bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200
Authors: Kobayashi Miharu , Salomon Carlos , Tapia Jorge , Illanes Sebastian E , Mitchell Murray D , Rice Gregory E
Published: January 2014

Background

The role of exosomes in the pathogenesis and metastatic spread of cancer remains to be fully elucidated. Recent studies support the hypothesis that the release of exosomes from cells modifies local extracellular conditions to promote cell growth and neovascularisation. In addition, exosomes may modify the phenotype of parent and/or target cell. For example, sequestration of signaling mediators into exosomes may reduce their intracellular bioavailability to the parent cell thereby altering cell phenotype and metastatic potential. The fusion of released exosomes with target cell and delivery may also modify cell function and activity. In this study, to further elucidate the role of exosomes in ovarian cancer, the release of exosomes from two ovarian cancer cell lines of different invasive capacity and their miRNA content of exosomes were compared. The hypothesis to be tested was that ovarian cancer cell invasiveness is associated with altered release of exosomes and discordant exosomal sequestration of miRNA.

Methods

High (SKOV-3) and low (OVCAR-3) invasive ovarian cancer cell lines were used to characterize their exosome release. SKOV-3 and OVCAR-3 cells were cultured (DMEM, 20% exosome-free FBS) under an atmosphere of 8% O2 for 24 hours. Cell-conditioned media were collected and exosomes were isolated by differential and buoyant density centrifugation and characterised by Western blot (CD63 and CD9). Exosomal microRNA (let-7a-f and miR-200a-c) content was established by real-time PCR.

Results

Exosomes were identified with by the presence of typical cup-shaped spherical vesicle and the expression of exosome markers: CD63, CD9. SKOV-3 cells released 2.7-fold more exosomes (1.22 ± 0.11 μg/106 cells) compared to OVCAR-3 (0.44 ± 0.05 μg/106 cells). The let-7 family miRNA transcripts were identified in both ovarian cancer cell lines and their exosomes. The let-7 family transcripts were more abundant in OVCAR-3 cell than SKOV-3 cells. In contrast, let-7 family transcripts were more abundant in exosomes from SKOV-3 than OVCAR-3. miR-200 family transcripts were only identified in OVCAR-3 cells and their exosomes.

Conclusions

The data obtained in this study are consistent with the hypothesis that the releases of exosomes varies significantly between ovarian cancer cell lines and correlates with their invasive potential.
The clinical significance of tumor-infiltrating neutrophils and neutrophil-to-CD8+ lymphocyte ratio in patients with resectable esophageal squamous cell carcinoma
Authors: Wang Jianbo , Jia Yibin , Wang Nana , Zhang Xiaomei , Tan Bingxu , Zhang Guangyu , Cheng Yufeng
Published: January 2014

Background

The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The main aims of the study were to investigate the clinical significance of tumor-infiltrating neutrophils and neturophil-to-CD8+ lymphocyte ratio (NLR), and to analyze the distribution of tumor-infiltrating neutrophils and CD8+ lymphocytes in ESCC treated by curative resection.

Methods

The expressions of CD66b and CD8 were assessed with double staining immunohistochemistry in the surgical specimens from 90 patients with ESCC treated by curative surgery.

Results

We showed that increased intratumoral neutrophils were significantly associated with lymph node metastasis (P = 0.016), and advanced pathological stages (P = 0.013). Decreased peritumoral CD8+ lymphocyte density was more frequently observed in patients with single positive lymph node (p = 0.045). Peritumoral NLR was significantly associated with advanced T stages (p < 0.001), lymph node metastasis (p = 0.041) and a trend towards advanced pathological stages (p = 0.053). Increased intratumoral neutrophils were significantly associated with decreased disease-free survival (p < 0.001) and overall survival (p < 0.001) in univariate analysis and were identified as an independent prognostic factor for disease-free survival (p = 0.006) and overall survival (p = 0.037) in multivariate analysis. Neither the density nor the distribution of tumor-infiltrating neutrophils was significantly correlated with that of CD8+ lymphocytes. The density of intratumoral CD8+ lymphocytes was significantly lower than (P < 0.001) and moderately correlated with (r = 0.434, p < 0.001) that in peritumoral area.

Conclusions

Increased intratumoral neutrophils were an independent poor prognostic factor and peritumoral NLR was significantly associated with disease progression in ESCC treated by curative surgery, suggesting the possible effect of immune misbalance of tumor microenvironment in facilitating ESCC progression. Immunotherapy targeted to the above predictors should be considered in the future.
Ferromagnetism and Ru-Ru distance in SrRuO3 thin film grown on SrTiO3 (111) substrate
Authors: Lee Bowha , Kwon O-Ung , Shin Ran Hee , Jo William , Jung Chang Uk
Published: January 2014

Epitaxial SrRuO3 thin films were grown on both (100) and (111) SrTiO3 substrates with atomically flat surfaces that are required to grow high-quality films of materials under debate. The following notable differences were observed in the (111)-oriented SrRuO3 films: (1) slightly different growth mode, (2) approximately 10 K higher ferromagnetic transition temperature, and (3) better conducting behavior with higher relative resistivity ratio, than (100)c-oriented SrRuO3 films. Together with the reported results on SrRuO3 thin films grown on (110) SrTiO3 substrate, the different physical properties were discussed newly in terms of the Ru-Ru nearest neighbor distance instead of the famous tolerance factor.

PACS

75.70.Ak; 75.60.Ej; 81.15.Fg
Linear impulsive Volterra integro-dynamic system on time scales
Authors: Agarwal Ravi P , Awan Abdul Sami , O’Regan Donal , Younus Awais
Published: January 2014

This paper deals with the asymptotic stability and boundedness of the solution of a time-varying impulsive Volterra integro-dynamic system on time scales in which the coefficient matrix is not necessarily stable. We generalize to a time scale some known properties concerning the asymptotic behavior and boundedness from the continuous case.
Face liveness detection using dynamic texture
Authors: Freitas Pereira Tiago de , Komulainen Jukka , Anjos André , De Martino José Mario , Hadid Abdenour , Pietikäinen Matti , Marcel Sébastien
Published: January 2014

User authentication is an important step to protect information, and in this context, face biometrics is potentially advantageous. Face biometrics is natural, intuitive, easy to use, and less human-invasive. Unfortunately, recent work has revealed that face biometrics is vulnerable to spoofing attacks using cheap low-tech equipment. This paper introduces a novel and appealing approach to detect face spoofing using the spatiotemporal (dynamic texture) extensions of the highly popular local binary pattern operator. The key idea of the approach is to learn and detect the structure and the dynamics of the facial micro-textures that characterise real faces but not fake ones. We evaluated the approach with two publicly available databases (Replay-Attack Database and CASIA Face Anti-Spoofing Database). The results show that our approach performs better than state-of-the-art techniques following the provided evaluation protocols of each database.
Personal networks: a tool for gaining insight into the transmission of knowledge about food and medicinal plants among Tyrolean (Austrian) migrants in Australia, Brazil and Peru
Authors: Haselmair Ruth , Pirker Heidemarie , Kuhn Elisabeth , Vogl Christian R
Published: January 2014

Background

Investigations into knowledge about food and medicinal plants in a certain geographic area or within a specific group are an important element of ethnobotanical research. This knowledge is context specific and dynamic due to changing ecological, social and economic circumstances. Migration processes affect food habits and the knowledge and use of medicinal plants as a result of adaptations that have to be made to new surroundings and changing environments. This study analyses and compares the different dynamics in the transmission of knowledge about food and medicinal plants among Tyrolean migrants in Australia, Brazil and Peru.

Methods

A social network approach was used to collect data on personal networks of knowledge about food and medicinal plants among Tyroleans who have migrated to Australia, Brazil and Peru and their descendants. A statistical analysis of the personal network maps and a qualitative analysis of the narratives were combined to provide insight into the process of transmitting knowledge about food and medicinal plants.

Results

56 personal networks were identified in all (food: 30; medicinal plants: 26) across all the field sites studied here. In both sets of networks, the main source of knowledge is individual people (food: 71%; medicinal plants: 68%). The other sources mentioned are print and audiovisual media, organisations and institutions. Personal networks of food knowledge are larger than personal networks of medicinal plant knowledge in all areas of investigation. Relatives play a major role as transmitters of knowledge in both domains.

Conclusions

Human sources, especially relatives, play an important role in knowledge transmission in both domains. Reference was made to other sources as well, such as books, television, the internet, schools and restaurants. By taking a personal network approach, this study reveals the mode of transmission of knowledge about food and medicinal plants within a migrational context.
Thioredoxin 1 as a serum marker for breast cancer and its use in combination with CEA or CA15-3 for improving the sensitivity of breast cancer diagnoses
Authors: Park Byung-Joon , Cha Mee-Kyung , Kim Il-Han
Published: January 2014

Background

The human cytosolic thioredoxin (Trx) contains a redox-active dithiol moiety in its conserved active-site sequence. Activation by a wide variety of stimuli leads to secretion of this cytoplasmic protein. Function of Trx1 has been implicated in regulating cell proliferation, differentiation, and apoptosis. The aim of this study was to assess the clinical significance of serum Trx1 level in patients with breast carcinoma.

Results

To clarify whether serum levels of Trx1 could be a serum marker for breast carcinoma, we measured the serum levels of Trx1 in patients with various carcinomas (breast, lung, colorectal, and kidney cancers) using an ELISA, and investigated its associations with the tumour grading from I to III. At the cut-off point 33.1725 ng/ml on the receiver operating characteristic curve (ROC) Trx1 could well discriminate breast carcinoma from normal controls with a sensitivity of 89.8%, specificity 78.0%, and area under the ROC (AUC) 0.901 ± 0.0252. The serum level was well correlated with the progress of the breast carcinoma. We also investigated the diagnostic capacity of CEA and CA15-3 for the early detection of metastatic breast cancer comparing that of Trx1. In contrast to the serum CEA and CA15-3 tumour markers, the serum Trx1 levels of the early cancer (grade I) patients were significantly higher than those of normal control subjects, showing a high diagnostic sensitivity and selectivity (89.4% sensitivity, and 72.0% specificity). The serum levels of Trx1 in various patients with lung, colorectal, and kidney carcinomas indicate that the level of Trx1 is significantly higher than those of other cancer patients. Combinational analysis of CEA or CA15-3 with Trx1 for the detection of breast cancer suggest that the diagnostic capacity of CEA or CA15-3 alone for the early detection of breast cancer, especially regarding sensitivity, is significantly improved by its combination with Trx1.

Conclusions

Taken together, we conclude that serum Trx1 is useful for the early diagnosis of breast cancer or the early prediction prognosis of breast cancer, and therefore has a valuable use as a diagnostic marker and companion marker to CEA and CA15-3 for breast cancer.
Prediction of novel drug indications using network driven biological data prioritization and integration
Authors: Qabaja Ala , Alshalalfa Mohammed , Alanazi Eisa , Alhajj Reda
Published: January 2014

Background

With the rapid development of high-throughput genomic technologies and the accumulation of genome-wide datasets for gene expression profiling and biological networks, the impact of diseases and drugs on gene expression can be comprehensively characterized. Drug repositioning offers the possibility of reduced risks in the drug discovery process, thus it is an essential step in drug development.

Results

Computational prediction of drug-disease interactions using gene expression profiling datasets and biological networks is a new direction in drug repositioning that has gained increasing interest. We developed a computational framework to build disease-drug networks using drug- and disease-specific subnetworks. The framework incorporates protein networks to refine drug and disease associated genes and prioritize genes in disease and drug specific networks. For each drug and disease we built multiple networks using gene expression profiling and text mining. Finally a logistic regression model was used to build functional associations between drugs and diseases.

Conclusions

We found that representing drugs and diseases by genes with high centrality degree in gene networks is the most promising representation of drug or disease subnetworks.
Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial
Authors: Mohebbi Niayesh , Khoshnevisan Alireza , Naderi Soheil , Abdollahzade Sina , Salamzadeh Jamshid , Javadi Mohammadreza , Mojtahedzadeh Mojtaba , Gholami Kheirollah
Published: January 2014

Background

Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery.

Results

Karnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048).

Conclusions

Significant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.
Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients
Authors: Gharekhani Afshin , Khatami Mohammad-Reza , Dashti-Khavidaki Simin , Razeghi Effat , Abdollahi Alireza , Hashemi-Nazari Seyed-Saeed , Mansournia Mohammad-Ali
Published: January 2014

Background

Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients.

Methods

In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention.

Results

45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively).

Conclusion

Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.
Pharmacokinetics of mirtazapine and its main metabolites after single intravenous and oral administrations in rats at two dose rates
Authors: Rouini Mohammad-Reza , Lavasani Hoda , Sheikholeslami Behjat , Owen Helen , Giorgi Mario
Published: January 2014

Background

Mirtazapine (MRZ) is a human antidepressant drug metabolized to 8-OH mirtazapine (8-OH) and dimethylmirtazapine (DMR) metabolites. Recently, this drug has been proposed as a potential analgesic for use in a multidrug analgesic regime in the context of veterinary medicine. The aim of this study was to assess the pharmacokinetics of MRZ and its metabolites DMR and 8-OH in rats.

Findings

Eighteen fasted, healthy male rats were randomly divided into 3 groups (n = 6). Animals in these groups were respectively administered MRZ at 2 and 10 mg/kg orally and 2 mg/kg intravenously. Plasma MRZ and metabolite concentrations were evaluated by HPLC-FL detection method. After intravenous administration, MRZ was detected in all subjects, while DMR was only detected in three. 8-OH was not detected. After oral administration, MRZ was detected in 3 out of 6 rats treated with 2 mg/kg, it was detected in 6 out of 6 animals in the 10 mg/kg group. DMR was only detectable in the latter group, while 8-OH was not detected in either group. The oral bioavailability was about 7% in both groups.

Conclusions

The plasma concentration of the MRZ metabolite 8-OH was undetectable, and the oral bioavailability of the parental drug was very low.
The effect of piperine on midazolam plasma concentration in healthy volunteers, a research on the CYP3A-involving metabolism
Authors: Rezaee Mohammad Mahdi , Kazemi Sohrab , Kazemi Mohammad Taghi , Gharooee Saeed , Yazdani Elham , Gharooee Hoda , Shiran Mohammad Reza , Moghadamnia Ali Akbar
Published: January 2014

Some studies showed that piperine (the alkaloid of piper nigrum) can change the activities of microsomal enzymes. Midazolam concentration is applied as a probe to determine the CYP3A enzyme activity. This study was done to determine piperine pretreatment role on midazolam plasma concentration.

Twenty healthy volunteers (14 men and 6 women) received oral dose of piperine (15 mg) or placebo for three days as pretreatment and midazolam (10 mg) on fourth day of study and the blood samples were taken at 0.5, 2.5 and 5 h after midazolam administration. The midazolam plasma levels were assayed using HPLC method (C18 analytical column, 75:25 methanol:water as mobile phase, UV detector at 242 nm wavelength and diazepam as internal standard). Data were fit in a “one-compartment PK model” using P-Pharm 1.5 software and analyzed under statistical tests.

The mean ±SD of the age and body mass index were 24.3 ± 1.83 years (range: 21–28 years) and 23.46± 2.85, respectively. The duration of sedation in piperine receiving group was greater that the placebo group (188±59 vs. 102±43 min, p<0.0001). Half-life and clearance of midazolam were higher in piperine pretreatment group compared to placebo [1.88±0.03 vs. 1.71± 0.04 h (p<0.0001) and 33.62 ± 0.4 vs. 37.09 ± 1.07 ml/min (p<0.0001), respectively].

According to the results, piperine can significantly increases half-life and decreases clearance of midazolam compared to placebo. It is suggested that piperine can demonstrate those effects by inhibition CYP3A4 enzyme activity in liver microsomal system.
Antinociceptive properties of new coumarin derivatives bearing substituted 3,4-dihydro-2H-benzothiazines
Authors: Alipour Masoumeh , Khoobi Mehdi , Emami Saeed , Fallah-Benakohal Saeed , Ghasemi-Niri Seyedeh Farnaz , Abdollahi Mohammad , Foroumadi Alireza , Shafiee Abbas
Published: January 2014

Background

Coumarins are an important class of widely distributed heterocyclic natural products exhibiting a broad pharmacological profile. In this work, a new series of coumarins bearing substituted 3,4-dihydro-2H-benzothiazines were described as potential analgesic agents. The clinical use of NSAIDs as traditional analgesics is associated with side effects such as gastrointestinal lesions and nephrotoxicity. Therefore, the discovery of new safer drugs represents a challenging goal for such a research area.

Results

The target compounds 3-(3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazin-3-yl)-2H-chromen-2-ones 2a-u were synthesized and characterized by spectral data. The antinociceptive properties of target compounds were determined by formalin-induced test and acetic acid-induced writhing test in mice. Among the tested compounds, compound 2u bearing 2-(4-(methylsulfonyl)benzoyl)- moiety on benzothiazine ring and 4-(methylsulfonyl)phenacyloxy- group on the 7 position of coumarin nucleus showed better profile of antinocecieption in both models. It was more effective than mefenamic acid during the late phase of formalin-induced test as well as in the acetic acid-induced writhing test.

Conclusion

Considering the significant antinoceciptive action of phenacyloxycoumarin derivatives, compound 2u prototype might be further used as model to obtain new more potent analgesic drugs.
Content of toxic and essential metals in recrystallized and washed table salt in Shiraz, Iran
Authors: Eftekhari Mohammad Hassan , Mazloomi Seyed Mohammad , Akbarzadeh Marzieh , Ranjbar Mojdeh
Published: January 2014

Background

Table salt is the most commonly used food additive. Since most of the salt consumed in Iran comes from mines, contamination with heavy metals is a health concern. The commonest salt purification method in Iran is washing with water. But recently, some industries have turned to recrystallization method. The present study aimed to determine the level of essential and non-essential heavy metals in the table salt refined with recrystallization and washing methods.

Methods

Thirty eight pre-packed salt samples were directly collected from retail market in Shiraz (22 samples refined with recrystallization method and 16 with washing method). The level of lead, cadmium, copper, zinc, nickel and cobalt was determined using Voltammetric method. Daily intakes of lead and cadmium as well as their weekly intakes were calculated.

Results

The levels of lead, cadmium, copper, zinc, nickel and cobalt in recrystallized samples were 0. 30 ± 0.26, 0.02 ± 0.02, 0.11 ± 0.06, 0.34 ± 0.22, 0.15 ± 0.19 and 0.008 ± 0.007 μg/g, respectively, and also 0.37 ± 0.27, 0.017 ± 0.021, 0.19 ± 0.18, 0.37 ± 0.20, 0.13 ± 0.23 and 0.037 ± 0.06 μg/g in washed salt samples. The calculated weekly intake of lead and cadmium was 0.216 and 0.014 μg/kg, respectively for the recrystallized and 0.2653 and 0.0119 μg/kg for the washed salts.

Conclusion

All values for toxic metals were lower than the permitted maximum for human consumption as prescribed by Codex and Institute of Standards and Industrial Research of Iran. Only 0.8652-1.0612% of lead and 0.17-0.2% of cadmium PTWIs are received via salt consumption weekly.
Knowledge of insulin use and its determinants among Nigerian insulin requiring diabetes patients
Authors: Jasper Unyime Sunday , Opara Macmillian Chinonso , Pyiki Edna Bawa , Akinrolie Olayinka
Published: January 2014

Background

Intensive insulin therapy is essential in the maintenance of strict glycemic control among insulin requiring patients with diabetes. However this presents a challenge in the face of the complexities associated with insulin use and also taking into consideration the potential dangers associated with inappropriate use. Insufficient knowledge of insulin use can result in preventable complications, adverse patient outcome, poor adherence to therapy and invariably poor glycemic control.

Methods

Insulin requiring diabetes patients (n = 54) attending the 2012 world diabetes day celebration in a Nigerian community were surveyed using a two part questionnaire. Section A elicited information on their demographics characteristics and participation in update courses, and exercise, while section B assessed knowledge of insulin use using the Michigan Diabetes Research and Training Centre's Brief Diabetes Knowledge Test. All participants who had a good grasp of English language or who could understand the contents of the questionnaire when it was explained to them, and were willing to participate in the study were assessed. Descriptive statistics of percentages was computed for the sociodemographic variables, previous education, satisfaction with education, involvement in regular exercise, knowledge of benefit of exercise and correct response to each question in section B. Analysis of variance (ANOVA) and independent t-test was used to determine the influence of sociodemographic variables on insulin use knowledge.

Results

Knowledge of insulin use is poor among insulin requiring patients with diabetes, with majority not conversant with such terms as ketoacidosis, insulin reaction and low blood sugar. Furthermore, they did not know how to modify their insulin dosage in relation to diet, exercise and infections (e.g. flu). Better knowledge of insulin use was associated with age, employment status, level of education attained, how frequent one reads/attends update courses and satisfaction with education received.

Conclusion

Poor knowledge of the causes and prevention of the ketoacidosis, insulin reaction and hypoglycemia increases their risk of developing them, which will invariably lead to poor adherence to insulin therapy. Therefore this study suggests a methodical, continuous and up-to-date tutelage if proper self management in terms of good glycemic control is to be achieved.
Extraction process optimization of polyphenols from Indian Citrus sinensis – as novel antiglycative agents in the management of diabetes mellitus
Authors: Shakthi Deve Asaithambi , Sathish kumar Thiyagarajan , Kumaresan Kuppamuthu , Rapheal Vinohar Stephen
Published: January 2014

Background

Diabetes mellitus is a chronic metabolic disorder characterized by increased blood glucose level. It has become an epidemic disease in the 21st century where, India leads the world with largest number of diabetic subjects. Non-enzymatic glycosylation (glycation) is severe form of diabetes, occurs between reducing sugar and proteins which results in the formation of advanced glycation end products (AGEs) that leads to the other complicated secondary disorders. In this context,Mangifera indica(Mango),Syzygium cumini(Jambul),Vitis vinifera(Grapes),Citrus sinensis(Orange),Artocarpus heterophyllus(Jackfruit),Manilkara zapota(Sapodilla) seeds were evaluated for their antiglyation activity. Attempts were made to isolate the polyphenols in the seeds that have recorded the maximum activity.

Methods

Different extraction methods (shake flask, centrifugation and pressurized hot water) using various extractants (organic solvents, hot water and pressurized hot water) were adopted to investigate thein vitroantiglycation activity. Central composite (CCD) design based Response Surface Methodology (RSM) was espoused to optimize the extraction process of polyphenols from the fruit seeds that have recorded poor antiglycation activity. The PTLC analysis was performed to isolate the polyphenols (Flavonoids and phenolic acids) and LC-PDA-MS analysis was done for structure prediction.

Results

Pressurized hot water extraction ofArtocarpus heterophyllus(87.52%) andCitrus sinensisseeds (74.79%) was found to possess high and low antiglycation activity, respectively. The RSM mediated optimization process adopted for theCitrus sinensisseeds have revealed that 1:15 solvent ratio (hexane to heptane), 6 minutes and 1:20 solid to liquid ratio as the optimal conditions for the extraction of polyphenols with a maximum antiglycation activity (89.79%). The LC-PDA-MS analysis of preparative thin layer chromatography (PTLC) eluates ofArtocarpus heterophyllusseed has showed the presence of compounds like quercetin (301.2), 4-hydroxy phenyl acetic acid (149.0), rhamnosyl-di-hexosyl quercetin sulphate (857.6), quercetin-3-O-xyloside (428.2), rutin (613.4), diosmetin (298.1) and luteolin (283.0).

Conclusion

TheArtocarpus heterophylluswas observed to possess a significant antiglycation activity and the activity ofCitrus sinensiswas improved after the optimization process, which proved that both the seeds may be used as a traditional medicine in the management of chronic diabetes mellitus.
Association between serum level of vitamin D and lipid profiles in type 2 diabetic patients in Iran
Authors: Saedisomeolia Ahmad , Taheri Ehsaneh , Djalali Mahmoud , Moghadam Ali Malekshahi , Qorbani Mostafa
Published: January 2014

Background

It is suggested that vitamin D deficiency is associated with cardiovascular disease (CVD) via its effect on lipid profiles. The objective of this study was to determine the association between fasting serum levels of 25(OH) D and lipid profiles in patients with type 2 diabetes.

Methods

This cross-sectional study was conducted on 108 type 2 diabetics. Patients were selected randomly among members of the Iranian Diabetes Association according to study criteria. Fasting concentration of 25(OH) D, calcium, phosphorus, parathyroid hormone (PTH) and lipid profiles (including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol) were measured.

Results

The mean serum levels of 25-hydroxyvitamin D (25(OH) D) and PTH were 53.41 ± 33.25 nmol/l and 40.24 ± 18.24 pmol/l, respectively, in type 2 diabetic patients. Prevalence of vitamin D deficiency was 58.34% and vitamin D sufficiency and insufficiency combined was 41.66%. Although in diabetic patients with vitamin D deficiency, serum levels of total cholesterol, TG, and LDL were higher and HDL was lower compared to patients with vitamin D sufficiency, this association was statistically significant only for serum level of TG (145.91 ± 79.00 vs. 122.95 ± 55.82 mg/dl).

Conclusions

The results of present study show that serum concentrations of 25(OH) D were inversely associated with TG. More interventional studies are needed to confirm the relationship between serum concentration of vitamin D and lipid profile in patients with type 2 diabetes.
Changes in the pharmacokinetic of sildenafil citrate in rats with Streptozotocin-induced diabetic nephropathy
Authors: Tripathi Alok S , Mazumder Papiya M , Chandewar Anil V
Published: January 2014

Aim

The present investigates deals with the change in the pharmacokinetic of Sildenafil citrate (SIL) in disease condition like diabetic nephropathy (DN).

Method

Diabetes was induced in rats by administering Streptozotocin i.e. STZ (60 mg/kg, IP) saline solution. Assessment of diabetes was done by GOD-POD method and conformation of DN was done by assessing the level of Creatinine, Blood Urea Nitrogen (BUN) and Albuminurea. After the conformation of DN single dose of drug SIL (2.5 mg/kg, p.o.) were given orally and Pharmacokinetic Parameters like [AUC o-t (ug.h/ml), AUC 0-∞, Cmax, Tmax, Kel, Clast] were estimated in the plasma by the help of HPLC-UV.

Result

There was significant increase (p < 0.01) in the Pharmacokinetic parameters of SIL in DN rat (AUC0-t, AUC0-∞, Cmax, Tmax and T1/2) compare to normal control rat and significant increase Kel in the DN rat compare to control rat.

Conclusion

The study concluded that there was significant (p < 0.01) increase in the bioavailability of SIL in DN.
A prospective single arm study of the effect of an acute oral glucose loading on the endothelial function of healthy participants
Authors: Wong Siew Yen , Hasan Tayyab , Yong Moi Ling , Chong Chee Fui
Published: January 2014

Background

Hyperglycaemic load has been shown to cause endothelial dysfunction in patients diagnosed with diabetes mellitus or the pre-diabetic state of glucose intolerance. In the non-disease state such as in healthy subjects, the effect of glucose loading is still uncertain with conflicting results. The aim of this study was to test the hypothesis that an oral 75 g glucose load will not adversely attenuate the endothelial function of healthy participants, 2 hours postprandial.

Methods

This is a prospective single arm study evaluating the brachial artery flow-mediated vasodilation of 12 healthy participants before and after a 75 g glucose loading. Participants’ age, body mass index, family history of diabetes, fasting blood glucose and 2 hour postprandial glucose levels were recorded. All data were analysed with SPSS 17.0 using Wilcoxon test.

Results

Primary analysis of the participants’ brachial artery flow mediated vasodilation before and 2 hours after 75 g oral glucose loading did not show any statistically significant attenuation (p > 0.05) in brachial artery flow-mediated vasodilation, although a trend for reduction in endothelial relaxation was observed. Subgroup analysis of healthy participants with a positive family history of diabetes confirmed a statistically significant attenuation (p < 0.05) in brachial artery flow-mediated vasodilation after acute glucose loading even though the 2 hour postprandial blood glucose level, with a median value of 4.6 ± 2.2 mmol/L was within normal limits. This was not observed in the group without a positive family history of diabetes.

Conclusion

Acute oral glucose loading significantly attenuates endothelial relaxation in healthy subjects with positive family history of diabetes but showed no effect in those without a positive family history of diabetes. The attenuation in endothelial relaxation was observed in the presence of normal glucose metabolism, suggesting a defect in endothelium relaxation even in the non-disease state in the group predisposed to diabetes.
Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction
Authors: Yang Xiaoqin , Yang Ji , Xing Xiaojing , Wan Linlin , Li Ming
Published: January 2014

Introduction

Although immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear. We aimed to investigate the presence of Th17 and Treg cells in SSc patients and the role of Th17 cells in collagen production in SSc fibroblasts.

Methods

We analyzed inflammatory cell profiles in the skin of 13 SSc patients by immunohistochemistry, the percentage of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) of 45 SSc patients and 24 healthy controls by flow cytometry, gene expression in PBMCs by real-time reverse transcription-polymerase chain reaction and interleukin-17 (IL-17) in sera and culture supernatants by enzyme-linked immunosorbent assay. We also investigated the effect of Th17 cell-derived IL-17 on fibroblast growth and collagen production.

Results

Infiltration of inflammatory cells including IL-17+ and Foxp3+ lymphocytes was detected in the skin of patients with early SSc. The percentages of circulating Th17 cells and IL-17 production were elevated in samples from patients with active SSc, whereas the percentage of circulating Treg cells was not affected. The number of Th17 cells was closely related to disease activity. IL-17 from SSc patients promoted fibroblast growth and collagen production, whereas IL-17 neutralizing antibody effectively blocked collagen production.

Conclusion

SSc progression might be linked to expansion of circulating Th17 cells and increased infiltration of IL-17+ cells in skin. Th17-derived IL-17 is involved in fibroblast growth and collagen production. IL-17 blocking antibody may be a useful tool for intervention in the fibrotic course of SSc.
New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells
Authors: Chang Ted H-T , Kunasegaran Kamini , Tarulli Gerard A , De Silva Duvini , Voorhoeve P Mathijs , Pietersen Alexandra M
Published: January 2014

Introduction

Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands.

Methods

We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein.

Results

After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis.

Conclusions

Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis.
Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial
Authors: Masson Serge , Caironi Pietro , Spanuth Eberhard , Thomae Ralf , Panigada Mauro , Sangiorgi Gabriela , Fumagalli Roberto , Mauri Tommaso , Isgrò Stefano , Fanizza Caterina , Romero Marilena , Tognoni Gianni , Latini Roberto , Gattinoni Luciano
Published: January 2014

Introduction

Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).

Methods

This is a retrospective, case–control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.

Results

Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).

Conclusions

In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.
Dynamic regulation of genome-wide pre-mRNA splicing and stress tolerance by the Sm-like protein LSm5 in Arabidopsis
Authors: Cui Peng , Zhang Shoudong , Ding Feng , Ali Shahjahan , Xiong Liming
Published: January 2014

Background

Sm-like proteins are highly conserved proteins that form the core of the U6 ribonucleoprotein and function in several mRNA metabolism processes, including pre-mRNA splicing. Despite their wide occurrence in all eukaryotes, little is known about the roles of Sm-like proteins in the regulation of splicing.

