bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Adiposity is a Strong Predictor of Non‐alcoholic Fatty Liver Disease (NAFLD) in South Asian Women
Authors: Albracht‐Schulte Kembra , Rosairo Shanthini , Ramalingam Latha , Wijetunge Sulochana , Ratnayake R.M.C.J. , Kotakadeniya H.M.S.R.B. , Dawson John A. , Kalupahana Nishan , Moustaid‐Moussa Naima 
Published: June 2021

Incidence of non‐alcoholic fatty liver disease (NAFLD) is increasing with increasing obesity rates due to its relation with the metabolic syndrome. This is of concern in the South Asian population since they develop metabolic complications at lower levels of obesity compared to their Western counterparts. Furthermore, the relationship between NAFLD, insulin resistance and obesity is not well characterized in humans. To address this issue, we used a convenience sample of Sri Lankan adult females (n = 34) and collected anthropometric data, adipose tissue specimens (for histology), and fasted serum samples (for metabolic and inflammatory markers). Hepatic steatosis was assessed by ultrasound scanning and used to classify participants as NAFL 0, NAFL 1, and NAFL 2. Waist circumference significantly increased with increasing NAFLD grade. Participants with NAFLD had significantly higher body mass index, hip circumference, and fasting blood glucose, as well as a higher mean adipocyte area in both omental and abdominal areas, indicating a higher degree of adipocyte hypertrophy associated with fatty liver. There were, however, no differences in measures of dyslipidemia. Various adipokines were measured; however, resistin was the only pro‐inflammatory adipokine significantly elevated in NAFL 2. These findings indicate that measures of adiposity and fasting blood glucose may be important indicators of NAFLD in South Asian women.Support or Funding InformationThis research was funded by an International Research/Development Seed Grant from the Office of International Affairs at Texas Tech University, an International Research Seed Grant from the College of Human Sciences at Texas Tech University, and the Obesity Research Cluster at Texas Tech University. NMM is in part supported by the National Institutes of Health National Center for Complementary and Integrative Health (NIH NCCIH) award number 1 R15 AT008879‐01A1. KAS is a United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) Fellow supported by an Agriculture and Food Research Initiative's (AFRI) Food, Agriculture, Natural Resources, and Human Sciences Education and Literacy Initiative (ELI) Predoctoral Fellowship under award number 2017‐67011‐26029. NSK was funded by the International Research Center, University of Peradeniya, Sri Lanka (InRC/2015/01).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antioxidant and hypoglycemic effects of Justicia spicigera in kidney from diabetic rats
Authors: Martínez‐Mora José Alberto , Murillo‐Villicaña Marina , Mejía‐Barajas Jorge A. , Salgado‐Garciglia Rafael , Peña‐Montes Donovan J. , Montoya‐Pérez Rocío , Noriega‐Cisneros Ruth , Saavedra‐Molina Alfredo 
Published: June 2021

Diabetes mellitus is a metabolic disease characterized by hyperglycemia, with alterations in the metabolism of carbohydrates, lipids and proteins, where there is an absolute or relative deficiency in the secretion and/or action of insulin, or both. Currently, the complications of DM with oxidative stress have been related, causing oxidative damage to biomolecules that can not be counteracted by the defense antioxidant systems, since they are diminished. Such oxidative damage can be counteracted with the administration of antioxidants such as those present in the leaves of Justicia spicigera. Solvents of different polarity were used: Hexane, ethyl acetate and ethanol, since each solvent carries different types of compounds and were tested in vitro antioxidants of: Antilipoperoxidation, reducing power, reduction of phosphomolybdenum and reduction of DPPH radical. In the reduction of the radical DPPH, the hexane and ethanolic extracts equalized the reduction of ascorbic acid with 100% and the ethyl acetate extract 70%. For the reduction of phosphomolybdenum, the hexane extract reduced it by 28%, the extract of ethyl acetate by 94%, and the extract ethanolic by 100%. The reduction of Fe3+ in the hexane extract was 9%; 17% ethyl acetate extract and the ethanolic extract reduced it by 25%. In the antilipoperoxidation technique, the hexanic and ethanolic extract inhibited lipoperoxidation by 82 and 79% respectively, while the extract of ethyl acetate by 53%. For the in vivo tests, male Wistar rats were used to obtain the kidneys. The GSH/GSSG ratio of the kidney mitochondria, the diabetic control group and the hexane and ethyl acetate extracts was of 0.8, unlike the ethanolic extract that significantly improved it to 2.0. Since in DM there is alteration in lipid and protein metabolism, it was of interest to analyze cholesterol, triglycerides, urea and serum creatinine. In the serological tests, the hexanic extract presented only hypolipidemic effect in the diabetic group. Ethyl acetate and ethanolic extracts had hypoglycemic and hypotriglyceridemic effects in diabetic rats. In conclusión, the hexane extracts, ethyl acetate and ethanol from the leaves of Justicia, are of beneficial effects of a serological and antioxidant level.Support or Funding InformationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hepatocyte Early Growth Response 1 (EGR1) Regulates Lipid Metabolism in Nonalcoholic Fatty Liver Disease
Authors: Magee Nancy S. , Zhang Yuxia 
Published: June 2021

ObjectiveNonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide due to significant increases in the prevalence of obesity, insulin resistance diabetes, and hyperlipidemia. A risk factor for NAFLD is insulin resistance as it promotes the excessive accumulation of lipids into the hepatocytes, causing cellular stress and death. As a stress response gene, early growth response 1 (EGR1) plays critical roles in inflammation and tissue repair. The aim for this study is to explore a novel role of hepatocyte EGR1 in the regulation of lipid metabolism in NAFLD.MethodsHuman microarray data from NCBI GEO database (accession #GSE48452) was used to obtain relative EGR1 expression in human normal and NAFLD livers. To determine the expression of EGR1 during the development of NAFLD, C57Bl6/J mice were fed a high in fat, cholesterol, and fructose (HFCF) for up to 9 months and EGR1 levels were examined. An in vitro insulin stimulation experiment was performed in wild type and Egr1‐deficient primary hepatocytes to assess insulin response. In vivo hepatocyte‐specific Egr1 knockout (Egr1‐HKO) mice was accomplished in 2‐month‐old Egr1flox/flox male mice by tail vein administration of adeno‐associated viral vector 8 (AAV8) expressing cre recombinase driven by thyroxine binding globulin (TBG) promoter (AAV8‐Tbg‐Cre). An empty vector AAV8‐Tbg‐Null was included as a control. WT and Egr1‐HKO mice were fed either a normal chow or HFCF diet for 5 months and followed by the examination of body composition, adiposity, metabolic rates, insulin sensitivity, and liver histology.ResultsEGR1 was dramatically induced by insulin and abundantly expressed in the postprandial liver. The expression of EGR1 was significantly reduced in human and mouse NAFLD livers, suggesting a biological relevance of EGR1 downregulation during the pathogenesis of NAFLD. In vitro hepatocyte cultures showed that Egr1‐deficient hepatocytes have impaired activation of AKT but enhanced de novo lipogenesis in response to insulin. In vivo knockout of hepatocyte‐specific Egr1 led to liver steatosis and increased whole body adiposity under the chow diet. Additionally, in vivo EGR1 deficiency in hepatocytes exacerbated NAFLD progression by promoting liver inflammation and fibrosis in mice fed a HFCF diet.ConclusionsOur studies reveal a previously unrecognized role of hepatic EGR1 in the regulation of lipid metabolism. Our findings suggest that hepatocyte EGR1 is crucial to maintain hepatic insulin response and loss of EGR1 in hepatocytes leads to liver steatosis that exacerbates NAFLD development and progression.Support or Funding InformationNCI K22CA184146 and NIH P20 GM103549 to Yuxia Zhang.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Effect of Curcumin against Nitrosamine‐induced Gastric Cancer in Rats
Authors: Waly Mostafa I. , Al‐Hinai Shaimaa , Al‐Bulushi Ismail , Rahman Mohammad Shafiur 
Published: June 2021

BackgroundNitrosamine acts as a carcinogenic agent and induces gastric cancer in rats. The mechanisms underlies nitrosamine‐mediated gastric cancer pathogenesis need to be investigated. Experimental studies continue to support the notion that curcumin combat cancer by acting as a dietary antioxidant.ObjectiveOur study model was undertaken to investigate the preventive effect of curcumin supplementation against nitrosamine‐induced oxidative stress and carcinogenesis in rat stomach.MethodsForty Sprague‐Dawley rats (8 weeks old) were randomly divided into 4 groups (10 rats/group). Control group was fed a standard rat chow diet; nitrosamine‐treated group was fed a standard rat chow diet and also received intraperitonial injections of nitrosamine. The other two groups received oral supplementations of curcumin in the presence or absence of nitrosamine injection. All animals were fed ad‐libitum for 16 weeks. At the end of the experiment all rats were sacrificed and the gastric tissues were examined microscopically for gastric cancer lesions development, and for biochemical measurements of oxidative stress indices.ResultsOur results showed that nitrosamine causes gastric cancer development, as well as inducing oxidative stress in gastric tissue as evidenced by glutathione depletion and inhibition of antioxidant enzymes. The concomitant treatment of nitrosamine with curcumin significantly ameliorated the cytotoxic effects of nitrosamine.ConclusionThe results of this study provide in vivo evidence that curcumin supplementation protects against nitrosamine‐induced gastric cancer in the used animal model.Support or Funding InformationThis research was supported by Strategic Grant Funding (CL/SQU‐UAEU/15/03) and Internal Grant Funding (IG/AGR/FOOD/17/1), College of Agricultural and Marine Sciences, Sultan Qaboos UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
THE IMPACT OF THE AFFORDABLE CARE ACT ON RURAL HEALTHCARE
Authors: Boyd‐Seng Tina L. , Einstein George P. , Tulp Orien L. 
Published: June 2021

In 2010 The Affordable Care Act (ACA) was passed by the U.S. Congress, in a governmental attempt to address the healthcare issues faced by the country. Designed to provide greater coverage to more American citizens, the law has caused an irreversible change in the healthcare systems of the U.S., and in many cases, costs have increased while healthcare quality has decreased. Rural regions suffer additional issues as low competition drives high costs in generally poor areas. In order to gauge the impact of these changes on some rural communities, a local rural community was surveyed using a researcher‐developed quantitative descriptive survey focused on assessing the effects on the quality of the healthcare patients receive, as well as their expenses and level of satisfaction (affordability, availability, accessibility, accommodation, acceptability) following the passage of the ACA. Also, the study sought to compare the results obtained from each different insurance option (employer‐based, self‐paying, personal based, or ACA) in terms of the view of access to healthcare since passing of the ACA. Through comparisons of average scores in each category before and after the passage of the ACA, assessments of the effects of the law on the patient‐perceived quality of healthcare can be made. Analysis of the results showed a statistically committed relationship between age and healthcare provider as well as between income and healthcare provider (both with p< 0.001), and all the comparisons between the perceptions of affordability, availability, accessibility, accommodations and acceptability before the implementation of ACA and after the implementation of ACA were significant (all p's < 0.01). An inspection of the mean differences reveals that on all questions the perceptions and/or beliefs became more negative. These results indicate that among the sampled population, the passing of the ACA has, in most cases, decreased the quality of healthcare provided to patients, at a higher cost than before the law was enactedSupport or Funding InformationSupported by Institutional Resources of USAT Montserrat and the Einstein Medical Institute, N. Palm Beach, FL, USA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Generating 3D artificial melanoma tumor tissues using CellMate™ hydrogels.
Authors: Lyden Timothy , Dahlberg Declan , Martin Mike 
Published: June 2021

We have previously reported on the successful use of natural 3D ECM materials as artificial tissue scaffolds to generate tissue‐like constructs of melanoma using the ATCC cell lines B16F1and B16F10. In that earlier work we observed that 3D constructs like these undergo a progressive scaffold colonization, tissue development and maturation in‐vitro which closely parallels tumor progression in‐vivo. Now, we have extended that work by applying a new and unique 3D hydrogel matrix called CellMate™. This material is an embedding hydrogel comprised of hyaluronate and chitosan which crosslink to generate a matrix scaffolding for cell attachment and tissue development. In these new experiments, B16F1 and B16F10 cell lines were each seeded into CellMate™ at densities of 10 and 20 million cells per scaffold. The resulting structures where then maintained for 6 months of continuous culture with periodic new plates and regular media exchanges at 3 day intervals. This approach resulted in even more physiological artificial tumors, than previously developed on ECM scaffolds. As previously seen on natural scaffolds, these new artificial tumors develop two distinct cell populations which closely reflect the normal in‐vivo tumor structures seen in the clinical setting. These two cell types include pigmented cells with a relatively dendritic appearance and non‐pigmented cells with relatively less dendritic and more rounded cell bodies. These cellular phenotypes also gave rise to distinct tissue‐level structural phenotypes as well. Pigmented tissue regions tended to present with less regular surfaces and more tendency to produce branching structures that extend away from the construct. In contrast, non‐pigmented cell regions generated large rounded and bulging features which often resembled ridges of tissue and which had very smooth surface features. Additionally these structures also appeared to be highly friable and prone to peeling off the main pigmented tumor structure. Colonies and later cell‐strains were developed from these shed structures and these retained their non‐pigmented phenotypes through multiple passages in 2D monolayers. Collectively these studies illustrate the efficacy of using 3D artificial tissues to create better in‐vitro tumor models of melanoma.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhaled Corticosteroids Stimulate cAMP Production and Enhance βAR Signaling In a Non‐Genomic Fashion In Human Airway Smooth Muscle Cells
Authors: Corpuz Maia , Johnstone Timothy , Kazarian Austin , Ostrom Rennolds 
Published: June 2021

Inhaled corticosteroids have been shown to be highly beneficial when combined with β‐adrenergic receptor (βAR) agonists in treatment of asthma. The mechanism for this synergy has never been fully clear, but corticosteroids have been shown to increase βAR expression and reverse βAR desensitization via canonical genomic actions. The current study investigated whether inhaled corticosteroids have an effect on cAMP production in both primary and immortalized human airway smooth muscle (HASM) cells. We measured real‐time cAMP dynamics in live HASM cells using the downward cAMP difference detector in situ (cADDis) cAMP sensor (Montana Molecular, Bozeman MT). Addition of various concentrations of either prednisone, fluticasone or allopregnanolone increased cAMP production over basal within 3 min without phosphodiesterase inhibitors present. We examined various passages of HASM cells and cells from different patients and found fluticasone consistently increased cAMP production at concentrations between 10 nM and 10 μM. We also examined cAMP responses to fluticasone in human embryonic kidney (HEK‐293) cells and observed no increases in cAMP production in response to fluticasone, prednisone, or progesterone. We repeated studies in the presence of glucocorticoid receptor GR‐α antagonists, RU‐486 and GSK‐9027, to understand how corticosteroids may be increasing cAMP levels. Pretreatment with either antagonist attenuated cAMP responses to all activators, including forskolin and βAR agonists, implying these drugs have considerable non‐specific effects. We also evaluated how corticosteroids would alter responses to other cAMP‐elevating agents. Fluticasone (0.1 to 1 μM) increased the potency and maximal effect of isoproterenol, PGE2 and forskolin. These findings are consistent with the idea that corticosteroids directly stimulate cAMP signaling in a non‐genomic manner and can enhance signaling by βAR and prostaglandin E receptors. Future studies will identify the molecular mechanism for this effect and determine if GR‐α is required. These findings reveal an unappreciated action of inhaled corticosteroids that may help explain how these drugs are beneficial in combination with β‐adrenergic receptor agonists for the treatment of asthma.Support or Funding InformationThis work was supported by NIH grant GM107094 (RO)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Poly(ADP‐ribosyl)ation of Signal Transducer and Activator of Transcription (STAT)6 by poly(ADP‐ribose) polymerase (PARP)‐1 is critical for its integrity, nuclear retention, and subsequent regulation of Th2 cytokines during asthma
Authors: Wang Jeffrey , Ghonim Mohamed A. , Ibba Salome Valentina , Pyakurel Kusma , Lammi Matthew R. , Boulares Hamid 
Published: June 2021

BackgroundAlthough asthma is often controlled by corticosteroids and β2‐adrenergic agonists, many individuals cannot control the disease with these therapies. Identifying the key molecular mechanisms behind the disease is crucial for establishing strategies to improve the quality of life for asthmatics. Our laboratory performed a series of pioneering studies revealing the critical role of PARP‐1, classically regarded as a DNA repair enzyme, in asthma pathogenesis by controlling NF‐κB nuclear retention and STAT6 integrity. PARP‐1 inhibition destabilizes STAT6, a transcription factor central to Th2 cytokine signaling, upon IL‐4 or allergen exposure, potentially through a calpain‐dependent mechanism.HypothesisPARP‐1 interacts with IL‐4‐activated STAT6 and modifies it for maintaining STAT6 integrity and trafficking, leading, ultimately, to the expression of Th2 cytokines.MethodsI utilized cell‐free recombinant protein‐based enzymatic reactions, in vitro stimulation of primary splenocytes and PBMCs with IL‐4, histidine‐tag pulldown, immunofluorescence, and co‐immunoprecipitation with subsequent immunoblot to conduct the studies.ResultsPARP‐1 was activated in lungs and PBMCs of human asthmatics. STAT6 interacted with and was poly(ADP‐ribosyl)ated (PARylated) by PARP‐1 in both the cell‐free system and in IL‐4‐treated mouse splenocytes. PARylation of STAT6 was enhanced upon by JAK3. μ‐calpain‐mediated degradation is highly selective for STAT6, and phosphorylation of STAT6 rendered it more susceptible to degradation, but PARylation protected it from such degradation. Intriguingly, these events occurred in the complete absence of damaged DNA, as IL‐4 stimulation‐induced PARylation of STAT6 by PARP‐1 was not accompanied with a DNA damage response as assessed by p53 phosphorylation. PARP inhibition also prevented STAT6 translocation after IL‐4 stimulation in PBMCs.ConclusionModification of STAT6 by PARP‐1 through a DNA damage‐independent mechanism is critical in Th2 responses and overall asthma pathogenesis. Based on the prediction that the IL4/STAT6 pathway is upregulated in asthma, concomitant with elevated phosphorylation of STAT6, activated STAT6 in cells of patients with the disease should be highly susceptible to degradation upon PARP inhibition, leading to an extensive reduction in the expression of Th2 genes.Support or Funding InformationTHIS WORK WAS SUPPORTED IN PART BY AMERICAN HEART ASSOCIATION GRANT# 149740335A/JEFFREY WANG/2017 and the Louisiana Cancer Research Center Stanley S. Scott Cancer CenterThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mutations in Lyn Kinase Causes Changes in Neutrophil Function and Migration
Authors: Chini Julia A. , Bennin David A. , de Jesus Adriana Almeida , Goldbach‐Mansky Raphaela , Huttenlocher Anna 
Published: June 2021

The Src Family Kinase (SFK) Lyn plays important regulatory roles in immune cells including neutrophils. As a signaling protein, Lyn has been shown to regulate neutrophil migration and endothelial adhesion, contributing to inflammation. Lyn contains a tyrosine kinase domain as well as SH2 and SH3 domains allowing for adaptor functions. A set of patients with systemic neutrophil‐induced inflammation have been shown to have de novo germline mutations in Lyn, Y508* and Y508F, affecting the negative regulatory tyrosine residue of Lyn. The purpose of this study is to evaluate the physiological, cellular, and biochemical effects of this mutation, and further understand the role of Lyn Kinase in neutrophil function. Patients were found to have a gain‐of‐function mutation and presented with skin vasculitis that improved with administration of the SFK inhibitor, dasatinib. We generated stable expression lines of WT, Y508*, and Y508F pMX‐Lyn‐GFP in neutrophil‐like PLB‐985 cells. Kinase activity assays show increased phosphorylation of SFK substrate, SAM68, and overall tyrosine phosphorylation with both Y508*and Y508F expression compared to WT, indicating higher kinase activity in the mutants. Further experiments using kinase‐dead mutants indicate that the higher kinase activity is caused by increases in Lyn's kinase activity and not its adaptor function. In addition, we evaluated the chemotaxis of PLB‐985 cells towards the chemoattractant fmlp using transwell migration assays and microfluidic devices that allow for the generation of chemoattractant gradients. Y508* and Y508F PLB‐985 cells were found to have significantly increased chemotaxis towards 10 mM fmlp (p<0.05) than WT Lyn. Our data supports the role of Lyn as a positive regulator of migration, demonstrating that disruption in the regulatory domain of Lyn can cause cellular and physiological changes. Furthermore, it highlights the role of the de novo germline mutations in Lyn as a cause of human inflammatory disease.Support or Funding InformationSupported by the Hilldale Undergraduate Research FellowshipThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.