Digital Commons Network^™

Vitamin D Status Of Anabaptist Children In Southwestern Ontario, Canada, Janis A. Randall Simpson, Natalee Miller, Taylor Hartwig, Jane Leach, Melissa Purdy, Emily Roth, Victoria Mok Siue, Cynthia Soulliere, Jacqui Tam, Ann Watt

Journal of Amish and Plain Anabaptist Studies

The objective was to determine vitamin D status of Old Order Anabaptist children in rural Southwestern, Ontario, Canada, given concerns of community healthcare professionals. Fifty-two children (2.5 months - 6.5 years) (56% female) were recruited. Finger prick blood spot (BSp) samples were analyzed for 25-hydroxy (OH) vitamins D2 & D3 (BSp25(OH)D). Three-day food records were evaluated using Dietary Reference Intakes and Canada’s Food Guide (CFG) (Bush, et al. 2007). Compared to national Canadian data: mean BSp25(OH)D concentrations (78±31 nmol/L) were similar; a slightly smaller proportion (0% vs 2%) were at risk of deficiency (<30 nmol/L) or had inadequate status (4% vs 7%) (<40 nmol/L); and 10% vs 1% had BSp25(OH)D higher than 125 nmol/L. BSp25(OH)D was significantly associated (r2=0.358; p=0.001) with total vitamin D intake. From food alone, vitamin D intake was 68±39 IU/day, lower than the Recommended Dietary Allowance (RDA) of 600 IU/day, and intakes were all below the Estimated Average Requirement (EAR) of 400 IU. Even including supplemental vitamin D, 87% were below the EAR (total intake=213±194 IU/day). No children had vitamin D intakes greater than the Upper Limit. Servings of milk and alternates were 1.6±0.8/day (CFG=2/day). Unfortified farm milk was consumed by 88% of children and 89% received a vitamin D supplement. Results were comparable to recent Canadian data suggesting that most children have adequate vitamin D status. Nevertheless, these findings support the need to encourage appropriate vitamin D intake (from food and supplements) to achieve the RDA for Old Order Anabaptist children in these communities. [Abstract by authors.]

Tuftelin1 Drives Experimental Pulmonary Fibrosis Progression By Facilitating Stress Fiber Assembly, Caoyuan Niu, Kai Xu, Yanan Hu, Yanling Jia, Yuexia Yang, Xiaoyue Pan, Ruyan Wan, Hui Lian, Qiwen Wang, Juntang Yang, Yajun Li, Ivan Rosas, Lan Wang, Guoying Yu

Children’s Nutrition Research Center Staff Publications

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive.

Methods: To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis.

Results: Our results demonstrated a significant …

Gpr84-Mediated Signal Transduction Affects Metabolic Function By Promoting Brown Adipocyte Activity, Xue-Nan Sun, Yu A An, Vivian A Paschoal, Camila O De Souza, May-Yun Wang, Lavanya Vishvanath, Lorena Ma Bueno, Ayanna S Cobb, Joseph A Nieto Carrion, Madison E Ibe, Chao Li, Harrison A Kidd, Shiuhwei Chen, Wenhong Li, Rana K Gupta, Da Young Oh

Faculty, Staff and Student Publications

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes …

A Comprehensive Program Evaluation Of Colorectal Rescreening Initiatives In Rural Virginia, Sarah E. Stowell

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Background: Despite low-cost and effective screening tools, colorectal cancer (CRC) mortality remains high in the U.S., particularly in rural areas like Virginia’s Northern Shenandoah Valley, where screening rates are low. While literature highlights barriers to CRC screening in these communities and suggests improvement strategies, few studies focus on long-term adherence to screening in rural health clinics (RHCs).

Purpose: This program evaluation assessed the impact and effectiveness of the Rural Colorectal Cancer Rescreening Initiative (RCRI), a pilot program to increase colorectal cancer rescreening rates in a local RHC. It also offers recommendations for optimizing future RCRI efforts. Methods: The program evaluation …

Genotype, Oxidase Status, And Preceding Infection Or Autoinflammation Do Not Affect Allogeneic Hct Outcomes For Cgd, Jennifer W Leiding, Danielle E Arnold, Suhag Parikh, Brent Logan, Rebecca A Marsh, Linda M Griffith, Ruizhe Wu, Sharon Kidd, Kanwaldeep Mallhi, Deepak Chellapandian, Stephanie J Si Lim, Eyal Grunebaum, E Liana Falcone, Luis Murguia-Favela, Debbi Grossman, Vinod K Prasad, Jennifer R Heimall, Fabien Touzot, Lauri M Burroughs, Jack Bleesing, Neena Kapoor, Jasmeen Dara, Olatundun Williams, Malika Kapadia, Benjamin R Oshrine, Jeffrey J Bednarski, Ahmad Rayes, Hey Chong, Geoffrey D E Cuvelier, Lisa R Forbes Satter, Caridad Martinez, Mark T Vander Lugt, Lolie C Yu, Shanmuganathan Chandrakasan, Avni Joshi, Susan E Prockop, Blachy J Dávila Saldaña, Victor Aquino, Larisa A Broglie, Christen L Ebens, Lisa M Madden, Kenneth Desantes, Jordan Milner, Hemalatha G Rangarajan, Ami J Shah, Alfred P Gillio, Alan P Knutsen, Holly K Miller, Theodore B Moore, Pamela Graham, Andrea Bauchat, Nancy J Bunin, Pierre Teira, Aleksandra Petrovic, Sharat Chandra, Hisham Abdel-Azim, Morna J Dorsey, Olga Birbrayer, Morton J Cowan, Christopher C Dvorak, Elie Haddad, Donald B Kohn, Luigi D Notarangelo, Sung-Yun Pai, Jennifer M Puck, Michael A Pulsipher, Troy R Torgerson, Harry L Malech, Elizabeth M Kang

Faculty, Staff and Students Publications

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score < 90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Frailty In End-Stage Liver Disease: Understanding Pathophysiology, Tools For Assessment, And Strategies For Management, Mazen Elsheikh, Ahmed El Sabagh, Islam B Mohamed, Megha Bhongade, Manal M Hassan, Prasun Kumar Jalal

Faculty, Staff and Students Publications

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical …

Decreased Fxr Agonism In The Bile Acid Pool Is Associated With Impaired Fxr Signaling In A Pig Model Of Pediatric Nafld, Magdalena A Maj, Douglas G Burrin, Rodrigo Manjarín

Faculty, Staff and Students Publications

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with …

Long Noncoding Rnas In Pancreas Cancer: From Biomarkers To Therapeutic Targets, Esra Güzel Tanoğlu, Seyfure Adigüzel, Alpaslan Tanoğlu, Zehra Betül Aydin, Güli̇zar Hocaoğlu, Samet Ebi̇nç

Turkish Journal of Medical Sciences

Long noncoding RNAs (lncRNAs) are noncoding RNA molecules with a heterogeneous structure consisting of 200 or more nucleotides. Because these noncoding RNAs are transcribed by RNA polymerase II, they have properties similar to messenger RNA (mRNA). Contrary to popular belief, the term "ncRNA" originated before the discovery of microRNAs. LncRNA genes are more numerous than protein-coding genes. They are the focus of current molecular research because of their pivotal roles in cancer-related processes such as cell proliferation, differentiation, and migration. The incidence of pancreatic cancer (PC) is increasing around the world and research on the molecular aspects of PC are …

[6]-Shogaol And [6]-Gingerol Active Ingredients May Improve Neuropathic Pain By Suppressing Cytokine Levels In An Experimental Model, Fi̇kri̇ Özdemi̇r, Güven Akçay, Sevi̇l Özkinali, Çağla Çeli̇k

Turkish Journal of Medical Sciences

Background/aim: Neuropathic pain (NP) is a type of chronic pain usually caused by damage to the somatosensory system. Bioactive antioxidant compounds, such as curcumin and ginger, are widely preferred in the treatment of NP. However, the ingredient-based mechanism that underlies their pain-relieving activity remains unknown. The aim of this study was to investigate the therapeutic effects of trans-[6]-Shogaol and [6]-Gingerol active ingredients of the Zingiber officinale Roscoe extract on the spinal cord and cortex in the neuroinflammatory pathway in rats with experimental sciatic nerve injury. Materials and methods: Forty-six volatile phenolic components were identified in ginger samples using gas chromatography-mass …

Effect Of Humanine On The Notch Signaling Pathway In Myocardial Infarction, Eli̇f Onat, Ebru Önalan, Berna Özdem, Merve Kavak Balgeti̇r, Tuncay Kuloğlu

