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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum
Electronic Theses and Dissertations
Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …
The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen
The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen
Electronic Theses and Dissertations
Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Metabolic-Epigenetic Regulation Of Macrophage Polarization., Jordan T. Noe
Electronic Theses and Dissertations
Tumor-associated macrophages polarized to an M2 phenotype (M2-TAMs) promote neo-angiogenesis, tumor-stromal matrix remodeling, and immuno-evasion, which, collectively, contribute to immunotherapeutic resistance and reduced cancer patient survival. Highly glycolytic “Warburg” cancer cells produce lactate that independently drives naïve M0→immunosuppressive M2 (M0→M2) macrophage polarization, but the mechanisms have not been fully elucidated. The atypical cytokine macrophage migration inhibitory factor (MIF) is a fundamental underlying requirement for immunosuppressive M2 macrophage polarization. Still, it is unknown whether a molecular link exists between lactate-supported and MIF-dependent M2 macrophage polarization. Using a combination of gene expression assays, chromatin immunoprecipitation, and metabolomic analyses, we identified that M2 …
Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey
Tumor-Derived Exosomes Drive Immunosuppressive Macrophages In A Pre-Metastatic Niche Through Nf-Kβ Dependent Glycolytic Metabolic Reprogramming., Samantha M. Morrissey
Electronic Theses and Dissertations
The formation of a pre-metastatic niche is a fundamental requirement for primary tumor metastasis. One of the defining characteristics of a pre-metastatic niche is infiltration of immunosuppressive macrophages. However, how these macrophages acquire their immunosuppressive phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDE) polarize macrophages towards an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent metabolic reprogramming in mice and humans. While NF-κB has previously been shown to act as a direct transcription factor for PD-L1, we report a novel mechanism where TDE-induced NF-κB activation drives PD-L1 expression by augmenting the glycolytic capacity of macrophages through …
Markers And Mechanisms Of Metabolic Aging., Peter Dziewornu Ahiawodzi
Markers And Mechanisms Of Metabolic Aging., Peter Dziewornu Ahiawodzi
Electronic Theses and Dissertations
Oxidative stress has been implicated in aging and age-related diseases. Using three distinct studies, this dissertation examines associations between lifestyle factors and oxidative stress, and their effects on advanced glycation end products, telomere length, and type II diabetes. Carboxymethyl-lysine (CML), an advanced glycation end-product, has been linked to oxidative stress, cardiovascular and other age-related diseases. The first study investigates the association between sleep disordered breathing (SDB), a source of oxidative stress, and CML. 1002 participants with sleep data from the Cardiovascular Health Study (CHS) were analyzed. SDB was not significantly associated with CML, but after stratification by gender and hemoglobin …