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[] | DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia. | train |
[
"haloperidol"
] | We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. 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. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. 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 × 10(-6), odds ratio 2.32 in the combined sample). 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. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD. | train |
[] | Nanosilver effects on growth parameters in experimental aflatoxicosis in broiler chickens. | train |
[
"aflatoxin"
] | Aflatoxicosis is a cause of economic losses in broiler production. 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. 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. 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. Data on body weight, body weight gain (BWG), feed intake, and feed conversion ratio (FCR) were recorded at weekly intervals. Also cumulative data were assessed. 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. 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. | train |
[] | The influence of the intensity of smoking and years of work in the metallurgy on pro-oxidant/antioxidant balance in the blood of smelters. | train |
[
"nitric oxide",
"Mercury"
] | Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. | train |
[
"nitric oxide",
"mercury"
] | Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-κB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense. | train |
[
"chromium"
] | Toxic effects of chromium on tannery workers at Sialkot (Pakistan). | train |
[
"graphite",
"chromium",
"Chromium",
"malondialdehyde"
] | Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. 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. 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). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. 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). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes. | train |
[] | Fish, contaminants and human health: quantifying and weighing benefits and risks. | train |
[] | This paper describes a quantitative risk-benefit assessment of fish consumption. We compare the net health effect expressed in DALYs of two scenarios. The reference scenario is the current fish intake of the Dutch population, which is less than what is recommended by the health authorities. The alternative scenario describes the health effects if the population consumes 200g of fish per week, which is close to the recommendation. All health effects due to fish consumption for which there is convincing evidence are incorporated in the assessment. The QALIBRA software (www.qalibra.eu) is used to simulate the two scenarios. The results show there is a net benefit for the population if it consumes 200g of fish each week. | train |
[] | Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats. | train |
[] | Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. 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. 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. 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. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. 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. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats. | train |
[] | Allelopathic activity studies of Mikania scandens. | train |
[
"mikanolide"
] | 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. 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 µM mL(-1). 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. | train |
[
"polycyclic aromatic hydrocarbons"
] | Detection of polycyclic aromatic hydrocarbons in different types of processed foods. | train |
[
"benzo(a)anthracene",
"fluoranthene",
"cyclohexane",
"benzoflouroanthene",
"benzo(a)pyrene",
"Polycyclic aromatic hydrocarbons",
"benzo(e)pyrene",
"PCAHs",
"methanolic potassium hydroxide",
"pyrene"
] | Polycyclic aromatic hydrocarbons (PCAHs), particularly those with a high molecular weight, have been classified as probable carcinogens to humans. 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. Different samples will be collected and analyzed for five PCAHs including pyrene, benzo(a)anthracene, benzo(e)pyrene, benzoflouroanthene, and benzo(a)pyrene. The analytical method involves saponification with methanolic potassium hydroxide, extraction with cyclohexane, and determination by high-performance liquid chromatography. The obtained results showed that there is a variation in the detected PCAHs in different foodstuffs. Fried potato processed by conventional oven or microwave oven showed none of the selected studied PCAHs. It was found that, chicken showed higher content levels of total PCAHs than the meat and fish. Data are the highest mean concentrations of fluoranthene and benzo(a)pyrene but within low limit. The obtained results were compared with international permissible levels to avoid pollution, which may cause hazardous effects on individual and society. | train |
[
"Thiovit"
] | Effect of Thiovit(R) Jet on the structure of thoracic microtrichia/trichomes in Drosophila melanogaster. | train |
[
"Thiovit",
"captafol",
"captan"
