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Full-Text Articles in Medicine and Health Sciences
Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson
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 …
Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty
Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty
Electronic Theses and Dissertations
This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …
Development Of A Vascularized, Induced Pluripotent Stem Cell-Derived Liver-Tissue Mimic For Therapeutic Applications., Venkat Madhav Ramakrishnan
Development Of A Vascularized, Induced Pluripotent Stem Cell-Derived Liver-Tissue Mimic For Therapeutic Applications., Venkat Madhav Ramakrishnan
Electronic Theses and Dissertations
This dissertation describes the incorporation of several technologies (stem cells, gene therapy, tissue engineering and regenerative medicine) into a single project that aims to produce a liver-tissue mimic for therapeutic applications. The liver is arguably one of the most complex organs in the body. In addition to its remarkable capacity to regenerate, it performs a host of vital functions. As a result, its impairment has widespread systemic consequences. The work described herein focused on the liver in the context of cardiovascular disease and used the heritable disorder Familial Hypercholesterolemia (FH) as a clinical disease model. As (a) the only definitive …