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Modulation Of Diet-Induced Gut Inflammation In Slowing Initiation Of Hematologic Malignancies, Esther Nyarkoa Mensah Jan 2024

Modulation Of Diet-Induced Gut Inflammation In Slowing Initiation Of Hematologic Malignancies, Esther Nyarkoa Mensah

Theses, Dissertations and Capstones

The intestinal tract serves as a host to an extremely complex microbial system. Microbes in the gut regulate their metabolism in response to chemicals generated by other microorganisms as well as nutrition supply from dietary intake. Alterations in gut bacteria have been implicated in the development of metabolic disorders such as obesity and the progression of diseases such as Myelodysplastic syndromes (MDS). Although the cause of obesity is multifactorial, the consumption of high-fat or sugar-rich diets (Western diets) has been proposed as a significant contributor to this global epidemic. Obesity is a major public health concern that has been extensively …


High Body Mass Index Changes Peri-Tumor Adipose Tissue Which In Turn Promotes Triple Negative Breast Cancer, Cora Elizabeth Miracle Jan 2023

High Body Mass Index Changes Peri-Tumor Adipose Tissue Which In Turn Promotes Triple Negative Breast Cancer, Cora Elizabeth Miracle

Theses, Dissertations and Capstones

Cancer is one of the leading causes of death worldwide, responsible for over half a million deaths each year. There are multiple risk factors associated with the development of cancer. Some of these risks include genetics, smoking, and most recently, obesity (Lewandowska et al., 2019) (De Pergola & Silvestris, 2013). Research has shown that obesity is linked to the promotion of fourteen different cancers, including aggressive triple negative breast cancer (TNBC). Patients that are obese are more likely to develop cancer (Park et al., 2014). In addition, if the patient is obese at the time of a cancer diagnosis, they …


Gut Microbial Metabolite Indole: A Stimulator Of Enteroendocrine Cell Differentiation Via Activation Of Aryl Hydrocarbon Receptor, James Hart Jan 2023

Gut Microbial Metabolite Indole: A Stimulator Of Enteroendocrine Cell Differentiation Via Activation Of Aryl Hydrocarbon Receptor, James Hart

Theses, Dissertations and Capstones

Enteroendocrine cells (EECs) regulate energy balance and glucose homeostasis by releasing hormones in response to food intake. Dysregulated EEC differentiation is observed in obesity, while gut microbiota metabolites influence this process. Here, we investigated the role of indole, a biologically active gut microbial metabolite, in EEC differentiation through aryl hydrocarbon receptor (AhR) activation. Human intestinal organoids derived from jejunal mucosal biopsies were exposed to indole. Indole treatment significantly increased mRNA levels of chromogranin A, an EEC marker. The effect was reversed by an AhR antagonist, indicating AhR involvement. Indole also upregulated AhR target gene mRNA levels. These findings highlight the …


Naktide Targeted To Adipocytes Ameliorates Western Diet Induced Obesity, Rebecca D. Pratt Jan 2019

Naktide Targeted To Adipocytes Ameliorates Western Diet Induced Obesity, Rebecca D. Pratt

Theses, Dissertations and Capstones

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. It is believed that cellular oxidant stress plays a key role in both the development and maintenance of obesity as well as its associated comorbidities such as diabetes, cardiovascular disease, and nonalcoholic steatohepatitis (NASH). We have previously reported that systemic administration of pNaKtide, which targets the Na/K-ATPase oxidant amplification loop was able to decrease oxidative stress and adiposity in mice fed a high fat and fructose supplemented western diet (WD). As adipocytes are believed to play an active role in the development of obesity and …


Endogenous Antioxidant Overexpression As An Adjuvant To Diet Or Exercise Intervention As Therapy To Counteract Obesity And Beneficially Shift The Gut Microbiome, Deborah Lynn Amos Jan 2019

Endogenous Antioxidant Overexpression As An Adjuvant To Diet Or Exercise Intervention As Therapy To Counteract Obesity And Beneficially Shift The Gut Microbiome, Deborah Lynn Amos

Theses, Dissertations and Capstones

Oxidative stress plays a key role in metabolic syndrome which includes obesity and cardiometabolic diseases. It is implicated that oxygen-derived free radicals generated during the mitochondrial electron transport chain alter the function of specific biological components, thus activating obesogenic pathways such as glucose and lipid signaling. Research on this topic is of vital importance as obesity is a high-risk factor in the development and progression of severe, debilitating, life-threatening maladies such as cardiometabolic diseases, chronic inflammatory pathologies, and cancer. Furthermore, there is no universal effective therapy to combat the rising rates of obesity with over 1.9 billion (39%) adults classified …


Role Of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-Sdkp) And Renal Hemodynamics On Obesity Related Renal Damage, Mani Maheshwari Jan 2018

Role Of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-Sdkp) And Renal Hemodynamics On Obesity Related Renal Damage, Mani Maheshwari

Theses, Dissertations and Capstones

Obesity is a public health problem and is associated with salt-sensitive hypertension, kidney inflammation and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra-peptide with anti-inflammatory and anti-fibrotic properties but its effect on kidney damage in obesity is unknown. We hypothesized that high salt fed Zucker obese (ZO) rats develop renal damage, inflammation and fibrosis and that Ac-SDKP prevents these changes. Zucker lean (ZL) rats served as controls. Animals were treated with Ac-SDKP while maintained on either a normal-salt or HS diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation and fibrosis were evaluated. HS diet increased macrophage infiltration in the …


Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin Jan 2016

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …


The Characterization Of Two Differentially Expressed Plasma Proteins In Obese Versus Lean Rats In Two Rodent Models Of Obesity, Roger D. Boggs Jan 2003

The Characterization Of Two Differentially Expressed Plasma Proteins In Obese Versus Lean Rats In Two Rodent Models Of Obesity, Roger D. Boggs

Theses, Dissertations and Capstones

Zucker fa and La/N faf rats are widely studied models of genetic obesity and its complications. These two rodent models of obesity were utilized to search for a circulating protein marker for obesity. Plasma samples from both of these models of obesity were collected and analyzed via SDS-PAGE analysis. Two proteins were found which demonstrate differential expression between lean and obese rats. Both proteins demonstrated increased expression in the obese rats compared to the lean. One differentially expressed protein migrated on SDS-PAGE gels at 116 KD while the second migrated at 22 KD compared to molecular weight markers. The 22 …