bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screen for Chemical Modulators of the Laminin‐induced Clustering of Dystroglycan Reveals Novel Inhibitors of Aquaporin‐4 Polarized Distribution in Astrocytes
Authors: Noel Geoffroy Pierre , Stevenson Sarah , Moukhles Hakima 
Published: June 2021

Aquaporin‐4 (AQP4) is the principal water channel in the brain and is mainly concentrated at perivascular astrocyte endfeet. This distribution of AQP4 is of major importance because it renders the channel capable of regulating water fluxes between the brain and the bloodstream and therefore plays a role in the water homeostasis. Evidence points to a role of the dystrophin‐associated protein (DAP) complex in the localization of AQP4 at astrocyte endfeet, via dystroglycan (DG) interaction with perivascular laminin. Interestingly, lack of AQP4 concentration at these endfeet in the dystrophin null mouse has been associated with a delayed onset of brain edema. It is therefore of particular importance to identify molecules that modulate the perivascular localization of AQP4. Here, we carried out a high‐throughput screen, using a chemical library of 3,594 small molecules, to identify modulators of the laminin‐induced co‐clustering of the DAP complex and AQP4 in primary astrocyte cultures. Of the 6 inhibitory molecules identified, one induced the reduction of the clustering by promoting the metalloproteinase‐mediated shedding of DG. These findings demonstrate the robustness of our in vitro model that provides a powerful tool for high‐throughput screening and allows us to identify and validate new compounds capable of disrupting the laminin‐induced co‐clustering of the DAP complex with AQP4.Grant Funding Source: Canadian Institutes of Health Research (CIHR), Muscular Dystrophy Canada (MDC)
Associations Between Folate, DNA Methylation, Methylenetetrahydrofolate Reductase Polymorphisms, and Colorectal Cancer Risk: A Review
Authors: Miszewski Susan Grace , Nazmi Aydin , Derelian Doris 
Published: June 2021

A review of twelve studies showed consistent links between folate and colorectal cancer (CRC). Low dietary folate may lead to reduced levels of 5,10‐methylenetetrahydrofolate and accumulation of deoxsyuridylate in DNA which decreases DNA integrity and chromosomal breaks and increases CRC risk. Low dietary folate also leads to decreased DNA methylation; hypomethylation is suggested to inactive the p53 tumor suppressor gene. Folate deficiency produces strand breaks in human DNA, specifically in exons 5–8 of the p53 gene. These possible epigenetic factors depend on methylenetetrahydrofolate reductase genotype. Individuals with the 1298CC genotype showed lower risk of rectal cancer compared to those with the 1298AA or 1298AC genotypes. Individuals with the 677TT genotype showed reduced risk of rectal cancer when compared to those with the 677CT and 677CC genotypes. Levels of DNA methylation were consistently determined by folate status for those with the 677TT genotype, suggesting a possible role for plasma folate as an effect modifier among these individuals. Dietary folate status impacts risk for CRC via DNA methylation and chromosomal integrity, only in individuals with the 677TT genotype.Source of Support: None
Selenium (Se) supplementation for 6 months increases plasma selenium levels in HIV+ adults in Botswana
Authors: Sales Sabrina , Tsalaile Lesedi , Burns Patricia J , Campa Adriana , Makhema Joseph , Marlink Richard , Baum Marianna K 
Published: June 2021