Results

Here, through comprehensive transcriptome analyses, we demonstrate that depletion of the Arabidopsis supersensitive to abscisic acid and drought 1 gene (SAD1), which encodes Sm-like protein 5 (LSm5), promotes an inaccurate selection of splice sites that leads to a genome-wide increase in alternative splicing. In contrast, overexpression of SAD1 strengthens the precision of splice-site recognition and globally inhibits alternative splicing. Further, SAD1 modulates the splicing of stress-responsive genes, particularly under salt-stress conditions. Finally, we find that overexpression of SAD1 in Arabidopsis improves salt tolerance in transgenic plants, which correlates with an increase in splicing accuracy and efficiency for stress-responsive genes.

Conclusions

We conclude that SAD1 dynamically controls splicing efficiency and splice-site recognition in Arabidopsis, and propose that this may contribute to SAD1-mediated stress tolerance through the metabolism of transcripts expressed from stress-responsive genes. Our study not only provides novel insights into the function of Sm-like proteins in splicing, but also uncovers new means to improve splicing efficiency and to enhance stress tolerance in a higher eukaryote.
Genome-wide analysis of light-regulated alternative splicing mediated by photoreceptors in Physcomitrella patens
Authors: Wu Hshin-Ping , Su Yi-shin , Chen Hsiu-Chen , Chen Yu-Rong , Wu Chia-Chen , Lin Wen-Dar , Tu Shih-Long
Published: January 2014

Background

Light is one of the most important factors regulating plant growth and development. Light-sensing photoreceptors tightly regulate gene expression to control photomorphogenic responses. Although many levels of gene expression are modulated by photoreceptors, regulation at the mRNA splicing step remains unclear.

Results

We performed high-throughput mRNA sequencing to analyze light-responsive changes in alternative splicing in the moss Physcomitrella patens, and found that a large number of alternative splicing events were induced by light in the moss protonema. Light-responsive intron retention preferentially occurred in transcripts involved in photosynthesis and translation. Many of the alternatively spliced transcripts were expressed from genes with a function relating to splicing or light signaling, suggesting a potential impact on pre-mRNA splicing and photomorphogenic gene regulation in response to light. Moreover, most light-regulated intron retention was induced immediately upon light exposure, while motif analysis identified a repetitive GAA motif that may function as an exonic regulatory cis element in light-mediated alternative splicing. Further analysis in gene-disrupted mutants was consistent with a function for multiple red-light photoreceptors in the upstream regulation of light-responsive alternative splicing.

Conclusions

Our results indicate that intensive alternative splicing occurs in non-vascular plants and that, during photomorphogenesis, light regulates alternative splicing with transcript selectivity. We further suggest that alternative splicing is rapidly fine-tuned by light to modulate gene expression and reorganize metabolic processes, and that pre-mRNA cis elements are involved in photoreceptor-mediated splicing regulation.
PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast
Authors: Webb Shaun , Hector Ralph D , Kudla Grzegorz , Granneman Sander
Published: January 2014

Background

Nrd1 and Nab3 are essential sequence-specific yeast RNA binding proteins that function as a heterodimer in the processing and degradation of diverse classes of RNAs. These proteins also regulate several mRNA coding genes; however, it remains unclear exactly what percentage of the mRNA component of the transcriptome these proteins control. To address this question, we used the pyCRAC software package developed in our laboratory to analyze CRAC and PAR-CLIP data for Nrd1-Nab3-RNA interactions.

Results

We generated high-resolution maps of Nrd1-Nab3-RNA interactions, from which we have uncovered hundreds of new Nrd1-Nab3 mRNA targets, representing between 20 and 30% of protein-coding transcripts. Although Nrd1 and Nab3 showed a preference for binding near 5′ ends of relatively short transcripts, they bound transcripts throughout coding sequences and 3′ UTRs. Moreover, our data for Nrd1-Nab3 binding to 3′ UTRs was consistent with a role for these proteins in the termination of transcription. Our data also support a tight integration of Nrd1-Nab3 with the nutrient response pathway. Finally, we provide experimental evidence for some of our predictions, using northern blot and RT-PCR assays.

Conclusions

Collectively, our data support the notion that Nrd1 and Nab3 function is tightly integrated with the nutrient response and indicate a role for these proteins in the regulation of many mRNA coding genes. Further, we provide evidence to support the hypothesis that Nrd1-Nab3 represents a failsafe termination mechanism in instances of readthrough transcription.