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The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

Determining The Protective Effects Of Quercetin Against Cadmium Toxicity In Human Embryonic Kidney Cells, Caroline N. Smith

Undergraduate Theses

Cadmium is a toxic industrial and environmental pollutant found in groundwater, air, soils, food and cigarettes. Chronic intake of low levels of cadmium has been shown to result in renal dysfunction due to cell death which can occur via apoptosis as well as necrosis. Previous studies have shown that plant extracts containing quercetin, a flavonoid found in many fruits and vegetables, protect against cadmium toxicity in rat liver hepatocytes. To determine if quercetin may have a protective effect in a cadmium-treated human embryonic kidney cell line, HEK-293 cells were treated using concentrations of cadmium chloride from 10 to 50 μM …

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski

Toxicology and Cancer Biology Faculty Publications

Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing …

Endoscopic Gastrojejunostomy: A Novel Approach To Roux Limb Obstructions Following Roux-En-Y Hepaticojejunostomy., Travis Magdaleno Md, Eric Nellis Md, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Week Of April 24, 2017, New York Medical College

InTouch

• SHSP Celebrates National Public Health Week
• Camille A. Clare, M.D., M.P.H. '11, Named Associate Dean of Diversity and Inclusion for the School of Medicine
• Sarah Cottet Named Acting Director of the Department of Facilities

Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort …

Post-Intensive Care Syndrome: Comparison Of Educational Interventions To Educate Parents Of Children Hospitalized In The Pediatric Intensive Care Unit At St. Louis Children’S Hospital, Stephanie A. Esses

Dissertations

Background: Family members of children hospitalized in the pediatric intensive care unit (PICU) can develop cognitive, psychological, and physical manifestations of post-intensive care syndrome (PICS). Targeted education to help parents/caregivers recognize the signs and symptoms of PICS may result in better awareness of the syndrome and greater willingness to seek and receive support during their child’s PICU admission.

Objective: to evaluate three targeted PICS educational interventions to increase PICS awareness among parents/caregivers in the St. Louis Children’s Hospital (SLCH) PICU.

Results: A total of 62 parents/caregivers received one of three educational interventions: informational brochures (n=22), scripted informational conversation (n=20), or …

Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD).

METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals …

A Review Of The Role Of Interleukin-6 On Disease Progression In Epithelial Ovarian Cancer, Urmimala Chaudhuri

Browse all Theses and Dissertations

Ovarian cancer is one of the most harmful gynecological cancers and has one of the highest mortality rates. As ovarian cancer progresses, the patient has changes to the immune system and energy metabolism with symptoms being weight loss, nausea, and fatigue. Changes to the immune system include overexpression of proinflammatory cytokines. One such cytokine is Interleukin-6 (IL-6), which is a useful prognostic marker to measure disease progression. IL-6 is thought to promote cancer cell proliferation by upregulating apoptosis inhibitory proteins. IL-6 also plays a role in ascites formation. While tumors may initially respond to chemotherapy treatment, most patients will have …

Clinical Significance Of A False Positive Glucose Challenge Test In Patients With A High Body Mass Index, A Borja, M Moretti, Nisha Lakhi

NYMC Faculty Publications

OBJECTIVE: To determine if there is an increased maternal or neonatal morbidity in overweight and obese patients with a false positive glucose challenge test (GCT). METHODS: Patients with a body mass index (BMI) >/=25.0 at registration were included in this prospective 36-month study. The study cohort consisted of patients with a false positive (FP) GCT, with two comparison cohorts: those with a (1) screen negative (SN) GCT result and (2) true positive (TP) GCT result. Risks were reported as odd ratios with 95% confidence intervals, with a P/=4000 g in the FP cohort, but this fell short of reaching statistical …

Cis-Eqtl-Based Trans-Ethnic Meta-Analysis Reveals Novel Genes Associated With Breast Cancer Risk, Joshua Hoffman, Rebecca Graff, Nima Emami, Caroline Tai, Michael Passarelli

Dartmouth Scholarship

Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute's "Up for a Challenge" (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to …

Effects Of Storage Time On Glycolysis In Donated Human Blood Units, Zhen Qi, John D. Roback, Eberhard O. Voit

Toxicology and Cancer Biology Faculty Publications

Background: Donated blood is typically stored before transfusions. During storage, the metabolism of red blood cells changes, possibly causing storage lesions. The changes are storage time dependent and exhibit donor-specific variations. It is necessary to uncover and characterize the responsible molecular mechanisms accounting for such biochemical changes, qualitatively and quantitatively; Study Design and Methods: Based on the integration of metabolic time series data, kinetic models, and a stoichiometric model of the glycolytic pathway, a customized inference method was developed and used to quantify the dynamic changes in glycolytic fluxes during the storage of donated blood units. The method provides a …

Occurrence Of Potential Adverse Drug Events From Prescribing Errors In A Pediatric Intensive And High Dependency Unit In Hong Kong: An Observational Study, Chad A. Knoderer, Celeste L. Ewig, Hon Ming Cheung, Kwok Ho Kam, Hiu Lam Wong

Scholarship and Professional Work – COPHS

No abstract provided.

Role Of Cytokines And Chemokines In Alcohol-Induced Tumor Promotion, Danlei Chen, Fengyun Zhang, Haifeng Ren, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

Excessive chronic alcohol consumption has become a worldwide health problem. The oncogenic effect of chronic alcohol consumption is one of the leading concerns. The mechanisms of alcohol-induced tumorigenesis and tumor progression are largely unknown, although many factors have been implicated in the process. This review discusses the recent progress in this research area with concentration on alcohol-induced dysregulation of cytokines and chemokines. Based on the available evidence, we propose that alcohol promotes tumor progression by the dysregulation of the cytokine/chemokine system. In addition, we discuss specific transcription factors and signaling pathways that are involved in the action of these cytokines/chemokines …

A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee

Pharmacology and Physiology Faculty Publications

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes …

Mammary Epithelial Polarity And Macrophage Infiltration, Ren Xu

Pharmacology and Nutritional Sciences Faculty Publications

Loss of epithelial cell polarity and inflammation are hallmarks of breast cancer development. Although the association between the disruption of tissue polarity and inflammation has been demonstrated, we know little about how these two events are coupled. Using the 3D co-culture model of mammary epithelial cells and monocytes, a recent study reveals a link between disruption of epithelial polarity and monocytes infiltration.

Lactose Intolerance: An Overview Of The Facts And Their Implications, Noelle M. Yeo

Honors Program: Senior Projects (Public)

Lactose intolerance is often blamed for the symptoms such as bloating, diarrhea, gas, abdominal pain, and nausea, that ail many people. Patients often do not seek proper diagnosis from a physician and create their own treatment plans, severely restricting lactose intake, without professional guidance. Even those who do seek the care of a physician find that diagnosis is complicated by less-than ideal testing and confusion due to the symptoms common to many other conditions. The misconceptions and inability to confirm a diagnosis of lactose intolerance can cause nutrient deficiencies in these patients, as well as begin a pattern of unnecessary …

Sex-Dependent Effects Of Ho-1 Deletion From Adipocytes In Mice, Peter A. Hosick, Mary Frances Weeks, Michael W. Hankins, Kyle H. Moore, David E. Stec

Department of Exercise Science and Physical Education Scholarship and Creative Works

Induction of heme oxygenase-1 (HO-1) has been demonstrated to decrease body weight and improve insulin sensitivity in several models of obesity in rodents. To further study the role of HO-1 in adipose tissue, we created an adipose-specific HO-1 knockout mouse model. Male and female mice were fed either a control or a high-fat diet for 30 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were determined every six weeks. Adipocyte-specific knockout of HO-1 had no significant effect on body weight in mice fed a high-fat diet but increased body weight in female mice …

P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince

Western Research Forum

Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at …

Capillaries, Old Age And Alzheimer’S Disease, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Many of the minor complaints of old age may have a common etiology and are grouped together here under the term ‘the lesser ailments of aging’ (LAA). This essay proposes that they are due in large part to an age-linked reduced microcirculation. Capillary density (CD) in the tissues is determined by levels of angiogenic growth factors (AGFs). Over 47 studies have reported a reduced CD and/or waning AGFs throughout the bodies of aging animals and people. More convincing than such a generalization are the 80 sets of data comparing these two parameters in adult vs. the aged. These data have …

Na/K-Atpase Signaling And Salt Sensitivity: The Role Of Oxidative Stress, Jiang Liu, Yanling Yan, Ying Nie

Biochemistry and Microbiology

Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Cpt1a Methylation Is Associated With Plasma Adiponectin, S. Aslibekyan, A. N. Do, H. Xu, S. Li, M. R. Irvin, D Zhi, H. K. Tiwari, D. M. Absher, A. R. Shuldiner, T. Zhang, W. Chen, K. Tanner, C. Hong, B. D. Mitchell, G. Berenson, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.

Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression …

Emerging Roles Of Xenobiotic Detoxification Enzymes In Metabolic Diseases, Michael C. Petriello, Jessie B. Hoffman, Andrew J. Morris, Bernhard Hennig

Superfund Research Center Faculty Publications

Mammalian systems have developed extensive molecular mechanisms to protect against the toxicity of many exogenous xenobiotic compounds. Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases. This mini-review will focus on two such instances: the role of flavin-containing monooxygenase 3 (FMO3) in the formation of the cardiometabolic disease biomarker trimethylamine-N-oxide (TMAO) and the role of AhR as a sensor of endogenous ligands such as those generated by the gut microbiota. Understanding …

Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley

Articles, Abstracts, and Reports

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches …

The Host Microbiome Regulates And Maintains Human Health: A Primer And Perspective For Non-Microbiologists, Sunil Thomas, Jacques Izard, Emily Walsh, Kristen Batich, Pakawat Chongsathidkiet, Gerard Clarke, David A. Sela, Alexander J. Muller, James M. Mullin, Korin Albert, John P. Gilligan, Katherine Diguilio, Rima Dilbarova, Walker Alexander, George P. Prendergast

Department of Food Science and Technology: Faculty Publications

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active …

Foxo3 Increases Mir-34a To Cause Palmitate-Induced Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Bailey A. Stringham, Ashley M. Mohr, Cody J. Wehrkamp, Sizhao Lu, Mary Anne Phillippi, Duygu Dee Harrison-Findik, Justin L. Mott

School of Veterinary and Biomedical Sciences: Faculty Publications

Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. …

Improving Antiretroviral Therapy Adherence In Resource-Limited Settings At Scale: A Discussion Of Interventions And Recommendations, Jessica E. Haberer, Lora Sabin, K. Rivet Amico, Catherine Orrell, Omar Galarraga, Alexander C. Tsai, Rachel C. Vreeman, Ira Wilson, Nadia A. Sam-Agudu, Terrence F. Blaschke, Bernard Vrijens, Claude Mellins, Robert H. Remien, Sheri D. Weiser, Elizabeth Lolwenthal, Michael J. Stirratt, Papa Salif Sow, Bruce Thomas, Nathan Ford, Edward Mills, Richard Lester, Jean B. Nachega, Bosco M. Bwana, Fred Ssewamala, Lawrence Mbuagbaw, Paula Munderi, Elvin H. Geng, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

INTRODUCTION:

Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings.

METHODS:

In …

Comparative Study On The In Vitro Effects Of Pseudomonas Aeruginosa And Seaweed Alginates On Human Gut Microbiota, Shaofeng Bai, Huahai Chen, Liying Zhu, Wei Liu, Hongwei Yu, Xin Wang, Yeshi Yin

Biochemistry and Microbiology

Alginates pertain to organic polysaccharides that have been extensively used in food- and medicine-related industries. The present study obtained alginates from an alginate overproducing Pseudomonas aeruginosa PAO1 mutant by screening transposon mutagenesis libraries. The interaction between bacterial and seaweed alginates and gut microbiota were further studied by using an in vitro batch fermentation system. Thin-layer chromatography (TLC) analysis indicated that both bacterial and seaweed alginates can be completely degraded by fecal bacteria isolated from study volunteers, indicating that a minor structural difference between bacterial and seaweed alginates (O-acetylation and lack of G-G blocks) didn’t affect the digestion of alginates by …

A Blueprint To Evaluate One Health, Simon R. Rüegg, Barry J. Mcmahon, Barbara Häsler, Roberto Esposito, Helen O'Shea, Et Al

Department of Biological Sciences Publications

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during …

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …