Medicine and Health Sciences Commons^™

Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart

Electronic Thesis and Dissertation Repository

Sepsis is a dysregulated immune response to infection and the leading cause of mortality globally, accounting for 11 million deaths in 2017. To date, no therapeutics are available to treat the underlying septic response. Previous research from our laboratory has shown that annexin A5 (Anx5) treatment increased survival by 40% in mice with endotoxemia, a model of sepsis. During sepsis, activated platelets release membrane fragments called extracellular vesicles (EVs) with externalization of phosphatidylserine to which annexin A5 binds with a high affinity. We hypothesized that annexin A5 will block the pro-inflammatory response induced by activated platelets and EVs in vascular …

Does Epa Cause A Decrease In Inflammation Of Bend.3 Cells Through Ffar4?, Clay J. Weidenhamer

Masters Theses

Atherosclerosis is an inflammatory disease initiated by low and oscillatory shear stress on the endothelium. The inflammatory process recruits leukocytes to the vessel wall by expression of the adhesion molecule VCAM-1. Activation of the NF-κB inflammatory signaling pathway is responsible for the increase in VCM-1 expression. Omega 3 FAs, such as EPA, reduce the risk of atherosclerosis by decreasing this inflammatory response. The pathway by which omega 3 FAs is proposed to inhibit inflammation includes activating FFAR4 to decrease NF-κB activation thereby reducing expression of adhesion molecules. We hypothesized that treatment of endothelial cells with 30 μM EPA would decrease …

Epithelial Memory Of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis, I-Lin Ho

Dissertations & Theses (Open Access)

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma. When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Inflammation, Diet, And Depression, Kareem F. Hamada

College Honors Program

Although it is well established that inflammation contributes to cardiovascular disease (CVD), this thesis considers the potential for dietary-induced inflammation to also play a role in the development of depression. Even though the association between inflammation and depression was initially proposed over 100 years ago, treatment of depression has focused on psychopharmacological and psychotherapy. In addition to the increases in the chronic diseases that are the leading causes of death, including CVD, diabetes, and several forms of cancer, consumption of meat, dairy, and highly processed foods have also increased dramatically in recent decades. The resulting Standard American Diet (S.A.D.) is …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

MSU Graduate Theses

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Potential Bioactives And Inflammatory Mediators Regulating Adipose Tissue Function In Obesity, Seok-Yeong Yu

Doctoral Dissertations

Obesity is a serious health problem in the U.S. and worldwide and is associated with non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Observational studies have also shown an inverse relationship between obesity and reduced bioavailability of fat-soluble vitamins, which is due in part to increased sequestration in expanded adipose tissue (AT). AT serves as the primary site of storage organ for excess energy, however, in morbid obesity enlarged adipocytes exhibit decreased lipid uptake, impaired lipid hydrolysis and oxidation and increased inflammation, which are collectively referred to as AT dysfunction. Substantial evidence characterizes AT …

The Effects Of Interleukin-1Β On Cardiac Reserve And Exercise Capacity In The Mouse, Habeebah Z. Vohra

Theses and Dissertations

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle …

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

A Role For Endothelial Tissue-Nonspecific Alkaline Phosphatase In Blood-Tissue Barrier Health And Disease, Allison L. Brichacek

Graduate Theses, Dissertations, and Problem Reports

Sepsis is a disorder that targets the microcirculation with significant effects at blood-tissue barriers such as the blood-brain barrier (BBB) and gut-vascular barrier (GVB). Intestinal barrier dysfunction is thought to be one of the most important contributors to multi-organ dysfunction in sepsis. As a common site of infection, the impaired gut allows the dissemination of bacteria, which exacerbates the disease pathophysiology, and can lead to long-term morbidity and mortality. The mechanisms that influence altered barrier permeability in the GVB in sepsis and other inflammatory disorders are not well understood. Tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity, which has been shown to …

Dietary Assessments And Their Association With Psychological Factors, Inflammation, And Cardiovascular Health Outcomes, Junghee Kang

Theses and Dissertations--Nursing

Cardiovascular diseases (CVDs), a group of disorders of the heart and blood vessels, are the leading cause of death worldwide, causing one-third of deaths each year. Diet is one of the most important behavioral risk factors for CVD. The effects of behavioral risk factors, such as diet, may lead to increased blood pressure, increased blood glucose, raised blood lipids, and overweight and obesity. Inflammation contributes to the development of CVD and can be influenced by diet. Dietary assessment indices can measure diet quality from an individual's dietary intake by scoring food and nutrient intakes. However, the mediation effects of diet …