Turkish Journal of Medical Sciences

Background/aim: By applying humanin (HN) before myocardial infarction (MI), its protection in myocardial injury and the possible roles of its cellular mechanism in the Notch pathway were investigated. Materials and methods: The study was carried out at Fırat University Experimental Research Center (12/24/2018-12/23/2019). Spraque-Dawley rats were divided into 10 groups: I (control) (n = 6), II (HN 6 h) (n = 6), III (HN 24 h) (n = 6), IV (HN day 7) (n = 6), V (MI 6 h) (n = 7), VI (MI 24 h) (n = 7), VII (MI day 7) (n = 7), VIII (MI+HN 6 …

Positive Effects Of Health Behaviors Acquired During The Covid-19 Pandemic Process On The Prevention Of Other Infectious Diseases, Asi̇ye Çi̇ğdem Şi̇mşek, Turan Buzgan, Fatma Nur Baran Aksakal, Şuayip Bi̇ri̇nci̇, Hülya Şi̇ri̇n

Turkish Journal of Medical Sciences

Background/aim: It was aimed to evaluate the positive effects of health behaviors (general hygiene, wearing face masks, physical distancing, and travel restrictions) acquired during the coronavirus disease 2019 (COVID-19) pandemic on the prevention of other infectious diseases in Ankara Province, Türkiye. Materials and methods: This study was designed retrospectively. Among the notifiable group A infectious diseases, acute intestinal infections (AIIs) with International Classification of Diseases, Tenth Revision diagnosis codes A09 (diarrhea and gastroenteritis presumed to be of infectious origin), R11 (nausea and vomiting), and K52 (other noninfectious gastroenteritis and colitis) , as well as influenza, tuberculosis, measles, varicella, malaria, and …

Assessment Of Changes In Macular Structural Retinal Layers In Patients With Pathological Myopia, Mehmet Çitirik, Kami̇l Yavuzer, Fatma Bağci

Turkish Journal of Medical Sciences

Background/aim: This study aimed to examine changes in the thickness of individual macular retinal layers in eyes with pathological myopia (PM) and to compare the thickness of each retinal layer between the PM and control groups to gain insights into retinal perfusion. Materials and methods: The study included 51 eyes in the PM group and 51 eyes in the control group. Optical coherence tomography (OCT) was used to measure the thickness of each retinal layer in the central fovea, parafoveal, and perifoveal regions. Optical coherence tomography angiography (OCT-A) was used to evaluate the retinal capillary density. Results: In the PM …

Protective Effects Of Swimming Exercises And Metformin On Cardiac And Aortic Damage Caused By A High-Fat Diet In Obese Rats With Type 2 Diabetes, By Regulating The Bcl2/Bax Signaling Pathway, Ebru Özüdoğru, Emrah Atay, Mehtap Savran, Hali̇l Aşci, Özlem Özmen, Şenay Topsakal

Turkish Journal of Medical Sciences

Background/aim: Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Materials and methods: Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), …

Expression Of Pfkfb Isoenzymes During In Vitro Differentiation Of Mouse Embryonic Stem Cells Into Insulin-Producing Cells, Sai̇me Güzel, Abdullah Yalçin, Yunus Gürpinar, Sabi̇re Güler

Turkish Journal of Medical Sciences

Background/aim: Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing cells (IPCs) and still has no effective cure. Better understanding of the molecular mechanisms involved in the differentiation of embryonic stem cells (ESCs) into IPCs may help us improve the therapeutic strategies for treating T1DM. 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatases (Pfkfb1-4) are key regulators of glucose metabolism. Although Pfkfb3 has been shown to be required for the growth of early differentiated mouse ESCs (mESCs), more studies are needed to further assess the roles of Pfkfb isoenzymes in embryonic development and differentiation, particularly into specific cell types. In this study, …

Ss-D-Glucan Promotes Nf-Κb Activation And Ameliorates High-Let Carbon-Ion Irradiation-Induced Human Umbilical Vein Endothelial Cell Injury, Fang Liu, Yanting Wei, Zhuanzi Wang

