbutoxy ) - 3, 3 ', 4 ', 5, 8 - pentamethoxyflavone ( 5 ), were isolated from the leaves of Melicope triphylla.", "output": "flavonoids, 5 , 8 - dihydroxy - 3 , 7 - dimethoxy - 3 ' , 4 ' - methylenedioxyflavone, 7 - hydroxy - 3 , 5 - dimethoxy - 3 ' , 4 ' - methylenedioxyflavone, 7 - ( 2 , 3 - dihydroxy - 3 - methylbutoxy ) - 3 , 5 - dimethoxy - 3 ' , 4 ' - methylenedioxyflavone, 7 - ( 2 , 3 - dihydroxy - 3 - methylbutoxy ) - 3 , 3 ' , 4 ' , 5 - tetramethoxyflavone, 7 - ( 2 , 3 - dihydroxy - 3 - methylbutoxy ) - 3 , 3 ' , 4 ' , 5 , 8 - pentamethoxyflavone." }, { "input": "In addition, six known flavonoids were detected: 3, 4 ', 5 - trihydroxy - 3 ', 7, 8 - trimethoxyflavone ( 6 ), 5, 7 - dihydroxy - 3 - methoxy - 3 ', 4 ' - methylenedioxyflavone ( 7 ), 4 ', 5, 7 - trihydroxy - 3, 3 ' - dimethoxyflavone ( 8 ), 4 ', 7 - dihydroxy - 3, 3 ', 5, 8 - tetramethoxyflavone ( 9 ), 4 ', 7 - dihydroxy - 3, 3 ', 5 - trimethoxyflavone ( 10 ), and 4 ', 5, 7 - trihydroxy - 3, 3 ', 8 - trimethoxyflavone ( 11 ).", "output": "flavonoids, 3 , 4 ' , 5 - trihydroxy - 3 ' , 7 , 8 - trimethoxyflavone, 5 , 7 - dihydroxy - 3 - methoxy - 3 ' , 4 ' - methylenedioxyflavone, 4 ' , 5 , 7 - trihydroxy - 3 , 3 ' - dimethoxyflavone, 4 ' , 7 - dihydroxy - 3 , 3 ' , 5 , 8 - tetramethoxyflavone, 4 ' , 7 - dihydroxy - 3 , 3 ' , 5 - trimethoxyflavone, 4 ' , 5 , 7 - trihydroxy - 3 , 3 ' , 8 - trimethoxyflavone." }, { "input": "The new compound structures were determined by spectroscopic methods.", "output": "There is no related enetity." }, { "input": "Compounds 1 - 5 did not exhibit any ichthyotoxic activity against Japanese killifish ( medaka in Japanese ) ( Oryzias latipes var. ) at 10 ppm.", "output": "There is no related enetity." }, { "input": "Synthesis of 2, 3 - Bis ( halomethyl ) quinoxaline Derivatives and Evaluation of Their Antibacterial and Antifungal Activities.", "output": "2 , 3 - Bis ( halomethyl ) quinoxaline." }, { "input": "Quinoxaline derivatives having bis ( fluoromethyl ), bis ( chloromethyl ), or bis ( iodomethyl ) groups at the 2 - and 3 - positions, and various electron - donating / withdrawing substituents at the 6 - and / or 7 - positions, were synthesized.", "output": "Quinoxaline, bis ( fluoromethyl ), bis ( chloromethyl ), bis ( iodomethyl )." }, { "input": "Their antibacterial and antifungal activities were evaluated by means of minimum inhibitory concentration assays.", "output": "There is no related enetity." }, { "input": "The relationships between the substituents and the antimicrobial activities of the quinoxaline derivatives indicate that the electrophilicity of the halomethyl units plays an important role in generating the antimicrobial activity.", "output": "quinoxaline, halomethyl." }, { "input": "Medicinal Flowers.", "output": "There is no related enetity." }, { "input": "XXXVIII.", "output": "There is no related enetity." }, { "input": "Structures of Acylated Sucroses and Inhibitory Effects of Constituents on Aldose Reducatase from the Flower Buds of Prunus mume.", "output": "Acylated Sucroses." }, { "input": "The methanolic extract from the flower buds of Prunus mume, cultivated in Zhejiang province, China, showed an inhibitory effect on aldose reductase.", "output": "aldose." }, { "input": "From the methanolic extract, five new acylated sucroses, mumeoses F - J, were isolated together with 29 known compounds.", "output": "acylated sucroses, mumeoses F - J." }, { "input": "The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence.", "output": "There is no related enetity." }, { "input": "The inhibitory effects of the isolated compounds on aldose reductase were also investigated.", "output": "aldose." }, { "input": "Acylated quinic acid analogs, which are one of the major compounds of the flower buds of P. mume, were shown to substantially inhibit aldose reductase.", "output": "Acylated quinic acid, aldose." }, { "input": "In particular, mumeic acid - A was found to exhibit a potent inhibitory effect [ IC50 = 0. 4 micro m ].", "output": "mumeic acid - A." }, { "input": "Antimutagenic and genoprotective effects of Saraca asoca bark extract.", "output": "There is no related enetity." }, { "input": "< abstract > Aim of the study: Traditionally herbal formulations have been used effectively for the management of disorders that are now being accepted worldwide.", "output": "There is no related enetity." }, { "input": "Saraca asoca bark extract ( SAE ) finds use in traditional herbal medicine.", "output": "There is no related enetity." }, { "input": "In the present study, SAE were studied for their antioxidant, antimutagenic, and antigenotoxic properties.", "output": "There is no related enetity." }, { "input": "METHODS: SAE were evaluated for antimutagenic property in Salmonella strains ( TA97a, TA98, TA100, and TA102 ), in the presence and absence of metabolic activation ( S9 ).", "output": "There is no related enetity." }, { "input": "The SAE was also studied for antigenotoxic property against cyclophosphamide ( CP ) in Swiss albino male mice in vivo.", "output": "cyclophosphamide." }, { "input": "The extract was analyzed using high - performance liquid chromatography ( HPLC ).", "output": "There is no related enetity." }, { "input": "RESULTS: The study reveals antimutagenic property of the bark extract in Salmonella strains in the presence and absence of metabolic activation ( S9 ).", "output": "There is no related enetity." }, { "input": "The study reports antigenotoxic property of the bark extract against CP in vivo.", "output": "There is no related enetity." }, { "input": "Thiobarbituric acid reactive species assay on the bark extract revealed antioxidant property.", "output": "Thiobarbituric acid." }, { "input": "HPLC revealed the presence of two peaks corresponding to gallic acid and ( - ) - epicatechin, respectively.", "output": "gallic acid, ( - ) - epicatechin." }, { "input": "CONCLUSION: The study clearly reveals the antimutagenic and antigenotoxic properties of SAE.", "output": "There is no related enetity." }, { "input": "< / abstract >", "output": "There is no related enetity." }, { "input": "Azidoacetylene - interpretation of gas phase infrared spectra based on high - level vibrational configuration interaction calculations.", "output": "Azidoacetylene." }, { "input": "Azidoacetylene is a highly explosive substance, which has been synthesized and characterized for the first time quite recently [ Banert et al., Angew. Chem., Int. Ed., 2012, 51, 7515 ].", "output": "Azidoacetylene." }, { "input": "As outlined in this work, the vibrational spectrum of azidoacetylene is dominated by strong couplings.", "output": "azidoacetylene." }, { "input": "For that reason, we have studied the vibrational spectrum of the title compound by gas phase measurements and high - level vibrational structure calculations beyond the harmonic approximation.", "output": "There is no related enetity." }, { "input": "Based on the interplay of theory and experiment, we were able to identify all fundamentals, strong Fermi resonances and intense overtones, which contribute to the spectrum.", "output": "There is no related enetity." }, { "input": "A 5 ' flanking region of Gonadotropin Regulated Testicular RNA Helicase ( GRTH / DDX25 ) gene directs its cell specific androgen regulated gene expression in testicular germ cells.", "output": "androgen." }, { "input": "Gonadotropin Regulated Testicular RNA Helicase ( GRTH / Ddx25 ) is a post - transcriptional regulator of genes that are essential for spermatid elongation and completion of spermatogenesis.", "output": "There is no related enetity." }, { "input": "It also prevents Leydig cells ( LC ) from gonadotropin overstimulation of androgen production.", "output": "androgen." }, { "input": "In transgenic ( Tg ) mice carrying deletions of the GRTH 5 ' flanking regions we previously demonstrated that the - 1085 bp to ATG contains the elements for basal and androgen - induced LC specific expression.", "output": "androgen." }, { "input": "No expression in germ cells ( GC ) was found with sequences extended up to - 3. 6 Kb.", "output": "There is no related enetity." }, { "input": "To define regulatory regions of GRTH required for expression in GC, Tg mice were generated with 5 ' flanking sequence 6. 4 Kb ( 6. 4 Kb - Tg ) and / or deletion using GFP as reporter gene in the present study.", "output": "There is no related enetity." }, { "input": "GFP was expressed in all lines.", "output": "There is no related enetity." }, { "input": "Immuno - histochemistry analysis showed that 6. 4Kb - Tg directed GFP expression in both GC and LC.", "output": "There is no related enetity." }, { "input": "Deletion of the sequence - 205 bp to - 3. 6 Kb ( 6. 4Kb / del - Tg ) directs GFP expression only in meiotic and haploid GCs.", "output": "There is no related enetity." }, { "input": "This indicated that the distal region - 6. 4 Kb / - 3. 6 Kb is required for GRTH cell specific expression in GC.", "output": "There is no related enetity." }, { "input": "Also, it inhibits the expression of GRTH in LC directed by the 205 bp promoter, an effect that is neutralized by the - 3. 6Kb / - 205bp sequence.", "output": "There is no related enetity." }, { "input": "Flutamide treatment prevents GFP / GRTH expression in Tg lines demonstrating in vivo direct and indirect effects of endogenous androgen on GC and LC, respectively.", "output": "androgen." }, { "input": "Our studies have generated and characterized transgenic lines that can be utilized to define requirements for cell specific expression of the GRTH gene and to further advance our knowledge on the regulation of GRTH by androgen in germ cells.", "output": "androgen." }, { "input": "Estrogen Receptor - alpha Variant, ER - alpha 36, is Involved in Tamoxifen Resistance and Estrogen Hypersensitivity.", "output": "Estrogen, Tamoxifen, Estrogen." }, { "input": "Antiestrogens such as tamoxifen provided a successful treatment for ER - positive breast cancer for the past two decades.", "output": "tamoxifen." }, { "input": "However, most breast tumors are eventually resistant to tamoxifen therapy.", "output": "tamoxifen." }, { "input": "The molecular mechanisms underlying tamoxifen resistance have not been well established.", "output": "tamoxifen." }, { "input": "Recently, we reported that breast cancer patients with tumors expressing high concentrations of ER - alpha 36, a variant of ER - alpha, benefited less from tamoxifen therapy than those with low concentrations of ER - alpha 36, suggesting that increased ER - alpha 36 concentration is one of the underlying mechanisms of tamoxifen resistance.", "output": "tamoxifen, tamoxifen." }, { "input": "Here, we investigated the function and underlying mechanism of ER - alpha 36 in tamoxifen resistance.", "output": "tamoxifen." }, { "input": "We found that tamoxifen increased ER - alpha 36 concentrations and tamoxifen - resistant MCF7 cells expressed high concentrations of ER - alpha 36.", "output": "tamoxifen, tamoxifen." }, { "input": "In addition, MCF7 cells with forced expression of recombinant ER - alpha 36 and H3396 cells expressing high concentrations of endogenous ER - alpha 36 were resistant to tamoxifen.", "output": "tamoxifen." }, { "input": "ER - alpha 36 downregulation in tamoxifen - resistant cells with the shRNA method restored tamoxifen sensitivity.", "output": "tamoxifen, tamoxifen." }, { "input": "We also found tamoxifen acted as a potent agonist by activating phosphorylation of the AKT kinase in ER - alpha 36 expressing cells.", "output": "tamoxifen." }, { "input": "Finally, we found that cells with high concentration of ER - alpha 36 protein were hypersensitive to estrogen; activating ERK phosphorylation at pM range.", "output": "estrogen." }, { "input": "Our results thus demonstrated that elevated ER - alpha 36 concentration is one of the mechanisms by which ER - positive breast cancer cells escape tamoxifen therapy and provided a rational to develop novel therapeutic approaches for tamoxifen resistant patients by targeting ER - alpha 36.", "output": "tamoxifen, tamoxifen." }, { "input": "Ovarian Expression of Insulin - Like Peptide 3 ( INSL3 ) and Its Receptor ( RXFP2 ) During Development of Bovine Antral Follicles and Corpora Lutea and Measurement of Circulating INSL3 Levels During Synchronized Estrous Cycles.", "output": "There is no related enetity." }, { "input": "Insulin - like peptide 3 ( INSL3 ), a major product of testicular Leydig cells, is also expressed by the ovary, but its functional role remains poorly understood.", "output": "There is no related enetity." }, { "input": "Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna cell ( TIC ) and granulosa cell compartments of developing bovine antral follicles and in corpora lutea ( CL ).", "output": "There is no related enetity." }, { "input": "INSL3 and RXFP2 mRNA levels were much higher in TIC than granulosa cell and increased progressively during follicle maturation with INSL3 peaking in large ( 11 - 18 mm ) estrogen - active follicles and RXFP2 peaking in 9 - to 10 - mm follicles before declining in larger ( 11 - 18 mm ) follicles.", "output": "estrogen." }, { "input": "Expression of both INSL3 and RXFP2 in CL was much lower than in TIC.", "output": "There is no related enetity." }, { "input": "In situ hybridization and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein in TIC.", "output": "There is no related enetity." }, { "input": "These observations indicate follicular TIC rather than CL as the primary site of both INSL3 production and action, implying a predominantly autocrine / paracrine role in TIC.", "output": "There is no related enetity." }, { "input": "To corroborate the above findings, we showed that in vitro exposure of TIC to a luteinizing concentration of LH greatly attenuated expression of both INSL3 and its receptor while increasing progesterone secretion and expression of STAR and CYP11A1.", "output": "progesterone." }, { "input": "Moreover, in vivo, a significant cyclic variation in plasma INSL3 was observed during synchronized estrous cycles.", "output": "There is no related enetity." }, { "input": "INSL3 and estradiol - 17 beta followed a similar pattern, both increasing after luteolysis, before falling sharply after the LH surge.", "output": "estradiol - 17 beta." }, { "input": "Thus, theca - derived INSL3, likely from the dominant preovulatory follicle, is detectable in peripheral blood of cattle, and expression is down - regulated during luteinization induced by the preovulatory LH surge.", "output": "There is no related enetity." }, { "input": "Collectively, these findings underscore the likely role of INSL3 as an important intrafollicular modulator of TIC function / steroidogenesis, while raising doubts about its potential contribution to CL function.", "output": "There is no related enetity." }, { "input": "Ionizing radiation - inducible microRNA miR - 193a - 3p induces apoptosis by directly targeting Mcl - 1.", "output": "There is no related enetity." }, { "input": "The functions of microRNAs ( miRNAs ) as either oncogenes or tumor suppressors in regulating cancer - related events have been established.", "output": "There is no related enetity." }, { "input": "We analyzed the alterations in the miRNA expression profile of the glioma cell line U - 251 caused by ionizing radiation ( IR ) by using an miRNA array and identified several miRNAs whose expression was significantly affected by IR.", "output": "There is no related enetity." }, { "input": "Among the IR - responsive miRNAs, we further examined the function of miR - 193a - 3p, which exhibited the most significant growth - inhibiting effect.", "output": "There is no related enetity." }, { "input": "miR - 193a - 3p was observed to induce apoptosis in both U - 251 and HeLa cells.", "output": "There is no related enetity." }, { "input": "We also demonstrated that miR - 193a - 3p induces the accumulation of intracellular reactive oxygen species ( ROS ) and DNA damage as determined by the level of gamma H2AX and by performing the comet assay.", "output": "oxygen." }, { "input": "The induction of both apoptosis and DNA damage by miR - 193a - 3p was blocked by antioxidant treatment, indicating the crucial role of ROS in the action of miR - 193a - 3p.", "output": "There is no related enetity." }, { "input": "Among the putative target proteins, the expression of Mcl - 1, an anti - apoptotic Bcl - 2 family member, decreased because of miR - 193a - 3p transfection.", "output": "There is no related enetity." }, { "input": "A reporter assay using a luciferase construct containing the 3 ' - untranslated region of Mcl - 1 confirmed that Mcl - 1 is a direct target of miR - 193a - 3p.", "output": "There is no related enetity." }, { "input": "Down - regulation of Mcl - 1 by siRNA transfection closely mimicked the outcome of miR - 193a - 3p transfection showing increased ROS, DNA damage, cytochrome c release, and apoptosis.", "output": "There is no related enetity." }, { "input": "Ectopic expression of Mcl - 1 suppressed the pro - apoptotic action of miR - 193a - 3p, suggesting that Mcl - 1 depletion is critical for miR - 193a - 3p induced apoptosis.", "output": "There is no related enetity." }, { "input": "Collectively, our results suggest a novel function for miR - 193a - 3p and its potential application in cancer therapy.", "output": "There is no related enetity." }, { "input": "Site - specific O - glycosylation on the MUC2 mucin inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease ( RgpB ).", "output": "O, cysteine." }, { "input": "The colonic epithelial surface is protected by an inner mucus layer which the commensal microflora cannot penetrate.", "output": "There is no related enetity." }, { "input": "We previously demonstrated that Entamoeba histolytica ( E. h. ) secretes a protease capable of dissolving this layer that is required for parasite penetration.", "output": "There is no related enetity." }, { "input": "Here, we asked if there are bacteria that can secrete similar proteases.", "output": "There is no related enetity." }, { "input": "We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component and the only gel - forming mucin in the colonic mucus.", "output": "There is no related enetity." }, { "input": "MUC2 has two central heavily O - glycosylated mucin domains that are protease - resistant and has cysteine rich N - and C - termini responsible for polymerization.", "output": "O, cysteine, N, C." }, { "input": "Culture supernatants of Porphyromonas gingivalis ( P. g. ), a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 - C terminal region, whereas the N - terminal region was unaffected.", "output": "N." }, { "input": "The active enzyme was isolated and identified as Arg - gingipain B ( RgpB ).", "output": "There is no related enetity." }, { "input": "Two cleavage sites were localized to IR v TT and NR v QA.", "output": "There is no related enetity." }, { "input": "IR v TT cleavage will disrupt the MUC2 polymers.", "output": "There is no related enetity." }, { "input": "As this site has two potential O - glycosylation sites we tested whether recombinant GalNAc - transferases ( GalNAc - Ts ) could glycosylate a synthetic peptide covering the IRTT sequence.", "output": "O, GalNAc, GalNAc." }, { "input": "Only GalNAc - T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB.", "output": "GalNAc." }, { "input": "Furthermore, when GalNAc - T3 was expressed in CHO - cells expressing the MUC2 C - terminal, the second threonine was glycosylated and the protein became resistant to RgpB cleavage.", "output": "GalNAc, C, threonine." }, { "input": "These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site - specific O - glycosylation.", "output": "O." }, { "input": "Biological Active Analogues of the Opioid Peptide Biphalin: Mixed alpha / beta ( 3 ) - Peptides.", "output": "Biphalin." }, { "input": "Natural residues of the dimeric opioid peptide Biphalin were replaced by the corresponding homo - beta ( 3 ) amino acids.", "output": "Biphalin, homo - beta ( 3 ) amino acids." }, { "input": "The derivative 1 containing h beta ( 3 ) Phe in place of Phe showed good mu - and delta - receptor affinities ( Ki ( delta ) = 0. 72 nM; Ki ( mu ) = 1. 1 nM ) and antinociceptive activity in vivo together with an increased enzymatic stability in human plasma.", "output": "h beta ( 3 ) Phe, Phe." }, { "input": "3 - Hydroxypyridin - 2 - thione as Novel Zinc Binding Group for Selective Histone Deacetylase Inhibition.", "output": "3 - Hydroxypyridin - 2 - thione, Zinc." }, { "input": "Small molecules bearing hydroxamic acid as the zinc binding group ( ZBG ) have been the most effective histone deacetylase inhibitors ( HDACi ) to date.", "output": "zinc." }, { "input": "However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety have stimulated research efforts aimed at finding alternative nonhydroxamate ZBGs.", "output": "hydroxamic acid." }, { "input": "We have identified 3 - hydroxypyridin - 2 - thione ( 3 - HPT ) as a novel ZBG that is compatible with HDAC inhibition.", "output": "3 - hydroxypyridin - 2 - thione, 3 - HPT." }, { "input": "3 - HPT inhibits HDAC 6 and HDAC 8 with an IC50 of 681 and 3675 nM, respectively.", "output": "3 - HPT." }, { "input": "Remarkably, 3 - HPT gives no inhibition of HDAC 1.", "output": "3 - HPT." }, { "input": "Subsequent optimization led to several novel 3HPT - based HDACi that are selective for HDAC 6 and HDAC 8.", "output": "3HPT." }, { "input": "Furthermore, a subset of these inhibitors induces apoptosis in various cancer cell lines.", "output": "There is no related enetity." }, { "input": "Oxadiazole - isopropylamides as potent and non - covalent proteasome inhibitors.", "output": "Oxadiazole - isopropylamides." }, { "input": "Abstract Screening of the 50, 000 ChemBridge compound library led to the identification of the oxadiazole - isopropylamide 1 ( PI - 1833 ) which inhibited CT - L activity ( IC50 0. 60 mu M ) with little effects on the other 2 major proteasome proteolytic activities, T - L and PGPH - L.", "output": "oxadiazole - isopropylamide, PI - 1833." }, { "input": "LC / MS - MS and dialysis show that 1 is a non - covalent and rapidly reversible CT - L inhibitor.", "output": "There is no related enetity." }, { "input": "Focused library synthesis provided 11ad ( PI - 1840 ) with CT - L activity ( IC50 27 nM ).", "output": "PI - 1840." }, { "input": "Detailed SAR studies indicate that the amide moiety and the 2 phenyl rings are sensitive toward modifications.", "output": "amide, phenyl." }, { "input": "Hydrophobic residues, such as propyl or butyl, in the para - position ( not ortho or meta ) of the A - ring and a meta - pyridyl group as B - ring significantly improve activity.", "output": "propyl, butyl, meta - pyridyl." }, { "input": "Compound 11ad ( IC50 0. 37 micro M ) is more potent than 1 ( IC50 3. 5 micro M ) at inhibiting CT - L activity in intact MDA - MB - 468 human breast cancer cells and inhibiting their survival.", "output": "There is no related enetity." }, { "input": "The activity of 11ad warrants further pre - clinical investigation of this class as non - covalent proteasome inhibitors.", "output": "There is no related enetity." }, { "input": "Potent Proteasome Inhibitors Derived from the Unnatural Cis - Cyclopropane Isomer of Belactosin A: Synthesis, Biological Activity, and Mode of Action.", "output": "Cis - Cyclopropane, Belactosin A." }, { "input": "The natural product belactosin A ( 1 ) with a trans - cyclopropane structure is a useful prototype compound for developing potent proteasome ( core particle, CP ) inhibitors.", "output": "belactosin A, trans - cyclopropane." }, { "input": "To date, 1 and its analogs are the only CP ligands bind to both the non - primed S1 pocket as well as the primed substrate binding channel, however, these molecules harbor a high IC50 value of more than 1 micro M.", "output": "There is no related enetity." }, { "input": "We have performed structure activity relationship studies, hereby elucidating unnatural cis - cyclopropane derivatives of 1 that exhibit high potency to primarily block the chymotrypsin - like active site of the human constitutive ( cCP ) and immunoproteasome ( iCP ).", "output": "cis - cyclopropane." }, { "input": "The most active compound 3e reversibly inhibits cCP and iCP similarly with an IC50 of 5. 7 nM.", "output": "There is no related enetity." }, { "input": "X - ray crystallographic analysis of the yeast proteasome in complex with 3e revealed that the ligand accommodates predominantly to the primed substrate binding channel and covalently binds to the active site threonine residue via its beta - lactone ring - opening.", "output": "threonine, beta - lactone." }, { "input": "Development of an ALK2 - Biased BMP Type I Receptor Kinase Inhibitor.", "output": "There is no related enetity." }, { "input": "The bone morphogenetic protein ( BMP ) signaling pathway has essential functions in development, homeostasis, and the normal and pathophysiologic remodeling of tissues.", "output": "There is no related enetity." }, { "input": "Small molecule inhibitors of the BMP receptor kinase family have been useful for probing physiologic functions of BMP signaling in vitro and in vivo and may have roles in the treatment of BMP - mediated diseases.", "output": "There is no related enetity." }, { "input": "Here we describe the development of a selective and potent inhibitor of the BMP type I receptor kinases, LDN - 212854, which in contrast to previously described BMP receptor kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the closely related TGF - beta and Activin type I receptors.", "output": "LDN - 212854." }, { "input": "In vitro, LDN - 212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2 - mediated signaling, transcriptional activity, and function.", "output": "LDN - 212854." }, { "input": "LDN - 212854 potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva.", "output": "LDN - 212854." }, { "input": "These findings represent a significant step toward developing selective inhibitors targeting individual members of the highly homologous BMP type I receptor family.", "output": "There is no related enetity." }, { "input": "Such inhibitors would provide greater resolution as probes of physiologic function and improved selectivity against therapeutic targets.", "output": "There is no related enetity." }, { "input": "Bacteria - adsorbed palygorskite stabilizes the quaternary phosphonium salt with specific - targeting capability, long - term antibacterial activity, and lower cytotoxicity.", "output": "palygorskite, quaternary phosphonium salt." }, { "input": "In order to extend the antibacterial time of quaternary phosphonium salt in bacteria, palygorskite ( PGS ) is used as the carrier of dodecyl triphenyl phosphonium bromide ( DTP ), and a DTP - PGS hybrid is prepared.", "output": "quaternary phosphonium salt, palygorskite, PGS, dodecyl triphenyl phosphonium bromide, DTP, DTP, PGS." }, { "input": "Antibacterial performance of this novel hybrid is investigated for both Gram - positive and Gram - negative bacteria.", "output": "There is no related enetity." }, { "input": "The results show that the DTP could be absorbed on the surface of PGS which had bacteria - adsorbed capability.", "output": "DTP, PGS." }, { "input": "The DTP - PGS hybrid, combining the advantages of PGS and DTP, display specific - targeting capability, long - term antibacterial activity, and lower cytotoxicity, suggesting the great potential application as PGS - based antibacterial powder.", "output": "DTP, PGS, PGS, DTP, PGS." }, { "input": "Artificial Neural Networks for Efficient Clustering of Conformational Ensembles and their Potential for Medicinal Chemistry.", "output": "There is no related enetity." }, { "input": "The biological function of proteins is strictly related to their molecular flexibility and dynamics: enzymatic activity, protein - protein interactions, ligand binding and allosteric regulation are important mechanisms involving protein motions.", "output": "There is no related enetity." }, { "input": "Computational approaches, such as Molecular Dynamics ( MD ) simulations, are now routinely used to study the intrinsic dynamics of target proteins as well as to complement molecular docking approaches.", "output": "There is no related enetity." }, { "input": "These methods have also successfully supported the process of rational design and discovery of new drugs.", "output": "There is no related enetity." }, { "input": "Identification of functionally relevant conformations is a key step in these studies.", "output": "There is no related enetity." }, { "input": "This is generally done by cluster analysis of the ensemble of structures in the MD trajectory.", "output": "There is no related enetity." }, { "input": "Recently Artificial Neural Network ( ANN ) approaches, in particular methods based on Self - Organising Maps ( SOMs ), have been reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data - mining problems.", "output": "There is no related enetity." }, { "input": "In the specific case of conformational analysis, SOMs have been successfully used to compare multiple ensembles of protein conformations demonstrating a potential in efficiently detecting the dynamic signatures central to biological function.", "output": "There is no related enetity." }, { "input": "Moreover, examples of the use of SOMs to address problems relevant to other stages of the drug - design process, including clustering of docking poses, have been reported.", "output": "There is no related enetity." }, { "input": "In this contribution we review recent applications of ANN algorithms in analysing conformational and structural ensembles and we discuss their potential in computer - based approaches for medicinal chemistry.", "output": "There is no related enetity." }, { "input": "PFKFB3 activation in cancer cells by the p38 / MK2 pathway in response to stress stimuli.", "output": "There is no related enetity." }, { "input": "PFK - 2 / FBPase - 2 ( 6 - phosphofructo - 2 - kinase / fructose - 2, 6 - bisphosphatase ) catalyses the synthesis and degradation of Fru - 2, 6 - P2 ( fructose - 2, 6 - bisphosphate ), a key modulator of glycolysis and gluconeogenesis.", "output": "Fru - 2 , 6 - P2, fructose - 2 , 6 - bisphosphate." }, { "input": "The PFKFB3 gene is involved in cell proliferation owing to its role in carbohydrate metabolism.", "output": "carbohydrate." }, { "input": "Here we analyze its mechanism of regulation as an immediately early gene controlled by stress stimuli that activate p38 / MK2 pathway.", "output": "There is no related enetity." }, { "input": "We report that exposure of HeLa and T98G cells to different stress stimuli ( NaCl, H2O2, UV radiation and anisomycin ) leads to a rapid increase ( 15 - 30 minutes ) in PFKFB3 mRNA levels.", "output": "NaCl, H2O2, anisomycin." }, { "input": "The use of specific inhibitors in combination with MK2 - deficient cells implicate control by MK2 protein kinase.", "output": "There is no related enetity." }, { "input": "Transient transfection of HeLa cells with deleted gene promoter constructs allowed us to identify a Serum Response Element ( SRE ) to which Serum Response Factor ( SRF ) binds and thus transactivates PFKFB3 gene transcription.", "output": "There is no related enetity." }, { "input": "Direct Binding of phospho - SRF to the SRE sequence ( - 918 nt ) was confirmed by ChIP ( chromatin immunoprecipiation ) assays.", "output": "There is no related enetity." }, { "input": "Moreover, PFKFB3 isoenzyme phosphorylation at Ser461 by MK2 increases PFK - 2 activity.", "output": "Ser461." }, { "input": "Together, the results suggest a multimodal mechanism of stress stimuli affecting PFKFB3 transcriptional regulation and kinase activation by protein phosphorylation, resulting in an increase in Fru - 2, 6 - P2 concentration and stimulation of glycolysis in cancer cells.", "output": "Fru - 2 , 6 - P2." }, { "input": "Identification of a new interaction mode between the Src homology 2 ( SH2 ) domain of C - terminal Src kinase ( Csk ) and Csk - binding protein ( Cbp ) / phosphoprotein associated with glycosphingolipid microdomains ( PAG ).", "output": "C." }, { "input": "Proteins with Src homology 2 ( SH2 ) domains play major roles in tyrosine kinase signaling.", "output": "tyrosine." }, { "input": "Structures of many SH2 domains have been studied, and the regions involved in their interactions with ligands have been elucidated.", "output": "There is no related enetity." }, { "input": "However, these analyses have been performed using short peptides comprising phosphotyrosine followed by a few amino acids, which are described as the canonical recognition sites.", "output": "phosphotyrosine, amino acids." }, { "input": "Here we report the solution structure of the SH2 domain of C - terminal Src kinase ( Csk ) in complex with a longer phosphopeptide from Csk - binding protein ( Cbp ).", "output": "C." }, { "input": "This structure, together with biochemical experiments, revealed the existence of a novel binding region in addition to the canonical phosphotyrosine - 314 binding site of Cbp.", "output": "phosphotyrosine." }, { "input": "Mutational analysis of this second region in cells showed that both canonical and novel binding sites are required for tumor suppression through the Cbp - Csk interaction.", "output": "There is no related enetity." }, { "input": "Furthermore, the data indicate an allosteric connection between Cbp binding and Csk activation that arises from residues in the beta B / beta C loop of the SH2 domain.", "output": "There is no related enetity." }, { "input": "G - protein coupled receptor agonist BV8 / prokineticin - 2 and STAT3 form a feed - forward loop in both normal and malignant myeloid cells.", "output": "There is no related enetity." }, { "input": "An important role of Bv8 in mobilization of myeloid cells and myeloid cell - dependent angiogenesis has been established.", "output": "There is no related enetity." }, { "input": "Recently, it has also been shown that granulocyte colony stimulating factor ( G - CSF ) - induced Bv8 expression is Stat3 dependent in CD11b + Gr1 + myeloid cells.", "output": "There is no related enetity." }, { "input": "However, Bv8 downstream signaling pathway ( s ) intrinsic to myeloid cells crucial for angiogenesis, and potentially also for development of cancers of myeloid origin, remains largely unknown.", "output": "There is no related enetity." }, { "input": "Here we show that BV8 activates STAT3, which is critical for regulating genes important for both tumor cell proliferation / survival and tumor angiogenesis, in both normal and malignant myeloid cells.", "output": "There is no related enetity." }, { "input": "Further, BV8 - induced STAT3 activation requires Janus activated kinase 2 ( JAK2 ) activity as shown by both genetic and pharmacologic inhibition.", "output": "There is no related enetity." }, { "input": "Knocking down BV8 in human myeloid leukemia cells inhibits STAT3 activity and expression of STAT3 - downstream angiogenic and pro - proliferation / survival genes, leading to a decrease in tumor cell viability.", "output": "There is no related enetity." }, { "input": "BV8 shRNA expressing leukemia cells exhibit reduced STAT3 activity and tumor growth in vivo.", "output": "There is no related enetity." }, { "input": "Taken together, we have delineated a signaling pathway downstream of BV8 that plays critical roles in both the tumor microenvironment and malignant myeloid cells for angiogenesis and tumor cell proliferation / survival.", "output": "There is no related enetity." }, { "input": "Visual evoked potentials in children prenatally exposed to methylmercury.", "output": "methylmercury." }, { "input": "Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes.", "output": "methylmercury." }, { "input": "However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors.", "output": "There is no related enetity." }, { "input": "We evaluated the effect of prenatal methylmercury exposure on visual evoked potential ( VEP ) latencies in Faroese children with elevated prenatal methylmercury exposure.", "output": "methylmercury, methylmercury." }, { "input": "A cohort of 182 singleton term births was assembled in the Faroe Islands during 1994 - 1995.", "output": "There is no related enetity." }, { "input": "At age 7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of subjects with abnormal vision conditions.", "output": "There is no related enetity." }, { "input": "We used multiple regression analysis to evaluate the association of mercury concentrations in cord blood and maternal hair at parturition with VEP latencies after adjustment for potential confounders that included the cord - serum phospholipid concentration of n - 3 polyunsaturated fatty acids ( PUFAs ) and the duration of breastfeeding.", "output": "mercury, polyunsaturated fatty acids, PUFAs." }, { "input": "Unadjusted correlations between mercury exposure and VEP latencies were equivocal.", "output": "mercury." }, { "input": "Multiple regression models showed that increased mercury concentrations, especially in maternal hair, were associated with delayed latencies for VEP peak N145.", "output": "mercury." }, { "input": "After covariate adjustment, a delay of 2. 22ms ( p = 0. 02 ) was seen for each doubling of the mercury concentration in maternal hair.", "output": "mercury." }, { "input": "In agreement with neuropsychological findings, the present study suggests that prenatal methylmercury exposure may have an adverse effect on VEP findings despite the absence of clinical toxicity to the visual system.", "output": "methylmercury." }, { "input": "However, this association was apparent only after adjustment for n - 3 PUFA status.", "output": "PUFA." }, { "input": "Spongiatriol inhibits nuclear factor kappa B activation and induces apoptosis in pancreatic cancer cells.", "output": "Spongiatriol." }, { "input": "Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation.", "output": "There is no related enetity." }, { "input": "The majority of pro - inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B ( NF kappa B ), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis.", "output": "There is no related enetity." }, { "input": "In an effort to identify novel inhibitors of NF kappa B, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NF kappa B.", "output": "There is no related enetity." }, { "input": "Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NF kappa B inhibitors.", "output": "There is no related enetity." }, { "input": "Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NF kappa B transcriptional activity in a reporter cell line, to reduce levels of phosphorylated ( active ) NF kappa B in the AsPC - 1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC - 1, BxPC - 3, MiaPaCa - 2 and Panc - 1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC - 1 and the Panc - 1 cell lines.", "output": "Spongiatriol, furanoditerpenoid." }, { "input": "Is There Visceral Adipose Tissue ( VAT ) Intracellular Hypercortisolism in Human Obesity?", "output": "There is no related enetity." }, { "input": "The fact that obesity is a prominent feature of Cushing ' s syndrome ( systemic hypercortisolism of adrenocortical origin ) stimulated a 40 - year search for evidence of systemic hypercortisolism in human obesity.", "output": "There is no related enetity." }, { "input": "That search has failed to find such evidence.", "output": "There is no related enetity." }, { "input": "For the past 15 years, however, studies have been done to evaluate a possible alternative type of hypercortisolism in obesity, namely visceral adipose tissue ( VAT ) intracellular hypercortisolism.", "output": "There is no related enetity." }, { "input": "The current review summarizes the evidence published so far about this possibility.", "output": "There is no related enetity." }, { "input": "There have been three types of evidence studied: direct measurement of the VAT levels of 11 beta - hydroxysteroid dehydrogenase type I ( 11 - HSD - 1 ), which converts biologically inactive cortisone to biologically active cortisol; direct measurement of splanchnic cortisol production; and evaluation of the effect of a specific inhibitor of 11 - HSD - 1 on metabolic abnormalities associated with obesity, particularly diabetes mellitus.", "output": "11 beta - hydroxysteroid, cortisone, cortisol, cortisol." }, { "input": "The results are complex and difficult to interpret.", "output": "There is no related enetity." }, { "input": "Our conclusion is that the presence of VAT intracellular hypercortisolism in human obesity is possible but unlikely.", "output": "There is no related enetity." }, { "input": "Long - term Effects of Perinatal Androgenization on Reproductive Parameters of Male Rat Offspring Androgenization and Male Rat Reproduction.", "output": "There is no related enetity." }, { "input": "It is known that during sex differentiation, fetal androgens are critical determinants of the male phenotype.", "output": "androgens." }, { "input": "Although testosterone is necessary for normal development of male sexual behavior, perinatal androgen treatment can result in disruption of normal male sexual reproduction.", "output": "testosterone, androgen." }, { "input": "Pregnant Wistar rats were administered either corn oil ( vehicle ) or testosterone propionate at 0. 2 mg / kg from gestational day 12 until the end of lactation and the reproductive function of male offspring was evaluated at 90 ( adulthood ) and 270 ( middle age ) days of age.", "output": "testosterone propionate." }, { "input": "Perinatal androgenization in the rat provoked a reduction in sperm production and reserves in adulthood that did not affect fertility and did not persist at more advanced ages, as shown by the results at post - natal day 270.", "output": "There is no related enetity." }, { "input": "If perinatal androgenization promotes similar effects in humans of reproductive age, the results of the present work can impact male reproduction health, given the less efficient spermatogenesis and lower sperm reserves in the human epididymis, compared to rodents.", "output": "There is no related enetity." }, { "input": "The CYP2B6 * 6 Allele Significantly Alters the N - demethylation of Ketamine Enantiomers In Vitro.", "output": "Ketamine." }, { "input": "Ketamine is primarily metabolized to norketamine by hepatic cytochrome P450 ( CYP ) 2B6 and CYP3A4 - mediated N - demethylation.", "output": "Ketamine, norketamine." }, { "input": "However, the relative contribution from each enzyme remains controversial.", "output": "There is no related enetity." }, { "input": "The CYP2B6 * 6 allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in ketamine metabolism.", "output": "ketamine." }, { "input": "We examined the N - demethylation of individual ketamine enantiomers using human liver microsomes ( HLMs ) genotyped for the CYP2B6 * 6 allele, insect cell expressed recombinant CYP2B6 and CYP3A4 enzymes and COS - 1 cell expressed recombinant CYP2B6. 1 and CYP2B6. 6 protein variant.", "output": "ketamine." }, { "input": "Effects of CYP - selective inhibitors on norketamine formation were also determined in HLMs.", "output": "norketamine." }, { "input": "The two - enzyme Michaelis - Menten model best fitted the HLM kinetic data.", "output": "There is no related enetity." }, { "input": "The Km value for the high affinity enzyme and the low affinity enzyme were similar to those for the expressed CYP2B6 and CYP3A4, respectively.", "output": "There is no related enetity." }, { "input": "The intrinsic clearance for both ketamine enantiomers by the high affinity enzyme in HLMs with CYP2B6 * 1 / * 1 genotype were at least 2 - fold and 6 - fold higher, respectively, than those for CYP2B6 * 1 / * 6 genotype and CYP2B6 * 6 / * 6 genotype.", "output": "ketamine." }, { "input": "The Vmax and Km values for CYP2B6. 1 were approximately 160 % and 70 % of those for CYP2B6. 6, respectively.", "output": "There is no related enetity." }, { "input": "ThioTEPA ( CYP2B6 inhibitor, 25 mu M ) and the monoclonal antibody against CYP2B6 but not troleandomycin ( CYP3A4 inhibitor, 25 mu M ) or the monoclonal antibody against CYP3A4 inhibited ketamine N - demethylation at clinically relevant concentrations.", "output": "ThioTEPA, troleandomycin, ketamine." }, { "input": "The degree of inhibition was significantly reduced in HLMs with the CYP2B6 * 6 allele ( gene - dose P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "These results indicate a major role of CYP2B6 in ketamine N - demethylation in vitro and a significant impact of the CYP2B6 * 6 allele on enzyme - ketamine binding and catalytic activity.", "output": "ketamine, ketamine." }, { "input": "Molecular Dynamics Simulations of CO2 Formation in Interstellar Ices.", "output": "CO2." }, { "input": "CO2 ice is one of the most abundant components in ice - coated interstellar ices besides H2O and CO, but the most favorable path to CO2 ice is still unclear.", "output": "CO2, H2O, CO, CO2." }, { "input": "Molecular dynamics calculations on the ultraviolet photodissociation of different kinds of CO - H2O ice systems have been performed at 10 K in order to demonstrate that the reaction between CO and an OH molecule resulting from H2O photodissociation through the first excited state is a possible route to form CO2 ice.", "output": "CO, H2O, CO, OH, H2O, CO2." }, { "input": "However, our calculations, which take into account different ice surface models, suggest that there is another product with a higher formation probability ( ( 3. 00 +/- 0. 07 ) x 10 ( - 2 ) ), which is the HOCO complex, whereas the formation of CO2 has a probability of only ( 3. 6 +/- 0. 7 ) x 10 ( - 4 ).", "output": "HOCO, CO2." }, { "input": "The initial location of the CO is key to obtain reaction and form CO2: the CO needs to be located deep into the ice.", "output": "CO, CO2, CO." }, { "input": "The HOCO complex becomes trapped in the cold ice surface in the trans - HOCO minimum because it quickly loses its internal energy to the surrounding ice, preventing further reaction to H + CO2.", "output": "HOCO, trans - HOCO, H, CO2." }, { "input": "Several laboratory experiments have been carried out recently, and they confirm that CO2 can also be formed through other, different routes.", "output": "CO2." }, { "input": "Here we compare our theoretical results with the data available from experiments studying the formation of CO2 through a similar pathway as ours, even though the initial conditions were not exactly the same.", "output": "CO2." }, { "input": "Our results also show that the HCO van der Waals complex can be formed through the interaction of CO with the H atom that is formed as a product of H2O photodissociation.", "output": "HCO, CO, H, H2O." }, { "input": "Thus, the reaction of the H atom photofragment following H2O photodissociation with CO can be a possible route to form HCO ice.", "output": "H, H2O, CO, HCO." }, { "input": "Thermal Stability of Peroxy Acyl Nitrates Formed in the Oxidation of CxF2x + 1CH2C ( O ) H ( x = 1, 6 ) in the Presence of NO2.", "output": "Peroxy Acyl Nitrates, CxF2x + 1CH2C ( O ) H, NO2." }, { "input": "The formation of CxF2x + 1CH2C ( O ) OONO2 ( x = 1, 6 ) from the photooxidation of CxF2x + 1CH2C ( O ) H ( x = 1, 6 ) in the presence of NO2 was investigated.", "output": "CxF2x + 1CH2C ( O ) OONO2, CxF2x + 1CH2C ( O ) H, NO2." }, { "input": "The infrared spectrum of C6F13CH2C ( O ) OONO2 is reported for the first time, and thermal stability for both peroxynitrates at 295 K and 9. 0 mbar is informed.", "output": "C6F13CH2C ( O ) OONO2." }, { "input": "Kinetic parameters ( activation energy and pre - exponential factor ) for CF3CH2C ( O ) OONO2 at 9. 0 and 1000 mbar are: 108 +/- 2 kJ / mol, 1. 5 x 10 ( 15 ) and 114 +/- 2 kJ / mol, 2. 4 x 10 ( 16 ), respectively.", "output": "CF3CH2C ( O ) OONO2." }, { "input": "A comparison is made between fluoro and hydrogenated peroxy acyl nitrates.", "output": "peroxy acyl nitrates." }, { "input": "Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial.", "output": "pioglitazone." }, { "input": "AIMS: This study examined the effects of pioglitazone on body weight and bone mineral density ( BMD ) prospectively in patients with impaired glucose tolerance as pioglitazone ( TZD ) increases body weight and body fat in diabetic patients and increases the risk of bone fractures.", "output": "pioglitazone, glucose, pioglitazone, TZD." }, { "input": "METHODS: A total of 71 men and 163 women aged 49. 3 ( 10. 7 ) years [ mean ( s. d. ) ]; body mass index ( BMI ), 34. 5 ( 5. 9 ) kg / m ( 2 ) were recruited at five sites for measurements of body composition by dual energy X - ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted.", "output": "There is no related enetity." }, { "input": "RESULTS: Mean follow - up was 33. 6 months in the pioglitazone group and 32. 1 months in the placebo group.", "output": "pioglitazone." }, { "input": "Body weight increased 4. 63 +/- 0. 60 ( m +/- s. e. ) kg in the pioglitazone group compared to 0. 98 +/- 0. 62 kg in the PIO group ( p < 0. 0001 ).", "output": "pioglitazone." }, { "input": "Body fat rose 4. 89 +/- 0. 42 kg in the pioglitazone group compared to 1. 41 +/- 0. 44 kg, ( p < 0. 0001 ) in placebo - treated subjects.", "output": "pioglitazone." }, { "input": "The increase in fat was greater in legs and trunk than in the arms.", "output": "There is no related enetity." }, { "input": "BMD was higher in all regions in men and significantly so in most.", "output": "There is no related enetity." }, { "input": "PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men.", "output": "There is no related enetity." }, { "input": "Bone mineral content also decreased significantly in arms, legs, trunk and in the total body.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body.", "output": "Pioglitazone." }, { "input": "Cis - silencing of PIP5K1B evidenced in Friedreich ' s ataxia patient cells results in cytoskeleton anomalies.", "output": "There is no related enetity." }, { "input": "Friedreich ' s ataxia ( FRDA ) is a progressive neurodegenerative disease characterized by ataxia, variously associating heart disease, diabetes mellitus and / or glucose intolerance.", "output": "glucose." }, { "input": "It results from intronic expansion of GAA triplet repeats at the FXN locus.", "output": "There is no related enetity." }, { "input": "Homozygous expansions cause silencing of the FXN gene and subsequent decreased expression of the encoded mitochondrial frataxin.", "output": "There is no related enetity." }, { "input": "Detailed analyses in fibroblasts and neuronal tissues from FRDA patients have revealed profound cytoskeleton anomalies.", "output": "There is no related enetity." }, { "input": "So far, however, the molecular mechanism underlying these cytoskeleton defects remains unknown.", "output": "There is no related enetity." }, { "input": "We show here that gene silencing spreads in cis over the PIP5K1B gene in cells from FRDA patients ( circulating lymphocytes and primary fibroblasts ), correlating with expanded GAA repeat size.", "output": "There is no related enetity." }, { "input": "PIP5K1B encodes phosphatidylinositol 4 - phosphate 5 - kinase beta type I ( pip5k1 beta ), an enzyme functionally linked to actin cytoskeleton dynamics that phosphorylates phosphatidylinositol 4 - phosphate [ PI ( 4 ) P ] to generate phosphatidylinositol - 4, 5 - bisphosphate [ PI ( 4, 5 ) P2 ].", "output": "phosphatidylinositol 4 - phosphate, phosphatidylinositol 4 - phosphate, PI ( 4 ) P, phosphatidylinositol - 4 , 5 - bisphosphate, PI ( 4 , 5 ) P2." }, { "input": "Accordingly, loss of pip5k1 beta function in FRDA cells was accompanied by decreased PI ( 4, 5 ) P2 levels and was shown instrumental for destabilization of the actin network and delayed cell spreading.", "output": "PI ( 4 , 5 ) P2." }, { "input": "Knockdown of PIP5K1B in control fibroblasts using shRNA reproduced abnormal actin cytoskeleton remodeling, whereas over - expression of PIP5K1B, but not FXN, suppressed this phenotype in FRDA cells.", "output": "There is no related enetity." }, { "input": "In addition to provide new insights into the consequences of the FXN gene expansion, these findings raise the question whether PIP5K1B silencing may contribute to the variable manifestation of this complex disease.", "output": "There is no related enetity." }, { "input": "Evaluation of in vitro and in vivo genotoxicity of single - walled carbon nanotubes.", "output": "carbon." }, { "input": "Single - walled carbon nanotubes ( SWCNTs ) have extensive potential industrial applications due to their unique physical and chemical properties; yet this also increases the chance of human and environment exposure to SWCNTs.", "output": "carbon." }, { "input": "Due to the current lack of hazardous effect information on SWNCTs, a standardized genotoxicity battery test was conducted to clarify the genetic toxicity potential of SWCNTs ( diameter: 1 - 1. 2 nm, length: ~ 20 mu m ) according to Organization for Economic Cooperation and Development test guidelines 471 ( bacterial reverse mutation test ), 473 ( in vitro chromosome aberration test ), and 474 ( in vivo micronuclei test ) with a good laboratory practice system.", "output": "There is no related enetity." }, { "input": "The test results showed that the SWCNTs did not induce significant bacterial reverse mutations at 31. 3 - 500 mu g / plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 or in Escherichia coli strain WP2uvrA, with and without a metabolic activation system.", "output": "There is no related enetity." }, { "input": "Furthermore, the in vitro chromosome aberration test showed no significant increase in structural or numerical chromosome aberration frequencies at SWCNT dose levels of 12. 5 - 50 mu g / ml in the presence and absence of metabolic activation.", "output": "There is no related enetity." }, { "input": "However, dose - dependent cell growth inhibition was found at all the SWCNT dose levels and statistically significant cytotoxic effects observed at certain concentrations in the presence and absence of metabolic activation.", "output": "There is no related enetity." }, { "input": "Finally, the SWCNTs did not evoke significant in vivo micronuclei frequencies in the polychromatic erythrocytes of an imprinting control region mice at 25 - 100 mg / kg.", "output": "There is no related enetity." }, { "input": "Thus, according to the results of the present study, the SWCNTs were not found to have a genotoxic effect on the in vitro and in vivo test systems.", "output": "There is no related enetity." }, { "input": "Potential anticancer activity of carvone in N2a neuroblastoma cell line.", "output": "carvone." }, { "input": "Carvone ( CVN ) is a monocyclic monoterpene found in the essential oils of Mentha spicata var. crispa ( Lamiaceae ) and Carum carvi L.", "output": "Carvone, CVN, monocyclic monoterpene." }, { "input": "( Apiaceae ) plants and has been reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor activities.", "output": "There is no related enetity." }, { "input": "The beneficial health properties of CVN have encouraged us to look into its anticancer activity.", "output": "CVN." }, { "input": "To the best of our knowledge, reports are not available on the anticancer activity of CVN in cultured primary rat neuron and N2a neuroblastoma ( NB ) cells.", "output": "CVN." }, { "input": "Therefore, the present study is an attempt toward exploring the potential anticancer activity of CVN, if any, in cultured primary rat neuron and N2a NB cells.", "output": "CVN." }, { "input": "Our results indicated that CVN ( only at 25 mg / L ) treatment led to an increase in the total antioxidant capacity levels in cultured primary rat neuron cells compared with control cells.", "output": "CVN." }, { "input": "Also, CVN ( at concentrations higher than 100 mg / L ) treatment led to an increase in the total oxidative stress levels in both cell types.", "output": "CVN." }, { "input": "The mean values of the total scores of cells showing DNA damage ( for comet assay ) were not found to be significantly different from the control values in both cells ( p > 0. 05 ).", "output": "There is no related enetity." }, { "input": "On the other hand, after 24 h treatment with CVN, 3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 diphenyltetrazolium bromide assay showed that CVN application significantly reduced the cell viability rates in both cell types at concentrations higher than 100 mg / L.", "output": "CVN, 3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 diphenyltetrazolium bromide, CVN." }, { "input": "Summarizing, our data suggest that CVN represents little potential for promising anticancer agent to improve brain tumors therapy.", "output": "CVN." }, { "input": "Modeling CO2 reduction on Pt ( 111 ).", "output": "CO2, Pt ( 111 )." }, { "input": "Density functional theory was used to model the electrochemical reduction of CO2 on Pt ( 111 ) with an explicit solvation layer and the presence of extra hydrogen atoms to represent a negatively charged electrode.", "output": "CO2, Pt ( 111 ), hydrogen." }, { "input": "We focused on the electronic energy barriers for the first four lowest energy proton - electron transfer steps for reducing CO2 on Pt ( 111 ) beginning with adsorbed * CO2 and continuing with * COOH, * CO + H2O, * COH, and ending with * C + H2O.", "output": "CO2, Pt ( 111 ), CO2, COOH, CO, H2O, COH, C, H2O." }, { "input": "We find that simple elementary steps in which a proton is transferred to an adsorbate ( such as the protonation of * CO to * COH ) have small barriers on the order of 0. 1 eV.", "output": "CO, COH." }, { "input": "Elementary steps in which a proton is transferred and a C - O bond is simultaneously cleaved show barriers on the order of 0. 5 eV.", "output": "C - O." }, { "input": "All barriers calculated for these steps show no sign of being insurmountable at room temperature.", "output": "There is no related enetity." }, { "input": "To explain why these barriers are so small, we analyze the charge density and the density of states plots to see that first, the electron transfer is decoupled from the proton transfer so that in the initial state, the surface and adsorbate are already charged up and can easily accept the proton from solution.", "output": "There is no related enetity." }, { "input": "Also, we see that in the cases where barriers are on the order of 0. 1 eV, electron density in the initial state localizes on the oxygen end of the adsorbate, while electron density is more spread out on the surface for initial states of the C - O bond cleaving elementary steps.", "output": "oxygen, C - O." }, { "input": "Comparing molecular photofragmentation dynamics in the gas and liquid phases.", "output": "There is no related enetity." }, { "input": "This article explores the extent to which insights gleaned from detailed studies of molecular photodissociations in the gas phase ( i. e. under isolated molecule conditions ) can inform our understanding of the corresponding photofragmentation processes in solution.", "output": "There is no related enetity." }, { "input": "Systems selected for comparison include a thiophenol ( p - methylthiophenol ), a thioanisole ( p - methylthioanisole ) and phenol, in vacuum and in cyclohexane solution.", "output": "thiophenol, p - methylthiophenol, thioanisole, p - methylthioanisole, phenol, cyclohexane." }, { "input": "UV excitation in the gas phase results in RX - Y ( X = O, S; Y = H, CH3 ) bond fission in all cases, but over timescales that vary by ~ 4 orders of magnitude - all of which behaviours can be rationalised on the basis of the relevant bound and dissociative excited state potential energy surfaces ( PESs ) accessed by UV photoexcitation, and of the conical intersections that facilitate radiationless transfer between these PESs.", "output": "RX - Y, O, S, H, CH3." }, { "input": "Time - resolved UV pump - broadband UV / visible probe and / or UV pump - broadband IR probe studies of the corresponding systems in cyclohexane solution reveal additional processes that are unique to the condensed phase.", "output": "cyclohexane." }, { "input": "Thus, for example, the data clearly reveal evidence of ( i ) vibrational relaxation of the photoexcited molecules prior to their dissociation and of the radical fragments formed upon X - Y bond fission, and ( ii ) geminate recombination of the RX and Y products ( leading to reformation of the ground state parent and / or isomeric adducts ).", "output": "RX." }, { "input": "Nonetheless, the data also show that, in each case, the characteristics ( and the timescale ) of the initial bond fission process that occurs under isolated molecule conditions are barely changed by the presence of a weakly interacting solvent like cyclohexane.", "output": "cyclohexane." }, { "input": "These condensed phase studies are then extended to an ether analogue of phenol ( allyl phenyl ether ), wherein UV photo - induced RO - allyl bond fission constitutes the first step of a photo - Claisen rearrangement.", "output": "ether, phenol, allyl phenyl ether, RO, allyl." }, { "input": "Characterization and Expression of the Gene Encoding En - MAPK1, an Intestinal Cell Kinase ( ICK ) - like Kinase Activated by the Autocrine Pheromone - Signaling Loop in the Polar Ciliate, Euplotes nobilii.", "output": "There is no related enetity." }, { "input": "In the protozoan ciliate Euplotes, a transduction pathway resulting in a mitogenic cell growth response is activated by autocrine receptor binding of cell type - specific, water - borne signaling protein pheromones.", "output": "There is no related enetity." }, { "input": "In Euplotes raikovi, a marine species of temperate waters, this transduction pathway was previously shown to involve the phosphorylation of a nuclear protein kinase structurally similar to the intestinal - cell and male germ cell - associated kinases described in mammals.", "output": "There is no related enetity." }, { "input": "In E. nobilii, which is phylogenetically closely related to E. raikovi but inhabits Antarctic and Arctic waters, we have now characterized a gene encoding a structurally homologous kinase.", "output": "There is no related enetity." }, { "input": "The expression of this gene requires + 1 translational frameshifting and a process of intron splicing for the production of the active protein, designated En - MAPK1, which contains amino acid substitutions of potential significance for cold - adaptation.", "output": "amino acid." }, { "input": "Intracellular cleavable poly ( 2 - dimethylaminoethyl methacrylate ) functionalized mesoporous silica nanoparticles for efficient siRNA delivery in vitro and in vivo.", "output": "poly ( 2 - dimethylaminoethyl methacrylate ), silica." }, { "input": "A low cytotoxicity and high efficiency delivery system with the advantages of low cost and facile fabrication is needed for the application of small interfering RNA ( siRNA ) delivery both in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "For these prerequisites, cationic polymer - mesoporous silica nanoparticles ( ssCP - MSNs ) were prepared by surface functionalized mesoporous silica nanoparticles with disulfide bond cross - linked poly ( 2 - dimethylaminoethyl methacrylate ) ( PDMAEMA ).", "output": "silica, silica, disulfide, poly ( 2 - dimethylaminoethyl methacrylate ), PDMAEMA." }, { "input": "In vitro and in vivo evaluations were performed.", "output": "There is no related enetity." }, { "input": "The synthesized ssCP - MSNs are 100 - 150 nm in diameter with a pore size of 10 nm and a positively charged surface with a high zeta potential of 27 mV.", "output": "There is no related enetity." }, { "input": "Consequently, the ssCP - MSNs showed an excellent binding capacity for siRNA, and an enhancement in the cell uptake and cytosolic availability of siRNA.", "output": "There is no related enetity." }, { "input": "Furthermore, the intracellular reducing cleavage of the disulfide bonds cross - linking the PDMAEMA segments led to intracellular cleavage of PDMAEMA from ssCP - MSNs, which facilitated the intracellular triggered release of siRNA.", "output": "disulfide, PDMAEMA, PDMAEMA." }, { "input": "Therefore, promoted RNA interference was observed in HeLa - Luc cells, which was equal to that of Lipofectamine 2000.", "output": "There is no related enetity." }, { "input": "Significantly, compared to Lipofectamine 2000, the ssCP - MSNs were more biocompatible, with low cytotoxicity ( even non - cytotoxicity ) and promotion of cell proliferation to HeLa - Luc cells.", "output": "There is no related enetity." }, { "input": "The in vivo systemic distribution studies certified that ssCP - MSNs / siRNA could prolong the duration of siRNA in vivo, and that they accumulated in the adrenal gland, liver, lung, spleen, kidney, heart and thymus after intravenous injection.", "output": "There is no related enetity." }, { "input": "Encouragingly, with the ability to deliver siRNA to a tumor, ssCP - MSNs / siRNA showed a tumor suppression effect in the HeLa - Luc xenograft murine model after intravenous injection.", "output": "There is no related enetity." }, { "input": "Therefore, the ssCP - MSNs cationic polymer - mesoporous silica nanoparticles with low cytotoxicity are promising for siRNA delivery.", "output": "There is no related enetity." }, { "input": "Effects of mixtures of azole fungicides in postimplantation rat whole - embryo cultures.", "output": "azole." }, { "input": "The effect of mixtures of azole fungicides on development of postimplantation rat whole - embryos cultured in vitro has been tested.", "output": "azole." }, { "input": "On the basis of bench mark dose ( BMD ) modeling of the in vitro effect in rat embryo, the potency of 7 azoles was determined and compared.", "output": "azoles." }, { "input": "Then, relative potency factors have been derived based on either the NOAEL or on the BMD curve.", "output": "There is no related enetity." }, { "input": "Alternatively, each compound was used as index compound ( IC ), and IC - equivalent concentrations have been calculated for each mixture.", "output": "There is no related enetity." }, { "input": "Expected effects of such IC - equivalent concentrations of the mixture were derived from the appropriate BMD curve.", "output": "There is no related enetity." }, { "input": "Test mixture includes the agrochemicals triadimefon and imazalil ( MIX2 ) or triadimefon, imazalil, and the clinically used fluconazole ( MIX3 ) at their previously determined no - effect concentration, corresponding to approximately a benchmark response of 5 - 10 %.", "output": "triadimefon, imazalil, triadimefon, imazalil, fluconazole." }, { "input": "Subsequently, we tested the effect of a mixture of the agrochemicals triadimefon, imazalil, triadimenol, cyproconazole, tebuconazole, and flusilazole ( MIX6 ) at concentration levels derived from their established human acceptable daily intake.", "output": "triadimefon, imazalil, triadimenol, cyproconazole, tebuconazole, flusilazole." }, { "input": "MIX6 was also added with fluconazole at concentration levels indicated as the minimum therapeutically effective plasmatic concentration ( MIX7A ) or ten times this level ( MIX7B ).", "output": "fluconazole." }, { "input": "Generally, the experimental response was higher than the estimated one, by a factor of 2 - 6.", "output": "There is no related enetity." }, { "input": "Our data suggest that it is in principle correct to assume that azoles act as teratogens via a common mode of action and therefore should be grouped together for risk assessment.", "output": "There is no related enetity." }, { "input": "The synergistic effect needs to be confirmed with more combinations of concentrations / compounds in vitro and with specific in vivo experiments.", "output": "There is no related enetity." }, { "input": "High responsivity, fast ultraviolet photodetector fabricated from ZnO nanoparticle - graphene core - shell structures.", "output": "ZnO, graphene." }, { "input": "We report a simple, efficient and versatile method for assembling metal oxide nanomaterial - graphene core - shell structures.", "output": "metal oxide, graphene." }, { "input": "An ultraviolet photodetector fabricated from the ZnO nanoparticle - graphene core - shell structures showed high responsivity and fast transient response, which are attributed to the improved carrier transport efficiency arising from graphene encapsulation.", "output": "ZnO, graphene, graphene." }, { "input": "Adsorption of diferrocenylacetylene on Au ( 111 ) studied by scanning tunneling microscopy.", "output": "diferrocenylacetylene, Au ( 111 )." }, { "input": "Scanning tunneling microscopy images of diferrocenylacetylene ( DFA ) coadsorbed with benzene on Au ( 111 ) show individual and close - packed DFA molecules, either adsorbed alongside benzene or on top of a benzene monolayer.", "output": "diferrocenylacetylene, DFA, benzene, Au ( 111 ), DFA, benzene, benzene." }, { "input": "Images acquired over a range of positive and negative tip - sample bias voltages show a shift in contrast, with the acetylene linker appearing brighter than the ferrocenes at positive sample bias ( where unoccupied states primarily contribute ) and the reverse contrast at negative bias.", "output": "acetylene, ferrocenes." }, { "input": "Density functional theory was used to calculate the electronic structure of the gas - phase DFA molecule, and simulated images produced through two - dimensional projections of these calculations approximate the experimental images.", "output": "DFA." }, { "input": "The symmetry of both experimental and calculated molecular features for DFA rules out a cis adsorption geometry, and comparison of experiment to simulation indicates torsion around the inter - ferrocene axis between 90 degrees and 180 degrees ( trans ); the cyclopentadienyl rings are thus angled with respect to the surface.", "output": "DFA, ferrocene, cyclopentadienyl." }, { "input": "Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis.", "output": "Axitinib." }, { "input": "Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second - line therapy for advanced renal cell carcinoma ( RCC ).", "output": "Axitinib." }, { "input": "Axitinib population pharmacokinetic and pharmacokinetic / pharmacodynamic relationships were evaluated.", "output": "Axitinib." }, { "input": "Using nonlinear mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients with metastatic RCC, and 26 patients with other solid tumors in 17 trials, the disposition of axitinib was best described by a 2 - compartment model with first - order absorption and a lag time, with estimated mean systemic clearance ( CL ) of 14. 6 L / h and central volume of distribution ( Vc ) of 47. 3 L.", "output": "axitinib." }, { "input": "Of 12 covariates tested, age over 60 years and Japanese ethnicity were associated with decreased CL, whereas Vc increased with body weight.", "output": "There is no related enetity." }, { "input": "However, the magnitude of predicted changes in exposure based on these covariates does not warrant dose adjustments.", "output": "There is no related enetity." }, { "input": "Multivariate Cox proportional hazard regression and logistic regression analyses showed that higher exposure and diastolic blood pressure were independently associated with longer progression - free and overall survivals and higher probability of partial response in metastatic RCC patients.", "output": "There is no related enetity." }, { "input": "These findings support axitinib dose titration to increase plasma exposure in patients who tolerate axitinib, and also demonstrate diastolic blood pressure as a potential marker of efficacy.", "output": "axitinib, axitinib." }, { "input": "Aerosol particle size does not predict pharmacokinetic determined lung dose in children.", "output": "There is no related enetity." }, { "input": "In vitro measures of aerosol particles size, such as the fine particle mass, play a pivotal role for approval of inhaled anti - asthmatic drugs.", "output": "There is no related enetity." }, { "input": "However, the validity as a measure of dose to the lungs in children lacks evidence.", "output": "There is no related enetity." }, { "input": "In this study we investigated for the first time the association between an in vivo estimate of lung dose of inhaled drug in children and the corresponding particle size segments assessed ex vivo.", "output": "There is no related enetity." }, { "input": "Lung dose of fluticasone propionate after inhalation from a dry powder inhaler ( Diskus (R) ) was studied in 23 children aged 4 - 7 and 12 - 15 years with mild asthma.", "output": "fluticasone propionate, Diskus." }, { "input": "Six - hour pharmacokinetics was assessed after single inhalation.", "output": "There is no related enetity." }, { "input": "The corresponding emitted mass of drug in segments of aerosol particle size was assessed ex vivo by replicating the inhalation flows recorded by transducers built into the Diskus (R) inhaler and re - playing them in a breathing simulator.", "output": "Diskus." }, { "input": "There was no correlation between any inhaled particle size segment and lung dose assessed by pharmacokinetics and adjusted for age and body size.", "output": "There is no related enetity." }, { "input": "Measures of particles size segments were not related to lung dose in children.", "output": "There is no related enetity." }, { "input": "Until further evidence is provided it may be warranted to emphasize pharmacokinetic or pharmacodynamic assessments of drug delivery to the lung.", "output": "There is no related enetity." }, { "input": "The N - and C - termini of ZO - 1 are surrounded by distinct proteins and functional protein networks.", "output": "There is no related enetity." }, { "input": "The proteins and functional protein networks of the tight junction remain incompletely defined.", "output": "There is no related enetity." }, { "input": "Among the currently known proteins are barrier forming proteins like occludin and the claudin family, scaffolding proteins like ZO - 1, and some cytoskeletal, signaling and cell polarity proteins.", "output": "There is no related enetity." }, { "input": "To define a more complete list of proteins and infer their functional implications, we identified the proteins which are within molecular dimensions of ZO - 1 by fusing biotin ligase to either its N - or C - terminus, expressing these fusion proteins in MDCK epithelial cells and purifying and identifying the resulting biotinylated proteins by mass spectrometry.", "output": "biotin." }, { "input": "Out of a predicted proteome of =~ 9000 we identified more than 400 proteins tagged by biotin ligase fused to ZO - 1, with both identical and distinct proteins near the N - and C - terminal ends.", "output": "biotin, N, C." }, { "input": "Those proximal to the N - terminus were enriched in transmembrane tight junction proteins and those proximal to the C - terminus were enriched in cytoskeletal proteins.", "output": "There is no related enetity." }, { "input": "We also identified many unexpected, but easily rationalized proteins.", "output": "There is no related enetity." }, { "input": "In addition, functional networks of interacting proteins were tagged, such as the basolateral but not apical polarity network.", "output": "There is no related enetity." }, { "input": "These results provide a rich inventory of proteins and potential novel insights into functions and protein networks that should catalyze further understanding of tight junction biology.", "output": "There is no related enetity." }, { "input": "Unexpectedly, the technique demonstrates high spatial resolution which could be generally applied to defining subcellular protein compartmentalization.", "output": "There is no related enetity." }, { "input": "Treatment -, Patient -, and Disease - Related Factors and the Emergence of Adverse Events with Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia.", "output": "Tyrosine." }, { "input": "Four breakpoint cluster region ( BCR ) - ABL1 tyrosine kinase inhibitors ( TKIs ) are currently available for the treatment of chronic myeloid leukemia ( CML ): imatinib, nilotinib, dasatinib, and bosutinib.", "output": "tyrosine, imatinib, nilotinib, dasatinib, bosutinib." }, { "input": "Choosing the most appropriate TKI requires clinicians to consider a host of patient -, disease -, and treatment - related factors, not the least of which include the safety profiles of the agents.", "output": "There is no related enetity." }, { "input": "This review discusses the potential impact of treatment -, patient -, and disease - related characteristics on the emergence of adverse events during TKI therapy, with a focus on the underlying mechanisms believed to be responsible for a number of important adverse events associated with these agents and what implications they may have for treatment choice, particularly in the setting of first - line treatment.", "output": "There is no related enetity." }, { "input": "A literature search of the PubMed database was conducted to identify articles that described the molecular mechanisms of BCR - ABL1 - mediated leukemic transformation, the efficacy and safety of imatinib, nilotinib, dasatinib, and bosutinib in patients with CML, the kinase - binding spectrum of each TKI, and evidence suggesting a link between the TKI - binding profile and adverse events.", "output": "imatinib, nilotinib, dasatinib, bosutinib." }, { "input": "The pattern of adverse events associated with each agent is important when selecting treatment with a TKI.", "output": "There is no related enetity." }, { "input": "Clinical studies suggest that imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles, which are in part attributable to the specificity and selectivity of each agent.", "output": "imatinib, nilotinib, dasatinib, bosutinib." }, { "input": "Although much basic research must be conducted to further illuminate the mechanisms responsible for TKI - related adverse events, on - and off - target effects are believed to be at least partly responsible for cardiovascular toxicity, myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic toxicity.", "output": "There is no related enetity." }, { "input": "Increased understanding of the factors that affect TKI - associated adverse events and long - term safety data will enable a more informed approach to the selection of therapy best suited to the individual needs of patients with CML.", "output": "There is no related enetity." }, { "input": "A Localized Surface Plasmon Resonance - Based Multicolor Electrochromic Device with Electrochemically Size - Controlled Silver Nanoparticles.", "output": "Silver." }, { "input": "The first localized surface plasmon resonance ( LSPR ) - based multicolor electrochromic device with reversible five optical states is demonstrated.", "output": "There is no related enetity." }, { "input": "In this device, the size of deposited silver nanoparticles is electrochemically controlled using a voltage - step method in which two different voltages are applied successively.", "output": "silver." }, { "input": "The electrochemically size - controlled silver nanoparticles enable a reversible multiple - color change by a shift of the LSPR band.", "output": "silver." }, { "input": "Validation of a Novel Approach for Dose Individualization in Pharmacotherapy Using Gabapentin in a Proof of Principles Study.", "output": "Gabapentin." }, { "input": "STUDY OBJECTIVE: To demonstrate the premise of individualized dosing charts ( IDCs ) as a clinical - bedside decision - support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic ( PK ) behavior of the patient, to calculate the optimal sampling schedule ( OSS ), which minimizes the number of blood samples per patient.", "output": "There is no related enetity." }, { "input": "The approach is illustrated with available PK data for gabapentin.", "output": "gabapentin." }, { "input": "DESIGN: Retrospective proof of principles study using gabapentin PK data from a published clinical trial.", "output": "gabapentin." }, { "input": "PATIENTS: Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36 hours after administration of a single dose of gabapentin 400 mg, and plasma concentrations were determined at 14 time points.", "output": "gabapentin, gabapentin." }, { "input": "MEASUREMENTS AND MAIN RESULTS: When the PK profiles were different between subjects, the IDCs are dramatically different from each other and from the IDC for an \" average \" patient representing the patient population.", "output": "There is no related enetity." }, { "input": "The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range.", "output": "There is no related enetity." }, { "input": "An optimal sampling methodology based on the assumption - free Bayesian approach is used to distinguish the PK profile of an individual patient from the patient population.", "output": "There is no related enetity." }, { "input": "In the case of gabapentin, only two optimally selected test blood samples, at 1. 5 and 6 hours after administration of a single doses, were necessary.", "output": "gabapentin." }, { "input": "The average sensitivity and the average specificity of the OSS was 99 % and 96 %, respectively.", "output": "There is no related enetity." }, { "input": "CONCLUSION: IDCs display the risk of a patient violating the target concentration range for any dosage regimen.", "output": "There is no related enetity." }, { "input": "They can be used as a clinical - bedside decision - support tool in a patient - physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance.", "output": "There is no related enetity." }, { "input": "By using the assumption - free Bayesian approach and the OSS, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity.", "output": "There is no related enetity." }, { "input": "Prospective studies are being planned to validate the encouraging results.", "output": "There is no related enetity." }, { "input": "This approach can be extended to any drug if PK data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention.", "output": "There is no related enetity." }, { "input": "Impact of Sildenafil on Survival of Patients With Eisenmenger Syndrome.", "output": "Sildenafil." }, { "input": "The favorable effects of short - term use of sildenafil on patients with Eisenmenger syndrome have been reported.", "output": "sildenafil." }, { "input": "We further studied the impact of long - term use of sildenafil on survival of these patients.", "output": "sildenafil." }, { "input": "In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected.", "output": "There is no related enetity." }, { "input": "Patients were followed - up either by telephone contacts or during visits in our out - patient clinic.", "output": "There is no related enetity." }, { "input": "A total of 121 patients ( 68 patients in conventional group and 53 patients in sildenafil group ) were finally included and 29 patients were re - evaluated after sildenafil therapy for 3 - 4 months.", "output": "sildenafil, sildenafil." }, { "input": "Compared with the baseline, a 6 - minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment.", "output": "sildenafil." }, { "input": "During a median follow - up period of 35. 8 months, 15 patients died ( 11 patients in conventional group ).", "output": "There is no related enetity." }, { "input": "The 1 - and 3 - year survival rates in sildenafil group were 97. 0 % and 95. 2 %, significantly higher than 90. 6 % and 82. 9 % in conventional group P =. 025 ).", "output": "sildenafil." }, { "input": "Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival.", "output": "sildenafil." }, { "input": "Therefore, long - term sildenafil therapy improved survival in patients with Eisenmenger syndrome.", "output": "sildenafil." }, { "input": "Clinical update on the management of atrial fibrillation.", "output": "There is no related enetity." }, { "input": "Atrial fibrillation ( AF ) is a cardiac arrhythmia associated with significant morbidity and mortality, affecting more than 3 million people in the United States and 1 - 2 % of the population worldwide.", "output": "There is no related enetity." }, { "input": "Its estimated prevalence is expected to double within the next 50 years.", "output": "There is no related enetity." }, { "input": "During the past decade, there have been significant advances in the treatment of AF.", "output": "There is no related enetity." }, { "input": "Studies have demonstrated that a rate control strategy, with a target resting heart rate between 80 and 100 beats / minute, is recommended over rhythm control in the vast majority of patients.", "output": "There is no related enetity." }, { "input": "The CHA2 DS2 >= ( congestive heart failure, hypertension, age >= 65 yrs, diabetes mellitus, stroke or transient ischemic attack, vascular disease, female gender ) scoring system is a potentially useful stroke risk stratification tool that incorporates additional risk factors to the commonly used CHADS2 ( congestive heart failure, hypertension, age >= 75 years, diabetes mellitus, stroke transient ischemic attack ) scoring tool.", "output": "There is no related enetity." }, { "input": "Similarly, a convenient scheme, termed HAS - BLED ( hypertension, abnormal renal / liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs / alcohol concomitantly ), to assess bleeding risk has emerged that may be useful in select patients.", "output": "alcohol." }, { "input": "Furthermore, new antithrombotic strategies have been developed as potential alternatives to warfarin, including dual - antiplatelet therapy with clopidogrel plus aspirin and the development of new oral anticoagulants such as dabigatran, rivaroxaban, and apixaban.", "output": "warfarin, clopidogrel, aspirin, dabigatran, rivaroxaban, apixaban." }, { "input": "Vernakalant has emerged as another potential option for pharmacologic conversion of AF, whereas recent trials have better defined the role of dronedarone in the maintenance of sinus rhythm.", "output": "Vernakalant, dronedarone." }, { "input": "Finally, catheter ablation represents another alternative to manage AF, whereas upstream therapy with inhibitors of the renin - angiotensin - aldosterone system, statins, and polyunsaturated fatty acids could potentially prevent the occurrence of AF.", "output": "aldosterone, statins, polyunsaturated fatty acids." }, { "input": "Despite substantial progress in the management of AF, significant uncertainty surrounds the optimal treatment of this condition.", "output": "There is no related enetity." }, { "input": "An analysis of skeletal development in osteoblast - and chondrocyte - specific Runx2 knockout mice.", "output": "There is no related enetity." }, { "input": "Global gene deletion studies in mice and humans have established the pivotal role of runt related transcription factor - 2 ( Runx2 ) in both intramembranous and endochondral ossification processes during skeletogenesis.", "output": "There is no related enetity." }, { "input": "In this study, we for the first time generated mice carrying a conditional Runx2 allele with exon 4, which encodes the Runt domain, flanked by loxP sites.", "output": "There is no related enetity." }, { "input": "These mice were crossed with alpha 1 ( I ) - collagen - Cre or alpha 1 ( II ) - collagen - Cre transgenic mice to obtain osteoblast - or chondrocyte - specific Runx2 deficient mice, respectively.", "output": "There is no related enetity." }, { "input": "As seen in Runx2 ( - / - ) mice, perinatal lethality was observed in alpha 1 ( II ) - Cre; Runx2 ( flox / flox ) mice, but this was not the case in animals in which alpha 1 ( I ) - collagen - Cre was used to delete Runx2.", "output": "There is no related enetity." }, { "input": "When using double staining with Alizarin red for mineralized matrix and Alcian blue for cartilaginous matrix, we observed previously that mineralization was totally absent at embryonic day 15. 5 throughout the body in Runx2 ( - / - ) mice, but was found in areas undergoing intramembranous ossification such as skull and clavicles in alpha 1 ( II ) - Cre; Runx2 ( flox / flox ) mice.", "output": "Alizarin red, Alcian blue." }, { "input": "In newborn alpha 1 ( II ) - Cre; Runx2 ( flox / flox ) mice, mineralization impairment was restricted to skeletal areas undergoing endochondral ossification including long bones and vertebrae.", "output": "There is no related enetity." }, { "input": "In contrast, no apparent skeletal abnormalities were seen in mutant embryo, newborn, and 3 - to 6 - week old - mice in which Runx2 had been deleted with the alpha 1 ( I ) - collagen - Cre driver.", "output": "There is no related enetity." }, { "input": "These results suggest that Runx2 is absolutely required for endochondral ossification during embryonic and postnatal skeletogenesis, but that disrupting its expression in already committed osteoblasts as achieved here with the alpha 1 ( I ) - collagen - Cre driver does not affect overtly intramembranous and endochondral ossification.", "output": "There is no related enetity." }, { "input": "The Runx2 floxed allele established here is undoubtedly useful for investigating the role of Runx2 in particular cells.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "Bone stiffness and failure load are related with clinical parameters in men with chronic obstructive pulmonary disease.", "output": "There is no related enetity." }, { "input": "Osteoporosis is frequently seen in patients with chronic obstructive pulmonary disease ( COPD ).", "output": "There is no related enetity." }, { "input": "Since research on bone structure and bone strength in COPD patients is limited, the objectives of this pilot study were: 1.", "output": "There is no related enetity." }, { "input": "To compare bone structure, stiffness and failure load, measured at the peripheral skeleton, between men with and without COPD after stratification for areal bone mineral density ( aBMD ), and 2.", "output": "There is no related enetity." }, { "input": "To relate clinical parameters with bone stiffness and failure load in men with COPD.", "output": "There is no related enetity." }, { "input": "We included 30 men with COPD ( normal aBMD n = 18, osteoporosis n = 12 ) and 17 men without COPD ( normal aBMD n = 9, osteoporosis n = 8 ).", "output": "There is no related enetity." }, { "input": "We assessed pack - years of smoking, body mass index ( BMI ), fat free mass index ( FFMI ), pulmonary function ( FEV1, FEV1 / FVC, DLCO and KCO ) and extent of emphysema.", "output": "There is no related enetity." }, { "input": "Bone structure of the distal radius and tibia was assessed by high resolution peripheral quantitative computed tomography ( HR - pQCT ), and bone stiffness and failure load of the distal radius and tibia were estimated from micro finite element analysis ( micro FEA ).", "output": "There is no related enetity." }, { "input": "After stratification for aBMD and COPD, men with osteoporosis showed abnormal bone structure ( p < 0. 01 ), lower bone stiffness ( p < 0. 01 ) and lower failure load ( p < 0. 01 ) compared with men with normal aBMD, and men with COPD had comparable bone structure, stiffness and failure load compared with men without COPD.", "output": "There is no related enetity." }, { "input": "In men with COPD, lower FFMI was related with lower bone stiffness and failure load of the radius and tibia and lower DLCO and KCO were related with lower bone stiffness and failure load of the tibia after normalization with respect to femoral neck aBMD.", "output": "There is no related enetity." }, { "input": "Thus, this pilot study could not detect differences in bone structure, stiffness and failure load between men with and without COPD after stratification for aBMD.", "output": "There is no related enetity." }, { "input": "FFMI and gas transfer capacity of the lung were significantly related with bone stiffness and failure load in men with COPD after normalization with respect to femoral neck aBMD.", "output": "There is no related enetity." }, { "input": "(c) 2013 American Society for Bone and Mineral Research.", "output": "There is no related enetity." }, { "input": "In Situ Study of CO Oxidation on HOPG - Supported Pt Nanoparticles.", "output": "CO, Pt." }, { "input": "Catalyzed CO oxidation: A newly designed high - pressure flow cell is utilized to study CO oxidation on Pt nanoparticles in situ by simultaneous quadrupole mass spectrometry and high - pressure X - ray photoelectron spectroscopy.", "output": "CO, CO, Pt." }, { "input": "The spectroscopy data show that the active catalyst consists of metallic Pt with both chemisorbed O and patches / shell of surface oxides.", "output": "Pt, O, oxides." }, { "input": "Clinical Study to Assess the Efficacy and Safety of a Citrus Polyphenolic Extract of Red Orange, Grapefruit, and Orange ( Sinetrol - XPur ) on Weight Management and Metabolic Parameters in Healthy Overweight Individuals.", "output": "There is no related enetity." }, { "input": "The present study investigated the efficacy and safety effects of Sinetrol - XPur ( polyphenolic citrus dry extract ) in weight management; metabolic parameters; and inflammatory, glycemic and oxidative status.", "output": "There is no related enetity." }, { "input": "In a 12 - week, randomized, double - blind, placebo - controlled trial, Sinetrol - XPur was given to overweight subjects twice daily with meals in the tested group ( N = 47 ) versus a placebo group ( N = 48 ).", "output": "There is no related enetity." }, { "input": "Waist and hip circumference and abdominal fat were decreased in the Sinetrol - XPur group as compared with the placebo group ( p < 0. 0001 ) ( - 5. 71 % vs - 1. 56 % for waist, - 4. 71 % vs - 1. 35 % for hip and - 9. 73 % vs - 3. 18 % for fat ).", "output": "There is no related enetity." }, { "input": "Inflammatory markers were reduced ( C - reactive protein: - 22. 87 % vs + 61 %; fibrinogen: - 19. 93 % vs - 1. 61 %, p < 0. 01 ).", "output": "There is no related enetity." }, { "input": "Oxidative stress was lowered as seen by the reduction of malondialdehyde ( - 14. 03 % vs 2. 76 % ) and the increase in superoxide dismutase and glutathione ( 17. 38 % vs 2. 19 % and 4. 63 % vs - 2. 36 %, respectively, p < 0. 01 ).", "output": "malondialdehyde, superoxide, glutathione." }, { "input": "No adverse effects were observed.", "output": "There is no related enetity." }, { "input": "Kidney, liver, and lipid panels remained unchanged.", "output": "There is no related enetity." }, { "input": "These results indicated that Sinetrol - XPur supplementation is a viable option for reducing abdominal fat, waist and hip circumference, and body weight and for improving inflammatory, glycemic, and oxidative status in healthy overweight individuals.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "The electronic origin of unusually large ( n ) JFN coupling constants in some fluoroximes.", "output": "fluoroximes." }, { "input": "SOPPA ( CCSD ) calculations show that the FC term is the most important contribution to the through - space transmission of JFN coupling constants for the fluoroximes studied in this work.", "output": "fluoroximes." }, { "input": "Because of the well - known behavior of FC term, a new rationalization for the experimental ( TS ) JFN SSCC is presented.", "output": "There is no related enetity." }, { "input": "It is mainly based on the overlap matrix ( Sij ) between fluorine and nitrogen lone pairs obtained from NBO analyses.", "output": "fluorine, nitrogen." }, { "input": "An expression is proposed to take into account the influence of the electronic density ( Dij ) between coupled nuclei as well as the s % character at the site of the coupling nuclei of bonds and non - bonding electron pairs involved in Dij.", "output": "There is no related enetity." }, { "input": "In using this approach, a linear correlation between ( TS ) JFN versus Dij is obtained.", "output": "There is no related enetity." }, { "input": "The most important aspect of this rationalization is related to the facility for understanding the behavior of some unusual experimental coupling constants.", "output": "There is no related enetity." }, { "input": "It is shown that, at least in this case, the electronic origin of the so - called through - space coupling is transmitted through to the overlap of orbitals on the coupled atoms, suggesting that, at least for these compounds, instead of through - space coupling, it should better be dubbed as ' through overlapping orbital coupling '.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Vibrational sum - frequency generation activity of a 2, 4 - dinitrophenyl phospholipid hybrid bilayer: retrieving orientational parameters from a DFT analysis of experimental data.", "output": "2 , 4 - dinitrophenyl." }, { "input": "The vibrational nonlinear activity of films of 2, 4 - dinitrophenyl phospholipid ( DNP ) at the solid interface is measured by sum - frequency generation spectroscopy ( SFG ).", "output": "2 , 4 - dinitrophenyl." }, { "input": "Hybrid bilayers are formed by a Langmuir - Schaefer approach in which the lipid layer is physisorbed on top of a self - assembled monolayer of dodecanethiol on Pt with the polar heads pointing out from the surface.", "output": "dodecanethiol, Pt." }, { "input": "The SFG response is investigated in two vibrational frequency domains, namely, 3050 - 2750 and 1375 - 1240 cm ( - 1 ).", "output": "There is no related enetity." }, { "input": "The first region probes the CH stretching modes of DNP films, and the latter explores the vibrational nonlinear activity of the 2, 4 - dinitroaniline moiety of the polar head of the lipid.", "output": "CH, 2 , 4 - dinitroaniline." }, { "input": "Analysis of the CH stretching vibrations suggests substantial conformational order of the aliphatic chains with only a few gauche defects.", "output": "CH." }, { "input": "To reliably assign the detected SFG signals to specific molecular vibrations, DFT calculations of the IR and Raman activities of molecular models are performed and compared to experimental solid - state spectra.", "output": "There is no related enetity." }, { "input": "This allows unambiguous assignment of the observed SFG vibrations to molecular modes localized on the 2, 4 - dinitroaniline moiety of the polar head of DNP.", "output": "2 , 4 - dinitroaniline." }, { "input": "Then, SFG spectra of DNP in the 1375 - 1240 cm ( - 1 ) frequency range are simulated and compared with experimental ones, and thus the 1, 4 - axis of the 2, 4 - dinitrophenyl head is estimated to have tilt and rotation angles of 45 +/- 5 degrees and 0 +/- 30 degrees, respectively.", "output": "2 , 4 - dinitrophenyl." }, { "input": "Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers.", "output": "There is no related enetity." }, { "input": "The binding of transcription factors ( TFs ) to their specific motifs in genomic regulatory regions is commonly studied in isolation.", "output": "There is no related enetity." }, { "input": "However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers, and to infer the precise nature of these interactions.", "output": "There is no related enetity." }, { "input": "So far, only a small number of such dimeric complexes are known.", "output": "There is no related enetity." }, { "input": "Here, we present an algorithm for predicting cell - type - specific TF - TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines.", "output": "There is no related enetity." }, { "input": "We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell - type - specific DNase I hypersensitive sites.", "output": "There is no related enetity." }, { "input": "Based on ~ 1. 4 billion tests for motif complex enrichment, we predicted 603 highly significant cell - type - specific TF dimers, the vast majority of which are novel.", "output": "There is no related enetity." }, { "input": "Our predictions included 76 % ( 19 / 25 ) of the known dimeric complexes and showed significant overlap with an experimental database of protein - protein interactions.", "output": "There is no related enetity." }, { "input": "They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns.", "output": "There is no related enetity." }, { "input": "Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA - bound complex.", "output": "There is no related enetity." }, { "input": "Overall, our results indicate that chromatin openness profiles are highly predictive of cell - type - specific TF - TF interactions.", "output": "There is no related enetity." }, { "input": "Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types.", "output": "There is no related enetity." }, { "input": "Genomic variation in the MAP3K5 gene is associated with beta - thalassemia disease severity and hydroxyurea treatment efficacy.", "output": "hydroxyurea." }, { "input": "Aim: In this study we explored the association between genetic variations in MAP3K5 and PDE7B genes, residing on chromosome 6q23, and disease severity in beta - hemoglobinopathy patients, as well as the association between these variants with response to hydroxyurea ( HU ) treatment.", "output": "hydroxyurea." }, { "input": "Furthermore, we examined MAP3K5 expression in the context of high fetal hemoglobin ( HbF ) and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals.", "output": "There is no related enetity." }, { "input": "Materials & methods: For this purpose, we genotyped beta - thalassemia intermedia and major patients and healthy controls, as well as a cohort of compound heterozygous sickle cell disease / beta - thalassemia patients receiving HU as HbF augmentation treatment.", "output": "There is no related enetity." }, { "input": "Furthermore, we examined MAP3K5 expression in the context of high HbF and upon HU treatment in erythroid progenitor cells from healthy and KLF1 haploinsufficient individuals.", "output": "There is no related enetity." }, { "input": "Results: A short tandem repeat in the MAP3K5 promoter and two intronic MAP3K5 gene variants, as well as a PDE7B variant, are associated with low HbF levels and a severe disease phenotype.", "output": "There is no related enetity." }, { "input": "Moreover, MAP3K5 mRNA expression levels are altered in the context of high HbF and are affected by the presence of HU.", "output": "There is no related enetity." }, { "input": "Lastly, the abovementioned MAP3K5 variants are associated with HU treatment efficacy.", "output": "There is no related enetity." }, { "input": "Conclusion: Our data suggest that these MAP3K5 variants are indicative of beta - thalassemia disease severity and response to HU treatment.", "output": "There is no related enetity." }, { "input": "Original submitted 24 September 2012; Revision submitted 4 February 2013.", "output": "There is no related enetity." }, { "input": "Association of ATP - binding cassette transporter variants with the risk of Alzheimer ' s disease.", "output": "ATP." }, { "input": "Aim: A number of studies have demonstrated that ABCB1 and BCRP ( ABCG2 ) actively transport A beta.", "output": "There is no related enetity." }, { "input": "We aimed to investigate the association of genetic variants of selected multidrug transporters with Alzheimer ' s disease ( AD ) in histopathologically confirmed AD cases and controls.", "output": "There is no related enetity." }, { "input": "Materials & methods: DNA from brain tissue of 71 AD cases with Consortium to Establish a Registry for Alzheimer ' s Disease ( CERAD ) neuropathological stages B / C and 81 controls was genotyped for selected variants in ABCA1, ABCA7, ABCB1, ABCC2 and ABCG2.", "output": "There is no related enetity." }, { "input": "In addition, the APOE4 status was analyzed.", "output": "There is no related enetity." }, { "input": "Results: The novel ABCA7 SNP, rs3752246, tended to be associated with AD in our study.", "output": "There is no related enetity." }, { "input": "Variants in ABCB1 were significantly less frequent in AD cases older than 65 years of age and among females.", "output": "There is no related enetity." }, { "input": "This association of ABCB1 2677G > T ( rs2032582 ) was more pronounced in APOE4 - negative cases ( p = 0. 005 ).", "output": "There is no related enetity." }, { "input": "However, only ABCC2 3972C > T ( rs3740066 ) was significantly associated with AD risk after logistic regression analysis including all variants.", "output": "There is no related enetity." }, { "input": "Other transporters showed a lack of association.", "output": "There is no related enetity." }, { "input": "Conclusion: Our results support the hypothesis that ABCB1 and possibly other ABC - transporters are involved in the process of A beta accumulation in the aging brain and may modulate the risk for AD in an allele - specific manner, and thus might represent a new target for prevention and treatment of AD.", "output": "There is no related enetity." }, { "input": "Original submitted 8 October 2012; Revision submitted 22 January 2013.", "output": "There is no related enetity." }, { "input": "Association of a functional FAAH polymorphism with methamphetamine - induced symptoms and dependence in a Malaysian population.", "output": "methamphetamine." }, { "input": "Aim: FAAH is a membrane enzyme that terminates the activity of a large class of endogenous signaling lipids.", "output": "There is no related enetity." }, { "input": "Recent studies suggest that the FAAH Pro129Thr polymorphism is a common mutation in the FAAH gene that is significantly associated with drug - addictive traits.", "output": "There is no related enetity." }, { "input": "This study investigated the association of the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence, methamphetamine - induced psychosis, manic episodes and panic disorder in a Malaysian population.", "output": "methamphetamine, methamphetamine." }, { "input": "Materials & methods: This polymorphism was genotyped in 232 male methamphetamine - dependent subjects and in 241 male controls of four different ethnicities: Malay, Chinese, Kadazan - Dusun and Bajau.", "output": "methamphetamine." }, { "input": "Intergroup statistical analyses were performed by using the chi ( 2 ) - square test and Fisher ' s exact test, where necessary.", "output": "There is no related enetity." }, { "input": "In cases of multiple comparisons, the Bonferroni correction was performed.", "output": "There is no related enetity." }, { "input": "Results: Our results indicated that the FAAH Pro129Thr polymorphism showed a significant association with risk of methamphetamine dependence in the pooled subjects ( odds ratio [ OR ]: 2. 017; p < 0. 001 ) and in the Malay ( OR: 2. 829; p < 0. 001 ) and Chinese ( OR: 3. 685; p < 0. 001 ) groups.", "output": "methamphetamine." }, { "input": "We also found an association of this polymorphism with episodes of methamphetamine - induced mania in the Malay group ( OR: 2. 836; p = 0. 035 ).", "output": "methamphetamine." }, { "input": "However, there was no association between this polymorphism and age of onset of drug use or the occurrence of methamphetamine - induced psychosis or of panic disorder.", "output": "methamphetamine." }, { "input": "Conclusion: Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to methamphetamine dependence in the Malay and Chinese ethnic groups.", "output": "methamphetamine." }, { "input": "Original submitted 4 October 2012; Revision submitted 1 February 2013.", "output": "There is no related enetity." }, { "input": "Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg.", "output": "There is no related enetity." }, { "input": "Opioids are the cornerstone of analgesic therapy and are used as a substitution therapy for opiate addiction.", "output": "There is no related enetity." }, { "input": "Interindividual variability in response to opioids is a significant challenge in the management of pain and substitution.", "output": "There is no related enetity." }, { "input": "Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations.", "output": "There is no related enetity." }, { "input": "Many studies have investigated the association between genetic factors and the variability of response to opioids.", "output": "There is no related enetity." }, { "input": "Variants in genes encoding proteins implied in opioid pharmacokinetics ( absorption, distribution, metabolism, excretion and toxicity ), together with those implied in opioids direct and indirect pharmacodynamics ( genes of opioid receptors and monoaminergic systems ), are the most studied.", "output": "There is no related enetity." }, { "input": "Many association studies have not been replicated.", "output": "There is no related enetity." }, { "input": "The purpose of this article is to summarize pharmacogenetic data associated with some opioids frequently encountered in managed care settings.", "output": "There is no related enetity." }, { "input": "New Analysis of the nu 3 and nu 4 Bands of HNO3 in the 7. 6 mu m Region.", "output": "HNO3." }, { "input": "A new line position analysis of the nu3 and nu4 bands of nitric acid ( HNO3 ) at 1326. 186 and 1303. 072 cm - 1 together with its associated interacting bands is presented.", "output": "nitric acid, HNO3." }, { "input": "The 3 ^ 1 and 4 ^ 1 energy levels were obtained from an extended analysis of high resolution Fourier transform spectra recorded at Giessen in the 7. 6 micro m region.", "output": "There is no related enetity." }, { "input": "The energy levels of 3 ^ 1 and 4 ^ 1 upper states of nitric acid are strongly interacting with those of the 9 ^ 3, 6 ^ 2, 5 ^ 19 ^ 1 and 7 ^ 18 ^ 1 dark states centered at 1288. 899, 1289. 46, 1341. 05 and 1343. 78 cm - 1, respectively.", "output": "nitric acid." }, { "input": "Informations on these perturbing dark states were achieved through previous partial investigations of hot bands in high resolution Fourier transform spectra recorded at 22 micro m in Giessen ( for 3nu9 - 2nu9 and 3nu9 - nu5 ), at 12 micro m in Denver ( for 3nu9 - nu9 ), and at 11 micro m in Orsay ( for nu5 + nu9 - nu9 ).", "output": "There is no related enetity." }, { "input": "The energy levels calculation accounts for the various Fermi, anharmonic, A - type, B - type and C - type Coriolis resonances which couple together the { 6 ^ 2, 9 ^ 3, 4 ^ 1, 3 ^ 1, 5 ^ 19 ^ 1, 7 ^ 18 ^ 1 } interacting energy levels.", "output": "There is no related enetity." }, { "input": "For nitric acid the nu9 mode ( OH torsion relative to the - NO2 moiety ) is a large amplitude motion.", "output": "nitric acid, OH, NO2." }, { "input": "The theoretical model used in this work accounts also for large amplitude effects in the 93 dark state which lead to a splitting of the 93 energy levels of about 0. 060 cm - 1.", "output": "There is no related enetity." }, { "input": "In this way the existence of \" torsional \" splittings for several nu4 perturbed lines was explained by the occurrence of local A - type and B - type Coriolis resonances coupling the 4 ^ 1 energy levels with those of 93.", "output": "There is no related enetity." }, { "input": "Because four dark bands had to be accounted for in the model, the results of the energy levels calculations are reasonable, although not perfect.", "output": "There is no related enetity." }, { "input": "However a very significant improvement was achieved in term of understanding the 7. 6 micro m absorbing bands of nitric acid as compared to the analysis of the nu3 and nu4 bands performed several years ago [ Perrin, A.; Lado - Bordowski, O.; Valentin, A. Mol. Phys. 1989, 67, 249 - 267 ].", "output": "nitric acid." }, { "input": "Finally the present analysis also features, for the first time, the nu3 + nu9 - nu9 hot band located at 1331. 09 cm - 1.", "output": "There is no related enetity." }, { "input": "Impact of longitudinal exposure to mycophenolic acid on acute rejection in renal - transplant recipients using a joint modeling approach.", "output": "mycophenolic acid." }, { "input": "This study aimed to investigate the association between longitudinal exposure to mycophenolic acid ( MPA ) and acute rejection ( AR ) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association.", "output": "mycophenolic acid, MPA, MPA." }, { "input": "A joint model, adjusted for monitoring strategy ( fixed - dose versus concentration - controlled ) and recipient age, was developed; it combined a mixed - effects model to describe the whole pattern of MPA exposure ( i. e. area under the concentration - time curve ( AUC ) ) and a survival model.", "output": "MPA." }, { "input": "MPA AUC thresholds were determined using time - dependent receiver - operating characteristics ( ROC ) curves.", "output": "MPA." }, { "input": "Data from 490 adult renal - transplant recipients, representative of the general population of adult renal - transplant patients ( i. e. including patients considered at low immunological risk - enrolled in the OPERA trial as well as second renal transplant and patients co - treated by either cyclosporine or tacrolimus ), were analyzed.", "output": "cyclosporine, tacrolimus." }, { "input": "A significant association was found between the longitudinal exposure to MPA ( MPA AUCs = f ( t ) ) and AR ( p = 0. 0081 ), and validated by bootstrapping.", "output": "MPA, MPA." }, { "input": "A significant positive correlation was observed between time post - transplantation and ROC thresholds which increased in average from 35mgh / L in the first days to 41mgh / L beyond six months post - transplantation ( p < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Using a new modeling approach which recognizes the repeated measures in a same patient, this study supports the association between MPA exposure and AR.", "output": "MPA." }, { "input": "One - year supplementation with a grape extract containing resveratrol modulates inflammatory - related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.", "output": "resveratrol." }, { "input": "Numerous studies have shown that resveratrol ( RES ) exerts anti - inflammatory effects but human trials evidencing these effects in vivo are limited.", "output": "resveratrol, RES." }, { "input": "Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood.", "output": "RES." }, { "input": "Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( PBMCs ) associated to the one - year daily intake of a RES enriched ( 8mg ) grape extract ( GE - RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ).", "output": "RES, RES." }, { "input": "We used microarrays and RT - PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE - RES in comparison to a placebo and GE lacking RES.", "output": "RES, RES." }, { "input": "We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers.", "output": "There is no related enetity." }, { "input": "Our results showed that supplementation with GE or GE - RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients.", "output": "RES, glucose." }, { "input": "We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL - 6 levels.", "output": "There is no related enetity." }, { "input": "The expression of the pro - inflammatory cytokines CCL3, IL - 1 beta and TNF - alpha was significantly reduced and that of the transcriptional repressor LRRFIP - 1 increased in PBMCs from patients taking the GE - RES extract.", "output": "RES." }, { "input": "Also, a group of miRs involved in the regulation of the inflammatory response: miR - 21, miR - 181b, miR - 663, miR - 30c2, miR - 155 and miR - 34a were found to be highly correlated and altered in the group consuming the GE - RES for 12 months.", "output": "RES." }, { "input": "Our results provide preliminary evidence that long - term supplementation with a grape extract containing RES downregulates the expression of key pro - inflammatory cytokines with the involvement of inflammation - related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.", "output": "RES." }, { "input": "Systems analysis of genetic variation in MPTP neurotoxicity in mice.", "output": "MPTP." }, { "input": "We analyzed genetic variation in severity of neuronal damage using the known dopaminergic neurotoxicant, MPTP, as a prototypical chemical denervation agent.", "output": "MPTP." }, { "input": "Male mice from ten members of the BXD family of recombinant inbred strains received 12. 5mg / kg MPTP s. c.", "output": "MPTP." }, { "input": "( vs. saline ) and 48h later brains were taken for multiple related biochemical analyses.", "output": "There is no related enetity." }, { "input": "Striatal dopamine ( DA ) and its metabolites, DOPAC and HVA, and serotonin and its metabolite, 5 - HIAAA, were analyzed by HPLC.", "output": "dopamine, DOPAC, HVA, serotonin, 5 - HIAAA." }, { "input": "DA turnover was assessed using DOPAC / DA and HVA / DA ratios.", "output": "DOPAC, HVA." }, { "input": "Striatal tyrosine hydroxylase ( TH ), glial fibrilary acidic protein ( GFAP ), and iron content in ventral midbrain were quantified.", "output": "tyrosine, iron." }, { "input": "All dopamine measures, as well as TH and GFAP, demonstrated wide, genotype - dependent differences in response to MPTP.", "output": "dopamine, MPTP." }, { "input": "Serotonin was largely unaffected.", "output": "Serotonin." }, { "input": "Principal components analysis ( PC ) on difference values, saline minus MPTP, for DA, DOPAC, HVA, and TH, yielded a dominant principal component.", "output": "MPTP, DOPAC, HVA." }, { "input": "The PC trait residuals for each genotype were compared against complementary expression data for striatum of the same strains.", "output": "There is no related enetity." }, { "input": "Three transcripts representing Mtap2, Lancl 1, and Kansl1l were highly correlated with the PC, as was the difference score, MPTP minus saline for GFAP.", "output": "MPTP." }, { "input": "This systems approach to the study of environmental neurotoxicants holds promise to define individual genetic differences that contribute to variability in susceptibility to risk factors for diseases such as Parkinson ' s disease.", "output": "There is no related enetity." }, { "input": "Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives.", "output": "rotundic acid." }, { "input": "In the present investigation, 16 new rotundic acid ( RA ) derivatives modified at the C - 3, C - 23 and C - 28 positions were synthesized.", "output": "rotundic acid." }, { "input": "The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC - A1 and NCI - H446 human tumor cell lines by MTT assay.", "output": "MTT." }, { "input": "Among these derivatives, compounds 4 - 7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 < 10 mu M.", "output": "There is no related enetity." }, { "input": "The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis.", "output": "There is no related enetity." }, { "input": "The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase - 3 and Bax, and decreasing protein expression of Bcl - 2.", "output": "There is no related enetity." }, { "input": "In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate.", "output": "There is no related enetity." }, { "input": "Inhibition of PDGFR alpha by MEDI - 575 Reduces Tumor Growth and Stromal Fibroblast Content in a Model of Non - Small Cell Lung Cancer.", "output": "There is no related enetity." }, { "input": "Platelet - derived growth factor receptor alpha ( PDGFR alpha ) is a receptor tyrosine kinase that promotes cell survival and is expressed in both the tumor and the stromal components of human cancers.", "output": "tyrosine." }, { "input": "We have developed a fully human monoclonal antibody, MEDI - 575, that selectively binds to human PDGFR alpha with high affinity, with no observable affinity for murine PDGFR alpha.", "output": "There is no related enetity." }, { "input": "To more fully characterize the role of PDGFR alpha in the regulation of tumor stroma, we evaluated the in vivo antitumor effects of MEDI - 575 in tumor - bearing SCID mice and in genetically altered SCID mice expressing human PDGFR alpha in place of murine PDGFR alpha.", "output": "There is no related enetity." }, { "input": "We utilized the Calu - 6 non - small cell lung cancer model, because it lacks an in vitro proliferative response to PDGFR alpha activation.", "output": "There is no related enetity." }, { "input": "Antitumor activity was observed when the study was performed in mice expressing the human receptor, but no activity was observed in the mice expressing the murine receptor.", "output": "There is no related enetity." }, { "input": "Immunohistological analysis of tumors from mice expressing human PDGFR alpha showed a highly significant reduction in stromal fibroblast content and only minor changes in tumor proliferative index in tumors exposed to MEDI - 575 compared to the results seen in vehicle - treated tumors or tumors from mice expressing murine PDGFR alpha.", "output": "There is no related enetity." }, { "input": "Additional in vitro studies indicated that exposure of primary cancer - associated fibroblasts to MEDI - 575 can directly affect proliferation and key signaling pathways in these cells.", "output": "There is no related enetity." }, { "input": "These results highlight the potential for observing antitumor activity with MEDI - 575 through modulation of the stromal component of tumors and confirm that the PDGFR alpha pathway can play a role in maintaining a tumor microenvironment conducive to tumor growth.", "output": "There is no related enetity." }, { "input": "Supramolecular H - bonded porous networks at surfaces: exploiting primary and secondary interactions in a bi - component melamine - xanthine system.", "output": "H, melamine, xanthine." }, { "input": "The control over the formation of a bi - component porous network was attained by the self - assembly at a solid - liquid interface by exploiting both primary and secondary non - covalent interactions between melamine and N ( 3 ) - alkylated xanthine modules.", "output": "melamine, N ( 3 ) - alkylated xanthine." }, { "input": "Porphyromonas gingivalis virulence factor gingipain RgpB shows a unique zymogenic mechanism for cysteine peptidases.", "output": "cysteine." }, { "input": "Zymogenicity is a regulatory mechanism which prevents inadequate catalytic activity in the wrong context.", "output": "There is no related enetity." }, { "input": "It plays a central role in maintaining microbial virulence factors in an inactive form inside the pathogen until secretion.", "output": "There is no related enetity." }, { "input": "Among these virulence factors is the cysteine peptidase gingipain B ( RgpB ), which is the major virulence factor secreted by the periodontopathogen Porphyromonas gingivalis that attacks host vasculature and defense proteins.", "output": "cysteine." }, { "input": "The structure of the complex between soluble mature RgpB, consisting of a catalytic domain and an immunoglobulin - superfamily domain, and its 205 - residue N - terminal pro - domain, the largest structurally characterized to date for a cysteine peptidase, reveals a novel fold for the pro - domain that is distantly related to sugar - binding lectins.", "output": "N, cysteine, sugar." }, { "input": "It attaches laterally to the catalytic domain through a large concave surface.", "output": "There is no related enetity." }, { "input": "The main determinant for latency is a surface inhibitory loop, which approaches the active - site cleft of the enzyme on its non - primed side in a substrate - like manner.", "output": "There is no related enetity." }, { "input": "It inserts an arginine ( R126 ) into the S1 pocket, thus matching the substrate specificity of the enzyme.", "output": "arginine." }, { "input": "Downstream of R126, the polypeptide leaves the cleft, thereby preventing cleavage.", "output": "There is no related enetity." }, { "input": "Moreover, the carbonyl group of R126 establishes a very strong hydrogen bond with the co - catalytic histidine, H440, pulling it away from the catalytic cysteine, C473, and towards E381, which probably plays a role orienting the side chain of H440 during catalysis.", "output": "carbonyl, hydrogen, histidine, cysteine." }, { "input": "The present results provide the structural determinants of zymogenic inhibition of RgpB by way of a novel inhibitory mechanism for peptidases in general and open the field for the design of novel inhibitory strategies in the treatment of human periodontal disease.", "output": "There is no related enetity." }, { "input": "Disruption of Ttll5 / Stamp gene ( Tubulin tyrosine ligase - like protein 5 / SRC - 1 and TIF2 associated modulatory protein gene ) in male mice causes sperm malformation and infertility.", "output": "There is no related enetity." }, { "input": "Tubulin tyrosine ligase - like family member 5 ( TTLL5 / STAMP ) has multiple activities in cells.", "output": "There is no related enetity." }, { "input": "TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators ( SRC - 1 and TIF2 ) in glucocorticoid receptor - regulated gene induction and repression, and displays steroid - independent growth activity with several cell types.", "output": "There is no related enetity." }, { "input": "To examine TTLL5 / STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene.", "output": "There is no related enetity." }, { "input": "This mutation causes both reduced levels of STAMP mRNA and C - terminal truncation of STAMP protein.", "output": "C." }, { "input": "Homozygous targeted mutant ( Stamptm / tm ) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility.", "output": "There is no related enetity." }, { "input": "Abnormal axonemal structures with loss of tubulin doublets occur in most Stamptm / tm sperm tails in conjunction with substantial reduction in alpha - tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA.", "output": "There is no related enetity." }, { "input": "The axonemes in other structures appear unaffected.", "output": "There is no related enetity." }, { "input": "There is no obvious change in the organs for sperm development of wt vs. Stamptm / tm males despite the levels of wt STAMP mRNA in testes being 20 - fold higher than in any other organ examined.", "output": "There is no related enetity." }, { "input": "This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function.", "output": "There is no related enetity." }, { "input": "Thus, STAMP appears to participate in a unique, tissue - selective TTLL - mediated pathway for alpha - tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility.", "output": "There is no related enetity." }, { "input": "Impaired in vivo binding of MeCP2 to chromatin in the absence of its DNA methyl - binding domain.", "output": "methyl." }, { "input": "MeCP2 is a methyl - CpG - binding protein that is a main component of brain chromatin in vertebrates.", "output": "methyl." }, { "input": "In vitro studies have determined that in addition to its specific methyl - CpG - binding domain ( MBD ) MeCP2 also has several chromatin association domains.", "output": "methyl." }, { "input": "However, the specific interactions of MeCP2 with methylated or non - methylated chromatin regions and the structural characteristics of the resulting DNA associations in vivo remain poorly understood.", "output": "There is no related enetity." }, { "input": "We analysed the role of the MBD in MeCP2 - chromatin associations in vivo using an MeCP2 mutant Rett syndrome mouse model ( Mecp2 ( tm ) ( 1 ) (. ) ( 1 ) ( Jae ) ) in which exon 3 deletion results in an N - terminal truncation of the protein, including most of the MBD.", "output": "N." }, { "input": "Our results show that in mutant mice, the truncated form of MeCP2 ( Delta MeCP2 ) is expressed in different regions of the brain and liver, albeit at 50 % of its wild - type ( wt ) counterpart.", "output": "There is no related enetity." }, { "input": "In contrast to the punctate nuclear distribution characteristic of wt MeCP2, Delta MeCP2 exhibits both diffuse nuclear localization and a substantial retention in the cytoplasm, suggesting a dysfunction of nuclear transport.", "output": "There is no related enetity." }, { "input": "In mutant brain tissue, neuronal nuclei are smaller, and Delta MeCP2 chromatin is digested faster by nucleases, producing a characteristic nuclease - resistant dinucleosome.", "output": "There is no related enetity." }, { "input": "Although a fraction of Delta MeCP2 is found associated with nucleosomes, its interaction with chromatin is transient and weak.", "output": "There is no related enetity." }, { "input": "Thus, our results unequivocally demonstrate that in vivo the MBD of MeCP2 together with its adjacent region in the N - terminal domain are critical for the proper interaction of the protein with chromatin, which cannot be replaced by any other of its protein domains.", "output": "There is no related enetity." }, { "input": "E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3.", "output": "There is no related enetity." }, { "input": "The ' activating ' E2fs ( E2f1 - 3 ) are transcription factors that potently induce quiescent cells to divide.", "output": "There is no related enetity." }, { "input": "Work on cultured fibroblasts suggested they were essential for division, but in vivo analysis in the developing retina and other tissues disproved this notion.", "output": "There is no related enetity." }, { "input": "The retina, therefore, is an ideal location to assess other in vivo adenovirus E2 promoter binding factor ( E2f ) functions.", "output": "There is no related enetity." }, { "input": "It is thought that E2f1 directly induces apoptosis, whereas other activating E2fs only induce death indirectly by upregulating E2f1 expression.", "output": "There is no related enetity." }, { "input": "Indeed, mouse retinoblastoma ( Rb ) - null retinal neuron death requires E2f1, but not E2f2 or E2f3.", "output": "There is no related enetity." }, { "input": "However, we report an entirely distinct mechanism in dying cone photoreceptors.", "output": "There is no related enetity." }, { "input": "These neurons survive Rb loss, but undergo apoptosis in the cancer - prone retina lacking both Rb and its relative p107.", "output": "There is no related enetity." }, { "input": "We show that while E2f1 killed Rb / p107 null rod, bipolar and ganglion neurons, E2f2 was required and sufficient for cone death, independent of E2f1 and E2f3.", "output": "There is no related enetity." }, { "input": "Moreover, whereas E2f1 - dependent apoptosis was p53 and p73 - independent, E2f2 caused p53 - dependent cone death.", "output": "There is no related enetity." }, { "input": "Our in vivo analysis of cone photoreceptors provides unequivocal proof that E2f - induces apoptosis independent of E2f1, and reveals distinct E2f1 - and E2f2 - activated death pathways in response to a single tumorigenic insult. Cell Death and Differentiation advance online publication, 5 April 2013; doi: 10. 1038 / cdd. 2013. 24.", "output": "There is no related enetity." }, { "input": "Glucose and memory: The influence of drink, expectancy, and beliefs.", "output": "Glucose." }, { "input": "RATIONALE: An increasing number of studies suggest that glucose can enhance aspects of memory and the central methodology is the use of the glucose - placebo design.", "output": "glucose, glucose." }, { "input": "One critical issue therefore is separating the pharmacological effects of glucose from the expectancies created by consuming a drink that might contain glucose.", "output": "glucose." }, { "input": "OBJECTIVE: A modified balanced placebo design examined the role that expectancy and belief about the drink consumed has on the pharmacological changes observed following glucose consumption.", "output": "glucose." }, { "input": "METHOD: Ninety - three participants, allocated according to a drink ( glucose, placebo ) x message ( told glucose, told nothing, told placebo ) unrelated design, were administered tasks assessing immediate and delayed verbal free recall, spatial recognition and semantic verification.", "output": "glucose, glucose." }, { "input": "Each task has some evidence for hippocampus involvement, and variations in task difficulty were used to assess the idea that glucose effects are sensitive to task difficulty.", "output": "glucose." }, { "input": "RESULTS: While the messages biased drink judgements in the expected direction, judgements of drink content were at chance and glucose only enhanced delayed free recall.", "output": "glucose." }, { "input": "The subtle effects of the messages did not modify the glucose enhancement.", "output": "glucose." }, { "input": "However, believing glucose had been consumed showed an independent improvement in delayed free recall.", "output": "glucose." }, { "input": "There was no evidence that task complexity enhanced the glucose effect.", "output": "glucose." }, { "input": "CONCLUSIONS: The findings indicate that expectancy effects are unlikely to be confused with glucose enhancements, but beliefs about consuming glucose can augment performance on delayed free recall.", "output": "glucose, glucose." }, { "input": "The discussion considers the hippocampus and complexity hypotheses of glucose ' s mode of action and proposes the routine collection of drink beliefs in future studies.", "output": "glucose." }, { "input": "Kinetics of Apoptosis and Expression of Apoptosis - Related Proteins in Rat CA3 Hippocampus Cells After Experimental Diffuse Brain Injury.", "output": "There is no related enetity." }, { "input": "The present study examined kinetics of apoptosis and expression of apoptosis - related proteins Bcl - 2, Bax, and caspase - 3 in the CA3 hippocampus cells after diffuse brain injury ( DBI ) induced experimentally in rats.", "output": "There is no related enetity." }, { "input": "Percentage of apoptotic cells and expressions of above proteins were examined by flow cytometry and immunohistochemistry.", "output": "There is no related enetity." }, { "input": "Substantial neuronal apoptosis was documented in the CA3 hippocampus cells after DBI ( 22. 26 +/- 2. 97 % at 72 h after DBI vs. 2. 92 +/- 0. 88 % in sham - operated animals ).", "output": "There is no related enetity." }, { "input": "Expression of Bc1 - 2 decreased, while expression of Bax and caspase - 3 increased after DBI, with caspase - 3 expression peaking after that of Bax ( 72 vs. 48 h, respectively ).", "output": "There is no related enetity." }, { "input": "Further, the Bc1 - 2 / Bax expression ratio decreased prior to increase of caspase - 3 expression.", "output": "There is no related enetity." }, { "input": "In conclusion, cell apoptosis and altered expressions of Bcl - 2, Bax, and caspase - 3 are present in the CA3 region of hippocampus after experimental DBI.", "output": "There is no related enetity." }, { "input": "Changes in the Bc1 - 2 / Bax expression ratio may facilitate activation of caspase - 3 and aggravate neuronal apoptosis after brain injury.", "output": "There is no related enetity." }, { "input": "Molecule - Induced Peroxide Homolysis.", "output": "Peroxide." }, { "input": "The homolytic cleavage of peroxide bonds, leading to the formation of free radicals, plays an important role in the ( spontaneous ) oxidation of a wide variety of hydrocarbons in the presence of oxygen.", "output": "peroxide, hydrocarbons, oxygen." }, { "input": "Such aerobic oxidations can be desired ( e. g. for industrially applied autoxidations ) or undesired ( e. g. food deterioration ).", "output": "There is no related enetity." }, { "input": "In this contribution we provide experimental and computational evidence for a molecule - induced homolytic dissociation mechanism between alkyl peroxide and compounds featuring weakly bonded H atoms such as ( di ) unsaturated hydrocarbons.", "output": "alkyl peroxide, H, ( di ) unsaturated hydrocarbons." }, { "input": "Takotsubo cardiomyopathy associated with thyrotoxicosis: A case report and review of the literature.", "output": "There is no related enetity." }, { "input": "Background: Takotsubo or stress - induced cardiomyopathy is a form of reversible cardiomyopathy, commonly associated with emotional or physical stress.", "output": "There is no related enetity." }, { "input": "Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy with only eleven cases reported in the literature.", "output": "There is no related enetity." }, { "input": "Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves ' disease.", "output": "There is no related enetity." }, { "input": "Patient Findings: A 71 - year - old woman presented with abdominal pain, vomiting, confusion and history of weight loss.", "output": "There is no related enetity." }, { "input": "She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation due to concern for acute coronary syndrome.", "output": "There is no related enetity." }, { "input": "A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization.", "output": "There is no related enetity." }, { "input": "At that time, she was diagnosed and treated for thyroid storm.", "output": "There is no related enetity." }, { "input": "Follow - up 7 - weeks later, revealed improvement of her cardiac function and near - normalization of thyroid hormone levels.", "output": "There is no related enetity." }, { "input": "Summary: In this patient who presented with symptoms of congestive heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation.", "output": "There is no related enetity." }, { "input": "Conclusions: Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system.", "output": "There is no related enetity." }, { "input": "Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity.", "output": "catecholamine." }, { "input": "Metal - dependent protein phosphatase 1A functions as an extracellular signal - regulated kinase phosphatase.", "output": "There is no related enetity." }, { "input": "Protein phosphorylation is an important post - translational modification that regulates almost every aspect of signal transduction in cells.", "output": "There is no related enetity." }, { "input": "Activation of the mitogen - activated protein kinase ( MAPK ) family kinase extracellular signal - regulated kinase ( ERK ) is a point of convergence for many cellular activities in response to external stimulation.", "output": "There is no related enetity." }, { "input": "With stimuli, ERK activity is significantly increased by the phosphorylation of Thr202 and Tyr204 at its activation loop.", "output": "Thr202, Tyr204." }, { "input": "Downregulation of ERK phosphorylation at these two sites by several phosphatases, such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for maintaining appropriate ERK function in different cellular processes.", "output": "There is no related enetity." }, { "input": "However, it is unknown whether metal - dependent protein phosphatase ( PPM ) family phosphatases directly dephosphorylate ERK.", "output": "There is no related enetity." }, { "input": "In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation.", "output": "There is no related enetity." }, { "input": "Additional kinetic studies revealed that key residues participated in phospho - ERK recognition by PPM1A.", "output": "phospho." }, { "input": "Importantly, PPM1A preferred the phospho - ERK peptide sequence over a panel of other phosphopeptides through the interactions of basic residues in the active site of PPM1A with the pThr - Glu - pTyr motif of ERK.", "output": "phospho, pThr - Glu - pTyr." }, { "input": "Whereas Lys165 and Arg33 were required for efficient catalysis or phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A substrate specificity.", "output": "Lys165, Arg33, Gln185, Arg186." }, { "input": "The interaction between Arg186 of PPM1A and Glu203 and pTyr204 of phospho - ERK was identified as a hot - spot for phospho - ERK - PPM1A interaction.", "output": "Arg186, Glu203, phospho, phospho." }, { "input": "STRUCTURED DIGITAL ABSTRACT: PPM1A physically interacts with ERK2 by pull down ( View interaction ) PPM1A dephosphorylates p38 by phosphatase assay ( View Interaction: 1, 2 ) PPM1A binds to ERK2 by pull down ( View interaction ) PPM1A dephosphorylates ERK2 by phosphatase assay ( View Interaction: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 ).", "output": "There is no related enetity." }, { "input": "Star Polymers with a Cationic Core Prepared by ATRP for Cellular Nucleic Acids Delivery.", "output": "There is no related enetity." }, { "input": "Poly ( ethylene glycol ) ( PEG ) - based star polymers with a cationic core were prepared by atom transfer radical polymerization ( ATRP ) for in vitro nucleic acid ( NA ) delivery.", "output": "Poly ( ethylene glycol ), PEG." }, { "input": "The star polymers were synthesized by ATRP of 2 - ( dimethylamino ) ethyl methacrylate ( DMAEMA ) and ethylene glycol dimethacrylate ( EGDMA ).", "output": "2 - ( dimethylamino ) ethyl methacrylate, DMAEMA, ethylene glycol dimethacrylate, EGDMA." }, { "input": "Star polymers were characterized by gel permeation chromatography, zeta potential, and dynamic light scattering.", "output": "There is no related enetity." }, { "input": "These star polymers were combined with either plasmid DNA ( pDNA ) or short interfering RNA ( siRNA ) duplexes to form polyplexes for intracellular delivery.", "output": "There is no related enetity." }, { "input": "These polyplexes with either siRNA or pDNA were highly effective in NA delivery, particularly at relatively low star polymer weight or molar ratios, highlighting the importance of NA release in efficient delivery systems.", "output": "There is no related enetity." }, { "input": "Intake of mulberry 1 - deoxynojirimycin prevents diet - induced obesity through increases in adiponectin in mice.", "output": "There is no related enetity." }, { "input": "In this study, the anti - obesity effect of 1 - deoxynojirimycin ( DNJ ) was examined in the diet - induced obese mouse model.", "output": "1 - deoxynojirimycin, DNJ." }, { "input": "Mulberry DNJ was administered to the obese mice for 12weeks.", "output": "DNJ." }, { "input": "As a result, DNJ decreased both the visceral fat weight and adipocyte size.", "output": "DNJ." }, { "input": "To determine the influence of DNJ on lipid metabolism, lipid parameters of the plasma and the liver and the activities of several molecules related to lipid metabolism in the liver were measured.", "output": "DNJ." }, { "input": "DNJ activated the beta - oxidation system, suppressed lipid accumulation in the liver and reduced plasma triacylglycerol.", "output": "DNJ, triacylglycerol." }, { "input": "Since it was thought that the factor activated in the beta - oxidation system was adiponectin, plasma adiponectin levels were measured and it was shown that plasma adiponectin was increased with DNJ.", "output": "DNJ." }, { "input": "Therefore, it was suggested that DNJ promoted an increase in plasma adiponectin and activated the beta - oxidation system.", "output": "DNJ." }, { "input": "Overall, it was shown that DNJ prevents diet - induced obesity through an increase in adiponectin.", "output": "DNJ." }, { "input": "Proanthocyanidin profile of cowpea ( Vigna unguiculata ) reveals catechin - O - glucoside as the dominant compound.", "output": "Proanthocyanidin, catechin - O - glucoside." }, { "input": "Proanthocyanidin ( PA ) profile and content can have important nutritional and health implications on plant foods.", "output": "Proanthocyanidin." }, { "input": "Six diverse cowpea phenotypes ( black, red, green, white, light - brown and golden - brown ) were investigated for PA composition using normal - phase HPLC and reversed - phase UPLC - TQD - MS.", "output": "There is no related enetity." }, { "input": "Catechin and ( epi ) afzelechin were the major flavan - 3 - ol units.", "output": "Catechin, ( epi ) afzelechin, flavan - 3 - ol." }, { "input": "Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers.", "output": "There is no related enetity." }, { "input": "The PA content of cowpea ( dry basis ) ranged between 2. 2 and 6. 3mg / g.", "output": "There is no related enetity." }, { "input": "Monomeric flavan - 3 - ols were the largest group of PA ( 36 - 69 % ) in cowpea, with catechin - 7 - O - glucoside accounting for most ( about 88 % ) of the monomers.", "output": "flavan - 3 - ols, catechin - 7 - O - glucoside." }, { "input": "The oligomers with degree of polymerization ( DP ) 2 - 4 ranged from 0. 41 to 1. 3mg / g ( 15 - 20 % ), whereas DP > 10 polymers accounted for only 13. 5 % of PA.", "output": "There is no related enetity." }, { "input": "Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted.", "output": "There is no related enetity." }, { "input": "Blueberry estimated harvest from seven new cultivars: Fruit and anthocyanins.", "output": "anthocyanins." }, { "input": "This study compares the yields, weights and anthocyanin contents of fruit from a group of seven new cultivars released from the New Zealand blueberry breeding programme and selected for the longest possible combined harvest season.", "output": "anthocyanin." }, { "input": "The measured factors were primarily influenced by cultivar, and seasonal variations had relatively minor effects.", "output": "There is no related enetity." }, { "input": "The late - ripening cultivars ' Velluto Blue ' and ' Centra Blue ' had the highest fruit yields, anthocyanin contents and estimated total anthocyanin harvestable from a given area.", "output": "anthocyanin, anthocyanin." }, { "input": "' Blue Moon ' and ' Sky Blue ' had the largest fruit sizes.", "output": "There is no related enetity." }, { "input": "The early - ripening cultivars ' Blue Bayou ', ' Blue Moon ' and ' Sunset Blue ' had the lowest anthocyanin contents.", "output": "anthocyanin." }, { "input": "The yield, fruit size and total anthocyanin content results obtained from any single year were highly correlated with the average of the three years, which makes pursuing the evaluation for these traits from a single year and at an early stage of plant development a practical proposition.", "output": "anthocyanin." }, { "input": "Changes in selected parameters related to proteolysis during ageing of dry - cured pork loins inoculated with probiotics.", "output": "There is no related enetity." }, { "input": "The effect of inoculation with a probiotic strain, Lactobacillus casei L OCK 0900, on selected parameters related to proteolysis of dry - cured pork loins during ageing was studied.", "output": "There is no related enetity." }, { "input": "Moisture content decreased significantly ( p < 0. 05 ) throughout ageing, accompanied by a progressive reduction in water activity.", "output": "There is no related enetity." }, { "input": "The total nitrogen ( TN ) content increased during ageing with no effect ( p < 0. 05 ) of inoculation with L. casei on its level.", "output": "nitrogen." }, { "input": "The greatest increase in non - protein nitrogen ( NPN ) content during ageing occurred in an inoculated sample, corresponding with the more pronounced decrease in pH.", "output": "nitrogen." }, { "input": "The intensity of proteolysis, as assessed by proteolysis index ( PI ), remained statistically significantly ( p < 0. 05 ) unchanged during examined ageing periods.", "output": "There is no related enetity." }, { "input": "Inoculation with a probiotic strain does not significantly affect the degree of proteolysis in examined meat products after 21 and 28days of ageing.", "output": "There is no related enetity." }, { "input": "The enhancement of antioxidant compounds extracted from Thymus vulgaris using enzymes and the effect of extracting solvent.", "output": "There is no related enetity." }, { "input": "We evaluate the total phenolic compounds ( TPC ) content and the antioxidant activity ( AA ) of extracts obtained from ground fresh thyme ( FT ) and depleted thyme ( DT ), a by - product of the process of essential oil extraction.", "output": "phenolic." }, { "input": "In addition, enzymatic treatments were evaluated to improve the extraction yields of polyphenolic compounds from thyme.", "output": "polyphenolic." }, { "input": "Extractions were performed using several solvents as methanol, ethanol, and water.", "output": "methanol, ethanol." }, { "input": "Enzymes were applied prior to extraction or during the extraction process.", "output": "There is no related enetity." }, { "input": "The best results were obtained using a mixture of methanol and water, resulting in 2790 and 220mg Gallic acid equivalent ( GAE ) / L of TPC for FT and DT, respectively.", "output": "methanol, Gallic acid." }, { "input": "A similar result was observed for AA.", "output": "There is no related enetity." }, { "input": "With regard to enzymatic treatment, application of Grindamyl CA 150 enzyme as a pre - treatment resulted in the production of an extract from DT with 614mg TE ( trolox equivalent ) / L of AA, 70 % more than the control, and an AA of 621mg TE / L ( 74 % more than the control sample ) was obtained using Grindamyl CA 150 during the extraction process.", "output": "trolox." }, { "input": "These results suggest that enzymatic treatment is an interesting alternative for producing antioxidant extracts from DT.", "output": "There is no related enetity." }, { "input": "Flavonoids from the capitula of Eriocaulon australe.", "output": "Flavonoids." }, { "input": "A flavan, eriocaulin A ( 1 ), and three flavone acyl glucosides, eriocaulosides A - C ( 2 - 4 ) were isolated from the capitula of Eriocaulon australe R.", "output": "flavan, eriocaulin A, flavone acyl glucosides, eriocaulosides A - C." }, { "input": "Br.", "output": "There is no related enetity." }, { "input": "( Eriocaulaceae ), a Chinese medicine and an herb for health care beverages, together with seven known flavones and three isoflavones ( 5 - 14 ).", "output": "flavones, isoflavones." }, { "input": "The new flavonoids were elucidated as ( 2S ) - 3 ', 4 ' - methylenedioxy - 5 - methoxy - 7 - hydroxyflavan ( 1 ), hispidulin 7 - O - beta - d - ( 6 - O - cinnamoyl ) glucopyranoside ( 2 ), jaceosidin 7 - O - beta - d - ( 6 - O - p - coumaroyl ) glucopyranoside ( 3 ), jaceosidin 7 - O - beta - d - ( 6 - O - p - hydroxybenzoyl ) glucopyranoside ( 4 ) based on their spectroscopic data.", "output": "flavonoids, ( 2S ) - 3 ' , 4 ' - methylenedioxy - 5 - methoxy - 7 - hydroxyflavan, hispidulin 7 - O - beta - d - ( 6 - O - cinnamoyl ) glucopyranoside, jaceosidin 7 - O - beta - d - ( 6 - O - p - coumaroyl ) glucopyranoside, jaceosidin 7 - O - beta - d - ( 6 - O - p - hydroxybenzoyl ) glucopyranoside." }, { "input": "All the 14 flavonoids were obtained from this species for the first time.", "output": "flavonoids." }, { "input": "The in vitro cytotoxicity of compounds 1 - 14 against human lung adenocarcinoma A549, human breast adenocarcinoma MCF - 7, and human cervical carcinoma HeLa cell lines was evaluated using the MTT colourimetric assay.", "output": "MTT." }, { "input": "Compounds 1, 7, and 9 were cytotoxic to A549, compounds 1, 2, 7, 9, 12, and 14 to MCF - 7, and compounds 7, 9, and 14 to HeLa cells, with IC50 values ranging from 7. 17 to 29. 57 mu g / ml, while the others were inactive ( IC50 > 50 mu g / ml ).", "output": "There is no related enetity." }, { "input": "Influence of air - drying temperature on drying kinetics, colour, firmness and biochemical characteristics of Atlantic salmon ( Salmo salar L. ) fillets.", "output": "There is no related enetity." }, { "input": "In this work the drying kinetics of Atlantic salmon ( Salmo salar L. ) fillets and the influence of air drying temperature on colour, firmness and biochemical characteristics were studied.", "output": "There is no related enetity." }, { "input": "Experiments were conducted at 40, 50 and 60 degrees C.", "output": "There is no related enetity." }, { "input": "Effective moisture diffusivity increased with temperature from 1. 08 x 10 ( - 10 ) to 1. 90 x 10 ( - 10 ) m ( 2 ) s ( - 1 ).", "output": "There is no related enetity." }, { "input": "The colour difference, determined as Delta E values ( from 9. 3 to 19. 3 ), as well as firmness ( from 25 to 75Nmm ( - 1 ) ) of dried samples increased with dehydration temperature.", "output": "There is no related enetity." }, { "input": "The lightness value L ( * ) and yellowness value b ( * ) indicated formation of browning products at higher drying temperatures, while redness value a ( * ) showed dependence on astaxanthin value.", "output": "astaxanthin." }, { "input": "Compared with fresh fish samples, palmitic acid and tocopherol content decreased in a 20 % and 40 %, respectively, with temperature.", "output": "palmitic acid, tocopherol." }, { "input": "While eicosapentaenoic acid ( EPA ) content remained unchanged and docosahexaenoic acid ( DHA ) content changed slightly.", "output": "eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA." }, { "input": "Anisidine and thiobarbituric acid values indicated the formation of secondary lipid oxidation products, which is more relevant for longer drying time than for higher drying temperatures.", "output": "Anisidine, thiobarbituric acid." }, { "input": "Interlocking of beta - carotene in beta - lactoglobulin aggregates produced under high pressure.", "output": "beta - carotene." }, { "input": "Vitamin A deficiency is one of the major causes of mortality and morbidity in the developing World.", "output": "Vitamin A." }, { "input": "This deficiency can be prevented by alimentary or pharmaceutical supplementation.", "output": "There is no related enetity." }, { "input": "However, both vitamin A oxidation and isomerization should be prevented, as these phenomenons result in loss of nutritional efficacy.", "output": "vitamin A." }, { "input": "The aim of this study was to investigate the effect of a food protein matrix, beta - lactoglobulin ( beta - Lg ) aggregates produced by high pressure ( HP ), on the stabilization of beta - carotene during storage and gastro - duodenal digestion and therefore on its bioavailability.", "output": "beta - carotene." }, { "input": "In vitro gastro - duodenal digestion of beta - Lg aggregates entrapping beta - carotene showed that up to 12 % and 33 % of total beta - carotene was released after peptic and pancreatic digestion, respectively.", "output": "beta - carotene, beta - carotene." }, { "input": "Overall, our study showed that beta - Lg aggregates are efficient for caging and stabilization of beta - carotene during storage and digestion.", "output": "beta - carotene." }, { "input": "Hence, it may be an interesting approach for the protection and the delivery of vitamin A.", "output": "vitamin A." }, { "input": "Research on the preparation of antioxidant peptides derived from egg white with assisting of high - intensity pulsed electric field.", "output": "There is no related enetity." }, { "input": "Egg white protein powder, one of the main egg products, was hydrolysed by Alcalase, Trypsin, and Pepsin respectively to prepare antioxidant peptides.", "output": "There is no related enetity." }, { "input": "All hydrolysates were assayed by determination of reducing power ( RP ) ability.", "output": "There is no related enetity." }, { "input": "Three kinds of hydrolysates were prepared under optimal enzymatic parameters that were obtained from the preliminary one - factor - at - a - time ( OFAT ) and response surface methodology ( RSM ) experiments.", "output": "There is no related enetity." }, { "input": "The results showed that the Alcalase hydrolysates exerted the best RP ability.", "output": "There is no related enetity." }, { "input": "Thereafter, the Alcalase hydrolysates were sequentially fractionated by ultra filtration membranes in cut - off molecular weight ( MW ) of 30, 10, and 1kDa, and tested their antioxidant activities in terms of RP ability, DPPH radical scavenging ability, ABTS radical scavenging ability, and FRAP assay.", "output": "DPPH, ABTS." }, { "input": "Effects of high intensity pulsed electric field treatment were further investigated on antioxidant peptides to improve their activities.", "output": "There is no related enetity." }, { "input": "The results showed that Alcalase hydrolysates possessed the strongest antioxidant ability compared with the other two hydrolysates, particularly for the Fraction - 3 with MW < 1kDa.", "output": "There is no related enetity." }, { "input": "After PEF treatment, this fraction showed a significant improvement of RP ability within 5h ( P < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Anticancer activity and mediation of apoptosis in human HL - 60 leukaemia cells by edible sea cucumber ( Holothuria edulis ) extract.", "output": "There is no related enetity." }, { "input": "Sea cucumbers have been a dietary delicacy and important ingredient in Asian traditional medicinal over many centuries.", "output": "There is no related enetity." }, { "input": "In this study, edible sea cucumber Holothuria edulis was evaluated for its in vitro anticancer potential.", "output": "There is no related enetity." }, { "input": "An aqueous fraction of the edible sea cucumber ( ESC - AQ ) has been shown to deliver a strong cytotoxic effect against the human HL - 60 leukaemia cell line.", "output": "There is no related enetity." }, { "input": "An induction effect of apoptotic body formation in response to ESC - AQ treatment was confirmed in HL - 60 cells stained with Hoechst 33342 and confirmed via flow cytometry analysis.", "output": "Hoechst 33342." }, { "input": "The up regulation of Bax and caspase - 3 protein expression was observed while the expression of Bcl - xL protein was down regulated in ESC - AQ treated HL - 60 cells.", "output": "There is no related enetity." }, { "input": "Due to the profound anticancer activity, ESC - AQ appears to be an economically important biomass fraction that can be exploited in numerous industrial applications as a source of functional ingredients.", "output": "There is no related enetity." }, { "input": "A new process for obtaining hydroxytyrosol using transformed Escherichia coli whole cells with phenol hydroxylase gene from Geobacillus thermoglucosidasius.", "output": "hydroxytyrosol, phenol." }, { "input": "Phenol hydroxylase gene cloning from the thermophilic bacteria Geobacillus thermoglucosidasius was used to develop an effective method to convert tyrosol into the high - added - value compound hydroxytyrosol by hydroxylation.", "output": "Phenol, tyrosol, hydroxytyrosol." }, { "input": "Phenol hydroxylase is a two - component enzyme encoded by pheA1 and pheA2 genes and strictly dependent on NADH and FAD.", "output": "Phenol, NADH, FAD." }, { "input": "These two genes were subcloned together as a 2kb fragment into Escherichia coli Rosetta cells, and the transformants were able to grow and effectively transform up to 5mM of phenol and tyrosol using IPTG ( isopropyl - beta - d - thiogalactopyranoside ) as inducer.", "output": "phenol, tyrosol, IPTG, isopropyl - beta - d - thiogalactopyranoside." }, { "input": "In addition, when a new fragment with a 340pb upstream pheA1 gene was subcloned, a similar biotransformation rate was attained without IPTG, confirming that this fragment encodes for a phenol hydroxylase promoter that can be recognised by E. coli.", "output": "IPTG, phenol." }, { "input": "Both transformants brought about the total bioconversion of monophenols at a high concentration ( 5mM ), which represents an increase, both in concentration and in yield, compared with that previously described in the bibliography.", "output": "monophenols." }, { "input": "The use of the transformant with its constitutive promoter was more interesting from a biotechnological point of view, since it is not necessary to use IPTG.", "output": "IPTG." }, { "input": "It also gave rise to greater operational stability.", "output": "There is no related enetity." }, { "input": "Comparison of biogenic amine and polyphenol profiles of grape berries and wines obtained following conventional, organic and biodynamic agricultural and oenological practices.", "output": "amine, polyphenol." }, { "input": "The bio - active compounds present in food and beverages have a high potential influence on the future health of humans.", "output": "There is no related enetity." }, { "input": "The levels of biogenic amines, anthocyanins, polyphenols and antioxidant activity were measured in white ( Pignoletto ) and red ( Sangiovese ) grape berries and wines from the Emilia - Romagna region ( Italy ) obtained following conventional, organic and biodynamic agricultural and oenological practices.", "output": "amines, anthocyanins, polyphenols." }, { "input": "No significant difference was shown among the samples coming from different agricultural and winemaking practices.", "output": "There is no related enetity." }, { "input": "Principal Component Analysis was also performed.", "output": "There is no related enetity." }, { "input": "Biogenic amine amounts were higher in red than in white berries, while in the wines an opposite trend was observed, with histamine, tyramine and putrescine being the most abundant in Pignoletto wines.", "output": "amine, histamine, tyramine, putrescine." }, { "input": "Red grapes and wines were richer in anthocyanins and showed higher antioxidant activity than white ones.", "output": "anthocyanins." }, { "input": "The total level of polyphenols was similar in red and white berries, but with different metabolite profiles depending on the grape variety.", "output": "polyphenols." }, { "input": "Effect of nitrite on the odourant volatile fraction of cooked ham.", "output": "nitrite." }, { "input": "The aim of this work was to reliably identify the key odour compounds in cooked ham and acquire new knowledge on the role of sodium nitrite on the formation of its aroma.", "output": "sodium nitrite." }, { "input": "Gas chromatography coupled with mass spectrometry and ( or ) olfactometry was used.", "output": "There is no related enetity." }, { "input": "In all, 24 odourants were identified in the volatile fraction of cooked ham.", "output": "There is no related enetity." }, { "input": "Their main origins are discussed.", "output": "There is no related enetity." }, { "input": "Orthonasal sniffing of the hams was used to study how these substances contributed to the overall aroma of the product.", "output": "There is no related enetity." }, { "input": "The aroma of cooked ham is a balance between that of certain sulfur compounds produced during cooking and that of oxidation compounds commonly found in cooked meats.", "output": "sulfur." }, { "input": "In the absence of nitrite, this balance is disturbed by extensive formation of oxidation compounds that mask the meaty notes induced by the sulfur compounds.", "output": "nitrite, sulfur." }, { "input": "Isolation of new monoterpene coumarins from Micromelum minutum leaves and their cytotoxic activity against Leishmania major and cancer cells.", "output": "monoterpene coumarins." }, { "input": "On the basis of a leishmanicidal assay - guided isolation, two new monoterpene coumarins, minutin A and minutin B, were purified from Micromelum minutum leaves together with four known coumarins, 8, 4 '' - dihydroxy - 3 '', 4 '' - dihydrocapnolactone - 2 ', 3 ' - diol, 8 - hydroxyisocapnolactone - 2 ', 3 ' - diol, 8 - hydroxy - 3 '', 4 '' - dihydrocapnolactone - 2 ', 3 ' - diol, and clauslactone E.", "output": "monoterpene coumarins, minutin A, minutin B, coumarins, 8 , 4 '' - dihydroxy - 3 '' , 4 '' - dihydrocapnolactone - 2 ' , 3 ' - diol, 8 - hydroxyisocapnolactone - 2 ' , 3 ' - diol, 8 - hydroxy - 3 '' , 4 '' - dihydrocapnolactone - 2 ' , 3 ' - diol, clauslactone E." }, { "input": "Among these compounds, minutin A, minutin B, 8 - hydroxyisocapnolactone - 2 ', 3 ' - diol and clauslactone E showed a significant cytotoxic activity against Leishmania major with IC50 values of 26. 2, 20. 2, 12. 1, and 9. 8 mu M, respectively, while 8, 4 '' - dihydroxy - 3 '' 4 '' - dihydrocapnolactone - 2 ', 3 ' - diol and 8 - hydroxy - 3 '', 4 '' - dihydrocapnolactone - 2 ', 3 ' - diol were not active.", "output": "minutin A, minutin B, 8 - hydroxyisocapnolactone - 2 ' , 3 ' - diol, clauslactone E, 8 , 4 '' - dihydroxy - 3 '' 4 '' - dihydrocapnolactone - 2 ' , 3 ' - diol, 8 - hydroxy - 3 '' , 4 '' - dihydrocapnolactone - 2 ' , 3 ' - diol." }, { "input": "However, all these compounds exhibited some inhibitory activity against one or more lung adenocarcinoma ( SBC3 and A549 ) and leukaemia ( K562, and K562 / ADM ) cell lines.", "output": "There is no related enetity." }, { "input": "Amongst these, clauslactone E, minutin B and 8 - hydroxyisocapnolactone - 2 ', 3 ' - diol possessed the strongest cytotoxic activity against SBC3, A549, K562, and K562 / ADM cell lines, with IC50 values of 3. 7, 10. 4, 12. 1, and 10. 8 mu M for clauslactone E; 9. 6, 17. 5, 8. 7 and 6. 7 mu M for minutin B; 8. 8, 10. 1, 16. 9, and 10. 1 mu M for 8 - hydroxyisocapnolactone - 2 ', 3 ' - diol, respectively.", "output": "clauslactone E, minutin B, 8 - hydroxyisocapnolactone - 2 ' , 3 ' - diol, clauslactone E, minutin B, 8 - hydroxyisocapnolactone - 2 ' , 3 ' - diol." }, { "input": "Pesticide residues determination in Polish organic crops in 2007 - 2010 applying gas chromatography - tandem quadrupole mass spectrometry.", "output": "There is no related enetity." }, { "input": "A sensitive, accurate and reliable multiresidue method based on the application of gas chromatography - tandem quadrupole mass spectrometry ( GC - QqQ - MS / MS ) has been established for screening, identification and quantification of a large number of pesticide residues in produce.", "output": "There is no related enetity." }, { "input": "The method was accredited in compliance with PN - EN ISO / IEC 17025: 2005 standard and it was operated under flexible scope as PB - 11 method.", "output": "There is no related enetity." }, { "input": "The flexible scope of accreditation allowed for minor modifications and extension of the analytical scope while using the same analytical technique.", "output": "There is no related enetity." }, { "input": "During the years 2007 - 2010, the method was used for the purpose of verification of organic crop production by multiresidue analysis for the presence of pesticides.", "output": "There is no related enetity." }, { "input": "A total of 528 samples of differing matrices such as fruits, vegetables, cereals, plant leaves and other green parts were analysed, of which 4. 4 % samples contained pesticide residues above the threshold value of 0. 01mg / kg.", "output": "There is no related enetity." }, { "input": "A total of 20 different pesticide residues were determined in the samples.", "output": "There is no related enetity." }, { "input": "4 - Methyl - 7 - hydroxycoumarin antifungal and antioxidant activity enhancement by substitution with thiosemicarbazide and thiazolidinone moieties.", "output": "4 - Methyl - 7 - hydroxycoumarin, thiosemicarbazide, thiazolidinone." }, { "input": "According to literature data, thiosemicarbazide and thiazolidinone moieties should enhance biological properties of coumarin.", "output": "thiosemicarbazide, thiazolidinone, coumarin." }, { "input": "Antioxidant, metal - chelating and antifungal activities of all compounds were investigated and compared to the activity of the starting material, 7 - hydroxy - 4 - methylcoumarin, and were proven to possess potent antioxidant and antifungal activity.", "output": "7 - hydroxy - 4 - methylcoumarin." }, { "input": "In general, thiosemicarbazides showed higher scavenging activity towards DPPH and galvinoxyl radicals than did 4 - thiazolidinones and some of them had the same or even better activity than had ascorbic acid itself, depending on the free radical used.", "output": "thiosemicarbazides, DPPH, galvinoxyl, 4 - thiazolidinones, ascorbic acid." }, { "input": "In antifungal activity tests towards four foodborne mycotoxigenic fungi, Aspergillus flavus, Aspergillus ochraceus.", "output": "There is no related enetity." }, { "input": "Fusarium graminearum and Fusarium verticillioides, coumarin derivatives were proven to possess a very high activity in terms of growth inhibition, depending on the fungi investigated.", "output": "coumarin." }, { "input": "In general, 4 - thiazolidinones showed better antifungal activity than did thiosemicarbazides.", "output": "4 - thiazolidinones, thiosemicarbazides." }, { "input": "F. graminearum was the most susceptible to the compounds investigated and F. verticillioides was proven to be the most resistant.", "output": "There is no related enetity." }, { "input": "Two compounds, both coumarinyl thiosemicarbazides, were found to possess both antifungal and antioxidant activity which could be useful for applications in medicine, food industry and agriculture.", "output": "coumarinyl thiosemicarbazides." }, { "input": "Anti - inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus.", "output": "There is no related enetity." }, { "input": "Mushroom Inonotus obliquus ( I. obliquus ) has been used as functional food and traditional Chinese herbs for long time.", "output": "There is no related enetity." }, { "input": "An efficient method for bioassay - guided preparative isolation was used for identifying the anti - inflammatory and anticancer constituents in I. obliquus.", "output": "There is no related enetity." }, { "input": "The petroleum ether and ethyl acetate fractions were found to have significant inhibition effects on NO production and NF - kappa B luciferase activity in macrophage RAW 264. 7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA - MB - 231.", "output": "petroleum ether, ethyl acetate, NO." }, { "input": "Six main constituents were isolated from these two fractions and they were identified as lanosterol ( 1 ), 3 beta - hydroxy - 8, 24 - dien - 21 - al ( 2 ), ergosterol ( 3 ), inotodiol ( 4 ), ergosterol peroxide ( 5 ) and trametenolic acid ( 6 ).", "output": "lanosterol, 3 beta - hydroxy - 8 , 24 - dien - 21 - al, ergosterol, inotodiol, ergosterol peroxide, trametenolic acid." }, { "input": "Compound ergosterol, ergosterol peroxide and trametenolic acid showed anti - inflammatory activities and ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA - MB - 231 cell.", "output": "ergosterol, ergosterol peroxide, trametenolic acid, ergosterol peroxide, trametenolic acid." }, { "input": "The results obtained in this work might contribute to understanding the biological activity of mushroom I. obliquus for food and drug application.", "output": "There is no related enetity." }, { "input": "Enzyme - assisted extraction of bioactive compounds from ginger ( Zingiber officinale Roscoe ).", "output": "There is no related enetity." }, { "input": "Ginger ( Zingiber officinale R. ) is a popular spice used in various foods and beverages.", "output": "There is no related enetity." }, { "input": "6 - Gingerol is the major bioactive constituent responsible for the antiinflammatory, antitumour and antioxidant activities of ginger.", "output": "6 - Gingerol." }, { "input": "The effect of application of alpha - amylase, viscozyme, cellulase, protease and pectinase enzymes to ginger on the oleoresin yield and 6 - gingerol content has been investigated.", "output": "6 - gingerol." }, { "input": "Pre - treatment of ginger with alpha - amylase or viscozyme followed by extraction with acetone afforded higher yield of oleoresin ( 20 % +/- 0. 5 ) and gingerol ( 12. 2 % +/- 0. 4 ) compared to control ( 15 % +/- 0. 6 oleoresin, 6. 4 % +/- 0. 4 gingerol ).", "output": "acetone, gingerol, gingerol." }, { "input": "Extraction of ginger pre - treated with enzymes followed by extraction with ethanol provided higher yield of gingerol ( 6. 2 - 6. 3 % ) than the control ( 5. 5 % ) with comparable yields of the oleoresin ( 31 - 32 % ).", "output": "ethanol, gingerol." }, { "input": "Also, ethanol extract of cellulase pre - treated ginger had the maximum polyphenol content ( 37. 5mg / g ).", "output": "ethanol, polyphenol." }, { "input": "Apart from 6 - gingerol, 6 - paradol along with 6 - and 8 - methyl shogaols were the other important bio - active constituents in the oleoresin from cellulase - treated ginger.", "output": "6 - gingerol, 6 - paradol, 6 - and 8 - methyl shogaols." }, { "input": "Chemical profile and sensory properties of different foods cooked by a new radiofrequency oven.", "output": "There is no related enetity." }, { "input": "Radio frequency ( RF ) heating has been used for numerous applications in the food industry such as baking, thawing or pasteurisation.", "output": "There is no related enetity." }, { "input": "It reduces cooking time, and it helps to retain acceptable food colour and texture.", "output": "There is no related enetity." }, { "input": "In this paper, chemical and sensory data obtained from broccoli, potatoes, salmon and cocoa cakes cooked using an innovative RF oven were reported.", "output": "There is no related enetity." }, { "input": "The oven has an algorithm able to monitor the energy feedback from the cavity and to adjust the energy output accordingly.", "output": "There is no related enetity." }, { "input": "The different foods were cooked to the same end point and the concentration of phytochemicals, vitamins and acrylamide were assessed.", "output": "vitamins, acrylamide." }, { "input": "Results demonstrated that RF oven preserved ascorbic acid and increased glucosinolates concentration in broccoli and it decreased the formation of acrylamide in roasted potatoes more than 50 %.", "output": "ascorbic acid, glucosinolates, acrylamide." }, { "input": "The total amount of vitamins B was 30 % and 50 % higher in RF cooked salmon than conventionally cooked salmon prepared at 55 and 75 degrees C, respectively.", "output": "vitamins B." }, { "input": "Changes in polyphenol content during production of grape juice concentrate.", "output": "polyphenol." }, { "input": "The production of grape juice concentrate on an industrial scale was evaluated and samples from the main steps of processing have been collected and analyzed.", "output": "There is no related enetity." }, { "input": "The sampling steps included the selection and washing of grapes ( Nevsehir Patlak variety ), pressing in order to obtain the juice separate from the seed and the skin fraction, pasteurization, clarification, filtration, evaporation, and filling - packing at 27 degrees C with a Brix of 45 degrees.", "output": "There is no related enetity." }, { "input": "Samples from each of the processing steps were analyzed by a number of spectrophotometric analyses.", "output": "There is no related enetity." }, { "input": "A series of anthocyanin compounds was identified using HPLC - MS, and the fate of anthocyanins, quercetin rutinoside and procyanidins was followed using HPLC.", "output": "anthocyanin, anthocyanins, quercetin rutinoside, procyanidins." }, { "input": "The results indicate that the removal of seed and fruit skin removes most of the procyanidins and anthocyanins, while subsequent clarification and filtration treatments further reduce the anthocyanin content.", "output": "procyanidins, anthocyanins, anthocyanin." }, { "input": "Chemical stability of astaxanthin nanodispersions in orange juice and skimmed milk as model food systems.", "output": "astaxanthin." }, { "input": "Solubilising astaxanthin in nanodispersion systems is a promising approach to incorporate astaxanthin into water - based food formulations.", "output": "astaxanthin, astaxanthin." }, { "input": "In this research, the chemical stabilities of astaxanthin nanodispersions diluted in orange juice and skimmed milk as model food systems and in deionised water as a control were evaluated.", "output": "astaxanthin." }, { "input": "The nanodispersions displayed significantly ( p < 0. 05 ) better stability in food systems compared to the control.", "output": "There is no related enetity." }, { "input": "The effects of stabilisers and dilution factor were also studied.", "output": "There is no related enetity." }, { "input": "In skimmed milk and deionised water, the type of stabiliser had a significant effect ( p < 0. 05 ) on astaxanthin degradation during storage.", "output": "astaxanthin." }, { "input": "In vitro cellular uptake of astaxanthin from diluted astaxanthin nanodispersions in selected food systems was also evaluated.", "output": "astaxanthin, astaxanthin." }, { "input": "The cellular uptake of astaxanthin nanodispersions in skimmed milk was significantly higher ( p < 0. 05 ) than that of astaxanthin nanodispersions in orange juice and deionised water.", "output": "astaxanthin, astaxanthin." }, { "input": "High in vitro cellular uptake of astaxanthin from the prepared astaxanthin nanodispersions can be achieved via incorporation into protein - based foods such as milk.", "output": "astaxanthin, astaxanthin." }, { "input": "The effect of interesterification on the bioavailability of fatty acids in structured lipids.", "output": "fatty acids." }, { "input": "Fatty acid ( FA ) profile is a critical factor in the nutritional properties of fats, but, stereochemistry may also play a fundamental role in the rate and extent to which FAs are absorbed and become available.", "output": "Fatty acid, FAs." }, { "input": "To better understand this phenomenon, we evaluated the bioavailability of FAs in linseed - oil and palm - stearin blends compared to their interesterified mix, using a sn - 1, 3 stereospecific lipase, to determine if there was any difference in terms of FA availability when using this technology.", "output": "FAs." }, { "input": "Test meals were fed through an intragastric feeding tube on Sprague - Dawley male rats after 18h fasting.", "output": "There is no related enetity." }, { "input": "Postprandial blood samples were collected after meal or physiological serum ( control ) administration and the FA profile of plasma lipids was determined.", "output": "There is no related enetity." }, { "input": "Results showed that modification of the melting profile through interesterification, without altering the bioavailability determined by sn - 2 stereochemistry, could delay lipid absorption at the beginning, but had no effect on total lipid absorption.", "output": "There is no related enetity." }, { "input": "Probing the binding between norbixin and dairy proteins by spectroscopy methods.", "output": "norbixin." }, { "input": "Annatto ( norbixin ) has been used to color cheeses for centuries, but there is very little knowledge about interactions between the pigment and dairy proteins.", "output": "Annatto, norbixin." }, { "input": "In this study, binding of norbixin with whey protein isolate ( WPI ), sodium caseinate ( NaCN ), and 6 individual dairy proteins was investigated by using fluorescence spectroscopy, Fourier transform infrared spectroscopy ( FTIR ), circular dichroism ( CD ) and differential scanning calorimetry ( DSC ).", "output": "norbixin, sodium." }, { "input": "Norbixin was observed to effectively quench the fluorescence of WPI and NaCN by forming complexes.", "output": "Norbixin." }, { "input": "The binding affinity between NaCN and norbixin was higher than that of WPI - norbixin.", "output": "norbixin, norbixin." }, { "input": "For individual proteins, bovine serum albumin had higher binding affinity with norbixin than beta - lactoglobulin and alpha - lactalbumin, while kappa - casein bound with norbixin better than alpha - and beta - caseins.", "output": "norbixin, norbixin." }, { "input": "Binding changed the conformation of WPI and NaCN, but the extent and trend varied for individual proteins.", "output": "There is no related enetity." }, { "input": "Characterization of Hachi ( Camelus dromedarius ) fat extracted from the hump.", "output": "There is no related enetity." }, { "input": "In this work, the characteristics of fat from the hump of young camels ( Hachi ) were evaluated.", "output": "There is no related enetity." }, { "input": "The physicochemical properties of the fat were as follows: melting point, 45 degrees C; saponification value, 202. 3mg KOH / g oil; refractive index ( 60 degrees C ), 1. 468; unsaponifiable matter, 1. 37 %; free fatty acids ( as the percentage of oleic acid ), 0. 96 %; and peroxide value, 3. 37mequiv.", "output": "KOH, fatty acids, oleic acid, peroxide." }, { "input": "O2 / kg oil.", "output": "O2." }, { "input": "High - resolution ( 1 ) H nuclear magnetic resonance ( ( 1 ) H NMR ) was used for the direct determination of the iodine value of Hachi fat ( 62. 74g / 100g oil ).", "output": "( 1 ) H, ( 1 ) H, iodine." }, { "input": "The Hachi fat was composed primarily of oleic acid ( 33. 35 % ), followed by palmitic acid ( 26. 16 % ), stearic acid ( 10. 07 % ), palmitelaidic acid ( 9. 56 % ) and myristic acid ( 8. 83 % ).", "output": "oleic acid, palmitic acid, stearic acid, palmitelaidic acid, myristic acid." }, { "input": "The thermal properties were assessed by thermogravimetry ( TG ) and derivative thermogravimetry ( DTG ).", "output": "There is no related enetity." }, { "input": "The results of the present analytical study showed that Hachi fat could be used in food products and as an important source of biological materials.", "output": "There is no related enetity." }, { "input": "A method for determining regioisomer abundances of polyunsaturated triacylglycerols in omega - 3 enriched fish oils using reversed - phase liquid chromatography and triple - stage mass spectrometry.", "output": "polyunsaturated triacylglycerols." }, { "input": "Reversed - phase high performance liquid chromatography ( RP - HPLC ), followed by post - column addition of lithium salts and electrospray ionisation triple - stage mass spectrometry ( ESI - MS ( 3 ) ) of lithiated TAG adducts, is shown to provide a useful method for the positional analysis of triacylglycerols ( TAGs ) in fish oils containing eicosapentaenoic ( EPA, 20: 5 ) and docosahexaenoic acids ( DHA, 22: 6 ).", "output": "lithiated TAG, triacylglycerols, TAGs, eicosapentaenoic, EPA, docosahexaenoic acids, DHA." }, { "input": "One prominent fragmentation pathway in the ESI - MS ( 3 ) of these adduct ions involves the loss of a fatty acid from the sn - 1 / 3 position in the first step followed by the loss of an alpha, beta - unsaturated fatty acid from the sn - 2 position in the second.", "output": "fatty acid, alpha , beta - unsaturated fatty acid." }, { "input": "Regioisomeric TAGs of the type ABA and AAB produced abundant product ions - [ ABA + Li - RACOOH - R ' BCHCHCOOH ] ( + ) and [ AAB + Li - RACOOH - R ' ACHCHCOOH ] ( + ) - the relative intensities of which were dependent on the position of acyl substituents.", "output": "TAGs, Li - RACOOH, R ' BCHCHCOOH, Li - RACOOH, R ' ACHCHCOOH, acyl." }, { "input": "Standard solutions of TAGs containing different ratios of the regioisomeric pairs MME / MEM, PPE / PEP, PPD / PDP, EEP / EPE and DDP / DPD ( M = 14: 0, P = 16: 0, E = 20: 5, D = 22: 6 ) were analysed by ESI - MS ( 3 ) with a quadrupole linear ion trap instrument.", "output": "TAGs." }, { "input": "Methodology developed on the standards was applied to quantifying the relative isomeric abundances of EPA and DHA in several fish oil samples.", "output": "EPA, DHA." }, { "input": "DHA was preferentially located at the sn - 2 position in both DHA - containing TAGs studied, while EPA was either observed at near equal levels in all positions, or predominantly at the sn - 1 and - 3 positions in some cases.", "output": "DHA, DHA, TAGs, EPA." }, { "input": "The analysis protocol allows for quantification of the designated regioisomers in one simple, rapid chromatographic procedure using a single column and has the advantage of specificity over other methods for the positional analysis of TAGs, since it eliminates interferences associated with co - eluting TAGs of the same molecular weight that yield isobaric diacylglycerol - like product ions.", "output": "TAGs, TAGs, diacylglycerol." }, { "input": "Effect of calcium on the kinetics of free fatty acid release during in vitro lipid digestion in model emulsions.", "output": "calcium, fatty acid." }, { "input": "The effects of different calcium salts on in vitro lipid digestion were examined by determining the free fatty acids released from various oil - in - water emulsions.", "output": "calcium, fatty acids." }, { "input": "The kinetics of the total and individual free fatty acids released by lipolysis were monitored by the pH - stat method and gas chromatography, respectively.", "output": "fatty acids." }, { "input": "The rate and the extent of free fatty acid release increased with an increase in the added calcium concentration, but the increase was dependent on the emulsifying agent.", "output": "fatty acid, calcium." }, { "input": "The effect of calcium was diminished when the emulsion contained phosphate.", "output": "calcium, phosphate." }, { "input": "Soluble calcium salts, such as calcium gluconate, calcium acetate and CaCl2, had greater effects on the rate and extent of free fatty acid release than did insoluble salts, such as CaO and CaSO4, suggesting that the ionic state of calcium plays a critical role in lipid digestion in emulsions.", "output": "calcium, calcium gluconate, calcium acetate, CaCl2, fatty acid, CaO, CaSO4, calcium." }, { "input": "The addition of calcium did not alter the profiles of the individual free fatty acids released.", "output": "calcium, fatty acids." }, { "input": "This study provides useful information for food formulation with respect to lipid digestion.", "output": "There is no related enetity." }, { "input": "Chemical, rheological and surface morphologic characterisation of spent hen proteins extracted by pH - shift processing with or without the presence of cryoprotectants.", "output": "There is no related enetity." }, { "input": "The chemical and rheological properties of spent hen proteins recovered by acid and alkaline extraction have been studied with / without cryoprotectants ( CP ) after 3weeks of frozen storage.", "output": "There is no related enetity." }, { "input": "Four pH values ( 2. 0, 2. 5, 11. 5, and 12. 0 ) were used for extraction.", "output": "There is no related enetity." }, { "input": "CP addition prevented freeze - induced denaturation and oxidation in all extracted proteins, as revealed by significant increases in reactive sulphydryl groups ( p < 0. 0001 ), and a decrease in the formation of carbonyl groups ( p < 0. 0001 ).", "output": "sulphydryl, carbonyl." }, { "input": "The alkaline extracted proteins with CP formed more viscoelastic gels compared to the others, while samples without CP failed to form a gel network.", "output": "There is no related enetity." }, { "input": "FTIR of the protein isolates with CP showed a protective effect on the secondary structure of the isolated proteins.", "output": "There is no related enetity." }, { "input": "Scanning electron micrographs showed a protective shield of CP around the isolated proteins.", "output": "There is no related enetity." }, { "input": "Carotenoids and tocopherols in yellow and red raspberries.", "output": "tocopherols." }, { "input": "The composition of carotenoids, chlorophyll derivatives and tocopherols in raspberries of different varieties, including yellow and red varieties, over different ripening stages has been studied.", "output": "chlorophyll, tocopherols." }, { "input": "The profile of pigments in ripening raspberries changes drastically, with a dramatic decrease of beta - carotene and chlorophyll derivatives, the xanthophyll lutein has also decreased but not to the same extent.", "output": "beta - carotene, chlorophyll, xanthophyll, lutein." }, { "input": "In contrast esterified lutein increased and is present in ripe raspberries esterified with saturated fatty acids with C8 - C16 chains.", "output": "lutein, fatty acids, C8 - C16." }, { "input": "Ripe raspberries contain considerable amounts of free lutein, esterified lutein, and tocopherols ( up to 20, 49 and 366mg / kg dry weight, respectively ).", "output": "lutein, lutein, tocopherols." }, { "input": "The different samples analysed show different contents of carotenoids and tocopherols.", "output": "tocopherols." }, { "input": "Whether the differences arise from the variety or other factors such as the environmental conditions needs to be ascertained but isoprenoids should not be neglected when considering raspberry antioxidant and nutraceutical composition.", "output": "isoprenoids." }, { "input": "Rapid chemical profiling of saponins in the flower buds of Panax notoginseng by integrating MCI gel column chromatography and liquid chromatography / mass spectrometry analysis.", "output": "saponins." }, { "input": "The flower buds of Panax notoginseng ( Notoginseng flower, FBP ) are used as the traditional Chinese medicine San - Qi - Hua.", "output": "There is no related enetity." }, { "input": "In this study, we conducted column chromatography fractionation and liquid chromatography / mass spectrometry ( LC / MS ) analysis to comprehensively profile bioactive notoginseng saponins ( ginsenosides ) in FBP.", "output": "saponins, ginsenosides." }, { "input": "MCI gel column chromatography allowed separation and enrichment of minor saponins.", "output": "saponins." }, { "input": "Electrospray ionization tandem mass spectrometry of [ M - H ] ( - ) and [ M + Na ] ( + ) precursor ions of the saponins provided reliable structural information for the sapogenin, and sequence of sugar chains.", "output": "H, Na, sugar." }, { "input": "Confirmed by high - accuracy Q - TOF analysis, 170 notoginseng saponins were characterized from FBP, and 91 of them were reported from Panax species for the first time.", "output": "saponins." }, { "input": "The new ginsenosides contain acyl groups on alpha - chain, malonyl group at 20 - OH, or di - malonyl groups.", "output": "ginsenosides, acyl, malonyl, OH, di - malonyl." }, { "input": "This study also indicated that the flower buds of P. notoginseng contained more protopanaxadiol - type but less protopanaxatriol - type ginsenosides than the roots.", "output": "protopanaxadiol, protopanaxatriol, ginsenosides." }, { "input": "Effect of flavonoid structure on the fluidity of model lipid membranes.", "output": "flavonoid." }, { "input": "We investigated how the structural properties of ( + ) - catechin, ( - ) - epicatechin, ( - ) - epigallocatechin ( EGC ) and ( - ) - epigallocatechin - 3 - gallate ( EGCG ) and butylated hydroxytoluene ( BHT ) correlate with structural changes of phosphatidylcholine plus sphingomyelin ( 2. 4: 1 ) model lipid membranes.", "output": "( + ) - catechin, ( - ) - epicatechin, ( - ) - epigallocatechin, EGC, ( - ) - epigallocatechin - 3 - gallate, EGCG, butylated hydroxytoluene, BHT, phosphatidylcholine, sphingomyelin." }, { "input": "Changes were measured by fluorescence anisotropy, electron paramagnetic resonance, and differential scanning calorimetry.", "output": "There is no related enetity." }, { "input": "Two fluorophores and two spin probes were used to monitor membrane characteristics close to water - lipid interface and in the middle of the bilayer.", "output": "There is no related enetity." }, { "input": "The data obtained were correlated to the amount of bounded compounds, the number of H - bonds, and the topological polar surface area ( TPSA ) of the compounds.", "output": "H." }, { "input": "These correlations reflect the behaviours of ( + ) - catechin, ( - ) - epicatechin, EGC, EGCG and BHT.", "output": "( + ) - catechin, ( - ) - epicatechin, EGC, EGCG, BHT." }, { "input": "Our results confirm that phenolics studied here are bounded to a membrane surface predominantly via hydrogen bonds, while BTH is inserted into the lipid bilayer.", "output": "hydrogen, BTH." }, { "input": "Effects of industrial processing on folate content in green vegetables.", "output": "folate." }, { "input": "Folates are described to be sensitive to different physical parameters such as heat, light, pH and leaching.", "output": "Folates." }, { "input": "Most studies on folates degradation during processing or cooking treatments were carried out on model solutions or vegetables only with thermal treatments.", "output": "folates." }, { "input": "Our aim was to identify which steps were involved in folates loss in industrial processing chains, and which mechanisms were underlying these losses.", "output": "folates." }, { "input": "For this, the folates contents were monitored along an industrial canning chain of green beans and along an industrial freezing chain of spinach.", "output": "folates." }, { "input": "Folates contents decreased significantly by 25 % during the washing step for spinach in the freezing process, and by 30 % in the green beans canning process after sterilisation, with 20 % of the initial amount being transferred into the covering liquid.", "output": "Folates." }, { "input": "The main mechanism involved in folate loss during both canning green beans and freezing spinach was leaching.", "output": "folate." }, { "input": "Limiting the contact between vegetables and water or using steaming seems to be an adequate measure to limit folates losses during processing.", "output": "folates." }, { "input": "Home conservation strategies for tomato ( Solanum lycopersicum ): Storage temperature vs. duration - Is there a compromise for better aroma preservation?", "output": "There is no related enetity." }, { "input": "Expression of dissatisfaction with tomato aroma prompted us to lead this study on the impact of domestic storage conditions on volatile compounds.", "output": "There is no related enetity." }, { "input": "Two storage modalities ( 20 and 4 degrees C ) and two cultivars ( Levovil and LCx ) were used.", "output": "There is no related enetity." }, { "input": "Volatile compounds were analysed by gas chromatography - mass spectrometry detection after accelerated solvent extraction.", "output": "There is no related enetity." }, { "input": "Physical characteristics, lipoxygenase activity, hydroperoxide lyase activity; linoleic acid and linolenic acid were monitored.", "output": "hydroperoxide, linoleic acid, linolenic acid." }, { "input": "Storing tomatoes at 4 degrees C induced a drastic loss in volatiles, whatever their biosynthetic origin.", "output": "There is no related enetity." }, { "input": "After 30days at 4 degrees C, the concentration of volatiles had decreased by 66 %.", "output": "There is no related enetity." }, { "input": "Reconditioning for 24h at 20 degrees C was able to recover some aroma production after up to 6days storage at 4 degrees C.", "output": "There is no related enetity." }, { "input": "Volatile degradation products arising from carotenoids and amino acids increased when tomatoes were kept at 20 degrees C, while lipid degradation products did not vary.", "output": "amino acids." }, { "input": "Storing tomatoes at fridge temperature, even for short durations, was detrimental for their aroma.", "output": "There is no related enetity." }, { "input": "This should be taken into account to formulate practical advice for consumers.", "output": "There is no related enetity." }, { "input": "High performance thin layer chromatography - densitometry: A step further for quality control of cranberry extracts.", "output": "There is no related enetity." }, { "input": "A method for selective quantitation of catechin, proanthocyanidin ( PAC ) A2 and PAC - B1 in American cranberry ( Vaccinium macrocarpon ) extracts using high performance thin layer chromatography ( HPTLC ) - densitometry is presented.", "output": "catechin, proanthocyanidin, PAC, PAC - B1." }, { "input": "Methylene chloride / ethyl acetate / formic acid ( 6: 10: 1, v / v ) as the mobile phase and 1 % vanillin hydrochloric solution as staining reagent were used.", "output": "Methylene chloride, ethyl acetate, formic acid, vanillin hydrochloric." }, { "input": "In these conditions, three standards considered as quality markers, catechin, PAC - A2 and PAC - B1, were well resolved allowing simultaneous quantitation on one plate.", "output": "catechin, PAC - A2, PAC - B1." }, { "input": "All standards were quantified in the range of 0. 7 - 5 mu g with RSD of repeatability and intermediate precision not exceeding 5 %.", "output": "There is no related enetity." }, { "input": "Catechin, PAC - A2 and PAC - B1 profiles of cranberry extracts were analysed regarding global PAC amounts obtained by BL - DMAC assay.", "output": "Catechin, PAC - A2, PAC - B1, PAC." }, { "input": "It appears clearly that HPTLC - densitometry process provides additional information which, combined with BL - DMAC results, allows qualitative and quantitative control of cranberry extracts.", "output": "There is no related enetity." }, { "input": "Particularly, densitometric assay highlighted degradation of PACs in a 7day - extract, leading to high overestimation with BL - DMAC protocol.", "output": "PACs." }, { "input": "Modulating beta - carotene bioaccessibility by controlling oil composition and concentration in edible nanoemulsions.", "output": "beta - carotene." }, { "input": "Diets rich in carotenoids have been correlated with a reduced risk of developing certain types of chronic diseases, but these bioactive components have low intestinal absorption due to their hydrophobic nature.", "output": "There is no related enetity." }, { "input": "The aim of this work was to study the effect of carrier oil composition ( medium - chain triglyceride ( MCT ) to long - chain triglyceride ( LCT ) ratio ) and total carrier oil concentration ( 1 % or 4 % w / w ) on the physical stability, lipid digestibility and bioaccessibility of beta - carotene - loaded nanoemulsions, using a simulated digestion process.", "output": "triglyceride, triglyceride, beta - carotene." }, { "input": "Lipolysis led to an appreciable increase in the size and negative charge on the particles in the system.", "output": "There is no related enetity." }, { "input": "The total fraction of triacylglycerols converted to free fatty acids decreased as the percentage of LCT within the lipid phase increased, particularly for the nanoemulsions with higher fat contents.", "output": "triacylglycerols, fatty acids." }, { "input": "There was an increase in beta - carotene bioaccessibility as the LCT within the lipid phase increased for low fat nanoemulsions, which was attributed to the increased solubilisation capacity of mixed micelles formed by LCT.", "output": "beta - carotene." }, { "input": "beta - carotene bioaccessibility showed a complex relationship on LCT content for high fat nanoemulsions, due to the opposing effects of lipid digestion and micelle solubilisation.", "output": "beta - carotene." }, { "input": "These results may facilitate the optimisation of delivery systems for lipophilic bioactive compounds for food or pharmaceutical applications.", "output": "There is no related enetity." }, { "input": "Antibacterial activity - guided purification and identification of a novel C - 20 oxygenated ent - kaurane from Rabdosia serra ( MAXIM. ) HARA.", "output": "C - 20 oxygenated ent - kaurane." }, { "input": "The objective of this work was to conduct an activity - guided isolation of antibacterial compounds from Rabdosia serra.", "output": "There is no related enetity." }, { "input": "The ethanol extracts of R. serra leaf and stem were partitioned sequentially into petroleum ether, ethyl acetate, butanol and water fractions, respectively.", "output": "ethanol, petroleum ether, ethyl acetate, butanol." }, { "input": "The ethanol extract of leaf evidenced broad - spectrum antibacterial activity against Gram - positive bacterial, including Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Listeria monocytogenes.", "output": "ethanol." }, { "input": "The ethyl acetate fractions of leaf and stem exhibited strong inhibition against Gram - positive bacteria, and were then purified further.", "output": "ethyl acetate." }, { "input": "On the basis of antibacterial assay - guided purification, three phenolic compounds ( rosmarinic acid, methyl rosmarinate and pedalitin ) and four C - 20 oxygenated ent - kauranes ( effusanin E, lasiodin, rabdosichuanin D and a new compound namely effusanin F ) were obtained, whose contents were determined by HPLC analysis.", "output": "rosmarinic acid, methyl rosmarinate, pedalitin, C - 20 oxygenated ent - kauranes, effusanin E, lasiodin, rabdosichuanin D, effusanin F." }, { "input": "The broth microdilution method confirmed the important inhibition potential of C - 20 oxygenated ent - kauranes with low minimum inhibitory concentration ( MIC ) values.", "output": "C - 20 oxygenated ent - kauranes." }, { "input": "Effusanin E, lasiodin and effusanin F could be useful for the development of new antibacterial agents.", "output": "Effusanin E, lasiodin, effusanin F." }, { "input": "Preparative separation of triterpene alcohol ferulates from rice bran oil using a high performance counter - current chromatography.", "output": "triterpene alcohol." }, { "input": "A novel method for the separation of two major triterpene alcohol ferulates from rice bran oil ( RBO ) was developed using a high performance counter - current chromatography ( HPCCC ).", "output": "triterpene alcohol." }, { "input": "A two - phase solvent system of n - hexane - acetonitrile ( 1: 1, v / v ) was applied to purify cycloartenyl ferulate ( CAF ) and 24 - methylene cycloartanyl ferulate ( 24 - mCAF ) from RBO.", "output": "n - hexane, acetonitrile, cycloartenyl ferulate, CAF, 24 - methylene cycloartanyl ferulate, 24 - mCAF." }, { "input": "The yields were 20. 50 +/- 2. 60mg CAF and 12. 62 +/- 1. 15mg 24 - mCAF from 390mg RBO through a two - step separation procedure.", "output": "CAF, 24 - mCAF." }, { "input": "The purities of the two compounds were 97. 97 +/- 0. 90 % and 95. 50 +/- 0. 75 %, respectively, as determined by high performance liquid chromatography ( HPLC ).", "output": "There is no related enetity." }, { "input": "Their chemical structures were confirmed by ultra performance liquid chromatography - quadrupole time - of - flight mass spectrometry ( UPLC - Q - TOF - MS ), and ( 1 ) H, ( 13 ) C and 2D nuclear magnetic resonance ( NMR ).", "output": "( 1 ) H, ( 13 ) C." }, { "input": "This represents the first report on direct separation of CAF and 24 - mCAF from RBO by HPCCC.", "output": "CAF, 24 - mCAF." }, { "input": "Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and beta - oxidation: A proof of concept study.", "output": "alkylresorcinols." }, { "input": "Alkylresorcinols ( AR ) are phenolic lipids present in the bran of some cereals.", "output": "Alkylresorcinols, phenolic." }, { "input": "AR may serve as a biomarker for whole grain wheat and rye intake.", "output": "There is no related enetity." }, { "input": "While AR pharmacokinetics and two major metabolites have been reported, the metabolic pathways contributing to their relatively rapid elimination from the circulation remain to be speculative.", "output": "There is no related enetity." }, { "input": "In this study, we investigated if omega - and beta - oxidation mediate catabolism of the AR homologue C19: 0 to form 3, 5 - dihydroxybenzoic acid and 3 - ( 3, 5 - dihydroxyphenyl ) - 1 - propanoic acid ( DHPPA ), using 3 in vitro platforms, human cytochrome P450 4F2 ( CYP4F2 ), human liver S9, and HepG2 cells.", "output": "3 , 5 - dihydroxybenzoic acid, 3 - ( 3 , 5 - dihydroxyphenyl ) - 1 - propanoic acid, DHPPA." }, { "input": "One hydroxylated C19: 0 metabolite was formed by CYP4F2 and one hydroxylated and one carboxylated C19: 0 were tentatively identified after incubation of AR with S9.", "output": "There is no related enetity." }, { "input": "The formation of DHPPA was quantifiable when HepG2 cells were treated with C19: 0 for 48h.", "output": "DHPPA." }, { "input": "Our results are consistent with a metabolic pathway by which AR are degraded to phenolic acids via CYP4F2 - mediated omega - oxidation and subsequent beta - oxidation.", "output": "There is no related enetity." }, { "input": "Modifications of Kyoho grape berry quality under long - term NaCl treatment.", "output": "NaCl." }, { "input": "Different concentrations of a sodium chloride spray were applied to the grapevine cultivar Kyoho to determine the effects of salinity on berry quality.", "output": "sodium chloride." }, { "input": "The fruit ' s fresh weight, relative water content, hardness and titratable acid were gradually enhanced with increased salt concentrations.", "output": "There is no related enetity." }, { "input": "Anthocyanin and soluble solids increased after treatment with moderate salinity ( 20 and 60mM ); however, the results were reversed under high salinity ( 100 and 150mM ).", "output": "Anthocyanin." }, { "input": "The soluble sugars glucose, fructose and sucrose increased after treatment with moderate salinity, whereas glucose and fructose declined under high salinity.", "output": "sugars, glucose, fructose, sucrose, glucose, fructose." }, { "input": "For the six organic acids tested, their total levels were elevated by salinity, which increased the production of tartaric and malic acids.", "output": "tartaric and malic acids." }, { "input": "The aroma of the berry was extremely sensitive to salinity and showed a considerable decline in abundance and variety at 20mM NaCl.", "output": "NaCl." }, { "input": "In summary, moderate salinity enhanced the overall berry quality, but decreased the aroma quality, whereas high salinity decreased the berry quality.", "output": "There is no related enetity." }, { "input": "The impact of Ca ( 2 + ) combination with organic acids on green tea infusions.", "output": "Ca ( 2 + )." }, { "input": "The effect of Ca ( 2 + ) in brewing water on the organic acid content, turbidity, and formation of tea cream and sediment in green tea infusions was studied.", "output": "Ca ( 2 + )." }, { "input": "When the Ca ( 2 + ) concentration of the brewing water was > 40mgL ( - 1 ), the green tea infusion became more turbid.", "output": "Ca ( 2 + )." }, { "input": "The turbidity of the tea infusion was highly negatively correlated with the contents of oxalic acid ( R = - 0. 89, p < 0. 01 ), quinic acid ( R = - 0. 90, p < 0. 01 ) and tartaric acid ( R = - 0. 82, p < 0. 01 ).", "output": "oxalic acid, quinic acid, tartaric acid." }, { "input": "Oxalic acid on its own interacted with Ca ( 2 + ) at low concentrations, whereas polyphenols and protein did not.", "output": "Oxalic acid, Ca ( 2 + ), polyphenols." }, { "input": "In conclusion, Ca ( 2 + ) in brewing water influences the quality of a tea infusion by inducing tea cream and sediment formation from combination of Ca ( 2 + ) and organic acids, such as oxalic acid, quinic acid and tartaric acid.", "output": "Ca ( 2 + ), Ca ( 2 + ), oxalic acid, quinic acid, tartaric acid." }, { "input": "Ca ( 2 + ) and oxalate are the main metal ion and anion, respectively, involved in tea cream and sediment formation on tea infusion cooling or concentrating.", "output": "Ca ( 2 + ), oxalate." }, { "input": "Development of electrochemical biosensor with nano - interface for xanthine sensing - A novel approach for fish freshness estimation.", "output": "xanthine." }, { "input": "Highly sensitive, selective and mediator - free electrochemical biosensor with nano - interface for sensing xanthine using xanthine oxidase ( XOx ) has been developed.", "output": "xanthine, xanthine." }, { "input": "Towards the preparation of nano - interface, Fe3O4 nanoparticles were synthesized by thermal co - precipitation method and structural, morphological characterizations were carried out using X - ray diffraction ( XRD ), field emission scanning electron microscope ( FE - SEM ) and field emission transmission electron microscope ( FE - TEM ) respectively.", "output": "Fe3O4." }, { "input": "The modified electrode with the covalently linked XOx was confirmed by FT - IR.", "output": "There is no related enetity." }, { "input": "With the modified electrode as working electrode, electrochemical studies were carried out.", "output": "There is no related enetity." }, { "input": "The linear range was found to be from 0. 4 to 2. 4nM.", "output": "There is no related enetity." }, { "input": "The biosensor exhibited an optimum response in less than 2s and was not prone to interferences from ascorbic acid, urea and sucrose.", "output": "ascorbic acid, urea, sucrose." }, { "input": "The Michaelis - Menten constant ( Km ) was found to be 1. 3nM.", "output": "There is no related enetity." }, { "input": "The limit of detection is found to be 2. 5pM and limit of quantification as 8. 3pM.", "output": "There is no related enetity." }, { "input": "The developed biosensor was used for the real time measurement of fish freshness.", "output": "There is no related enetity." }, { "input": "Cultivating conditions effects on kefiran production by the mixed culture of lactic acid bacteria imbedded within kefir grains.", "output": "lactic acid." }, { "input": "The influence of fermentation temperature, agitation rate, and additions of carbon sources, nitrogen sources, vitamins and minerals on production of kefiran by kefir grains lactic acid bacteria was studied in a series of experiments.", "output": "carbon, nitrogen, lactic acid." }, { "input": "The main aim of the work was to increase the exopolysaccharide ( EPS ) production where customised milk was used as fermentation medium.", "output": "There is no related enetity." }, { "input": "It was proved that the controlling of culturing conditions and the modifying of fermentation medium conditions ( i. e., carbon, nitrogen, mineral sources and vitamins ) can dramatically enhance the production of the EPS.", "output": "carbon, nitrogen." }, { "input": "The temperature and agitation rate were critical for kefiran production during the 24h cultivation of grains; our optimised conditions being 25 degrees C and 80rpm, respectively.", "output": "There is no related enetity." }, { "input": "In addition, when optimising the effects of additional nutrition, it was found that 5 % ( w / v ) lactose, 0. 1 % ( w / v ) thiamine, and 0. 1 % ( w / v ) FeCl3 led to the maximal production of EPS.", "output": "lactose, thiamine, FeCl3." }, { "input": "The results indicate that nutrients can be utilised to improve the production of EPS and that good kefir grains growth does not appear to be a determining factor for a high production yield of EPS.", "output": "There is no related enetity." }, { "input": "A Rapid tool for the stability assessment of natural food colours.", "output": "There is no related enetity." }, { "input": "Natural food colours lack stability under a number of conditions such as pH variation, oxidation, hydration, heat treatment and, most importantly, exposure to daylight.", "output": "There is no related enetity." }, { "input": "Stability tests to assess shelf life of natural colours under light irradiation can be time consuming.", "output": "There is no related enetity." }, { "input": "Thus, an accelerated test carried out under high light intensity irradiation that can be related to normal daylight irradiation conditions is highly desirable.", "output": "There is no related enetity." }, { "input": "Samples of various natural colouring solutions were prepared in aqueous model matrices at a range of pH values to mimic the majority of food matrices, pasteurised and irradiated under normal D65 light ( 0. 2W / m ( 2 ) ) at 25 degrees C, and in parallel under high light intensity irradiation ( 30W / m ( 2 ) ) at 3 different temperatures ( 25, 35 and 45 degrees C ).", "output": "There is no related enetity." }, { "input": "Similarly to the already known Q10 parameters for temperature, acceleration factors QL for irradiation, were determined and used for the first time to obtain a link between colour degradation under normal and accelerated conditions.", "output": "There is no related enetity." }, { "input": "It was possible, using these acceleration factors, to greatly reduce the time required to predict and compare the shelf life stability for a series of natural colours in aqueous model systems.", "output": "There is no related enetity." }, { "input": "A micellar improved method for trace levels selenium quantification in food samples, alcoholic and nonalcoholic beverages through CPE / FAAS.", "output": "selenium." }, { "input": "A useful preconcentration and determination method was proposed for trace selenium in food samples.", "output": "selenium." }, { "input": "The procedure is based on complex formation of Pyronine B with Se ( IV ) ions in the presence of sodium dodecyl sulphate ( SDS ) and Ponpe 7. 5.", "output": "Pyronine B, Se ( IV ), sodium dodecyl sulphate, SDS." }, { "input": "The variables affecting complex formation, extraction and phase separation were studied and optimised.", "output": "There is no related enetity." }, { "input": "Under the experimental conditions used, the calibration graph was linear in the range of 20 - 1700 mu gL ( - 1 ) for Se ( IV ) ions.", "output": "Se ( IV )." }, { "input": "The limit of detection was 3. 81 mu gL ( - 1 ) of Se ( IV ) and the relative standard deviation for 5 replicate determinations at 250 mu gL ( - 1 ) concentration level was 2. 45 %.", "output": "Se ( IV )." }, { "input": "Recovery values were obtained between 97. 8 % and 102. 8 % for spiked samples.", "output": "There is no related enetity." }, { "input": "The method was successfully applied to the determination of total selenium in some food samples and alcoholic and nonalcoholic beverages.", "output": "selenium." }, { "input": "Its validity was checked by the analysis of four certified reference materials.", "output": "There is no related enetity." }, { "input": "The results obtained by the proposed method were quantitatively in good agreement with the certified values.", "output": "There is no related enetity." }, { "input": "Effect of Saccharomyces strains on the quality of red wines aged on lees.", "output": "There is no related enetity." }, { "input": "Ageing on lees involves ageing the wine in contact with yeast cells after fermentation.", "output": "There is no related enetity." }, { "input": "If combined with the addition of oak chips, it can soften the wood flavour and increase the aromatic complexity of wine.", "output": "There is no related enetity." }, { "input": "The aim of the present work is to optimise both ageing techniques through selection of an adequate Saccharomyces cerevisiae strain.", "output": "There is no related enetity." }, { "input": "The study lasted 6months and content of polysaccharides, anthocyanins, proanthocyanidins, volatile compounds, colour parameters and sensory analysis, were periodically evaluated.", "output": "anthocyanins, proanthocyanidins." }, { "input": "Among the strains tested, G37 showed the highest release of polysaccharides ( 24. 4 +/- 5. 5mgl ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "Vanillin, syringaldehyde and furfuryl alcohol increased with ageing time in 7VA2 treatment.", "output": "Vanillin, syringaldehyde, furfuryl alcohol." }, { "input": "The wine aged with CTPL14 strain presented fewer monomeric and oligomeric proanthocyanidins ( 12. 4 +/- 0. 6 and 83. 4 +/- 8. 3mgl ( - 1 ), respectively ), and showed the lowest astringency and bitterness sensations.", "output": "proanthocyanidins." }, { "input": "Results show an improvement in the sensory profile of the red wine aged with a combination of these two techniques.", "output": "There is no related enetity." }, { "input": "Diversity of ( dihydro ) hydroxycinnamic acid conjugates in Colombian potato tubers.", "output": "( dihydro ) hydroxycinnamic acid." }, { "input": "In potato tuber, caffeic acid ( the predominant hydroxycinnamic acid ( HCA ) ), its conjugates ( HCAcs; i. e. chlorogenic acid ( ChA ), crypto - ChA, and neo - ChA ), and anthocyanin - linked HCAs have been extensively described in the literature.", "output": "caffeic acid, hydroxycinnamic acid, HCA, chlorogenic acid, ChA, crypto - ChA, neo - ChA, anthocyanin, HCAs." }, { "input": "In contrast, only little information is available on the occurrence of other HCAcs and didydrohydroxycinnamic acid conjugates ( DHCAcs ).", "output": "didydrohydroxycinnamic acid." }, { "input": "Fifteen Colombian potato cultivars were screened for these less commonly described conjugates by reversed - phase ultrahigh performance liquid chromatography coupled to a diode array detector and a heated electrospray ionisation mass spectrometer.", "output": "There is no related enetity." }, { "input": "A total of 62 HCAs / HCAcs / DHCAcs were found in extracts from peel and flesh.", "output": "HCAs." }, { "input": "Among them, only twelve compounds were common to all cultivars in both peel and flesh.", "output": "There is no related enetity." }, { "input": "The less commonly described compounds accounted for 7. 1 - 20. 1 % w / w of the total amount of HCAs / HCAcs / DHCAcs in whole tubers, highlighting their contribution to the total phenolic profile of potato tubers.", "output": "HCAs." }, { "input": "Among all cultivars, the abundance ( mg / 100g DW whole tuber ) of neo - ChA ( 0. 8 - 7. 4 ) ranged in similar quantities as the less commonly reported feruloyl octopamine ( 1. 2 - 5. 2 ), 5 - O - feruloyl quinic acid ( 0. 1 - 7. 5 ), cis - ChA ( 1. 1 - 2. 2 ), caffeoyl putrescine ( 0. 6 - 2. 5 ), sinapoyl hexose ( 0. 1 - 1. 8 ), N ( 1 ), N ( 14 ) - bis - ( dihydrocaffeoyl ) spermine ( 0. 2 - 1. 7 ), N ( 1 ), N ( 10 ) - bis - ( dihydrocaffeoyl ) spermidine ( 1. 1 - 2. 6 ), and N ( 1 ), N ( 5 ), N ( 14 ) - tris - ( dihydrocaffeoyl ) spermine ( trace - 11. 1 ).", "output": "neo - ChA, feruloyl octopamine, 5 - O - feruloyl quinic acid, cis - ChA, caffeoyl putrescine, sinapoyl hexose, N ( 1 ) , N ( 14 ) - bis - ( dihydrocaffeoyl ) spermine, N ( 1 ) , N ( 10 ) - bis - ( dihydrocaffeoyl ) spermidine, N ( 1 ) , N ( 5 ) , N ( 14 ) - tris - ( dihydrocaffeoyl ) spermine." }, { "input": "Separation and purification of the antioxidant compounds, caffeic acid phenethyl ester and caffeic acid from mushrooms by molecularly imprinted polymer.", "output": "caffeic acid phenethyl ester, caffeic acid." }, { "input": "Caffeic acid phenethyl ester ( CAPE ) and caffeic acid ( CA ), two naturally occurring phenolic antioxidants, have been reported to have a diversity of biological activities.", "output": "Caffeic acid phenethyl ester, CAPE, caffeic acid." }, { "input": "In this investigation, a novel approach to separate and enrich CAPE and CA from 25 species of mushrooms using molecularly imprinted polymers ( MIPs ) as the sorbent material is reported.", "output": "CAPE." }, { "input": "The MIPs were synthesized using CAPE as the template, and its adsorption behavior was investigated in detail.", "output": "CAPE." }, { "input": "In comparison with C18 - solid phase extraction ( SPE ), MIP - SPE displayed high selectivity and good affinity for CAPE and CA.", "output": "CAPE." }, { "input": "The antioxidant potential of the mushroom extracts, before and after preconcentration using MIPs, was assayed by inhibition of erythrocyte hemolysis and lipid peroxidation.", "output": "There is no related enetity." }, { "input": "Application of MIPs with a high affinity toward CAPE and CA provides a novel method for obtaining active compounds from natural products.", "output": "CAPE." }, { "input": "Raggin ' on T - bet.", "output": "There is no related enetity." }, { "input": "Although increasing adiposity is usually associated with adipose tissue infiltration by inflammatory cells and systemic insulin resistance, Stolarczyk et al.", "output": "There is no related enetity." }, { "input": "( 2013 ) report in this issue that mice deficient in the T - box transcription factor, T - bet, display a dissociated phenotype with enhanced perigonadal adipose but enhanced insulin sensitivity.", "output": "There is no related enetity." }, { "input": "The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders.", "output": "There is no related enetity." }, { "input": "Endocannabinoids and cannabinoid CB1 receptors are known to play a generalized role in energy homeostasis.", "output": "There is no related enetity." }, { "input": "However, clinical trials with the first generation of CB1 blockers, now discontinued due to psychiatric side effects, were originally designed to reduce food intake and body weight rather than the metabolic risk factors associated with obesity.", "output": "There is no related enetity." }, { "input": "In this review, we discuss how, in addition to promoting energy intake, endocannabinoids control lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue.", "output": "There is no related enetity." }, { "input": "Direct actions in skeletal muscle and pancreas are also emerging.", "output": "There is no related enetity." }, { "input": "This knowledge may help in the design of future therapies for the metabolic syndrome.", "output": "There is no related enetity." }, { "input": "Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure.", "output": "There is no related enetity." }, { "input": "Mitochondrial fusion, fission, and mitophagy form an essential axis of mitochondrial quality control.", "output": "There is no related enetity." }, { "input": "However, quality control might not be the only task carried out by mitochondrial dynamics.", "output": "There is no related enetity." }, { "input": "Recent studies link mitochondrial dynamics to the balance between energy demand and nutrient supply, suggesting changes in mitochondrial architecture as a mechanism for bioenergetic adaptation to metabolic demands.", "output": "There is no related enetity." }, { "input": "By favoring either connected or fragmented architectures, mitochondrial dynamics regulates bioenergetic efficiency and energy expenditure.", "output": "There is no related enetity." }, { "input": "Placement of bioenergetic adaptation and quality control as competing tasks of mitochondrial dynamics might provide a new mechanism, linking excess nutrient environment to progressive mitochondrial dysfunction, common to age - related diseases.", "output": "There is no related enetity." }, { "input": "Improved Insulin Sensitivity despite Increased Visceral Adiposity in Mice Deficient for the Immune Cell Transcription Factor T - bet.", "output": "There is no related enetity." }, { "input": "Low - grade inflammation in fat is associated with insulin resistance, although the mechanisms are unclear.", "output": "There is no related enetity." }, { "input": "We report that mice deficient in the immune cell transcription factor T - bet have lower energy expenditure and increased visceral fat compared with wild - type mice, yet paradoxically are more insulin sensitive.", "output": "There is no related enetity." }, { "input": "This striking phenotype, present in young T - bet ( - / - ) mice, persisted with high - fat diet and increasing host age and was associated with altered immune cell numbers and cytokine secretion specifically in visceral adipose tissue.", "output": "There is no related enetity." }, { "input": "However, the favorable metabolic phenotype observed in T - bet - deficient hosts was lost in T - bet ( - / - ) mice also lacking adaptive immunity ( T - bet ( - / - ) xRag2 ( - / - ) ), demonstrating that T - bet expression in the adaptive rather than the innate immune system impacts host glucose homeostasis.", "output": "glucose." }, { "input": "Indeed, adoptive transfer of T - bet - deficient, but not wild - type, CD4 ( + ) T cells to Rag2 ( - / - ) mice improved insulin sensitivity.", "output": "There is no related enetity." }, { "input": "Our results reveal a role for T - bet in metabolic physiology and obesity - associated insulin resistance.", "output": "There is no related enetity." }, { "input": "Quantitative protein analysis using ( 13 ) C7 - labeled iodoacetanilide and d5 - labeled N - ethylmaleimide by nano liquid chromatography / nanoelectrospray ionization ion trap mass spectrometry.", "output": "( 13 ) C7, iodoacetanilide, d5, N - ethylmaleimide." }, { "input": "We have developed a methodology for quantitative analysis and concurrent identification of proteins by the modification of cysteine residues with a combination of iodoacetanilide ( IAA, 1 ) and ( 13 ) C7 - labeled iodoacetanilide ( ( 13 ) C7 - IAA, 2 ), or N - ethylmaleimide ( NEM, 3 ) and d5 - labeled N - ethylmaleimide ( d5 - NEM, 4 ), followed by mass spectrometric analysis using nano liquid chromatography / nanoelectrospray ionization ion trap mass spectrometry ( nano LC / nano - ESI - IT - MS ).", "output": "cysteine, iodoacetanilide, IAA, ( 13 ) C7, iodoacetanilide, ( 13 ) C7, IAA, N - ethylmaleimide, NEM, d5, N - ethylmaleimide, d5, NEM." }, { "input": "The combinations of these stable isotope - labeled and unlabeled modifiers coupled with LC separation and ESI mass spectrometric analysis allow accurate quantitative analysis and identification of proteins, and therefore are expected to be a useful tool for proteomics research.", "output": "There is no related enetity." }, { "input": "Social information signaling by neurons in primate striatum.", "output": "There is no related enetity." }, { "input": "Social decisions depend on reliable information about others.", "output": "There is no related enetity." }, { "input": "Consequently, social primates are motivated to acquire information about the identity, social status, and reproductive quality of others [ 1 ].", "output": "There is no related enetity." }, { "input": "Neurophysiological [ 2 ] and neuroimaging [ 3, 4 ] studies implicate the striatum in the motivational control of behavior.", "output": "There is no related enetity." }, { "input": "Neuroimaging studies specifically implicate the ventromedial striatum in signaling motivational aspects of social interaction [ 5 ].", "output": "There is no related enetity." }, { "input": "Despite this evidence, precisely how striatal neurons encode social information remains unknown.", "output": "There is no related enetity." }, { "input": "Therefore, we probed the activity of single striatal neurons in monkeys choosing between visual social information at the potential expense of fluid reward.", "output": "There is no related enetity." }, { "input": "We show for the first time that a population of neurons located primarily in medial striatum selectively signals social information.", "output": "There is no related enetity." }, { "input": "Surprisingly, representation of social information was unrelated to simultaneously expressed social preferences.", "output": "There is no related enetity." }, { "input": "A largely nonoverlapping population of neurons that was not restricted to the medial striatum signaled information about fluid reward.", "output": "There is no related enetity." }, { "input": "Our findings demonstrate that information about social context and nutritive reward are maintained largely independently in striatum, even when both influence decisions to execute a single action.", "output": "There is no related enetity." }, { "input": "Genome - wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing.", "output": "There is no related enetity." }, { "input": "SR proteins are well - characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers ( ESEs ).", "output": "There is no related enetity." }, { "input": "However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell.", "output": "There is no related enetity." }, { "input": "Here, we report global analyses of two prototypical SR proteins, SRSF1 ( SF2 / ASF ) and SRSF2 ( SC35 ), using splicing - sensitive arrays and CLIP - seq on mouse embryo fibroblasts ( MEFs ).", "output": "There is no related enetity." }, { "input": "Unexpectedly, we find that these SR proteins promote both inclusion and skipping of exons in vivo, but their binding patterns do not explain such opposite responses.", "output": "There is no related enetity." }, { "input": "Further analyses reveal that loss of one SR protein is accompanied by coordinated loss or compensatory gain in the interaction of other SR proteins at the affected exons.", "output": "There is no related enetity." }, { "input": "Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes.", "output": "There is no related enetity." }, { "input": "The pathological effects of Heminecrolysin, a dermonecrotic toxin from Hemiscorpius lepturus scorpion venom are mediated through its lysophospholipase D activity.", "output": "There is no related enetity." }, { "input": "We have previously identified Heminecrolysin, a sphingomyelinase D ( SMaseD ), as the major protein responsible for the main pathological effects observed following Hemiscorpius ( H. ) lepturus scorpion envenomation.", "output": "There is no related enetity." }, { "input": "We aimed herein to further investigate the kinetics and molecular mechanisms triggered by Heminecrolysin to initiate hematological disorders and inflammatory reaction.", "output": "There is no related enetity." }, { "input": "We show that Heminecrolysin highly hydrolyzes lysophosphatidylcholine ( LPC ) into lysophosphatidic acid ( LPA ) and choline, with a Vmax = 1481 +/- 51 mu mol / min / mg and a Km = 97 +/- 16. 78 mu M, at a much lesser extend sphingomyelin but not phosphatidylcholine substrates.", "output": "lysophosphatidylcholine, LPC, lysophosphatidic acid, LPA, choline, sphingomyelin, phosphatidylcholine." }, { "input": "Its lysophospholipase D ( lysoPLD ) catalytic efficiency, up to three orders of magnitude higher, comparatively to spider ' s SMaseDs ( newly referred as phospholipases D; PLDs ), could explain its strong hemolytic capacity.", "output": "There is no related enetity." }, { "input": "Chelating agents such as EDTA, EGTA, and 1, 10 - phenantroline blocked Heminecrolysin - induced LPC hydrolysis at 98, 48, and 70 % respectively.", "output": "EDTA, EGTA, 1 , 10 - phenantroline." }, { "input": "Hemolysis blockade occurs only when the toxin is added to erythrocytes in the presence of serum, source of LPC and complement, indicating that the production of LPA and the presence of complement are mandatory for hemolysis.", "output": "LPC, LPA." }, { "input": "Moreover, we show that Heminecrolysin efficiently binds to erythrocyte ' s membrane and provokes phosphatidylserine ( PS ) translocation without cleavage of glycophorin A, suggesting that, unlike spider ' s PLDs, complement was activated only via the classical pathway.", "output": "phosphatidylserine." }, { "input": "Interestingly, Heminecrolysin was found to induce PS exposure on human nucleated Jurkat T cells, to stimulate secretion of the pro - inflammatory ( TNF - alpha, IL - 6 ), and anti - inflammatory ( IL - 10 ) cytokines by human monocytes, and to provoke a disseminated intravascular coagulation on chick embryo chorioallantoic membrane model system.", "output": "There is no related enetity." }, { "input": "Taken together, our results indicate that Heminecrolysin evokes the major characteristic clinical features of H. lepturus envenomation by using mainly its lysoPLD, rather than its SMaseD ' s, activity.", "output": "There is no related enetity." }, { "input": "Structure - activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin H.", "output": "ilicicolin H." }, { "input": "Ilicicolin H is a broad spectrum antifungal agent showing sub micro g / mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp.", "output": "Ilicicolin H." }, { "input": "It is a potent inhibitor ( C50 2 - 3ng / mL ) of the mitochondrial cytochrome bc1 reductase with over 1000 - fold selectivity against rat liver cytochrome bc1 reductase.", "output": "There is no related enetity." }, { "input": "Structure - activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19 - hydroxy derivative produced by biotransformation have been described.", "output": "ilicicolin H, 19 - hydroxy." }, { "input": "Basic 4 ' - esters and moderately polar N - and O - alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities.", "output": "4 ' - esters, N, O." }, { "input": "4 ', 19 - Diacetate and 19 - cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20 - fold improvement of plasma protein binding.", "output": "4 ' , 19 - Diacetate, 19 - cyclopropyl acetate." }, { "input": "Therapeutic targeting of chitosan - PEG - folate - complexed oncolytic adenovirus for active and systemic cancer gene therapy.", "output": "PEG, folate." }, { "input": "Adenovirus ( Ad ) - based cancer therapies have shown much promise.", "output": "There is no related enetity." }, { "input": "However, until now, Ad has only been delivered directly to primary tumors because the therapeutic efficacy of systemic delivery is limited by the immune response of the host, short blood circulation times, and non - specific liver uptake of Ad.", "output": "There is no related enetity." }, { "input": "In order to circumvent the issues regarding systemic delivery and to increase the safety and efficacy of Ad therapies, the surface of oncolytic Ad was coated with cationic polymer chitosan via ionic crosslinking ( Ad / chitosan ), after which polyethylene glycol ( PEG ) and / or folic acid ( FA ) was chemically conjugated onto the surface of Ad / chitosan, generating Ad / chitosan - FA, Ad / chitosan - PEG, and Ad / chitosan - PEG - FA nanocomplex.", "output": "polyethylene glycol, PEG, folic acid, PEG, PEG - FA." }, { "input": "The FA - coordinated Ad nanocomplexes ( Ad / chitosan - FA & Ad / chitosan - PEG - FA ) elicited folate receptor ( FR ) - selective cancer cell killing efficacy.", "output": "PEG - FA, folate." }, { "input": "In vivo administration of Ad / chitosan - PEG or Ad / chitosan - PEG - FA into mice demonstrated that PEGylation greatly increased blood circulation time, resulting in 9. 0 - fold and 48. 9 - fold increases at 24h after injection compared with naked Ad, respectively.", "output": "PEG, PEG - FA." }, { "input": "In addition, generation of Ad - specific neutralizing antibodies in mice treated with Ad / chitosan - PEG - FA was markedly decreased by 75. 3 % compared with naked Ad.", "output": "PEG - FA." }, { "input": "The quantitative polymerase chain reaction assay results showed a 285. 0 - fold increase in tumor tissues and a 378 - fold reduction of Ad / chitosan - PEG - FA in liver tissues compared with naked Ad.", "output": "PEG - FA." }, { "input": "Bioluminescence imaging study further supported the enhanced tumor - to - liver ratio of Ad / chitosan - PEG - FA.", "output": "PEG - FA." }, { "input": "Consequently, systemic delivery of Ad / chitosan - PEG - FA significantly inhibited the growth of FR - positive tumor, decreasing 52. 8 % compared to the naked Ad - treated group.", "output": "PEG - FA." }, { "input": "Importantly, PEGylated oncolytic Ad nanocomplexes showed no elevation of both alanine transaminase and aspartate transaminase levels, demonstrating that systemically delivered Ad - related hepatic damage can be completely eliminated with PEG conjugation.", "output": "alanine, aspartate, PEG." }, { "input": "In sum, these results demonstrate that conjugation of chitosan - PEG - FA to oncolytic Ad significantly improves antitumor efficacy and safety profiles, suggesting that Ad / chitosan - PEG - FA has potential as a therapeutic agent to target FR - positive cancer via systemic administration.", "output": "PEG - FA, PEG - FA." }, { "input": "Novel iontophoretic administration method for local therapy of breast cancer.", "output": "There is no related enetity." }, { "input": "Ductal drug therapy is a novel therapeutic approach for primary breast cancers, particularly those involving ductal carcinoma in situ lesions.", "output": "There is no related enetity." }, { "input": "Total or partial mastectomy with or without radiotherapy is the standard local therapy for primary breast cancer.", "output": "There is no related enetity." }, { "input": "Here, we propose a novel drug administration method for ductal drug therapy based on a drug delivery system ( DDS ) for primary breast cancer.", "output": "There is no related enetity." }, { "input": "This DDS was designed to deliver miproxifen phosphate ( TAT - 59 ), an antiestrogen drug, to ductal lesions via the milk duct, where carcinomas originate, more efficiently than systemic administration, using an iontophoretic technique applied to the nipple ( IP administration ).", "output": "miproxifen phosphate, TAT - 59." }, { "input": "Autoradiography imaging confirmed that TAT - 59 was directly delivered to the milk duct using IP administration.", "output": "TAT - 59." }, { "input": "The plasma concentrations of TAT - 59 and its active metabolite DP - TAT - 59 were quite low with IP administration.", "output": "TAT - 59, DP - TAT - 59." }, { "input": "The area under the curve value of DP - TAT - 59 in the mammary tissue was approximately 3 times higher with IP administration than with oral administration, at a 6 - fold lower dose, indicating higher availability of the drug delivered via DDS than via systemic administration.", "output": "DP - TAT - 59." }, { "input": "The low plasma concentrations would limit adverse effects to minor ones.", "output": "There is no related enetity." }, { "input": "These characteristics show that this DDS is suitable for the delivery of active DP - TAT - 59 to ductal lesions.", "output": "DP - TAT - 59." }, { "input": "Cavitation - enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.", "output": "There is no related enetity." }, { "input": "Oncolytic viruses ( OV ) and ultrasound - enhanced drug delivery are powerful novel technologies.", "output": "There is no related enetity." }, { "input": "OV selectively self - amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor.", "output": "There is no related enetity." }, { "input": "Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported.", "output": "There is no related enetity." }, { "input": "By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co - injected with microbubbles.", "output": "There is no related enetity." }, { "input": "Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage.", "output": "There is no related enetity." }, { "input": "Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure.", "output": "There is no related enetity." }, { "input": "Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real - time monitoring of successful viral delivery.", "output": "There is no related enetity." }, { "input": "Individual and combined cytotoxic effects of Fusarium toxins ( deoxynivalenol, nivalenol, zearalenone and fumonisins B1 ) on swine jejunal epithelial cells.", "output": "deoxynivalenol, nivalenol, zearalenone, fumonisins B1." }, { "input": "Fusarium mycotoxins occur worldwide in foods such as cereals and animal forages, leading to acute and chronic exposures in human and animals.", "output": "There is no related enetity." }, { "input": "Intestinal epithelial cells ( IECs ) are an important first target site for these dietary toxins.", "output": "There is no related enetity." }, { "input": "This study investigated the cytotoxicity of four common Fusarium mycotoxins, deoxynivalenol ( DON ), nivalenol ( NIV ), zearalenone ( ZEA ) and fumonisin B1 ( FB1 ) on a normal porcine jejunal epithelial cell line, IPEC - J2.", "output": "deoxynivalenol, DON, nivalenol, NIV, zearalenone, ZEA, fumonisin B1, FB1." }, { "input": "A dose response relationship between individual mycotoxins and cell viability ( MTT assay ) was initially investigated, and subsequently cytotoxic and non - cytotoxic concentrations were selected to investigate combinations of two, three and all four of the mycotoxins.", "output": "MTT." }, { "input": "For individual mycotoxins, a dose response was observed with cell viability, such that the potency ranking was NIV > DON > ZEA > FB1.", "output": "NIV, DON, ZEA, FB1." }, { "input": "At cytotoxic doses of individual mycotoxins, all mixtures gave reduced cell viability compared to control.", "output": "There is no related enetity." }, { "input": "At noncytotoxic concentrations of individual mycotoxins, all mixtures were cytotoxic with DON - NIV, DON - ZEA, DON - NIV - FB1, DON - ZEA - FB1, NIV - ZEA - FB1 and all four mixed causing the greatest loss of cell viability.", "output": "DON, NIV, DON, ZEA, DON, NIV, FB1, DON, ZEA, FB1, NIV, ZEA, FB1." }, { "input": "The latter observation in particular raises concerns over safety margins based on single toxin species, and suggests that the effects of multiple complex mixtures need to be better understood to assess health risks.", "output": "There is no related enetity." }, { "input": "CYP - 450 isoenzymes catalyze the generation of hazardous aromatic amines after reaction with the azo dye Sudan III.", "output": "aromatic amines, azo, Sudan III." }, { "input": "This work describes the mutagenic response of Sudan III, an adulterant food dye, using Salmonella typhimurium assay and the generation of hazardous aromatic amines after different oxidation methods of this azo dye.", "output": "Sudan III, aromatic amines, azo." }, { "input": "For that, we used metabolic activation by S9, catalytic oxidation by ironporphyrin and electrochemistry oxidation in order to simulate endogenous oxidation conditions.", "output": "ironporphyrin." }, { "input": "The oxidation reactions promoted discoloration from 65 % to 95 % of Sudan III at 1 x 10 ( - 4 ) molL ( - 1 ) and generation of 7. 6 x 10 ( - 7 ) molL ( - 1 ) to 0. 31 x 10 ( - 4 ) molL ( - 1 ) of aniline, o - anisidine, 2 - methoxi - 5 - methylaniline, 4 - aminobiphenyl, 4, 4 ' - oxydianiline; 4, 4 ' - diaminodiphenylmethane and 2, 6 - dimethylaniline.", "output": "Sudan III, aniline, o - anisidine, 2 - methoxi - 5 - methylaniline, 4 - aminobiphenyl, 4 , 4 ' - oxydianiline, 4 , 4 ' - diaminodiphenylmethane, 2 , 6 - dimethylaniline." }, { "input": "The results were confirmed by LC - MS - MS experiments.", "output": "There is no related enetity." }, { "input": "We also correlate the mutagenic effects of Sudan III using S. typhimurium with the strain TA1535 in the presence of exogenous metabolic activation ( S9 ) with the metabolization products of this compound.", "output": "Sudan III." }, { "input": "Our findings clearly indicate that aromatic amines are formed due to oxidative reactions that can be promoted by hepatic cells, after the ingestion of Sudan III.", "output": "aromatic amines, Sudan III." }, { "input": "Considering that, the use of azo compounds as food dyestuffs should be carefully controlled.", "output": "azo." }, { "input": "Bisphenol A affects androgen receptor function via multiple mechanisms.", "output": "Bisphenol A, androgen." }, { "input": "Bisphenol A ( BPA ), is a well - known endocrine disruptor compound ( EDC ) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear.", "output": "Bisphenol A, BPA." }, { "input": "To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain ( LBD ) - linked to the beta - Gal reporter were examined by a quantitative high throughput screening ( qHTS ) format in the Tox21 Screening Program of the NIH.", "output": "BPA." }, { "input": "The results showed that two receptors, estrogen receptor alpha ( ER alpha ) and androgen receptor ( AR ), are affected by BPA in opposite direction.", "output": "estrogen, androgen, BPA." }, { "input": "To confirm the observed effects of BPA on ER alpha and AR, we performed transient transfection experiments with full - length receptors and their corresponding response elements linked to luciferase reporters.", "output": "BPA." }, { "input": "We also included in this study two BPA analogs, bisphenol AF ( BPAF ) and bisphenol S ( BPS ).", "output": "BPA, bisphenol AF, BPAF, bisphenol S, BPS." }, { "input": "As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ER alpha agonists ( half maximal effective concentration EC50 of 10 - 100nM ) and as AR antagonists ( half maximal inhibitory concentration IC50 of 1 - 2 mu M ).", "output": "BPA, BPAF." }, { "input": "Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881.", "output": "BPA, BPAF, androgen, R1881." }, { "input": "BPS with lower estrogenic activity ( EC50 of 2. 2 mu M ), did not compete with R1881 for AR binding, when tested at 30 mu M.", "output": "BPS, R1881." }, { "input": "Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF - tagged receptors.", "output": "BPA." }, { "input": "Similar to 17 beta - estradiol ( E2 ) which was used as control, BPA was able to enhance ER alpha nuclear foci formation but at a 100 - fold higher concentration.", "output": "17 beta - estradiol, BPA." }, { "input": "Although BPA was able to bind AR, the nuclear translocation was reduced.", "output": "BPA." }, { "input": "Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.", "output": "BPA, BPA." }, { "input": "Loss of FMR2 further emphasizes the link between deregulation of immediate early response genes FOS and JUN and intellectual disability.", "output": "There is no related enetity." }, { "input": "Loss of FMR2 causes Fragile X E ( FRAXE ) site - associated intellectual disability ( ID ).", "output": "There is no related enetity." }, { "input": "FMR2 regulates transcription, promotes alternative splicing with preference for G - quartet structure harbouring exons and is localized to the nuclear speckles.", "output": "There is no related enetity." }, { "input": "In primary skin fibroblasts from FRAXE patients ( n = 8 ), we found a significant reduction in the number, but a significant increase in the size, of nuclear speckles, when compared with the controls ( n = 4 ).", "output": "There is no related enetity." }, { "input": "Since nuclear speckles are enriched with factors involved in pre - mRNA processing, we explored the consequence of these defects and the loss of FMR2 on the transcriptome.", "output": "There is no related enetity." }, { "input": "We performed whole genome expression profiling using total RNA extracted from these cell lines and found 27 genes significantly deregulated by at least 2 - fold at P < 0. 05 in the patients.", "output": "There is no related enetity." }, { "input": "Among these genes, FOS was significantly upregulated and was further investigated due to its established role in neuronal cell function.", "output": "There is no related enetity." }, { "input": "We showed that ( i ) 30 % depletion of Fmr2 in mouse primary cortical neurons led to a 2 - fold increase in Fos expression, ( ii ) overexpression of FMR2 significantly decreased FOS promoter activity in luciferase assays, and ( iii ) as FOS promoter contains a serum response element, we found that not FOS, but JUN, which encodes for a protein that forms a transcriptional activator complex with FOS, was significantly upregulated in the patients ' cell lines upon mitogen stimulation.", "output": "There is no related enetity." }, { "input": "These results suggest that FMR2 is an upstream regulator of FOS and JUN, and further link deregulation of the immediate early response genes to the pathology of ID - and FRAXE - associated ID in particular.", "output": "There is no related enetity." }, { "input": "Optical modulation of ZnO microwire optical resonators with a parallelogram cross - section.", "output": "ZnO." }, { "input": "A novel ZnO microwire optical resonator with a parallelogram cross - section is fabricated, which can effectively control the light field in two dimensions.", "output": "ZnO." }, { "input": "Wave - guided Fabry - P e rot modes with different polarizations are directly observed and further investigated systematically.", "output": "There is no related enetity." }, { "input": "Such a ZnO optical resonator offers another building block for the development of optoelectronic devices.", "output": "ZnO." }, { "input": "Molecular dynamics in liquid and glassy states of non - steroidal anti - inflammatory drug: Ketoprofen.", "output": "Ketoprofen." }, { "input": "Ketoprofen is a well known nonsteroidal anti - inflammatory drug ( NSAID ) with analgesic and antipyretic effects.", "output": "Ketoprofen." }, { "input": "It acts by inhibiting the body ' s production of prostaglandin.", "output": "prostaglandin." }, { "input": "The molecular mobility of amorphous ketoprofen has been investigated by broadband dielectric spectroscopy ( BDS ) covering wide temperature and frequency range.", "output": "ketoprofen." }, { "input": "Multiple relaxation processes were observed.", "output": "There is no related enetity." }, { "input": "Besides the primary alpha - relaxation, one secondary relaxation, gamma - have been identified.", "output": "There is no related enetity." }, { "input": "The gamma - process visible in the dielectric spectra at very low temperature is non - JG relaxation, and has an activation energy E = 37. 91kJ / mol typical for local mobility.", "output": "There is no related enetity." }, { "input": "Based on Ngai ' s coupling model smaller n or a larger Kohlrausch exponent ( 1 - n ) of the alpha - relaxation associated with larger tau beta ( Tg ).", "output": "There is no related enetity." }, { "input": "In the case of ketoprofen we conclude that the secondary relaxation ( beta ) emerging from intermolecular motions, is hidden under the dominant alpha - peak.", "output": "ketoprofen." }, { "input": "The temperature dependence of the relaxation time of the alpha - process can be described over the entire measured range by a single Vogel - Fulcher - Tammann ( VFT ) equation.", "output": "There is no related enetity." }, { "input": "From VFT fits, the glass transition temperature ( Tg ) was estimated as 267. 07K, and a fragility or steepness index m = 86. 57 was calculated, showing that ketoprofen is a fragile glass former.", "output": "ketoprofen." }, { "input": "Our differential scanning calorimetry ( DSC ) study shows that ketoprofen is a non - crystallizing compound.", "output": "ketoprofen." }, { "input": "To confirm the hydrogen bond patterns of ketoprofen FTIR spectroscopy was applied in both crystalline and amorphous phases.", "output": "ketoprofen." }, { "input": "Solubility test performed at 37 degrees C proved that amorphous phase is more soluble than the crystalline phase.", "output": "There is no related enetity." }, { "input": "A possible role of partially pyrolysed essential oils in Australian Aboriginal traditional ceremonial and medicinal smoking applications of Eremophila longifolia ( R. Br. ) F.", "output": "There is no related enetity." }, { "input": "Muell ( Scrophulariaceae ).", "output": "There is no related enetity." }, { "input": "ETHNOPHARMACOLOGICAL SIGNIFICANCE: Eremophila longifolia is one of the most respected of the traditional medicines used by Australian Aboriginal people.", "output": "There is no related enetity." }, { "input": "Customary use involves smoldering the leaves over hot embers of a fire to produce an acrid smoke, believed to have therapeutic effects broadly consistent with antimicrobial, antifungal and anti - inflammatory capacity.", "output": "There is no related enetity." }, { "input": "AIM OF THE STUDY: The current study aims to examine the contribution of partially pyrolysed and non - pyrolysed essential oils in traditional usage of Eremophila longifolia.", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: Non - pyrolysed and partially pyrolysed essential oils were produced by hydrodistillation and part - wet / part - dry distillation, respectively.", "output": "There is no related enetity." }, { "input": "All samples were tested for antimicrobial activity by broth dilution.", "output": "There is no related enetity." }, { "input": "Some of these samples were further treated to an incrementally stepped temperature profile in a novel procedure employing a commercial thermocycler in an attempt to mimic the effect of temperature gradients produced during smoking ceremonies.", "output": "There is no related enetity." }, { "input": "Components from the pyrodistilled oils were compared with the non - pyrodistilled oils, using GC - MS, GC - FID and HPLC - PAD.", "output": "There is no related enetity." }, { "input": "The 2, 2 - diphenyl - 1 - picrylhydrazyl method, was used to compare free radical scavenging ability.", "output": "2 , 2 - diphenyl - 1 - picrylhydrazyl." }, { "input": "RESULTS: Partially pyrolysed oils had approximately three or more times greater antimicrobial activity, enhanced in cultures warmed incrementally to 60 degrees C and held for 30s and further enhanced if held for 2min.", "output": "There is no related enetity." }, { "input": "Partially pyrolysed oils showed a radical scavenging capacity 30 - 700 times greater than the corresponding non - pyrolysed oils.", "output": "There is no related enetity." }, { "input": "HPLC - PAD revealed the presence of additional constituents not present in the fresh essential oil.", "output": "There is no related enetity." }, { "input": "CONCLUSION: These results, by showing enhanced antimicrobial and antioxidant activities, provide the first known Western scientific justification for the smoking ceremonies involving leaves of Eremophila longifolia.", "output": "There is no related enetity." }, { "input": "During customary use, both partially pyrolysed as well as non - pyrolysed essential oils may contribute significantly to the overall intended medicinal effect.", "output": "There is no related enetity." }, { "input": "Myeloid cell RelA / p65 promotes lung cancer proliferation through Wnt / beta - catenin signaling in murine and human tumor cells.", "output": "There is no related enetity." }, { "input": "Smoking is the most important risk factor for both lung cancer ( LC ) and chronic obstructive pulmonary disease.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate the role of myeloid cell nuclear factor - kappa B in the regulation of tumor cell growth signaling.", "output": "There is no related enetity." }, { "input": "We subjected mice lacking myeloid RelA / p65 ( rela ( Delta - / - ) ) to a metastatic LC model.", "output": "There is no related enetity." }, { "input": "Cigarette smoke ( CS ) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild - type mice.", "output": "There is no related enetity." }, { "input": "In CS - exposed rela ( Delta - / - ) mice, the tumor growth was largely inhibited.", "output": "There is no related enetity." }, { "input": "Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt / beta - catenin pathway.", "output": "There is no related enetity." }, { "input": "In conclusion, myeloid RelA / p65 is necessary to link smoke - induced inflammation with LC growth and has a role in the activation of Wnt / beta - catenin signaling in tumor cells. Oncogene advance online publication, 8 April 2013; doi: 10. 1038 / onc. 2013. 75.", "output": "There is no related enetity." }, { "input": "Correlation between activation of PPAR gamma and resistin downregulation in a mouse adipocyte cell line by a series of thiazolidinediones.", "output": "thiazolidinediones." }, { "input": "The present study shows significant correlations between the EC50 for PPAR gamma activation in a reporter gene cell line and resistin downregulation in mouse adipocytes, and between the IC50 for resistin downregulation and the already published minimum effective dose for antihyperglycemic activity in a mouse model.", "output": "There is no related enetity." }, { "input": "These correlations indicate that PPAR gamma mediated downregulation of resistin might promote insulin sensitivity and that downregulation of resistin in mouse adipocytes provides an adequate and possibly more direct bioassay for screening of newly developed antihyperglycemic compounds.", "output": "There is no related enetity." }, { "input": "Because of the higher throughput of the PPAR gamma the resistin downregulation assays seems most suitable to be used as a second tier in a tiered screening strategy.", "output": "There is no related enetity." }, { "input": "No mutations in the serotonin related TPH1 and HTR1B genes in patients with monogenic sclerosing bone disorders.", "output": "serotonin." }, { "input": "Since the identification of LRP5 as the causative gene for the osteoporosis pseudoglioma syndrome ( OPPG ) as well as the high bone mass ( HBM ) phenotype, LRP5 and the Wnt / beta - catenin signaling have been extensively studied for their role in the differentiation and proliferation of osteoblasts, in the apoptosis of osteoblasts and osteocytes and in the response of bone to mechanical loading.", "output": "There is no related enetity." }, { "input": "However, more recently the direct effect of LRP5 on osteoblasts and bone formation has been questioned.", "output": "There is no related enetity." }, { "input": "Gene expression studies showed that mice lacking lrp5 have increased expression of tph1, the rate limiting enzyme for the production of serotonin in the gut.", "output": "serotonin." }, { "input": "Furthermore mice lacking either tph1 or htr1B, the receptor for serotonin on the osteoblasts, were reported to have an increased bone mass due to increased bone formation.", "output": "serotonin." }, { "input": "This led to the still controversial hypothesis that LRP5 influences bone formation indirectly by regulating the expression of thp1 and as a consequence influencing the production of serotonin in the gut.", "output": "serotonin." }, { "input": "Based on these data we decided to evaluate the role of TPH1 and HTR1B in the development of craniotubular hyperostoses, a group of monogenic sclerosing bone dysplasias.", "output": "There is no related enetity." }, { "input": "We screened the coding regions of both genes in 53 patients lacking a mutation in the known causative genes LRP5, LRP4 and SOST.", "output": "There is no related enetity." }, { "input": "We could not find disease - causing coding variants in neither of the tested genes and therefore, we cannot provide support for an important function of TPH1 and HTR1B in the pathogenesis of sclerosing bone dysplasias in our tested patient cohort.", "output": "There is no related enetity." }, { "input": "Incidentally discovered thyroid nodules: frequency in an adult population during Doppler ultrasonographic evaluation of cervical vessels.", "output": "There is no related enetity." }, { "input": "In this study, the frequency of thyroid nodules was searched in a population of consecutive patients undergoing routine cervical Doppler evaluation with the use of high - end color Doppler ultrasound units equipped with new technologies that increase nodule conspicuity.", "output": "There is no related enetity." }, { "input": "Three hundred and fifteen subjects, who had been referred for Doppler ultrasonography of cervical vessel examination, were enrolled in the study.", "output": "There is no related enetity." }, { "input": "During the examinations, the presence or absence of thyroid nodules, if present, their number ( as \" single \" or \" multiple \" ), the longest diameter, and internal echo pattern of the largest nodule were noted.", "output": "There is no related enetity." }, { "input": "As a result, one hundred and sixty - one subjects ( 51 % ) were shown to have at least one thyroid nodule.", "output": "There is no related enetity." }, { "input": "In this subgroup, 54 cases had single and 107 cases had multiple nodules.", "output": "There is no related enetity." }, { "input": "Incidental thyroid nodules were detected in similar ratios in both men and women ( p = 0. 34 ).", "output": "There is no related enetity." }, { "input": "The results of the study led to the conclusion that half of the elder adult population had at least one thyroid nodule.", "output": "There is no related enetity." }, { "input": "Use of ultrasound technologies with increasing resolution seems to help significantly in detecting and also evaluating smaller and previously unknown nodules.", "output": "There is no related enetity." }, { "input": "The role of P - glycoprotein in CNS antihistamine effects.", "output": "There is no related enetity." }, { "input": "RATIONALE: P - glycoprotein ( P - gp ) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood - brain barrier.", "output": "There is no related enetity." }, { "input": "Studies in rodents have demonstrated that antihistamines that are substrates of the P - gp transporter display no or minor central nervous system ( CNS ) effects as compared to antihistamines that are not P - gp transporter substrates.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: The present study explored whether P - gp contributes in similar ways to the occurrence of sedative effects of antihistamines in humans.", "output": "There is no related enetity." }, { "input": "METHODS: An fMRI study was conducted according to a double - blind, randomized, placebo - controlled, cross - over design in 13 healthy volunteers.", "output": "There is no related enetity." }, { "input": "Participants received cetirizine 15 mg ( an antihistamine ), verapamil 120 mg ( a P - gp blocker ), a combination of cetirizine + verapamil, and a placebo.", "output": "cetirizine, verapamil, cetirizine, verapamil." }, { "input": "Brain activity was assessed while conducting the attention network test ( ANT ) in a 3T magnetic resonance scanner.", "output": "There is no related enetity." }, { "input": "The ANT measures three independent attention domains: i. e., alerting, orienting, and executive attention.", "output": "There is no related enetity." }, { "input": "It was expected that the combined treatment of cetirizine with verapamil would prevent efflux of cetirizine from the CNS, thus increasing attentional impairment, as compared to cetirizine administered alone.", "output": "cetirizine, verapamil, cetirizine, cetirizine." }, { "input": "RESULTS: The present study provides evidence that the P - gp transporter is involved in central antihistamine effects in humans.", "output": "There is no related enetity." }, { "input": "Participants were less alert during the combined treatment of cetirizine and verapamil as indicated by longer reaction times and decreased blood oxygen level - dependent response in the right superior temporal gyrus.", "output": "cetirizine, verapamil, oxygen." }, { "input": "CONCLUSION: It is concluded that the affinity for the P - gp transporter may contribute to the lower incidence of CNS side effects of certain antihistamines.", "output": "There is no related enetity." }, { "input": "A large gap opening of graphene induced by the adsorption of CO on the Al - doped site.", "output": "graphene, CO, Al." }, { "input": "We investigated CO adsorption on the pristine, Stone - Wales ( SW ) defected, Al - and Si - doped graphenes by using density functional calculations in terms of geometric, energetic and electronic properties.", "output": "CO, Al, Si, graphenes." }, { "input": "It was found that CO molecule is weakly adsorbed on the pristine and SW defected graphenes and their electronic properties were slightly changed.", "output": "CO, graphenes." }, { "input": "The Al - and Si - doped graphenes show high reactivity toward CO, so calculated adoption energies are about - 11. 40 and - 13. 75 kcal mol ( - 1 ) in the most favorable states.", "output": "Al, Si, CO." }, { "input": "It was found that, among all the structures, the electronic properties of Al - doped graphene are strongly sensitive to the presence of CO molecule.", "output": "Al, graphene, CO." }, { "input": "We demonstrate the existence of a large Eg opening of 0. 87 eV in graphene which is induced by Al - doping and CO adsorption.", "output": "graphene, Al, CO." }, { "input": "A Microscale Neuron and Schwann Cell Coculture Model for Increasing Detection Sensitivity of Botulinum Neurotoxin Type A.", "output": "There is no related enetity." }, { "input": "Botulinum neurotoxin ( BoNT ) is a potent and specific biomolecule that is both implicated as a potential threat in bioterrorism and used in therapeutics.", "output": "There is no related enetity." }, { "input": "Highly sensitive and robust assays that measure BoNT activity are needed to manage outbreak or controlled distribution of BoNT.", "output": "There is no related enetity." }, { "input": "Current in vivo and in vitro assays have limitations, including high costs and variability for mouse bioassays, extensive preparations for primary and stem cell - derived neurons, and inherent low sensitivity for cell lines.", "output": "There is no related enetity." }, { "input": "Sensitivity of cell lines can be increased by direct differentiation and with their physiological relevance ( compared with cell - free strategies ) and robustness ( compared with primary cell strategies ); adopting cell lines is an attractive alternative to in vivo assays.", "output": "There is no related enetity." }, { "input": "Here, we present two distinct strategies that improved sensitivity of a cell line to BoNT serotype A ( BoNT / A ) without direct differentiation.", "output": "There is no related enetity." }, { "input": "We developed a cell - based BoNT assay using microscale culture and coculture of neuronal and Schwann cell lines, NG108 - 15 and S16, respectively, to improve both sensitivity and physiological relevance.", "output": "There is no related enetity." }, { "input": "Results showed that NG108 - 15 and S16 coculture decreased EC50 from 12. 5 to 0. 8ng / micro l ( p < 0. 001 ) in macroscale and from 2. 6 to 1. 1ng / micro l ( p = 0. 006 ) in microscale.", "output": "There is no related enetity." }, { "input": "In addition, NG108 - 15 monoculture at microscale decreased EC50 from 12. 5 to 2. 6ng / micro l ( p < 0. 001 ) compared with macroscale.", "output": "There is no related enetity." }, { "input": "Finally, controlling the spatial arrangement of microscale coculture revealed that S16 - derived soluble factors can increase sensitivity.", "output": "There is no related enetity." }, { "input": "Thus, our study demonstrates two distinct strategies for increasing the sensitivity of a cell line to BoNT using coculture and microscale culture, thereby advancing assay technology for BoNT detection.", "output": "There is no related enetity." }, { "input": "A Hydroxylated Metabolite of Flame - Retardant PBDE - 47 Decreases the Survival, Proliferation, and Neuronal Differentiation of Primary Cultured Adult Neural Stem Cells and Interferes with Signaling of ERK5 MAP Kinase and Neurotrophin 3.", "output": "PBDE - 47." }, { "input": "Polybrominated diphenyl ethers ( PBDEs ) are a group of organobromine compounds widely used as flame retardants.", "output": "Polybrominated diphenyl ethers, PBDEs, organobromine." }, { "input": "PBDE - 47 is one of the most prominent PBDE congeners found in human tissues, and it can be transformed into several metabolites, including 6 - OH - PBDE - 47.", "output": "PBDE - 47, PBDE, 6 - OH - PBDE - 47." }, { "input": "Recent studies have shown that PBDE - 47 is neurotoxic to animals and possibly humans.", "output": "PBDE - 47." }, { "input": "However, the basis for the neurotoxicity of PBDEs and their metabolites is unclear.", "output": "PBDEs." }, { "input": "For example, it is not known whether PBDEs affect adult neurogenesis, a process implicated in learning and memory and in olfactory behavior.", "output": "PBDEs." }, { "input": "In this study, we examined the toxicity of PBDEs for primary adult neural stem / progenitor cells ( aNSCs ) isolated from the subventricular zone ( SVZ ) of adult mice.", "output": "PBDEs." }, { "input": "We discovered that 6 - OH - PBDE - 47, but not its parent compound PBDE - 47, is cytotoxic for aNCSs using MTS metabolism and cell number as a measure of cytotoxicity.", "output": "6 - OH - PBDE - 47, PBDE - 47." }, { "input": "Interestingly, 6 - OH - PBDE - 47 induced apoptosis at concentrations above 7. 5 mu M inhibited proliferation at 2. 5 - 5 mu M while suppressing neuronal and oligodendrocyte differentiation at submicromolar concentrations ( <= 1 mu M ).", "output": "6 - OH - PBDE - 47." }, { "input": "The effect on proliferation was reversed upon removal of 6 - OH - PBDE - 47 and correlated with selective but reversible inhibition of ERK5 activation by mitogenic growth factors EGF and bFGF.", "output": "6 - OH - PBDE - 47." }, { "input": "6 - OH - PBDE - 47 also inhibited the proneuronal differentiation effect of neurotrophin 3 ( NT3 ) and NT3 activation of ERK5.", "output": "6 - OH - PBDE - 47." }, { "input": "Together, these data show that 6 - OH - PBDE - 47 is more toxic than its parent compound for SVZ - derived aNSCs and that it inhibits multiple aspects of adult neurogenesis.", "output": "6 - OH - PBDE - 47." }, { "input": "Furthermore, inhibition of ERK5 signaling may underlie the adverse effect of 6 - OH - PBDE - 47 on proliferation and neuronal differentiation.", "output": "6 - OH - PBDE - 47." }, { "input": "Our data suggest that exposure to PBDE - based flame retardants could cause neurotoxicity in the adult brain by interfering with adult neurogenesis.", "output": "PBDE." }, { "input": "ALLERGIC SKIN INFLAMMATION INDUCED BY CHEMICAL SENSITIZERS IS CONTROLLED BY THE TRANSCRIPTION FACTOR NRF2.", "output": "There is no related enetity." }, { "input": "Allergic contact dermatitis ( ACD ) is induced by low molecular weight electrophilic chemicals and metal ions.", "output": "There is no related enetity." }, { "input": "Chemical contact sensitizers trigger reactive oxygen species ( ROS ) production and provoke electrophilic stress leading to the accumulation of the transcription factor nuclear related factor 2 ( Nrf2 ) in innate immune cell types.", "output": "oxygen." }, { "input": "The objective of this work was to identify the role of Nrf2 in the regulation of ACD.", "output": "There is no related enetity." }, { "input": "We used the Local Lymph Node Assay ( LLNA ) and the Mouse Ear Swelling Test ( MEST ) to study the role of Nrf2 in both the sensitization and elicitation phase in nrf2 knock out ( nrf2 ( - / - ) ) and wild type ( nrf2 ( + / + ) ) mice.", "output": "There is no related enetity." }, { "input": "Five chemicals were used: two compounds known to react with cysteine residues, 2, 4 - dinitrochlorobenzene ( DNCB ) and cinnamaldehyde ( CinA ); one sensitizer known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate ( IPDI ); and one reacting specifically with lysine residues, trimellitic anhydride ( TMA ) and croton oil a well - known irritant.", "output": "cysteine, 2 , 4 - dinitrochlorobenzene, DNCB, cinnamaldehyde, CinA, cysteine, lysine, isophorone diisocyanate, IPDI, lysine, trimellitic anhydride, TMA." }, { "input": "In the MEST assay, DNCB ( 1 % and 2 % ) induced a significant increase in ear thickness in nrf2 ( - / - ) as compared to nrf2 ( + / + ) mice suggesting a role for Nrf2 in the control of the inflammatory process.", "output": "DNCB." }, { "input": "When DNCB was used at 0. 25 % and 0. 5 % or when mice were treated with CinA, inflammation was found only in nrf2 ( - / - ) mice.", "output": "DNCB, CinA." }, { "input": "In the LLNA all chemical sensitizers induced an increase of lymphocyte proliferation in nrf2 ( - / - ) compared to nrf2 ( + / + ) mice for the same chemical concentration. These results reveal an important role for Nrf2 in controlling ACD and lymphocyte proliferation in response to sensitizers.", "output": "There is no related enetity." }, { "input": "NH2 - Terminal Probrain Natriuretic Peptide Is a Stronger Predictor of Cardiovascular Mortality Than C - Reactive Protein and Albumin Excretion Rate in Elderly Patients With Type 2 Diabetes: The Casale Monferrato population - based study.", "output": "NH2." }, { "input": "OBJECTIVETo study whether NH2 - terminal probrain natriuretic peptide ( NT - proBNP ) is a short - term independent predictor of both all - cause and cardiovascular ( CV ) mortality in type 2 diabetic patients and to establish whether albuminuria and C - reactive protein ( CRP ) affect this relationship. RESEARCH DESIGN AND METHODSThe prospective study included 1, 825 type 2 diabetic patients from the population - based cohort of the Casale Monferrato study.", "output": "NH2." }, { "input": "CV risk factors, preexisting CVD, and NT - proBNP levels were evaluated at baseline.", "output": "There is no related enetity." }, { "input": "All - cause and CV mortality were assessed 5. 5 years after baseline examination.", "output": "There is no related enetity." }, { "input": "Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios ( HRs ). RESULTSDuring the follow - up period, 390 people died ( 175 for CVD ) out of 9, 101 person - years of observations.", "output": "There is no related enetity." }, { "input": "A significantly increased mortality risk by quartiles of NT - proBNP was observed ( test for trend, P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "NT - proBN P values > 91 pg / mL conferred HRs of 2. 05 ( 95 % CI 1. 47 - 2. 86 ) for all - cause and 4. 47 ( 2. 38 - 8. 39 ) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate ( AER ).", "output": "There is no related enetity." }, { "input": "The association was also significant for modest rises in NT - proBNP levels and in patients without microalbuminuria and CVD at baseline ( upper quartiles HRs 3. 82 [ 95 % CI 1. 24 - 13. 75 ] ) and 3. 14 [ 1. 00 - 9. 94 ] ).", "output": "There is no related enetity." }, { "input": "Albuminuria and NT - proBNP had an additive effect on mortality, though the association was stronger for NT - proBNP. CONCLUSIONSNT - proBNP is a strong independent predictor of short - term CV mortality risk in elderly people with type 2 diabetes, including those without preexisting CVD.", "output": "There is no related enetity." }, { "input": "This association is evident even in people with slightly increased values, is not modified by CRP, and is additive to that provided by AER.", "output": "There is no related enetity." }, { "input": "Promoter Sequence Determines the Relationship between Expression Level and Noise.", "output": "There is no related enetity." }, { "input": "The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation.", "output": "There is no related enetity." }, { "input": "A change in transcription factor ( TF ) activity results in changes in the expression of its targets, but the way in which cell - to - cell variability in expression ( noise ) changes as a function of TF activity, and whether targets of the same TF behave similarly, is not known.", "output": "There is no related enetity." }, { "input": "Here, we measure expression and noise as a function of TF activity for 16 native targets of the transcription factor Zap1 that are regulated by it through diverse mechanisms.", "output": "There is no related enetity." }, { "input": "For most activated and repressed Zap1 targets, noise decreases as expression increases.", "output": "There is no related enetity." }, { "input": "Kinetic modeling suggests that this is due to two distinct Zap1 - mediated mechanisms that both change the frequency of transcriptional bursts.", "output": "There is no related enetity." }, { "input": "Notably, we found that another mechanism of repression by Zap1, which is encoded in the promoter DNA, likely decreases the size of transcriptional bursts, producing a unique transcriptional state characterized by low expression and low noise.", "output": "There is no related enetity." }, { "input": "In addition, we find that further reduction in noise is achieved when a single TF both activates and represses a single target gene.", "output": "There is no related enetity." }, { "input": "Our results suggest a global principle whereby at low TF concentrations, the dominant source of differences in expression between promoters stems from differences in burst frequency, whereas at high TF concentrations differences in burst size dominate.", "output": "There is no related enetity." }, { "input": "Taken together, we show that the precise amount by which noise changes with expression is specific to the regulatory mechanism of transcription and translation that acts at each gene.", "output": "There is no related enetity." }, { "input": "Applicability of a Blood - Brain Barrier Specific Artificial Membrane Permeability Assay at the Early Stage of Natural Product - Based CNS Drug Discovery.", "output": "There is no related enetity." }, { "input": "While numerous natural products ( NPs ) possess activity on central nervous system ( CNS ) targets, there has been no analytical approach to effectively identify compounds with high brain penetration potential in complex mixtures at the early stage of drug discovery.", "output": "There is no related enetity." }, { "input": "To overcome this issue, the performance of an in vitro parallel artificial membrane permeability assay for the blood - brain barrier ( PAMPA - BBB ) for natural products and for plant extracts has been validated and characterized.", "output": "There is no related enetity." }, { "input": "It was found that the PAMPA - BBB assay preserves its predictive power in the case of natural products and provides high phytochemical selectivity, which enables its use as a unique filtering tool in terms of selecting brain - penetrable compounds from plant extracts.", "output": "There is no related enetity." }, { "input": "Moreover, the present study has demonstrated that simple modifications in the assay design allow the direct use of PAMPA - BBB filtered samples in a dereplication process, as performed by NMR and LC - MS.", "output": "There is no related enetity." }, { "input": "The applicability of this procedure was demonstrated using extracts prepared from Tanacetum parthenium, Vinca major, Salvia officinalis, and Corydalis cava, representing different types of chemical diversity and complexity.", "output": "There is no related enetity." }, { "input": "Thus, the proposed protocol represents a potentially valuable strategy in the NP - based CNS drug discovery environment with a high - throughput screening platform.", "output": "There is no related enetity." }, { "input": "In vitro evaluation of the effects of various additives and polymers on nerve growth factor microspheres.", "output": "There is no related enetity." }, { "input": "Abstract Objective: To evaluate the effects of various additives or polymers on the in vitro characteristics of nerve growth factor ( NGF ) microspheres.", "output": "There is no related enetity." }, { "input": "Materials and methods: NGF microspheres were fabricated using polyethylene glycol ( PEG ), ovalbumin ( OVA ), bovine serum albumin ( BSA ) or glucose as protein protectors, and poly ( lactide - co - glycolide ) ( PLGA ) or poly ( lactic acid ) ( PLA ) / PLGA blends as encapsulation materials.", "output": "polyethylene glycol, PEG, glucose, poly ( lactide - co - glycolide ), PLGA, poly ( lactic acid ), PLA, PLGA." }, { "input": "Results: Encapsulation efficiencies of the NGF microspheres with various additives or polymers were not more than 30 %.", "output": "There is no related enetity." }, { "input": "A comparative study revealed that OVA was somewhat superior over others, and was thus chosen as the protective additive in subsequent experiments.", "output": "There is no related enetity." }, { "input": "Polymer analysis showed that NGF release from 1: 1 PLA ( eta = 0. 8 ): PLGA ( 75 / 25, eta = 0. 45 ) microspheres lasted for 90 d with a burst release rate of 12. 7 %.", "output": "PLA, PLGA." }, { "input": "About 40 % of the original bioactivity was retained on the 28th day, while 10 % was left on the 90th day.", "output": "There is no related enetity." }, { "input": "Discussion and conclusion: The combination of OVA as an additive and the PLA / PLGA blend as the coating matrix is suitable for encapsulation of NGF in microspheres for extended release.", "output": "PLA, PLGA." }, { "input": "Predicting Transition Temperatures of Elastin - Like Polypeptide Fusion Proteins.", "output": "There is no related enetity." }, { "input": "Elastin - like polypeptides ( ELPs ) are thermally sensitive peptide polymers that undergo thermally triggered phase separation and this behavior is imparted to soluble proteins when they are fused to an ELP.", "output": "There is no related enetity." }, { "input": "The transition temperature of the ELP fusion protein is observed to be different than that of a free ELP, indicating that the surface properties of the fused protein modulate the thermal behavior of ELPs.", "output": "There is no related enetity." }, { "input": "Understanding this effect is important for the rational design of applications that exploit the phase transition behavior of ELP fusion proteins.", "output": "There is no related enetity." }, { "input": "We had previously developed a biophysical model that explained the effect of hydrophobic proteins on depressing the transition temperature of ELP fusion proteins relative to free ELP.", "output": "There is no related enetity." }, { "input": "Here, we extend the model to elucidate the effect of hydrophilic proteins on the thermal behavior of ELP fusion proteins.", "output": "There is no related enetity." }, { "input": "A linear correlation was found between overall residue composition of accessible protein surface weighted by a characteristic transition temperature for each residue and the difference in transition temperatures between the ELP protein fusion and the corresponding free ELP.", "output": "There is no related enetity." }, { "input": "In breaking down the contribution of residues to polar, nonpolar, and charged, the model revealed that charged residues are the most important parameter in altering the transition temperature of an ELP fusion relative to the free ELP.", "output": "There is no related enetity." }, { "input": "Silver Chloride as a Heterogeneous Nucleant for the Growth of Silver Nanowires.", "output": "Silver Chloride, Silver." }, { "input": "Various additives are employed in the polyol synthesis of silver nanowires ( Ag NWs ), which are typically halide salts such as NaCl.", "output": "polyol, silver, Ag, halide, NaCl." }, { "input": "A variety of mechanistic roles have been suggested for these additives.", "output": "There is no related enetity." }, { "input": "We now show that the early addition of NaCl in the polyol synthesis of Ag NWs from AgNO3 in ethylene glycol results in the rapid formation of AgCl nanocubes, which induce the heterogeneous nucleation of metallic Ag upon their surfaces.", "output": "NaCl, polyol, Ag, AgNO3, ethylene glycol, AgCl, Ag." }, { "input": "Ag NWs subsequently grow from these nucleation sites.", "output": "Ag." }, { "input": "The conclusions are supported by studies using ex situ generated AgCl nanocubes.", "output": "AgCl." }, { "input": "Androgen receptor: past, present and future.", "output": "Androgen." }, { "input": "Androgens and the androgen receptor have been the focus of prostate cancer research since the early 1940s, when Huggins and Hodges demonstrated that removal of androgens caused advanced prostate cancer to regress.", "output": "Androgens, androgen, androgens." }, { "input": "Since that time, a large number of androgen deprivation therapies have been developed in an effort to cure this disease, but prostate cancer remains one of the leading causes of cancer death in males worldwide.", "output": "androgen." }, { "input": "This is due in part to the emergence of castration - recurrent prostate cancer in patients with advanced disease who have failed androgen deprivation therapy.", "output": "androgen." }, { "input": "The androgen receptor is still a major player in castration - recurrent disease, and though much has been discovered since the early work of Huggins and Hodges regarding how prostate cancer cells manage to avoid the effects of androgen deprivation, survival times for men with advanced prostate cancer have changed only modestly.", "output": "androgen, androgen." }, { "input": "Research is now directed toward delineating the mechanisms of action of the androgen receptor under castrate conditions, whether through amplification of the AR, mutation, expression of splice variants, use of alternate signaling pathways, aberrant expression and activation of coregulators, or intratumoral androgen biosynthesis.", "output": "androgen." }, { "input": "Genome - wide association studies are also adding to the wealth of knowledge surrounding the androgen receptor, and with this knowledge comes the ability to design new drug therapies directed toward eradication of this disease.", "output": "androgen." }, { "input": "Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration - resistant prostate cancer.", "output": "androgen." }, { "input": "The growth and dependence of Prostate Cancer ( PCa ) on androgen stimulation led to the use of castration to reduce circulating levels of androgens and anti - androgens to directly target the androgen receptor ( AR ) ligand - binding domain ( LBD ).", "output": "androgen, androgens, androgens, androgen." }, { "input": "However, castration - resistant prostate cancer ( CRPC ) resistant to anti - androgens invariably develops and can be associated with AR genomic aberrations ( mutations, amplification ) and / or an increase in AR mRNA expression.", "output": "androgens." }, { "input": "Efforts to more effectively target the AR in CRPC led to the rational design of CYP17A1 inhibitors and more potent antiandrogens.", "output": "antiandrogens." }, { "input": "The front - runner 2nd generation rationally - designed therapeutics targeting the AR, abiraterone and enzalutamide have been shown to improve survival and clinical outcome for CRPC patients.", "output": "There is no related enetity." }, { "input": "Several other CYP17A1 inhibitors and anti - androgens are in clinical and preclinical development.", "output": "androgens." }, { "input": "However, patients ultimately progress and current evidence suggests that this can occur through reactivation of AR signaling.", "output": "There is no related enetity." }, { "input": "Several ongoing programs aim to develop LBD independent therapeutic strategies that for example target the N terminus domain ( NTD ) of the AR or chaperone proteins.", "output": "N." }, { "input": "Rationally - designed approaches combining different strategies for targeting the AR or associated pathways also warrant clinical evaluation.", "output": "There is no related enetity." }, { "input": "Amino Acid - nucleotide - lipids: effect of amino Acid on the self - assembly properties.", "output": "Amino Acid, nucleotide, amino Acid." }, { "input": "Hybrid amphiphiles composed of a lipid covalently linked to biomolecules are attracting considerable attention, owing to their unique physicochemical and biological properties.", "output": "There is no related enetity." }, { "input": "Herein, we have synthesized novel amino acid - nucleotide - lipids ( ANLs ), presenting phenylalanine and thymidine residues and saturated or unsaturated diacyl glycerol lipid moieties to investigate the effect of the specific aminoacid moieties on both aggregation properties and interactions of ANLs with single strand polyA RNA.", "output": "amino acid, nucleotide, phenylalanine, thymidine, saturated or unsaturated diacyl glycerol, aminoacid." }, { "input": "Physicochemical studies ( DLS, cryo - TEM, and small angle X - ray scattering ) indicate that phenylanaline amino acids inserted at the 5 ' position of the nucleotide - lipids stabilize multilamellar systems, whereas unilamellar vesicles are formed preferentially in the case of nucleotide - lipids ( NLs ).", "output": "phenylanaline, amino acids, nucleotide, nucleotide." }, { "input": "Both NLs and ANLs exhibit weak interactions with complementary polyA RNA as revealed by isothermal titration calorimetry investigations.", "output": "There is no related enetity." }, { "input": "The multilamellar vesicles obtained with ANLs could be used as a versatile carrier, suitable for both hydrophobic and hydrophilic therapeutic molecules.", "output": "There is no related enetity." }, { "input": "Spatially Resolved Mapping of Oxygen Reduction / Evolution Reaction on Solid - Oxide Fuel Cell Cathodes with Sub - 10 nm Resolution.", "output": "Oxygen." }, { "input": "Spatial localization of the oxygen reduction / evolution reactions on lanthanum strontium cobaltite ( LSCO ) surfaces with perovskite and layered perovskite structures is studied at the sub - 10 nm level.", "output": "oxygen, lanthanum strontium cobaltite, LSCO, perovskite, perovskite." }, { "input": "Comparison between electrochemical strain microscopy ( ESM ) and structural imaging by scanning transmission electron microscopy ( STEM ) suggests that small - angle grain boundaries act as regions with enhanced electrochemical activity.", "output": "There is no related enetity." }, { "input": "The ESM activity is compared across a family of LSCO samples, demonstrating excellent agreement with macroscopic behaviors.", "output": "LSCO." }, { "input": "This study potentially paves the way for deciphering the mechanisms of electrochemical activity of solids on the level of single extended structural defects such as grain boundaries and dislocations.", "output": "There is no related enetity." }, { "input": "Conformational Plasticity of Hydrogen Bonded Bis - urea Supramolecular Polymers.", "output": "Hydrogen, Bis - urea." }, { "input": "We report a detailed structural investigation of supramolecular polymers formed by hydrogen bonded self - assembly of bis - urea monomers.", "output": "hydrogen, bis - urea." }, { "input": "The careful exploration of the energy landscape by molecular mechanics / molecular dynamics ( MM / MD ) simulations has allowed us to identify three distinct self - assembled structures of similar stabilities.", "output": "There is no related enetity." }, { "input": "These structures have been compared to X - ray crystal data.", "output": "There is no related enetity." }, { "input": "We observe that a slight change in the molecular structure can favor a particular structure over the others.", "output": "There is no related enetity." }, { "input": "Detailed analysis shows that hydrogen bonds stabilize all three structures to a similar extent.", "output": "hydrogen." }, { "input": "Therefore, it is the interactions among the lateral substituents, and with the filament environment, that are the decisive factors in the competition between the possible self - assembled structures.", "output": "There is no related enetity." }, { "input": "This study constitutes a clear reminder that the conformation of a supramolecular polymer is a sensitive function of the molecular structure and may significantly differ from the solid - state conformation of a model compound.", "output": "There is no related enetity." }, { "input": "4 - Hydroxypyridazin - 3 ( 2H ) - one Derivatives as Novel d - Amino Acid Oxidase Inhibitors.", "output": "4 - Hydroxypyridazin - 3 ( 2H ) - one, d - Amino Acid." }, { "input": "d - Amino acid oxidase ( DAAO ) catalyzes the oxidation of d - amino acids including d - serine, a coagonist of the N - methyl - d - aspartate receptor.", "output": "d - Amino acid, d - amino acids, d - serine, N - methyl - d - aspartate." }, { "input": "We identified a series of 4 - hydroxypyridazin - 3 ( 2H ) - one derivatives as novel DAAO inhibitors with high potency and substantial cell permeability using fragment - based drug design.", "output": "4 - hydroxypyridazin - 3 ( 2H ) - one." }, { "input": "Comparisons of complex structures deposited in the Protein Data Bank as well as those determined with in - house fragment hits revealed that a hydrophobic subpocket was formed perpendicular to the flavin ring by flipping Tyr224 in a ligand - dependent manner.", "output": "Tyr224." }, { "input": "We investigated the ability of the initial fragment hit, 3 - hydroxy - pyridine - 2 ( 1H ) - one, to fill this subpocket with the aid of complex structure information.", "output": "3 - hydroxy - pyridine - 2 ( 1H ) - one." }, { "input": "3 - Hydroxy - 5 - ( 2 - phenylethyl ) pyridine - 2 ( 1H ) - one exhibited the predicted binding mode and demonstrated high inhibitory activity for human DAAO in enzyme - and cell - based assays.", "output": "3 - Hydroxy - 5 - ( 2 - phenylethyl ) pyridine - 2 ( 1H ) - one." }, { "input": "We further designed and synthesized 4 - hydroxypyridazin - 3 ( 2H ) - one derivatives, which are equivalent to the 3 - hydroxy - pyridine - 2 ( 1H ) - one series but lack cell toxicity.", "output": "4 - hydroxypyridazin - 3 ( 2H ) - one, 3 - hydroxy - pyridine - 2 ( 1H ) - one." }, { "input": "6 - [ 2 - ( 3, 5 - Difluorophenyl ) ethyl ] - 4 - hydroxypyridazin - 3 ( 2H ) - one was found to be effective against MK - 801 - induced cognitive deficit in the Y - maze.", "output": "6 - [ 2 - ( 3 , 5 - Difluorophenyl ) ethyl ] - 4 - hydroxypyridazin - 3 ( 2H ) - one, MK - 801." }, { "input": "Determination of the alpha - Conotoxin Vc1. 1 Binding Site on the alpha 9 alpha 10 Nicotinic Acetylcholine Receptor.", "output": "Acetylcholine." }, { "input": "alpha - Conotoxin Vc1. 1 specifically and potently inhibits the nicotinic acetylcholine receptor subtype alpha 9 alpha 10 ( alpha 9 alpha 10 nAChR ) and is a potential novel treatment for neuropathic pain.", "output": "acetylcholine." }, { "input": "Here, we used a combination of computational modeling and electrophysiology experiments to determine the Vc1. 1 binding site on the alpha 9 alpha 10 nAChR.", "output": "There is no related enetity." }, { "input": "Interactions of Vc1. 1 with two probable binding sites, alpha 9 alpha 10 and alpha 10 alpha 9, were modeled.", "output": "There is no related enetity." }, { "input": "Mutational energies calculated by assuming specific interactions in the alpha 10 alpha 9 binding site correlated better with electrophysiological recordings than those assuming interactions with the alpha 9 alpha 10 binding site.", "output": "There is no related enetity." }, { "input": "Two novel Vc1. 1 analogues, [ N9F ] Vc1. 1 and [ N9W ] Vc1. 1, were predicted to have large differences in affinity between the two binding sites.", "output": "There is no related enetity." }, { "input": "Data from functional studies were consistent with computational predictions that assumed preferred binding of Vc1. 1 to the alpha 10 alpha 9 pocket.", "output": "There is no related enetity." }, { "input": "Moreover, our modeling study suggested that a single hydrogen bond formed between Vc1. 1 and position 59 of the alpha 10 alpha 9 pocket confers specificity to rat versus human alpha 9 alpha 10 nAChRs.", "output": "hydrogen." }, { "input": "Discovery and synthesis of novel 4 - aminopyrrolopyrimidine Tie - 2 kinase inhibitors for the treatment of solid tumors.", "output": "4 - aminopyrrolopyrimidine." }, { "input": "The synthesis and biological evaluation of novel Tie - 2 kinase inhibitors are presented.", "output": "There is no related enetity." }, { "input": "Based on the pyrrolopyrimidine chemotype, several new series are described, including the benzimidazole series by linking a benzimidazole to the C5 - position of the 4 - amino - pyrrolopyrimidine core and the ketophenyl series synthesized by incorporating a ketophenyl group to the C5 - position.", "output": "pyrrolopyrimidine, benzimidazole, benzimidazole, 4 - amino - pyrrolopyrimidine, ketophenyl, ketophenyl." }, { "input": "Medicinal chemistry efforts led to potent Tie - 2 inhibitors.", "output": "There is no related enetity." }, { "input": "Compound 15, a ketophenyl pyrrolopyrimidine urea analog with improved physicochemical properties, demonstrated favorable in vitro attributes as well as dose responsive and robust oral tumor growth inhibition in animal models.", "output": "ketophenyl pyrrolopyrimidine urea." }, { "input": "Prediction of dose - hepatotoxic response in humans based on toxicokinetic / toxicodynamic modeling with or without in vivo data: A case study with acetaminophen.", "output": "acetaminophen." }, { "input": "In the present legislations, the use of methods alternative to animal testing is explicitly encouraged, to use animal testing only ' as a last resort ' or to ban it.", "output": "There is no related enetity." }, { "input": "The use of alternative methods to replace kinetics or repeated dose in vivo tests is a challenging issue.", "output": "There is no related enetity." }, { "input": "We propose here a strategy based on in vitro tests and QSAR ( Quantitative Structure Activity Relationship ) models to calibrate a dose - response model predicting hepatotoxicity.", "output": "There is no related enetity." }, { "input": "The dose response consists in calibrating and coupling a PBPK ( physiologically - based pharmacokinetic ) model with a toxicodynamic model for cell viability.", "output": "There is no related enetity." }, { "input": "We applied our strategy to acetaminophen and compared three different ways to calibrate the PBPK model: only with in vitro and in silico methods, using rat data or using all available data including data on humans.", "output": "acetaminophen." }, { "input": "Some estimates of kinetic parameters differed substantially among the three calibration processes, but, at the end, the three models were quite comparable in terms of liver toxicity predictions and close to the usual range of human overdose.", "output": "There is no related enetity." }, { "input": "For the model based on alternative methods, the good adequation with the two other models resulted from an overestimated renal elimination rate which compensated for the underestimation of the metabolism rate.", "output": "There is no related enetity." }, { "input": "Our study points out that toxicokinetics / toxicodynamics approaches, based on alternative methods and modelling only, can predict in vivo liver toxicity with accuracy comparable to in vivo methods.", "output": "There is no related enetity." }, { "input": "Antibacterial, cytotoxic activities and chemical composition of fruits of two Cameroonian Zanthoxylum species.", "output": "There is no related enetity." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum leprieurii ( Syn. Fagara leprieurii ) is a plant extensively used by traditional healers in Cameroon for the treatment of stomach disorders, gonorrhea, intestinal parasites and sterility.", "output": "There is no related enetity." }, { "input": "The infusion from the fruit is taken in Cameroon for the treatment of sickle cell anemia, as well.", "output": "There is no related enetity." }, { "input": "Similarly, the roots of Zanthoxylum zanthoxyloides ( Syn. Fagara zanthoxyloides ) are also used for wound dressing, sickle cell anemia and as pain reliever, in addition to the uses mentioned for Zanthoxylum leprieurii.", "output": "There is no related enetity." }, { "input": "AIM OF THE STUDY: To scientifically validate their traditional use, the in vitro antimicrobial and anticancer assays were performed.", "output": "There is no related enetity." }, { "input": "In addition, chemical compositions of their fruit extracts and essential oils were also studied.", "output": "There is no related enetity." }, { "input": "MATERIAL AND METHODS: The chemical compositions of their essential oils and methanol extracts were studied.", "output": "There is no related enetity." }, { "input": "GC and GC - MS were used for analyzing the essential oils while various chromatographic methods were used to isolate the pure compounds from methanol extracts.", "output": "methanol." }, { "input": "MTT assay was used for the cytotoxic studies of methanol extracts, their fractions and some pure compounds.", "output": "MTT, methanol." }, { "input": "Antimicrobial activity of methanol extracts, some isolated compounds as well as essential oils was tested against a panel of human pathogenic bacteria by diffusion and dilution methods.", "output": "methanol." }, { "input": "RESULTS: The principal constituents of the essential oil of Zanthoxylum zanthoxyloides were identified as citronellol and geraniol whereas Zanthoxylum leprieurii was rich in E - beta - ocimene.", "output": "citronellol, geraniol, E - beta - ocimene." }, { "input": "Furthermore, we report for the first time, the presence of 7, 8 - dimethoxycoumarin and sinapic acid in the methanol extract of Zanthoxylum leprieurii.", "output": "7 , 8 - dimethoxycoumarin, sinapic acid, methanol." }, { "input": "In vitro bioassays reveal that the methanol extracts, essential oil and some of the isolated compounds from fruits of both the plants exhibit moderate anticancer and antimicrobial activities.", "output": "methanol." }, { "input": "CONCLUSION: Altogether, the present findings justify the traditional use of Zanthoxylum zanthoxyloides and Zanthoxylum leprieurii in the treatment of stomach disorders and cancer disease.", "output": "There is no related enetity." }, { "input": "The antimicrobial properties in the essential oil of Zanthoxylum zanthoxyloides are of additional significance.", "output": "There is no related enetity." }, { "input": "Hemolysin from Escherichia coli induces oxidative stress in blood.", "output": "There is no related enetity." }, { "input": "Hemolysin ( HlyA ) produced by some stains of Escherichia coli is considered to be an important virulence factor of those bacteria.", "output": "There is no related enetity." }, { "input": "On the other hand, reactive oxygen species ( ROS ) have been reported to be involved in the pathogenesis of different diseases via oxidative stress generation.", "output": "oxygen." }, { "input": "The purpose of this study was to analyze the capacity of HlyA to induce oxidative stress in whole blood cultures ( WBCs ).", "output": "There is no related enetity." }, { "input": "To this end, ROS production, the damage induced in lipids and proteins, and the antioxidant defense system was evaluated in blood cultures exposed to low concentrations of HlyA.", "output": "There is no related enetity." }, { "input": "We found that HlyA increased the level of free radicals detected by chemiluminescence assay.", "output": "There is no related enetity." }, { "input": "Moreover, lipid peroxidation and protein damage was significantly increased in cultures treated with HlyA in comparation with those found in control cultures.", "output": "There is no related enetity." }, { "input": "On the other hand, a decrease in total antioxidant capacity of plasma and in the activity of superoxide dismutase ( SOD ) was observed in plasma from blood treated with HlyA.", "output": "superoxide." }, { "input": "Collectively, our data demonstrate that low concentrations of E. coli hemolysin induced oxidative stress in WBCs with the induction of different oxidative damage biomarkers.", "output": "There is no related enetity." }, { "input": "Internalization of Bacillus intermedius ribonuclease ( BINASE ) induces human alveolar adenocarcinoma cell death.", "output": "There is no related enetity." }, { "input": "Ribonuclease ( RNase ) treatment represents a novel mechanism based approach to anticancer therapy as an alternative to the DNA damaging drugs commonly used in clinical practice.", "output": "There is no related enetity." }, { "input": "Apart from their ribonucleolytic activity, cytotoxic effects have attracted a considerable attention to RNases because of their potential as selective agents for treatment of certain malignancies.", "output": "There is no related enetity." }, { "input": "Among these enzymes, Binase, an RNase from Bacillus intermedius, has shown promising results.", "output": "There is no related enetity." }, { "input": "Here, we have found that binase selectively attacked human A549 alveolar adenocarcinoma cells to trigger an apoptotic response, whereas normal lung epithelial cells LEK were not affected by the ribonuclease.", "output": "There is no related enetity." }, { "input": "The tumor transformation led to the modification of certain cellular characteristics causing cell sensitivity to binase.", "output": "There is no related enetity." }, { "input": "Although a general mode for RNases cytotoxicity includes their penetration into the cell, translocation to the cytosol and degradation of ribonucleic acid, many aspects of this process have not been fully elucidated.", "output": "There is no related enetity." }, { "input": "Our data revealed the following time - dependent changes induced by binase in A549 cells: ( a ) fast permanent internalization of the enzyme during the first hours of treatment; ( b ) temporary increase in cellular permeability for macromolecules during the 4 - 6 h of treatment; ( c ) apoptotic alterations in population after 24 h and ( d ) DNA fragmentation and cell death after 72 h of treatment with binase.", "output": "There is no related enetity." }, { "input": "Elucidation of these molecular strategies used by this promising toxin provides us essential information for the development of new anticancer drugs.", "output": "There is no related enetity." }, { "input": "Photochemical internalization ( PCI ) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.", "output": "There is no related enetity." }, { "input": "CD133 is a putative cancer stem cell ( CSC ) marker for a number of different cancers and is suggested to be a therapeutic target.", "output": "There is no related enetity." }, { "input": "Since also normal stem cells express CD133 it is of paramount importance that targeting strategies provide a specific and efficient delivery of cytotoxic drugs in only CD133 - positive CSCs.", "output": "There is no related enetity." }, { "input": "In this study, we have employed photochemical internalization ( PCI ), a minimally invasive method for light - controlled, specific delivery of membrane - impermeable macromolecules from endocytic vesicles to the cytosol, to specifically target CD133 - positive cancer cells.", "output": "There is no related enetity." }, { "input": "We demonstrate that PCI increases the cytotoxic effect of an immunotoxin ( IT ) targeting CD133 - expressing cancer cells of colon ( WiDr and HCT116 ) and pancreas ( BxPC - 3 ) origin.", "output": "There is no related enetity." }, { "input": "The IT consisted of the mAb CD133 / 1 ( AC133 ) bound to the ribosome inactivating plant toxin saporin ( anti - CD133 / 1 - sap ).", "output": "There is no related enetity." }, { "input": "We show that TPCS2a - PCI of anti - CD133 / 1 - sap is specific, and highly cytotoxic at femto - molar concentrations.", "output": "There is no related enetity." }, { "input": "Specific binding and uptake of CD133 / 1, was shown by fluorescence microscopy and co - localization with TPCS2a in endosomes / lysosomes was determined by confocal microscopy.", "output": "There is no related enetity." }, { "input": "CD133 ( high ) WiDr cells, isolated by fluorescence activated cell sorting, had a 7 - fold higher capacity to initiate spheroids than CD133 ( low ) cells ( P < 0. 001 ) and were resistant to photodynamic therapy ( PDT ).", "output": "There is no related enetity." }, { "input": "However, PDT - resistance was bypassed by the PCI strategy.", "output": "There is no related enetity." }, { "input": "Tumor initiation and aggressive growth in athymic nude mice was obtained with only 10 CD133 ( high ) cells in contrast to CD133 ( low ) cells where substantially higher cell numbers were needed.", "output": "There is no related enetity." }, { "input": "The excellent high efficacy and selectivity of eliminating CD133 - expressing cells by PCI warrant further pre - clinical evaluations of this novel therapeutic approach.", "output": "There is no related enetity." }, { "input": "Evidence for a new mechanism behind HIFU - triggered release from liposomes.", "output": "There is no related enetity." }, { "input": "A promising approach for local drug delivery is high - intensity focused ultrasound ( HIFU ) - triggered release of drugs from stimuli - responsive nanoparticles such as liposomes.", "output": "There is no related enetity." }, { "input": "The aim of this study was to investigate whether another release mechanism is involved with HIFU - triggered release from liposomes beside cavitation and temperature.", "output": "There is no related enetity." }, { "input": "Furthermore, it was studied whether this new release mechanism allows the release of lipophilic compounds.", "output": "There is no related enetity." }, { "input": "Therefore, both a lipophilic ( Nile red ) and a hydrophilic ( fluorescein ) compound were loaded into thermosensitive ( TSL ) or non - thermosensitive liposomes ( NTSL ) and the liposomes were subjected both to continuous wave - ( CW ) and pulsed wave ( PW ) - HIFU.", "output": "Nile red, fluorescein." }, { "input": "The mean liposome size varied from 97 to 139nm with a polydispersity index ( PDI ) <= 0. 06 for the different formulations.", "output": "There is no related enetity." }, { "input": "The Tm of the phospholipid bilayer of the TSL was around 42 degrees C.", "output": "There is no related enetity." }, { "input": "Approximately 80 % of fluorescein was released within 15min from TSL at temperatures >= 42 degrees C.", "output": "fluorescein." }, { "input": "In contrast, no fluorescein release from NTSL and NR release from both TSL and NTSL was observed at temperatures up to 60 degrees C.", "output": "fluorescein." }, { "input": "CW - HIFU exposure of TSL resulted in rapid temperature elevation up to 52 degrees C and subsequently almost quantitative fluorescein release.", "output": "fluorescein." }, { "input": "Fluorescein release from NTSL was also substantial ( ~ 64 % after 16min at 20W ).", "output": "Fluorescein." }, { "input": "Surprisingly, CW - HIFU exposure ( 20W for 16min ) resulted in the release of NR from TSL ( ~ 66 % of the loaded amount ), and this was even higher from NTSL ( ~ 78 % ).", "output": "There is no related enetity." }, { "input": "PW - HIFU exposure did not result in temperatures above the Tm of TSL.", "output": "There is no related enetity." }, { "input": "However, nearly 85 % of fluorescein was released from TSL after 32min at 20W of PW - HIFU exposure, whereas the release from NTSL was around 27 %.", "output": "fluorescein." }, { "input": "Interestingly, NR release from NTSL was ~ 30 % after 2min PW - HIFU exposure and increased to ~ 70 % after 32min.", "output": "There is no related enetity." }, { "input": "Furthermore, addition of microbubbles to the liposomes prior to PW - HIFU exposure did not result in more release, which suggests that cavitation can be excluded as the main mechanism responsible for the triggered release of both a hydrophilic and a lipophilic model compound from liposomes.", "output": "There is no related enetity." }, { "input": "Dynamic light scattering analysis showed that the mean size and PDI of the liposomes did not significantly change after CW - and PW - HIFU exposure.", "output": "There is no related enetity." }, { "input": "Taken together, it is therefore concluded that neither temperature elevation nor inertial cavitation is essential for the release of both hydrophilic and lipophilic compounds from liposomes.", "output": "There is no related enetity." }, { "input": "It is assumed that the release originates from radiation force - induced acoustic streaming, causing the liposomes to collide at the walls of the exposure chamber leading to shear forces which in turn results in reversible liposome destabilization and release of both hydrophilic and lipophilic compounds.", "output": "There is no related enetity." }, { "input": "Lactosylated gramicidin - based lipid nanoparticles ( Lac - GLN ) for targeted delivery of anti - miR - 155 to hepatocellular carcinoma.", "output": "There is no related enetity." }, { "input": "Lactosylated gramicidin - containing lipid nanoparticles ( Lac - GLN ) were developed for delivery of anti - microRNA - 155 ( anti - miR - 155 ) to hepatocellular carcinoma ( HCC ) cells.", "output": "There is no related enetity." }, { "input": "MiR - 155 is an oncomiR frequently elevated in HCC.", "output": "There is no related enetity." }, { "input": "The Lac - GLN formulation contained N - lactobionyl - dioleoyl phosphatidylethanolamine ( Lac - DOPE ), a ligand for the asialoglycoprotein receptor ( ASGR ), and an antibiotic peptide gramicidin A.", "output": "N - lactobionyl - dioleoyl phosphatidylethanolamine, Lac - DOPE." }, { "input": "The nanoparticles exhibited a mean particle diameter of 73nm, zeta potential of + 3. 5mV, anti - miR encapsulation efficiency of 88 %, and excellent colloidal stability at 4 degrees C.", "output": "There is no related enetity." }, { "input": "Lac - GLN effectively delivered anti - miR - 155 to HCC cells with a 16. 1 - and 4. 1 - fold up - regulation of miR - 155 targets C / EBP beta and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000.", "output": "There is no related enetity." }, { "input": "In mice, intravenous injection of Lac - GLN containing Cy3 - anti - miR - 155 led to preferential accumulation of the anti - miR - 155 in hepatocytes.", "output": "There is no related enetity." }, { "input": "Intravenous administration of 1. 5mg / kg anti - miR - 155 loaded Lac - GLN resulted in up - regulation of C / EBP beta and FOXP3 by 6. 9 - and 2. 2 - fold, respectively.", "output": "There is no related enetity." }, { "input": "These results suggest potential application of Lac - GLN as a liver - specific delivery vehicle for anti - miR therapy.", "output": "There is no related enetity." }, { "input": "Recent advances in theranostic nanocarriers of doxorubicin based on iron oxide and gold nanoparticles.", "output": "doxorubicin, iron oxide." }, { "input": "Hybrid ( organic / inorganic ) nanoparticles emerged as a simple solution to build \" theranostic \" systems.", "output": "There is no related enetity." }, { "input": "Due to their physical properties, superparamagnetic iron oxide nanoparticles ( SPIONs ) and plasmonic gold nanoparticles ( Au - NPs ) are extensively studied as a part of diagnostic and therapeutic strategies in cancer treatments.", "output": "iron oxide, Au." }, { "input": "They can be used as agents for in vitro or in vivo imaging, for magnetic drug targeting and / or thermal therapy.", "output": "There is no related enetity." }, { "input": "Their functionalization with organic shells enhances their potential performance in tumor targeting and drug delivery.", "output": "There is no related enetity." }, { "input": "The advances in such hybrid nanocarriers are well illustrated with the example of the anticancer drug doxorubicin ( DOX ).", "output": "doxorubicin, DOX." }, { "input": "The aim of this review is to give a multidisciplinary overview of such smart nanosystems loaded with DOX, based on examples taken from recent publications.", "output": "DOX." }, { "input": "From a physico - chemical point of view, we discuss the choices for the strategies for loading DOX and the consequences on drug release.", "output": "DOX." }, { "input": "From a biological point of view, we analyze the in vitro and in vivo assays concerning tumor imaging, targeted drug delivery and anticancer efficiency.", "output": "There is no related enetity." }, { "input": "Future opportunities and challenges are also addressed.", "output": "There is no related enetity." }, { "input": "Bisphenol A: Update on newly developed data and how they address NTP ' s 2008 finding of \" Some Concern \"", "output": "Bisphenol A." }, { "input": "Bisphenol A ( BPA ) is a component of polycarbonate plastics and epoxy resins used in many commercial products including coatings and liners of food containers.", "output": "Bisphenol A, BPA, polycarbonate, epoxy." }, { "input": "Low levels of BPA can be detected in over 90 % of human urine samples in the US, indicating that exposure to BPA is widespread.", "output": "BPA, BPA." }, { "input": "In 2008, the US National Toxicology Program ' s Center for the Evaluation of Risks to Human Reproduction ( NTP - CERHR ) expressed concerns regarding BPA ' s potential health effects, and suggested improved study designs and methodologies that they believed would address those concerns.", "output": "BPA." }, { "input": "This paper discusses some of the controversial issues surrounding BPA, summarizes the current regulatory status of BPA, reviews recent pharmacokinetic studies, and describes ongoing and planned research on the effects of BPA.", "output": "BPA, BPA, BPA." }, { "input": "In addition, we evaluate two papers studying BPA neurobehavioral effects, identified by the European Food Safety Authority and the German Federal Institute for Risk Assessment as being valid for use in risk assessment, to determine whether they address the NTP - CERHR methodological concerns.", "output": "BPA." }, { "input": "The data from these studies would likely be sufficient for NTP to lower its concern level for neurobehavioral effects of BPA.", "output": "BPA." }, { "input": "At this time, many regulatory agencies from around the world support the use of BPA in food contact materials.", "output": "BPA." }, { "input": "A Review of the \" Omics \" Approach to Biomarkers of Oxidative Stress in Oryza sativa.", "output": "There is no related enetity." }, { "input": "Physiological and ecological constraints that cause the slow growth and depleted production of crops have raised a major concern in the agriculture industry as they represent a possible threat of short food supply in the future.", "output": "There is no related enetity." }, { "input": "The key feature that regulates the stress signaling pathway is always related to the reactive oxygen species ( ROS ).", "output": "oxygen." }, { "input": "The accumulation of ROS in plant cells would leave traces of biomarkers at the genome, proteome, and metabolome levels, which could be identified with the recent technological breakthrough coupled with improved performance of bioinformatics.", "output": "There is no related enetity." }, { "input": "This review highlights the recent breakthrough in molecular strategies ( comprising transcriptomics, proteomics, and metabolomics ) in identifying oxidative stress biomarkers and the arising opportunities and obstacles observed in research on biomarkers in rice.", "output": "There is no related enetity." }, { "input": "The major issue in incorporating bioinformatics to validate the biomarkers from different omic platforms for the use of rice - breeding programs is also discussed.", "output": "There is no related enetity." }, { "input": "The development of powerful techniques for identification of oxidative stress - related biomarkers and the integration of data from different disciplines shed light on the oxidative response pathways in plants.", "output": "There is no related enetity." }, { "input": "Inhibition of proteases as a novel therapeutic strategy in the treatment of metabolic, inflammatory and functional diseases of the gastrointestinal tract.", "output": "There is no related enetity." }, { "input": "Proteases are widely distributed in the human body and are crucially involved in the modulation of physiological processes in the gastrointestinal ( GI ) tract.", "output": "There is no related enetity." }, { "input": "They also have a major role in the etiology and the course of GI diseases.", "output": "There is no related enetity." }, { "input": "This review discusses the pharmacology of proteases and medical application of their inhibitors in the GI tract.", "output": "There is no related enetity." }, { "input": "In particular, we focus on metabolic disorders, such as diabetes type 2, inflammatory bowel diseases ( IBD ), irritable bowel syndrome ( IBS ) and abdominal pain.", "output": "There is no related enetity." }, { "input": "Based on recent papers in the field of pharmacology and documented clinical trials, we suggest future treatment options employing protease inhibitors.", "output": "There is no related enetity." }, { "input": "Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes.", "output": "perfluoroalkyl acid." }, { "input": "While perfluorooctanoic acid ( PFOA ) and perfluorooctane sulfonate ( PFOS ) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids ( PFAAs ) detected in the environment.", "output": "perfluorooctanoic acid, PFOA, perfluorooctane sulfonate, PFOS, perfluoroalkyl acids, PFAAs." }, { "input": "Using a transient transfection assay developed in COS - 1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator - activated receptor alpha ( PPAR alpha ).", "output": "PFAAs." }, { "input": "Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays.", "output": "PFAAs." }, { "input": "Primary mouse and human hepatoyctes were cultured for 48h in the presence of varying concentrations of 12 different PFAAs or Wy14, 643, a known activator of PPAR alpha.", "output": "PFAAs, Wy14 , 643." }, { "input": "Total RNA was collected and the expression of 48 mouse or human genes evaluated.", "output": "There is no related enetity." }, { "input": "Gene selection was based on either in - house liver microarray data ( mouse ) or published data using primary hepatocytes ( human ).", "output": "There is no related enetity." }, { "input": "Gene expression in primary mouse hepatocytes was more restricted than expected.", "output": "There is no related enetity." }, { "input": "Genes typically regulated in whole tissue by PPAR alpha agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1.", "output": "There is no related enetity." }, { "input": "Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up - regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes.", "output": "androstane, PFAAs." }, { "input": "Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells.", "output": "There is no related enetity." }, { "input": "A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult.", "output": "There is no related enetity." }, { "input": "This likely reflects weaker activation of PPAR alpha in human versus rodent cells as well as variation among individual cell donors.", "output": "There is no related enetity." }, { "input": "Unlike mouse cells, CYP2B6 was up - regulated in human hepatocytes by a number of PFAAs as was PPAR delta.", "output": "PFAAs." }, { "input": "Rankings were conducted on the limited dataset.", "output": "There is no related enetity." }, { "input": "In mouse hepatocytes, the pattern was similar to that previously observed in the COS - 1 reporter cell assay.", "output": "There is no related enetity." }, { "input": "With the exception of PFHxA, longer chain PFAA carboxylates were the most active.", "output": "PFAA, carboxylates." }, { "input": "The pattern was similar in human hepatocytes, although PFDA and PFOS showed higher activity than previously observed while PFOA showed somewhat less activity.", "output": "PFDA, PFOS, PFOA." }, { "input": "These data reflect inherent challenges in using primary hepatocytes to predict toxicological response.", "output": "There is no related enetity." }, { "input": "Gene Cloning, Expression and Characterization of a Novel Xylanase from the Marine Bacterium, Glaciecola mesophila KMM241.", "output": "There is no related enetity." }, { "input": "Marine xylanases are rather less studied compared to terrestrial xylanases.", "output": "There is no related enetity." }, { "input": "In this study, a new xylanase gene, xynB, was cloned from the marine bacterium, Glaciecola mesophila KMM241, and expressed in Escherichia coli.", "output": "There is no related enetity." }, { "input": "xynB encodes a multi - domain xylanase XynB of glycoside hydrolase ( GH ) family 8.", "output": "There is no related enetity." }, { "input": "The recombinant XynB comprises an N - terminal domain ( NTD ) with unknown function and a catalytic domain, which is structurally novel among the characterized xylanases of GH family 8.", "output": "N." }, { "input": "XynB has the highest identity ( 38 % ) to rXyn8 among the characterized xylanases.", "output": "There is no related enetity." }, { "input": "The recombinant XynB showed maximal activity at pH 6 - 7 and 35 degrees C.", "output": "There is no related enetity." }, { "input": "It is thermolabile and salt - tolerant.", "output": "There is no related enetity." }, { "input": "XynB is an endo - xylanase that demands at least five sugar moieties for effective cleavage and to hydrolyze xylohexaose and xylopentaose into xylotetraose, xylotriose and xylobiose.", "output": "xylohexaose, xylopentaose, xylotetraose, xylotriose, xylobiose." }, { "input": "NTD was expressed in Escherichia coli to analyze its function.", "output": "There is no related enetity." }, { "input": "The recombinant NTD exhibited a high binding ability to insoluble xylan and avicel and little binding ability to chitosan and chitin.", "output": "There is no related enetity." }, { "input": "Since the NTD shows no obvious homology to any known carbohydrate - binding module ( CBM ) sequence in public databases, XynB may contain a new type of CBM.", "output": "carbohydrate." }, { "input": "Variations in polyethylene glycol brands and their influence on the preparation process of hydrogel microspheres.", "output": "polyethylene glycol." }, { "input": "Hydrogel microspheres, e. g. for the use as protein carriers, can be prepared without the use of organic solvents via an emulsified aqueous two - phase system ( ATPS ) that is based on two immiscible polymer solutions.", "output": "There is no related enetity." }, { "input": "The type and concentration of the polymers can affect the ATPS and finally the distribution of incorporated drugs between the aqueous phases.", "output": "There is no related enetity." }, { "input": "For the preparation of hydrogel microspheres based on hydroxyethyl starch - hydroxyethyl methacrylate ( HES - HEMA ), hydroxyethyl starch - methacrylate ( HES - MA ), and hydroxyethyl starch - polyethylene glycol methacrylate ( HES - P ( EG ) 6MA ), polyethylene glycol 12, 000 ( PEG 12, 000 ) was used as second polymer.", "output": "hydroxyethyl, hydroxyethyl methacrylate, HES - HEMA, hydroxyethyl, methacrylate, HES - MA, hydroxyethyl, polyethylene glycol methacrylate, HES - P ( EG ) 6MA, polyethylene glycol, PEG." }, { "input": "The particle size distribution and encapsulation efficiency of the microspheres depended dramatically on the type of PEG 12, 000 that was used in the second phase of the ATPS.", "output": "PEG." }, { "input": "Analysis of different PEG 12, 000 brands by various methods revealed differences in the salt composition and molecular weight distribution of the polymers which can explain the results from the production process.", "output": "PEG." }, { "input": "The results illustrate that the range of product specifications may not always be tight enough to avoid variability in pharmaceutical processes like the preparation of hydrogel microspheres by an aqueous two - phase preparation process.", "output": "There is no related enetity." }, { "input": "Evaluation of 7 - O - galloyl - d - sedoheptulose, isolated from Corni Fructus, in the adipose tissue of type 2 diabetic db / db mice.", "output": "7 - O - galloyl - d - sedoheptulose." }, { "input": "The aim of the present study was to evaluate the beneficial effects of 7 - O - galloyl - d - sedoheptulose ( GS ), isolated from Corni Fructus, using type 2 diabetic mice.", "output": "7 - O - galloyl - d - sedoheptulose." }, { "input": "GS was orally administered to db / db mice at doses of 20 and 100mg / kg body weight per day for 6weeks, and the effects of GS on biochemical factors in serum and adipose tissue were investigated.", "output": "There is no related enetity." }, { "input": "To define the underlying mechanism of these effects, protein expressions related to lipid metabolism, inflammation, fibrosis, and apoptosis, were measured.", "output": "There is no related enetity." }, { "input": "The results showed that levels of glucose, leptin, insulin, C - peptide, resistin, tumor necrosis factor - alpha, interleukin - 6, triglycerides, total cholesterol, non - esterified fatty acids, high - density lipoprotein cholesterol, very low - density lipoprotein cholesterol / low - density lipoprotein cholesterol, reactive oxygen species ( ROS ), and thiobarbituric acid - reactive substance ( TBARS ) in serum were down - regulated, while adiponectin was augmented by GS treatment.", "output": "glucose, triglycerides, cholesterol, fatty acids, cholesterol, cholesterol, cholesterol, oxygen, thiobarbituric acid." }, { "input": "In addition, the elevated lipid, ROS, and TBARS contents in adipose tissue as well as serum levels in db / db mice were significantly decreased by the oral administration of GS.", "output": "There is no related enetity." }, { "input": "From protein analysis, the decreased expressions of peroxisome proliferator activated receptor ( PPAR ) alpha, PPAR gamma, and B - cell lymphoma 2 were up - regulated in the adipose tissue of db / db mice.", "output": "There is no related enetity." }, { "input": "The administration of GS significantly decreased sterol regulatory element binding protein - 1, nuclear factor - kappa? > Bp65, cyclooxygenase - 2, inducible nitric oxide synthase, monocyte chemotactic protein - 1, intracellular adhesion molecule - 1, phosphor c - Jun N - terminal kinase, activator protein - 1, transforming growth factor - beta 1, Bax, cytochrome c, and caspase - 3 expressions.", "output": "sterol, nitric oxide, N." }, { "input": "These results suggest that GS acts as a regulator of oxidative stress, inflammation, fibrosis, and apoptosis in the adipose tissue of db / db mice.", "output": "There is no related enetity." }, { "input": "Polysulfones of new structural types as perspective antioxidant agents.", "output": "Polysulfones." }, { "input": "A series of polysulfones of new structural types on the basis of azanorbornenes, 2, 2 - diallyl - 1, 1, 3, 3 - tetraethylguanidiniumchloride and tris ( diethylamino ) diallylaminophosphonium salts were obtained by free radical polymerization reaction.", "output": "polysulfones, azanorbornenes, 2 , 2 - diallyl - 1 , 1 , 3 , 3 - tetraethylguanidiniumchloride and tris ( diethylamino ) diallylaminophosphonium salts." }, { "input": "Their antioxidant properties in lipid peroxidation induced by iron / ascorbate and in erythrocyte hemolysis by H2O2 were evaluated.", "output": "iron, ascorbate, H2O2." }, { "input": "The polysulfone of 2, 2 - diallyl - 1, 1, 3, 3 - tetraethylguanidinium chloride showed protection of erythrocytes against hydrogen peroxide and thermal shock, protected epithelial cells against UV irradiation, was not toxic for erythrocytes, epithelial cells SPEV and 3T3 fibroblasts.", "output": "polysulfone, 2 , 2 - diallyl - 1 , 1 , 3 , 3 - tetraethylguanidinium chloride, hydrogen peroxide." }, { "input": "The polysulfone of N - benzyl - 2 - azanorbornene - 5 inhibited lipid peroxidation in liver homogenate, did not exhibit cytotoxicity in SPEV and 3T3 cells, protected these against UV irradiation.", "output": "polysulfone, N - benzyl - 2 - azanorbornene - 5." }, { "input": "Both compounds had low bioavailability and may be recommended for further investigations as excipients to be externally applied.", "output": "There is no related enetity." }, { "input": "Design, synthesis and antiproliferative properties of some new 5 - substituted - 2 - iminobenzimidazole derivatives.", "output": "5 - substituted - 2 - iminobenzimidazole." }, { "input": "Some new 1, 3, 5 - substituted - 2, 3 - dihydro - 2 - imino - benzimidazoles were synthesized under solid - liquid phase transfer catalysis conditions using 5 - substituted - 2 - aminobenzimidazoles as precursors in order to assess their cytotoxicity respectively proliferative activity.", "output": "1 , 3 , 5 - substituted - 2 , 3 - dihydro - 2 - imino - benzimidazoles, 5 - substituted - 2 - aminobenzimidazoles." }, { "input": "The structures of the compounds were confirmed by IR, ( 1 ) H NMR, ( 13 ) C NMR and elemental analysis.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "Compounds 9 - 10, 12 and 16 - 17 were evaluated for their cytotoxical effect on four cancer cell lines: HT - 29, breast cancer cells MDA - MB - 231, HeLa, HepG2 and as well as human diploid cell line Lep - 3.", "output": "There is no related enetity." }, { "input": "Significant cytotoxicity of hydrazone 16 against MDA - MB - 231 was established by biologically study, the IC50 was 6. 2 nM while the EC50 value to Lep 3 is 0. 21 nM.", "output": "hydrazone." }, { "input": "Relative high antiproliferative effects of the acetate 12 and compound 16 against HT - 29 were ascertained and the calculated IC50 values were IC50 - 0. 85 nM and IC50 - 2. 83 nM respectively.", "output": "acetate." }, { "input": "Cytotoxic activity against HeLa and HepG2 cells was demonstrated by hydrazone 17, IC50 was 7. 2 nM and 117 nM respectively.", "output": "hydrazone." }, { "input": "All tested compounds revealed proliferative activities to human diploid cell line Lep - 3.", "output": "There is no related enetity." }, { "input": "The EC50 values were in the range from 0. 05 to 16. 91 nM.", "output": "There is no related enetity." }, { "input": "The obtained results prove the selective cytotoxicity of the tested compounds and are promising for further evaluation of the investigated compounds in vivo experiments using experimentally induced tumors in laboratory animals.", "output": "There is no related enetity." }, { "input": "Identification, structural and pharmacological characterization of tau - CnVA, a conopeptide that selectively interacts with somatostatin sst3 receptor.", "output": "tau - CnVA." }, { "input": "Conopeptides are a diverse array of small linear and reticulated peptides that interact with high potency and selectivity with a large diversity of receptors and ion channels.", "output": "There is no related enetity." }, { "input": "They are used by cone snails for prey capture or defense.", "output": "There is no related enetity." }, { "input": "Recent advances in venom gland transcriptomic and venom peptidomic / proteomic technologies combined with bioactivity screening approaches lead to the identification of new toxins with original pharmacological profiles.", "output": "There is no related enetity." }, { "input": "Here, from transcriptomic / proteomic analyses of the Conus consors cone snail, we identified a new conopeptide called tau - CnVA, which displays the typical cysteine framework V of the T1 - conotoxin superfamily.", "output": "tau - CnVA, cysteine." }, { "input": "This peptide was chemically synthesized and its three - dimensional structure was solved by NMR analysis and compared to that of TxVA belonging to the same family, revealing very few common structural features apart a common orientation of the intercysteine loop.", "output": "There is no related enetity." }, { "input": "Because of the lack of a clear biological function associated with the T - conotoxin family, tau - CnVA was screened against more than fifty different ion channels and receptors, highlighting its capacity to interact selectively with the somatostatine sst3 receptor.", "output": "tau - CnVA." }, { "input": "Pharmacological and functional studies show that tau - CnVA displays a micromolar ( Ki of 1. 5 mu M ) antagonist property for the sst3 receptor, being currently the only known toxin to interact with this GPCR subfamily.", "output": "tau - CnVA." }, { "input": "Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.", "output": "There is no related enetity." }, { "input": "Over the past 50 years, numerous advances in treatment have produced dramatic increases in the cure rates of pediatric leukemias.", "output": "There is no related enetity." }, { "input": "Despite this progress, the majority of children with relapsed leukemia are not expected to survive.", "output": "There is no related enetity." }, { "input": "With current chemotherapy regimens, approximately 15 % of children with acute lymphoblastic leukemia and 45 % of children with acute myeloid leukemia will have refractory disease or experience a relapse.", "output": "There is no related enetity." }, { "input": "Advances in the treatment of pediatric relapsed leukemia have not mirrored the successes of upfront therapy, and newer treatments are desperately needed in order to improve survival in these challenging patients.", "output": "There is no related enetity." }, { "input": "Recent improvements in our knowledge of cancer biology have revealed an extensive number of targets that have the potential to be exploited for anticancer therapy.", "output": "There is no related enetity." }, { "input": "These advances have led to the development of a number of new treatments that are now being explored in children with relapsed or refractory leukemia.", "output": "There is no related enetity." }, { "input": "Novel agents seek to exploit the same molecular aberrations that contribute to leukemia development and resistance to therapy.", "output": "There is no related enetity." }, { "input": "Newer classes of drugs, including monoclonal antibodies, tyrosine kinase inhibitors and epigenetic modifiers are transforming the treatment of patients who are not cured with conventional therapies.", "output": "tyrosine." }, { "input": "As the side effects of many new agents are distinct from those seen with conventional chemotherapy, these treatments are often explored in combination with each other or combined with conventional treatment regimens.", "output": "There is no related enetity." }, { "input": "This review discusses the biological rationale for the most promising new agents and the results of recent studies conducted in pediatric patients with relapsed leukemia.", "output": "There is no related enetity." }, { "input": "Profiling glycosyltransferase activities by tritium imaging of glycan microarrays.", "output": "tritium." }, { "input": "High - throughput microarray technology has been combined with ultrasensitive and high - resolution tritium autoradiography to create a new platform for the quantitative detection of glycosyltransferase activity on glycan arrays.", "output": "tritium." }, { "input": "In addition, we show full compatibility with the use of fluorescently labeled lectins to help with the stereochemical assignment of newly formed glycoside linkages.", "output": "There is no related enetity." }, { "input": "Potent Inhibitors of Phosphatidylinositol 3 ( PI3 ) Kinase that have Antiproliferative Activity Only When Delivered as Prodrug Forms.", "output": "Phosphatidylinositol." }, { "input": "Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase ( PI3K ) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation.", "output": "phosphatidylinositol, LY294002." }, { "input": "Two tetrazolyl - substituted analogues were further derivatized as prodrugs resulting in restoration of cell - based activity.", "output": "tetrazolyl." }, { "input": "These data provide a conceptual model for development of tumor - targeting prodrug forms of cell - impermeable PI3K inhibitors.", "output": "There is no related enetity." }, { "input": "Rhenium Complexes with Visible - Light - Induced Anticancer Activity.", "output": "Rhenium." }, { "input": "Shedding light on the matter: Rhenium ( I ) indolato complexes with highly potent visible - light - triggered antiproliferative activity ( complex 1: EC50 light = 0. 1 mu M vs EC50 dark = 100 mu M ) in 2D - and 3D - organized cancer cells are reported and can be traced back to an efficient generation of singlet oxygen, causing rapid morphological changes and an induction of apoptosis.", "output": "Rhenium ( I ) indolato complexes, oxygen." }, { "input": "Toxicokinetics of acrylamide in primary rat hepatocytes: coupling to glutathione is faster than conversion to glycidamide.", "output": "acrylamide, glutathione, glycidamide." }, { "input": "Acrylamide ( AA ), classified as class 2A carcinogen ( probably carcinogenic to humans ) by the International Agency for Research on Cancer ( IARC ), is formed during heating of food from reducing carbohydrates and asparagine by Maillard reaction chemistry.", "output": "Acrylamide, carbohydrates, asparagine." }, { "input": "After dietary uptake, AA is in part metabolically converted into the proximate genotoxic phase I metabolite glycidamide ( GA ).", "output": "glycidamide." }, { "input": "GA reacts with nucleophilic base positions in DNA, primarily forming N7 - ( 2 - carbamoyl - 2 - hydroxyethyl ) guanine ( N7 - GA - Gua ) adducts.", "output": "N7 - ( 2 - carbamoyl - 2 - hydroxyethyl ) guanine, N7 - GA - Gua." }, { "input": "In a competing phase II biotransformation pathway AA, as well as its phase I metabolite GA, is coupled to glutathione ( GSH ).", "output": "glutathione, GSH." }, { "input": "The GSH coupling products are further biotransformed and excreted via urine as mercapturic acids ( MA ), N - acetyl - S - ( 2 - carbamoylethyl ) cysteine ( AAMA ), and N - acetyl - S - ( 2 - hydroxy - 2 - carbamoylethyl ) cysteine ( GAMA ).", "output": "GSH, mercapturic acids, N - acetyl - S - ( 2 - carbamoylethyl ) cysteine, AAMA, N - acetyl - S - ( 2 - hydroxy - 2 - carbamoylethyl ) cysteine, GAMA." }, { "input": "In the present study, hepatic biotransformation pathways and DNA adduct formation were studied in primary rat hepatocytes, incubated with AA ( 0. 2 - 2, 000 mu M ) for up to 24 h.", "output": "There is no related enetity." }, { "input": "Contents of AA - GSH, GA, AAMA, and GAMA were measured in the cell culture medium after solid phase extraction ( SPE ).", "output": "AA - GSH, AAMA, GAMA." }, { "input": "N7 - GA - Gua adducts in DNA of hepatocytes were determined by HPLC - ESI - MS / MS after lysis of the cells and neutral thermal hydrolysis.", "output": "N7 - GA - Gua." }, { "input": "Formation of AA - GSH was linear with AA concentration and incubation time and became detectable already at 0. 2 mu M ( 4 h ).", "output": "AA - GSH." }, { "input": "In contrast to AA, GA was not detected before 16 h incubation at 10 - fold higher AA concentration ( 2 mu M ).", "output": "There is no related enetity." }, { "input": "In summary, the rate of AA - GSH formation was found to be about 1. 5 - 3 times higher than that of GA formation.", "output": "AA - GSH." }, { "input": "N7 - GA - Gua adducts were found only at the highest AA concentration tested ( 2, 000 mu M ).", "output": "N7 - GA - Gua." }, { "input": "Differential levels of brain amino acids in rat models presenting learned helplessness or non - learned helplessness.", "output": "amino acids." }, { "input": "RATIONALE: Glutamatergic and gamma - aminobutyric acid ( GABA ) ergic abnormalities have recently been proposed to contribute to depression.", "output": "gamma - aminobutyric acid, GABA." }, { "input": "The learned helplessness ( LH ) paradigm produces a reliable animal model of depression that expresses a deficit in escape behavior ( LH model ); an alternative phenotype that does not exhibit LH is a model of resilience to depression ( non - LH model ).", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We measured the contents of amino acids in the brain to investigate the mechanisms involved in the pathology of depression.", "output": "amino acids." }, { "input": "METHODS: LH and non - LH models were subjected to inescapable electric footshocks at random intervals following a conditioned avoidance test to determine acquirement of predicted escape deficits.", "output": "There is no related enetity." }, { "input": "Tissue amino acid contents in eight brain regions were measured via high - performance liquid chromatography.", "output": "amino acid." }, { "input": "RESULTS: The non - LH model showed increased GABA levels in the dentate gyrus and nucleus accumbens and increased glutamine levels in the dentate gyrus and the orbitofrontal cortex.", "output": "GABA, glutamine." }, { "input": "The LH model had reduced glutamine levels in the medial prefrontal cortex.", "output": "glutamine." }, { "input": "Changes in the ratios of GABA, glutamine, and glutamate were detected in the non - LH model, but not in the LH model.", "output": "GABA, glutamine, glutamate." }, { "input": "Reductions in threonine levels occurred in the medial prefrontal cortex in both models, whereas elevated alanine levels were detected in the medial prefrontal cortex in non - LH animals.", "output": "threonine, alanine." }, { "input": "CONCLUSIONS: The present study demonstrates region - specific compensatory elevations in GABA levels in the dentate gyrus and nucleus accumbens of non - LH animals, supporting the implication of the GABAergic system in the recovery of depression.", "output": "GABA." }, { "input": "On the persistence of cocaine - induced place preferences and aversions in rats.", "output": "cocaine." }, { "input": "RATIONALE: Rats develop preferences for places associated with the immediate rewarding effects of cocaine and aversions for places paired with the drug ' s delayed negative effects.", "output": "cocaine." }, { "input": "The motivation to seek cocaine should therefore depend upon the relative magnitude of these two opposing effects of the drug.", "output": "cocaine." }, { "input": "OBJECTIVE: The current study tested this notion by assessing the relative persistence of the positive and negative associations formed between environmental cues and the immediate or delayed effects of cocaine.", "output": "cocaine." }, { "input": "METHODS: Rats were administered 1. 0 mg / kg intravenous cocaine and placed into a distinctive environment either immediately or 15 - min after injection, alternating daily with pairings of a second environment with saline.", "output": "cocaine." }, { "input": "After four drug - place and four saline - place pairings, rats were returned to their home cages for 1, 7, or 21 days after which a 15 - min place preference test was conducted.", "output": "There is no related enetity." }, { "input": "In a second experiment, the effectiveness of a single reconditioning session ( one drug - place and one saline - place pairing ) to reactivate learned cocaine - place associations was assessed after 1 or 3 weeks of drug abstinence.", "output": "cocaine." }, { "input": "RESULTS: Places associated with the immediate effects of cocaine were preferred ( CPP ), while places associated with the delayed effects of cocaine were avoided ( CPA ).", "output": "cocaine, cocaine." }, { "input": "The persistence of these effects differed with CPP remaining viable at 3 weeks of withdrawal, while CPA was no longer present after 1 week.", "output": "There is no related enetity." }, { "input": "Reconditioning with an additional cocaine - place pairing failed to reinstate the CPA.", "output": "cocaine." }, { "input": "CONCLUSIONS: Cue - induced \" relapse \" of cocaine - seeking behavior may be fueled in part by an increased persistence of positive relative to negative associations with drug - paired stimuli.", "output": "cocaine." }, { "input": "Direct measurement of contact angles of silica particles in relation to double inversion of pickering emulsions.", "output": "silica." }, { "input": "In an alkane - water system containing submicrometer silica particles at high pH, double emulsion inversion from oil - in - water ( o / w ) to water - in - oil ( w / o ) to oil - in - water can be effected by increasing the concentration of a dichain cationic surfactant in water.", "output": "silica." }, { "input": "The contact angle theta of the particles at the planar oil - water interface has been measured directly using freeze - fracture shadow - casting cryo - scanning electron microscopy, enabling single - particle measurements of high accuracy.", "output": "There is no related enetity." }, { "input": "theta passes through a maximum with respect to surfactant concentration.", "output": "There is no related enetity." }, { "input": "It is shown that particles undergo a hydrophilic - hydrophobic - hydrophilic transition corresponding closely to the o / w - w / o - o / w transformation observed in emulsions.", "output": "There is no related enetity." }, { "input": "These results unequivocally link the single - particle contact angles to the type of particle - stabilized emulsion, confirming macroscopic emulsion inversion on the microscopic level.", "output": "There is no related enetity." }, { "input": "Modular stitching to image single - molecule DNA transport.", "output": "There is no related enetity." }, { "input": "For study of time - dependent conformation, all previous single - molecule imaging studies of polymer transport involve fluorescence labeling uniformly along the chain, which suffers from limited resolution due to the diffraction limit.", "output": "There is no related enetity." }, { "input": "Here we demonstrate the concept of submolecular single - molecule imaging with DNA chains assembled from DNA fragments such that a chain is labeled at designated spots with covalently attached fluorescent dyes and the chain backbone with dyes of different color.", "output": "There is no related enetity." }, { "input": "High density of dyes ensures good signal - to - noise ratio to localize the designated spots in real time with nanometer precision and prevents significant photobleaching for long - time tracking purposes.", "output": "There is no related enetity." }, { "input": "To demonstrate usefulness of this approach, we image electrophoretic transport of lambda - DNA through agarose gels.", "output": "There is no related enetity." }, { "input": "The unexpected pattern is observed that one end of each molecule tends to stretch out in the electric field while the other end remains quiescent for some time before it snaps forward and the stretch - recoil cycle repeats.", "output": "There is no related enetity." }, { "input": "These features are neither predicted by prevailing theories of electrophoresis mechanism nor detectable by conventional whole - chain labeling methods, which demonstrate pragmatically the usefulness of modular stitching to reveal internal chain dynamics of single molecules.", "output": "There is no related enetity." }, { "input": "Chemoselective metal - free aerobic alcohol oxidation in lignin.", "output": "There is no related enetity." }, { "input": "An efficient organocatalytic method for chemoselective aerobic oxidation of secondary benzylic alcohols within lignin model compounds has been identified.", "output": "benzylic alcohols." }, { "input": "Extension to selective oxidation in natural lignins has also been demonstrated.", "output": "There is no related enetity." }, { "input": "The optimal catalyst system consists of 4 - acetamido - TEMPO ( 5 mol %; TEMPO = 2, 2, 6, 6 - tetramethylpiperidine - N - oxyl ) in combination with HNO3 and HCl ( 10 mol % each ).", "output": "4 - acetamido - TEMPO, TEMPO, 2 , 2 , 6 , 6 - tetramethylpiperidine - N - oxyl, HNO3, HCl." }, { "input": "Preliminary studies highlight the prospect of combining this method with a subsequent oxidation step to achieve C - C bond cleavage.", "output": "C - C." }, { "input": "Ultrafast Charge Transfer at Monolayer Graphene Surfaces with Varied Substrate Coupling.", "output": "Graphene." }, { "input": "The charge transfer rates of a localized excited electron to graphene monolayers with variable substrate coupling have been investigated by the core hole clock method with adsorbed argon.", "output": "graphene." }, { "input": "Expressed as charge transfer times, we find strong variations between ~ 3 fs ( on graphene \" valleys \" on Ru ( 0001 ) ) to ~ 16 fs ( quasi - free graphene on SiC, O / Ru ( 0001 ), or SiO2 / Ru ).", "output": "graphene, Ru, graphene, SiC, O, Ru, SiO2, Ru." }, { "input": "The values for the \" hills \" on Gr / Ru and on Gr / Pt ( 111 ) are in between, with the ratio 1. 7 between the charge transfer times measured on \" hills \" and \" valleys \" of Gr / Ru.", "output": "Ru, Pt ( 111 ), Ru." }, { "input": "We discuss the results for Gr on metals in terms of hybridized Ru - C orbitals, which change with the relative Gr - Ru alignment and distance.", "output": "Ru, C, Ru." }, { "input": "The charge transfer on the decoupled graphene layers must represent the intrinsic coupling to the graphene empty pi * states.", "output": "graphene, graphene." }, { "input": "Its low rate may be influenced by processes retarding the spreading of charge after transfer.", "output": "There is no related enetity." }, { "input": "Coalescence of Repelling Colloidal Droplets: A Route to Monodisperse Populations.", "output": "There is no related enetity." }, { "input": "Populations of droplets or particles dispersed in a liquid may evolve through Brownian collisions, aggregation, and coalescence.", "output": "There is no related enetity." }, { "input": "We have found a set of conditions under which these populations evolve spontaneously toward a narrow size distribution.", "output": "There is no related enetity." }, { "input": "The experimental system consists of poly ( methyl methacrylate ) ( PMMA ) nanodroplets dispersed in a solvent ( acetone ) + nonsolvent ( water ) mixture.", "output": "poly ( methyl methacrylate ), PMMA, acetone." }, { "input": "These droplets carry electrical charges, located on the ionic end groups of the macromolecules.", "output": "There is no related enetity." }, { "input": "We used time - resolved small angle X - ray scattering to determine their size distribution.", "output": "There is no related enetity." }, { "input": "We find that the droplets grow through coalescence events: the average radius < R > increases logarithmically with elapsed time while the relative width sigma R / < R > of the distribution decreases as the inverse square root of < R >.", "output": "There is no related enetity." }, { "input": "We interpret this evolution as resulting from coalescence events that are hindered by ionic repulsions between droplets.", "output": "There is no related enetity." }, { "input": "We generalize this evolution through a simulation of the Smoluchowski kinetic equation, with a kernel that takes into account the interactions between droplets.", "output": "There is no related enetity." }, { "input": "In the case of vanishing or attractive interactions, all droplet encounters lead to coalescence.", "output": "There is no related enetity." }, { "input": "The corresponding kernel leads to the well - known \" self - preserving \" particle distribution of the coalescence process, where sigma R / < R > increases to a plateau value.", "output": "There is no related enetity." }, { "input": "However, for droplets that interact through long - range ionic repulsions, \" large + small \" droplet encounters are more successful at coalescence than \" large + large \" encounters.", "output": "There is no related enetity." }, { "input": "We show that the corresponding kernel leads to a particular scaling of the droplet - size distribution - known as the \" second - scaling law \" in the theory of critical phenomena, where sigma R / < R > decreases as 1 / sqrt < R > and becomes independent of the initial distribution.", "output": "There is no related enetity." }, { "input": "We argue that this scaling explains the narrow size distributions of colloidal dispersions that have been synthesized through aggregation processes.", "output": "There is no related enetity." }, { "input": "Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants.", "output": "There is no related enetity." }, { "input": "In the growing field of genomics, the utility of returning certain research results to participants has become a highly debated issue.", "output": "There is no related enetity." }, { "input": "Existing guidelines are not explicit as to the kind of genomic information that should be returned to research participants.", "output": "There is no related enetity." }, { "input": "Moreover, very few current recommendations and articles in the literature address the return of pharmacogenomic results.", "output": "There is no related enetity." }, { "input": "Although genetics and pharmacogenomics have many similarities, the circumstances in which disclosure could have a benefit for the participants are different.", "output": "There is no related enetity." }, { "input": "This review aims to describe the conditions in which disclosure of pharmacogenomic results is appropriate.", "output": "There is no related enetity." }, { "input": "Polymersomes from Dual Responsive Block Copolymers: Drug Encapsulation by Heating and Acid - Triggered Release.", "output": "There is no related enetity." }, { "input": "A series of well - defined thermoresponsive diblock copolymers ( PEO45 - b - PtNEAn, n = 22, 44, 63, 91, 172 ) were prepared by the atom transfer radical polymerization of trans - N - ( 2 - ethoxy - 1, 3 - dioxan - 5 - yl ) acrylamide ( tNEA ) using a poly ( ethylene oxide ) ( PEO45 ) macroinitiator.", "output": "PEO45, trans - N - ( 2 - ethoxy - 1 , 3 - dioxan - 5 - yl ) acrylamide, tNEA, poly ( ethylene oxide ), PEO45." }, { "input": "All copolymers are water - soluble at low temperature, but upon quickly heating to 37 degrees C, laser light scattering ( LLS ) and transmission electron microscopy ( TEM ) characterizations indicate that these copolymers self - assemble into aggregates with different morphologies depending on the chain length of PtNEA and the polymer concentration; the morphologies gradually evolved from spherical solid nanoparticles to a polymersome as the degree of polymerization ( \" n \" ) of PtNEA block increased from 22 to 172, with the formation of clusters with rod - like structure at the intermediate PtNEA length.", "output": "PtNEA, PtNEA, PtNEA." }, { "input": "Both the spherical nanoparticle and the polymersome are stable at physiological pH but susceptible to the mildly acidic medium.", "output": "There is no related enetity." }, { "input": "Acid - triggered hydrolysis behaviors of the aggregates were investigated by LLS, Nile red fluorescence, TEM, and ( 1 ) H NMR spectroscopy.", "output": "( 1 ) H." }, { "input": "The results revealed that the spherical nanoparticles formed from PEO45 - b - PtNEA44 dissociated faster than the polymersomes of PEO45 - b - PtNEA172, and both aggregates showed an enhanced hydrolysis under acidic conditions.", "output": "PEO45, PEO45." }, { "input": "Both the spherical nanoparticle and polymersome are able to efficiently load the hydrophobic doxorubicin ( DOX ), and water - soluble fluorescein isothiocyanate - lysozyme ( FITC - Lys ) can be conveniently encapsulated into the polymersome without using any organic solvent.", "output": "doxorubicin, DOX, fluorescein isothiocyanate, FITC." }, { "input": "Moreover, FITC - Lys and DOX could be coloaded in the polymersome.", "output": "FITC, DOX." }, { "input": "The drugs loaded either in the polymersome or in the spherical nanoparticle could be released by acid triggering.", "output": "There is no related enetity." }, { "input": "Finally, the DOX - loaded assemblies display concentration - dependent cytotoxicity to HepG2 cells, while the copolymers themselves are nontoxic.", "output": "DOX." }, { "input": "Discovery of Thieno [ 3, 2 - d ] pyrimidine - 6 - carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3.", "output": "Thieno [ 3 , 2 - d ] pyrimidine - 6 - carboxamides." }, { "input": "The sirtuins SIRT1, SIRT2, and SIRT3 are NAD ( + ) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders.", "output": "NAD ( + )." }, { "input": "Encoded library technology ( ELT ) was used to affinity screen a 1. 2 million heterocycle enriched library of DNA encoded small molecules, which identified pan - inhibitors of SIRT1 / 2 / 3 with nanomolar potency ( e. g., 11c: IC50 = 3. 6, 2. 7, and 4. 0 nM for SIRT1, SIRT2, and SIRT3, respectively ).", "output": "There is no related enetity." }, { "input": "Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31.", "output": "There is no related enetity." }, { "input": "Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C - pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR.", "output": "carboxamide, nicotinamide." }, { "input": "These pan SIRT1 / 2 / 3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.", "output": "There is no related enetity." }, { "input": "Laccase - mediated coupling of nonpolar chains for the hydrophobization of lignocellulose.", "output": "There is no related enetity." }, { "input": "We investigate the use of laccase enzymes for coupling short nonpolar chains containing aromatic rings onto flax fibers and nanofibrillated cellulose ( NFC ) with different lignin contents.", "output": "lignin." }, { "input": "Trametes villosa, Pycnoporus cinnabarinus and Myceliophthora thermophila were used to facilitate surface coupling and to produce materials with different levels of hydrophobicity.", "output": "There is no related enetity." }, { "input": "Heat treatment of fiber webs after lacccase - mediated coupling markedly increased the resistance to water absorption.", "output": "There is no related enetity." }, { "input": "The highest hydrophobization levels of flax fibers was achieved by coupling dodecyl 3, 4, 5 - trihydroxybenzoate ( HB - C12 ), which yielded water contact angles ( WCA ) of 80 - 96 degrees and water absorption times ( drop tests ) of ca.", "output": "dodecyl 3 , 4 , 5 - trihydroxybenzoate, HB - C12." }, { "input": "73 min.", "output": "There is no related enetity." }, { "input": "The results from apparent aromatic content and FTIR analyses confirmed the laccase - mediated coupling of HB - C12 onto the cellulose fibers.", "output": "HB - C12." }, { "input": "Substrates consisting of ultrathin films of NFC were also used as substrates for enzyme - mediated hydrophobization with HB - C12.", "output": "HB - C12." }, { "input": "In these cases water contact angles in the range of 87 - 104 degrees were achieved, depending on the conditions.", "output": "There is no related enetity." }, { "input": "Quartz crystal microgravimetry ( QCM ) was used to study the dynamics and the extent of the coupling process onto cellulose.", "output": "Quartz." }, { "input": "The results help to better understand the mechanisms involved in laccase - mediated hydrophobization and provide a proof of a biotechnological platform for the development of added - value fiber products.", "output": "There is no related enetity." }, { "input": "Retention and Release of Cinnamaldehyde from Wheat Protein Matrices.", "output": "Cinnamaldehyde." }, { "input": "Cinnamaldehyde treatment of gliadin films provided a means of decreasing their solubility, increasing their molecular weight profile, and reducing their overall migration into food simulants as a consequence of the high degree of polymerization achieved.", "output": "Cinnamaldehyde." }, { "input": "Despite losses incurred in the film manufacturing process, and the amount that remained covalently bonded with protein because of cross - linking, the addition of 1. 5, 3, and 5 % of cinnamaldehyde ( g / 100 g protein ) to gliadins at pH 2 rendered 1. 8, 4. 8, and 11. 0 mg cinnamaldehyde / g film, respectively, available to be released, and therefore to exert antimicrobial activity.", "output": "cinnamaldehyde, cinnamaldehyde." }, { "input": "Cinnamaldehyde diffusivity was largely dependent on environmental conditions, increasing from 0. 49 x 10 ( - 15 ) m ( 2 ) / s at 30 % relative humidity ( RH ) to 13. 1 x 10 ( - 15 ) m ( 2 ) / s at 90 % RH and 23 degrees C.", "output": "Cinnamaldehyde." }, { "input": "This water sensitivity of films provides a mechanism with a noteworthy potential to retain the compound before its use, to trigger its release when needed, and to modulate the release rate according to the product humidity.", "output": "There is no related enetity." }, { "input": "Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors.", "output": "Urea." }, { "input": "RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain ( MLC ).", "output": "There is no related enetity." }, { "input": "Inhibition of the RhoA / ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease.", "output": "There is no related enetity." }, { "input": "In 2010, our group reported urea - based ROCK inhibitors as potential antiglaucoma agents.", "output": "urea." }, { "input": "These compounds showed potent IC50 values in enzymatic and cell - based assays and significant intraocular pressure ( IOP ) - lowering effects in rats ( ~ 7 mmHg ).", "output": "There is no related enetity." }, { "input": "( 22 ) To develop more advanced ROCK inhibitors targeting various potential applications ( such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc. ) in addition to glaucoma, a thorough SAR for this urea - based scaffold was studied.", "output": "urea." }, { "input": "The detailed optimization process, counter - screening, and in vitro and in vivo DMPK studies are discussed.", "output": "There is no related enetity." }, { "input": "Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.", "output": "There is no related enetity." }, { "input": "Self - Repair of a Biological Fiber Guided by an Ordered Elastic Framework.", "output": "There is no related enetity." }, { "input": "Incorporating sacrificial cross - links into polymers represents an exciting new avenue for the development of self - healing materials, but it is unclear to what extent their spatial arrangement is important for this functionality.", "output": "There is no related enetity." }, { "input": "In this respect, self - healing biological materials, such as mussel byssal threads, can provide important chemical and structural insights.", "output": "There is no related enetity." }, { "input": "In this study, we employ in situ small - angle X - ray scattering ( SAXS ) measurements during mechanical deformation to show that byssal threads consist of a partially crystalline protein framework capable of large reversible deformations via unfolding of tightly folded protein domains.", "output": "There is no related enetity." }, { "input": "The long - range structural order is destroyed by stretching the fiber but reappears rapidly after removal of load.", "output": "There is no related enetity." }, { "input": "Full mechanical recovery, however, proceeds more slowly, suggesting the presence of strong and slowly reversible sacrificial cross - links.", "output": "There is no related enetity." }, { "input": "One likely role of the highly ordered elastic framework is to bring sacrificial binding sites back into register upon stress release, facilitating bond reformation and self - repair.", "output": "There is no related enetity." }, { "input": "Design and evaluation of polyamidoamine dendrimer conjugate with PEG, alpha - cyclodextrin and lactose as a novel hepatocyte - selective gene carrier in vitro and in vivo.", "output": "polyamidoamine, PEG, alpha - cyclodextrin, lactose." }, { "input": "Abstract To develop a novel hepatocyte - selective gene carrier, we prepared polyamidoamine starburst dendrimer ( generation 3, G3 ) conjugates with three functional molecules, i. e. alpha - cyclodextrin, polyethylene glycol ( PEG, molecular weight = 2170 ) and lactose ( PEG - L alpha Cs ), and evaluated gene delivery efficiency of these conjugates in vitro and in vivo.", "output": "polyamidoamine, alpha - cyclodextrin, polyethylene glycol, PEG, lactose, PEG - L alpha Cs." }, { "input": "PEG - L alpha C ( G3, degrees of substitution of the PEG moiety ( DSP ) 2. 1 ) showed higher gene transfer activity than other PEG - L alpha Cs ( G3, DSP4. 0, 6. 2 ) in HepG2 cells, expressing asialoglycoprotein receptor, and the activity decreased in HeLa cells, non - expressing the receptor and in the presence of asialofetuin.", "output": "PEG - L alpha C, PEG, PEG - L alpha Cs." }, { "input": "High gene transfer activity of PEG - L alpha C ( G3, DSP2. 1 ) was retained even in the presence of 50 % serum, although the activity of alpha - cyclodextrin / lactosylated dendrimer ( G3 ) conjugate ( Lac - alpha - CDE ( G3 ) ), which is lacking a PEG moiety, was severely decreased in the presence of 20 % serum.", "output": "PEG - L alpha C, alpha - cyclodextrin, Lac - alpha - CDE, PEG." }, { "input": "PEG - L alpha C ( G3, DSP2. 1 ) provided negligible cytotoxicity up to a charge ratio of 50 ( carrier / pDNA ) in HepG2 cells and less acute organ toxicity.", "output": "PEG - L alpha C." }, { "input": "PEG - L alpha C ( G3, DSP2. 1 ) showed selective gene transfer activity to hepatic parenchymal cells rather than hepatic non - parenchymal cells.", "output": "PEG - L alpha C." }, { "input": "These results suggest that PEG - L alpha C ( G3, DSP2. 1 ) is useful as a hepatocyte - selective gene carrier in vitro and in vivo.", "output": "PEG - L alpha C." }, { "input": "New dimeric and trimeric coumarin glucosides from Daphne retusa Hemsl.", "output": "coumarin." }, { "input": "New dimeric and a trimeric coumarin glucosides namely Daphneretusin A ( 1 ) Daphneretusin B ( 2 ) along with three known oligomers ( 3 - 5 ) were obtained as a result of bioassay guided fractionation of Daphne retusa Hemsl.", "output": "coumarin, Daphneretusin A, Daphneretusin B." }, { "input": "Fractions ( n - hexane, CHCl3, AcOEt, CH3OH and water ) exhibited potent radical scavenging activity in relevant non - physiological bioassays.", "output": "n - hexane, CHCl3, AcOEt, CH3OH." }, { "input": "The structures of isolated compounds were elucidated by UV, IR, EIMS, FAB - MS, 1D, and 2D NMR spectroscopic analysis.", "output": "There is no related enetity." }, { "input": "Goniolandrene A and B from Goniothalamus macrophyllus.", "output": "Goniolandrene A and B." }, { "input": "Goniothalamus macrophyllus ( Blume ) Hook.", "output": "There is no related enetity." }, { "input": "f.", "output": "There is no related enetity." }, { "input": "& Thoms.", "output": "There is no related enetity." }, { "input": "is a plant widely distributed in Malaysia.", "output": "There is no related enetity." }, { "input": "The aim of this study is to identify compounds from the roots of G. macrophyllus.", "output": "There is no related enetity." }, { "input": "The ground roots were extracted with aqueous methanol and partitioned sequentially with n - hexane, chloroform and butanol.", "output": "methanol, n - hexane, chloroform, butanol." }, { "input": "Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene - A ( 1 ), - B ( 2 ).", "output": "goniolandrene - A ( 1 ) , - B ( 2 )." }, { "input": "The absolute configuration of goniolandrene B ( 2 ) was established by circular dichrosim.", "output": "goniolandrene B." }, { "input": "The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0. 42 to 160 mu M.", "output": "There is no related enetity." }, { "input": "Goniothalamin ( 3 ) exhibited the highest inhibition of 0. 42 mu M.", "output": "Goniothalamin." }, { "input": "Electromagnetic - pulse - induced activation of p38 MAPK pathway and disruption of blood - retinal barrier.", "output": "There is no related enetity." }, { "input": "The blood - retinal barrier ( BRB ) is critical for maintaining retina homeostasis and low permeability.", "output": "There is no related enetity." }, { "input": "In this study, we evaluated the effects of electromagnetic pulse ( EMP ) exposure on the permeability of BRB, alterations of tight junction ( TJ ) proteins of BRB and if any, involvement of mitogen - activated protein kinase ( MAPK ) pathway.", "output": "There is no related enetity." }, { "input": "Male Sprague - Dawley ( SD ) rats and RF / 6A cells which were pretreated with or without MAPKs inhibitors were sham exposed or exposed to EMP at 200kV / m for 200 pulses.", "output": "There is no related enetity." }, { "input": "The alteration of BRB permeability was examined through fluorescence microscope and quantitatively assessed using Evans blue ( EB ) and endogenous albumin as tracers.", "output": "There is no related enetity." }, { "input": "The expressions of TJ proteins and some signaling molecules of MAPK pathway were measured by Western blots.", "output": "There is no related enetity." }, { "input": "The observations were that EMP exposure resulted in increased BRB permeability concurrent with the decreased expressions of occludin and claudin - 5, which were correlated with the increased expressions of phospho - p38, phospho - JNK and phospho - ERK and could be blocked when pretreated with p38 MAPK inhibitor.", "output": "There is no related enetity." }, { "input": "Thus, the results suggested that the alterations of occludin and claudin - 5 may play an important role in the disruption of TJs, which may lead to the transient breakdown of BRB after EMP exposure with the involvement of p38 MAPK pathway through phosphorylation of signaling molecules.", "output": "There is no related enetity." }, { "input": "Suppression of nuclear factor erythroid 2 - related factor 2 via extracellular signal - regulated kinase contributes to bleomycin - induced oxidative stress and fibrogenesis.", "output": "bleomycin." }, { "input": "Pulmonary fibrosis is a serious and irreversible lung injury with obscure etiologic mechanisms and no effective treatment to date.", "output": "There is no related enetity." }, { "input": "This study explored a crucial link between oxidative stress and pulmonary fibrogenesis, focusing on nuclear factor erythroid 2 - related factor 2 ( Nrf2 ), a core transcription factor in antioxidative regulation systems.", "output": "There is no related enetity." }, { "input": "Treatment of C57 BL / 6 mice with bleomycin increased fibroblast viability and collagen production and significantly downregulated Nrf2.", "output": "bleomycin." }, { "input": "In addition, prominent oxidative stress was indicated by changes in superoxide dismutase, catalase activity, and glutathione and thiobarbituric acid - reactive substance levels.", "output": "superoxide, glutathione, thiobarbituric acid." }, { "input": "In a cell - based model, bleomycin suppressed Nrf2 activation via extracellular signal - related kinase phosphorylation, enhancing intracellular reactive oxygen species in lung fibroblasts and stimulating abnormal cell proliferation and collagen secretion.", "output": "bleomycin, oxygen." }, { "input": "To confirm this novel mechanism of bleomycin - induced fibrogenesis, we attempted to upregulate Nrf2 and related antioxidant proteins in bleomycin - treated fibroblasts using a putative Nrf2 activator, caffeic acid phenethyl ester, and the results showed that bleomycin - induced fibroblast proliferation and collagen content were attenuated through improved redox balance.", "output": "bleomycin, caffeic acid phenethyl ester, bleomycin." }, { "input": "Collectively, these results disclose a potential regulatory mechanism in pulmonary fibrosis that will aid the development of new therapies.", "output": "There is no related enetity." }, { "input": "Proteomic Analysis of Arsenic - Exposed Zebrafish ( Danio rerio ) Identifies Altered Expression in Proteins Involved in Fibrosis and Lipid Uptake in a Gender - Specific Manner.", "output": "Arsenic." }, { "input": "The zebrafish ( Danio rerio ) was used to investigate protein expression in the liver following arsenic exposure.", "output": "arsenic." }, { "input": "Several disorders have been linked to arsenic exposure, including cancer, diabetes, and cardiovascular disease.", "output": "arsenic." }, { "input": "The mechanisms of arsenic toxicity are poorly understood.", "output": "arsenic." }, { "input": "Prior studies have described altered gene expression, inflammation, and mitogenic signaling in acute or chronic exposure models.", "output": "There is no related enetity." }, { "input": "A proteomic approach was employed to investigate arsenic - induced alteration in the zebrafish liver proteome following a 7 - day exposure to 50 ppb sodium arsenite.", "output": "arsenic, sodium arsenite." }, { "input": "Over 740 unique proteins were identified, with fewer than 2 % showing differential expression.", "output": "There is no related enetity." }, { "input": "Molecular pathway analysis software identified lipid metabolism and transport as potential molecular targets.", "output": "There is no related enetity." }, { "input": "Immunoblots were used to confirm protein expression changes, whereas qPCR was employed to investigate gene expression changes.", "output": "There is no related enetity." }, { "input": "Overall, 25 proteins were differentially expressed in a gender - specific manner, 11 in males and 14 in females.", "output": "There is no related enetity." }, { "input": "Of these 25, a single protein, hydroxysteroid dehydrogenase like 2, showed decreased expression in both males and females following arsenic exposure.", "output": "hydroxysteroid, arsenic." }, { "input": "These findings indicate that protein expression is altered following arsenic exposure.", "output": "arsenic." }, { "input": "The changes presented here seem to be most prevalent in lipid transport and metabolic pathways, suggesting a potential increase in fibrosis in males and decreased lipid accumulation and uptake in females.", "output": "There is no related enetity." }, { "input": "Additional Histopathologic Examination of the Lungs from a 3 - Month Inhalation Toxicity Study with Multiwall Carbon Nanotubes in Rats.", "output": "Carbon." }, { "input": "For hazard assessment of multiwalled carbon nanotubes ( MWCNTs ), a 90 - day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline.", "output": "carbon." }, { "input": "MWCNTs produced no systemic toxicity.", "output": "There is no related enetity." }, { "input": "However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra - alveolar lipoproteinosis were observed in lung and lung - associated lymph nodes at 0. 5 and 2. 5mg / m ( 3 ).", "output": "There is no related enetity." }, { "input": "Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs.", "output": "There is no related enetity." }, { "input": "The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed.", "output": "There is no related enetity." }, { "input": "The pleura did not reveal any increase in collagen fibers.", "output": "There is no related enetity." }, { "input": "Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0. 5 and 2. 5mg / m ( 3 ) concentration group was noted.", "output": "There is no related enetity." }, { "input": "In the 0. 1mg / m ( 3 ) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma.", "output": "There is no related enetity." }, { "input": "No increase in reticulin was observed.", "output": "There is no related enetity." }, { "input": "Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages.", "output": "There is no related enetity." }, { "input": "Occasionally electron dense particles / detritus were observed within membrane - bound vesicles ( interpreted as phagosomes ), which could represent degraded MWCNTs.", "output": "There is no related enetity." }, { "input": "If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung.", "output": "There is no related enetity." }, { "input": "Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups.", "output": "There is no related enetity." }, { "input": "Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and / or fibrosis leading to mesotheliomas, are absent.", "output": "There is no related enetity." }, { "input": "Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells.", "output": "flavonoids." }, { "input": "Quercetin and rutin are common flavonoids in fruit and vegetables, and have been reported to affect bone development.", "output": "Quercetin, rutin, flavonoids." }, { "input": "However, the effect of flavonoids on osteoblast differentiation remains a matter of controversy.", "output": "flavonoids." }, { "input": "In the present study, mouse bone marrow mesenchymal stem cells ( BMMSCs ) were isolated and characterized for their use in osteoblast differentiation using two flavonoids, quercetin and rutin.", "output": "flavonoids, quercetin, rutin." }, { "input": "BMMSCs were cultured in various concentrations of quercetin and rutin during the osteoblast differentiation period of 10 days.", "output": "quercetin, rutin." }, { "input": "Both quercetin and rutin were found to up regulate the osteoblast differentiation in dose dependent manner, albeit to lesser extent in case of former than that of latter.", "output": "quercetin, rutin." }, { "input": "Quercetin and rutin also increased alkaline phosphatase activity by about 150 and 240 % and demonstrated mineralization up to 110 and 200 % respectively as compared to control ( which was considered as 100 % ).", "output": "Quercetin, rutin." }, { "input": "Further, both the flavonoids were also found to increase the expression of some of the prominent markers for differentiation of osteoblast like osteopontin, osterix, RunX2, osteoprotegerin and osteocalcin.", "output": "flavonoids." }, { "input": "The current data suggests that certain classes of flavonoids like rutin and quercetin can be used in the cure and management of osteodegenerative disorders due to their osteoblast specific differentiation activities.", "output": "flavonoids, rutin, quercetin." }, { "input": "Quantification of the Young ' s modulus of the primary plant cell wall using Bending - Lab - On - Chip ( BLOC ).", "output": "There is no related enetity." }, { "input": "Biomechanical and mathematical modeling of plant developmental processes requires quantitative information about the structural and mechanical properties of living cells, tissues and cellular components.", "output": "There is no related enetity." }, { "input": "A crucial mechanical property of plant cells is the mechanical stiffness or Young ' s modulus of its cell wall.", "output": "There is no related enetity." }, { "input": "Measuring this property in situ at single cell wall level is technically challenging.", "output": "There is no related enetity." }, { "input": "Here, a bending test is implemented in a chip, called Bending - Lab - On - a - Chip ( BLOC ), to quantify this biomechanical property for a widely investigated cellular model system, the pollen tube.", "output": "There is no related enetity." }, { "input": "Pollen along with culture medium is introduced into a microfluidic chip and the growing pollen tube is exposed to a bending force created through fluid loading.", "output": "There is no related enetity." }, { "input": "The flexural rigidity of the pollen tube and the Young ' s modulus of the cell wall are estimated through finite element modeling of the observed fluid - structure interaction.", "output": "There is no related enetity." }, { "input": "An average value of 350 MPa was experimentally estimated for the Young ' s modulus in longitudinal direction of the cell wall of Camellia pollen tubes.", "output": "There is no related enetity." }, { "input": "This value is in agreement with the result of an independent method based on cellular shrinkage after plasmolysis and with the mechanical properties of in vitro reconstituted cellulose - callose material.", "output": "There is no related enetity." }, { "input": "Therapeutic Cleavage of Anti - Aquaporin - 4 Autoantibody in Neuromyelitis Optica by an Igg - Selective Proteinase.", "output": "There is no related enetity." }, { "input": "Neuromyelitis optica ( NMO ) is an inflammatory demyelinating disease of the central nervous system caused by binding of pathogenic IgG autoantibodies ( NMO - IgG ) to astrocyte water channel aquaporin - 4 ( AQP4 ).", "output": "There is no related enetity." }, { "input": "Astrocyte damage and downstream inflammation require NMO - IgG effector function to initiate complement - dependent cytotoxicity ( CDC ) and antibody - dependent cell - mediated cytotoxicity ( ADCC ).", "output": "There is no related enetity." }, { "input": "Here, we evaluated the potential therapeutic utility of the bacterial enzyme IdeS ( IgG - degrading enzyme of Streptococcus pyogenes ), which selectively cleaves IgG antibodies to yield Fc and F ( ab ' ) 2 fragments.", "output": "There is no related enetity." }, { "input": "In AQP4 - expressing cell cultures, IdeS treatment of monoclonal NMO - IgGs and NMO patient sera abolished CDC and ADCC, even when IdeS was added after NMO - IgG was bound to AQP4.", "output": "There is no related enetity." }, { "input": "Binding of NMO - IgG to AQP4 was similar to that of the NMO - F ( ab ' ) 2 generated by IdeS cleavage.", "output": "There is no related enetity." }, { "input": "NMO - F ( ab ' ) 2 competitively displaced pathogenic NMO - IgG, preventing cytotoxicity, and the Fc fragments generated by IdeS cleavage reduced CDC and ADCC.", "output": "There is no related enetity." }, { "input": "IdeS efficiently cleaved NMO - IgG in mice in vivo, and greatly reduced NMO lesions in mice administered NMO - IgG and human complement.", "output": "There is no related enetity." }, { "input": "IgG - selective cleavage by IdeS thus neutralizes NMO - IgG pathogenicity, and yields therapeutic F ( ab ' ) 2 and Fc fragments.", "output": "There is no related enetity." }, { "input": "IdeS treatment, by therapeutic apheresis or direct administration, may be beneficial in NMO.", "output": "There is no related enetity." }, { "input": "Structure - based Identification of OATP1B1 / 3 Inhibitors.", "output": "There is no related enetity." }, { "input": "Several recent studies show that inhibition of the hepatic transport proteins organic - anion transporting polypeptide 1B1 ( OATP1B1 ) and 1B3 ( OATP1B3 ) can result in clinically relevant drug - drug interactions ( DDI ).", "output": "There is no related enetity." }, { "input": "To avoid late - stage development drug failures due to OATP1B - mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process.", "output": "There is no related enetity." }, { "input": "In the present study, we first developed a high - throughput in vitro transporter inhibition assay for the OATP1B subfamily.", "output": "There is no related enetity." }, { "input": "A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1 or 1B3 - transfected CHO cells.", "output": "sodium fluorescein." }, { "input": "At an equimolar substrate - inhibitor concentration of 10 mu M, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively ( min 50 % inhibition ).", "output": "There is no related enetity." }, { "input": "For 69 compounds, previously not identified as OATP1B inhibitors, concentration dependent inhibition was also determined, yielding Ki values ranging from 0. 06 to 6. 5 mu M.", "output": "There is no related enetity." }, { "input": "Based on these in vitro data, we subsequently developed a proteochemometrics - based in silico model, which predicted OATP1B inhibitors in the test group ( 20 % of the dataset ) with high specificity ( 86 % ) and sensitivity ( 78 % ).", "output": "There is no related enetity." }, { "input": "Moreover, several physicochemical compound properties and substructures related to OATP1B1 / 1B3 inhibition or inactivity were identified.", "output": "There is no related enetity." }, { "input": "Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset.", "output": "There is no related enetity." }, { "input": "This validation indicated that 80 % and 74 % of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.", "output": "There is no related enetity." }, { "input": "Pomalidomide: first global approval.", "output": "Pomalidomide." }, { "input": "Pomalidomide ( Pomalyst ( (R) ) ) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases.", "output": "Pomalidomide, Pomalyst, thalidomide." }, { "input": "Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low - dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib.", "output": "Pomalidomide, dexamethasone, lenalidomide, bortezomib." }, { "input": "The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial.", "output": "pomalidomide." }, { "input": "The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis.", "output": "There is no related enetity." }, { "input": "Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft - versus - host disease, and Waldenstrom ' s macroglobulinaemia.", "output": "Pomalidomide." }, { "input": "This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma.", "output": "pomalidomide." }, { "input": "S - nitrosation of glutathione transferase P1 - 1 is controlled by the conformation of a dynamic active - site helix.", "output": "S, glutathione." }, { "input": "S - nitrosation is a post - translational modification of protein cysteine residues which occurs in response to cellular oxidative stress.", "output": "S, cysteine." }, { "input": "Although it is increasingly being linked to physiologically important processes, the molecular basis for protein regulation by this modification remains poorly understood.", "output": "There is no related enetity." }, { "input": "We used transient kinetic methods to determine a minimal mechanism for spontaneous GSNO - mediated transnitrosation of human glutathione transferase ( GST ) P1 - 1, a major detoxification enzyme and key regulator of cell proliferation.", "output": "glutathione." }, { "input": "C47 of GSTP1 - 1 is S - nitrosated in two steps, with the chemical step limited by a pre - equilibrium between the open and closed conformations of helix alpha 2 at the active site.", "output": "S." }, { "input": "C101, in contrast, is S - nitrosated in a single step but is subject to negative cooperativity due to steric hindrance at the dimer interface.", "output": "S." }, { "input": "Despite the presence of a GSNO binding site at the active site of GSTP1 - 1, isothermal titration calorimetry as well as nitrosation experiments using CysNO demonstrate that GSNO binding does not precede S - nitrosation of GSTP1 - 1.", "output": "CysNO, S." }, { "input": "Kinetics experiments using the cellular reductant GSH show that C101 - NO is substantially more resistant to denitrosation than C47 - NO, suggesting a potential role for C101 - NO in long term nitric oxide storage or transfer.", "output": "GSH, NO, NO, NO, nitric oxide." }, { "input": "These results constitute the first report of the molecular mechanism of spontaneous protein transnitrosation, providing insight into the post - translational control of GSTP1 - 1 as well as the process of protein transnitrosation in general.", "output": "There is no related enetity." }, { "input": "HCV NS5A Replication Complex Inhibitors.", "output": "There is no related enetity." }, { "input": "Part 4.", "output": "There is no related enetity." }, { "input": "( 1 ) Optimization for Genotype 1a Replicon Inhibitory Activity.", "output": "There is no related enetity." }, { "input": "A series of symmetrical E - stilbene prolinamides that originated from the library - synthesized lead 3 was studied with respect to HCV genotype 1a ( G - 1a ) and genotype 1b ( G - 1b ) replicon inhibition and selectivity against BVDV and cytotoxicity.", "output": "E - stilbene, prolinamides." }, { "input": "SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G - 1a and G - 1b replicons.", "output": "prolinamide." }, { "input": "Additional structural refinements resulted in the identification of 30 as a potent, dual G - 1a / 1b HCV NS5A inhibitor.", "output": "There is no related enetity." }, { "input": "Tailoring of morphology and surface properties of syndiotactic polystyrene aerogels.", "output": "syndiotactic polystyrene." }, { "input": "This study evaluates a method for rendering syndiotactic polystyrene ( sPS ) aerogels hydrophilic using polyethylene oxide ( PEO ) of different molecular weights.", "output": "syndiotactic polystyrene, sPS, polyethylene oxide, PEO." }, { "input": "The highly porous sPS aerogels are inherently hydrophobic although applications involving absorption of moisture and removal of particulate solids may benefit from the high surface area of sPS aerogels provided some degree of hydrophilicity is induced in these materials.", "output": "sPS, sPS." }, { "input": "In this work, sPS gels are prepared by thermo - reversible gelation in tetrahydrofuran in the presence of PEO.", "output": "sPS, tetrahydrofuran, PEO." }, { "input": "The gels are dried under supercritical conditions to obtain aerogels.", "output": "There is no related enetity." }, { "input": "The aerogels are characterized by scanning electron microscopy, nitrogen - adsorption porosimetry, helium pycnometry, and contact angle measurements.", "output": "nitrogen, helium." }, { "input": "The data reveal that the pore structures and surface energy can be controlled by varying the concentration and molecular weight of PEO and using different cooling rates during thermo - reversible gelation.", "output": "PEO." }, { "input": "In the first case, sPS aerogels, aerogels containing PEO of a low molecular weight or low concentration show superhydrophobic surface presenting the \" lotus effect \".", "output": "sPS, PEO." }, { "input": "In the second case, PEO at a higher concentration or with higher molecular weight forms phase - separated domains yielding new hydrophilic macropores ( > 10 mu m ) in the aerogel structures.", "output": "PEO." }, { "input": "These macropores contribute to the superhydrophobic surface with the \" petal effect \".", "output": "There is no related enetity." }, { "input": "The cooling rate during gelation shows a strong influence on these two cases.", "output": "There is no related enetity." }, { "input": "Photorheological Response of Aqueous Wormlike Micelles with Photocleavable Surfactant.", "output": "There is no related enetity." }, { "input": "Recently, we have reported a new cinnamic acid - type photocleavable surfactant, C4 - C - N - PEG9 that experiences a photocleavage through UV - induced cyclization in aqueous solution, yielding a coumarin derivative ( 7 - butoxy - 2H - chromen - 2 - one ) and an aminated polyoxyethylene compound.", "output": "cinnamic acid, C4 - C - N - PEG9, coumarin, 7 - butoxy - 2H - chromen - 2 - one, polyoxyethylene." }, { "input": "Here, we have studied the effects of C4 - C - N - PEG9 on the photorheological behavior of viscoelastic wormlike micelles formed by aqueous mixture of nonionic surfactants, polyoxyethylene phytosterol ether ( PhyEO20 ) and tetraoxyethylene dodecyl ether ( C12EO4 ).", "output": "C4 - C - N - PEG9, polyoxyethylene phytosterol ether, PhyEO20, tetraoxyethylene dodecyl ether, C12EO4." }, { "input": "The 4. 9 wt % PhyEO20 / H2O + 2. 4 wt % C12EO4 solution forms wormlike micelles, and its viscosity is ~ 10 Pa. s.", "output": "PhyEO20, H2O, C12EO4." }, { "input": "We have found that the addition of C4 - C - N - PEG9 into this viscous, non - Newtonian fluid system decreases the viscosity.", "output": "C4 - C - N - PEG9." }, { "input": "Viscosity decreased in parallel to the C4 - C - N - PEG9 concentration reaching ~ 0. 003 Pa. s at 2. 5 wt % of C4 - C - N - PEG9.", "output": "C4 - C - N - PEG9, C4 - C - N - PEG9." }, { "input": "However, viscosity of the C4 - C - N - PEG9 incorporated system increased significantly ( ~ 200 times at 1. 5 wt % of C4 - C - N - PEG9 system ) upon UV irradiation.", "output": "C4 - C - N - PEG9, C4 - C - N - PEG9." }, { "input": "Small - Angle X - ray scattering studies have shown that addition of C4 - C - N - PEG9 favors wormlike - to - sphere type transition in the micellar structure.", "output": "C4 - C - N - PEG9." }, { "input": "However, UV irradiation in the C4 - C - N - PEG9 incorporated system causes one - dimensional micellar growth.", "output": "C4 - C - N - PEG9." }, { "input": "Since C4 - C - N - PEG9 has relatively bigger headgroup size compared to the C12EO4, addition of C4 - C - N - PEG9 into wormlike micelles reduces the critical packing parameter resulting in the formation of spherical aggregates.", "output": "C4 - C - N - PEG9, C12EO4, C4 - C - N - PEG9." }, { "input": "UV irradiation induced one - dimensional micellar growth is caused due to photocleavage of the C4 - C - N - PEG9 into a less surface - active coumarin derivative and an aminated polyoxyethylene compound, as confirmed by UV - vis spectrometry and HPLC measurements.", "output": "C4 - C - N - PEG9, coumarin, polyoxyethylene." }, { "input": "The hydrophobic coumarin derivative formed after cleavage of C4 - C - N - PEG9 goes to the micellar core and is responsible for decreasing the viscosity.", "output": "coumarin, C4 - C - N - PEG9." }, { "input": "However, the hydrophilic aminated polyoxyethylene prefers to reside at the vicinity of headgroup of PhyEO20 reducing the interhead repulsion, increasing the critical packing parameter and the viscosity as well.", "output": "polyoxyethylene, PhyEO20." }, { "input": "Dual - Purpose Polymer Labels for Fluorescent and Mass Cytometric Affinity Bioassays.", "output": "There is no related enetity." }, { "input": "We describe the synthesis and characterization of a family of poly ( N - alkylacrylamide ) polymers carrying 2 - 6 fluorescent dye molecules, ~ 70 pendant DTPA ( diethylenetriaminepentaacetic acid ) groups, and an orthogonal maleimide end - group for covalent attachment to an antibody ( Ab ).", "output": "poly ( N - alkylacrylamide ), DTPA, diethylenetriaminepentaacetic acid, maleimide." }, { "input": "These dual - purpose labels were designed for use in multiplexed immunoassays based on both mass cytometry and fluorescent flow cytometry.", "output": "There is no related enetity." }, { "input": "A challenge in the polymer synthesis was finding conditions for attaching a sufficient number of dye molecules to each polymer chain.", "output": "There is no related enetity." }, { "input": "Although attachment of a terminal maleimide to the polymers was not as efficient as anticipated, the end - functional polymers were still effective in labeling Abs.", "output": "maleimide." }, { "input": "Secondary goat antimouse IgG was labeled with the four dual - label polymers as well as a control polymer, and while the resultant antibody - polymer conjugates showed positive performance in mass cytometric and fluorescent assays, some trials showed problems such as low signal and nonspecific adsorption.", "output": "There is no related enetity." }, { "input": "Four primary antibody conjugates were prepared and used to stain cells in 4 - plex assays.", "output": "There is no related enetity." }, { "input": "The results of both primary assays are bittersweet in that the CD3 - FITC and CD45 - DyLight 649 conjugates performed well, while the CD13 - DyLight 405 and the CD38 - DyLight 549 conjugates did not.", "output": "There is no related enetity." }, { "input": "A Facile Integration of Zero - ( I - III - VI Quantum Dots ) and One - ( Single SnO2 Nanowire ) Dimensional Nanomaterials: Fabrication of a Nanocomposite Photodetector with Ultrahigh Gain and Wide Spectral Response.", "output": "SnO2." }, { "input": "Via the integration of nanocomposites comprising I - III - VI semiconductor quantum dots ( QDs ) decorated onto a single SnO2 nanowire ( NW ), we successfully fabricate an ultrahigh - sensitivity and wide spectral - response photodetector.", "output": "SnO2." }, { "input": "Under the illumination of He - Cd laser ( 325 nm ) with the photon energy larger than the band gap of SnO2 nanowire, remarkably, an ultrahigh photocurrent gain up to 2. 5 x 10 ( 5 ) has been achieved, and an enhancement factor can reach up to 700 % ( cf. bare SnO2 NW ) as light illumination onto the wire with an excitation intensity of 15 W / m ( 2 ).", "output": "He, Cd, SnO2, SnO2." }, { "input": "Also, a high gain value up to 1. 3 x 10 ( 5 ) is attained with the excited photon energy ( 488 nm ) smaller than the band gap of SnO2 nanowire.", "output": "SnO2." }, { "input": "Several key factors contribute to ultrahigh photocurrent gain and wide spectral response.", "output": "There is no related enetity." }, { "input": "First, the decorated quantum dot processes an inherent nature of a large absorption coefficient above its band gap.", "output": "There is no related enetity." }, { "input": "Furthermore, the single SnO2 nanowire provides an excellent conduction path for the photogenerated carriers as well as bears a large surface - to - volume ratio so that the coupling strength with quantum dots can be greatly enhanced.", "output": "SnO2." }, { "input": "Most importantly, the spatial separation of photogenerated electrons and holes can be easily achieved due to the charge transfer arising from a type II band alignment between QDs and SnO2 NW.", "output": "SnO2." }, { "input": "This work thus demonstrates a new approach in which by selectively decorating suitable QDs the photocurrent gain of SnO2 NWs can be greatly enhanced and extended to a wide spectral range of photoresponse previously inaccessible, providing a very useful guideline to create cheap, nontoxic, and highly efficient photodetectors.", "output": "SnO2." }, { "input": "Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation.", "output": "There is no related enetity." }, { "input": "Stephanolepis hispidus is one of the most common filefish species in Brazil.", "output": "There is no related enetity." }, { "input": "Its skin is traditionally used as a complementary treatment for inflammatory disorders.", "output": "There is no related enetity." }, { "input": "However, there are very few studies on chemical and pharmacological properties using the skin of this fish.", "output": "There is no related enetity." }, { "input": "This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin ( SAE ) in different nociception models.", "output": "There is no related enetity." }, { "input": "Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice.", "output": "acetic acid." }, { "input": "In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 ( PGE2 ) in mice.", "output": "prostaglandin E2, PGE2." }, { "input": "This potent antinociceptive effect was observed in the hot plate model too, but not in tail - flick test.", "output": "There is no related enetity." }, { "input": "Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models.", "output": "Naloxone." }, { "input": "In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells.", "output": "There is no related enetity." }, { "input": "Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system.", "output": "There is no related enetity." }, { "input": "Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.", "output": "There is no related enetity." }, { "input": "Solution processed zinc oxide nanopyramid / silver nanowire transparent network films with highly tunable light scattering properties.", "output": "zinc oxide, silver." }, { "input": "Metal nanowire transparent networks are promising replacements to indium tin oxide ( ITO ) transparent electrodes for optoelectronic devices.", "output": "indium tin oxide, ITO." }, { "input": "While the transparency and sheet resistance are key metrics for transparent electrode performance, independent control of the film light scattering properties is important to developing multifunctional electrodes for improved photovoltaic absorption.", "output": "There is no related enetity." }, { "input": "Here we show that controlled incorporation of ZnO nanopyramids into a metal nanowire network film affords independent, highly tunable control of the scattering properties ( haze ) with minimal effects on the transparency and sheet resistance.", "output": "ZnO." }, { "input": "Varying the zinc oxide / silver nanostructure ratios prior to spray deposition results in sheet resistances, transmission ( 600 nm ), and haze ( 600 nm ) of 6 - 30 Omega * ( - 1 ), 68 - 86 %, and 34 - 66 %, respectively.", "output": "zinc oxide, silver." }, { "input": "Incorporation of zinc oxide nanopyramid scattering agents into the conducting nanowire mesh has a negligible effect on mesh connectivity, providing a straightforward method of controlling electrode scattering properties.", "output": "zinc oxide." }, { "input": "The decoupling of the film scattering power and electrical characteristics makes these films promising candidates for highly scattering transparent electrodes in optoelectronic devices and can be generalized to other metal nanowire films as well as carbon nanotube transparent electrodes.", "output": "carbon." }, { "input": "Sarmentosumols A to F, New Mono - and Dimeric Alkenylphenols from Piper sarmentosum.", "output": "Sarmentosumols A to F, Mono - and Dimeric Alkenylphenols." }, { "input": "Two new mono - and four new dimeric alkenylphenols, namely sarmentosumols A to F ( 1 - 6 ), were isolated from the aerial parts of Piper sarmentosum.", "output": "dimeric alkenylphenols, sarmentosumols A to F." }, { "input": "The structures of these compounds were determined through a detailed analysis of NMR and MS data.", "output": "There is no related enetity." }, { "input": "Their antimicrobial activity against Escherichia coli, Staphyloccocus aureus, and Candida albicans, and their cytotoxic activity against human myeloid leukemia ( K562 ) and human lung adenocarcinoma ( A549 ) cell lines were also evaluated.", "output": "There is no related enetity." }, { "input": "Except for sarmentosumol A ( 1 ), whose MIC on S. aureus was reported to be 7. 0 micro g / mL, none of the other newly discovered compounds exhibited antimicrobial property.", "output": "sarmentosumol A." }, { "input": "The studied compounds did not possess any cytotoxic property.", "output": "There is no related enetity." }, { "input": "In Vitro and In Vivo Enzyme - Mediated Biomineralization of Oligo ( poly ( ethylene glycol ) Fumarate Hydrogels.", "output": "Oligo ( poly ( ethylene glycol ) Fumarate." }, { "input": "The enzyme alkaline phosphatase ( ALP ) is added at different concentrations ( i. e., 0, 2. 5, and 10 mg. ml ( - 1 ) ) to oligo ( poly ( ethylene glycol ) fumarate ) ( OPF ) hydrogels.", "output": "oligo ( poly ( ethylene glycol ) fumarate ), OPF." }, { "input": "The scaffolds are either incubated in 10 mM calcium glycerophosphate ( Ca - GP ) solution for 2 weeks or implanted in a rat subcutaneous model for 4 weeks.", "output": "calcium glycerophosphate, Ca - GP." }, { "input": "Fourier transform infrared ( FTIR ) spectroscopy, X - ray diffraction ( XRD ), scanning electron microscopy ( SEM ), energy dispersive spectroscopy ( EDS ), and alizarin red staining show a strong ability to form minerals exclusively in ALP - containing hydrogels in vitro.", "output": "alizarin red." }, { "input": "Additionally, the calcium content increases with increasing ALP concentration.", "output": "calcium." }, { "input": "Similarly, only ALP - containing hydrogels induce mineralization in vivo.", "output": "There is no related enetity." }, { "input": "Specifically, small ( =~ 5 - 20 micro m ) mineral deposits are observed at the periphery of the hydrogels near the dermis / scaffold interface using Von Kossa and alizarin red staining.", "output": "alizarin red." }, { "input": "\" Raisin Bun \" - Like Nanocomposites of Palladium Clusters and Porphyrin for Superior Formic Acid Oxidation.", "output": "Palladium, Porphyrin, Formic Acid." }, { "input": "A novel \" raisin bun \" - like nanocomposite, where Pd clusters are embedded in porphyrin matrix, is developed as a promising electrocatalyst.", "output": "Pd, porphyrin." }, { "input": "Thanks to the synergy between the Pd clusters and the porphyrin matrix, this composite exhibits a low oxidation potential, high mass activity and excellent stability toward electrochemical oxidation of formic acid, which opens new routes for the design of high - performance catalysts in fuel cells.", "output": "Pd, porphyrin, formic acid." }, { "input": "Carboxylate - Assisted Formation of Alkylcarbonate Species from CO2 and Tetramethylammonium Salts with a beta - Amino Acid Anion.", "output": "Carboxylate, Alkylcarbonate, CO2, Tetramethylammonium, beta - Amino Acid." }, { "input": "Tetramethylammonium - based molten salts bearing a beta - amino acid anion ( TMAAs ) are synthesized through Michael addition reactions of amines with methyl acrylate followed by hydrolysis and subsequent neutralization by using aqueous tetramethylammonium hydroxide.", "output": "Tetramethylammonium, beta - amino acid, amines, methyl acrylate, tetramethylammonium hydroxide." }, { "input": "The CO2 capture performances of the TMAAs are evaluated and are shown to interact with CO2 in a 1: 1 mode in both water and alcohol.", "output": "CO2, CO2, alcohol." }, { "input": "FTIR and ( 13 ) C NMR spectroscopic studies on the interactions of TMAAs with CO2 indicate that the type of CO2 adduct varies with the solvent used.", "output": "( 13 ) C, CO2, CO2." }, { "input": "When water is used as the solvent, a bicarbonate species is produced, whereas hydroxyethylcarbonate and methylcarbonate species are generated in ethylene glycol and methanol, respectively.", "output": "bicarbonate, hydroxyethylcarbonate, methylcarbonate, ethylene glycol, methanol." }, { "input": "Computational calculations show that the carboxylate groups of TMAAs contribute towards the formation and stabilization of 1: 1 CO2 adducts through hydrogen bonding interactions with the hydrogen atoms of the amino groups.", "output": "carboxylate, CO2, hydrogen, hydrogen, amino." }, { "input": "Synthesis and evaluation of biphenyl compounds as Kinesin spindle protein inhibitors.", "output": "biphenyl." }, { "input": "Kinesin spindle protein ( KSP ), an ATP - dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase ( M phase ) of the normal cell cycle.", "output": "ATP." }, { "input": "KSP has emerged as a novel target for antimitotic anticancer drug development.", "output": "There is no related enetity." }, { "input": "In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression.", "output": "biphenyl." }, { "input": "Antiproliferation ( MTT ( = 3 - ( 4, 5 - dimethylthiazol - 2 - yl ) - 2, 5 - diphenyl - 2H - tetrazolium bromide ) ) assays, combined with fluorescence - assisted cell sorting ( FACS ) and Western blot studies analyzing cell - cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines.", "output": "MTT, 3 - ( 4 , 5 - dimethylthiazol - 2 - yl ) - 2 , 5 - diphenyl - 2H - tetrazolium bromide, biphenyl." }, { "input": "Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity.", "output": "biphenyl." }, { "input": "However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines.", "output": "urea." }, { "input": "Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7, exerts its pharmacologic effect specifically in the M phase and induces monoaster formation.", "output": "biphenyl." }, { "input": "These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds.", "output": "biphenyl." }, { "input": "Tirucallane Triterpenoids from the Stems of Brucea mollis.", "output": "Tirucallane, Triterpenoids." }, { "input": "Three new tirucallane triterpenoids, brumollisols A - C ( 1 - 3, resp. ), together with five known analogues, ( 23R, 24S ) - 23, 24, 25 - trihydroxytirucall - 7 - ene - 3, 6 - dione ( 4 ), piscidinol A ( 5 ), 24 - epipiscidinol A ( 6 ), 21 alpha - methylmelianodiol ( 7 ), and 21 beta - methylmelianodiol ( 8 ), were isolated from an EtOH extract of the stems of Brucea mollis.", "output": "tirucallane, triterpenoids, brumollisols A - C, ( 23R , 24S ) - 23 , 24 , 25 - trihydroxytirucall - 7 - ene - 3 , 6 - dione, piscidinol A, 24 - epipiscidinol A, 21 alpha - methylmelianodiol, 21 beta - methylmelianodiol, EtOH." }, { "input": "Their structures were elucidated by means of spectroscopic methods including 1D - and 2D - NMR techniques and mass spectrometry.", "output": "There is no related enetity." }, { "input": "In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC - 823 cancer cells with IC50 values of 1. 16 and 3. 01 mu M, respectively.", "output": "There is no related enetity." }, { "input": "At a concentration of 10 mu M, compounds 1 - 5, 7, and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39. 8 +/- 7. 7 to 68. 2 +/- 4. 5 %.", "output": "NO." }, { "input": "Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug - Resistant Bacteria.", "output": "Demethylvancomycin." }, { "input": "Five novel N - substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure - based approach.", "output": "demethylvancomycin." }, { "input": "The in vitro antibacterial activities against methicillin - resistant Staphylococcus aureus ( MRSA ), gentamicin - resistant Enterococcus faecalis ( GRE ), methicillin - resistant Streptococcus pneumoniae ( MRS ), and vancomycin - resistant Enterococcus faecalis ( VRE ) were evaluated.", "output": "methicillin, gentamicin, methicillin, vancomycin." }, { "input": "One of the compounds, N - ( 6 - phenylheptyl ) demethylvancomycin ( 12 a ), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin.", "output": "N - ( 6 - phenylheptyl ) demethylvancomycin, vancomycin, demethylvancomycin." }, { "input": "Compound 12 a was also found to be ~ 18 - fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS.", "output": "vancomycin." }, { "input": "Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half - life of 5. 11 +/- 0. 52 h, which is longer than that of vancomycin ( 4. 3 +/- 1. 9 h ).", "output": "vancomycin." }, { "input": "These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.", "output": "There is no related enetity." }, { "input": "Microrheology of highly crosslinked microtubule networks is dominated by force - induced crosslinker unbinding.", "output": "There is no related enetity." }, { "input": "We determine the time - and force - dependent viscoelastic responses of reconstituted networks of microtubules that have been strongly crosslinked by biotin - streptavidin bonds.", "output": "biotin." }, { "input": "To measure the microscale viscoelasticity of such networks, we use a magnetic tweezers device to apply localized forces.", "output": "There is no related enetity." }, { "input": "At short time scales, the networks respond nonlinearly to applied force, with stiffening at small forces, followed by a reduction in the stiffening response at high forces, which we attribute to the force - induced unbinding of crosslinks.", "output": "There is no related enetity." }, { "input": "At long time scales, force - induced bond unbinding leads to local network rearrangement and significant bead creep.", "output": "There is no related enetity." }, { "input": "Interestingly, the network retains its elastic modulus even under conditions of significant plastic flow, suggesting that crosslinker breakage is balanced by the formation of new bonds.", "output": "There is no related enetity." }, { "input": "To better understand this effect, we developed a finite element model of such a stiff filament network with labile crosslinkers obeying force - dependent Bell model unbinding dynamics.", "output": "There is no related enetity." }, { "input": "The coexistence of dissipation, due to bond breakage, and the elastic recovery of the network is possible because each filament has many crosslinkers.", "output": "There is no related enetity." }, { "input": "Recovery can occur as long as a sufficient number of the original crosslinkers are preserved under the loading period.", "output": "There is no related enetity." }, { "input": "When these remaining original crosslinkers are broken, plastic flow results.", "output": "There is no related enetity." }, { "input": "Flexibly timed once - daily dosing with degludec: a new ultra - long - acting basal insulin.", "output": "There is no related enetity." }, { "input": "Insulin treatment in type 1 and type 2 diabetes ( T1D and T2D ) is highly efficacious, but in practice, non - adherence and ineffective dose titration limit its effectiveness.", "output": "There is no related enetity." }, { "input": "Barriers to more effective insulin treatment are numerous, including hypoglycaemia, fear of hypoglycaemia and concern about weight gain.", "output": "There is no related enetity." }, { "input": "The regular treatment timing needed with conventional basal insulins [ neutral protamine Hagedorn ( NPH ) insulin and the first - generation analogues glargine and detemir ] may also make adherence to these treatments problematic for many patients.", "output": "There is no related enetity." }, { "input": "Indeed, surveys indicate that the rigidity of this schedule induces some patients with T1D and T2D to omit insulin doses.", "output": "There is no related enetity." }, { "input": "Degludec is a novel, ultra - long - acting basal insulin analogue that is as effective as insulin glargine, but significantly reduces patients ' risk of nocturnal hypoglycaemia.", "output": "There is no related enetity." }, { "input": "Because of its peakless, extended and highly predictable glucose - lowering effect, once - daily dosing on a flexible schedule may be feasible with degludec.", "output": "glucose." }, { "input": "Studies testing this possibility suggest that degludec tolerates day - to - day variation in dose timing while maintaining full efficacy and low risk of nocturnal hypoglycaemia.", "output": "There is no related enetity." }, { "input": "Degludec would appear to be an appropriate choice for patients being considered for a basal analogue, and it may be particularly well suited to patients with unpredictable social or work schedules, those who travel frequently and those who find rigid scheduling of their insulin injections a burden or barrier to regular treatment.", "output": "There is no related enetity." }, { "input": "New dipyranocoumarin from the leaves of Calophyllum apetalum Willd.", "output": "dipyranocoumarin." }, { "input": "A new dipyranocoumarin, alpha - hydroxytomentolide A ( 1 ) was isolated from the leaves of Calophyllum apetalum together with the known compounds friedelin ( 2 ), apetalactone ( 3 ), inophyllum C ( 4 ) and canophyllol ( 5 ).", "output": "dipyranocoumarin, alpha - hydroxytomentolide A, friedelin, apetalactone, inophyllum C, canophyllol." }, { "input": "The structure of the new compound was established by spectroscopic studies which include ( 1 ) H NMR, ( 13 ) C NMR, NOESY, HetCOSY, COLOC experiments and single crystal X - ray diffraction analysis.", "output": "( 1 ) H, ( 13 ) C." }, { "input": "In vitro antimicrobial activity of 20 selected climber species from the Bignoniaceae family.", "output": "There is no related enetity." }, { "input": "Hydroalcoholic and aqueous extracts of some climber species from the Bignoniaceae family that grow in the north of Argentina were evaluated for in vitro antibacterial activity against Gram - positive and Gram - negative strains.", "output": "There is no related enetity." }, { "input": "By means of bioautography and disc diffusion methods, it could be determined that all infusions were not active, whereas the hydroalcoholic extracts of seven species were able to inhibit bacterial growth.", "output": "There is no related enetity." }, { "input": "The minimum inhibitory concentration and minimum bactericidal concentration observed were between 62. 5 and 1000 mu g gallic acid equivalent ( GAE ) / mL and between 125 and 1000 mu g GAE / mL, respectively.", "output": "gallic acid." }, { "input": "The tested extracts were more active against Gram - positive microorganisms.", "output": "There is no related enetity." }, { "input": "Time - kill experiments indicated that all extracts have bacteriostatic activity.", "output": "There is no related enetity." }, { "input": "Phytochemical screening showed the presence of terpenoids, phenols and flavonoids.", "output": "terpenoids, phenols, flavonoids." }, { "input": "The amount of phenolic compounds and flavonoids was higher in tinctures when compared with infusions.", "output": "phenolic, flavonoids." }, { "input": "These results suggest the presence of antibacterial substances in the hydroalcoholic extracts, which could be used for the treatment of infections.", "output": "There is no related enetity." }, { "input": "The potential role of T cell migration and chemotaxis as targets of glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis.", "output": "There is no related enetity." }, { "input": "Glucocorticoids ( GCs ) are the most commonly prescribed drugs for the treatment of acute disease bouts in multiple sclerosis ( MS ) patients.", "output": "There is no related enetity." }, { "input": "While T lymphocytes were shown to be essential targets of GC therapy, at least in animal models of MS, the mechanisms by which GCs modulate T cell function are less clear.", "output": "There is no related enetity." }, { "input": "Until now, apoptosis induction and repression of pro - inflammatory cytokines in T cells have been considered the most critical mechanisms in ameliorating disease symptoms.", "output": "There is no related enetity." }, { "input": "However, this notion is being challenged by increasing evidence that the control of T cell migration and chemotaxis by GCs might be even more important for the treatment of neuroinflammatory diseases.", "output": "There is no related enetity." }, { "input": "In this review we aim to provide an overview of how GCs impact the morphological alterations that T cells undergo during activation and migration as well as the influences that GCs have on the directed movement of T cells under the influence of chemokines.", "output": "There is no related enetity." }, { "input": "A deeper understanding of these processes should not only help to advance our understanding of how GCs exert their beneficial effects in MS therapy but may reveal future strategies to intervene in the pathogenesis of neuroinflammatory diseases.", "output": "There is no related enetity." }, { "input": "Significance of the transient receptor potential canonical 2 ( TRPC2 ) channel in the regulation of rat thyroid FRTL - 5 cell proliferation, migration, adhesion and invasion.", "output": "There is no related enetity." }, { "input": "Mammalian transient receptor potential ( TRP ) channels are involved in many physiologically important processes.", "output": "There is no related enetity." }, { "input": "Here, we have studied the significance of the TRPC2 channel in the regulation of rat thyroid FRTL - 5 cell proliferation, migration, adhesion and invasion, using stable TRPC2 ( shTRPC2 ) knock - down cells.", "output": "There is no related enetity." }, { "input": "In the shTRPC2 cells, proliferation was decreased due to a prolonged G1 / S cell cycle phase.", "output": "There is no related enetity." }, { "input": "The tumor suppressor p53 and the cyclin - dependant kinase inhibitors p27 and p21 were upregulated.", "output": "There is no related enetity." }, { "input": "Cell invasion, adhesion and migration were also attenuated in shTRPC2 cells, probably due to decreased activity of both Rac and calpain, and a decreased secretion and activity of matrix metalloproteinase 2.", "output": "There is no related enetity." }, { "input": "The attenuated proliferation, migration, invasion and ATP - evoked calcium entry was mimicked by overexpressing a non - conducting, truncated TRPC2 ( TRPC2 - DN ) in wild type cells, and was reversed by overexpression of TRPC2 - GFP in shTRPC2 cells.", "output": "ATP, calcium." }, { "input": "In conclusion, TRPC2 is an important regulator of rat thyroid cell function.", "output": "There is no related enetity." }, { "input": "Inhibitory effect of skullcap ( Scutellaria baicalensis ) extract on ovalbumin permeation in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Scutellaria baicalensis Georgi ( skullcap ) has been widely used as a dietary ingredient.", "output": "There is no related enetity." }, { "input": "The purpose of this study was to reveal novel function of skullcap and its mechanism on allergen permeation in intestinal epithelial cells.", "output": "There is no related enetity." }, { "input": "Intestinal epithelial Caco - 2 cell monolayers were used to evaluate the inhibitory effect of skullcap on ovalbumin ( OVA ) permeation by measuring transepithelial electrical resistance ( TEER ) and the quantity of permeated OVA.", "output": "There is no related enetity." }, { "input": "TEER increased and the OVA flux decreased in a dose - dependent manner through up - regulating tight junction - related proteins in cells incubated with increasing concentrations of skullcap extract.", "output": "There is no related enetity." }, { "input": "In the in vivo study, the amounts of OVA from orally ingested albumen reduced on administration of the skullcap extract.", "output": "There is no related enetity." }, { "input": "We also revealed for the first time that the active component of skullcap extract for inhibition of OVA permeation was baicalein.", "output": "baicalein." }, { "input": "These findings demonstrated that skullcap extract might attenuate a food allergic response by inhibiting allergen permeation in vitro and in vivo.", "output": "There is no related enetity." }, { "input": "Volatile release and structural stability of beta - lactoglobulin primary and multilayer emulsions under simulated oral conditions.", "output": "There is no related enetity." }, { "input": "The relationship between emulsion structure and the release of volatile organic compounds ( VOCs ) was investigated using a model mouth system under oral conditions ( tongue mastication, artificial saliva, pH and salt ).", "output": "There is no related enetity." }, { "input": "The VOCs were monitored on - line by proton transfer reaction mass spectrometry ( PTR - MS ).", "output": "There is no related enetity." }, { "input": "Two types of emulsion system were compared: primary and multilayer oil - in - water ( P - O / W, M - O / W ) emulsions consisting of soy oil coated by beta - lactoglobulin and pectin layers.", "output": "There is no related enetity." }, { "input": "The P - O / W emulsions showed intensive flocculation at pH 5 and above 200mM NaCl where the electrostatic repulsive charge was at a minimum.", "output": "NaCl." }, { "input": "Bridging and depletion flocculation were mostly observed for P - O / W emulsions containing artificial saliva with 1wt % mucin.", "output": "There is no related enetity." }, { "input": "The VOC release was found to increase when the emulsion droplets flocculated, thus changing the oil volume phase distribution.", "output": "There is no related enetity." }, { "input": "The adsorbed pectin layer stabilised the emulsion structure under conditions of short - time oral processing, and hindered the release of hydrophobic VOCs.", "output": "There is no related enetity." }, { "input": "LC / MS analysis of proteolytic peptides in wheat extracts for determining the content of the allergen amylase / trypsin inhibitor CM3: Influence of growing area and variety.", "output": "There is no related enetity." }, { "input": "Food allergy from wheat is triggered by several protein classes, such as LTPs, omega 5 - gliadins and alpha - amylase / trypsin inhibitors.", "output": "There is no related enetity." }, { "input": "The latter proteins, belonging to the prolamin superfamily, are mostly involved in baker ' s asthma, a form of occupational allergy in which the sensitization occurs through the respiratory tract.", "output": "There is no related enetity." }, { "input": "alpha - Amylase / trypsin inhibitors were also found to be involved in wheat - related atopic dermatitis.", "output": "There is no related enetity." }, { "input": "In this work, the allergen Tri a 30 ( the CM3 alpha - amylase / trypsin inhibitor ) was quantified in durum wheat salt soluble extracts using a peptidomic approach.", "output": "There is no related enetity." }, { "input": "CM3 protein identification was confirmed by using LTQ - OrbiTrap analysis on peptides obtained from the enzymatically digested protein separated by gel electrophoresis.", "output": "There is no related enetity." }, { "input": "Then, marker peptides derived from the protein after enzymatic cleavage of the full wheat extracts were identified by LC - MS / MS.", "output": "There is no related enetity." }, { "input": "One of them was used as marker for quantitative determination on an UPLC / ESI - MS system by using its isotopically labelled analogue as internal standard, allowing to assess the protein content in the different samples.", "output": "There is no related enetity." }, { "input": "The CM3 allergenic proteins were found to greatly vary among different cultivation areas.", "output": "There is no related enetity." }, { "input": "A study of the precursors of the natural antioxidant phenol 3, 4 - dihydroxyphenylglycol in olive oil waste.", "output": "phenol 3 , 4 - dihydroxyphenylglycol." }, { "input": "3, 4 - Dihydroxyphenylglycol ( DHPG ) is a potent antioxidant recently found in the free form in olive oil and table olives.", "output": "3 , 4 - Dihydroxyphenylglycol, DHPG." }, { "input": "DHPG can be recovered from olive oil solid waste by a hydrothermal treatment.", "output": "DHPG." }, { "input": "It was observed that an increase in the concentration of DHPG occurred when alperujo aqueous extracts were subjected to mild thermal conditions ( post - treatment ).", "output": "DHPG." }, { "input": "This fact indicates that certain solubilized compounds or precursors containing DHPG which is released with the post - treatment.", "output": "DHPG." }, { "input": "In the present study, the precursors of DHPG were identified and characterized after extraction from alperujo using thermal treatment and purification by fractionation on Amberlite (R) XAD16 polyamide and semi - preparative reverse - phase HPLC columns.", "output": "DHPG." }, { "input": "Their structures were elucidated using HPLC coupled to diode array detector ( DAD ) and electrospray ionization mass spectrometry ( ESI - MS ).", "output": "There is no related enetity." }, { "input": "The results identified three compounds as precursors, and their structures can be attributed to the diastereoisomeric forms of the two beta - hydroxy derivatives of verbascoside and isoverbascoside ( beta - hydroxyacteoside and beta - hydroxyisoacteoside ), and 2 '' - hydroxyoleuropein, all of which contain a DHPG moiety, potentially explaining the increases in the concentration of this phenolic compound in olive oil waste.", "output": "beta - hydroxy, verbascoside, isoverbascoside, beta - hydroxyacteoside, beta - hydroxyisoacteoside, 2 '' - hydroxyoleuropein, DHPG, phenolic." }, { "input": "Antioxidant ability of fractionated apple peel phenolics to inhibit fish oil oxidation.", "output": "There is no related enetity." }, { "input": "Polyphenols isolated from frozen and dried apple peels were studied as potential natural antioxidants to stabilize omega - 3 polyunsaturated fatty acid ( omega 3 PUFA ) enriched fish oil.", "output": "Polyphenols, omega - 3 polyunsaturated fatty acid, omega 3 PUFA." }, { "input": "The ethanolic extracts of apple peels were fractionated by reversed phase chromatography using gradient elution of 20 - 100 % aqueous ethanol.", "output": "ethanol." }, { "input": "The collected fractions were analyzed by ultra pressure liquid chromatography coupled with tandem mass spectrometry ( UPLC - MS / MS ).", "output": "There is no related enetity." }, { "input": "The total phenolic content and antioxidant capacity of each fraction were evaluated by Folin - Ciocalteu ( FC ), ferric reducing antioxidant power ( FRAP ) and 1, 1 - diphenyl - 2 - picrylhydrazyl radical ( DPPH ) scavenging assays.", "output": "ferric, 1 , 1 - diphenyl - 2 - picrylhydrazyl, DPPH." }, { "input": "Inhibition of fish oil oxidation was studied using the thiobarbituric acid reactive substances ( TBARS ) assay.", "output": "thiobarbituric acid." }, { "input": "Polyphenols fractionated using frozen apple peel extract had significantly higher FC, FRAP and DPPH (. ) scavenging values than those of dried apple peel ( p < 0. 05 ).", "output": "Polyphenols, DPPH ( . )." }, { "input": "The flavonol - rich fractions inhibited fish oil oxidation by 40 - 62 % at a total phenolic concentration of 200 mu g / ml.", "output": "There is no related enetity." }, { "input": "The fractionated polyphenols from both dried and frozen apple peel showed higher inhibition of lipid oxidation compared to alpha - tocopherol, butylated hydroxytoluene and crude apple peel extracts.", "output": "polyphenols, alpha - tocopherol, butylated hydroxytoluene." }, { "input": "Pilot study on levels of perfluorooctane sulfonic acid ( PFOS ) and perfluorooctanoic acid ( PFOA ) in selected foodstuffs and human milk from Italy.", "output": "perfluorooctane sulfonic acid, PFOS, perfluorooctanoic acid, PFOA." }, { "input": "Despite the health risks associated with perfluorinated compounds ( PFC ) exposure and the detection of these compounds in many countries around the world, little is known on their occurrence in Italy.", "output": "There is no related enetity." }, { "input": "The results of a study on levels of perfluorooctane sulfonate ( PFOS ) and perfluorooctanoic acid ( PFOA ), analysed by HPLC - ESI - MS, in human milk and food samples from the city of Siena and its province ( central Italy ) are here reported.", "output": "perfluorooctane sulfonate, PFOS, perfluorooctanoic acid, PFOA." }, { "input": "PFOS was found in 13 out of 49 breast milk samples ( 0. 76 +/- 1. 27ng / g ), while PFOA was detected in one sample ( 8. 04ng / g ).", "output": "PFOS, PFOA." }, { "input": "Only PFOS was found in food samples.", "output": "PFOS." }, { "input": "Fish were the most contaminated samples ( 7. 65 +/- 34. 2ng / g ); mean concentrations in meat and milk and dairy products were similar ( 1. 43 +/- 7. 21ng / g and 1. 35 +/- 3. 45ng / g, respectively ).", "output": "There is no related enetity." }, { "input": "In all cereal - based food, eggs, vegetables, honey and beverages PFOS concentration was < LOD.", "output": "PFOS." }, { "input": "These data show that consumption of most breast milk analysed would not result in children exceeding their total daily intakes for perfluorinated compounds.", "output": "There is no related enetity." }, { "input": "Effect of salt solutions applied during wheat conditioning on lipase activity and lipid stability of whole wheat flour.", "output": "There is no related enetity." }, { "input": "Lipolytic activity in whole wheat flour ( WWF ) is largely responsible for the loss in baking quality during storage.", "output": "There is no related enetity." }, { "input": "Metal ions affect the activity of seed lipases; however, no previous studies have applied this information to WWF in a way that reduces lipase activity, is practical for commercial manufacture, and uses common food ingredients.", "output": "There is no related enetity." }, { "input": "NaCl, KCl, Ca - propionate, or FeNa - ethylenediaminetetraacetic acid ( FeNa - EDTA ) were applied to hard red winter ( HRW ) and hard white spring ( HWS ) wheats during conditioning as aqueous solutions at concentrations that would be acceptable in baked goods.", "output": "NaCl, KCl, Ca - propionate, FeNa - ethylenediaminetetraacetic acid, FeNa - EDTA." }, { "input": "Salts affected lipase activity to different degrees depending on the type of wheat used.", "output": "There is no related enetity." }, { "input": "Inhibition was greater in HRW compared with HWS WWF, probably due to higher lipase activity in HRW wheat.", "output": "There is no related enetity." }, { "input": "In HRW WWF, 1 % NaCl ( flour weight ) reduced hydrolytic and oxidative rancidity and resulted in higher loaf volume and lower firmness than untreated WWF after 24weeks of storage.", "output": "NaCl." }, { "input": "Garnacha Tintorera - based sweet wines: Chromatic properties and global phenolic composition by means of UV - Vis spectrophotometry.", "output": "There is no related enetity." }, { "input": "Valdeorras ( the N. W. corner of Spain ) wants to promote the production and marketing of new sweet wines.", "output": "There is no related enetity." }, { "input": "The present work represents the first study on sweet wines manufactured with red grapes Vitis vinifera L.", "output": "There is no related enetity." }, { "input": "Garnacha Tintorera, a teinturier cultivar.", "output": "There is no related enetity." }, { "input": "Two different red sweet wines were elaborated: the first one was made with dried grapes; Vitis vinifera L.", "output": "There is no related enetity." }, { "input": "Garnacha Tintorera has excellent potential to produce wines from raisined grapes; the second one, a fortified sweet wine aged in oak barrels.", "output": "There is no related enetity." }, { "input": "Different red Garnacha Tintorera - based wines ( a dry base wine, GBW; a naturally sweet wine, GNSW; and a fortified sweet wine, GFSW ) were characterized.", "output": "There is no related enetity." }, { "input": "Chromatic characteristics and phenolic compounds were established by spectrophotometric methods in order to assess the technology of Garnacha Tintorera - based sweet wines.", "output": "phenolic." }, { "input": "High molecular weight brown polymers, produced during the grape drying process and isolated from sweet wines by the dialysis process, were responsible for the brown colour of sweet wines.", "output": "There is no related enetity." }, { "input": "As a consequence, yellowness of sweet wines was also higher which was confirmed by colorimetric indexes.", "output": "There is no related enetity." }, { "input": "With respect to phenolic content, GFSW presented the lowest content because the maceration - alcoholic fermentation was stopped through the addition of alcohol before the diffusion of red pigments from skins to must was complete.", "output": "alcoholic, alcohol." }, { "input": "GNSW presented the highest phenolic content due to the concentration effect resulting from evaporation of water from the grapes.", "output": "There is no related enetity." }, { "input": "Anthocyanins of sweet wines were polymerised in great extent.", "output": "Anthocyanins." }, { "input": "The percentage of polymerised tannins was sufficient to guarantee the aging process of sweet wines.", "output": "tannins." }, { "input": "C - Phycocyanin from Oscillatoria tenuis exhibited an antioxidant and in vitro antiproliferative activity through induction of apoptosis and G0 / G1 cell cycle arrest.", "output": "There is no related enetity." }, { "input": "This study was undertaken to develop an efficient single step chromatographic method for purification of C - phycocyanin ( CPC ) from species of Oscillatoria tenuis.", "output": "There is no related enetity." }, { "input": "Purification of CPC involves a multistep treatment of the crude extract by precipitation with ammonium sulphate, followed by gel filtration chromatography.", "output": "ammonium sulphate." }, { "input": "Pure CPC was finally obtained from O. tenuis with purity ratio ( A620 / A280 ) 4. 88.", "output": "There is no related enetity." }, { "input": "SDS - PAGE of pure CPC yielded two bands corresponding to alpha and beta subunits; the molecular weight of alpha subunit is 17. 0kDa, whereas the molecular weight of beta subunit is 19. 5kDa.", "output": "There is no related enetity." }, { "input": "Fluorescence and phase contrast microscopy revealed characteristic apoptotic features like cell shrinkage, membrane blebbing, nuclear condensation and DNA fragmentation.", "output": "There is no related enetity." }, { "input": "CPC exhibited antioxidant and antiproliferative activity against human cancer cells through apoptosis; nuclear apoptosis induction was accompanied by G0 / G1 phase arrest and DNA fragmentation.", "output": "There is no related enetity." }, { "input": "CPC is a natural pigment with potential as an anticancer agent.", "output": "There is no related enetity." }, { "input": "Effect of 5 - hydroxymethylfurfural derived from processed Cornus officinalis on the prevention of high glucose - induced oxidative stress in human umbilical vein endothelial cells and its mechanism.", "output": "5 - hydroxymethylfurfural, glucose." }, { "input": "The aim of this study was to investigate the protective effect of 5 - HMF on human umbilical vein endothelial cells ( HUVECs ) injured by high glucose in vitro, and the mechanism underlying this process.", "output": "5 - HMF, glucose." }, { "input": "Our results demonstrated that high glucose - induced oxidative stress in HUVECs was mainly mediated through activation of reactive oxygen species ( ROS ), Jun N - kinase 2 / 3 ( JNK2 / 3 ) and plasma interleukin - 8 ( IL - 8 ), and inactivation of phosphorylated protein kinase B ( P - Akt ).", "output": "glucose, oxygen." }, { "input": "Treatment of HUVECs with media containing high glucose ( 4. 5 % ) in the presence of 5 - HMF ( 100, 200 and 400 mu M ) resulted in significant inhibition of high glucose - induced oxidative stress and expression of JNK1 and JNK2 / 3.", "output": "glucose, 5 - HMF, glucose." }, { "input": "Furthermore, 5 - HMF rapidly inhibited high glucose - induced activation of IL - 8, a downstream activator of P - Akt.", "output": "5 - HMF, glucose." }, { "input": "Diabetes mellitus can cause a wide variety of vascular complications and high glucose can induce vascular endothelial cell apoptosis.", "output": "glucose." }, { "input": "Free radicals are formed disproportionately in diabetes by glucose oxidation.", "output": "glucose." }, { "input": "The finding of this study highlights the pharmacological application of 5 - HMF for preventing cardiovascular and diabetes mellitus diseases, and provides the theoretical basis for further development of a Cornus officinalis agent for diabetes - associated vascular diseases.", "output": "5 - HMF." }, { "input": "Development and validation of ethylenethiourea determination in foods using methanol - based extraction, solid - phase extraction cleanup and LC - MS / MS.", "output": "ethylenethiourea, methanol." }, { "input": "To response to the need for a rapid, cost - effective, eco - friendly and efficient extraction process, a sensitive method for the determination of ethylenethiourea ( ETU ) in food matrices by high - performance liquid chromatography - mass spectrometry ( HPLC - LC / MS ) was developed and validated.", "output": "ethylenethiourea, ETU." }, { "input": "ETU was extracted from food commodities with methanol, cleaned up by alumina - SPE column, and then determined by HPLC - MS / MS.", "output": "ETU, methanol, alumina." }, { "input": "The MS detection was operated in positive ionization mode.", "output": "There is no related enetity." }, { "input": "For confirmation of target compound, two precursor ion > product ion transitions were selected by multi - reaction monitoring mode ( MRM ).", "output": "There is no related enetity." }, { "input": "The method showed good linearity with correlation coefficient higher than 0. 9950.", "output": "There is no related enetity." }, { "input": "Recoveries at three spiked levels ( 10, 50, 100ng / g ) in random selected food matrices were in range of 71 - 121 % with RSDs not larger than 25 %.", "output": "There is no related enetity." }, { "input": "The limit of quantitation for the analyte was estimated at 5ng / g.", "output": "There is no related enetity." }, { "input": "Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia.", "output": "hydroethanolic." }, { "input": "Antioxidant properties and protective effect of aged garlic extract ( AGE ) and of 20 % hydroethanolic fresh extracts from garlic clove ( GCE ) and skin ( GSE ) on cerebral ischemia were evaluated by administering extracts at the beginning of reperfusion in a rat model of stroke.", "output": "hydroethanolic." }, { "input": "All three extracts scavenged superoxide anion, peroxynitrite anion, and peroxyl radicals, but with different efficiencies; furthermore, GCE and GSE scavenged hydroxyl radicals and GSE scavenged singlet oxygen.", "output": "superoxide, peroxynitrite, peroxyl, hydroxyl, oxygen." }, { "input": "These extracts significantly prevented reduction of neuronal nuclear antigen in the infarcted area, although no improvement in neurological function was observed.", "output": "There is no related enetity." }, { "input": "Importantly, GCE and GSE contained S - allylcystein, a compound associated with AGE ' s neuroprotective effect against damage induced by cerebral ischemia.", "output": "S - allylcystein." }, { "input": "Extracts decreased mRNA expression of NR1 - and NR2B - NMDA - receptor subunits and prevented ischemia - induced reduction in mitochondrial potential and in ATP synthesis.", "output": "NMDA, ATP." }, { "input": "These results indicate that antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro - survival pathways, and attenuate mitochondrial dysfunction.", "output": "There is no related enetity." }, { "input": "A calibrator plasmid for quantitative analysis of insect resistant maize ( Yieldgard MON 810 ).", "output": "There is no related enetity." }, { "input": "Real - time PCR ( RT - PCR ) is the preferred method for the quantification of genetically modified organisms ( GMOs ) and implementation of labeling regulations.", "output": "There is no related enetity." }, { "input": "The precision, sensitivity, and reproducibility of RT - PCR data depend on the use of external calibrators.", "output": "There is no related enetity." }, { "input": "In this investigation, a dual target plasmid designated pRSETMON - 02 comprising of MON 810 maize event specific and endogenous zein gene sequences in 1: 1 ratio in tandem was constructed and validated.", "output": "There is no related enetity." }, { "input": "Commutability of plasmid DNA ( pDNA ) and genomic DNA ( gDNA ) calibrators for the quantification of MON 810 maize was assessed by employing a TaqMan RT - PCR targeting the P - 35S and zein gene.", "output": "There is no related enetity." }, { "input": "Higher PCR efficiencies, good linearity and lower relative standard deviation ( RSD ) values were associated with pRSETMON - 02 as opposed to gDNA calibrants.", "output": "There is no related enetity." }, { "input": "pDNA calibrants exhibited better performance characteristic in terms of closeness to the expected value of unknown samples than their genomic counterparts.", "output": "There is no related enetity." }, { "input": "Short term stability study of the pRSETMON - 02 plasmid stored at different temperatures showed that pDNA is stable for 45days at - 20, and 4 degrees C.", "output": "There is no related enetity." }, { "input": "The results demonstrated that the developed dual target plasmid pRSETMON - 02 is fit for the intended use of quantifying MON 810 maize and is a better alternative to conventional seed powder calibrants.", "output": "There is no related enetity." }, { "input": "Novel ROS - activated agents utilize a tethered amine to selectively target acute myeloid leukemia.", "output": "tethered amine." }, { "input": "This study explores the possible use of reactive oxygen - activated DNA modifying agents against acute myeloid leukemia ( AML ).", "output": "oxygen." }, { "input": "A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency.", "output": "amine." }, { "input": "The two best compounds were screened via the NCI - 60 cell panel.", "output": "There is no related enetity." }, { "input": "These two compounds had potency between 200 and 800nM against many of the leukemia cancer cell types.", "output": "There is no related enetity." }, { "input": "Subsequent experiments explored activity against a transformed AML model that mimics the molecular signatures identified in primary AML patient samples.", "output": "There is no related enetity." }, { "input": "A lead compound had an IC50 of 760nM against this AML cell line as well as a therapeutic index of 7. 7 +/- 3 between the transformed AML model cell line and non - cancerous human CD34 + blood stem / progenitor cells ( UCB ).", "output": "There is no related enetity." }, { "input": "The selectivity was much greater than the mainstays of AML treatment: doxorubicin and cytarabine.", "output": "doxorubicin, cytarabine." }, { "input": "This manuscript demonstrates that this novel type of agent may be useful against AML.", "output": "There is no related enetity." }, { "input": "Personalized medicine: predicting responses to therapy in patients with RA.", "output": "There is no related enetity." }, { "input": "Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine.", "output": "There is no related enetity." }, { "input": "The identification of predictors of response is the first step toward this.", "output": "There is no related enetity." }, { "input": "In rheumatoid arthritis ( RA ), several prediction matrices were designed to predict the risk of rapid radiological progression ( RRP ) in the first year of treatment, on either disease modifying anti - rheumatic drug ( DMARD ) monotherapy or combination therapy with prednisone or a biological agent.", "output": "prednisone." }, { "input": "Both clinical markers and biomarkers of response to either anti - TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies.", "output": "There is no related enetity." }, { "input": "Most of these markers need validation in other cohorts.", "output": "There is no related enetity." }, { "input": "Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA.", "output": "There is no related enetity." }, { "input": "Evaluation of a predictive in vitro Leydig cell assay for anti - androgenicity of phthalate esters in the rat.", "output": "phthalate esters." }, { "input": "An in vitro assay using the rat Leydig cell line R2C was evaluated for its ability to quantitatively predict inhibition of testosterone synthesis.", "output": "testosterone." }, { "input": "Results obtained for endocrine active phthalates ( MEHP, MBP ), and inactive phthalates ( MMP and MEP ) were highly consistent with in vivo results based on tissue and media concentrations.", "output": "phthalates, MEHP, MBP, phthalates, MMP, MEP." }, { "input": "Statistically significant inhibition of testosterone synthesis ( p < 0. 05, 1 - way ANOVA ) was observed at 1 mu M MBP and 3 mu M MEHP, while MEP and MMP did not affect inhibition of testosterone synthesis until much higher concentrations ( >> 100 mu M ).", "output": "testosterone, MBP, MEHP, MEP, MMP, testosterone." }, { "input": "Concentrations causing 50 % inhibition of testosterone synthesis for MBP and MEHP ( 3 and 6 mu M respectively ), were similar to in vivo values ( 3 and 7 mu M ).", "output": "testosterone, MBP, MEHP." }, { "input": "The R2C assay was used to determine the relative potency of 14 structurally diverse monoesters and oxidative metabolites of MEHP.", "output": "monoesters, MEHP." }, { "input": "Monoesters with alkyl chains 4 - 5 carbons in length had the highest potency for testosterone inhibition, while 0 - 2 carbon alkyl chains were least potent.", "output": "Monoesters, carbons, testosterone, carbon." }, { "input": "Phase I metabolism did not completely inactivate MEHP, underscoring the need for metabolism data when interpreting in vitro pharmacodynamic data.", "output": "MEHP." }, { "input": "This steroid inhibition assay provides a predictive in vitro alternative to expensive and timeconsuming developmental rat studies for phthalate - induced antiandrogenicity.", "output": "steroid, phthalate." }, { "input": "Effects of chronic methylphenidate on cocaine self - administration under a progressive - ratio schedule of reinforcement in rhesus monkeys.", "output": "methylphenidate, cocaine." }, { "input": "It has been hypothesized that drugs that serve as substrates for dopamine ( DA ) and norepinephrine ( NE ) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters.", "output": "dopamine, norepinephrine, cocaine." }, { "input": "Previous studies have shown that the DA / NE releaser d - amphetamine can decrease cocaine self - administration in preclinical and clinical studies.", "output": "d - amphetamine, cocaine." }, { "input": "The present study examined the effects of methylphenidate ( MPD ), a DA uptake inhibitor, for its ability to decrease cocaine self - administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy.", "output": "methylphenidate, MPD, cocaine, cocaine." }, { "input": "Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed - ratio 50 schedule of reinforcement; cocaine was self - administered under a progressiveratio schedule of reinforcement in the evening.", "output": "cocaine." }, { "input": "After cocaine ( 0. 003 - 0. 56 mg / kg per injection, i. v. ) dose - response curves were determined, self - administration sessions were suspended and MPD ( 0. 003 - 0. 0056 mg / kg per hr, i. v. or 1. 0 - 9. 0 mg / kg p. o., b. i. d. ) was administered for several weeks.", "output": "cocaine, MPD." }, { "input": "A cocaine self - administration session was conducted every 7 days.", "output": "cocaine." }, { "input": "When a MPD dose was reached that either persistently decreased cocaine self - administration or produced disruptive effects, the cocaine dose - effect curve was re - determined.", "output": "MPD, cocaine, cocaine." }, { "input": "In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine selfadministration; it took several weeks for these effects to dissipate.", "output": "MPD, cocaine." }, { "input": "These data are consistent with the largely negative results of clinical trials with MPD.", "output": "MPD." }, { "input": "In contrast to the positive effects with the monoamine releaser d - amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.", "output": "monoamine, d - amphetamine, monoamine, MPD, cocaine." }, { "input": "Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study.", "output": "There is no related enetity." }, { "input": "OBJECTIVEMacrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes. RESEARCH DESIGN AND METHODSEight - hundred thirty - one men and women ( aged 60 - 75 years ) attended two waves of the prospective Edinburgh Type 2 Diabetes Study ( ET2DS ).", "output": "There is no related enetity." }, { "input": "At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima - media thickness ( cIMT ), ankle brachial index ( ABI ), and serum N - terminal probrain natriuretic peptide ( NT - proBNP ).", "output": "N." }, { "input": "Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor ( g ).", "output": "There is no related enetity." }, { "input": "Adjustment of follow - up g for baseline g assessed 4 - year cognitive change.", "output": "There is no related enetity." }, { "input": "Adjustment for vocabulary ( estimated premorbid ability ) was used to estimate lifetime cognitive change. RESULTSMeasures of cognitive decline were significantly associated with stroke, NT - proBNP, ABI, and cIMT, but not with nonstroke vascular events.", "output": "There is no related enetity." }, { "input": "The association of stroke with increased estimated lifetime cognitive decline ( standardized beta, - 0. 12 ) and of subclinical markers with actual 4 - year decline ( standardized beta, - 0. 12, 0. 12, and - 0. 15 for NT - proBNP, ABI, and cIMT, respectively ) reached the Bonferroni - adjusted level of statistical significance ( P < 0. 006 ).", "output": "There is no related enetity." }, { "input": "Results altered only slightly on adjustment for vascular risk factors. CONCLUSIONSStroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes.", "output": "There is no related enetity." }, { "input": "Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.", "output": "There is no related enetity." }, { "input": "Co - Ni layered double hydroxides for water oxidation in neutral electrolyte.", "output": "Co, Ni, hydroxides." }, { "input": "The electrochemical properties of Co - Ni layered double hydroxides ( LDHs ) as efficient electrocatalysts for water oxidation were investigated in potassium phosphate electrolyte under neutral pH condition.", "output": "Co, Ni, hydroxides, potassium phosphate." }, { "input": "The Co - Ni LDHs with a core - shell structure were fabricated using a facile route from a Co - Ni hydroxide precursor with iodine as a topotactic oxidizer.", "output": "Co, Ni, Co, Ni, hydroxide, iodine." }, { "input": "The unique core - shell morphology is likely due to the enrichment of Co ( iii ) hydroxide in the inner core indicated by selected area electron diffraction and energy - dispersive spectroscopy.", "output": "Co ( iii ), hydroxide." }, { "input": "Through a self - assembling process at the organic / inorganic interface and dip - coating, the Co - Ni LDHs were deposited onto FTO glass substrates to prepare composite electrodes.", "output": "Co, Ni." }, { "input": "Low over - potential and high current density was achieved in the oxygen evolution reaction.", "output": "oxygen." }, { "input": "The excellent electrocatalytic activity of Co - Ni LDHs may be attributed to more accessible Co active sites and rapid movement of interlayer ions within their layered structure.", "output": "Co, Ni, Co." }, { "input": "Acute alcohol effects on subtypes of impulsivity and the role of alcohol - outcome expectancies.", "output": "alcohol, alcohol." }, { "input": "RATIONALE: It is well established that alcohol acutely impairs the ability to inhibit a pre - potent response ( motor impulsivity ), but its effects on cognitive impulsivity, including temporal ( delayed gratification ) and reflection ( decision making ) impulsivity, are not clear.", "output": "alcohol." }, { "input": "An important factor contributing to the effects of alcohol is cognitive expectancies of alcohol - related outcomes.", "output": "alcohol, alcohol." }, { "input": "OBJECTIVES: The current study investigated the effect of alcohol, and alcohol outcome expectancies, on subtypes of impulsivity.", "output": "alcohol, alcohol." }, { "input": "METHODS: Impulsivity was tested using the Stop Signal, the Single Key Impulsivity and the Information Sampling Task for motor, temporal and reflection impulsivity, respectively.", "output": "There is no related enetity." }, { "input": "Participants ( n = 48 ) received placebo, a low ( 0. 4 g / kg ) or high dose ( 0. 8 g / kg ) of alcohol, before completing the impulsivity measures.", "output": "alcohol." }, { "input": "RESULTS: Motor impulsivity was affected by alcohol dose; participants receiving a high dose displayed reduced inhibitory control.", "output": "alcohol." }, { "input": "Reflection impulsivity was affected by cognitive alcohol expectancies, but not by alcohol condition; participants expecting greater cognitive and behavioural impairment by alcohol exhibited low impulsivity.", "output": "alcohol, alcohol, alcohol." }, { "input": "Temporal impulsivity was not affected by either alcohol dose or outcome expectancies.", "output": "alcohol." }, { "input": "CONCLUSIONS: These data suggest that the effects of alcohol on the subtypes of impulsivity are dissociable.", "output": "alcohol." }, { "input": "Motor impulsivity is sensitive to the pharmacological effects of alcohol, whereas the reflection subtype is affected by cognitive alcohol expectancies.", "output": "alcohol, alcohol." }, { "input": "The findings have implications for the understanding of impulsive behaviour under the influence of alcohol.", "output": "alcohol." }, { "input": "A New Strategy for Selective Targeting of Progesterone Receptor with Passive Antagonists.", "output": "Progesterone." }, { "input": "Currently available progesterone receptor ( PR ) antagonists, such as mifepristone ( RU486 ), lack specificity and display partial agonist properties, leading to potential drawbacks in their clinical use.", "output": "progesterone, mifepristone, RU486." }, { "input": "Recent X - ray crystallographic studies have identified key contacts involved in the binding of agonists and antagonists with PR opening the way for a new rational strategy for inactivating PR.", "output": "There is no related enetity." }, { "input": "We report here the synthesis and characterization of a novel class of PR antagonists designed from such studies.", "output": "There is no related enetity." }, { "input": "The lead molecule, the homosteroid APR19, displays in vivo endometrial antiprogesterone activity.", "output": "homosteroid, APR19." }, { "input": "APR19 inhibits progesterone - induced PR recruitment and transactivation from synthetic and endogenous gene promoters.", "output": "APR19, progesterone." }, { "input": "Importantly, it exhibits high PR selectivity with respect to other steroid hormone receptors, and is devoid of any partial agonist activity on PR target gene transcription.", "output": "steroid." }, { "input": "Two - hybrid and immunostaining experiments reveal that APR19 - bound PR is unable to interact with either transcriptional coactivators ( SRC1, SCR2 ) or corepressors ( NCoR, SMRT ), in contrast to RU486 - PR complexes.", "output": "APR19, RU486." }, { "input": "APR19 also inhibits agonist - induced phosphorylation of serine 294 regulating PR transcriptional activity and turnover kinetics.", "output": "APR19, serine." }, { "input": "In - silico docking studies based on the crystal structure of the PR ligand - binding domain show that, in contrast to progesterone, APR19 does not establish stabilizing hydrogen bonds with the ligand binding cavity, resulting in an unstable ligand - receptor complex.", "output": "progesterone, APR19, hydrogen." }, { "input": "Altogether, these properties highly distinguish APR19 from RU486 and likely its derivatives, suggesting that it belongs to a new class of pure antiprogestins which inactivate PR by a passive mechanism.", "output": "APR19, RU486." }, { "input": "These specific PR antagonists open new perspectives for long term hormonal therapy.", "output": "There is no related enetity." }, { "input": "Cellular insulin resistance disrupts leptin - mediated control of neuronal signaling and transcription.", "output": "There is no related enetity." }, { "input": "Central resistance to the actions of insulin and leptin is associated with the onset of obesity and type 2 diabetes mellitus ( T2DM ), whereas leptin and insulin signaling is essential for both glucose and energy homeostasis.", "output": "glucose." }, { "input": "Although it is known that leptin resistance can lead to attenuated insulin signaling, whether insulin resistance can lead to or exacerbate leptin resistance is unknown.", "output": "There is no related enetity." }, { "input": "To investigate the molecular events underlying crosstalk between these signaling pathways, immortalized hypothalamic neuronal models, rHypoE - 19 and mHypoA - 2 / 10, were utilized.", "output": "There is no related enetity." }, { "input": "Prolonged insulin exposure was used to induce cellular insulin resistance, and thereafter leptin - mediated regulation of signal transduction and gene expression was assessed.", "output": "There is no related enetity." }, { "input": "Leptin directly repressed agouti - related peptide ( AgRP ) mRNA levels, but induced urocortin - 2 ( UCN2 ), insulin receptor substrate - 1 ( IRS1 ), IRS2, and IR transcription, through leptin - mediated phosphatidylinositol - 3 - kinase ( PI3K ) / Akt activation.", "output": "phosphatidylinositol." }, { "input": "Neuronal insulin resistance, as assessed by attenuated Akt phosphorylation, blocked leptin - mediated signal transduction, and AgRP, UCN2, IRS1, IRS2 and IR synthesis.", "output": "There is no related enetity." }, { "input": "Insulin resistance caused a substantial decrease in IR protein levels, forkhead box protein 1 ( FoxO1 ) phosphorylation, and an increase in suppressor of cytokine signaling 3 ( SOCS3 ) protein levels.", "output": "There is no related enetity." }, { "input": "Cellular insulin resistance may cause or exacerbate neuronal leptin resistance, and by extension, obesity.", "output": "There is no related enetity." }, { "input": "It is essential to unravel the effects of neuronal insulin resistance given that both peripheral, as well as the less widely studied central insulin resistance, may contribute to the development of metabolic, reproductive and cardiovascular disorders.", "output": "There is no related enetity." }, { "input": "This study provides an improved understanding of the complex cellular crosstalk between insulin - leptin signal transduction that is disrupted during neuronal insulin resistance.", "output": "There is no related enetity." }, { "input": "VERY HIGH PREVALENCE OF ULTRASOUND THYROID SCAN ABNORMALITIES IN HEALTHY VOLUNTEERS IN MODENA, ITALY.", "output": "There is no related enetity." }, { "input": "Background: Italy is characterized by high prevalence of goiter.", "output": "There is no related enetity." }, { "input": "To date, only limited data about the prevalence of goiter in the Italian adult population are available.", "output": "There is no related enetity." }, { "input": "Aim.", "output": "There is no related enetity." }, { "input": "To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer ( DTC ) obtained by this intervention.", "output": "There is no related enetity." }, { "input": "Methods.", "output": "There is no related enetity." }, { "input": "US thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy.", "output": "There is no related enetity." }, { "input": "135 women and 66 men ( n = 201 ), unaware of any thyroid disease ( mean age of 46 +/- 10. 7 years ) underwent their first thyroid US scan.", "output": "There is no related enetity." }, { "input": "Results.", "output": "There is no related enetity." }, { "input": "US thyroid abnormalities were found in 101 subjects ( 50. 3 % ): 91 nodular goiters ( 45. 2 % ) and 13 US - thyroiditis ( 6. 5 % ) associated with positive auto - antibodies in 11 of them.", "output": "There is no related enetity." }, { "input": "17 subjects ( 18 % ) with nodules underwent US - FNAB with the following cytological class ( C ) outcome: 14 patients C2 ( 82 % ), 1 patient C3 ( 6 % ), 2 patients had C4 ( 12 % ), the latter received histological confirmation.", "output": "There is no related enetity." }, { "input": "Conclusions.", "output": "There is no related enetity." }, { "input": "The prevalence of thyroid abnormalities, is very high in subjects unaware of any thyroid disease.", "output": "There is no related enetity." }, { "input": "DTC was found in 1 % of subjects and in 2 % of those affected by nodular goiter.", "output": "There is no related enetity." }, { "input": "Compared to the detection rate of the well - established screening programs for breast ( 0. 45 % ) and colorectal ( 0. 27 % ) cancer, the prevalence of DTC seems to be much higher.", "output": "There is no related enetity." }, { "input": "Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage.", "output": "There is no related enetity." }, { "input": "Thus, US screening not necessarily results in the over - diagnosis of clinically not relevant thyroid diseases.", "output": "There is no related enetity." }, { "input": "Female sexual dysfunction in women with thyroid disorders.", "output": "There is no related enetity." }, { "input": "Background.", "output": "There is no related enetity." }, { "input": "Few data exist on the prevalence of FSD in thyroid disorders.", "output": "There is no related enetity." }, { "input": "Aim.", "output": "There is no related enetity." }, { "input": "We evaluated FSD in women with thyroid diseases and in control age matched healthy women to investigate the relationship between sexual function, and thyroid hormones.", "output": "There is no related enetity." }, { "input": "Methods.", "output": "There is no related enetity." }, { "input": "One hundred and four women with thyroid diseases and 53 controls participated in the study.", "output": "There is no related enetity." }, { "input": "Eighteen with hyperthyroidism ( Group1 ), 22 hypothyroidism ( Group2 ), 45 Hashimoto ' s thyroiditis ( Group3 ), 19 nodular goiter ( Group4 ) underwent thyroid function evaluation and sonography.", "output": "There is no related enetity." }, { "input": "The Female Sexual Function Index ( FSFI ) assessed sexual function.", "output": "There is no related enetity." }, { "input": "Results.", "output": "There is no related enetity." }, { "input": "The prevalence of FSD was 46. 1 % in thyroid diseases and 20. 7 % in controls.", "output": "There is no related enetity." }, { "input": "Only in Group4, the prevalence ( 68. 4 % ) was significantly higher than in controls ( P < 0. 005 ).", "output": "There is no related enetity." }, { "input": "The mean total FSFI score were 20. 1 +/- 7. 1 in women with thyroid diseases and 25. 6 +/- 4. 7 in the controls ( P < 0. 001 ).", "output": "There is no related enetity." }, { "input": "Compared with controls, there was a significant decrease of desire in Group2; desire, arousal and lubrication in Group3; desire, arousal, lubrication, orgasm and satisfaction in Group4.", "output": "There is no related enetity." }, { "input": "In thyroid diseases the prevalence of FSD was 53 % and 42 %, while in the controls was 55 % and 20 %, in menopausal and pre - menopausal groups, respectively.", "output": "There is no related enetity." }, { "input": "We found a significant inverse correlation between TSH and FSFI ( r = - 0. 7, P = 0. 01 ) in Group 4, which showed the lowest FSFI score ( 17. 8 +/- 5. 7 ) and the highest BMI ( 28. 4 +/- 7. 1 Kg / m2 ). Conclusions: Women with thyroid diseases present a higher prevalence of FSD than controls.", "output": "There is no related enetity." }, { "input": "Although our findings suggest a higher impairment of sexual function in Group4 and a role for TSH in FSD, further researches are needed.", "output": "There is no related enetity." }, { "input": "A XAS study of the luminescent Eu centers in thiosilicate phosphors.", "output": "Eu, thiosilicate." }, { "input": "Due to its bright yellow - to - red emission, europium doped Ca2SiS4 is a very interesting material for phosphor converted light emitting diodes.", "output": "europium, Ca2SiS4." }, { "input": "The emission spectrum is highly dependent on the Eu concentration and can consist of more than one emission band.", "output": "Eu." }, { "input": "We combined X - ray absorption fine structure and photoluminescence measurements to analyze the structure of europium centers in ( Ca, Eu ) 2SiS4 luminescent powders.", "output": "europium, ( Ca , Eu ) 2SiS4." }, { "input": "This paper provides an explanation for the concentration dependency of the emission spectra.", "output": "There is no related enetity." }, { "input": "We find that at low dopant concentrations a large fraction of trivalent europium ions is unexpectedly present in the powders.", "output": "europium." }, { "input": "These trivalent europium ions tend to form defect clusters in the luminescent powders.", "output": "europium." }, { "input": "Furthermore we observe a preferential substitution of the europium ions over the two different substitutional Ca sites, which changes upon increasing the dopant concentration.", "output": "europium, Ca." }, { "input": "At high dopant concentration, the powder crystallizes in the monoclinic Eu2SiS4 structure.", "output": "monoclinic Eu2SiS4." }, { "input": "Once more a preferential substitution of the europium ions is observed.", "output": "europium." }, { "input": "Summarizing, the influence of the concentration on the emission spectrum is explained by a difference in preferential occupation of the Eu ions in the lattice.", "output": "Eu." }, { "input": "Anti - asthmatic Effects of Baicalin in a Mouse Model of Allergic Asthma.", "output": "Baicalin." }, { "input": "The aim of the study was to investigate the anti - asthmatic effects of baicalin ( BA ) and the possible mechanisms.", "output": "baicalin." }, { "input": "Asthma model was established by ovalbumin ( OVA ) intraperitoneal injection.", "output": "There is no related enetity." }, { "input": "A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone ( 2 mg / kg ), and BA ( 10 mg / kg, 20 mg / kg, 40 mg / kg ).", "output": "dexamethasone." }, { "input": "Airway resistance ( RI ) and lung compliance ( Cdyn ) were measured, histological studies were evaluated by the hematoxylin and eosin staining, Th1 / Th2, OVA - specific serum, and BALF IgE levels and Th17 cytokines were evaluated by enzyme - linked immunosorbent assay, and Th17 cells was evaluated by flow cytometry ( FCM ).", "output": "hematoxylin, eosin." }, { "input": "Our study demonstrated that BA inhibited OVA - induced increases in RI and eosinophil count; interleukin ( IL ) - 4, IL - 17A levels, and Cdyn were recovered and increased IFN - gamma level in bronchoalveolar lavage fluid.", "output": "There is no related enetity." }, { "input": "Histological studies demonstrated that BA substantially inhibited OVA - induced eosinophilia in lung tissue and airway tissue.", "output": "There is no related enetity." }, { "input": "FCM studies demonstrated that BA substantially inhibited Th17 cells.", "output": "There is no related enetity." }, { "input": "These findings suggest that BA may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.", "output": "There is no related enetity." }, { "input": "Copyright (c) 2013 John Wiley & Sons, Ltd.", "output": "There is no related enetity." }, { "input": "Solvent - induced delamination of a multifunctional two dimensional coordination polymer ( adv. Mater. 15 / 2013 ).", "output": "There is no related enetity." }, { "input": "Unprecedented full delamination of a multifunctional 2D metal - organic framework ( MOF ) assisted only by solvent interaction is carried out on page 2141 by F e lix Zamora, Salome Delgado, and co - workers.", "output": "There is no related enetity." }, { "input": "This observation is a direct consequence of the structure of the starting material, characterized by interlayer cavities that can be filled by the solvent molecules, producing delamination in a simple and reproducible way.", "output": "There is no related enetity." }, { "input": "Age - Related Macular Degeneration.", "output": "There is no related enetity." }, { "input": "Age - related macular degeneration ( AMD ) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years.", "output": "There is no related enetity." }, { "input": "It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors.", "output": "There is no related enetity." }, { "input": "Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease.", "output": "There is no related enetity." }, { "input": "AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular ( dry ) type and the neovascular ( wet ) type.", "output": "There is no related enetity." }, { "input": "The results from the Age - Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high - dose antioxidants ( vitamin C, vitamin E, and beta - carotene ) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye.", "output": "vitamin C, vitamin E, beta - carotene, zinc." }, { "input": "As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors.", "output": "There is no related enetity." }, { "input": "In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended.", "output": "sodium, sugars, cholesterol." }, { "input": "To date, no study has demonstrated that AMD can be cured or effectively prevented.", "output": "There is no related enetity." }, { "input": "Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease.", "output": "There is no related enetity." }, { "input": "Low Driving Voltage and High Mobility Ambipolar Field - Effect Transistors with PbS Colloidal Nanocrystals.", "output": "PbS." }, { "input": "PbS colloidal nanocrystals ( NCs ) are promising materials for optoelectronic devices, due to their size - tunable properties.", "output": "PbS." }, { "input": "However, there is still minimal understanding of their charge transport mechanism.", "output": "There is no related enetity." }, { "input": "Through a combination of ligand selections, ambipolar transistor structure optimization, and electrochemical gating usage, high carrier mobility is achieved.", "output": "There is no related enetity." }, { "input": "The outstanding device characteristics open possibility to investigate the intrinsic transport properties of PbS NCs.", "output": "PbS." }, { "input": "Large Areal Mass, Flexible and Free - Standing Reduced Graphene Oxide / Manganese Dioxide Paper for Asymmetric Supercapacitor Device.", "output": "Graphene Oxide, Manganese Dioxide." }, { "input": "Well - separated RGO sheets decorated with MnO2 nanoparticles facilitate easy access of the electrolyte ions to the high surface area of the paper electrode, enabling fabrication of thicker electrode with heavier areal mass and higher areal capacitance ( up to 897 mF cm ( - 2 ) ).", "output": "MnO2." }, { "input": "Electrochemical performance of the bent asymmetric device with total active mass of 15 mg remains similar to the one in the flat configuration, demonstrating good mechanical robustness of the device.", "output": "There is no related enetity." }, { "input": "A lipoprotein receptor cluster IV mutant preferentially binds amyloid - beta and regulates its clearance from the mouse brain.", "output": "There is no related enetity." }, { "input": "Soluble low - density lipoprotein receptor - related protein - 1 ( sLRP1 ) binds ~ 70 % of amyloid beta - peptide ( A beta ) in human plasma.", "output": "There is no related enetity." }, { "input": "In Alzheimer ' s disease ( AD ) and individuals with mild cognitive impairment converting to AD, plasma sLRP1 levels are reduced and sLRP1 is oxidized which results in diminished A beta peripheral binding and higher levels of free A beta in plasma.", "output": "There is no related enetity." }, { "input": "Experimental studies have shown that free circulating A beta re - enters the brain and that sLRP1 and / or its recombinant wild - type cluster IV ( WT - LRPIV ) prevent A beta from entering the brain.", "output": "There is no related enetity." }, { "input": "Treatment of Alzheimer ' s APPsw + / 0 mice with WT - LRPIV has been shown to reduce brain A beta pathology.", "output": "There is no related enetity." }, { "input": "In addition to A beta, LRPIV binds multiple ligands.", "output": "There is no related enetity." }, { "input": "To enhance LRPIV binding for A beta relative to other LRP1 ligands, we generated a library of LRPIV - derived fragments and full - length LRPIV variants with glycine ( G ) replacing aspartic acid ( D ) residues 3394, 3556 and 3674 in the calcium binding sites.", "output": "glycine, aspartic acid, calcium." }, { "input": "Compared to WT - LRPIV, a lead LRPIV - D3674G mutant had 1. 6 - fold and 2. 7 - fold higher binding affinity for A beta 40 and A beta 42 in vitro, respectively, and a lower binding affinity for other LRP1 ligands, e. g., apoliporotein E2, E3 and E4 ( 1. 3 - 1. 8 - fold ), tissue plasminogen activator ( 2. 7 - fold ), matrix metalloproteinase - 9 ( 4. 1 - fold ) and Factor Xa ( 3. 8 - fold ).", "output": "There is no related enetity." }, { "input": "LRPIV - D3674G cleared mouse endogenous brain A beta 40 and A beta 42 25 - 27 % better than WT - LRPIV.", "output": "There is no related enetity." }, { "input": "A 3 - month subcutaneous treatment of APPsw + / 0 mice with LRPIV - D3674G ( 40 mu g / kg / day ) reduced A beta 40 and A beta 42 levels in the hippocampus, cortex and cerebrospinal fluid by 60 - 80 %, and improved cerebral blood flow responses and hippocampal function at 9 months of age.", "output": "There is no related enetity." }, { "input": "Thus, LRPIV - D3674G is an efficient new A beta clearance therapy.", "output": "There is no related enetity." }, { "input": "Synthesis of diazenido - ligated vanadium nanoparticles.", "output": "diazenido, vanadium." }, { "input": "Metallic vanadium nanoparticles stabilized with 4 - octylphenyldiazenido groups ( particle size: 1. 7 +/- 0. 2 nm ) were synthesized via the reduction of VCl4 with superhydride ( LiBHEt3 ) in the presence of 4 - octylphenyldiazonium salt in an Ar - filled glovebox.", "output": "vanadium, 4 - octylphenyldiazenido, VCl4, superhydride, LiBHEt3, 4 - octylphenyldiazonium." }, { "input": "The resulting particles were characterized using TEM, elemental analysis, and XPS measurements.", "output": "There is no related enetity." }, { "input": "The unusual reaction on the surface resulted in the passivation of V - N = N - Ar covalent bonds.", "output": "V - N = N - Ar." }, { "input": "The stabilization effect of dielectric constant and acidic amino acids on arginine - arginine ( arg - arg ) pairings: database survey and computational studies.", "output": "acidic amino acids, arginine, arginine." }, { "input": "Database survey in this study revealed that about one - third of the protein structures deposited in the Protein Data Bank ( PDB ) contain arginine - arginine ( Arg - Arg ) pairing with a carbon... carbon ( CZ... CZ ) interaction distance less than 5 A.", "output": "arginine, arginine, Arg - Arg, carbon, carbon." }, { "input": "All the Arg - Arg pairings were found to bury in a polar environment composed of acidic residues, water molecules, and strong polarizable or negatively charged moieties from binding site or bound ligand.", "output": "Arg - Arg." }, { "input": "Most of the Arg - Arg pairings are solvent exposed and 68. 3 % Arg - Arg pairings are stabilized by acidic residues, forming Arg - Arg - Asp / Glu clusters.", "output": "Arg - Arg, Arg - Arg, Arg - Arg - Asp, Glu." }, { "input": "Density functional theory ( DFT ) was then employed to study the effect of environment on the pairing structures.", "output": "There is no related enetity." }, { "input": "It was revealed that Arg - Arg pairings become thermodynamically stable ( about - 1 kcal / mol ) as the dielectric constant increases to 46. 8 ( DMSO ), in good agreement with the results of the PDB survey.", "output": "Arg - Arg." }, { "input": "DFT calculations also demonstrated that perpendicular Arg - Arg pairing structures are favorable in low dielectric constant environment, while in high dielectric constant environment parallel structures are favorable.", "output": "Arg - Arg." }, { "input": "Additionally, the acidic residues can stabilize the Arg - Arg pairing structures to a large degree.", "output": "Arg - Arg." }, { "input": "Energy decomposition analysis of Arg - Arg pairings and Arg - Arg - Asp / Glu clusters showed that both solvation and electrostatic energies contribute significantly to their stability.", "output": "Arg - Arg, Arg - Arg - Asp, Glu." }, { "input": "The results reported herein should be very helpful for understanding Arg - Arg pairing and its application in drug design.", "output": "Arg - Arg." }, { "input": "Enhanced Hematite Water Electrolysis Using a 3D Antimony - Doped Tin Oxide Electrode.", "output": "Hematite, Antimony - Doped Tin Oxide." }, { "input": "We present herein an example of nanocrystalline antimony - doped tin oxide ( nc - ATO ) disordered macroporous \" inverse opal \" 3D electrodes as efficient charge - collecting support structures for the electrolysis of water using a hematite surface catalyst.", "output": "antimony - doped tin oxide, ATO, hematite." }, { "input": "The 3D macroporous structures were created via templating of polystyrene spheres, followed by infiltration of the desired precursor solution and annealing at high temperature.", "output": "polystyrene." }, { "input": "Using cyclic voltammetry and electrochemical impedance spectroscopy, it was determined that the use of this 3D transparent conducting oxide with a hematite surface catalyst allowed for a seven - fold increase in active surface area for water splitting with respect to its 2D planar counterpart.", "output": "oxide, hematite." }, { "input": "This ratio of surface areas was evaluated based on the presence of oxidized trap states on the hematite surface, as determined from the equivalent circuit analysis of the Nyquist plots.", "output": "hematite." }, { "input": "Furthermore, the presence of nc - ATO 2D and 3D \" underlayer \" structures with hematite deposited on top resulted in decreased charge transfer resistances and an increase in the number of available active surface sites at the semiconductor - liquid junction when compared to hematite films lacking any nc - ATO substructures.", "output": "ATO, hematite, hematite, ATO." }, { "input": "Finally, absorption, transmission and reflectance spectra of all of the tested films were measured, suggesting the feasibility of using 3D disordered structures in photoelectrochemical reactions, due to the high absorption of photons by the surface catalyst material and trapping of light within the structure.", "output": "There is no related enetity." }, { "input": "Engineering bacterial efflux pumps for solar - powered bioremediation of surface waters.", "output": "There is no related enetity." }, { "input": "Antibiotics are difficult to selectively remove from surface waters by present treatment methods.", "output": "There is no related enetity." }, { "input": "Bacterial efflux pumps have evolved the ability to discriminately expel antibiotics and other noxious agents via proton and ATP driven pathways.", "output": "ATP." }, { "input": "Here, we describe light - dependent removal of antibiotics by engineering the bacterial efflux pump AcrB into a proteovesicle system.", "output": "There is no related enetity." }, { "input": "We have created a chimeric protein with the requisite proton motive force by coupling AcrB to the light - driven proton pump Delta - rhodopsin ( dR ) via a glycophorin A transmembrane domain.", "output": "There is no related enetity." }, { "input": "This creates a solar powered protein material capable of selectively capturing antibiotics from bulk solutions.", "output": "There is no related enetity." }, { "input": "Using environmental water and direct sunlight, our AcrB - dR vesicles removed almost twice as much antibiotic as the treatment standard, activated carbon.", "output": "carbon." }, { "input": "Altogether, the AcrB - dR system provides an effective means of extracting antibiotics from surface waters as well as potential antibiotic recovery through vesicle solubilization.", "output": "There is no related enetity." }, { "input": "Zinc Promotes the Death of Hypoxic Astrocytes by Upregulating Hypoxia - Induced Hypoxia - Inducible Factor - 1alpha Expression via Poly ( ADP - ribose ) Polymerase - 1.", "output": "Zinc, Poly ( ADP - ribose )." }, { "input": "AIM: Pathological release of excess zinc ions has been implicated in ischemic brain cell death.", "output": "zinc." }, { "input": "However, the underlying mechanisms remain to be elucidated.", "output": "There is no related enetity." }, { "input": "In stroke, ischemia - induced zinc release and hypoxia - inducible factor - 1 ( HIF - 1 ) accumulation concurrently occur in the ischemic tissue.", "output": "zinc." }, { "input": "The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP - 1 and HIF - 1 alpha during hypoxia, which significantly contributes to cell death during ischemia.", "output": "zinc." }, { "input": "METHODS: Primary cortical astrocytes and C8 - D1A cells were exposed to different concentrations of zinc chloride.", "output": "zinc chloride." }, { "input": "Cell death rate and protein expression of HIF - 1 and Poly ( ADP - ribose ) polymerase ( PARP ) - 1 were examined after 3 - h hypoxic treatment.", "output": "Poly ( ADP - ribose )." }, { "input": "RESULTS: Although 3 - h hypoxia or 100 mu M of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc - concentration - dependent manner.", "output": "zinc, zinc." }, { "input": "Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF - 1 alpha protein, which was further augmented by added exogenous zinc.", "output": "zinc, zinc." }, { "input": "Notably, HIF - 1 alpha knockdown blocked zinc - induced astrocyte death.", "output": "zinc." }, { "input": "Moreover, knockdown of PARP - 1, another important protein in the response of hypoxia, attenuated the overexpression of HIF - 1 alpha and reduced the cell death rate.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: Our studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF - 1 alpha via the cell fate determine factor PARP - 1 modification, which provides a novel mechanism for zinc - mediated ischemic brain injury.", "output": "zinc, zinc." }, { "input": "Type 2 innate signals stimulate fibro / adipogenic progenitors to facilitate muscle regeneration.", "output": "There is no related enetity." }, { "input": "In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process.", "output": "There is no related enetity." }, { "input": "However, the mechanisms by which innate signals might regulate stem cell functionality are unknown.", "output": "There is no related enetity." }, { "input": "Here, we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury.", "output": "There is no related enetity." }, { "input": "Muscle damage results in rapid recruitment of eosinophils, which secrete IL - 4 to activate the regenerative actions of muscle resident fibro / adipocyte progenitors ( FAPs ).", "output": "There is no related enetity." }, { "input": "In FAPs, IL - 4 / IL - 13 signaling serves as a key switch to control their fate and functions.", "output": "There is no related enetity." }, { "input": "Activation of IL - 4 / IL - 13 signaling promotes proliferation of FAPs to support myogenesis while inhibiting their differentiation into adipocytes.", "output": "There is no related enetity." }, { "input": "Surprisingly, type 2 cytokine signaling is also required in FAPs, but not in myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.", "output": "There is no related enetity." }, { "input": "Small RNA - Mediated Activation of Sugar Phosphatase mRNA Regulates Glucose Homeostasis.", "output": "Sugar, Glucose." }, { "input": "Glucose homeostasis is strictly controlled in all domains of life.", "output": "Glucose." }, { "input": "Bacteria that are unable to balance intracellular sugar levels and deal with potentially toxic phosphosugars cease growth and risk being outcompeted.", "output": "sugar, phosphosugars." }, { "input": "Here, we identify the conserved haloacid dehalogenase ( HAD ) - like enzyme YigL as the previously hypothesized phosphatase for detoxification of phosphosugars and reveal that its synthesis is activated by an Hfq - dependent small RNA in Salmonella typhimurium.", "output": "haloacid, phosphosugars." }, { "input": "We show that the glucose - 6 - P - responsive small RNA SgrS activates YigL synthesis in a translation - independent fashion by the selective stabilization of a decay intermediate of the dicistronic pldB - yigL messenger RNA ( mRNA ).", "output": "glucose." }, { "input": "Intriguingly, the major endoribonuclease RNase E, previously known to function together with small RNAs to degrade mRNA targets, is also essential for this process of mRNA activation.", "output": "There is no related enetity." }, { "input": "The exploitation of and targeted interference with regular RNA turnover described here may constitute a general route for small RNAs to rapidly activate both coding and noncoding genes.", "output": "There is no related enetity." }, { "input": "Discovery of novel orally bioavailable GPR40 agonists.", "output": "There is no related enetity." }, { "input": "The GPR40 ( FFA1 ) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency.", "output": "glucose." }, { "input": "A series of novel orally bioavailable GPR40 agonists was discovered.", "output": "There is no related enetity." }, { "input": "SAR study and structural optimization led to identification of compounds 28a and 30a as potent GPR40 agonists with superior physiochemical properties and robust in vivo efficacy in rhesus monkeys.", "output": "There is no related enetity." }, { "input": "Structure and T Cell Inhibition Properties of B7 Family Member, B7 - H3.", "output": "There is no related enetity." }, { "input": "T cell activity is controlled by a combination of antigen - dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen - independent interactions, including the recognition of the B7 family of ligands.", "output": "There is no related enetity." }, { "input": "B7 - H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis.", "output": "There is no related enetity." }, { "input": "We report the crystal structure of murine B7 - H3 at a 3 A resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain.", "output": "There is no related enetity." }, { "input": "We demonstrate that B7 - H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function.", "output": "There is no related enetity." }, { "input": "B7 - H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules.", "output": "There is no related enetity." }, { "input": "This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold.", "output": "There is no related enetity." }, { "input": "Mechanisms and Metabolic Implications of Regional Differences among Fat Depots.", "output": "There is no related enetity." }, { "input": "Fat distribution is closely linked to metabolic disease risk.", "output": "There is no related enetity." }, { "input": "Distribution varies with sex, genetic background, disease state, certain drugs and hormones, development, and aging.", "output": "There is no related enetity." }, { "input": "Preadipocyte replication and differentiation, developmental gene expression, susceptibility to apoptosis and cellular senescence, vascularity, inflammatory cell infiltration, and adipokine secretion vary among depots, as do fatty - acid handling and mechanisms of enlargement with positive - energy and loss with negative - energy balance.", "output": "fatty - acid." }, { "input": "How interdepot differences in these molecular, cellular, and pathophysiological properties are related is incompletely understood.", "output": "There is no related enetity." }, { "input": "Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question.", "output": "There is no related enetity." }, { "input": "Beyond the Sympathetic Tone: The New Brown Fat Activators.", "output": "There is no related enetity." }, { "input": "If we could avoid the side effects associated with global sympathetic activation, activating brown adipose tissue to increase thermogenesis would be a safe way to lose weight.", "output": "There is no related enetity." }, { "input": "The discovery of adrenergic - independent brown fat activators opens the prospect of developing this alternative way to efficiently and safely induce negative energy balance.", "output": "There is no related enetity." }, { "input": "Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90.", "output": "There is no related enetity." }, { "input": "Inducers of heat shock protein 70 ( Hsp70 ) commonly promote cancer cell viability whereas inhibitors of Hsp90 reduce it.", "output": "There is no related enetity." }, { "input": "The anticancer agent celastrol, interferes with signal transduction pathways involving these heat shock proteins.", "output": "celastrol." }, { "input": "The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol - induced tumor cell death.", "output": "celastrol." }, { "input": "Hsp70 siRNA loaded chitosan - TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field - flow fractionation combined with dynamic light scattering.", "output": "TPP." }, { "input": "Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan - TPP - Hsp70 siRNA particles.", "output": "TPP." }, { "input": "The results showed that silencing of Hsp70 by chitosan - TPP - Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative effects of celastrol in leukemia and glioblastoma cells.", "output": "TPP, celastrol." }, { "input": "In glioblastoma spheroids, higher concentrations of celastrol and Hsp70 siRNA in chitosan - TPP nanocarriers were necessary to induce cell death.", "output": "celastrol, TPP." }, { "input": "Two new steroidal saponins from Selaginella uncinata ( Desv. ) Spring and their protective effect against anoxia.", "output": "steroidal saponins." }, { "input": "Four steroidal saponins were isolated from the anti - anoxic fraction of the 60 % EtOH extract of Selaginella uncinata, including two new compounds, ( 3 beta, 7 beta, 12 beta, 25R ) - spirost - 5 - ene - 3, 7, 12 - triol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside ( 1 ), ( 2 alpha, 3 beta, 12 beta, 25R ) - spirost - 5 - ene - 2, 3, 12 - triol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside ( 2 ) and two known compounds, ( 3 beta, 12 beta, 25R ) - spirost - 5 - ene - 3, 12 - diol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside, ( 3 ), ( 1 alpha, 3 beta, 25R ) - spirost - 5 - ene - 2 - diol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl ( 1 --> 4 ) ] - O - beta - d - glucopyranoside ( 4 ).", "output": "steroidal saponins, EtOH, ( 3 beta , 7 beta , 12 beta , 25R ) - spirost - 5 - ene - 3 , 7 , 12 - triol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside, ( 2 alpha , 3 beta , 12 beta , 25R ) - spirost - 5 - ene - 2 , 3 , 12 - triol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside, ( 3 beta , 12 beta , 25R ) - spirost - 5 - ene - 3 , 12 - diol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl - ( 1 --> 4 ) ] - O - beta - d - glucopyranoside, ( 1 alpha , 3 beta , 25R ) - spirost - 5 - ene - 2 - diol - 3 - O - alpha - L - rhamnopyranosyl - ( 1 --> 2 ) - O - [ alpha - L - rhamnopyranosyl ( 1 --> 4 ) ] - O - beta - d - glucopyranoside." }, { "input": "The four compounds showed potent protective effect against anoxia in the anoxic PC12 cells assay, among which compounds 1 and 2 were the most active.", "output": "There is no related enetity." }, { "input": "To our knowledge, this is the first study to report the steroidal saponins in the plant S. uncinata and demonstrate their protective effect against anoxia in PC12 cell assay.", "output": "steroidal saponins." }, { "input": "Substituted methcathinones differ in transporter and receptor interactions.", "output": "methcathinones." }, { "input": "The use of synthetic methcathinones, components of \" bath salts, \" is a world - wide health concern.", "output": "methcathinones." }, { "input": "These compounds, structurally similar to methamphetamine ( METH ) and 3, 4 - methylendioxymethamphetamine ( MDMA ), cause tachycardia, hallucinations and psychosis.", "output": "methamphetamine, METH, 3 , 4 - methylendioxymethamphetamine, MDMA." }, { "input": "We hypothesized that these potentially neurotoxic and abused compounds display differences in their transporter and receptor interactions as compared to amphetamine counterparts.", "output": "amphetamine." }, { "input": "3, 4 - Methylenedioxypyrovalerone and naphyrone had high affinity for radioligand binding sites on recombinant human dopamine ( hDAT ), serotonin ( hSERT ) and norepinephrine ( hNET ) transporters, potently inhibited [ ( 3 ) H ] neurotransmitter uptake, and, like cocaine, did not induce transporter - mediated release.", "output": "3 , 4 - Methylenedioxypyrovalerone, naphyrone, dopamine, serotonin, norepinephrine, [ ( 3 ) H ], cocaine." }, { "input": "Butylone was a lower affinity uptake inhibitor.", "output": "Butylone." }, { "input": "In contrast, 4 - fluoromethcathinone, mephedrone and methylone had higher inhibitory potency at uptake compared to binding and generally induced release of preloaded [ ( 3 ) H ] neurotransmitter from hDAT, hSERT and hNET ( highest potency at hNET ), and thus are transporter substrates, similar to METH and MDMA.", "output": "4 - fluoromethcathinone, mephedrone, methylone, [ ( 3 ) H ], METH, MDMA." }, { "input": "At hNET, 4 - fluoromethcathinone was a more efficacious releaser than METH.", "output": "4 - fluoromethcathinone, METH." }, { "input": "These substituted methcathinones had low uptake inhibitory potency and low efficacy at inducing release via human vesicular monoamine transporters ( hVMAT2 ).", "output": "methcathinones, monoamine." }, { "input": "These compounds were low potency ( 1 ) h5 - HT1A receptor partial agonists, ( 2 ) h5 - HT2A receptor antagonists, ( 3 ) weak h5 - HT2C receptor antagonists.", "output": "There is no related enetity." }, { "input": "This is the first report on aspects of substituted methcathinone efficacies at serotonin ( 5 - HT ) receptors and in superfusion release assays.", "output": "methcathinone, serotonin, 5 - HT." }, { "input": "Additionally, the drugs had no affinity for dopamine receptors, and high - nanomolar to mid - micromolar affinity for hSigma1 receptors.", "output": "dopamine." }, { "input": "Thus, direct interactions with hVMAT2 and serotonin, dopamine, and hSigma1 receptors may not explain psychoactive effects.", "output": "serotonin, dopamine." }, { "input": "The primary mechanisms of action may be as inhibitors or substrates of DAT, SERT and NET.", "output": "There is no related enetity." }, { "input": "Optimization of a 1, 5 - dihydrobenzo [ b ] [ 1, 4 ] diazepine - 2, 4 - dione series of HIV capsid assembly inhibitors 1: Addressing configurational instability through scaffold modification.", "output": "1 , 5 - dihydrobenzo [ b ] [ 1 , 4 ] diazepine - 2 , 4 - dione." }, { "input": "The optimization of a 1, 5 - dihydrobenzo [ b ] [ 1, 4 ] diazepine - 2, 4 - dione series of inhibitors of HIV - 1 capsid assembly that possess a labile stereocenter at C3 is described.", "output": "1 , 5 - dihydrobenzo [ b ] [ 1 , 4 ] diazepine - 2 , 4 - dione." }, { "input": "Quaternization of the C3 position of compound 1 in order to prevent racemization gave compound 2, which was inactive in our capsid disassembly assay.", "output": "There is no related enetity." }, { "input": "A likely explanation for this finding was revealed by in silico analysis predicting a dramatic increase in energy of the bioactive conformation upon quaternization of the C3 position.", "output": "There is no related enetity." }, { "input": "Replacement of the C3 of the diazepine ring with a nitrogen atom to give the 1, 5 - dihydro - benzo [ f ] [ 1, 3, 5 ] triazepine - 2, 4 - dione analog 4 was well tolerated.", "output": "diazepine, 1 , 5 - dihydro - benzo [ f ] [ 1 , 3 , 5 ] triazepine - 2 , 4 - dione." }, { "input": "Introduction of a rigid spirocyclic system at the C3 position gave configurationally stable 1, 5 - dihydrobenzo [ b ] [ 1, 4 ] diazepine - 2, 4 - dione analog 5, which was able to access the bioactive conformation without a severe energetic penalty and inhibit capsid assembly.", "output": "1 , 5 - dihydrobenzo [ b ] [ 1 , 4 ] diazepine - 2 , 4 - dione." }, { "input": "Preliminary structure - activity relationships ( SAR ) and X - ray crystallographic data show that knowledge from the 1, 5 - dihydrobenzo [ b ] [ 1, 4 ] diazepine - 2, 4 - dione series of inhibitors of HIV - 1 capsid assembly can be transferred to these new scaffolds.", "output": "1 , 5 - dihydrobenzo [ b ] [ 1 , 4 ] diazepine - 2 , 4 - dione." }, { "input": "Variation in the dorsal gradient distribution is a source for modified scaling of germ layers in Drosophila.", "output": "There is no related enetity." }, { "input": "Specification of germ layers along the dorsoventral axis by morphogenetic gradients is an ideal model to study scaling properties of gradients and cell fate changes during evolution.", "output": "There is no related enetity." }, { "input": "Classical anatomical studies in divergent insects ( e. g., flies and grasshoppers ) revealed that the neuroectodermal size is conserved and originates similar numbers of neuroblasts of homologous identity [ 1 - 3 ].", "output": "There is no related enetity." }, { "input": "In contrast, mesodermal domains vary significantly in closely related Drosophila species [ 4 ].", "output": "There is no related enetity." }, { "input": "To further investigate the underlying mechanisms of scaling of germ layers across Drosophila species, we quantified the Dorsal ( Dl ) / NF - kappa B gradient, the main morphogenetic gradient that initiates separation of the mesoderm, neuroectoderm, and ectoderm [ 5 - 7 ].", "output": "There is no related enetity." }, { "input": "We discovered a variable range of Toll activation across species and found that Dl activates mesodermal genes at the same threshold levels in melanogaster sibling species.", "output": "There is no related enetity." }, { "input": "We also show that the Dl gradient distribution can be modulated by nuclear size and packing densities.", "output": "There is no related enetity." }, { "input": "We propose that variation in mesodermal size occurs at a fast evolutionary rate and is an important mechanism to define the ventral boundary of the neuroectoderm.", "output": "There is no related enetity." }, { "input": "Seasonal variation in the toxicological properties of size - segregated indoor and outdoor air particulate matter.", "output": "There is no related enetity." }, { "input": "Ambient air particulate matter ( PM ) as well as microbial contaminants in the indoor air are known to cause severe adverse health effects.", "output": "There is no related enetity." }, { "input": "It has been shown that there is a clear seasonal variation in the potency of outdoor air particles to evoke inflammation and cytotoxicity.", "output": "There is no related enetity." }, { "input": "However, the role of outdoor sources in the indoor air quality, especially on its toxicological properties, remains largely unknown.", "output": "There is no related enetity." }, { "input": "In this study, we collected size segregated ( PM10 - 2. 5, PM2. 5 - 0. 2 and PM0. 2 ) particulate samples with a high volume cascade impactor ( HVCI ) on polyurethane foam and fluoropore membrane filters.", "output": "polyurethane." }, { "input": "The samples were collected during four different seasons simultaneously from indoor and outdoor air.", "output": "There is no related enetity." }, { "input": "Thereafter, the samples were weighed and extracted with methanol from the filters before undergoing toxicological analyses.", "output": "methanol." }, { "input": "Mouse macrophages ( RAW264. 7 ) were exposed to particulate sample doses of 50, 150 and 300 mu g / ml for 24h.", "output": "There is no related enetity." }, { "input": "Thereafter, the levels of the proinflammatory cytokine ( TNF - alpha ), NO - production, cytotoxicity ( MTT - test ) and changes in the cell cycle ( SubG1, G1, S and G2 / M phases ) were investigated.", "output": "NO, MTT." }, { "input": "PM10 - 2. 5 particles evoked the highest inflammatory and cytotoxic responses.", "output": "There is no related enetity." }, { "input": "Instead, PM2. 5 - 0. 2 samples exerted the greatest effect on apoptotic activity in the macrophages.", "output": "There is no related enetity." }, { "input": "With respect to the outdoor air samples, particles collected during warm seasons had a stronger potency to induce inflammatory and cytotoxic responses, whereas no such clear effect was seen with the corresponding indoor air samples.", "output": "There is no related enetity." }, { "input": "Outdoor air samples were associated with higher inflammatory potential, whereas indoor air samples had overall higher cytotoxic properties.", "output": "There is no related enetity." }, { "input": "This indicates that the outdoor air has a limited influence on the indoor air quality in a modern house.", "output": "There is no related enetity." }, { "input": "Thus, the indoor sources dominate the toxicological responses obtained from samples collected inside house.", "output": "There is no related enetity." }, { "input": "( 1 ) H NMR - based metabonomics study on the toxicity alleviation effect of other traditional Chinese medicines in Niuhuang Jiedu tablet to realgar ( As2S2 ).", "output": "( 1 ) H." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Niuhuang Jiedu Tablet ( NJT ) is an effective prescription of traditional Chinese medicine ( TCM ) used in treating acute tonsillitis, pharyngitis, periodontitis and mouth ulcer.", "output": "There is no related enetity." }, { "input": "NJT is prepared from Xionghuang ( Realgar, As2S2 ), Rengong Niuhuang ( Bovis Calculus Artificialis ), Bingpian ( Borneolum Synthcticum ), Shigao ( Gypsum Fibrosum ), Dahuang ( Rhei Radix et Rhizoma ), Huangqin ( Scutellariae Radix ), Jiegeng ( Platycodonis Radix ) and Gancao ( Glycyrrhizae Radix et Rhizoma ).", "output": "There is no related enetity." }, { "input": "In the prescription, significant level of realgar ( As2S2 ) as a potentially toxic element is contained.", "output": "realgar, As2S2." }, { "input": "AIM OF THE STUDY: In this study, ( 1 ) H NMR - based metabonomics approach has been used to investigate the toxicity of realgar ( As2S2 ) after being counterbalanced by other TCMs in NJT.", "output": "( 1 ) H, realgar, As2S2." }, { "input": "MATERIALS AND METHODS: Male Wistar rats were divided into five groups: control, group I ( treated with Realgar ), group II ( treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma ), group III ( treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum and Gypsum Fibrosum ) and group IV ( treated with Realgar, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma ).", "output": "Realgar, Realgar, Realgar, Realgar." }, { "input": "Based on ( 1 ) H - NMR spectra of urine and serum from rats, PCA and PLS - DA were performed to identify different metabolic profiles.", "output": "( 1 ) H." }, { "input": "Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed.", "output": "There is no related enetity." }, { "input": "RESULTS: PLS - DA scores plots demonstrated that the cluster of group I was separated from that of control rats, while group II was located close to control rats, indicating that metabolic profiles of group II were restored toward those of control rats.", "output": "There is no related enetity." }, { "input": "The metabolic profiles of group III were similar to those of group I, while the metabolic profiles of group II were almost in line with those of group II.", "output": "There is no related enetity." }, { "input": "Statistics results were confirmed by the histopathological examination and biochemical assay.", "output": "There is no related enetity." }, { "input": "CONCLUSION: Our results indicated that it was more secure and much less toxic for counterbalanced realgar ( As2S2 ) in NJT.", "output": "realgar, As2S2." }, { "input": "The effective material bases of toxicity alleviation to realgar ( As2S2 ) were Dahuang ( Rhei Radix et Rhizoma ), Huangqin ( Scutellariae Radix ), Jiegeng ( Platycodonis Radix ) and Gancao ( Glycyrrhizae Radix et Rhizoma ), which regulated energy metabolism, choline metabolism, amino acid metabolism and gut flora disorder affected by realgar ( As2S2 ) exposure.", "output": "realgar, As2S2, choline, amino acid, realgar, As2S2." }, { "input": "Systematic characterization of structure - activity relationships and ADMET compliance: a case study.", "output": "There is no related enetity." }, { "input": "Traditionally, activity landscape modeling has been focused on analyzing SAR, despite the fact that lead optimization in drug discovery involves concurrent enhancements of activity and ADMET properties of leads.", "output": "There is no related enetity." }, { "input": "As a case study, we discuss the systematic analysis of activity landscapes, incorporating ADMET considerations, using a dataset of 166 compounds screened for kappa - opioid receptor activity.", "output": "There is no related enetity." }, { "input": "Pairwise MACCS / Tanimoto structure similarities, property similarities utilizing 33 ADMET descriptors and a 35 - dimensional ' violation bit vector ' representing drug - likeness are analyzed.", "output": "There is no related enetity." }, { "input": "We address the question about the range of ADMET property violations that arise from structural changes, subtle and significant.", "output": "There is no related enetity." }, { "input": "Pairs of compounds are identified bearing identical, comparable and significantly different drug - likeness in the three informative regions of structure - activity landscapes.", "output": "There is no related enetity." }, { "input": "Unraveling Hidden Regulatory Sites in Structurally Homologous Metalloproteases.", "output": "There is no related enetity." }, { "input": "Monitoring enzymatic activity in vivo of individual homologous enzymes such as the matrix metalloproteinases ( MMPs ) by antagonist molecules is highly desired for defining physiological and pathophysiological pathways.", "output": "There is no related enetity." }, { "input": "However, the rational design of antagonists targeting enzyme catalytic moieties specific to one of the homologous enzymes often appears to be an extremely difficult task.", "output": "There is no related enetity." }, { "input": "This is mainly due to the high structural homology at the enzyme active sites shared by members of the protein family.", "output": "There is no related enetity." }, { "input": "Accordingly, controlling enzymatic activity via alternative allosteric sites has become an attractive proposition for drug design targeting individual homologous enzymes.", "output": "There is no related enetity." }, { "input": "Yet, the challenge remains to identify such regulatory alternative sites that are often hidden and scattered over different locations on the protein ' s surface.", "output": "There is no related enetity." }, { "input": "We have designed branched amphiphilic molecules exhibiting specific inhibitory activity towards individual members of the MMP family.", "output": "There is no related enetity." }, { "input": "These amphiphilic isomers share the same chemical nature, providing versatile nonspecific binding reactivity that allows to probe hidden regulatory residues on a given protein surface.", "output": "There is no related enetity." }, { "input": "Using the advantage provided by amphiphilic ligands, here we explore a new approach for determining hidden regulatory sites.", "output": "There is no related enetity." }, { "input": "This approach includes diverse experimental analysis, such as structural spectroscopic analyses, NMR, and protein crystallography combined with computational prediction of effector binding sites.", "output": "There is no related enetity." }, { "input": "We demonstrate how our approach works by analyzing members of the MMP family that possess a unique set of such sites.", "output": "There is no related enetity." }, { "input": "Our work provides a proof of principle for using ligand effectors to unravel hidden regulatory sites specific to members of the structurally homologous MMP family.", "output": "There is no related enetity." }, { "input": "This approach may be exploited for the design of novel molecular effectors and therapeutic agents affecting protein catalytic function via interactions with structure - specific regulatory sites.", "output": "There is no related enetity." }, { "input": "Prior oral exposure to environmental immunosuppressive chemicals methoxychlor, parathion, or piperonyl butoxide aggravates allergic airway inflammation in NC / Nga mice.", "output": "methoxychlor, parathion, piperonyl butoxide." }, { "input": "BACKGROUND: Immunosuppressive environmental chemicals may increase the potency of allergens and thereby play a role in the development of respiratory tract allergies, such as allergic rhinitis and asthma.", "output": "There is no related enetity." }, { "input": "OBJECTIVES: We investigated the association between environmental immunosuppressive chemicals and the allergic airway inflammation development.", "output": "There is no related enetity." }, { "input": "METHODS: We used a mouse model of ovalbumin ( OVA ) - induced allergic airway inflammation.", "output": "There is no related enetity." }, { "input": "NC / Nga mice were exposed orally to pesticides parathion ( an organophosphate compound ) or methoxychlor ( an organochlorine compound ), or to an insecticide synergist piperonyl butoxide, prior to OVA intraperitoneal sensitization and inhalation challenge.", "output": "parathion, organophosphate, methoxychlor, organochlorine, piperonyl butoxide." }, { "input": "We assessed serum IgE levels, B - cell counts, cytokine production, IgE production in hilar lymph nodes, eosinophil counts, chemokine levels in bronchoalveolar lavage fluid, and cytokine gene expression in the lung.", "output": "There is no related enetity." }, { "input": "RESULTS: Exposure to environmental immunosuppressive chemicals markedly increased serum IgE - IgE - positive B - cells, IgE and cytokines in lymph nodes - eosinophils and chemokines in BALF - IL - 10a and IL - 17 in the lung.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: Allergic airway inflammation can be aggravated by prior exposure to immunosuppressive environmental chemicals.", "output": "There is no related enetity." }, { "input": "Aminopropylindenes derived from Grundmann ' s ketone as a novel chemotype of oxidosqualene cyclase inhibitors.", "output": "Aminopropylindenes, Grundmann ' s ketone." }, { "input": "A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase ( 1 ) ( OSC ) - mediated cyclization of 2, 3 - oxidosqualen to lanosterol was prepared from Grundmann ' s ketone.", "output": "aminopropylindenes, oxidosqualene, 2 , 3 - oxidosqualen, lanosterol, Grundmann ' s ketone." }, { "input": "Screening on OSCs from five different organisms revealed interesting activities and selectivities of some of the compounds.", "output": "There is no related enetity." }, { "input": "A N, N - dimethylaminopropyl derivative showed promising inhibition of Trypanosoma cruzi OSC in combination with low cytotoxicity, and showed significant reduction of cholesterol biosynthesis in a human cell line.", "output": "N , N - dimethylaminopropyl, cholesterol." }, { "input": "Pleiotropic effect of histamine H4 receptor modulation in the central nervous system.", "output": "histamine." }, { "input": "The histamine H4 receptor ( H4R ) is expressed primarily on cells involved in inflammation and immune responses.", "output": "histamine." }, { "input": "Recently, it has been reported the functional expression of H4R within neurons of the central nervous system, but their role has been poorly understood.", "output": "There is no related enetity." }, { "input": "The present study aimed to elucidate the physiopathological role of cerebral H4R in animal models by the intracerebroventricular administration of the H4R agonist VUF 8430 ( 20 - 40 mu g per mouse ).", "output": "VUF 8430." }, { "input": "Selectivity of results was confirmed by the prevention of the effects produced by the H4R antagonist JNJ 10191584 ( 3 - 9 mg / kg p. o. ).", "output": "JNJ 10191584." }, { "input": "Neuronal H4R activation induced acute thermal antinociception, indicating that neuronal histamine H4R might be involved in the production of antinociception in the absence of an inflammatory process.", "output": "histamine." }, { "input": "An anxiolytic - like effect of intensity comparable to that exerted by diazepam, used as reference drug, was produced in the light - dark box test.", "output": "diazepam." }, { "input": "VUF 8430 reversed the scopolamine - induced amnesia in the passive avoidance test and showed anorexant activity in food deprived mice.", "output": "VUF 8430, scopolamine." }, { "input": "Conversely, the H4R activation did not modify the immobility time in the tail suspension test.", "output": "There is no related enetity." }, { "input": "Rotarod performance test was employed to demonstrate that the effects observed following the administration of VUF 8430 and JNJ 10191584 were not due to impaired motor function of animals.", "output": "VUF 8430, JNJ 10191584." }, { "input": "Furthermore, both compounds did not alter spontaneous mobility and exploratory activity in the hole board test.", "output": "There is no related enetity." }, { "input": "These results show the antinociceptive, antiamnesic, anxiolytic and anorexant effects induced by neuronal H4R agonism, suggesting that H4 modulators may have broader utility further the control of inflammatory and immune processes.", "output": "There is no related enetity." }, { "input": "Lesions of the dorsomedial striatum impair formation of attentional set in rats.", "output": "There is no related enetity." }, { "input": "Behavioural flexibility refers to the ability to rapidly adapt to novel situations and it has been suggested that the frontal lobe and basal ganglia are implicated in various components of adjusting to changes in environmental contingencies.", "output": "There is no related enetity." }, { "input": "Behavioural flexibility can be assessed using attentional set - shifting tasks, in which performance is impaired after damage to the prefrontal cortex.", "output": "There is no related enetity." }, { "input": "The present study explores the downstream contribution of the prefrontal projection zone in the dorsomedial striatum ( DMS ) to attentional set shifting.", "output": "There is no related enetity." }, { "input": "Rats were tested in two set - shifting tasks following quinolinic acid injections bilaterally into the DMS.", "output": "quinolinic acid." }, { "input": "When tested in a rodent version of the set - shifting task, rats with a DMS lesion displayed a greater number of errors during the reversal stages of the task than sham lesion controls but the nature of the errors did not differ between the two groups.", "output": "There is no related enetity." }, { "input": "Interestingly, when the rats were tested in a modified version of the set - shifting task, directly designed for measuring the formation of an attentional set, sham lesion controls displayed a pronounced shift - cost, evident of successful set - formation.", "output": "There is no related enetity." }, { "input": "In contrast, rats with DMS lesions failed to form an attentional set, showing no performance cost when a shift of attention was required.", "output": "There is no related enetity." }, { "input": "These results support previous reports of the importance of the DMS in behavioural flexibility but also suggest that this region is vital for the formation of set, possibly by extrapolating different perceptions into a unified representation of a dimension.", "output": "There is no related enetity." }, { "input": "Poor - prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions.", "output": "There is no related enetity." }, { "input": "Colon cancer is a clinically diverse disease.", "output": "There is no related enetity." }, { "input": "This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents.", "output": "There is no related enetity." }, { "input": "More insight into the biological diversity of colon cancers, especially in relation to clinical features, is therefore needed.", "output": "There is no related enetity." }, { "input": "We demonstrate, using an unsupervised classification strategy involving over 1, 100 individuals with colon cancer, that three main molecularly distinct subtypes can be recognized.", "output": "There is no related enetity." }, { "input": "Two subtypes have been previously identified and are well characterized ( chromosomal - instable and microsatellite - instable cancers ).", "output": "There is no related enetity." }, { "input": "The third subtype is largely microsatellite stable and contains relatively more CpG island methylator phenotype - positive carcinomas but cannot be identified on the basis of characteristic mutations.", "output": "CpG." }, { "input": "We provide evidence that this subtype relates to sessile - serrated adenomas, which show highly similar gene expression profiles, including upregulation of genes involved in matrix remodeling and epithelial - mesenchymal transition.", "output": "There is no related enetity." }, { "input": "The identification of this subtype is crucial, as it has a very unfavorable prognosis and, moreover, is refractory to epidermal growth factor receptor - targeted therapy.", "output": "There is no related enetity." }, { "input": "Kinetics and mechanism of oxygen reduction in a protic ionic liquid.", "output": "oxygen." }, { "input": "The oxygen reduction reaction ( ORR ) has been studied at Pt surfaces in the protic ionic liquid diethylmethylammonium trifluoromethanesulfonate.", "output": "oxygen, diethylmethylammonium trifluoromethanesulfonate." }, { "input": "Water content measurements suggested that the ORR proceeded in the ionic liquid predominantly via a 4 - electron reduction to water.", "output": "There is no related enetity." }, { "input": "A mechanistic analysis using rotating ring - disk electrode ( RRDE ) voltammetry confirmed that negligible amounts of hydrogen peroxide were formed during the ORR.", "output": "hydrogen peroxide." }, { "input": "A kinetic analysis of the ORR was performed using rotating disk electrode ( RDE ) voltammetry and the importance of correcting for ohmic ( iR ) drop prior to performing kinetic measurements in the ionic liquid is demonstrated.", "output": "There is no related enetity." }, { "input": "A Tafel analysis of the RDE voltammetry data revealed a change in the ORR Tafel slope from 70 mV per decade at low ORR overpotentials to 117 mV per decade at high overpotentials, and the reason for this change is discussed.", "output": "There is no related enetity." }, { "input": "The change in the Tafel slope for the ORR with increasing overpotential meant that the exchange current density for the ORR varied from 0. 007 nA cm ( - 2 ) to 10 nA cm ( - 2 ), depending on the applied potential.", "output": "There is no related enetity." }, { "input": "Finally, the implications of these results for the development of protic ionic liquid fuel cells are discussed.", "output": "There is no related enetity." }, { "input": "Agomelatine: An antidepressant with new potent hepatoprotective effects on paracetamol - induced liver damage in rats.", "output": "Agomelatine, paracetamol." }, { "input": "Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage.", "output": "Paracetamol." }, { "input": "Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does.", "output": "Agomelatine, melatonin, melatonin." }, { "input": "In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol - induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines.", "output": "agomelatine, paracetamol, agomelatine." }, { "input": "A total of 42 rats were divided into 7 groups as each composed of 6 rats: ( 1 ) intact, ( 2 ) 40 mg / kg agomelatine, ( 3 ) 140 mg / kg N - acetylcysteine ( NAC ), ( 4 ) 2 g / kg paracetamol, ( 5 ) 2 g / kg paracetamol + 140 mg / kg NAC, ( 6 ) 2 g / kg paracetamol + 20 mg / kg agomelatine, and ( 7 ) 2 g / kg paracetamol + 40 mg / kg agomelatine groups.", "output": "agomelatine, N - acetylcysteine, NAC, paracetamol, paracetamol, NAC, paracetamol, agomelatine, paracetamol, agomelatine." }, { "input": "Paracetamol - induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically.", "output": "Paracetamol." }, { "input": "There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor - alpha ( TNF - alpha ) and interleukin - 6 ( IL - 6 ) and 8 - iso - prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol.", "output": "aspartate, alanine, 8 - iso - prostane, superoxide, glutathione, paracetamol." }, { "input": "Administration of agomelatine and NAC separately reversed these changes significantly.", "output": "agomelatine, NAC." }, { "input": "In conclusion, agomelatine administration protects liver cells from paracetamol - induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF - alpha and IL - 6.", "output": "agomelatine, paracetamol." }, { "input": "The influence of thermal degradation on the electrodeposition of aluminium from an air - and water - stable ionic liquid.", "output": "aluminium." }, { "input": "Aluminium electrodeposition is demonstrated from a thermally degraded ionic liquid solution.", "output": "Aluminium." }, { "input": "NMR and voltammetric analyses established that Al ( 3 + ) reduction was remarkably similar to that in non - degraded IL solutions suggesting that the electroactive metal - containing species was unaffected by heat treatment.", "output": "Al ( 3 + )." }, { "input": "Electron microscopy revealed a significant grain refinement of the deposited metal.", "output": "There is no related enetity." }, { "input": "Combined toxicity of ferroferric oxide nanoparticles and arsenic to the ciliated protozoa Tetrahymena Pyriformis.", "output": "ferroferric oxide, arsenic." }, { "input": "Fe3O4 nanoparticles ( NPs ) have a high affinity for arsenic.", "output": "Fe3O4, arsenic." }, { "input": "As a result of this association, Fe3O4 NPs loaded with high concentration of arsenic can enter into organisms and produce locally high concentrations of arsenic, which may lead to some unexpected toxicity to aquatic organisms.", "output": "Fe3O4, arsenic, arsenic." }, { "input": "The objectives of this research were to investigate the toxic effect of Fe3O4 NPs in combination with As ( V ).", "output": "Fe3O4, As ( V )." }, { "input": "Cultured Tetrahymena pyriformis was chosen as a research model organism to evaluate the toxic effects of the combined agents.", "output": "There is no related enetity." }, { "input": "The results showed that after 24h of As ( V ) exposure, the median effective concentration of As ( V ) to T. pyriformis was 1. 29mg / L.", "output": "As ( V ), As ( V )." }, { "input": "Fe3O4 NPs alone were not only non - toxic, but actually promoted the growth of T. pyriformis at the experimental doses.", "output": "Fe3O4." }, { "input": "After 24h exposure, the cell number increased by 32. 2 % at an exposure level of 3mg / L Fe3O4 NPs.", "output": "Fe3O4." }, { "input": "After 24h exposure to 1. 0mg / L As ( V ), the survival rate increased from 60. 5 % in the absence of Fe3O4 NPs to 73. 8 % and 83. 8 % in the presence of 13mg / L and 19mg / L Fe3O4 NPs, respectively.", "output": "As ( V ), Fe3O4, Fe3O4." }, { "input": "However, after 30h, the combined toxic effect of As ( V ) and Fe3O4 NPs on T. pyriformis was significantly enhanced and the survival rates for co - exposure to 1. 5mg / L As ( V ) and 13mg / L Fe3O4 NPs decreased from 92. 3 % after 18h to 45. 3 % after 30h.", "output": "As ( V ), Fe3O4, As ( V ), Fe3O4." }, { "input": "After 18h of exposure to Fe3O4 NPs alone, the intracellular ROS levels were markedly increased and achieved steady state.", "output": "Fe3O4." }, { "input": "Compared with the control group, the intracellular ROS levels were significantly increased ( 2. 56 - fold ) by the combination of 19mg / L Fe3O4 NPs and 1. 0mg / L As ( V ).", "output": "Fe3O4, As ( V )." }, { "input": "Accumulation of As ( V ) in T. pyriformis led to an increase in trivalent arsenics as a result of the saturation of the cellular arsenic methylation capability or / and redox reactions.", "output": "As ( V ), arsenics, arsenic." }, { "input": "These exposures also resulted in an imbalance between oxidants and antioxidants, resulting in oxidative damage and cell death.", "output": "There is no related enetity." }, { "input": "Transcriptomic analysis of cultured whale skin cells exposed to hexavalent chromium [ Cr ( VI ) ].", "output": "hexavalent chromium, Cr ( VI )." }, { "input": "Hexavalent chromium Cr ( VI ) is known to produce cytotoxic effects in humans and is a highly toxic environmental contaminant.", "output": "Hexavalent chromium, Cr ( VI )." }, { "input": "Interestingly, it has been shown that free ranging sperm whales ( Phyester macrocephalus ) may have exceedingly high levels of Cr in their skin.", "output": "Cr." }, { "input": "Also, it has been demonstrated that skin cells from whales appear more resistant to both cytotoxicity and clastogenicity upon Cr exposure compared to human cells.", "output": "Cr." }, { "input": "However, the molecular genetic mechanisms employed in whale skin cells that might lead to Cr tolerance are unknown.", "output": "Cr." }, { "input": "In an effort to understand the underlying mechanisms of Cr ( VI ) tolerance and to illuminate global gene expression patterns modulated by Cr, we exposed whale skin cells in culture to varying levels of Cr ( VI ) ( i. e., 0. 0, 0. 5, 1. 0 and 5. 0 mu g / cm ( 2 ) ) followed by short read ( 100bp ) next generation RNA sequencing ( RNA - seq ).", "output": "Cr ( VI ), Cr, Cr ( VI )." }, { "input": "RNA - seq reads from all exposures ( =~ 280 million reads ) were pooled to generate a de novo reference transcriptome assembly.", "output": "There is no related enetity." }, { "input": "The resulting whale reference assembly had 11K contigs and an N50 of 2954bp.", "output": "There is no related enetity." }, { "input": "Using the reads from each dose ( 0. 0, 0. 5, 1. 0 and 5. 0 mu g / cm ( 2 ) ) we performed RNA - seq based gene expression analysis that identified 35 up - regulated genes and 19 down - regulated genes.", "output": "There is no related enetity." }, { "input": "The experimental results suggest that low dose exposure to Cr ( 1. 0 mu g / cm ( 2 ) ) serves to induce up - regulation of oxidative stress response genes, DNA repair genes and cell cycle regulator genes.", "output": "Cr." }, { "input": "However, at higher doses ( 5. 0 mu g / cm ( 2 ) ) the DNA repair genes appeared down - regulated while other genes that were induced suggest the initiation of cytotoxicity.", "output": "There is no related enetity." }, { "input": "The set of genes identified that show regulatory modulation at different Cr doses provide specific candidates for further studies aimed at determination of how whales exhibit resistance to Cr toxicity and what role ( s ) reactive oxygen species ( ROS ) may play in this process.", "output": "Cr, Cr, oxygen." }, { "input": "miR - 194 suppresses metastasis of non - small cell lung cancer through regulating expression of BMP1 and p27 ( kip1. )", "output": "There is no related enetity." }, { "input": "MicroRNAs ( miRNAs ) are increasingly implicated in regulating tumor malignance through their capacity to coordinately repress expression of tumor - related genes.", "output": "There is no related enetity." }, { "input": "Here, we show that overexpression of miR - 194 in lung cancer cell lines, results in suppressing metastasis of lung cancer cells, while inhibiting its expression through ' miRNA sponge ' promotes the cancer cells to metastasize.", "output": "There is no related enetity." }, { "input": "miR - 194 expression is also found to be in strongly negative association with metastasis in clinical specimens of non - small cell lung cancer.", "output": "There is no related enetity." }, { "input": "We demonstrate that miR - 194 directly targets both BMP1 and p27 ( kip1 ).", "output": "There is no related enetity." }, { "input": "The resulting downregulation of BMP1 leads to suppression of TGF beta activity and, thus, to downregulation of the expression of key oncogenic genes ( matrix metalloproteinases MMP2 and MMP9 ).", "output": "There is no related enetity." }, { "input": "This leads, in turn, to decreased tumor invasion.", "output": "There is no related enetity." }, { "input": "In addition, the miRNA - 194 - induced suppression of p27 ( kip1 ) activates the RhoA pathway, producing enhanced development of actin stress fibers and impaired migration of cancer cells.", "output": "There is no related enetity." }, { "input": "These findings reveal two structurally independent but functionally linked branches of the regulatory and signaling pathway that together provide a bridge between the metastasis - depressing miRNA and the key genes that govern the malignancy of lung cancers. Oncogene advance online publication, 15 April 2013; doi: 10. 1038 / onc. 2013. 108.", "output": "There is no related enetity." }, { "input": "The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation.", "output": "There is no related enetity." }, { "input": "Stem cell differentiation depends on transcriptional activation driven by lineage - specific regulators as well as changes in chromatin organization.", "output": "There is no related enetity." }, { "input": "However, the coordination of these events is poorly understood.", "output": "There is no related enetity." }, { "input": "Here, we show that T - box proteins team up with chromatin modifying enzymes to drive the expression of the key lineage regulator, Eomes during endodermal differentiation of embryonic stem ( ES ) cells.", "output": "There is no related enetity." }, { "input": "The Eomes locus is maintained in a transcriptionally poised configuration in ES cells.", "output": "There is no related enetity." }, { "input": "During early differentiation steps, the ES cell factor Tbx3 associates with the histone demethylase Jmjd3 at the enhancer element of the Eomes locus to allow enhancer - promoter interactions.", "output": "There is no related enetity." }, { "input": "This spatial reorganization of the chromatin primes the cells to respond to Activin signalling, which promotes the binding of Jmjd3 and Eomes to its own bivalent promoter region to further stimulate Eomes expression in a positive feedback loop.", "output": "There is no related enetity." }, { "input": "In addition, Eomes activates a transcriptional network of core regulators of endodermal differentiation.", "output": "There is no related enetity." }, { "input": "Our results demonstrate that Jmjd3 sequentially associates with two T - box factors, Tbx3 and Eomes to drive stem cell differentiation towards the definitive endoderm lineage.", "output": "There is no related enetity." }, { "input": "Synthesis of 3 - O - propargylated betulinic acid and its 1, 2, 3 - triazoles as potential apoptotic agents.", "output": "3 - O - propargylated betulinic acid and its 1 , 2 , 3 - triazoles." }, { "input": "Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired.", "output": "There is no related enetity." }, { "input": "Chemical transformation studies carried out on betulinic acid, through concise 1, 2, 3 - triazole synthesis via click chemistry approach at C - 3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines.", "output": "betulinic acid, 1 , 2 , 3 - triazole, C." }, { "input": "Most of the derivatives have shown higher cytotoxic profiles than the parent molecule.", "output": "There is no related enetity." }, { "input": "Two compounds i. e. 3 { 1N ( 2 - cyanophenyl ) - 1H - 1, 2, 3 - triazol - 4yl } methyloxy betulinic acid ( 7 ) and 3 { 1N ( 5 - hydroxy - naphth - 1yl ) - 1H - 1, 2, 3 - triazol - 4yl } methyloxy betulinic acid ( 13 ) displayed impressive IC50 values ( 2. 5 and 3. 5 mu M respectively ) against leukemia cell line HL - 60 ( 5 - 7 - fold higher potency than betulinic acid ).", "output": "3 { 1N ( 2 - cyanophenyl ) - 1H - 1 , 2 , 3 - triazol - 4yl } methyloxy betulinic acid, 3 { 1N ( 5 - hydroxy - naphth - 1yl ) - 1H - 1 , 2 , 3 - triazol - 4yl } methyloxy betulinic acid." }, { "input": "As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated.", "output": "There is no related enetity." }, { "input": "Synthesis and in vitro antiproliferative effect of novel quinoline - based potential anticancer agents.", "output": "quinoline." }, { "input": "Several derivatives with a quinoline scaffold and a flexible, semi - flexible or rigid side chains at position 8 of the quinoline ring were synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA - MB231.", "output": "quinoline, quinoline." }, { "input": "The HT29 cell line was more refractory to the cytotoxic activity of some compounds, meanwhile all the quinoline derivatives except one displayed high to moderate activity against MDA - MB231 with IC50 values ranging between 4. 6 and 48. 2 mu M.", "output": "quinoline." }, { "input": "The most active derivative in this study against both tested cell lines was the Schiff ' s base 4e with IC50 of 4. 7 and 4. 6 mu M against HT29 and MDA - MB231, respectively.", "output": "Schiff ' s base." }, { "input": "Gene identification and comparative molecular modeling of a Trypanosoma rangeli major surface protease.", "output": "There is no related enetity." }, { "input": "Trypanosoma rangeli is a hemoflagellate parasite which is able to infect humans.", "output": "There is no related enetity." }, { "input": "Distinct from Trypanosoma cruzi, the causative agent of Chagas disease, T. rangeli is non - pathogenic to the vertebrate host.", "output": "There is no related enetity." }, { "input": "The manner by which the T. rangeli interacts with the host is still unknown, but it certainly depends on the surface molecules.", "output": "There is no related enetity." }, { "input": "Major surface proteins ( MSP ) are GPI - anchored, zinc - dependent metalloproteases present in the surface of all trypanosomatids studied so far, which are implicated as virulence factors in pathogenic trypanosomatids, such as Leishmania spp and T. cruzi.", "output": "There is no related enetity." }, { "input": "The aims of this work were to generate the complete sequence of a T. rangeli MSP ( TrMSP ) gene and to determine the 3D - structure of the predicted protein by homology modeling.", "output": "There is no related enetity." }, { "input": "The plasmid bearing a complete copy of a TrMSP gene was completely sequenced and the predicted protein was modeled using Modeller software.", "output": "There is no related enetity." }, { "input": "Results indicate that TrMSP open reading frame ( ORF ) codes for a predicted 588 amino acid protein and shows all elements required for its posttranslational processing.", "output": "amino acid." }, { "input": "Multiple sequence alignment of TrMSP with other trypanosomatids ' MSPs showed an extensive conservation of the N - terminal and central regions and a more divergent C - terminal region.", "output": "N, C." }, { "input": "Leishmania major MSP ( LmMSP ), which had its crystal structure previously determined, has an overall 35 % identity with TrMSP.", "output": "There is no related enetity." }, { "input": "This identity allowed the comparative molecular modeling of TrMSP, which demonstrated a high degree of structural conservation between MSPs from other trypanosomatids ( TrypMSPs ).", "output": "There is no related enetity." }, { "input": "All modeled MSPs have a conserved folding pattern, apart from structural divergences in the C - domain and discrete differences of charge and topology in the catalytic cleft, and present the same geometry of the canonical HEXXH zinc - binding motif.", "output": "zinc." }, { "input": "The determination of surface charges of the molecules revealed that TrMSP is a predominantly positive protein, whereas LmMSP and Trypanosoma cruzi MSP ( TcMSP ) are negative proteins, suggesting that substrates recognized by TcMSP and LmMSP could not interact with TrMSP.", "output": "There is no related enetity." }, { "input": "Moreover, the comparison between TrMSP and TcMSP protein sequences has revealed 45 non - neutral amino acid substitutions, which can be further assessed through protein engineering.", "output": "amino acid." }, { "input": "The characteristics of TrMSP could explain, at least in part, the lack of pathogenicity of T. rangeli to humans and point to the necessity of identifying the biological targets of this enzyme.", "output": "There is no related enetity." }, { "input": "Long single ZnO nanowire for logic and memory circuits: NOT, NAND, NOR gate, and SRAM.", "output": "ZnO." }, { "input": "We demonstrate logic and static random access memory ( SRAM ) circuits using a 100 mu m long and 100 nm thin single ZnO nanowire ( NW ), which acts as a channel of field - effect transistors ( FETs ) with Al2O3 dielectrics.", "output": "ZnO, Al2O3." }, { "input": "NW FETs are thus arrayed in one dimension to consist of NOT, NAND, and NOR gate logic, and SRAM circuits.", "output": "There is no related enetity." }, { "input": "Two respective top - gate NW FETs with Au and indium - tin - oxide ( ITO ) were connected to form an inverter, the basic NOT gate component, since the former gate leads to an enhanced mode FET while the latter to depletion mode due to their work function difference.", "output": "Au, indium - tin - oxide, ITO." }, { "input": "Our inverters showed a high voltage gain of 22 under a 5 V operational voltage, resulting in successful operation of all other devices.", "output": "There is no related enetity." }, { "input": "We thus conclude that our long single NW approach is quite promising to extend the field of nano - electronics.", "output": "There is no related enetity." }, { "input": "Induction of the metabolic regulator Txnip in fasting - induced and natural torpor.", "output": "There is no related enetity." }, { "input": "Torpor is a physiological state characterised by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions.", "output": "There is no related enetity." }, { "input": "The hypothalamus coordinates energy homeostasis and thermoregulation, and plays a key role in directing torpor.", "output": "There is no related enetity." }, { "input": "We recently showed that mice lacking the orphan G protein coupled receptor Gpr50 readily enter torpor in response to fasting, and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state.", "output": "There is no related enetity." }, { "input": "This revealed a strong induction of thioredoxin interacting protein ( Txnip ) in the hypothalamus of torpid mice, which was confirmed by quantitative RT - PCR and Western blot analyses.", "output": "There is no related enetity." }, { "input": "In situ hybridisation identified the ependyma lining the third ventricle as the principal site of torpor - related expression of Txnip.", "output": "There is no related enetity." }, { "input": "To characterise further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2 - deoxyglucose - induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster.", "output": "2 - deoxyglucose." }, { "input": "Strikingly, pronounced upregulation of Txnip expression was only observed in WT mice when driven into torpor, and during torpor in the Siberian hamster.", "output": "There is no related enetity." }, { "input": "Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice.", "output": "There is no related enetity." }, { "input": "Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel utilisation during the extreme hypometabolic state of torpor.", "output": "There is no related enetity." }, { "input": "Optimization of DDI Study Design: Comparison of Minimal PBPK Models on Prediction of CYP3A Inhibition by Ketoconazole.", "output": "There is no related enetity." }, { "input": "Ketoconazole is a potent CYP3A inhibitor used to assess the contribution of CYP3A to drug clearance and quantify the increase in drug exposure due to a strong inhibitor.", "output": "Ketoconazole." }, { "input": "Physiologically based pharmacokinetic ( PBPK ) models have been employed to evaluate dosing regimens resulting in maximal CYP3A inhibition by ketoconazole but have reached different conclusions.", "output": "ketoconazole." }, { "input": "We compare two PBPK models of the ketoconazole - midazolam interaction, Model 1 ( Chien et al., 2006 ) and Model 2 implemented in Simcyp ( version 11 ) to predict 16 published dosing regimens.", "output": "ketoconazole, midazolam." }, { "input": "Using Model 2, 41 % of the study point estimates of AUC ratio and 71 % of the 90 % confidence intervals were predicted within 1. 5 - fold of the observed but these increased to 82 % and 100 % respectively with Model 1.", "output": "There is no related enetity." }, { "input": "For midazolam, Model 2 predicted a maximal midazolam AUC ratio of 8 and a hepatic fraction metabolized by CYP3A of 0. 97 whereas Model 1 predicted 17 and 0. 90 respectively, which are more consistent with observed data.", "output": "midazolam, midazolam." }, { "input": "Based on Model 1, ketoconazole 400mg QD for at least 3 days and substrate administration within 2 hours is required for maximal CYP3A inhibition.", "output": "ketoconazole." }, { "input": "Ketoconazole dosing regimens that employ 200 mg BID underestimate the systemic fraction metabolized by CYP3A ( 0. 86 vs. 0. 90 ) for midazolam.", "output": "Ketoconazole, midazolam." }, { "input": "The systematic underprediction also applies to CYP3A substrates with high bioavailability and long half - lives.", "output": "There is no related enetity." }, { "input": "The superior predictive performance of Model 1 reflects the need for accumulation of ketoconazole at enzyme site and protracted inhibition.", "output": "ketoconazole." }, { "input": "Model 2 is not recommended for inferring optimal study design and estimation of fraction metabolized by CYP3A.", "output": "There is no related enetity." }, { "input": "Vandetanib: opening a new treatment practice in advanced medullary thyroid carcinoma.", "output": "Vandetanib." }, { "input": "Medullary thyroid cancer ( MTC ) is frequently diagnosed in a locally advanced or metastatic stage, and 10 - year survival rates in these cases are below 20 %.", "output": "There is no related enetity." }, { "input": "Cytotoxic chemotherapy has no significant impact on overall or progression - free survival.", "output": "There is no related enetity." }, { "input": "Vandetanib ( Caprelsa ( (R) ), AstraZeneca ) is a once - daily oral tyrosine kinase inhibitor that selectively inhibits signalling mediated by growth - factor receptor tyrosine kinase RET ( constitutively activated in roughly 60 % of all MTCs ), vascular endothelial growth - factor receptors 2 and 3, and epidermal growth - factor receptors.", "output": "Vandetanib, Caprelsa, tyrosine, tyrosine." }, { "input": "It is the first systemic drug with demonstrated anti - tumor benefits in advanced MTC, and it has recently been approved for locally advanced or metastatic MTC by the United States Food and Drug Administration ( April 2011 ) and the European Medicines Agency ( February 2012 ).", "output": "There is no related enetity." }, { "input": "This review, starting from the phases II and III efficacy and safety data that led to these approvals, explores important issues related to dosing, patient selection, and strategies for managing the substantial risk of toxicity associated with the drug ( including life - threatening cardiac events that are the subject of a black - box warning in the United States ).", "output": "There is no related enetity." }, { "input": "All these issues still remain to be defined.", "output": "There is no related enetity." }, { "input": "Vandetanib is becoming a standard of care for symptomatic, progressive, metastatic MTCs, to be used selectively in those patients who are likely to benefit from it.", "output": "Vandetanib." }, { "input": "Structural Transformation between Supramolecular Nanofibers with Drastic Change of Conductivity by Heat and Ultrasound.", "output": "There is no related enetity." }, { "input": "Transformation with every fiber of its being: Dehydrobenzoannulene derivatives with a boomerang shape, dipole moment, and substituents that make diverse interactions enable the contruction of stimuli - responsive nanofibers despite the lack of stimuli - responsive groups in these compounds.", "output": "There is no related enetity." }, { "input": "Interestingly, the supramolecular nanofibers obtained after ultrasonic treatment displayed an 80 % decrease in conductivity as compared to untreated nanofibers.", "output": "There is no related enetity." }, { "input": "This is the first example of an electronic wire for which the conductivity can be controlled by ultrasound.", "output": "There is no related enetity." }, { "input": "NMDA Receptor Activation Down - Regulates Expression of delta Subunit - Containing GABA - A Receptors in Cultured Hippocampal Neurons.", "output": "NMDA, GABA." }, { "input": "Neurosteroids are endogenous allosteric modulators of gamma amino - butyric acid type A receptors ( GABARs ), and enhance GABAR - mediated inhibition.", "output": "gamma amino - butyric acid." }, { "input": "However, GABARs expressed on hippocampal dentate granule neurons of epileptic animals are modified such that their neurosteroid sensitivity is reduced and delta subunit expression is diminished.", "output": "There is no related enetity." }, { "input": "The molecular mechanisms triggering this GABAR plasticity were explored.", "output": "There is no related enetity." }, { "input": "In the cultured hippocampal neurons treatment with NMDA ( 10 mu M ) for 48 hrs reduced surface expression of delta and alpha 4 subunits, but did not increase expression of gamma 2 subunits.", "output": "NMDA." }, { "input": "The tonic current recorded from neurons in NMDA - treated cultures was reduced, and its neurosteroid modulation was also diminished.", "output": "NMDA." }, { "input": "In contrast, synaptic inhibition and its modulation by neurosteroids were preserved in these neurons.", "output": "There is no related enetity." }, { "input": "The time course of NMDA effects on surface and total delta subunit expression were distinct; shorter ( 6 hrs ) treatment decreased surface expression, whereas longer treatment reduced both surface and total expression.", "output": "NMDA." }, { "input": "APV blocked NMDA effects on delta subunit expression.", "output": "APV, NMDA." }, { "input": "Chelation of calcium ions by BAPTA - AM or blockade of ERK1 / 2 activation by UO126 also prevented the NMDA effects.", "output": "calcium, BAPTA - AM, UO126, NMDA." }, { "input": "Thus prolonged activation of NMDA receptors in hippocampal neurons reduced GABAR delta subunit expression through Ca2 + entry and at least in part by ERK1 / 2 activation.", "output": "NMDA, Ca2 +." }, { "input": "Kinetic Evidence for a Non - Langmuir - Hinshelwood Surface Reaction: H / D Exchange over Pd Nanoparticles and Pd ( 111 ).", "output": "H, D, Pd, Pd ( 111 )." }, { "input": "The mechanism of hydrogen recombination on a Pd ( 111 ) single crystal and well - defined Pd nanoparticles is studied using pulsed multi - molecular beam techniques and the H2 / D2 isotope exchange reaction.", "output": "hydrogen, Pd ( 111 ), Pd, H2, D2." }, { "input": "The focus of this study is to obtain a microscopic understanding of the role of subsurface hydrogen in enhancing the associative desorption of molecular hydrogen.", "output": "hydrogen, hydrogen." }, { "input": "HD production from H2 and D2 over Pd is investigated using pulsed molecular beams, and the temperature dependence and reaction orders are obtained for the rate of HD production under various reaction conditions designed to modulate the amount of subsurface hydrogen present.", "output": "HD, H2, D2, Pd, HD, hydrogen." }, { "input": "The experimental data are compared to the results of kinetic modeling based on different mechanisms for hydrogen recombination.", "output": "hydrogen." }, { "input": "We found that under conditions where virtually no subsurface hydrogen species are present, the HD formation rate can be described exceptionally well by a classic Langmuir - Hinshelwood model.", "output": "hydrogen, HD." }, { "input": "However, this model completely fails to reproduce the experimentally observed high HD formation rates and the reaction orders under reaction conditions where subsurface hydrogen is present.", "output": "HD, hydrogen." }, { "input": "To analyze this phenomenon, we develop two kinetic models that account for the role of subsurface hydrogen.", "output": "hydrogen." }, { "input": "First, we investigate the possibility of a change in the reaction mechanism, where recombination of one subsurface and one surface hydrogen species ( known as a breakthrough mechanism ) becomes dominant when subsurface hydrogen is present.", "output": "hydrogen, hydrogen." }, { "input": "Second, we investigate the possibility of the modified Langmuir - Hinshelwood mechanism with subsurface hydrogen lowering the activation energy for recombination of two hydrogen species adsorbed on the surface.", "output": "hydrogen, hydrogen." }, { "input": "We show that the experimental reaction kinetics can be well described by both kinetic models based on non - Langmuir - Hinshelwood - type mechanisms.", "output": "There is no related enetity." }, { "input": "Accurate detection of differential RNA processing.", "output": "There is no related enetity." }, { "input": "Deep transcriptome sequencing ( RNA - Seq ) has become a vital tool for studying the state of cells in the context of varying environments, genotypes and other factors.", "output": "There is no related enetity." }, { "input": "RNA - Seq profiling data enable identification of novel isoforms, quantification of known isoforms and detection of changes in transcriptional or RNA - processing activity.", "output": "There is no related enetity." }, { "input": "Existing approaches to detect differential isoform abundance between samples either require a complete isoform annotation or fall short in providing statistically robust and calibrated significance estimates.", "output": "There is no related enetity." }, { "input": "Here, we propose a suite of statistical tests to address these open needs: a parametric test that uses known isoform annotations to detect changes in relative isoform abundance and a non - parametric test that detects differential read coverages and can be applied when isoform annotations are not available.", "output": "There is no related enetity." }, { "input": "Both methods account for the discrete nature of read counts and the inherent biological variability.", "output": "There is no related enetity." }, { "input": "We demonstrate that these tests compare favorably to previous methods, both in terms of accuracy and statistical calibrations.", "output": "There is no related enetity." }, { "input": "We use these techniques to analyze RNA - Seq libraries from Arabidopsis thaliana and Drosophila melanogaster.", "output": "There is no related enetity." }, { "input": "The identified differential RNA processing events were consistent with RT - qPCR measurements and previous studies.", "output": "There is no related enetity." }, { "input": "The proposed toolkit is available from http: / / bioweb. me / rdiff and enables in - depth analyses of transcriptomes, with or without available isoform annotation.", "output": "There is no related enetity." }, { "input": "The effect of PTH ( 1 - 34 ) on fracture healing during different loading conditions.", "output": "There is no related enetity." }, { "input": "Parathyroid hormone ( PTH ) and PTH ( 1 - 34 ) have been shown to promote bone healing in several animal studies.", "output": "There is no related enetity." }, { "input": "It is known that the mechanical environment is important in fracture healing.", "output": "There is no related enetity." }, { "input": "Furthermore, PTH and mechanical loading has been suggested to have synergistic effects on intact bone.", "output": "There is no related enetity." }, { "input": "The aim of the present study was to investigate whether the effect of PTH ( 1 - 34 ) on fracture healing in rats was influenced by reduced mechanical loading.", "output": "There is no related enetity." }, { "input": "For this purpose we used female, 25 - week - old ovariectomized rats.", "output": "There is no related enetity." }, { "input": "Animals were subjected to closed midshaft fracture of the right tibia ten weeks after ovariectomy.", "output": "There is no related enetity." }, { "input": "Five days before fracture, half of the animals received Botulinum Toxin A - injections in the muscles of the fractured leg to induce muscle paralysis ( unloaded group ), while the other half received saline injections ( control group ).", "output": "There is no related enetity." }, { "input": "For the following eight weeks, half of the animals in each group received injections of hPTH ( 1 - 34 ) ( 20 micro g / kg / day ) and the other half received vehicle treatment.", "output": "There is no related enetity." }, { "input": "Fracture healing was assessed by radiology, DXA, histology and bone strength analysis.", "output": "There is no related enetity." }, { "input": "We found that unloading reduced callus area significantly, while no effects of PTH ( 1 - 34 ) on callus area were seen in neither normally nor unloaded animals.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) increased callus bone mineral density ( BMD ) and bone mineral content ( BMC ) significantly, while unloading decreased callus BMD and BMC significantly.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) - treatment increased bone volume of the callus in both unloaded and control animals.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) - treatment increased ultimate force of the fracture by 63 % in both control and unloaded animals and no interaction of the two interventions could be detected.", "output": "There is no related enetity." }, { "input": "PTH ( 1 - 34 ) was able to stimulate bone formation in normally loaded as well as unloaded intact bone.", "output": "There is no related enetity." }, { "input": "In conclusion, the study confirms the stimulatory effect of PTH ( 1 - 34 ) on fracture healing and our data suggest that PTH ( 1 - 34 ) is able to promote fracture healing, as well as intact bone formation during conditions of reduced mechanical loading.", "output": "There is no related enetity." }, { "input": "Bottom - up Synthesis of Nanoscale Conjugation - Interrupted Frameworks and Their Electrical Properties.", "output": "There is no related enetity." }, { "input": "Soluble covalent organic nanoframeworks up to generation 2. 5 ( G2. 5 ) are synthesized with self - similar H - shaped conformations by using a bottom - up approach including iterative C - H bond functionalization.", "output": "C - H." }, { "input": "The electrical characteristics of nanoscale thin - film semiconductors of the conjugation - interrupted frameworks can be tuned by post - modification with diazonium salt.", "output": "diazonium." }, { "input": "Dual Growth Factor Delivery Using Biocompatible Core - Shell Microcapsules for Angiogenesis.", "output": "There is no related enetity." }, { "input": "An optimized electrodropping system produces homogeneous core - shell microcapsules ( C - S MCs ) by using poly ( L - lactic - co - glycolic acid ) ( PLGA ) and alginate.", "output": "poly ( L - lactic - co - glycolic acid ), PLGA." }, { "input": "Fluorescence imaging clearly shows the C - S domain in the MC.", "output": "There is no related enetity." }, { "input": "For release control, the use of high - molecular - weight PLGA ( HMW 270 000 ) restrains the initial burst release of protein compared to that of low - MW PLGA ( LMW 40 000 ).", "output": "PLGA, PLGA." }, { "input": "Layer - by - layer ( LBL ) assembly of chitosan and alginate on MCs is also useful in controlling the release profile of biomolecules.", "output": "There is no related enetity." }, { "input": "LBL ( 7 - layer ) treatment is effective in suppressing the initial burst release of protein compared to no LBL ( 0 - layer ).", "output": "There is no related enetity." }, { "input": "The difference of cumulative albumin release between HMW ( 7 - layer LBL ) and LMW ( 0 - layer LBL ) PLGA is determined to be more than 40 % on day 5.", "output": "PLGA." }, { "input": "When dual angiogenic growth factors ( GFs ), such as platelet - derived GF ( PDGF ) and vascular endothelial GF ( VEGF ), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30 % on day 7 with LMW core PLGA and more than 45 % with HMW core PLGA.", "output": "PLGA, PLGA." }, { "input": "As for the angiogenic potential of MC GFs with human umbilical vein endothelial cells ( HUVECs ), the fluorescence signal of CD31 + suggests that the angiogenic sprout of ECs is more active in MC - mediated GF delivery than conventional GF delivery, and this difference is significant, based on the number of capillary branches in the unit area.", "output": "There is no related enetity." }, { "input": "This study demonstrates that the fabrication of biocompatible C - S MCs is possible, and that the release control of biomolecules is adjustable.", "output": "There is no related enetity." }, { "input": "Furthermore, MC - mediated GFs remain in an active form and can upregulate the angiogenic activity of ECs.", "output": "There is no related enetity." }, { "input": "Surface Matters: Enhanced Bactericidal Property of Core - Shell Ag - Fe2 O3 Nanostructures to Their Heteromer Counterparts from One - Pot Synthesis.", "output": "Ag, Fe2 O3." }, { "input": "A facile one - pot synthesis of Ag @ Fe2 O3 core - shell and Ag - Fe2 O3 heteromer nanoparticles is developed, and the core - shell nanoparticles have shown superior antibacterial properties compared to their heteromer counterparts and plain Ag nanoparticles.", "output": "Ag, Fe2 O3, Ag, Fe2 O3, Ag." }, { "input": "The mechanism for the increased efficiency is proposed to be due to the enhanced Ag ion release from the iron oxide shell - protected pristine Ag surface.", "output": "Ag, iron oxide, Ag." }, { "input": "Glassy Interfacial Dynamics of Ni Nanoparticles: Part II Discrete Breathers as an Explanation of Two - Level Energy Fluctuations.", "output": "Ni." }, { "input": "Recent studies of the dynamics of diverse condensed amorphous materials have indicated significant heterogeneity in the local mobility and a progressive increase in collective particle motion upon cooling that takes the form of string - like particle rearrangements.", "output": "There is no related enetity." }, { "input": "In a previous paper ( Part I ), we examined the possibility that fluctuations in potential energy E and particle mobility mu associated with this ' dynamic heterogeneity ' might offer information about the scale of collective motion in glassy materials based on molecular dynamics simulations of the glassy interfacial region of Ni nanoparticles ( NPs ) at elevated temperatures.", "output": "Ni." }, { "input": "We found that the noise exponent associated with fluctuations in the Debye - Waller factor, a mobility related quantity, was directly proportional to the scale of collective motion L under a broad range of conditions, but the noise exponent associated with E ( t ) fluctuations was seemingly unrelated to L.", "output": "There is no related enetity." }, { "input": "In the present work, we focus on this unanticipated difference between potential energy and mobility fluctuations by examining these quantities at an atomic scale.", "output": "There is no related enetity." }, { "input": "We find that the string atoms exhibit a jump - like motion between two well - separated bands of energy states and the rate at which these jumps occur seems to be consistent with the phenomenology of the ' slow - beta ' relaxation process of glass - forming liquids.", "output": "There is no related enetity." }, { "input": "Concurrently with these local E ( t ) jumps, we also find ' quake - like ' particle displacements having a power - law distribution in magnitude so that particle displacement fluctuations within the strings are strikingly different from local E ( t ) fluctuations.", "output": "There is no related enetity." }, { "input": "An analysis of these E ( t ) fluctuations suggests that we are dealing with ' discrete breather ' excitations in which large energy fluctuations develop in arrays of non - linear oscillators by virtue of large anharmonicity in the interparticle interactions and discreteness effects associated with particle packing.", "output": "There is no related enetity." }, { "input": "We quantify string collective motions on a fast caging times scale ( picoseconds ) and explore the significance of these collective motions for understanding the Boson peak of glass - forming materials.", "output": "There is no related enetity." }, { "input": "Tuning the Emission Properties of Fluorescent Ligands by Changing pH: The Unusual Case of an Acridine - Containing Polyamine Macrocycle.", "output": "Acridine." }, { "input": "Synthesis and characterization of a new macrocyclic compound, composed by a triethylentetraamine chain linking the 4 and 5 positions of an acridine moiety, are reported.", "output": "triethylentetraamine, acridine." }, { "input": "The molecule, devised as a fluorescent chemosensor for anions, has revealed an intriguing pH - dependent spectroscopic behavior, whose features are the specific object of this article.", "output": "There is no related enetity." }, { "input": "Ligand protonation in aqueous solution has been analyzed by means of potentiometric, ( 1 ) H NMR, UV - vis, and fluorescence emission measurements.", "output": "( 1 ) H." }, { "input": "The molecule binds up to four protons in the pH range 2 - 11.", "output": "There is no related enetity." }, { "input": "Protonation takes place on the aliphatic tetraamine chain, while the acridine nitrogen does not participate to proton binding even at very low pH.", "output": "tetraamine, acridine, nitrogen." }, { "input": "Differently from acridine, the UV - vis spectra are almost unaffected by the pH.", "output": "acridine." }, { "input": "On the opposite, the emission spectra are strongly pH - dependent.", "output": "There is no related enetity." }, { "input": "In fact, at low pH values, the spectra show a blue - shifted emission, resembling that of unprotonated acridine, while at slightly acidic and alkaline pH the fluorescence features a red - shifted band similar to that of acridinium cation.", "output": "acridinium." }, { "input": "This unusual behavior occurs in the mono -, bi -, and triprotonated forms of the compound and is interpreted as due to an excited state proton transfer from an aliphatic ammonium group adjacent to the acridine moiety to the acridine nitrogen.", "output": "aliphatic ammonium, acridine, acridine, nitrogen." }, { "input": "In the fully protonated state, this process is prevented owing to unfavorable molecular arrangements mainly determined by electrostatic repulsions.", "output": "There is no related enetity." }, { "input": "This interpretation is supported by quantum mechanical calculations as well as molecular dynamics simulations.", "output": "There is no related enetity." }, { "input": "Self - Seeding in One Dimension: A Route to Uniform Fiber - like Nanostructures from Block Copolymers with a Crystallizable Core - Forming Block.", "output": "There is no related enetity." }, { "input": "One - dimensional micelles formed by the self - assembly of crystalline - coil poly ( ferrocenyldimethylsilane ) ( PFS ) block copolymers exhibit self - seeding behavior when solutions of short micelle fragments are heated above a certain temperature and then cooled back to room temperature.", "output": "poly ( ferrocenyldimethylsilane ), PFS." }, { "input": "In this process, a fraction of the fragments ( the least crystalline fragments ) dissolves at elevated temperature, but the dissolved polymer crystallizes onto the ends of the remaining seed fragments upon cooling.", "output": "There is no related enetity." }, { "input": "This process yields longer nanostructures ( up to 1 mu m ) with uniform width ( ca. 15 nm ) and a narrow length distribution.", "output": "There is no related enetity." }, { "input": "In this paper, we describe a systematic investigation of factors that affect the self - seeding behavior of PFS block copolymer micelle fragments.", "output": "PFS." }, { "input": "For PI1000 - PFS50 ( the subscripts refer to the number average degree of polymerization ) in decane, these factors include the presence of a good solvent ( THF ) for PFS and the effect of annealing the fragments prior to the self - seeding experiments.", "output": "decane, THF, PFS." }, { "input": "THF promoted the dissolution of the micelle fragments, while preannealing improved their stability.", "output": "THF." }, { "input": "We also extended our experiments to other PFS block copolymers with different corona - forming blocks.", "output": "PFS." }, { "input": "These included PI637 - PFS53 in decane, PFS60 - PDMS660 in decane ( PDMS = polydimethylsiloxane ), and PFS30 - P2VP300 in 2 - propanol ( P2VP = poly ( 2 - vinylpyridine ) ).", "output": "PDMS, polydimethylsiloxane, 2 - propanol, P2VP, poly ( 2 - vinylpyridine." }, { "input": "The most remarkable result of these experiments is our finding that the corona - forming chain plays an important role in affecting how the PFS chains crystallize in the core of the micelles and, subsequently, the range of temperatures over which the micelle fragments dissolve.", "output": "PFS." }, { "input": "Our results also show that self - seeding is a versatile approach to generate uniform PFS fiber - like nanostructures, and in principle, the method should be extendable to a wide variety of crystalline - coil block copolymers.", "output": "PFS." }, { "input": "Kinetics and Mechanism of the Tropospheric Oxidation of Vinyl Acetate Initiated by OH Radical: A Theoretical Study.", "output": "Vinyl Acetate, OH." }, { "input": "Vinyl acetate [ VA ( CH3COOC2H3 ) ] is an important unsaturated and oxygenated volatile organic compound responsible for atmospheric pollution.", "output": "Vinyl acetate, CH3COOC2H3." }, { "input": "In this work, possible reaction mechanisms for the degradation of OH - initiated atmospheric oxidation of VA are investigated.", "output": "OH." }, { "input": "The potential energy surfaces ( PESs ) for the reaction of OH radical with VA in the presence of O2 and NO have been studied using the M06 - 2X / 6 - 311 + + G ( d, p ) method.", "output": "OH, O2, NO." }, { "input": "The initial addition reactions of more and less substituted ethylenic C - atoms of VA are treated separately, followed by a conventional transition state theory ( TST ) calculation for reaction rates.", "output": "ethylenic, C." }, { "input": "The direct H - abstraction mechanism and kinetics have also been studied.", "output": "H." }, { "input": "The initial OH addition occurs through a prereactive complex, and the calculated rate constants in the temperature range 250 - 350 K for both the addition reactions are found to have negative temperature dependence.", "output": "OH." }, { "input": "The calculation indicates that the reaction proceeds predominantly via the addition of OH radical to the double bond rather than the direct abstraction of H - atoms in VA.", "output": "OH, H." }, { "input": "IM1 [ CH3C ( O ) O ( * ) CHCH2OH ] and IM2 [ CH3C ( O ) OCH ( OH ) ( * ) CH2 ], the OH adduct complexes formed initially, react with ubiquitous O2 followed by NO before their rearrangement.", "output": "CH3C ( O ) O ( * ) CHCH2OH, CH3C ( O ) OCH ( OH ) ( * ) CH2, OH, O2, NO." }, { "input": "The formation of the prereactive complex plays an important role in reaction mechanism and kinetics.", "output": "There is no related enetity." }, { "input": "The calculated rate constant, k298K = 1. 61 x 10 ( - 11 ) cm ( 3 ) molecule ( - 1 ) s ( - 1 ), is well harmonized with the previous experimental data, k298K = ( 2. 48 +/- 0. 61 ) x 10 ( - 11 ) cm ( 3 ) molecule ( - 1 ) s ( - 1 ) ( Blanco et al. ) and k298K = ( 2. 3 +/- 0. 3 ) x 10 ( - 11 ) cm ( 3 ) molecule ( - 1 ) s ( - 1 ) ( Picquet - Varrult et al. ).", "output": "There is no related enetity." }, { "input": "Additionally, consistent and reliable enthalpies of formation at 298. 15 K ( Delta fH degrees 298. 15 ) have been computed for all the species involved in the title reaction using the composite CBS - QB3 method.", "output": "There is no related enetity." }, { "input": "The theoretical results confirm that the major products are formic acetic anhydride, acetic acid, and formaldehyde in the OH - initiated oxidation of VA in the presence of O2 and NO, which are in excellent agreement with the experimental findings.", "output": "formic acetic anhydride, acetic acid, formaldehyde, OH, O2, NO." }, { "input": "Development of a Selective Peptide Macrocycle Inhibitor of Coagulation Factor XII toward the Generation of a Safe Antithrombotic Therapy.", "output": "There is no related enetity." }, { "input": "Inhibition of coagulation factor XII ( FXII ) activity represents an attractive approach for the treatment and prevention of thrombotic diseases.", "output": "There is no related enetity." }, { "input": "The few existing FXII inhibitors suffer from low selectivity.", "output": "There is no related enetity." }, { "input": "Using phage display combined to rational design, we developed a potent inhibitor of FXII with more than 100 - fold selectivity over related proteases.", "output": "There is no related enetity." }, { "input": "The highly selective peptide macrocycle is a promising candidate for the control of FXII activity in antithrombotic therapy and a valuable tool in hematology research.", "output": "There is no related enetity." }, { "input": "Structures of the Dehydrogenation Products of Methane Activation by 5d Transition Metal Cations.", "output": "Methane, Transition Metal." }, { "input": "The activation of methane by gas - phase transition metal cations ( M + ) has been studied extensively, both experimentally and using density functional theory ( DFT ).", "output": "methane, transition metal." }, { "input": "Methane is exothermically dehydrogenated by several 5d metal ions to form [ M, C, 2H ] + and H2.", "output": "Methane, C, 2H, H2." }, { "input": "However, the structure of the dehydrogenation product has not been established unambiguously.", "output": "There is no related enetity." }, { "input": "Two types of structures have been considered: a carbene structure where an intact CH2 fragment is bound to the metal ( M + - CH2 ) and a carbyne ( hydrido - methylidyne ) structure with both a CH and a hydrogen bound to the metal separately ( H - M + - CH ).", "output": "carbene, CH2, CH2, carbyne, hydrido - methylidyne, CH, hydrogen, H, CH." }, { "input": "For metal ions with empty d - orbitals, an agostic interaction can occur that could influence the competition between carbene and carbyne structures.", "output": "carbene, carbyne." }, { "input": "In this work, the gas phase [ M, C, 2H ] + ( M = Ta, W, Ir, Pt ) products are investigated by infrared multiple - photon dissociation ( IR - MPD ) spectroscopy using the Free Electron Laser for IntraCavity Experiments ( FELICE ).", "output": "C, 2H, Ta, W, Ir, Pt." }, { "input": "Metal cations are formed in a laser ablation source and react with methane pulsed into a reaction channel downstream.", "output": "There is no related enetity." }, { "input": "IRMPD spectra of the [ M, C, 2H ] + species are measured in the 300 - 3500 cm - 1 spectral range by monitoring the loss of H ( 2H in the case of [ Ir, C, 2H ] + ).", "output": "C, 2H, H, 2H, Ir, C, 2H." }, { "input": "For each system, the experimental spectrum closely resembles the calculated spectrum of the lowest energy structure calculated using DFT: for Pt, a classic C2v carbene structure; for Ta and W, carbene structures that are distorted by agostic interactions; and a carbyne structure for the Ir complex.", "output": "Pt, carbene, Ta, W, carbene, carbyne, Ir." }, { "input": "The Ir carbyne structure was not considered previously.", "output": "Ir, carbyne." }, { "input": "To obtain this agreement, the calculated harmonic frequencies are scaled with a scaling factor of 0. 939, which is fairly low and can be attributed to the strong redshift induced by the IR multiple - photon excitation process of these small molecules.", "output": "There is no related enetity." }, { "input": "These four - atomic species are among the smallest systems studied by IR - FEL based IR - MPD spectroscopy and their spectra demonstrate the power of IR spectroscopy in resolving long - standing chemical questions.", "output": "There is no related enetity." }, { "input": "Trapping of a Cross - Link Formed by a Major Purine Adduct of a Metabolite of the Carcinogen N - Nitrosomorpholine by Inorganic and Biological Reductants.", "output": "Purine, N - Nitrosomorpholine." }, { "input": "3 - Hydroperoxy - N - nitrosomorpholine in buffered aqueous media in the presence of calf thymus DNA was treated with a phosphine reductant to generate the transient alpha - hydroxynitrosamine and subsequent diazonium ion that alkylated the DNA, as previously reported.", "output": "3 - Hydroperoxy - N - nitrosomorpholine, alpha - hydroxynitrosamine, diazonium." }, { "input": "Subsequent addition of hydride donors, for 30 min, followed by acid hydrolysis of the mixture allowed detection and quantification of 6 - ( 2 - { 2 - [ ( 9H - purin - 6 - yl ) amino ] ethoxy } ethoxy ) - 9H - purin - 2 - amine, the reduced cross - link formed from deposition, via the diazonium ion, of a 3 - oxapentanal fragment on O ( 6 ) - Gua, and condensation with N ( 6 ) - Ade, presumably in the vicinity.", "output": "hydride, 6 - ( 2 - { 2 - [ ( 9H - purin - 6 - yl ) amino ] ethoxy } ethoxy ) - 9H - purin - 2 - amine, diazonium, 3 - oxapentanal, O, Gua, N, Ade." }, { "input": "Decreasing the temperature of the reaction mixtures and decreasing the pH modestly increased the yields of the trapped cross - link.", "output": "There is no related enetity." }, { "input": "Among three borohydride reductants, NaNCBH3 is superior, being ~ 4 times more effective on a molar basis, as opposed to a hydride equivalent basis, than NaBH4 or Na ( AcO ) 3BH.", "output": "borohydride, NaNCBH3, hydride, NaBH4, Na ( AcO ) 3BH." }, { "input": "For trapping with NaNCBH3, it is deduced that the reaction likely occurs with the iminium ion that is in protonic equilibrium with its conjugate base imine.", "output": "NaNCBH3, iminium, imine." }, { "input": "In an experiment in which the hydroperoxide was decomposed and NaNCBH3 was introduced after various periods of time, the amount of cross - link was observed to increase, nearly linearly, by ~ 4 - fold over 1 week.", "output": "hydroperoxide, NaNCBH3." }, { "input": "These data indicate that there are a minimum of two populations of cross - links, one that forms rapidly, in minutes, and another that grows in with time, over days.", "output": "There is no related enetity." }, { "input": "Reduced nicotinamide cofactors and ascorbate are observed to effect reduction ( over 3 days ) of the cross - links, confirming the possibility that otherwise reversible cross - links might be immortalized under biological conditions.", "output": "nicotinamide, ascorbate." }, { "input": "Recent advances in malaria drug discovery.", "output": "There is no related enetity." }, { "input": "This digest covers some of the most relevant progress in malaria drug discovery published between 2010 and 2012.", "output": "There is no related enetity." }, { "input": "There is an urgent need to develop new antimalarial drugs.", "output": "There is no related enetity." }, { "input": "Such drugs can target the blood stage of the disease to alleviate the symptoms, the liver stage to prevent relapses, and the transmission stage to protect other humans.", "output": "There is no related enetity." }, { "input": "The pipeline for the blood stage is becoming robust, but this should not be a source of complacency, as the current therapies set a high standard.", "output": "There is no related enetity." }, { "input": "Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria.", "output": "There is no related enetity." }, { "input": "A small molecule inhibitor of fungal histone acetyltransferase Rtt109.", "output": "There is no related enetity." }, { "input": "The histone acetyltransferase Rtt109 is the sole enzyme responsible for acetylation of histone H3 lysine 56 ( H3K56 ) in fungal organisms.", "output": "lysine." }, { "input": "Loss of Rtt109 renders fungal cells extremely sensitive to genotoxic agents, and prevents pathogenesis in several clinically important species.", "output": "There is no related enetity." }, { "input": "Here, via a high throughput chemical screen of > 300, 000 compounds, we discovered a chemical inhibitor of Rtt109 that does not inhibit other acetyltransferase enzymes.", "output": "There is no related enetity." }, { "input": "This compound inhibits Rtt109 regardless of which histone chaperone cofactor protein ( Asf1 or Vps75 ) is present, and appears to inhibit Rtt109 via a tight - binding, uncompetitive mechanism.", "output": "There is no related enetity." }, { "input": "Synthesis and antimicrobial activity of novel amphiphilic aromatic amino alcohols.", "output": "aromatic amino alcohols." }, { "input": "We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4 - alkyloxybenzaldehyde with 2 - amino - 2 - hydroxymethyl - propane - 1, 3 - diol.", "output": "aromatic amino alcohols, 4 - alkyloxybenzaldehyde, 2 - amino - 2 - hydroxymethyl - propane - 1 , 3 - diol." }, { "input": "The antibacterial activity was determined against four standard strains ( Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa ) and 21 clinical isolates of methicillin - resistant Staphylococcus aureus.", "output": "methicillin." }, { "input": "The antifungal activity was evaluated against four yeast ( Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis ).", "output": "There is no related enetity." }, { "input": "The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds.", "output": "There is no related enetity." }, { "input": "The best activities were obtained against the Gram - positive bacteria ( MIC = 2 - 16 mu gml ( - 1 ) ) for the five compounds bearing longer alkyl chains ( 4c - g; 8 - 14 carbons ), which were also the most active against Candida ( MIC = 2 - 64 mu gml ( - 1 ) ).", "output": "There is no related enetity." }, { "input": "Compound 4e exhibited the highest levels of inhibitory activity ( MIC = 2 - 16 mu gml ( - 1 ) ) against clinical isolates of MRSA.", "output": "There is no related enetity." }, { "input": "A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates.", "output": "There is no related enetity." }, { "input": "Role of BDNF epigenetics in activity - dependent neuronal plasticity.", "output": "There is no related enetity." }, { "input": "Brain - derived neurotrophic factor ( BDNF ) is a key mediator of the activity - dependent processes in the brain that have a major impact on neuronal development and plasticity.", "output": "There is no related enetity." }, { "input": "Impaired control of neuronal activity - induced BDNF expression mediates the pathogenesis of various neurological and psychiatric disorders.", "output": "There is no related enetity." }, { "input": "Different environmental stimuli, such as the use of pharmacological compounds, physical and learning exercises or stress exposure, lead to activation of specific neuronal networks.", "output": "There is no related enetity." }, { "input": "These processes entail tight temporal and spatial transcriptional control of numerous BDNF splice variants through epigenetic mechanisms.", "output": "There is no related enetity." }, { "input": "The present review highlights recent findings on the dynamic and long - term epigenetic programming of BDNF gene expression by the DNA methylation, histone - modifying and microRNA machineries.", "output": "There is no related enetity." }, { "input": "The review also summarizes the current knowledge on the activity - dependent BDNF mRNA trafficking critical for rapid local regulation of BDNF levels and synaptic plasticity.", "output": "There is no related enetity." }, { "input": "Current data open novel directions for discovery of new promising therapeutic targets for treatment of neuropsychiatric disorders.", "output": "There is no related enetity." }, { "input": "This article is part of a Special Issue entitled ' BDNF '.", "output": "There is no related enetity." }, { "input": "Effect of Korean pear ( Pyruspyrifolia cv. Shingo ) juice on hangover severity following alcohol consumption.", "output": "alcohol." }, { "input": "Korean pear has been used as a traditional prophylactic agent for alcohol hangover.", "output": "alcohol." }, { "input": "However, its mechanism was not investigated in human yet.", "output": "There is no related enetity." }, { "input": "Therefore, we performed a randomized single blind crossover trial with 14 healthy young men to examine effects of Korean pear juice on alcohol hangover.", "output": "alcohol." }, { "input": "All subjects consumed 540ml of spirits ( alcohol conc. 20. 1v / v % ) after 30min from the intervention, i. e. placebo or Korean pear juice treatment.", "output": "alcohol." }, { "input": "Blood and urine specimens were collected in time - courses ( 9 time - points for 15h after alcohol consumption ).", "output": "alcohol." }, { "input": "The total and average of hangover severity were alleviated to 16 % and 21 % by Korean pear juice at 15h after the alcohol consumption ( ps < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Particularly, ' trouble concentrating ' was significantly improved by the pear juice treatment ( p < 0. 05 ).", "output": "There is no related enetity." }, { "input": "Impaired memory, sensitivity to light and sound, and mean of hangover severity were significantly improved by Korean pear juice among the subjects with ALDH2 * 1 / * 1 or ALDH2 * 1 / * 2 genotypes ( ps < 0. 05 ) but not in the subjects with ALDH2 * 2 / * 2 genotype.", "output": "There is no related enetity." }, { "input": "In addition, the pear juice treatment lowered levels of blood alcohol ( p < 0. 01 ).", "output": "alcohol." }, { "input": "Therefore, Korean pear juice may alleviate alcohol - hangover and its detoxification of alcohol seems to be modified by the genetic variation of ALDH2.", "output": "alcohol." }, { "input": "Artemisia copa aqueous extract as vasorelaxant and hypotensive agent.", "output": "There is no related enetity." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia copa Phil.", "output": "There is no related enetity." }, { "input": "( Asteraceae ) is a medicinal plant commonly used in traditional medicine in Argentina.", "output": "There is no related enetity." }, { "input": "AIM OF THE STUDY: The vasorelaxant and hypotensive activities of the aqueous extract of Artemisia copa have been investigated.", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: The in vitro effect of the extract and isolated compounds from Artemisia copa was investigated using isolated rat aortic rings.", "output": "There is no related enetity." }, { "input": "The acute effect caused by the intravenous ( i. v. ) infusion ( 0. 1 - 300mg / kg ) on blood pressure and heart rate was evaluated in spontaneous hypertensive rats.", "output": "There is no related enetity." }, { "input": "In addition, a phytochemical analysis of the extract was performed by HPLC.", "output": "There is no related enetity." }, { "input": "RESULTS: Artemisia copa had a relaxant effect in endothelium - intact aortic rings that had been pre - contracted with 10 ( - 7 ) M phenylephrine ( Emax = 96. 7 +/- 1. 3 %, EC50 = 1. 1mg / ml ), 10 ( - 5 ) M 5 - hydroxytriptamine ( Emax = 96. 7 +/- 3. 5 %, EC50 = 1. 5mg / ml ) and 80mM KCl ( Emax = 97. 9 +/- 4. 4 %, EC50 = 1. 6mg / ml ).", "output": "phenylephrine, 5 - hydroxytriptamine, KCl." }, { "input": "In denuded aortic rings contracted by phenylephrine, a similar pattern was observed ( Emax = 92. 7 +/- 6. 5 %, EC50 = 1. 8mg / ml ).", "output": "phenylephrine." }, { "input": "l - NAME, indomethacin, tetraethylammonium and glibenclamide were not able to block the relaxation induced by the extract.", "output": "l - NAME, indomethacin, tetraethylammonium, glibenclamide." }, { "input": "Nevertheless, the pre - treatment with Artemisia copa attenuated the CaCl2 - induced contraction in a concentration - dependent manner ( Emax: 86 % of inhibition for 3mg / ml and 52 % de - inhibition for 1mg / ml ).", "output": "CaCl2." }, { "input": "This pre - treatment also induced a significant attenuation of the norepinephrine - induced contraction in a concentration - dependent manner ( Emax: 72. 7 % of inhibition for 3mg / ml and 27 % de inhibition for 1mg / ml ) in a Ca ( 2 + ) free medium.", "output": "norepinephrine, Ca ( 2 + )." }, { "input": "Upon analyzing the composition of the extract, the presence of p - coumaric acid, isovitexin, luteolin and chrysoeriol were found.", "output": "p - coumaric acid, isovitexin, luteolin, chrysoeriol." }, { "input": "Luteolin ( CE50: 1. 5 mu g / ml ), chrysoeriol ( CE50: 13. 2 mu g / ml ) and p - coumaric acid ( CE50: 95. 2 mu g / ml ), isolated from the aqueous extract, caused dilatation of thoracic aortic rings pre - contracted with phenylephrine.", "output": "Luteolin, chrysoeriol, p - coumaric acid, phenylephrine." }, { "input": "Artemisia copa administered i. v. also induced a decrease in the mean arterial pressure but did not affect the heart rate in hypertensive rats.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: The aqueous extract of Artemisia copa proved to have vasorelaxing and hypotensive effects through the inhibition of Ca ( 2 + ) influx via membranous calcium channels and intracellular stores.", "output": "Ca ( 2 + ), calcium." }, { "input": "The presence of luteolin, chrysoeriol and p - coumaric acid found in this plant could be involved in this effect.", "output": "luteolin, chrysoeriol, p - coumaric acid." }, { "input": "Characterization of volatiles and anti - ulcerogenic effect of Turkish sweetgum balsam ( Styrax liquidus ).", "output": "There is no related enetity." }, { "input": "ETHNOPHARMACOLOGICAL RELEVANCE: Sweetgum, Styrax liquidus ( Turkish sweetgum ) is a resinous exudate obtained from the wounded barks of Liquidambar orientalis Miller tree which belongs to Altingiaceae ( Hamamelidaceae ).", "output": "There is no related enetity." }, { "input": "The plant material has been used for the treatment of peptic ulcer symptoms in Turkish folk medicine since centuries.", "output": "There is no related enetity." }, { "input": "In order to evaluate the claimed activity, we studied the anti - ulcerogenic effect of Styrax liquidus by using an in vivo anti - ulcerogenic activity model and to determine the chemical composition of the balsam.", "output": "There is no related enetity." }, { "input": "MATERIALS AND METHODS: Anti - ulcerogenic effects of the balsam \" Styrax liquidus \" itself and its fractions obtained by successive solvent extractions with chloroform and n - butanol, were investigated against the ethanol - induced peptic ulcer model in rats.", "output": "chloroform, n - butanol, ethanol." }, { "input": "The chloroform extract demonstrated a statistically significant gastroprotective effect.", "output": "There is no related enetity." }, { "input": "In addition, the chemical characterization of the volatiles obtained by microdistillation technique from the balsam and the sub - extracts were analyzed by gas chromatography ( GC ) and gas chromatography - mass spectrometry ( GC - MS ), respectively.", "output": "There is no related enetity." }, { "input": "RESULTS: Pharmacological experiments have clearly demonstrated that 150 and 300mg / kg doses of Styrax liquidus given orally to rats showed significant gastric protection.", "output": "There is no related enetity." }, { "input": "On GC - MS analysis of the resin, overall, 31 compounds representing 99. 8 % of the total oil were identified where styrene ( 81. 9 % ), cinnamyl alcohol ( 6. 9 % ) and alpha - pinene ( 3. 5 % ) were identified as the major components.", "output": "styrene, cinnamyl alcohol, alpha - pinene." }, { "input": "CONCLUSION: Present study confirmed the anti - ulcerogenic activity of the local ethnobotanical usage of Styrax liquidus in Turkey.", "output": "There is no related enetity." }, { "input": "A DPYD Variant ( Y186C ) in Individuals of African Ancestry Is Associated With Reduced DPD Enzyme Activity.", "output": "There is no related enetity." }, { "input": "5 - Fluorouracil ( 5 - FU ) is used to treat many aggressive cancers, such as those of the colon, breast, and head and neck.", "output": "5 - Fluorouracil, 5 - FU." }, { "input": "The responses to 5 - FU, with respect to both toxicity and efficacy, vary among racial groups, potentially because of variability in the activity levels of the enzyme dihydropyrimidine dehydrogenase ( DPD, encoded by the DPYD gene ).", "output": "5 - FU, dihydropyrimidine." }, { "input": "In this study, the genetic associations between DPYD variations and circulating mononuclear - cell DPD enzyme activity were evaluated in 94 African - American and 81 European - American volunteers.", "output": "There is no related enetity." }, { "input": "The DPYD - Y186C variant was unique to individuals of African ancestry, and DPD activity was 46 % lower in carriers as compared with noncarriers ( 279 +/- 35 vs. 514 +/- 168 pmol 5 - FU min ( - 1 ) mg ( - 1 ); P = 0. 00029 ).", "output": "5 - FU." }, { "input": "In this study, 26 % of the African Americans with reduced DPD activity were carriers of Y186C.", "output": "There is no related enetity." }, { "input": "In the African - American cohort, after excluding Y186C carriers, homozygous carriers of C29R showed 27 % higher DPD activity as compared with noncarriers ( 609 +/- 152 and 480 +/- 152 pmol 5 - FU min ( - 1 ) mg ( - 1 ), respectively; P = 0. 013 ). Clinical Pharmacology & Therapeutics ( 2013 ); advance online publication 1 May 2013. doi: 10. 1038 / clpt. 2013. 69.", "output": "5 - FU." }, { "input": "Regulatory and Scientific Issues Regarding Use of Foreign Data in Support of New Drug Applications in the United States: An FDA Perspective.", "output": "There is no related enetity." }, { "input": "Globalization of clinical research has led to an increase in clinical trials conducted outside of the United States that are submitted to the US Food and Drug Administration ( FDA ) in new drug applications.", "output": "There is no related enetity." }, { "input": "This article discusses the FDA ' s experience with these submissions in specific therapeutic areas, including the extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA ' s approach to acceptance of these trials. Clinical Pharmacology & Therapeutics ( 2013 ); advance online publication 1 May 2013. doi: 10. 1038 / clpt. 2013. 70.", "output": "There is no related enetity." }, { "input": "Synergistic targeting / prodrug strategies for intravesical drug delivery - Lectin - modified PLGA microparticles enhance cytotoxicity of stearoyl gemcitabine by contact - dependent transfer.", "output": "PLGA, stearoyl gemcitabine." }, { "input": "The direct access to the urothelial tissue via intravesical therapy has emerged as a promising means for reducing the high recurrence rate of bladder cancer.", "output": "There is no related enetity." }, { "input": "However, few advanced delivery concepts have so far been evaluated to overcome critical inherent efficacy limitations imposed by short exposure times, low tissue permeability, and extensive washout.", "output": "There is no related enetity." }, { "input": "This study reports on a novel strategy to enhance gemcitabine treatment impact on urothelial cells by combining a pharmacologically advantageous prodrug approach with the pharmacokinetic benefits of a glycan - targeted carrier system.", "output": "gemcitabine." }, { "input": "The conversion of gemcitabine to its 4 - ( N ) - stearoyl derivative ( GEM - C18 ) allowed for stable, homogeneous incorporation into PLGA microparticles ( MP ) without compromising intracellular drug activation.", "output": "gemcitabine, 4 - ( N ) - stearoyl, GEM - C18, PLGA." }, { "input": "Fluorescence - labeled GEM - C18 - PLGA - MP were surface - functionalized with wheat germ agglutinin ( WGA ) or human serum albumin ( HSA ) to assess in direct comparison the impact of biorecognitive interaction on binding rate and anchoring stability.", "output": "GEM - C18 - PLGA." }, { "input": "MP adhesion on urothelial cells of non - malignant origin ( SV - HUC - 1 ), and low - ( 5637 ) or high - grade ( HT - 1376 ) carcinoma was correlated to the resultant antiproliferative and antimetabolic effect in BrdU and XTT assays.", "output": "BrdU." }, { "input": "More extensive and durable binding of the WGA - GEM - C18 - PLGA - MP induced a change in the pharmacological profile and substantially higher cytotoxicity, allowing for maximum response within the temporal restrictions of instillative administration ( 120min ).", "output": "GEM - C18 - PLGA." }, { "input": "Mechanistically, a direct, contact - dependent transfer of stearoyl derivatives from the particle matrix to the urothelial membrane was found to account for this effect.", "output": "stearoyl." }, { "input": "With versatile options for future application, our results highlight the potential offered by the synergistic implementation of targeting / prodrug strategies in delivery systems tailored to the intravesical route.", "output": "There is no related enetity." }, { "input": "Genome - Based Bacterial Vaccines: Current State and Future Outlook.", "output": "There is no related enetity." }, { "input": "Genome - based reverse vaccinology ( RV ) is a multi - step experimental strategy which starts from in silico analysis of whole genome sequences, from which vaccine candidates can be selected by using bioinformatic algorithms to identify putative protective antigens.", "output": "There is no related enetity." }, { "input": "In this review, we examine the current state of genome - based RV - engineered vaccines and future applications.", "output": "There is no related enetity." }, { "input": "The first product of genome - based RV is Bexsero ( (R) ), a vaccine developed for preventing Neisseria meningitidis serogroup B infection, and the strategy is currently being used for the development of new vaccines for other obdurate and emerging bacterial diseases.", "output": "There is no related enetity." }, { "input": "Improved sequencing technologies and the ongoing whole - genome sequence analyses of helminths, protozoa, and ectoparasites also currently serve as a basis for an RV strategy to produce new potential vaccines against eukaryotic pathogens.", "output": "There is no related enetity." }, { "input": "We also highlight an emerging approach - structure - based vaccinology - that exploits the information derived from the determined three - dimensional structures of vaccine candidates.", "output": "There is no related enetity." }, { "input": "Regardless, genome - based RV and other vaccine discovery platforms still depend on empirical experimental science to glean, from the hundreds of identified antigens from any one pathogen, those that should be combined to produce an effective vaccine.", "output": "There is no related enetity." }, { "input": "Adherence to preventive statin therapy according to socioeconomic position.", "output": "statin." }, { "input": "AIM: To explore whether long - term adherence to preventive statin therapy depends on socioeconomic position ( SEP ).", "output": "There is no related enetity." }, { "input": "METHODS: A cohort of individuals without established cardiovascular disease ( CVD ) or diabetes initiating preventive statin therapy during 2002 - 2005 was followed in the individual - level Danish registries for 4 years or until censoring events ( death, emigration, CVD or diabetes ).", "output": "There is no related enetity." }, { "input": "Only individuals aged 40 - 84 years for whom information was available on the SEP indicators, education and income were included ( N = 76, 038 ).", "output": "There is no related enetity." }, { "input": "Two different aspects of poor adherence were applied as outcome measures: ( 1 ) Proportion of days covered ( PDC ) with medication below 80 %, assuming a daily dose of one tablet ( continuity ); ( 2 ) Discontinuation defined as a gap between two consecutive prescriptions exceeding 365 days ( persistence ).", "output": "There is no related enetity." }, { "input": "Stratum - specific logistic regression analyses were applied to estimate the odds ratio ( OR ) for PDC < 80 % across SEP, adjusting for age and hypertension.", "output": "There is no related enetity." }, { "input": "Hazard ratio ( HR ) for discontinuation was estimated by Cox regression analyses.", "output": "There is no related enetity." }, { "input": "RESULTS: Adjusting mutually for income and education, the OR for PDC < 80 % decreased with increasing income.", "output": "There is no related enetity." }, { "input": "Comparing the highest income quintile with the lowest, the OR were 0. 64 ( 95 % Confidence Interval 0. 64 - 0. 65 ) and 0. 73 ( 0. 73 - 0. 74 ) in men aged 40 - 64 and 65 - 84 years, respectively; in women, the figures were 0. 79 ( 0. 79 - 0. 79 ) and 0. 95 ( 0. 94 - 0. 95 ), respectively.", "output": "There is no related enetity." }, { "input": "While observed increases in adherence with longer education in unadjusted analyses were attenuated after adjustment for income among men, the potential inverse relationship between length of education and adherence was enhanced among women.", "output": "There is no related enetity." }, { "input": "Applying discontinuation as outcome, analogous differences were demonstrated.", "output": "There is no related enetity." }, { "input": "CONCLUSION: Adherence to preventive statin therapy in Denmark decreases with decreasing income - especially in men aged 40 - 64 years.", "output": "There is no related enetity." }, { "input": "Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.", "output": "tacrolimus." }, { "input": "PURPOSES: Tacrolimus ( TAC ) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation.", "output": "Tacrolimus, TAC." }, { "input": "Its pharmacokinetics ( PK ) show considerable variability, making TAC a good candidate for therapeutic drug monitoring ( TDM ).", "output": "TAC." }, { "input": "The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation.", "output": "TAC." }, { "input": "METHODS: Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation.", "output": "TAC." }, { "input": "A population PK model was developed using nonlinear mixed - effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients ' demographics, biochemical test results and physiological characteristics.", "output": "TAC." }, { "input": "RESULTS: The PK of TAC were best described by a two - compartment model with first - order elimination.", "output": "TAC." }, { "input": "Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L / day and 314 L / day, respectively.", "output": "There is no related enetity." }, { "input": "The absorption first - order rate and volume of peripheral compartment were fixed to 4. 5 h ( - 1 ) and 100 L, respectively.", "output": "There is no related enetity." }, { "input": "While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution.", "output": "TAC." }, { "input": "CONCLUSIONS: We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.", "output": "TAC, TAC." }, { "input": "The prevalence and incidence of medicinal cannabis on prescription in The Netherlands.", "output": "There is no related enetity." }, { "input": "BACKGROUND: A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients.", "output": "There is no related enetity." }, { "input": "However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor ' s prescription.", "output": "There is no related enetity." }, { "input": "This study describes a retrospective database study of The Netherlands.", "output": "There is no related enetity." }, { "input": "METHODS: Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003 - 2010.", "output": "There is no related enetity." }, { "input": "Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties.", "output": "There is no related enetity." }, { "input": "RESULTS: Five thousand five hundred forty patients were identified.", "output": "There is no related enetity." }, { "input": "After an initial incidence of about 6 / 100, 000 inhabitants / year in 2003 and 2004, the incidence remained stable at 3 / 100, 000 / year in 2005 - 2010.", "output": "There is no related enetity." }, { "input": "The prevalence rate ranged from 5 to 8 per 100, 000 inhabitants.", "output": "There is no related enetity." }, { "input": "Virtually all patients used some form of prescription medication in the 6 months preceding start of cannabis use, most particularly psycholeptics ( 45. 5 % ), analgesics ( 44. 3 % ), anti - ulcer agents ( 35. 9 % ) and NSAIDs ( 30. 7 % ).", "output": "There is no related enetity." }, { "input": "We found no significant association between use of medication of common indications for cannabis ( pain, HIV / AIDS, cancer, nausea, glaucoma ) and variety of cannabis used.", "output": "There is no related enetity." }, { "input": "CONCLUSIONS: This is the first nationwide study into the extent of prescription of medicinal cannabis.", "output": "There is no related enetity." }, { "input": "Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ), no differences in choice of variety was found associated with indication.", "output": "tetrahydrocannabinol, THC, cannabidiol, CBD." }, { "input": "Emodin - 6 - O - beta - D - glucoside down - regulates endothelial protein C receptor shedding.", "output": "Emodin - 6 - O - beta - D - glucoside." }, { "input": "Endothelial protein C receptor ( EPCR ) plays an important role in the protein C anticoagulation pathway and in the cytoprotective pathway.", "output": "There is no related enetity." }, { "input": "Previously, EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor - alpha converting enzyme ( TACE ).", "output": "There is no related enetity." }, { "input": "Soluble EPCR levels are increased in patients with systemic inflammatory diseases.", "output": "There is no related enetity." }, { "input": "Recently, we reported that a new active compound, emodin - 6 - O - beta - D - glucoside ( EG ) from Reynoutria japonica, has anti - inflammatory activities.", "output": "emodin - 6 - O - beta - D - glucoside." }, { "input": "However, little is known of the effects of EG on EPCR shedding.", "output": "There is no related enetity." }, { "input": "Here, we investigated this issue by monitoring the effects of EG on the phorbol - 12 - myristate 13 - acetate ( PMA ) or the cecal ligation and puncture ( CLP ) - mediated EPCR shedding and its underlying mechanisms.", "output": "phorbol - 12 - myristate 13 - acetate, PMA." }, { "input": "Data showed that EG potently inhibited the PMA and CLP - induced EPCR shedding by suppressing TACE expression.", "output": "PMA." }, { "input": "Given these results, EG could be used as a candidate therapeutic for the treatment of vascular inflammatory diseases.", "output": "There is no related enetity." }, { "input": "Oromucosal delivery of venlafaxine by linseed mucilage based gel: in vitro and in vivo evaluation in rabbits.", "output": "venlafaxine." }, { "input": "Linseed is the crop that is used as a foodstuff in European and Asian countries.", "output": "There is no related enetity." }, { "input": "The objective of the present work was to extract mucilage from linseed, utilize it as mucoadhesive gelling agent along with synthetic polymers and administration of venlafaxine by buccal route in the gel form.", "output": "venlafaxine." }, { "input": "Buccal administration of venlafaxine will avoid first pass metabolism, which will increase the bioavailability of the drug.", "output": "venlafaxine." }, { "input": "Linseed mucilage based buccal mucoadhesive gel preparations in combination with chitosan, carbopol 934P, carboxy methylcellulose and polyvinyl pyrrolidone were formulated and the viscosity, gel strength, percentage mucoadhesion and in vitro diffusion of the formulation was evaluated.", "output": "carboxy, polyvinyl pyrrolidone." }, { "input": "Formulation ( F2 ) was subjected to in vivo analysis in rabbits.", "output": "There is no related enetity." }, { "input": "Formulation F2, which contained linseed mucilage ( 2 % ) and chitosan ( 0. 5 % ), showed the highest percentage of mucoadhesion, gel strength and sustained drug diffusion.", "output": "There is no related enetity." }, { "input": "The bioavailability by the oral route and buccal route were compared with that of the intravenous route.", "output": "There is no related enetity." }, { "input": "The bioavailability of venlafaxine in the formulation F2 was 63. 08 +/- 1. 28 % by buccal route, which was higher than by the oral route ( 39. 21 +/- 6. 18 % ).", "output": "venlafaxine." }, { "input": "Based on these results, the combination of linseed mucilage and chitosan can be used to form a buccal mucoadhesive gel and increase the bioavailability of venlafaxine.", "output": "venlafaxine." }, { "input": "Fluctuation analysis of an organic semiconductor - insulator interface.", "output": "There is no related enetity." }, { "input": "The space - charge region of an organic semiconductor ( OS ) - insulator interface is probed by analyzing the spontaneous, thermally driven drain current fluctuations of a field - effect transistor in which the OS forms the gate electrode.", "output": "There is no related enetity." }, { "input": "This so called \" excess drain current noise \" is the outcome of local fluctuations of the Fermi level, resulting from stochastic exchange of electrons between traps near the Fermi level.", "output": "There is no related enetity." }, { "input": "The power spectral density of this noise is characteristic of a Lorentzian process with a distribution of time constants, which is attributed to the disorder in the OS film.", "output": "There is no related enetity." }, { "input": "Furthermore, this disorder leads to local inhomogeneity of the work function in the film and a finite correlation length of the work function fluctuations.", "output": "There is no related enetity." }, { "input": "The measurement of work function noise is only possible within a correlation length of the OS - insulator interface.", "output": "There is no related enetity." }, { "input": "Through systematic variation of gate voltage, primary doping and secondary doping levels, the correlation length, disorder, and the trapping / de - trapping time constant are examined on polyaniline as a representative OS.", "output": "polyaniline." }, { "input": "A model is proposed for local work function variations and spontaneous charge - carrier fluctuations within polyaniline films with consequences for organic electronics using organic semiconductors.", "output": "polyaniline." }, { "input": "Modelling zirconium hydrides using the special quasirandom structure approach.", "output": "zirconium hydrides." }, { "input": "The study of the structure and properties of zirconium hydrides is important for understanding the embrittlement of zirconium alloys used as cladding in light water nuclear reactors.", "output": "zirconium hydrides, zirconium." }, { "input": "Simulation of the defect processes is complicated due to the random distribution of the hydrogen atoms.", "output": "hydrogen." }, { "input": "We propose the use of the special quasirandom structure approach as a computationally efficient way to describe this random distribution.", "output": "There is no related enetity." }, { "input": "We have generated six special quasirandom structure cells based on face centered cubic and face centered tetragonal unit cells to describe ZrH2 - x ( x = 0. 25 - 0. 5 ).", "output": "ZrH2." }, { "input": "Using density functional theory calculations we investigate the mechanical properties, stability, and electronic structure of the alloys.", "output": "There is no related enetity." }, { "input": "Fullerene Nanoarchitectonics: From Zero to Higher Dimensions.", "output": "Fullerene." }, { "input": "The strategic design of nanostructured materials, the properties of which could be controlled across different length scales and which, at the same time, could be used as building blocks for the construction of devices and functional systems into new technological platforms that are based on sustainable processes, is an important issue in bottom - up nanotechnology. Such strategic design has enabled the fabrication of materials by using convergent bottom - up and top - down strategies.", "output": "There is no related enetity." }, { "input": "Recent developments in the assembly of functional fullerene ( C60 ) molecules, either in bulk or at interfaces, have allowed the production of shape - controlled nano - to - microsized objects that possess excellent optoelectronic properties, thus enabling the fabrication of optoelectronic devices.", "output": "fullerene, C60." }, { "input": "Because fullerene molecules can be regarded as an ideal zero - dimensional ( 0D ) building units with attractive functions, the construction of higher - dimensional objects, that is, 1D, 2D, and 3D nanomaterials may realize important aspects of nanoarchitectonics.", "output": "fullerene." }, { "input": "This Focus Review summarizes the recent developments in the production of nanostructured fullerenes and techniques for the elaboration of fullerene nanomaterials into hierarchic structures.", "output": "fullerene." }, { "input": "Arsenic inhibits autophagic flux activating the Nrf2 - Keap1 pathway in a p62 - dependent manner.", "output": "Arsenic." }, { "input": "The Nrf2 - Keap1 signaling pathway is a protective mechanism promoting cell survival.", "output": "There is no related enetity." }, { "input": "Activation of the Nrf2 pathway by natural compounds has been proven to be an effective strategy for chemoprevention.", "output": "There is no related enetity." }, { "input": "Interestingly, a cancer - promoting function of Nrf2 has been recently observed in many types of tumors due to deregulation of the Nrf2 - Keap1 axis, which leads to constitutive activation of Nrf2.", "output": "There is no related enetity." }, { "input": "Here, we report a novel mechanism of Nrf2 activation by arsenic that is distinct from that of chemopreventive compounds.", "output": "There is no related enetity." }, { "input": "Arsenic deregulates the autophagic pathway through blockage of autophagic flux, resulting in accumulation of autophagosomes and sequestration of p62, Keap1, and LC3.", "output": "Arsenic." }, { "input": "Thus, arsenic activates Nrf2 through a non - canonical mechanism ( p62 - dependent ), leading to a chronic, sustained activation of Nrf2.", "output": "arsenic." }, { "input": "In contrast, activation of Nrf2 by sulforaphane and tert - butylhydroquinone depend upon Keap1 - C151 and not p62 ( the canonical mechanism ).", "output": "sulforaphane, tert - butylhydroquinone." }, { "input": "More importantly, SF and tBHQ do not have any effect on autophagy.", "output": "tBHQ." }, { "input": "In fact, SF and tBHQ alleviate arsenic - mediated deregulation of autophagy.", "output": "tBHQ, arsenic." }, { "input": "Collectively, these findings provide evidence that arsenic causes prolonged activation of Nrf2 through autophagy dysfunction, possibly providing a similar scenario to constitutive activation of Nrf2 found in certain human cancers.", "output": "arsenic." }, { "input": "This may represent a previously unrecognized mechanism underlying arsenic toxicity and carcinogenicity in humans.", "output": "arsenic." }, { "input": "Crop seed oil bodies: From challenges in protein identification to an emerging picture of the oil body proteome.", "output": "There is no related enetity." }, { "input": "Oleaginous seeds store lipids in specialized structures called oil bodies ( OBs ).", "output": "There is no related enetity." }, { "input": "These organelles consist of a core of neutral lipids bound by proteins embedded in a phospholipid monolayer.", "output": "There is no related enetity." }, { "input": "OB proteins are well conserved in plants and have long been grouped into only two categories: structural proteins or enzymes.", "output": "There is no related enetity." }, { "input": "Recent work, however, which identified other classes of proteins associated with OBs, clearly shows that this classification is obsolete.", "output": "There is no related enetity." }, { "input": "Proteomics - mediated OB protein identification is facilitated in plants for which the genome is sequenced and annotated.", "output": "There is no related enetity." }, { "input": "However, it is not clear whether this knowledge can be dependably transposed to less well characterized plants, including the well - established commercial sources of seed oil as well as the many others being proposed as novel sources for biodiesel, especially in Africa and Asia.", "output": "There is no related enetity." }, { "input": "Towards an update of the current data available on OB proteins this review discusses ( i ) the specific difficulties for proteomic studies of organelles; ( ii ) a 2012 census of the proteins found in seed OBs from various crops; ( iii ) the oleosin composition of OBs and their role in organelle stability; ( iv ) post translational modification of OB proteins as an emerging field of investigation; and finally we describe the emerging model of the OB proteome from oilseed crops.", "output": "There is no related enetity." }, { "input": "( 13 ) C - Detected Through - Bond Correlation Experiments for Protein Resonance Assignment by Ultra - Fast MAS Solid - State NMR.", "output": "( 13 ) C." }, { "input": "We present two sequences which combine ( ( 1 ) H, ( 15 ) N ) and ( ( 15 ) N, ( 13 ) C ) selective cross - polarization steps with an efficient variant of the J - based homonuclear transfer scheme, in which a spin - state - selective ( S ( 3 ) E ) block is incorporated to improve both resolution and sensitivity in the direct ( 13 ) C dimension.", "output": "( 1 ) H, ( 15 ) N, ( 15 ) N, ( 13 ) C, ( 13 ) C." }, { "input": "We propose these two sequences as a part of a suite of four N - C correlation experiments allowing for the assignment of protein backbone resonances in the solid state.", "output": "N - C." }, { "input": "We illustrate these experiments under ultra - fast magic angle spinning conditions on two samples of microcrystalline dimeric human superoxide dismutase ( SOD, 153 x 2 amino acids ), in its diamagnetic ( \" empty \", Zn ( II ) ) and paramagnetic ( Cu ( II ), Zn ( II ) ) states.", "output": "amino acids, Zn ( II ), Cu ( II ), Zn ( II )." }, { "input": "Wired Enzyme Electrodes - A Retroperspective Story about an Exciting Time at University of Texas at Austin and Its Impact on My Scientific Career.", "output": "There is no related enetity." }, { "input": "The present paper features an exciting time in the late 1980s when I, as a visiting scientist, had the privilege to participate in the early and very exciting development of the in vivo redox - polymer - wired glucose sensor in Professor Adam Heller ' s laboratory at the Department of Chemical Engineering at University of Texas at Austin.", "output": "glucose." }, { "input": "This story is followed by an overview of the research my visit initiated at Uppsala University.", "output": "There is no related enetity." }, { "input": "In collaboration with Swedish colleagues, we explored a few of the many possibilities to form new biosensors by utilizing Prof.", "output": "There is no related enetity." }, { "input": "Heller ' s concept of cross - linked redox - polymer / redox - enzyme electrodes.", "output": "There is no related enetity." }, { "input": "Direct Bio - electrocatalysis of O2 Reduction by Streptomyces coelicolor Laccase Orientated at Promoter - Modified Graphite Electrodes.", "output": "O2." }, { "input": "Bacterial laccase from Streptomyces coelicolor ( SLAC ) has been immobilised and orientated at promoter ( pyrene and neocuproine ) - modified electrodes productively both for direct electron transfer ( ET ) between the electrode and the T1 Cu site of SLAC and direct ( unmediated ) bio - electrocatalysis of dioxygen reduction.", "output": "pyrene, neocuproine, Cu, dioxygen." }, { "input": "Its T1 Cu potential ranges between 471 and 318 mV versus the normal hydrogen electrode, at pH 5. 5 and 8, respectively; this value is dependent both on the solution pH and electrode modification.", "output": "Cu, hydrogen." }, { "input": "In the presence of O2, Cu of the T2 / T3 trinuclear centre is distinguished electrochemically at 748 - 623 mV.", "output": "O2, Cu." }, { "input": "Depending on the promoter nature, different orientations of SLAC at pyrene - and neocuproine - modified electrodes can be followed from the kinetic analysis of the ET rates.", "output": "pyrene, neocuproine." }, { "input": "Bio - electrocatalytic reduction of oxygen starts from the T1 Cu potentials of SLAC, and is most efficient at the promoter - modified electrodes, thereby demonstrating good performance both in neutral and basic media and in solutions with a high NaCl content, such as sea water.", "output": "oxygen, Cu, NaCl." }, { "input": "The obtained results allow consideration of a broader bioenergetic application of laccases as biocathodes operating directly in such environmental media as sea water and physiological fluids.", "output": "There is no related enetity." }, { "input": "Cell - free co - production of an orthogonal transfer RNA activates efficient site - specific non - natural amino acid incorporation.", "output": "amino acid." }, { "input": "We describe a new cell - free protein synthesis ( CFPS ) method for site - specific incorporation of non - natural amino acids ( nnAAs ) into proteins in which the orthogonal tRNA ( o - tRNA ) and the modified protein ( i. e. the protein containing the nnAA ) are produced simultaneously.", "output": "amino acids." }, { "input": "Using this method, 0. 9 - 1. 7 mg / ml of modified soluble super - folder green fluorescent protein ( sfGFP ) containing either p - azido - l - phenylalanine ( pAzF ) or p - propargyloxy - l - phenylalanine ( pPaF ) accumulated in the CFPS solutions; these yields correspond to 50 - 88 % suppression efficiency.", "output": "p - azido - l - phenylalanine, pAzF, p - propargyloxy - l - phenylalanine, pPaF." }, { "input": "The o - tRNA can be transcribed either from a linearized plasmid or from a crude PCR product.", "output": "There is no related enetity." }, { "input": "Comparison of two different o - tRNAs suggests that the new platform is not limited by Ef - Tu recognition of the acylated o - tRNA at sufficiently high o - tRNA template concentrations.", "output": "There is no related enetity." }, { "input": "Analysis of nnAA incorporation across 12 different sites in sfGFP suggests that modified protein yields and suppression efficiencies ( i. e. the position effect ) do not correlate with any of the reported trends.", "output": "There is no related enetity." }, { "input": "Sites that were ineffectively suppressed with the original o - tRNA were better suppressed with an optimized o - tRNA ( o - tRNA ( opt ) ) that was evolved to be better recognized by Ef - Tu.", "output": "There is no related enetity." }, { "input": "This new platform can also be used to screen scissile ribozymes for improved catalysis.", "output": "There is no related enetity." }, { "input": "Understanding the thermodynamic micro - environment inside a pan coater using a data logging device.", "output": "There is no related enetity." }, { "input": "Abstract Objective: The objective of the current study was to establish the use of PyroButton data - logging device to monitor and quantify the thermodynamic environment ( temperature and humidity ) of a pan coating process.", "output": "There is no related enetity." }, { "input": "Material and methods: PyroButtons were placed ( fixed ) at various locations in a pan coater, including exhaust plenum, spray - gun bar, baffles and were also allowed to freely move with the tablet - bed.", "output": "There is no related enetity." }, { "input": "A full factorial design of experiments ( DOE ) study on three process parameters, exhaust temperature, pan speed and spray rate was conducted on a 24 inch pan coater, using a coating system and a core tablet combination expected to have a narrow process operating space.", "output": "There is no related enetity." }, { "input": "Results: It was shown that the PyroButtons can provide a detailed and useful signature of the coating process.", "output": "There is no related enetity." }, { "input": "PyroButton data showed that the tablet - bed temperature was always lower than exhaust temperature and that the difference was a function of the operating conditions such as spray rate.", "output": "There is no related enetity." }, { "input": "Similarly, the tablet - bed humidity was found to always be higher than exhaust humidity.", "output": "There is no related enetity." }, { "input": "Some of the DOE batches showed coating defects ( logo - bridging ).", "output": "There is no related enetity." }, { "input": "It was shown that the relative humidity ( RH ), as measured by the freely - moving PyroButtons in the tablet - bed, correlated well with the logo - bridging events.", "output": "There is no related enetity." }, { "input": "A critical RH value ( 30 % ) was established, above which logo - bridging was observed for the selected formulation.", "output": "There is no related enetity." }, { "input": "Conclusions: This study showed that PyroButtons can provide very meaningful micro - environmental data that can be correlated to coating defects, and can aid in establishing a process design space for a given coating and tablet formulation.", "output": "There is no related enetity." }, { "input": "Inflammation - Responsive Antioxidant Nanoparticles Based on a Polymeric Prodrug of Vanillin.", "output": "Vanillin." }, { "input": "Oxidative stress is induced by accumulation of hydrogen peroxide ( H2O2 ), and therefore, H2O2 could serve as a potential biomarker of various oxidative stress - associated inflammatory diseases.", "output": "hydrogen peroxide, H2O2, H2O2." }, { "input": "Vanillin is one of the major components of natural vanilla and has potent antioxidant and anti - inflammatory activities.", "output": "Vanillin." }, { "input": "In this work, we developed a novel inflammation - responsive antioxidant polymeric prodrug of vanillin, termed poly ( vanillin oxalate ) ( PVO ).", "output": "vanillin, poly ( vanillin oxalate ), PVO." }, { "input": "In design, PVO incorporates H2O2 - reacting peroxalate ester bonds and bioactive vanillin via acid - responsive acetal linkages in its backbone.", "output": "PVO, H2O2, peroxalate ester, vanillin, acetal." }, { "input": "Therefore, in cells undergoing damages by oxidative stress, PVO readily degrades into three nontoxic components, one of which is antioxidant and anti - inflammatory vanillin.", "output": "PVO, vanillin." }, { "input": "PVO nanoparticles exhibit potent antioxidant activities by scavenging H2O2 and inhibiting the generation of ROS ( reactive oxygen species ) and also reduce the expression of pro - inflammatory cytokines in activated macrophages in vitro and in vivo.", "output": "PVO, H2O2, oxygen." }, { "input": "We, therefore, anticipate that PVO nanoparticles have great potential as novel antioxidant therapeutics and drug delivery systems for ROS - associated inflammatory diseases.", "output": "PVO." }, { "input": "Fibrillar Morphology of Derivatives of Poly ( 3 - alkylthiophene ) s by Solvent Vapor Annealing: Effects of Conformational Transition and Conjugate Length.", "output": "Poly ( 3 - alkylthiophene ) s." }, { "input": "A fibrillar morphology was obtained, compared to the featherless pristine films, via solvent annealing the films of a series of derivatives of poly ( 3 - alkylthiophene ) s ( P3ATs ): poly ( 3 - dodecylthiophene ) ( P3DDT ), poly ( 3, 3 ''' - didodecyl - quaterthiophene ) ( PQT12 ), and poly ( 2, 5 - bis ( 3 - dodecylthiophen - 2 - yl ) thieno [ 3, 2 - b ] thiophene ) ( pBTTT12 ).", "output": "poly ( 3 - alkylthiophene ) s, P3ATs, poly ( 3 - dodecylthiophene ), P3DDT, poly ( 3 , 3 ''' - didodecyl - quaterthiophene ), PQT12, poly ( 2 , 5 - bis ( 3 - dodecylthiophen - 2 - yl ) thieno [ 3 , 2 - b ] thiophene ), pBTTT12." }, { "input": "Among the solvents used, including dichloromethane, chloroform, tetrahydrofuran, and carbon disulfide ( CS2 ), CS2 was the best to induce fibril formation because its solubility parameter is closest to those of the P3AT derivatives.", "output": "dichloromethane, chloroform, tetrahydrofuran, carbon disulfide, CS2, CS2, P3AT." }, { "input": "It was found that higher critical CS2 vapor pressures were needed to form crystal nuclei with increasing conjugation length and molecular weight of the P3AT derivatives; i. e., the critical vapor pressures for P3DDT 13. 9k and PQT12 15. 5k were 59. 0 % and 80. 7 %, respectively, and there were no nuclei of fibrils for pBTTT12 15. 6k with the highest conjugation length, even at a CS2 vapor pressure of 98. 3 %.", "output": "CS2, P3AT, P3DDT, PQT12, pBTTT12, CS2." }, { "input": "Meanwhile, at the highest vapor pressure, the fibril density decreased with increasing conjugation length and molecular weight of the P3AT derivatives.", "output": "P3AT." }, { "input": "This is attributed to the rod - like conformation prevailing for polymers with larger conjugation length and higher molecular weight during solvent annealing, making the conformational transition toward coils more difficult and hindering diffusion of molecules.", "output": "There is no related enetity." }, { "input": "The results presented here are expected to be helpful for the design and processing of conjugated semiconductor polymers.", "output": "There is no related enetity." }, { "input": "Hair as an alternative matrix in bioanalysis.", "output": "There is no related enetity." }, { "input": "Alternative matrices are steadily gaining recognition as biological samples for toxicological analyses.", "output": "There is no related enetity." }, { "input": "Hair presents many advantages over traditional matrices, such as urine and blood, since it provides retrospective information regarding drug exposure, can distinguish between chronic and acute or recent drug use by segmental analysis, is easy to obtain, and has considerable stability for long periods of time.", "output": "There is no related enetity." }, { "input": "For this reason, it has been employed in a wide variety of contexts, namely to evaluate workplace drug exposure, drug - facilitated sexual assault, pre - natal drug exposure, anti - doping control, pharmacological monitoring and alcohol abuse.", "output": "alcohol." }, { "input": "In this article, issues concerning hair structure, collection, storage and analysis are reviewed.", "output": "There is no related enetity." }, { "input": "The mechanisms of drug incorporation into hair are briefly discussed.", "output": "There is no related enetity." }, { "input": "Analytical techniques for simultaneous drug quantification in hair are addressed.", "output": "There is no related enetity." }, { "input": "Finally, representative examples of drug quantification using hair are summarized, emphasizing its potentialities and limitations as an alternative biological matrix for toxicological analyses.", "output": "There is no related enetity." }, { "input": "Few - Layer MoS2 with High Broadband Photogain and Fast Optical Switching for Use in Harsh Environments.", "output": "MoS2." }, { "input": "Few - layered MoS2 as Schottky metal - semiconductor - metal photodetectors ( MSM PDs ) for use in harsh environments makes its debut as two - dimensional ( 2D ) optoelectronics with high broadband gain ( up to 13. 3 ), high detectivity ( up to ~ 10 ( 10 ) cm Hz ( 1 / 2 ) / W ), fast photoresponse ( rise time of ~ 70 mu s and fall time of ~ 110 mu s ), and high thermal stability ( at a working temperature of up to 200 degrees C ).", "output": "MoS2." }, { "input": "Ultrahigh responsivity ( 0. 57 A / W ) of few - layer MoS2 at 532 nm is due to the high optical absorption ( ~ 10 % despite being less than 2 nm in thickness ) and a high photogain, which sets up a new record that was not achievable in 2D nanomaterials previously.", "output": "MoS2." }, { "input": "This study opens avenues to develop 2D nanomaterial - based optoelectronics for harsh environments in imaging techniques and light - wave communications as well as in future memory storage and optoelectronic circuits.", "output": "There is no related enetity." }, { "input": "High Level ab initio Calculations for ClFn ( + ) ( n = 1 - 6 ) Ions: Refining the Recoupled Pair Bonding Model.", "output": "ClFn ( + )." }, { "input": "Based on detailed, high level ab initio calculations on a number of halogenated compounds of second row, late p - block elements, the SFn, ClFn, PFn, SCln, and SFnCl families, we found that a new type of bond - the recoupled pair bond - accounts for the ability of these elements to form hypervalent, or hypercoordinated, compounds.", "output": "SFn, ClFn, PFn, SCln, SFnCl." }, { "input": "Hypervalent molecules are formed when it is energetically favorable for the electrons in a lone pair orbital to be recoupled, allowing each of the electrons to form chemical bonds with ligands.", "output": "There is no related enetity." }, { "input": "In this paper, we characterize the structures and energetics of the ground and low - lying excited states of the ClFn ( + ) ( n = 1 - 6 ) ions, using high level ab initio methods [ MRCI, CCSD ( T ) / RCCSD ( T ) ] with large correlation consistent basis sets.", "output": "ClFn ( + )." }, { "input": "We computed a number of quantities, including ClFn ( + ) structures, bond dissociation energies and ClFn ionization energies, and compare our results with the available experimental data.", "output": "ClFn ( + ), ClFn." }, { "input": "Both the bond dissociation energies and ionization energies oscillate, variations that are readily explained using the recoupled pair bonding model.", "output": "There is no related enetity." }, { "input": "Comparisons are drawn between the ClFn ( + ) cations and their counterparts in the isoelectronic SFn series, which possess many similarities.", "output": "ClFn ( + ), SFn." }, { "input": "We found two significant differences between the ClFn ( + ) and SFn series: ( i ) the bond dissociation energies of ClFn ( + ) are much weaker than those of the corresponding SFn species, and ( ii ) there is no stable ( 3 ) A2 state in ClF2 ( + ) corresponding to the stable state found in SF2.", "output": "ClFn ( + ), SFn, ClFn ( + ), SFn, ClF2 ( + ), SF2." }, { "input": "Examination of the Mulliken populations at the HF / AVTZ level for ClFn ( + ) and SFn species predicts that the F atom in the axial ( recoupled pair bonding ) position is more highly charged than the F atom in the equatorial ( covalent bonding ) position; there is also less change transfer to the F atoms in ClFn ( + ) than in SFn.", "output": "HF, ClFn ( + ), SFn, F, F, F, ClFn ( + ), SFn." }, { "input": "The positive charge on Cl ( + ) makes it more difficult for an F atom to attract electrons from Cl ( + ) than from S and correspondingly less favorable to recouple the electrons in the lone pair orbitals in the ClFn ( + ) species.", "output": "Cl ( + ), F, Cl ( + ), S, ClFn ( + )." }, { "input": "Interacting Glutamate Receptor - Like Proteins in Phloem Regulate Lateral Root Initiation in Arabidopsis.", "output": "Glutamate." }, { "input": "Molecular, genetic, and electrophysiological evidence indicates that at least one of the plant Glu receptor - like molecules, GLR3. 4, functions as an amino acid - gated Ca ( 2 + ) channel at the plasma membrane.", "output": "amino acid, Ca ( 2 + )." }, { "input": "The aspect of plant physiology, growth, or development to which GLR3. 4 contributes is an open question.", "output": "There is no related enetity." }, { "input": "Protein localization studies performed here provide important information.", "output": "There is no related enetity." }, { "input": "In roots, GLR3. 4 and the related GLR3. 2 protein were present primarily in the phloem, especially in the vicinity of the sieve plates.", "output": "There is no related enetity." }, { "input": "GLR3. 3 was expressed in most cells of the growing primary root but was not enriched in the phloem, including the sieve plate area.", "output": "There is no related enetity." }, { "input": "GLR3. 2 and GLR3. 4 physically interacted with each other better than with themselves as evidenced by a biophotonic assay performed in human embryonic kidney cells and Nicotiana benthamiana leaf cells.", "output": "There is no related enetity." }, { "input": "GLR3. 3 interacted poorly with itself or the other two GLRs.", "output": "There is no related enetity." }, { "input": "Mutations in GLR3. 2, GLR3. 4, or GLR3. 2 and GLR3. 4 caused the same and equally severe phenotype, namely, a large overproduction and aberrant placement of lateral root primordia.", "output": "There is no related enetity." }, { "input": "Loss of GLR3. 3 did not affect lateral root primordia.", "output": "There is no related enetity." }, { "input": "These results support the hypothesis that apoplastic amino acids acting through heteromeric GLR3. 2 / GLR3. 4 channels affect lateral root development via Ca ( 2 + ) signaling in the phloem.", "output": "amino acids, Ca ( 2 + )." }, { "input": "Docosahexaenoic acid ( DHA ) ameliorates paraquat - induced pulmonary fibrosis in rats possibly through up - regulation of Smad 7 and SnoN.", "output": "Docosahexaenoic acid, DHA, paraquat." }, { "input": "Paraquat ( PQ ) poisoning has caused a large number of human fatalities due to the progressive and irreversible pulmonary fibrosis.", "output": "Paraquat." }, { "input": "Docosahexaenoic acid ( DHA ) is well - recognized as important modulators of multiple biological pathways that affect health and disease.", "output": "Docosahexaenoic acid, DHA." }, { "input": "A line of studies have shown that DHA supplementation is associated with the alleviation of some tissue fibrosis.", "output": "DHA." }, { "input": "In the current study, pulmonary fibrosis of rats was produced by a single oral dose of 50mg / kgbw PQ treatment.", "output": "There is no related enetity." }, { "input": "Daily 500mg / kgbw DHA supplementation was provided 7days before PQ treatment and lasted for consecutive 35days.", "output": "DHA." }, { "input": "DHA was found to ameliorate the pulmonary fibrotic alterations induced by PQ, which was evidenced by significant reduction of histological changes, hydroxyproline content and level of the transforming growth factor - beta 1 ( TGF - beta 1 ) mRNA.", "output": "DHA, hydroxyproline." }, { "input": "Furthermore, the protein levels of Smad 7 and SnoN in the DHA supplemented rats were significantly increased compared with those in the rats of the PQ group.", "output": "DHA." }, { "input": "These results suggested that DHA ameliorated pulmonary fibrosis induced by PQ might be attributed to its enhancement of Smad 7 and SnoN expression.", "output": "DHA." }, { "input": "Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats.", "output": "Melatonin, ethanol, estradiol, progesterone, steroid." }, { "input": "Chronic ethanol intake is associated with sex hormone disturbances, and it is well known that melatonin plays a key role in regulating several reproductive processes.", "output": "ethanol, melatonin." }, { "input": "We report the effects of ethanol intake and melatonin treatment ( at doses of 100 mu g / 100gBW / day ) on sex hormones and steroid receptors in the ovaries, oviducts and uteri of ethanol - preferring rats.", "output": "ethanol, melatonin, steroid, ethanol." }, { "input": "After 150 days of treatment, animals were euthanized, and tissue samples were harvested to evaluate androgen, estrogen, progesterone and melatonin receptor subunits ( AR, ER - alpha and ER - beta, PRA, PRB and MT1R, respectively ).", "output": "androgen, estrogen, progesterone, melatonin." }, { "input": "Melatonin decreased estradiol ( E2 ) and increased progesterone ( P4 ) and 6 - sulfatoxymelatonin ( 6 - STM ), while an ethanol - melatonin combination reduced both P4 and E2.", "output": "Melatonin, estradiol, progesterone, 6 - sulfatoxymelatonin, 6 - STM, ethanol, melatonin." }, { "input": "Ovarian AR was not influenced by either treatment, and oviduct AR was reduced after ethanol - melatonin combination.", "output": "ethanol, melatonin." }, { "input": "Oviduct ER - alpha, ER - beta and uterine ER - beta were down - regulated by either ethanol or melatonin.", "output": "ethanol, melatonin." }, { "input": "Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol - melatonin combination, whereas PRA was down - regulated in the uterus and oviduct after ethanol consumption.", "output": "ethanol, ethanol, melatonin, ethanol." }, { "input": "MT1R was increased in ovaries and uteri of melatonin - treated rats.", "output": "melatonin." }, { "input": "Ethanol and melatonin exert opposite effects on E2 and P4, and they differentially regulate the expression of sex steroid receptors in female reproductive tissues.", "output": "Ethanol, melatonin, steroid." }, { "input": "A cyclodextrin - capped histone deacetylase inhibitor.", "output": "There is no related enetity." }, { "input": "We have synthesized a beta - cyclodextrin ( beta CD ) - capped histone deacetylase ( HDAC ) inhibitor 3 containing an alkyl linker and a zinc - binding hydroxamic acid motif.", "output": "beta - cyclodextrin, beta CD, zinc, hydroxamic acid." }, { "input": "Biological evaluation ( HDAC inhibition studies ) of 3 enabled us to establish the effect of replacing an aryl cap ( in SAHA ( vorinostat, ) ) 1 by a large saccharidic scaffold \" cap \".", "output": "SAHA, vorinostat." }, { "input": "HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8.", "output": "SAHA." }, { "input": "However, compound 3 displayed no cellular activity.", "output": "There is no related enetity." }, { "input": "Computer simulations of cluster impacts: effects of the atomic masses of the projectile and target.", "output": "There is no related enetity." }, { "input": "Cluster secondary ion mass spectrometry is now widely used for the characterization of nanostructures.", "output": "There is no related enetity." }, { "input": "In order to gain a better understanding of the physics of keV cluster bombardment of surfaces and nanoparticles ( NPs ), the effects of the atomic masses of the projectile and of the target on the energy deposition and induced sputtering have been studied by means of molecular dynamics simulations.", "output": "There is no related enetity." }, { "input": "10 keV C60 was used as a model projectile and impacts on both a flat polymer surface and a metal NP were analyzed.", "output": "C60." }, { "input": "In the first case, the mass of the impinging carbon atoms was artificially varied and, in the second case, the mass of the NP atoms was varied.", "output": "carbon." }, { "input": "The results can be rationalized on the basis of the different atomic mass ratios of the projectile and target.", "output": "There is no related enetity." }, { "input": "In general, the emission is at its maximum, when the projectile and target have the same atomic masses.", "output": "There is no related enetity." }, { "input": "In the case of the supported NP, the emission of the underlying organic material increases as the atomic mass of the NP decreases.", "output": "There is no related enetity." }, { "input": "However, it is always less than that calculated for the bare organic surface, irrespective of the mass ratio.", "output": "There is no related enetity." }, { "input": "The results obtained with C60 impacts on the flat polymer are also compared to simulations of C60 and monoatomic Ga impacts on the NP.", "output": "C60, C60, Ga." }, { "input": "New testing procedures of a capacitive deionization reactor.", "output": "There is no related enetity." }, { "input": "Currently, according to conventional charge - discharge profiles, energy consumed in charging Capacitive Deionization ( CDI ) systems is always a function of different parameters ( current used for charging, capacitance and current employed for discharging ) making it difficult to separate the effect of these parameters on CDI performance and energy efficiency.", "output": "There is no related enetity." }, { "input": "Thus, energy efficiencies are strongly influenced by the current in the preceding charge or discharge stage of the process.", "output": "There is no related enetity." }, { "input": "We find consistently that this phenomenon, which to our knowledge has not been addressed in previous CDI communications, is much more intense when different currents are applied for each of the charging and discharging cycles.", "output": "There is no related enetity." }, { "input": "The investigation reported here provides a mechanistic analysis of the operational aspects of CDI and develops a new procedure that allows for a precise evaluation of performance and energy efficiency.", "output": "There is no related enetity." }, { "input": "Furthermore, the model developed here allows one to separate charge and discharge cycles, and therefore contributes to the possibility of defining an operational mode for real - world devices in which effective separation of deionization and regeneration steps needs to be implemented.", "output": "There is no related enetity." }, { "input": "This method of analysis could be useful not only for CDI but also for other electrochemical systems such as in secondary batteries and supercapacitors where charge and discharge are typically employed.", "output": "There is no related enetity." }, { "input": "Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride - induced acute liver injury in rats.", "output": "methylsulfonylmethane, carbon tetrachloride." }, { "input": "This study evaluated the effect of methylsulfonylmethane ( MSM ) on carbon tetrachloride ( CCl4 ) - induced acute liver injury in rats.", "output": "methylsulfonylmethane, MSM, carbon tetrachloride, CCl4." }, { "input": "A single injection of CCl4 ( 2 ml / kg, i. p. ) increased serum aminotransferases ( ALT and AST ) activities.", "output": "CCl4." }, { "input": "In addition, CCl4 treatment led to elevation of hepatic malondialdehyde ( MDA ) content as well as decrease in superoxide dismutase ( SOD ) and catalase ( CAT ) activities.", "output": "CCl4, malondialdehyde, MDA, superoxide." }, { "input": "Furthermore, cytochrome P450 2E1 ( CYP2E1 ) content was suppressed while proinflammatory cytokines tumour necrosis factor - alpha ( TNF - alpha ) and interleukin - 6 ( IL - 6 ) levels increased in liver tissue after CCl4 administration.", "output": "CCl4." }, { "input": "We showed that acute CCl4 - induced damage was accompanied by a rise in Bax / Bcl2 ratio indicating apoptosis.", "output": "CCl4." }, { "input": "Pre - treatment with MSM ( 400 mg / kg ) inhibited the increases of serum ALT and AST activities, decreased hepatic MDA, TNF - alpha, IL - 6 and Bax / Bcl2 ratio compared to CCl4 treated group.", "output": "MSM, MDA, CCl4." }, { "input": "On the other hand, MSM raised SOD and CAT activities as well as CYP2E1 level in liver tissues.", "output": "MSM." }, { "input": "The present study shows that MSM possesses a hepatoprotective effect against CCl4 - induced liver injury in rats.", "output": "MSM, CCl4." }, { "input": "This protective effect might be through its antioxidant, anti - inflammatory and antiapoptotic properties.", "output": "There is no related enetity." }, { "input": "Selective kinin receptor agonists as cardioprotective agents in myocardial ischemia and diabetes.", "output": "There is no related enetity." }, { "input": "Cardiac ischemia is a leading cause of death, especially in diabetic patients.", "output": "There is no related enetity." }, { "input": "The diabetic ischemic heart is resistant experimentally to established cardioprotective treatments.", "output": "There is no related enetity." }, { "input": "New pharmacological approaches to cardiac protection are warranted.", "output": "There is no related enetity." }, { "input": "The kallikrein - kinin system is involved in myocardial protection in ischemia.", "output": "There is no related enetity." }, { "input": "Respective role of B1 ( B1R ) and B2 ( B2R ) receptors remains controversial.", "output": "There is no related enetity." }, { "input": "We tested whether pharmacological activation of kinin receptors may have therapeutic effect in cardiac ischemia - reperfusion in non diabetic ( NDiab ) and diabetic ( Diab ) mice.", "output": "There is no related enetity." }, { "input": "We assessed effect on infarct size ( IS ) and signaling pathways involved in myocardial protection of potent selective pharmacological agonists of B1R or B2R given at reperfusion.", "output": "There is no related enetity." }, { "input": "In NDiab mice, a B2R agonist reduced significantly IS by 47 %, similarly to ramiprilat or ischemic postconditioning, via activation of PI3K / Akt pathway leading to inhibition of GSK3 beta.", "output": "There is no related enetity." }, { "input": "B1R agonist has no effect on IS.", "output": "There is no related enetity." }, { "input": "In contrast, in Diab mice, the B2R agonist, ramiprilat or ischemic postconditioning failed to reduce IS but a B1R agonist significantly reduced IS by 44 % via activation of PI3K / Akt and ERK1 / 2, both leading to GSK3 beta inhibition.", "output": "ramiprilat." }, { "input": "Differential effect of B2R or B1R agonists in NDiab and Diab mice can be linked to inactivation of B2R signaling and induction of B1R in heart of Diab mice.", "output": "There is no related enetity." }, { "input": "Thus, a pharmacological B2R agonist is cardioprotective in acute ischemia in non diabetic animals.", "output": "There is no related enetity." }, { "input": "B1R agonist overcomes resistance of diabetic heart to cardioprotective treatments.", "output": "There is no related enetity." }, { "input": "Pharmacological activation of B1R and B2R may become treatment for diabetic and non diabetic patients respectively in acute coronary syndromes.", "output": "There is no related enetity." }, { "input": "Minireview: androgen metabolism in castration - resistant prostate cancer.", "output": "androgen." }, { "input": "The decades - old terminology of androgen independence has been replaced in recent years with castration - resistant prostate cancer.", "output": "androgen." }, { "input": "Biological and clinical evidence have together conspired to support the use of this revised terminology by demonstrating that in the vast majority of cases tumors are neither truly depleted of androgens, nor are they free of the requirement for androgens to sustain growth and progression.", "output": "androgens, androgens." }, { "input": "Abiraterone acetate, an androgen synthesis inhibitor, and enzalutamide, a potent androgen receptor antagonist, both exploit the continued requirement for androgens.", "output": "Abiraterone acetate, androgen, enzalutamide, androgen, androgens." }, { "input": "A central question, given the therapeutic gains enabled by further suppression of the androgen axis with these newer agents, is whether there may be additional clinical benefit gained by moving the goal posts of androgen suppression even further.", "output": "androgen, androgen." }, { "input": "The answer lies in part with the mechanisms utilized by tumors that enable resistance to these therapies.", "output": "There is no related enetity." }, { "input": "The aims of this review were to give a broad outline of steroidogenesis in prostate cancer and to highlight recent developments in understanding resistance to hormonal therapies.", "output": "There is no related enetity." }, { "input": "Nrf2 - activators Attenuate the Progression of Nonalcoholic Steatohepatitis - Related Fibrosis in a Dietary Rat Model.", "output": "There is no related enetity." }, { "input": "Oxidative stress is considered to be a key mechanism of hepatocellular injury and disease progression in patients with nonalcoholic steatohepatitis ( NASH ).", "output": "There is no related enetity." }, { "input": "The transcription factor Nrf2 plays a central role in stimulating expression of various antioxidant - associated genes in the cellular defense against oxidative stress.", "output": "There is no related enetity." }, { "input": "As the cytosolic repressor Keap1 negatively regulates Nrf2, activation of Nrf2 facilitated by its release from Keap1 may represent a promising strategy in the treatment of NASH.", "output": "There is no related enetity." }, { "input": "To test this hypothesis, we utilized two chemically distinct types of Nrf2 - activator.", "output": "There is no related enetity." }, { "input": "One is the thiol - reactive agent oltipraz ( OPZ ), a typical Nrf2 - activator, and the other is a novel biaryl urea compound, termed NK - 252.", "output": "thiol, oltipraz, OPZ, urea, NK - 252." }, { "input": "NK - 252 exhibits a greater Nrf2 - activating potential than OPZ.", "output": "NK - 252, OPZ." }, { "input": "Furthermore, in vitro binding studies revealed that NK - 252 interacts with the domain containing the Nrf2 - binding site of Keap1, whereas OPZ does not.", "output": "NK - 252, OPZ." }, { "input": "This finding indicates that NK - 252 is more potent than OPZ due to its unique mechanism of action.", "output": "NK - 252, OPZ." }, { "input": "For in vivo animal model studies, we employed rats on a choline - deficient L - amino acid - defined ( CDAA ) - diet, which demonstrate pathological findings similar to those seen in human NASH.", "output": "choline, L - amino acid." }, { "input": "The administration of OPZ or NK - 252 significantly attenuated the progression of histological abnormalities in rats on a CDAA diet, especially hepatic fibrosis.", "output": "OPZ, NK - 252." }, { "input": "In conclusion, by using Nrf2 - activators with independent mechanisms of action, we show in a rat model of NASH that the activation of Nrf2 is responsible for the anti - fibrotic effects of these drugs.", "output": "There is no related enetity." }, { "input": "This strategy of Nrf2 activation presents new opportunities for treatment of NASH patients with hepatic fibrosis.", "output": "There is no related enetity." }, { "input": "Design, Synthesis and Biological Evaluation of Trimethine Cyanine Dyes as Fluorescent Probes for the Detection of Tau Fibrils in Alzheimer ' s Disease Brain and Olfactory Epithelium.", "output": "Trimethine Cyanine." }, { "input": "Shedding light on grey matter: Fluorescent trimethine cyanines were evaluated as imaging probes for neurofibrillary tangles in post - mortem brain sections of Alzheimer ' s disease patients.", "output": "trimethine cyanines." }, { "input": "These probes bind to neurofibrillary tangles with high contrast and selectivity over amyloid beta plaques.", "output": "There is no related enetity." }, { "input": "EPITOPE RECOGNITION IN HLA - DR3 TRANSGENIC MICE IMMUNIZED TO TSH - R PROTEIN OR PEPTIDES.", "output": "There is no related enetity." }, { "input": "Development of Graves ' disease ( GD ) is related to HLA - DR3.", "output": "There is no related enetity." }, { "input": "The extracellular domain ( ECD ) of human TSH receptor ( hTSH - R ) is a crucial antigen in GD.", "output": "There is no related enetity." }, { "input": "hTSH - R peptide 37 ( AA 78 - 94 ) is an important immunogenic peptide in DR3 transgenic mice immunized to hTSH - R.", "output": "There is no related enetity." }, { "input": "This study 1 ) examines epitope recognition in DR3 transgenic mice immunized to hTSH - R protein, and 2 ) evaluates ability of a mutant hTSH - R peptide to attenuate immunogenicity of hTSH - R peptide 37. DR3 transgenic mice were immunized to recombinant hTSH - R - ECD protein or peptides.", "output": "There is no related enetity." }, { "input": "A mutant hTSH - R 37 peptide ( ISRIYVSIDATLSQLES: 37m ), in which DR3 binding motif position 5 was mutated V > A, and position 8 Q > S, was synthesized.", "output": "There is no related enetity." }, { "input": "37m should bind to HLA - DR3, but not bind T - cell receptors.", "output": "There is no related enetity." }, { "input": "DR3 transgenic mice were immunized to hTSH - R 37 and 37m. Mice immunized to hTSH - R - ECD protein developed strong anti hTSH - R antibody, and antisera reacted strongly with hTSH - R peptides 1 - 5 ( 20 - 94 ), 21 ( 258 - 277 ), 41 ( 283 - 297 ), 36 ( 376 - 389 ), and 31 ( 399 - 418 ).", "output": "There is no related enetity." }, { "input": "Strikingly, antisera raised to hTSH - R peptide 37 bound to hTSH - R peptides 1 - 7 ( 20 - 112 ), 10 ( 132 - 50 ), 33 ( 137 - 150 ), 41, 23 ( 286 - 305 ), 24 ( 301 - 320 ), 36, and 31, as well as to hTSH - R - ECD protein.", "output": "There is no related enetity." }, { "input": "Both antibody titers to hTSH - R 37, and reaction of splenocytes to hTSH - R 37, were significantly reduced in mice immunized to hTSH - R 37 plus 37m, compare to mice immunized to hTSH - R 37 alone. The ability of immunization to a single peptide to induce antibodies that bind hTSH - R - ECD protein, and multiple unrelated peptides, is a unique observation.", "output": "There is no related enetity." }, { "input": "Immunogenic reaction to hTSH - R peptide 37 was partially suppressed by 37m, and this may contribute to immunotherapy of AITD.", "output": "There is no related enetity." }, { "input": "Cubilin, a high affinity receptor for fibroblast growth factor 8, is required for cell survival in the developing vertebrate head.", "output": "There is no related enetity." }, { "input": "Cubilin ( Cubn ) is a multiligand endocytic receptor critical for the intestinal absorption of vitamin B12 and renal protein reabsorption.", "output": "vitamin B12." }, { "input": "During mouse development Cubn is expressed in both embryonic and extra - embryonic tissues and Cubn gene inactivation results in early embryo - lethality most likely due to the impairment of the function of extra - embryonic Cubn.", "output": "There is no related enetity." }, { "input": "We here focus on the developmental role of Cubn expressed in the embryonic head.", "output": "There is no related enetity." }, { "input": "We report that Cubn is a novel, interspecies conserved Fgf receptor.", "output": "There is no related enetity." }, { "input": "Epiblast - specific inactivation of Cubn in the mouse embryo as well as Cubn silencing in the anterior head of frog or the cephalic neural crest of chick embryos show that Cubn is required during early somite stages to convey survival signals in the developing vertebrate head.", "output": "There is no related enetity." }, { "input": "Surface Plasmon resonance analysis reveals that fibroblast growth factor 8 ( Fgf8 ), a key mediator of cell survival, migration, proliferation and patterning in the developing head is a high affinity ligand for Cubn.", "output": "There is no related enetity." }, { "input": "Cell uptake studies show that binding to Cubn is necessary for the phosphorylation of the Fgf signaling mediators MAPK and Smad1.", "output": "There is no related enetity." }, { "input": "Although Cubn may not form stable ternary complexes with Fgf receptors ( FgfRs ) it acts together with and / or is necessary for optimal FgfR activity.", "output": "There is no related enetity." }, { "input": "We propose that plasma membrane binding of Fgf8, and most likely of the Fgf8 family members Fgf17 and Fgf18, to Cubn improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity.", "output": "There is no related enetity." }, { "input": "Using partial least squares regression to analyze cellular response data.", "output": "There is no related enetity." }, { "input": "This Teaching Resource provides lecture notes, slides, and a problem set for a lecture introducing the mathematical concepts and interpretation of partial least squares regression ( PLSR ) that were part of a course entitled \" Systems Biology: Mammalian Signaling Networks. \" PLSR is a multivariate regression technique commonly applied to analyze relationships between signaling or transcriptional data and cellular behavior.", "output": "There is no related enetity." }, { "input": "Functional conservation and structural diversification of silk sericins in two moth species.", "output": "There is no related enetity." }, { "input": "Sericins are hydrophilic structural proteins produced by caterpillars in the middle section of silk glands and are layered over fibroin proteins secreted in the posterior section.", "output": "There is no related enetity." }, { "input": "In the process of spinning, fibroins form strong solid filaments, while sericins seal the pair of filaments into a single fiber and glue the fiber into a cocoon.", "output": "There is no related enetity." }, { "input": "Galleria mellonella and the previously examined Bombyx mori harbor three sericin genes that encode proteins containing long repetitive regions.", "output": "There is no related enetity." }, { "input": "Galleria sericin genes are similar to each other and the protein repeats are built from short and extremely serine - rich motifs, while Bombyx sericin genes are diversified and encode proteins with long and complex repeats.", "output": "serine." }, { "input": "Developmental changes in sericin properties are controlled at the level of gene expression and splicing.", "output": "There is no related enetity." }, { "input": "In Galleria, MG - 1 sericin is produced throughout larval life until the wandering stage, while the production of MG - 2 and MG - 3 reaches a peak during cocoon spinning.", "output": "There is no related enetity." }, { "input": "Is Diacetyl a Respiratory Sensitizer?", "output": "Diacetyl." }, { "input": "A Reconsideration Using QSAR, QMM, and Competition Experiments.", "output": "There is no related enetity." }, { "input": "Concerns have been raised that diacetyl ( DA ) might be a respiratory sensitizer based on its LUMO energy similar to that of the respiratory allergen toluene - 2, 4 - diisocyanate ( TDI ) and results of a local lymph node assay ( LLNA ) that reported an EC3 of 1. 9 %.", "output": "diacetyl, toluene - 2 , 4 - diisocyanate, TDI." } ] }