ObjectiveTo determine whether supplementing 200 mg/day of selenium (Se) for 6 months increases plasma Se in asymptomatic, ART naïve HIV+ adults in Botswana.MethodsAfter consenting, 79 participants were randomized into the Se supplementation (N=33) or placebo (N=46). Fasting blood was drawn for plasma Se levels, CD4 cell count and HIV viral load. Se deficiency was defined as <0.085 mg/L.ResultsMean age was 34.13±8.0 years and 72.2% were male. The prevalence of Se deficiency in this cohort was 94.9% (n=75). At baseline, there were no significant differences in mean Se levels between the two groups (0.065±0.010 mg/L vs. 0.070±0.024 mg/L, p=0.182). After 6 months of supplementation, there were significant differences in mean Se levels between the Se‐supplemented (0.147±0.153 mg/L) and not supplemented groups (0.069±0.121 mg/L, p<0.001). There were no significant differences in CD4 cell count and viral load between the groups at 6 months.ConclusionsSupplementation with Se for 6 months normalized plasma Se in those who were deficient, and increased Se levels in all supplemented participants. This study also demonstrates that Se may be used as an index of adherence in micronutrient supplementation studies that contain Se. Further research is needed to determine the length of supplementation needed at this dose to reach steady state and observe clinical benefits of supplementation.Funded by NIDA
Effects of decaffeination process on the phenolic content and antioxidant capacity of brewed coffees
Authors: Freeman Michelle Ruth , Landin Sarah Elizabeth , Wilson Ted 
Published: June 2021

Coffee is rich in phenolics which provide its color, taste and antioxidant capacity, although decaffeination may reduce coffee health benefits. Decaf methods, i.e. Swiss water (SW), supercritical CO2 (SCC), water:ethyl acetate(WEA), methylene chloride(MC), and water (H2O), may alter phenolic content, antioxidant capacity and health benefits. Decaf coffees were compared to regular caffeinated coffees (RC) of the same brand, bean, and roast. Phenolic content was measured in gallic acid equivalents (GAE in mg/L), RC: 143±2, SCC: 131±5, WEA:137±4, H2O: 146±5, MC 124±3, and SW 128±3(LSM ± SE). GAE of MC and SW were significantly lower than RC, whereas SCC, WEA, and H2O decaf methods did not affect GAE. Human LDL oxidation was induced with 10μM Cu++ in vitro and quantified (A234nm lag‐time) as % control in the presence/absence of diluted coffee. At 1:5,000 RC, SW, SCC, WEA, MC and H2O were protected LDL from oxidation vs control LDL oxidized without coffee. Antioxidant effects were less robust vs control at 10K and 50K dilutions. 5K dilutions of WEA, H2O, and MC had similar antioxidant capacities to RC, while SW and SCC were less than RC. TBARS confirmed RC and decaf coffee (5K) antioxidant capacities. This study suggests that some decaf methods may not alter phenolic content and antioxidant capacity. Decaf methods could be an independent factor for interpreting health benefit studies of decaf coffee.Grant Funding Source: WSU Foundation
Selective effect of dyslipidemic human sera on in vitro gene expression
Authors: Zirpoli Hylde , Caputo Mariella , Carraturo Antonio , Torino Gaetano , Fazio Alessia , Attya Mohamed , Rastrelli Luca , Tecce Mario Felice 
Published: June 2021

Since serum lipids are affected by nutritional intake and endogenous metabolism, we assayed the ability of human sera, differing in several metabolic and nutritional parameters, to affect specific gene expression in human hepatoma cells using sera from hypercholesterolemic subjects (LDL‐cholesterol median is 260mg/dl) vs normolipidemic subjects (LDL‐cholesterol median is 160mg/dl).Hypercholesterolemic sera decreased sterol regulatory element binding protein 1c (SREBP‐1c) mRNA by 40% (p<0.05). UDP‐glucuronosyltransferase 1A1 (UGT1A1) mRNA expression was significantly increased by hypercholesterolemic sera by 84% (p<0.01).Determination of fatty acids levels in sera showed that arachidonic acid (AA) was 88% more abundant in high cholesterol subjects (p<0.01) while docosahexaneoic and eicosopentanoic acids (DHA and EPA), as quota of total detected fatty acids, were significantly higher in low cholesterol subjects by 25% (p<0.05) and by 80% (p<0.01) respectively. Higher DHA EPA and AA concentrations link to a 2 fold higher expression of UGT1A1.Although individual serum components accounting for the observed effects cannot be distinguished, our data indicate that the serum cholesterol containing lipoproteins directly affect gene expression pathways involved in metabolic regulation.This work was supported from the FARB 2007 and 2008 grants of the University of Salerno.Grant Funding Source: Farb 2007/2008 grants of the university of salerno
Poly (ADP‐ribose) Polimerase (PARP) Inhibition in Experimental Acute Necrotizing Pancreatitis
Authors: Uysal Bulent , Yasar Mehmet , Oztas Emin , Sadir Serdar , Coskun Omer , Cayci Tuncer , Oter Sukru , Guven Ahmet , Korkmaz Ahmet 
Published: June 2021

