Medical Nutrition Commons^™

High Cholesterol Diet Induces Sudden Death In Mice With Impaired Reverse Cholesterol Transport, Misa Ito

Theses and Dissertations--Pharmacology and Nutritional Sciences

Unexplained sudden death continues to be a major public health crisis as AHA reports that 1,000 people suffer sudden cardiac arrest each day in the U.S. with only 10% surviving. A number of ongoing challenges hinder to understand the sudden death. Thus, investigating underlined mechanisms of sudden death is urgent. Unexpectedly, I found a high cholesterol diet (HCD)-induced sudden death preclinical model. Although HCD is associated with a higher risk of cardiovascular disease (CVD) and the subendothelial lipoprotein retention theory is well established for atherosclerosis development, these theories cannot explain the sudden death in my model because atherosclerosis and CVD …

Metabolism Reprogramming In Hexavalent Chromium-Induced Human Lung Carcinogenesis, James Tate Fortin Wise

Theses and Dissertations--Pharmacology and Nutritional Sciences

Hexavalent chromium, Cr(VI), is an established human carcinogen that is a worldwide environmental health concern. It is well understood that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to Cr(VI)-induced carcinogenesis. After decades of research some cancer hallmarks remain understudied for the mechanism of Cr(VI) carcinogenesis. Dysregulated cellular energetics have been established as a hallmark of cancer. Energy pathways that become dysregulated in cancer include mitochondrial respiration, lipogenesis, pentose phosphate pathway, one carbon metabolism, and increased anaerobic glycolysis in the presence of oxygen or ‘Warburg effect’.

To investigate metabolism changes in Cr(VI) carcinogenesis, we exposed …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …