Medicine and Health Sciences Commons^™

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 …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Modulation Of Inflammatory Pathway By Inflammatory Inhibitor Jsh-23 Mitigates Diabetic Retinopathy., Rubens Petit Homme

Electronic Theses and Dissertations

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Association Of Perfluorinated Chemicals With Endocrino-Carcinogenetic, Obesogenic And Metabolic Health And With Markers Of Chronic Inflammation And Oxidative Stress, Ogbebor Enaholo Omoike

Electronic Theses and Dissertations

First, this study examined the association of perfluorinated chemicals with 1) cardio-metabolic health outcomes and 2) the association of phthalates with cardiometabolic health outcomes, and 3) cardio-metabolic health outcomes while assessing the possibility of additive interactions between perfluorinated chemicals (PFCs) and phthalates. Second, association with markers of chronic inflammation and oxidative stress were explored. Finally, this study examined the association of these chemicals with estrogenic cancers- Breast cancer, prostate cancer, uterine cancer and ovarian cancer.

Using data from the National Health and Nutrition Examination Survey (NHANES), logistic regression models were used to investigate the relationship between PFCs and the cardio-metabolic …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Bovine Cellular And Innate Immune Response To Hemostatic Polysaccharides, Brian Kobylkevich

Electronic Theses and Dissertations

Chronic wounds are longstanding dermal wounds that do not heal in a normal amount of time and can commonly last for over a year. These wounds plague humans and farm animals alike. Wounds are characterized by chronic inflammation and are often painful, difficult to heal, have a high recurrence rate, and are potentially debilitating. Long term wounds that do not fully heal are distressing for both humans and animals, but understandably more resources have been directed towards humans. Some treatment options for humans may be suitable for adaptation into the field of animal care. Chronic lesions such as bovine digital …

Are Chronic Inflammatory Diseases Associated With Trauma Exposure And Gender? An Empirical Analysis Of Self-Reported Trauma And Health Histories Of Men And Women, Meghan Lacienski

Electronic Theses and Dissertations

A growing body of research indicates an association between trauma, inflammation, and chronic inflammatory disease; however, the mechanisms of this relationship are not fully understood, and the salience of potential risk factors, such as cumulative effects of trauma, trauma type, and gender, remain unclear. Trauma is associated with poor mental and physical health, such as PTSD, depression, and chronic inflammatory conditions, and this association may be stronger when certain risk factors are considered (Brody, Pratt, & Hughes, 2018; Groer, Kane, Williams, & Duffy, 2014; Husky, Mazure, & Kovess-Masfety, 2018; Kilpatrick et al., 2013). For example, sexual trauma and multiple traumatic …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

Effect Of Grape Components On Periodontal Disease., Juili Subodh Shivde

Electronic Theses and Dissertations

Background: Half of the adult American population (47 %) are victims of periodontitis, a chronic inflammatory disease which leads to destruction of the tissues supporting the tooth. Periodontitis is initiated by periodontal pathogens and caused by excessive or prolonged host mediated inflammation. Porphyromonas gingivalisis one important agent implicated in the etiopathogenesis of chronic periodontitis. Pro-inflammatory cytokines induced by periodontal pathogens can cause alveolar bone loss and periodontitis. Bone loss is caused by the imbalance of bone formation and bone resorption. Osteoclasts are major cells that cause bone resorption. Moreover, periodontal inflammation also leads to bone resorption. Grapes are rich …

Treg Regulation In Periodontal Disease During Pregnancy., Aislinn Leah Hays

Electronic Theses and Dissertations

Background: Although pregnancy is prone to induce more severe periodontal inflammation and tissue damage, its mechanism remains elusive. Periodontal diseases during pregnancy are associated with adverse pregnancy outcomes including preterm birth or low birth weight. Animal models are ideal for investigating immunological mechanisms in periodontal disease. With a newly modified ligature-induced disease model, we managed to develop periodontal disease in pregnant mice and investigate the immunological mechanism of more severe symptoms during pregnancy. Hypothesis: We hypothesis that P. gingivalis infection during pregnancy will lead to a down-regulation of Treg cells, therefore causing increased inflammation and disease severity. Methods: A ligature-induced …

Exploring A Novel Nf-ĸb- Inhibiting Nanoparticle For Periodontitis Therapy., Kameswara Satya Srikanth Upadhyayula

Electronic Theses and Dissertations

Periodontitis is an infection-driven inflammatory disease characterized by gingival inflammation and bone loss. The NF-ĸB signaling pathway is pivotal in osteoclastogenesis and infection-induced pro-inflammatory responses. The use of nanoparticles as a vehicle to deliver drug increases stability, loading capacity, and facilitates transmembrane transportation. The hypothesis was that a novel nanoparticle carrying therapeutic NBD inhibitory peptides (NBD-nanoparticles) will inhibit measures of periodontal disease. In this project, we tested the nanoparticles for their ability to directly inhibit osteoclastogenesis and inflammation as an original strategy for periodontitis therapy. We also tested the capability of the nanoparticles to inhibit gingival inflammation and alveolar bone …

The Role And Regulation Of Inhibitor Of Kappa B Kinase In The Impaired Monocyte Response., Norman James Galbraith

Electronic Theses and Dissertations

Trauma, major surgery and systemic infection can lead to a subsequent immunosuppressed state which can predispose patients to nosocomial infection and death. Approximately a sixth of patients will have impaired monocyte function, as determined by decreased HLA-DR expression or decreased TNF-α production in response to ex-vivo lipopolysaccharide (LPS) stimulation. This project aimed to develop an in-vitro model of impaired monocyte function using isolated monocytes from healthy volunteers, to study the effect of monocyte impairment on IκK signaling, and determine the role of IκK in the impaired monocyte response. These studies have provided the following results:

1. Monocytes treated with low dose …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair

Electronic Theses and Dissertations

MicroRNA-21 (miR-21) is an evolutionarily conserved microRNA, abundant in most cardiovascular tissues. It has been implicated in the pathogenesis of several cardiovascular diseases including restenosis, myocardial infarction, and heart failure. However, little is known about the contribution of miR-21 in atherosclerosis. My data show that expression of miR-21 is increased by >1.5-fold in murine atherosclerotic lesions and by 1.5-2.0-fold in the macrophages of Western diet (WD)-fed LDLR-KO mice (for 12-20 weeks). In vitro, LDL, oxidized LDL, acetylated LDL and LPS induced miR-21 by 2-4-fold and down-regulated its target protein, PDCD4, in bone marrow-derived macrophages. Basally, macrophages isolated from miR-21-KO …

Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte

Electronic Theses and Dissertations

Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding …