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Electronic Theses and Dissertations

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Articles 1 - 16 of 16

Full-Text Articles in Cellular and Molecular Physiology

Exposure To Pm2.5 And Aging., Daniel Chris Gomes Dec 2025

Exposure To Pm2.5 And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

Inhalation of fine airborne particulate matter (PM2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …

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Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells Aug 2025

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …

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The Role Of Cardiac Mitochondria In Arrhythmias And Sudden Unexpected Death In Epilepsy In Models Of Dravet Syndrome, Jessa L. Aldridge Aug 2024

The Role Of Cardiac Mitochondria In Arrhythmias And Sudden Unexpected Death In Epilepsy In Models Of Dravet Syndrome, Jessa L. Aldridge

Electronic Theses and Dissertations

Dravet Syndrome (DS) is a pediatric epilepsy disorder. Individuals with DS are at increased risk of Sudden Unexpected Death in Epilepsy (SUDEP). One mechanism implicated in the pathology of SUDEP is cardiac arrhythmias. A central element involved in cardiac regulation is mitochondria. In the heart, mitochondria maintain cardiomyocyte energy (ATP) generation and ion homeostasis but also produce harmful reactive oxygen species (ROS) byproducts. We hypothesized that deficits in cardiac mitochondria could underlie arrhythmias and SUDEP in two independent mouse models of DS. Mitochondria produce ATP through the mitochondrial respiratory chain, also called electron transport chain, comprised of a series of …

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Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump Dec 2023

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

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Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson Dec 2022

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …

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Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller Dec 2022

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

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Optimization Of Electrically Driven Fluid Flow Through Tissue Hydrogels, Joseph C. Walker Jan 2022

Optimization Of Electrically Driven Fluid Flow Through Tissue Hydrogels, Joseph C. Walker

Electronic Theses and Dissertations

No abstract provided.

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Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger Dec 2021

Pyridine Nucleotide Redox Potential In Coronary Smooth Muscle Couples Myocardial Blood Flow To Cardiac Metabolism., Marc Matthew Dwenger

Electronic Theses and Dissertations

The maintenance of myocardial oxygen supply during stress is essential for sustaining cardiac health. Enhancement of coronary blood flow upon increases in myocardial oxygen demand (i.e., hyperemia) relies on regulation of voltage-gated K+ (Kv) channels by their intracellular β subunits (i.e., Kvβ proteins). Considering that, Kvβ proteins are aldo-keto reductases (AKRs) and regulate Kv channel gating, we tested the hypothesis that elevation of myocardial oxygen demand modifies intracellular NAD(H) in arterial myocytes. Furthermore, we tested whether the resultant change in the redox state of the pyridine nucleotide pool directly regulates coronary Kv1 channel activity. High-resolution imaging mass spectrometry and …

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Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard Dec 2021

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …

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The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien Dec 2019

The Identification Of Long Non-Coding Rna Zfas1 Through An Exploratory Rna-Sequencing Analysis And Its Association With Epithelial-To-Mesenchymal Transition In Colon Cancer Adenocarcinoma., Stephen J. O'Brien

Electronic Theses and Dissertations

Colorectal adenocarcinoma is the fourth most common cancer diagnosed worldwide and is a significant cause of morbidity and mortality. This dissertation performed an exploratory RNA-sequencing analysis comparing gene expression between colon adenocarcinoma tissue and paired normal colon epithelium. After identification of a number of lncRNAs that were increased in expression in colon adenocarcinoma compared to normal colon epithelium, we aimed to validate the expression and investigate their function in vitro. Specifically, we focused on the lncRNA ZFAS1 and its association with epithelial-to-mesenchymal transition. These studies found the following: 1. Seven candidate lncRNAs were identified from the exploratory RNA-sequencing analysis to …

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The Effects Of Branched Chained Amino Acid Supplementation On Acute Markers Of Fatigue And Performance, Joseph Walters Aug 2019

The Effects Of Branched Chained Amino Acid Supplementation On Acute Markers Of Fatigue And Performance, Joseph Walters