Turkish Journal of Medical Sciences

Background/aim: Heavy-ion irradiation seriously perturbs cellular homeostasis and thus damages cells. Vascular endothelial cells (ECs) play an important role in the pathological process of radiation damage. Protecting ECs from heavy-ion radiation is of great significance in the radioprotection of normal tissues. In this study, the radioprotective effect of ß-D-glucan (BG) derived from Saccharomyces cerevisiae on human umbilical vein endothelial cell (EA.hy926) cytotoxicity produced by carbon-ion irradiation was examined and the probable mechanism was established. Materials and methods: EA.hy926 cells were divided into seven groups: a control group; 1, 2, or 4 Gy radiation; and 10 µg/mL BG pretreatment for 24 …

Formate Supplementation Enhances Antitumor Cd8+ T-Cell Fitness And Efficacy Of Pd-1 Blockade, Jared H Rowe, Ilaria Elia, Osmaan Shahid, Emily F Gaudiano, Natalia E Sifnugel, Sheila Johnson, Amy G Reynolds, Megan E Fung, Shakchhi Joshi, Martin W Lafleur, Joon Seok Park, Kristen E Pauken, Joshua D Rabinowitz, Gordon J Freeman, Marcia C Haigis, Arlene H Sharpe

Faculty, Staff and Student Publications

UNLABELLED: The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for …

Relation Of Salivary Alpha-Amylase (Saa) Concentration To Fatigue Biomarkers In Palm Oil Office Workers In Jambi Province: Preliminary Study, David Kusmawan, Willia Novita Eka Rini, Wahyu Indah Dewi Aurora

Makara Journal of Science

The salivary α-amylase (sAA) concentration has a potential role as a biological indicator of occupational fatigue. This study aimed to determine the levels of sAA and its influencing factors. This research used a cross-sectional design with a sample of 40 office staff respondents at PT. X (Persero). Mental workload (MWL), sleep quality, and occupational fatigue were measured using the NASA-Total Load Index (TLX), Pittsburgh Sleep Quality Index, and Industrial Fatigue Research Committee, respectively. Meanwhile, the basic sAA levels was measured through the sandwich enzyme-linked immunosorbent assay method using the Bioenzy® Kit Assay. Descriptive analysis showed that the workers were mostly …

Zuccagnia Punctata Cav, A Potential Environmentally Friendly And Sustainable Bionematicide For The Control Of Argentinean Horticultural Crops, Sofía Manrique, Jessica Gómez, Mauricio Piñeiro, Belén Ariza Sampietro, Maria L Peschiutta, Alejandro Tapia, Mario J Simirgiotis, Beatriz Lima

Faculty, Staff and Student Publications

This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential nematicidal properties of decoction (ZpDe), orange-yellow resin (ZpRe) and essential oil (ZpEO) from Argentinean medicinal plant Zuccagnia punctata Cav. Additionally, the antioxidant and antibacterial properties of ZpDe and ZpEO were determined. Metabolite profiling was obtained by an ultrahigh-resolution liquid chromatography MS analysis (UHPLC-ESI-QTOF/OT-MS-MS) and GCMS. The nematicidal activity was assayed by a standardized method against Meloidogyne incognita. The antioxidant properties were screened by four methods: (2,2-diphenyl-1-picrylhydrazyl assay (DPPH), Trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid …

Biomarkers For Heart Failure Prediction And Prevention, Prasanti Alekhya Kotta, Vijay Nambi, Biykem Bozkurt

Faculty, Staff and Students Publications

Heart failure (HF) is a global pandemic affecting over 64 million people worldwide. Its prevalence is on an upward trajectory, with associated increasing healthcare expenditure. Organizations including the American College of Cardiology (ACC) and the American Heart Association (AHA) have identified HF prevention as an important focus. Recently, the ACC/AHA/Heart Failure Society of America (HFSA) Guidelines on heart failure were updated with a new Class IIa, Level of Evidence B recommendation for biomarker-based screening in patients at risk of developing heart failure. In this review, we evaluate the studies that have assessed the various roles and contributions of biomarkers in …

Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Human sirtuin isoform 2 (SIRT2) is an NAD+-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking. Dimerized SIRT2 dissociates into monomers upon binding long fatty acylated substrates (decanoyl-, dodecanoyl-, and myristoyl-lysine). However, we did not observe dissociation of dimeric SIRT2 in the presence of acetyl-lysine. Analysis of X-ray crystal structures led us to discover a SIRT2 double mutant (Q142A/E340A) that …

