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Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation Of Mouse 3t3 Cells, Via Pgc-1Α Activation, Which Is Required For Ho-1 Expression And Increased Mitochondrial Function, Maayan Waldman, Lars Bellner, Luca Vanella, Joseph Schragenheim, Komal Sodhi, Shailendra P. Singh, Daohong Lin, Anand Lakhkar, Jiangwei Li, Edith Hochhauser, Michael Arad, Zbigniew Darzynkiewicz, Attallah Kappas, Nader G. Abraham 2016 Marshall University

Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation Of Mouse 3t3 Cells, Via Pgc-1Α Activation, Which Is Required For Ho-1 Expression And Increased Mitochondrial Function, Maayan Waldman, Lars Bellner, Luca Vanella, Joseph Schragenheim, Komal Sodhi, Shailendra P. Singh, Daohong Lin, Anand Lakhkar, Jiangwei Li, Edith Hochhauser, Michael Arad, Zbigniew Darzynkiewicz, Attallah Kappas, Nader G. Abraham

Biochemistry and Microbiology

Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P < 0.05, in PGC-1α and a decrease in mitochondria-derived ROS (MitoSox), P < 0.05. The EET increase in heme oxygenase-1 (HO-1) levels is dependent on activation of PGC-1α as cells deficient in PGC-1α (PGC-1α knockout adipocyte cell) have an impaired ability to express HO-1, P < 0.02. Additionally, adipocytes treated with EET exhibited an increase in mitochondrial superoxide dismutase (SOD) in a PGC-1α-dependent manner, P < 0.05. The increase in PGC-1α was associated with an increase in β-catenin, P < 0.05, adiponectin expression, P < 0.05, and lipid accumulation, P < 0.02. EET decreased heme levels and mitochondria-derived ROS (MitoSox), P < 0.05, compared to adipocytes that were untreated. EET also decreased mesoderm-specific transcript (MEST) mRNA and protein levels (P < 0.05). Adipocyte secretion of EET act in an autocrine/paracrine manner to increase PGC-1α is required for activation of HO-1 expression. This is the first study to dissect the mechanism by which the antiadipogenic and anti-inflammatory lipid, EET, induces the PGC-1α signaling cascade and reprograms the adipocyte phenotype by regulating mitochondrial function and HO-1 expression, leading to an increase in healthy, that is, small, adipocytes and a decrease in adipocyte enlargement and terminal differentiation. This is manifested by an increase in mitochondrial function and an increase in the canonical Wnt signaling cascade during adipocyte proliferation and terminal differentiation.


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Yanling Yan

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Cell-To-Cell Transmission Of Dipeptide Repeat Proteins Linked To C9orf72-Als/Ftd., Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti 2016 Jefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University

Cell-To-Cell Transmission Of Dipeptide Repeat Proteins Linked To C9orf72-Als/Ftd., Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti

Farber Institute for Neurosciences Faculty Papers

Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases. While DPR toxic mechanisms continue to be investigated, the potential for DPRs to spread has yet to be ...


Continuous Care In Complex Contexts: Access To Health Services For Noncommunicable Diseases Among Syrian Refugee Women In Jordanian Host Communities, Jennifer Ostrowski 2016 SIT Study Abroad

Continuous Care In Complex Contexts: Access To Health Services For Noncommunicable Diseases Among Syrian Refugee Women In Jordanian Host Communities, Jennifer Ostrowski

Independent Study Project (ISP) Collection

This study examines how, when and where Syrian refugee women living in a host community in central Jordan access health services related to noncommunicable diseases. Noncommunicable diseases are the leading cause of death and disability worldwide, but can be effectively managed through timely treatment. Examining access to care for these diseases in the context of humanitarian emergencies, such as war and displacement, is particularly important because they require continuous care, which may be interrupted during emergencies, and because they can cause acute complications, which may be exacerbated by emergencies (WHO, 2016).

Previous studies indicate a high burden of NCDs among ...


Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

Animal tests yield misleading results.


Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications ...


Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render ...


Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the ...


An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls 2016 British Union for the Abolition of Vivisection

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, Ph.D.

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species ...


Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey 2016 New England Anti-Vivisection Society

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, Ph.D.

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer ...


An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey 2016 New England Anti-Vivisection Society

An Examination Of Chimpanzee Use In Human Cancer Research, Jarrod Bailey

Jarrod Bailey, Ph.D.

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human ...


Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey 2016 New England Anti-Vivisection Society

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, Ph.D.

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis ...


Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority ...


Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were ...


Sample Size Formulas For Estimating Intraclass Correlation Coefficients In Reliability Studies With Binary Outcomes, Mengxiao Xu 2016 The University of Western Ontario

Sample Size Formulas For Estimating Intraclass Correlation Coefficients In Reliability Studies With Binary Outcomes, Mengxiao Xu

Electronic Thesis and Dissertation Repository

Introduction: Measurement errors can seriously affect quality of clinical practice and medical research. It is therefore important to assess such errors by conduct- ing studies to estimate a coefficients reliability and assessing its precision. The intraclass correlation coefficient (ICC), defined on a model that an observation is a sum of information and random error, has been widely used to quantify reliability for continuous measurements. Sample formulas have been derived for explicitly incorporation of a prespecified probability of achieving the prespecified precision, i.e., the width or lower limit of a confidence interval for ICC. Although the concept of ICC is ...


Oncology Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer, Mary Insana Fisher 2016 Baptist Health Lexington

Oncology Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Background: The medical treatment of prostate cancer results in multiple impairments in body structure and declines functional abilities, resulting in activity limitations and participation restrictions. Measurement of functional mobility is an essential outcome measure in survivorship care. Purpose: The purpose of this systematic review is to make recommendations of the best measurement tools to assess functional mobility in men treated for prostate cancer based on psychometric properties and clinical utility. Methods: Multiple electronic databases were searched from February to March 2014. Studies of tools used to assess functional mobility were included if they met the following criteria: reported psychometric properties ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Zijian Xie

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


Safety Of Infliximab In Children With Ibd: The Experience Of An Academic Center In Wv, Michael Northcutt MD, Awni Al-Subu MD, Brooke Bella RN, Yoram Elitsur MD 2016 Marshall University

Safety Of Infliximab In Children With Ibd: The Experience Of An Academic Center In Wv, Michael Northcutt Md, Awni Al-Subu Md, Brooke Bella Rn, Yoram Elitsur Md

Yoram Elitsur

BACKGROUND: The immune-modulating drug, infliximab, is approved for Inflammatory Bowel Disease (IBD) treatment in children. Chronic therapy with infliximab is associated with the development of early and delayed infusion reactions. We reviewed our experience with infliximab treatment and its side effects in a cohort of children diagnosed with IBD who were treated in our clinic. METHODS: A retrospective analysis of all IBD children treated with infliximab in our center from 2006-2011 was performed. The demographic, chronological and clinical data were recorded. The infliximab infusion was given at 5mg/ kg according to a standard protocol after pre-treatment with low dose steroid ...


Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro MD 2016 Marshall University

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Nader G. Abraham

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice ...


E-Cigarettes: An Up To Date Review And Discussion Of The Controversy, Zachary Sanford, Lynne J. Goebel MD 2016 Marshall University

E-Cigarettes: An Up To Date Review And Discussion Of The Controversy, Zachary Sanford, Lynne J. Goebel Md

Lynne J. Goebel

Electronic cigarettes (e-cigarettes) present a novel method for nicotine delivery that is reportedly advantageous when compared to traditional cigarette usage. Manufacturers and consumers claim reduced chemical exposure, decreased symptom profiles, and efficacy in smoking reduction and cessation greater than conventional nicotine replacement therapies (NRT). However these products present new challenges and concerns to legislators, clinicians, and public health advocates. Questions of authority in state and federal legislation, establishing product quality control, assessing long-term studies on e-cigarettes and quantifying usefulness in harm reduction represent only a portion of the many unanswered topics being discussed. The purpose of this article is to ...


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