Electronic Theses and Dissertations

The purposes of this dissertation were to investigate the acute effects of branched-chain amino acids on psychological, physiological, and subsequent performance changes following high volume resistance training. The rationale for this study design was based on abrupt or contiguous training/ competitions that specific athletes encounter in a competitive season. This study design also sought to fill some gaps in the scientific literature concerning the efficacy of BCAAs for subjective fatigue in a resistance training paradigm. To address the purposes of this dissertation, a one-week study was conducted on resistance trained males, in which half of the subjects were randomly selected …

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The Effect Of Alcohol Consumption On Adipokine Secretion, Ashley Degroat May 2018

The Effect Of Alcohol Consumption On Adipokine Secretion, Ashley Degroat

Electronic Theses and Dissertations

Alcoholic Fatty Liver Disease (AFLD) is caused by excessive alcohol consumption and is a leading cause of liver related mortalities, with currently no treatments available. The goal of this project was to establish the effect of alcohol consumption on adipose tissue-derived secreted factors, adiponectin and C1q TNF Related Proteins 1-3 (CTRP1-3). We propose that excessive alcohol consumption will reduce circulating levels of adiponectin and CTRPs 1-3. Mice were fed a Lieber-Decarli control or alcohol diet for 10-days with a gavage (NIAAA model) or 6-weeks with no gavage (chronic model). Serum and adipose tissue were collected and CTRPs 1-3 and adiponectin …

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Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield Dec 2017

Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield

Electronic Theses and Dissertations

Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the …

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Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel Aug 2017

Mitochondrial Transcription Factor A'S Role In Heart Failure., George H. Kunkel

Electronic Theses and Dissertations

Background: An essential mitochondrial component, Mitochondrial Transcription Factor A (TFAM) is reduced within the failing heart. TFAM maintains regulatory functions of cardiomyocyte physiology and stability. Mitochondrial Transcription Factor A forms a mitochondrial nucleoid anti-oxidant structure and reduces pathophysiological abnormalities to structural and contractile proteins. Overall, this functions to physically stabilize mtDNA. Significant molecular changes such as a loss of TFAM drive pathophysiological concentrations of cytoplasmic Ca2+ and reactive oxygen species. Both of these factors induce proteolytic enzymes to degrade the physiological cardiomyocyte. In TFAMs absence, heart function deteriorates and hypertrophic expansion ensues: thereby changing the physiological myocardium to a pathological …

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Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book May 2017

Enhancing Cell Therapy For Ischemic Cardiomyopathy., Michael J. Book

Electronic Theses and Dissertations

Cardiac cell therapy using cardiac mesenchymal cells (CMC) significantly reduces ventricular dysfunction in patients with ischemic cardiomyopathy. Despite the improvement in function, a modest number of CMCs survive in the heart post-transplantation. In this study, we sought to improve the survival and retention of transplanted CMCs to prolong the therapeutic benefits afforded by cardiac cell therapy. To do this, we targeted the enzyme telomerase (TERT), known to be active in some highly proliferating cells (e.g. germ, stem). TERT is responsible for preventing telomere attrition, thereby allowing continued proliferation. TERT has also been shown to be protective, improve cell migration and …

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Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp Aug 2016

Cardiovascular And Hematopoietic Responses To Volatile Benzene Exposure., Wesley Tyler Abplanalp

Electronic Theses and Dissertations

The rapid and recent increase in the global epidemic of diabetes and cardiovascular disease suggests a strong component of the environment is contributing. Benzene is a ubiquitous volatile pollutant generated by cigarette smoke, automobile exhaust, wildfires and industrial activities. Consequently, it is found in almost all urban and rural air samples. Benzene is known to cause hematotoxicity and its metabolism generates oxidative stress. Although, benzene has been studied for many years, few investigations have probed what influence benzene exposure may have on other physiological processes. Here we hypothesize that benzene metabolism by hepatic-CYP450 2E1 generates oxidative stress and inflammation, which …

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