] | Widely used fungicides and pesticides are known to have profound effect on several nontarget organisms, which is a cause of concern. The present study aims to demonstrate the effect of a fungicide, Thiovit(®) Jet on the structure of epidermal microtrichia (trichome) of the dorsal thorax in Drosophila melanogaster. 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 μg/ml). 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. Structural variations were observed to be associated with different concentrations of Thiovit Jet (30, 40 and 200 μg/ml), but the maximum notable change was found with 40 μg/ml treatment. The gross abnormality in the trichome structure may be due to mutation in proteins associated with normal cuticular deposition. | train |
[] | Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants. | train |
[
"MTT",
"3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide"
] | Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments. A large number of plants in Morocco were used in folk medicine to treat immune-related disorders. The objective of this study is to evaluate the immunomodulatory activity of protein extracts (PEs) of 14 Moroccan medicinal plants. This activity was tested on the proliferation of immune cells. 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. The results of this study indicated different activity spectra. Three groups of activities were observed. The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity. 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. The rest of the plant extracts did not alter the proliferation induced by Con-A. This result was more important for the PE than for the total extract. In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use. The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy. | train |
[
"steroidal saponins"
] | Determination of three steroidal saponins from Ophiopogon japonicus (Liliaceae) via high-performance liquid chromatography with mass spectrometry. | train |
[
"steroidal saponins",
"acetonitrile",
"formic acid"
] | 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. Separation was performed on a Tigerkin C(18) column and detection was performed by mass spectrometry. 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). The quantitative HPLC-MS method was validated for linearity, precision, repeatability, stability, recovery, limits of detection and quantification. 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. It could be considered as a suitable quality control method for O. japonicus. | train |
[
"steroidal glycosides"
] | Three new steroidal glycosides from roots of Reineckia carnea. | train |
[
"kitigenin-5β-O-β-D-glucopyranoside",
"MTT",
"reinocarnoside A (1), B (2) and C (3)",
"furostanol",
"(25S)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside",
"spirostanols"
] | 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)-1β,3β,4β-trihydroxyspirostan-5β-yl-O-β-D-glucopyranoside (4), kitigenin-5β-O-β-D-glucopyranoside (5). 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. | train |
[] | 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. | train |
[
"triclosan"
] | Drought episode modulates the response of river biofilms to triclosan. | train |
[
"TCS",
"triclosan",
"phosphate"
] | The consequences of global change on rivers include altered flow regime, and entrance of compounds that may be toxic to biota. When water is scarce, a reduced dilution capacity may amplify the effects of chemical pollution. 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. This work aims to investigate how an episode of drought might influence the response of river biofilms to pulses of triclosan (TCS). 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. 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. All channels were then left for 2 weeks under steady flow conditions, and their responses and recovery were studied. Several descriptors of biofilms were analyzed before and after each step. Flow reduction and subsequent interruption were found to provoke an increase in extracellular phosphatase activity, bacterial mortality and green algae biomass. The TCS pulses severely affected biofilms: they drastically reduced photosynthetic efficiency, the viability of bacteria and diatoms, and phosphate uptake. Latent consequences evidenced significant combined effects caused by the two stressors. 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. This finding has implications for river ecosystems, as it suggests that the toxicity of pollutants to biofilms may be exacerbated following a drought. | train |
[] | Determination of chemical composition and genotoxic effects of essential oil obtained from Nepeta nuda on Zea mays seedlings. | train |
[
"sodium dodecyl sulphate",
"4aα,7β,7aα-nepetalactone",
"elemol",
"germacrene",
"polyacrylamide",
"SDS"
] | We aimed to determine the genotoxic potential of essential oil (EO) obtained from Nepeta nuda. The chemical content of EO was measured via gas chromatography/mass spectrometry. The most abundant contents were 4aα,7β,7aα-nepetalactone (18.10%), germacrene (15.68%) and elemol (14.38%). For genotoxic effects of EO, Zea mays' seeds were exposed to four different concentrations of this oil. Inhibition of root and stem growth were observed with an increase in EO concentrations. Randomly amplified polymorphic DNA (RAPD) method was used to determine the genotoxic effects of EO. Some changes occurred in RAPD profiles of germinated EO-treated seeds. 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. We concluded that the basis of interactions between plants, like allelopathy, may be related with genotoxic effects of EO. | train |