IntroductionInhibition of poly(ADP‐ribose) polimerase (PARP) is shown to reduce inflammation in several entities. Thus, we designed a study to evaluate the efficacy of benzamide (B), a PARP inhibitor, in an experimental model of ANP.MethodsThirty Sprague‐Dawley rats were divided into 3 groups: sham, ANP, ANP+B groups. ANP was induced by infusing of 1 mL/kg of 3% sodium taurocholate into the common biliopancreatic duct. ANP+B group received 100 mg/kg/day benzamide i.p. for a total of 3 days after induction of ANP. The surviving animals were killed at the 4th day and their pancreas was harvested for biochemical, microbiological and histopathological analysis. Blood samples from animals were also obtained.ResultsIn the ANP group, a clear increase in serum amylase and neopterin levels and tissue oxidative stress indices were present; almost all of these changes were found to be reversed near to their normal values in ANP+B group. Histopathologic injury scores were significantly high in ANP group (p<0.05, ANP vs. sham) which were significantly lower in ANP+B group (p<0.05, ANP+B vs. ANP). Evaluation of bacterial translocation presented significantly less infected sites in ANP+B group than in ANP animals (p<0.01).ConclusionOur data showed that inhibition of PARP with benzamide reduced the severity, the mortality, bacterial translocation rates and neopterin levels in the experimental ANP model of rats.
NSAID‐activated gene‐1 as a molecular target for capsaicin‐induced apoptosis through a novel molecular mechanism involving GSK3beta, C/EBPbeta, and ATF3
Authors: Lee Seong‐Ho , Krisanapun Chutwadee , Baek Seung Joon 
Published: June 2021

NSAID‐activated gene‐1 (NAG‐1) is a cytokine associated with pro‐apoptotic and anti‐tumorigenic property in colon and lung cancer. Capsaicin, a natural product of the Capsicum species of red peppers, is known to induce apoptosis in colon cancer cells. This study was performed to determine molecular mechanism by which capsaicin activates transactivation of NAG‐1 gene in human colorectal cancer cells. Capsaicin increases apoptosis, and up‐regulates NAG‐1 gene expression at the transcriptional level through C/EBPbeta‐mediated pathway. We identified C/EBPbeta binding sites in the NAG‐1 promoter responsible for capsaicin‐induced NAG‐1 transactivation and EMSA and ChIP assay confirmed binding of C/EBPbeta to the NAG‐1 promoter. Capsaicin treatment increased C/EBPbeta phosphorylation, and enhanced binding of C/EBPbeta with GSK3beta, and ATF3. Knockdown of C/EBPbeta, GSK3beta or ATF3 ameliorates NAG‐1 expression induced by capsaicin treatment. These data indicate that C/EBPbeta phosphorylation through binding to GSK3beta may mediate capsaicin‐induced expression of NAG‐1 and apoptosis through cooperation with ATF3 in human colorectal cancer cells.Grant Funding Source: NIH, American Cancer Society
Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side‐by side comparison
Authors: Nutakul Wasamon , Sober Hana Shatara , Qiu Peiju , Dong Ping , Xiao Hang 
Published: June 2021

Resveratrol (REV) and pterostilbene (PTS) are structurally related stilbene compounds found in fruits such as grapes and blueberries. We compared their effects on three human colon cancer cells (HT29, HCT116 and Caco2). PTS showed much stronger growth inhibitory effects than REV. IC50 of PTS were 2~5‐fold lower than those of REV. In HCT116 and HT29 cells, PTS caused cell cycle arrest at G0/G1 and G2/M phases, respectively, while REV did not cause apparent change in cell cycle at same concentrations. In HT29 cells, PTS at 25 μM significantly enhanced apoptosis, while 75 μM of REV was needed to induce same magnitude of apoptosis. In contrast, PTS and REV showed similar potency in inducing apoptosis in HCT116 cells. These pro‐apoptotic effects were further confirmed by increased levels of cleaved PARP protein in cancer cells. Bioavailability is an important factor dictating the biological activity of dietary components. Using HPLC, we determined the cytosol levels of PTS and REV in cancer cells after treatments with two compounds at same concentration. In all three colon cancer cells tested, the cytosol levels of PTS were about 2~3‐fold higher than those of REV. These results indicated that two methyl groups in PTS facilitate the cellular uptake of PTS in comparison with REV. The increased intracellular levels of PTS may contribute considerably to the stronger growth inhibitory effects on colon cancer cells by PTS than by REV.Grant Funding Source: University of Masschuaetts Amherst
Perceived Determinants of Childhood Obesity Among WIC Participants
Authors: Mejia Maximino Alfredo , Montgomery Susanne B , Melgar‐Quinonez Hugo 
Published: June 2021

We conducted this study to identify perceived determinants of childhood obesity by Hispanic WIC participant mothers and to assess the feasibility of applying participatory research to develop interventions to reduce childhood obesity at WIC.MethodsWe conducted 12 theory‐based in‐depth, semi‐structured interviews with Hispanic mothers of overweight children enrolled in the WIC program. We framed open‐ended questions based on core constructs of the Health Belief Model and the PRECEDE‐PROCEED Model and we analyzed the qualitative data collected with NVivo 8 to identify emerging themes.ResultsAs a group, Hispanic mothers have a good understanding of the behavioral, environmental, and ecological determinants of childhood obesity. They identified key determinants of childhood obesity and their potential solutions. Hispanic mothers shared their stories and experiences for their peers to lower the obesity epidemic.ConclusionThe HBM and PRECEDE‐PROCEED Model provide a suitable framework to identify perceived determinants and solutions to deal with childhood obesity among Hispanics. Most of the perceived determinants of obesity identified in this study are in harmony with current literature. A participatory action research is feasible to design a primary prevention intervention of childhood.This study was supported by a USDA Bridge Grant.
The expression of enzymes related to reverse cholesterol transport metabolism in metabolic syndrome: KMSRI‐SEOUL Project
Authors: Park Mi Young , Kang In Hae , Lee So Youn , Park Kyung Min , Lee Myoung Sook 
Published: June 2021

Metabolic Syndrome(MetSyn) has continuously increased in Korea for the past 10 years(KNHNES 2005).To investigate the metabolic changes of reverse cholesterol transport(RCT) as a major reason in MetSyn, 373 out‐patients were recruited from Seoul Medical Center. Clinic and biochemical measurements included anthropometry, lipid biochemistry, apo E genotyping and the expression of enzymes related to RCT such as lecithin:cholesterol acyltransferase(LCAT), cholesteryl ester transfer protein(CETP) and lipoprotein lipase(LPL).The prevalence of MetSyn was 51.3% for men and 41.8% for women using the modified criteria for ATPIII and IDF for Korea MetSyn. The levels of LCAT, apo C‐II, and apo E were increased, but the masses of CETP and LPL were decreased in MetSyn patients. CETP showed a negative correlation with BP and TG. Consequently, high LCAT and low CETP levels resulted in the MetSyn attack in concomitant with insulin resistance markers such as high TG and low LPL levels. The normal type of e3 allele showed a negative correlation with LPL and TG, and a positive correlation in variants(e2, e4) cannot be observed, apoE variants had a little effect in the lipid circulation on RCT system in MetSyn. We concluded that the increasing TG corresponding to decreased LPL and CETP activites might be considered as the potential biomarkers in the insulin resistant MetSyn patients.
The expression of tetranectin is affected by polyunsaturated fatty acids in human adipocytes
Authors: Wang Ya‐Ching , Wu Hsin‐Ting , Lin Hsin‐Yu , Ding Shih‐Tong 
Published: June 2021

Tetranectin (TN) enhances fibrolysis specifically by binding to the plasminogen‐like hepatocyte growth factor and tissue‐type plasminogen activator (tPA). Tetranecttin is an inducer of plasminogen activation which is catalyzed by tPA. We detected the expression of TN in human adipocytes. Using the primers of TN exon1 to detect TN mRNA expression by real‐time PCR, we found that TN mRNA expression was positive correlated with both adipogenesis and human body mass index (BMI). Many genes involve in lipid metabolism is regulated by polyunsaturated fatty acids (PUFA) in adipocytes. PUFA also regulate the adipocyte differentiation, adipogenesis, and lipolysis. We treated human adipocytes with different PUFA, include docosahexaenoic acid, eicosapentaenoic acid, and arachinonic acid and found that PUFA decreased the expression of TN mRNA expression. These results suggest that TN may have a role related to regulating lipid metabolism in adipocytes.The project was funded in part by the National Science Council in Taiwan.Grant Funding Source: The project was funded in part by the National Science Council in Taiwan
Correlation between n‐3 fatty acid intakes estimated using a food frequency questionnaire and concentrations measured in plasma phospholipids
Authors: Garneau Veronique , Paradis Ann‐Marie , Godin Gaston , Julien Pierre , Perusse Louis , Vohl Marie‐Claude 
Published: June 2021

AimTo verify whether intakes of n‐3 fatty acids (FA) estimated from a food frequency questionnaire (FFQ) correlate with n‐3 FA concentrations measured in plasma phospholipids (PL).MethodsThe study sample consisted of 100 men and 100 women. Dietary data were collected using a FFQ administered by a dietitian. Plasma PL FA profile was measured by gas chromatography.ResultsDocosahexaenoic acid (DHA) (men: r=0.52, p<0.0001; women: r=0.57, p<0.0001) and total n‐3 FA (men: r=0.47, p<0.0001; women: r=0.52, p<0.0001) intakes were positively correlated to their respective plasma PL FA concentrations in both sexes. In women only, eicosapentaenoic acid (EPA) (r=0.44, p<0.0001) and docosapentaenoic acid (DPA) (r=0.23, p=0.02) intakes correlated with plasma PL FA concentrations. The quintile assignment analysis highlights the relation between the n‐3 FA estimated versus measured in plasma PL. DHA is the FA that was classified the most successfully (72% of men and 62% of women assigned in the same or adjacent quintiles) and DPA is the FA that had the smallest level of agreement between the 2 methods (around 50% for both sexes).ConclusionsIntakes of n‐3 FA estimated from a FFQ correlate with n‐3 FA concentrations measured in plasma PL. FFQ could be used as a simple, low cost tool in studies investigating effects of n‐3 FA intakes in some diseases. This study was supported by CIHR.
Differences in percent body fat and plant protein intake between females with and without polycystic ovary syndrome in South Korea
Authors: Park Seung‐hee , Hwang Ji‐Yun , Chang Namsoo , Chung Hey Won , Sung Yeon‐Ah 
Published: June 2021

Limited studies have reported that polycystic ovary syndrome (PCOS), which is closely associated with infertility, is known to be related to body fat and macronutrient intake. This study was to compare the anthropometric, hematological, and dietary factors between females with (n=214) and without PCOS (n=80) in Korea. Subjects (age, 21.28±4.12 y) with menstrual irregularity were recruited for the baseline investigation from December 2008 to May 2009 and they were classified as those with and without PCOS based on European Society of Human Reproduction and Embryology. Nutrient intake was measured by a 24‐hour recall for two days within the same week. Females with PCOS had higher BMI (22.0 kg/m2vs 20.9 kg/m2, p=0.01), waist‐hip ratio (0.83 vs 0.81, p<0.001), percent body fat (33.6% vs 31.6%, p=0.013), and Ferriman‐Gallwey score (5.18 vs 2.80, p<0.001) than those without PCOS. Hematocrit levels were significantly higher (38.1% vs 37.1%, p=0.013) and plant protein intake was lower (28.69g vs 36.09g, p=0.027) in females with PCOS than those without. Further studies are needed to investigate anthropometric and dietary factors related to PCOS with healthy females.This work was supported by the 2nd stage of Brain Korea 21 project.
Identification of a conformational epitope induced when plasminogen binds to fibrin
Authors: Kim Kee‐Hwan , Baik Nagyung , Parmer Robert J , Miles Lindsey A 
Published: June 2021

A key step in thrombolysis is the interaction of plasminogen with the substrate, fibrin. This results in marked enhancement of plasminogen activation. To study this mechanism we developed a monoclonal antibody (mAb 109) that reacts with fibrin‐bound plasminogen in the presence of a ≥ 50‐fold molar excess of soluble plasminogen. The objective of our study was to define the epitope recognized by mAb 109 that reports a conformational change in plasminogen upon binding to fibrin. Plasminogen was denatured in urea and reduced and alkylated followed by digestion with trypsin. Using western blotting and a specific mAb 109‐based ELISA for plasminogen, we established the concentration of trypsin that resulted in maximal digestion of plasminogen, while retaining reactivity with mAb 109. The plasminogen digest was applied to a mAb 109 immunoaffinity column. The eluate was subjected to LC‐MS‐MS. Two peaks with masses of 1298 AMU and 1030 AMU corresponding to a nonlinear epitope contained within H494‐R504 within the kringle 5 domain and L652‐K661 in the latent protease domain, respectively, were obtained. These results were corroborated in western blotting of plasminogen domains. Our data suggest that this domain becomes accessible to mAb 109 when plasminogen interacts with fibrin. Thus, the conformational change detected by mAb 109 is likely to enhance the ability of plasminogen to be activated on the fibrin surface.Supported by a Recovery Act Supplement to NIH HL081046 for Summer Research Experiences for Students and Science Educators and by the Department of Veterans Affairs.
Molecular Histology of Tissue using Imaging Mass Spectrometry and Classification Analysis
Authors: Cornett Dale Shannon , Schwamborn Kristina , Wild Peter , Caprioli Richard M 
Published: June 2021

IntroductionImaging mass spectrometry (IMS) applied to fresh frozen or formalin‐fixed tissues enables the visualization of tissue/cancer specific protein/peptide distribution without prior knowledge of the target compounds. Classification analyses of these ion images exhibit strong correlation to high resolution histological images.MethodSerial sections from a tissue microarray (TMA) with formalin‐fixed and paraffin‐embedded (FFPE) normal tissue samples (n=12), cancer samples (n=30) and cell lines (n=16) from different organ sites were analyzed by on‐tissue digestion followed by MALDI imaging and MS/MS analysis.Preliminary dataOn average, 210 high abundance peptides were observed in the mass range from m/z 600–4000. Analyses of serial sections performed on different days and two different instruments showed reproducible patterns. Spectra from various samples, when compared with high resolution histology, showed distinctive differences in peak patterns. For example, peptides detected at m/z 1650.0 and 2089.2 were at significantly higher expression in samples with leiomyosarcoma. Similarly, peptides at m/z 1506.7 and 1177.7 were also seen with significantly higher abundances in pancreas and astrozytoma, respectively.