A Literature Review On Thermogenesis As A Prospective Obesity Treatment, Kellyn Sheppard

Senior Honors Theses

The disease of obesity has quickly escalated from an epidemic to a worldwide pandemic in the last few decades, and viable treatment methods are being investigated with urgency. One such treatment method is increased induction of the thermogenesis pathway that is active in brown adipose tissue. This pathway is typically activated in mammals when they are exposed to cold temperatures for extended periods of time but can also be induced exogenously. Thermogenesis is a metabolically inefficient process that occurs in the mitochondria of a cell, meaning it uses substrate energy without generating ATP. The inefficiency of this process allows excess …

Green Tea Supplementation: An Effective Lifestyle Modification For Cholesterol Management, Samuel J. Nemati

MSN Capstone Projects

Hypercholesterolemia is an insidious disease and the leading factor to the deadliest killer in the United States – cardiovascular disease (Centers for Disease Control and Prevention, 2023a). Over 85 million American adults suffer from elevated cholesterol, and treatment can prove challenging and may require multiple modalities outside just pharmaceutical intervention – such as dietary and other lifestyle changes (Centers for Disease Control and Prevention, 2023b; Goldman, 2023). Green tea – among the most common teas consumed worldwide – exerts a uniquely antihyperlipidemic and cardioprotective effect that suggests its consideration as a potentially-viable nonpharmacological option for hypercholesterolemia (Harvard Health Publishing, 2012; …

Intouch Week Of December 4, 2023, New York Medical College

InTouch

• Get to Know Dr. Schluger, the New SOM Dean
• NYMC Celebrates Faculty Authorship at 30th Annual Recognition
• NYMC's Giving Tuesday Success Fuels Clinical Skills and Simulation Center Expansion
• Students Shine at 2023 Multidisciplinary Community Outreach
• NYMC Looks at the Future of the Life Sciences at the Innovation in Research Conference
• Study Finds Racial Disparities in Postoperative Outcomes for Cervical Stenosis

Hnf4Α Isoforms Regulate The Circadian Balance Between Carbohydrate And Lipid Metabolism In The Liver, Jonathan R Deans, Poonamjot Deol, Nina Titova, Sarah H Radi, Linh M Vuong, Jane R Evans, Songqin Pan, Johannes Fahrmann, Jun Yang, Bruce D Hammock, Oliver Fiehn, Baharan Fekry, Kristin Eckel-Mahan, Frances M Sladek

Faculty, Staff and Student Publications

Hepatocyte Nuclear Factor 4α (HNF4α), a master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2) which drive the expression of different isoforms. P1-HNF4α is the major isoform in the adult liver while P2-HNF4α is thought to be expressed only in fetal liver and liver cancer. Here, we show that P2-HNF4α is indeed expressed in the normal adult liver at Zeitgeber time (ZT)9 and ZT21. Using exon swap mice that express only P2-HNF4α we show that this isoform orchestrates a distinct transcriptome and metabolome via unique chromatin and protein-protein interactions, including with different clock proteins at different …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …

Deficiency Of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality And Lung Injury In Mice, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated …

Sprouty4 Is Epigenetically Upregulated In Human Colorectal Cancer, Alexei J. Stuckel, Shuai Zeng, Zhen Lyu, Wei Zhang, Xu Zhang, Urszula Dougherty, Reba Mustafi, Tripti Khare, Qiong Zhang, Trupti Joshi, Marc Bissonnette, Sharad Khare

Biomedical Sciences

Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were …

Chronic Stressors, Obesity Pathogenesis, And The Moderating Effect Of Internalized Weight Stigma; A Quantitative, Illinois Study, Karyn Byrne

Dissertations

The obesity epidemic is a ‘wicked’ problem with a complex web of determinants and outcomes. While generally higher for minoritized populations, prevalence rates manifest in surprising, nonlinear patterns. There is no consensus regarding treatment protocols or mitigation efforts, except that current efforts remain largely ineffective. Much research evidence that a profusion of determinants of health support obesity pathogenesis through various physiological processes and mechanisms, including the allostatic load, mitochondria functioning, the gut microbiome, and epigenetics. Intervening to support markers of the allostatic load (immunity, inflammation, and metabolic health) may provide a more effective treatment outcomes than traditional approaches, which tend …