[
"aluminum"
] | Lethality, accumulation and toxicokinetics of aluminum in some tissues of male albino rats. | train |
[
"Al",
"aluminum",
"Aluminum"
] | 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. The estimated LD50 at 24 h was 3.45 g Al/kg body weight (b.wt.). The utilized dose of Al was 1/50 LD50 (0.07 g Al/kg b.wt.). Aluminum residues, in Al-treated rats, were significantly decreased in response to the experimental periods and were negatively correlated with time. 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. Kinetically, the highest average of Al area under concentration - time curves (AUCtotal, μg/g day) and area under moment concentration - time curves (AUMCtotal, µg/g day(2)) recorded in the brain followed by kidney, serum, intestine and liver. 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. 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. 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. 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. The computed starting concentration (C 0, μg) of Al in serum was higher than its level in the intestine followed by the brain, kidney and liver. | train |
[] | RETRACTED: Biochemical changes in the Beluga Huso huso exposed to acute crude diesel oil. | train |
[] | RETRACTED. | train |
[
"monoglyceride"
] | Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer. | train |
[
"phosphoinositides",
"phosphatidic acid",
"phosphatidylinositol",
"PI(3,4,5)P3",
"phosphoinositol(3,4,5)P3",
"phosphoinositol(3,4)P2",
"monoglyceride",
"phosphoinositol(3,5)P2"
] | 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. 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. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. 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. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth. | train |
[] | Chemical constituents of the hemiparasitic plant Phoradendron brachystachyum DC Nutt (Viscaceae). | train |
[
"acacetin",
"triacontanol",
"moronic acid",
"acetone",
"β-sitosteryl and stigmasteryl linoleates",
"oleanolic acid",
"flavonoids",
"β-sitosterol",
"squalene, α- and β-amyrin",
"lupenone",
"betulonic acid",
"morolic acid",
"betulin aldehyde",
"acacetin 7-methyl ether",
"oleanolic aldehyde",
"stigmasterol",
"betulinic acid",
"lupeol",
"betulon aldehyde"
] | Phoradendron brachystachyum is a hemiparasitic plant widely distributed in México that belongs to the Viscaceae family. It has been commonly used in folk medicine as a substitute for the European mistletoe. In this chemical study, morolic acid was isolated as the major component (47.54% of the total composition of acetone extract) of this plant. In addition, 19 known compounds were identified: β-sitosteryl and stigmasteryl linoleates, β-sitosterol, stigmasterol, triacontanol, squalene, α- and β-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. There have been no previous reports in the literature on the chemical composition of this potential natural source of hypoglycaemic and antihypertensive compounds. | train |
[
"rapamycin"
] | MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells. | train |
[
"RAP",
"Rapamycin"
] | 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. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. 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. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. 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. | train |
[] | Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells. | train |
[
"gefitinib",
"WP1066",
"phosphatidyl inositol"
] | The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers. Previously, we demonstrated acquisition of epithelial-mesenchymal transition, a feature highly reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells (A549/GR). 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. A549/GR cells exhibited strong sphere-forming activity and high CXCR4 expression and SDF-1α secretion compared with parent cells. 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. A549/GR cells showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. 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. 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. 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. 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. 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. | train |
[] | Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS). | train |
[] | The oral delivery of hydrophobic drug presents a major challenge because of the low aqueous solubility of such compounds. 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. 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. Thus, only very specific pharmaceutical excipient combinations will lead to efficient self-emulsifying systems. 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. 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. | train |
[] | Chemical composition and antibacterial activity of the essential oil from Mentha requienii Bentham. | train |
[
"pulegone",
"menthone",
"isomenthone",
"limonene",
"isopulegone"
] | 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. The main constituents that resulted were pulegone (78%), menthone (0.5%), isomenthone (18%), isopulegone (1.3%) and limonene (1.76%). In vitro antifungal activity is evaluated in order to identify new means that could be helpful in the prevention of contamination in indoor environments. | train |
[
"Carbon",
"withanolide A"
] | Carbon sources and medium pH affects the growth of Withania somnifera (L.) Dunal adventitious roots and withanolide A production. | train |
[
"carbon",
"withanolide A",
"sucrose"
] | 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. 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%). 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). | train |
[
"nimesulide"
] | Comparison of pharmacokinetics in beagle dogs of nimesulide bilayer tablets with dispersible tablets. | train |
[
"nimesulide"
] | 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. The tablets were administered to beagle dogs and the plasma levels of nimesulide were determined by high-performance liquid chromatography-MS/MS. The pharmacokinetic parameters were calculated using a noncompartmental model. 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. The C(max), t(max), mean residence time (MRT), and area under the curve from 0 to 36 h were 10.8 ± 4.2 μg/mL, 2.3 ± 1.0 h, 6.7 ± 2.1 h, 81.5 ± 26.7 μg·h/mL for the bilayer tablets and 14.8 ± 5.8 μg/mL, 2.7 ± 0.8 h, 5.6 ± 0.9 h, 95.4 ± 44.2 μg·h/mL for the dispersible tablets. Compared with the dispersible tablets, the bilayer tablets have lower C(max), similar t(max), and longer MRT. The aforementioned pharmacokinetic parameters, especially the MRT demonstrated to be valuable for evaluating the biphasic characteristics. This study provides a promising in vivo evaluation method for the bilayer tablets with biphasic release pattern. | train |
[
"PLA",
"Ivermectin"
] | Injectable PLA-based in situ forming implants for controlled release of Ivermectin a BCS Class II drug: solvent selection based on physico-chemical characterization. | train |
[
"2-pyrrolidone",
"PLA",
"triacetine",
"NMP",
"benzyl benzoate",
"ivermectin",
"poly(D,L-lactide)",
"IVM",
"N-methyl-2-pyrrolidone"
] | 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. 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. The solvents evaluated were N-methyl-2-pyrrolidone (NMP), 2-pyrrolidone (2P), triacetine (TA) and benzyl benzoate (BB). Hansen's solubility parameters of solvents were used to explain polymer/solvent interactions leading to different rheological behaviours. The stability of the polymer and drug in the solvents were also evaluated by size exclusion and high performance liquid chromatography, respectively. 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. In general, the release rate increased with increasing water miscibility of the solvent and decreasing viscosity in the following order NMP>2P>TA>BB. 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. Finally, drug and polymer stability in the solvents followed the same trends, increasing when polymer-solvent affinities and water content in solvents decreased. IVM degradation was accelerated by the acid environment generated by the degradation of the polymer but the drug did not affect PLA stability. | train |
[] | Toxic effects of 50 Hz electromagnetic field on memory consolidation in male and female mice. | train |
[] | 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. For this purpose male and female mice were randomly distributed among six groups (n = 10 in each group). Using passive avoidance task, despite its natural tendency, mouse learns to stay on a small platform to avoidant electric shock. Immediately after the learning session, laboratory animals in the experimental groups were placed in an 8 mT, 50 Hz sinusoidal EMF for 4 h. The second male and female groups were sham exposed (exposure device off) and the third groups were considered as the controls. 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. 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. | train |
[
"9,10-seco-9,19-cyclolanostane",
"triterpene"
] | 9,10-seco-9,19-cyclolanostane triterpene from Salix caprea L. (goat willow). | train |
[
"fatty alcohols",
"triterpene",
"1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane"
] | Chemical investigation of low polar solvent extract of Salix caprea through chromatographic techniques led to the isolation of new triterpene as 1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane (1) along with fatty alcohols. The structure of compound 1 was established by IR, HRESI/MS and NMR including 1D and 2D experiments. The compound 1 showed moderate in vitro antiplasmodial activity. | train |
[] | Chemical constituents of Euphorbia hyberna L. (Euphorbiaceae). | train |
[
"cicloart-23-ene-3β,25-diol",
"triterpenoids",
"ellagic acid",
"glut-5-en-3β-ol",
"3β-O-octadecanoyllupeol",
"24-methylenecicloartan-3β-ol",
"3,3'-di-O-methylellagic acid"
] | Chemical investigation of the aerial part and the roots of Euphorbia hyberna L. subs. hyberna. resulted in the isolation and identification of four triterpenoids (3β-O-octadecanoyllupeol (1), glut-5-en-3β-ol (2), 24-methylenecicloartan-3β-ol (3) and cicloart-23-ene-3β,25-diol (6)) along with the phenolic compounds ellagic acid (4) and 3,3'-di-O-methylellagic acid (7). Although these are all known compounds, this is the first report of their isolation from this plant. Their structures were elucidated on the basis of spectral methods, including 2D NMR experiences, and confirmed by comparing with the literature data. | train |
[
"diketopiperazine"
] | Structure elucidation of a new natural diketopiperazine from a Microbispora aerata strain isolated from Livingston Island, Antarctica. | train |
[
"trans-cyclo-(D-tryptophanyl-L-tyrosyl)",
"amino acid",
"diketopiperazine",
"Trans-cyclo-(D-tryptophanyl-L-tyrosyl)"
] | 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. Compound 1 was purified consecutively by solvent extraction, silica gel column chromatography and preparative HPLC. The structure of the compound was elucidated by 1D and 2D NMR experiments and mass spectrometric investigations. The absolute configuration of compound 1 was determined by amino acid analysis and NOESY correlations. 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. Trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) did not show antimicrobial activity at a concentration of 50 µg per disc against Bacillus subtilis, Staphylococcus aureus, Streptomyces viridochromogenes, Escherichia coli, Candida albicans and Mucor miehei. | train |
[] | Comparative chemical composition and in vitro antioxidant activities of essential oil isolated from the leaves of Cinnamomum tamala and Pimenta dioica. | train |
[
"superoxide",
"eugenol",
"DPPH"
] | 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. In this study, we compared the chemical composition and antioxidant activities of tejpat and pimento essential oils by employing various in vitro methods. 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. 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. Among the two oils, tejpat oil showed better activity in terms of antioxidative potential. | train |
[
"iridoid glucosides"
] | Antioxidant and lipoxygenase inhibiting new iridoid glucosides from Caryopteris odorata. | train |
[
"ethylacetate",
"8-O-trans-cinnamoyl caryoptoside",
"8-O-cafeoyl massenoside",
"8-O-trans-cinnamoyl shanzhiside methylester",
"acetyl",
"iridoids",
"8-O-trans-cinnamoyl mussaenoside",
"iridoid glucosides"
] | 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). 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. The antioxidant potential of the isolated iridoids (1-4) was evaluated relative to conventionally used standards and these molecules exhibited good antioxidant potential. Moreover, their inhibitory potential was also screened against three enzymes, namely acetyl cholinesterase, butyrylcholinesterase and lipoxygenase. These iridoid glucosides were found to be inactive against acetyl and butyrylcholinesterases but active against lipoxygenase. | train |
[] | Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf. | train |
[
"glucose"
] | 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. 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. To address possible redundancies in cell death regulation and tumor suppression, we generated compound mutant mice lacking both genes. Our studies revealed lack of redundancy in most paradigms of lymphocyte apoptosis tested in tissue culture. 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. Of note, despite these minor apoptosis defects we observed compromised lymphocyte homeostasis in vivo that affected mainly the B-cell lineage. Long-term follow-up revealed significantly reduced latency to spontaneous tumor formation in aged mice when both genes were lacking. 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. | train |
[
"LY541850"
] | Differentiating the roles of mGlu2 and mGlu3 receptors using LY541850, an mGlu2 agonist/mGlu3 antagonist. | train |
[
"Glutamate",
"amphetamine",
"LY541850",
"phencyclidine",
"glutamate"
] | 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. LY541850 was claimed from human mGlu receptors expressed in non-neuronal cells to be a selective orthosteric mGlu2 agonist and mGlu3 antagonist. We have verified this pharmacological profile of LY541850 in hippocampal slices. 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. The group II agonist, DCG-IV, inhibited the fEPSP in all three genotypes. 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. These results confirm the selective mGlu2 agonist and mGlu3 antagonist actions of LY541850. A similar profile of activity was seen in medial perforant path synapse to the dentate gyrus. Systemic administration of LY541850 to wild-type mice, reduced the increase in locomotor activity following both phencyclidine and amphetamine administration. These data support the hypothesis that mGlu2 receptors mediate the antipsychotic effects of mixed group II agonists. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. | train |
[] | Antiproliferative and antiangiogenic properties of horse chestnut extract. | train |
[
"3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide"
] | This study was designed to examine the in vitro antiproliferative effect of the horse chestnut extract (HCE) on cancer cell lines. Furthermore, we have investigated the in vitro effect of HCE on some angiogenic events by using human umbilical vein endothelial cells. 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. To understand the growth inhibitory effects, carcinoma cell lines (Jurkat, CEM, HeLa, and MCF-7) were treated with various concentrations of HCE. Incubation of Jurkat, CEM, HeLa, and MCF-7 cancer cells with HCE at 125 µg/mL for 72 h caused 93.7%, 32.3%, 20.4% and 40.4% reduction in cell survival. Colony-forming assay also confirmed growth-inhibitory effects of the compound studied. 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. 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. These results generate a rationale for in vivo efficacy studies with horse chestnut in preclinical cancer models. | train |
[
"4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine"
] | Synthesis of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine derivatives as potent antimicrobial agent. | train |
[
"3-alkyl-2,6-diarylpiperidin-4-one",
"piperdin-4-ol",
"Grignard reagent",
"4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine"
] | 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. Structural assignments and conformational analysis of the compounds were established based on the spectral studies. All the piperdin-4-ol derivatives (7-12) were assayed for antibacterial, antifungal and anthelmintic activities and they exhibited significant results. | train |
[] | Phytochemical analysis of Gymnema sylvestre and evaluation of its antimicrobial activity. | train |
[
"diethyl ether",
"oleic acid",
"eicosane",
"stigmasterol",
"saponins",
"acetone",
"chloroform",
"vitamin E"
] | Gymnema sylvestre (CS 149), known to be a rich source of saponins and other valuable phytochemicals, has been analysed for antimicrobial activity. The chloroform extracts of aerial and root parts of G. sylvestre exhibited higher antimicrobial activity as compared to diethyl ether and acetone. 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. The GC-MS analysis of chloroform extracts has shown the presence of compounds like eicosane, oleic acid, stigmasterol and vitamin E. | train |
[] | Plant proteins, minerals and trace elements of Eurycoma longifolia (Tongkat Ali). | train |
[
"calcium",
"sodium dodecyl sulphate polyacrylamide",
"potassium",
"magnesium",
"arsenic",
"Isoleucine"
] | A water extraction method has been used to extract plant proteins from the roots of Eurycoma longifolia harvested from Perak and Pahang, Malaysia. 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. 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. Isoleucine was present in the highest concentration significantly. 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. The highly concerned toxic metals such as arsenic and lead were not detected. | train |
[] | In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system. | train |
[
"tetracycline",
"doxycycline"
] | 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. 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. A tetracycline-inducible transgenic mouse model expressing truncated β-catenin (ΔN89β-catenin) that exhibited a strong intestinal hyperplasia was analyzed during the removal of oncogenic β-catenin expression both in 3D 'crypt culture' and in vivo. Oncogenic Wnt signaling was rapidly and completely reversed. 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. In vitro, the small molecule Wnt inhibitor CCT036477 induced a response within 4 h of treatment. 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. 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. | train |
[] | miR-143 regulates hexokinase 2 expression in cancer cells. | train |
[
"glucose",
"oxygen",
"ATP",
"fatty acids"
] | 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. Accordingly, a variety of human tumors are characterized by elevated expression levels of the hexokinase 2 isoform (HK2). 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. 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. We demonstrate that miR143 inhibits HK2 expression both in primary keratinocytes and in head and neck squamous cell carcinoma (HNSCC)-derived cell lines. Importantly, we found that miR-143 inversely correlates with HK2 expression in HNSCC-derived cell lines and in primary tumors. 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. 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. | train |
[
"Glaucogenin E",
"C21",
"steroid"
] | Glaucogenin E, a new C21 steroid from Cynanchum stauntonii. | train |
[
"Glaucogenin E",
"C(21)",
"steroid"
] | 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. ex Levl. Their structures were established mainly by the spectroscopic analysis, including 2D NMR. All the isolated compounds were evaluated for their cytotoxicity against human cancer cell lines HeLa, Bel-7402, SGC-7901 and BGC-823. | train |
[
"boeravinone E",
"boeravinone B"
] | RP-HPLC method for the simultaneous quantitation of boeravinone E and boeravinone B in Boerhaavia diffusa extract and its formulation. | train |
[
"boeravinone E and B",
"boeravinone B",
"rotenoids",
"orthophosphoric acid",
"acetonitrile",
"boeravinone E"
] | 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. 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. The detection was carried out at 276 nm. The method was validated for specificity, precision, accuracy and robustness. The linearity (r (2) = 0.9989 and 0.9991) was found to be in the range of 7.26-35.75 µg mL(-1) and 2.20-11.00 µg mL(-1) for boeravinone E and B, respectively. The percent recovery observed from the extract sample was 95.22-95.83. | train |
[] | 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. | train |
[
"fluoro-indomethacin"
] | Evaluation of the physicochemical and biopharmaceutical properties of fluoro-indomethacin. | train |
[
"18F",
"indomethacin",
"IMC",
"18F-IMC",
"fluoro-indomethacin",
"F-IMC"
] | Drug nanocarriers have shown great potential in therapy and as diagnostic probes, e.g. in imaging of cancer and inflammation. Imaging can be applied to localize the carrier or the drug itself in the body and/or tissues. 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. 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. However, this is only possible if the derivative compound behaves similarly to the parent drug compound. 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). 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. In this context, both IMC and F-IMC were thermally and morphologically studied. 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. Finally, the transport across Caco- 2 monolayers of the IMC and F-IMC at physiological pH range was also investigated. The results obtained showed similar values in pKalogP, solubility, dissolution, cytotoxicity, and permeability for both compounds. Thus, there might be strong evidence that both IMC and F-IMC should have a similar ADME behavior and profiles in vivo. The results provide fundamental tools and ideas for further research with nanocarriers of 18F-IMC. | train |
[
"furostanol",
"saponins"
] | New furostanol saponins from the rhizomes of Tupistra chinensis. | train |
[
"furostanol",
"saponins",
"polyhydroxyl",
"saponin"
] | Three new furostanol saponins (1-3), including a polyhydroxyl saponin, were isolated from the rhizomes of Tupistra chinensis. The structures of these compounds were identified by NMR, MS spectral data and chemical methods. | train |
[
"AMPA",
"glutamate"
] | mGlu5R promotes glutamate AMPA receptor phosphorylation via activation of PKA/DARPP-32 signaling in striatopallidal medium spiny neurons. | train |
[
"Glutamate",
"AMPA",
"dopamine",
"(R,S)-3,5-dihydroxyphenylglycine",
"DHPG",
"glutamate",
"adenosine",
"2-methyl-6-(phenylethynyl)pyridine hydrochloride",
"cAMP",
"MPEP",
"Ser"
] | Group I metabotropic glutamate receptors (mGluRs), which comprise mGlu1Rs and mGlu5Rs, are enriched in striatal medium spiny neurons (MSNs), where they modulate glutamatergic transmission. 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. 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. This effect is prevented by 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), a selective mGlu5R antagonist. 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. 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). Thus, inactivation of the PKA phosphorylation site of DARPP-32 abolishes the effect of DHPG. Moreover, cell-specific knock out of DARPP-32 in striatopallidal, but not in striatonigral, MSNs prevents the increase in Ser845 phosphorylation induced by DHPG. 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. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. | train |
[
"rebamipide",
"poloxamer 407"
] | Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407. | train |
[
"rebamipide",
"Poloxamer 407",
"poloxamer 407",
"NaOH",
"sodium hydroxide"
] | 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. 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. Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co-grinding, physical mixing, melting or spray drying. SD was then characterized by dissolution test, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The spray dried SD of poloxamer 407 together with primary SD displayed highest dissolution rate of the drug of about 70% after 2 h. DSC, PXRD and FT-IR characterized the amorphous state and molecular dispersion of the drug in the SD. 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. | train |
[] | Chitin synthase inhibitors as antifungal agents. | train |
[
"nikkomycin",
"Nikkomycin Z",
"polyoxin"
] | 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. 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. Chitin synthase is one such promising target as it is absent in plants and mammals. Nikkomycin Z, a chitin synthase inhibitor is under clinical development. 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. | train |
[
"carbon dioxide",
"venlafaxine",
"pregabalin"
] | Evaluation of the effects of venlafaxine and pregabalin on the carbon dioxide inhalation models of Generalised Anxiety Disorder and panic. | train |
[
"CO(2)",
"Venlafaxine",
"lorazepam",
"paroxetine",
"pregabalin",
"venlafaxine",
"benzodiazepines"
] | 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. 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. Fifty-four participants were randomised to receive either placebo, venlafaxine or pregabalin. 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. Participants inhaled air 7.5% CO(2) for 20 minutes (single-blind presentation), and a non-blinded single vital capacity of 35% CO(2). Subjective ratings were recorded before and after each inhalation. 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. 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. 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. This may be due to a lack of sensitivity of the CO(2) challenges in healthy volunteers to these drug types. | train |
[
"N-isobutyl-4,5-epoxy-2(E)-decenamide"
] | Microwave-assisted synthesis of N-isobutyl-4,5-epoxy-2(E)-decenamide. | train |
[
"2-bromoacetic acid",
"N-isobutyl-4,5-epoxy-2(E)-decenamide",
"Octanal",
"amide"
] | 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. Octanal and 2-bromoacetic acid have been used as the starting materials. | train |
[] | Endoplasmic reticulum protein 29 regulates epithelial cell integrity during the mesenchymal-epithelial transition in breast cancer cells. | train |
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