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Modulating Cardiac Remodeling After Myocardial Infarction, Upendra Chalise May 2022

Modulating Cardiac Remodeling After Myocardial Infarction, Upendra Chalise

Theses & Dissertations

Cardiac remodeling after myocardial infarction (MI) is indicated by infarct wall thinning, reduced ejection fraction, and dilation of the left ventricle (LV). Inflammation presides in the early days of MI as a key event in cardiac wound healing. Infiltration of inflammatory cells, predominantly neutrophils and macrophages, is stimulated by ischemic cardiomyocytes that secrete inflammatory cues. This dissertation focused on identifying factors that influence cardiac remodeling after MI. S100A9 is a neutrophil-derived factor identified that exacerbated infarct wall thinning and cardiac dilation by increasing neutrophil and macrophage infiltration. Similarly, murinoglobulin 1 (Mug1) and galectin (Lgals)3 were macrophage-derived factors identified that regulate …


Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim May 2019

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …


Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo Aug 2016

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …


Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher Aug 2016

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …


Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh Aug 2016

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …


Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale May 2016

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be …