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Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla

Electronic Theses and Dissertations

Cytokines are key regulators of the inflammatory response and play an important role in facilitating intercellular communication between various immune cell types. Interleukin‑1β (IL‑1β) is a potent pro-inflammatory cytokine that is required for robust initiation of innate immune response and subsequent development of adaptive immunity. IL-1β is first synthesized as an inactive cytoplasmic, non‑glycosylated, precursor molecule (proIL‑1β) by monocytes and macrophages in response to invading pathogenic microbes. The activation of caspase‑1 by inflammasomes cleaves proIL-1β into mature biologically active IL-1β that is released from cells via a non-classical, endoplasmic reticulum‑independent secretory pathway directly from the cytoplasm via Gasdermin D membrane …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

Role Of Microbiome In Impacting Treatment Of Obesity And Type 2 Diabetes, Aneseh Adeshirlarijaney

Biology Dissertations

Metabolic Syndrome is a constellation of metabolic abnormalities associated with insulin resistance and obesity, including hyperglycemia and hypertension. Metabolic syndrome often progresses to type 2 diabetes, hypertension, cardiovascular disease, and liver disease. Metabolic syndrome is increasingly appreciated to be an inflammatory disease in that is associated with increased expression of pro-inflammatory genes and markers, remodeling of adipose tissue, and markedly increased incidence in the last 50 years. Additionally, both diseases alter the microbiota, specifically with alteration in gut microbiota composition. Metabolic syndrome requires a microbiota in that disease is not observed in germ- free mice, and some aspects of the …

Inflammation And Corrosion In Total Hip Prostheses: The Generation And Interaction Of Reactive Oxygen Species With Cocrmo Metallic Biomaterial Surfaces, Michael John Wiegand

All Dissertations

There are many molecules, species and mechanisms that contribute to the overall wear and degradation of biometallic alloys like cobalt-chromium-molybdenum (CoCrMo). Following implantation, orthopaedic alloys are subject to an encompassing inflammatory response that will either lead to foreign body giant cell formation and attachment to the surface or the fibrous tissue encapsulation, forming an inflamed periprosthetic joint. In addition to the inflammatory response, tribocorrosion-based processes of alloy-on-alloy or alloy-on-polymer couples release polymeric wear debris, oxides, hydroxides, and metal ions in response to excessive wear, loading and corrosion. It is hypothesized that these processes, biological and triboelectrochemical, are linked together in …

Anti-Inflammatory Effects Of Cruciferous And Apiaceous Vegetables In C57bl/6j Mice Colon, Rosa Moreno Narvaez

Graduate Theses and Dissertations

Previous studies have demonstrated chemo-preventive potential of cruciferous and apiaceous vegetables against colon cancer. Colon inflammation is one condition closely related with colon cancer initiation. Therefore, we wanted to compare if total western diet (TWD) was as pro-inflammatory as died-induced obesity (DIO) and a better dietary model for human conditions, and determine if diet supplementation with cruciferous (broccoli, watercress and cabbage) or apiaceous vegetables (celery and parsnip) could reduce dietary inflammation, and which vegetable was more effective.

Male CBL57/6J mice were fed chow for seven days, on day eight, mice were assigned to one of the following diets: American Institute …

Effects Of Dietary Copper, Zinc And Manganese Source And Level On The Acute Inflammatory Response Of Broilers, Chelsea Ellington

Graduate Theses and Dissertations

Trace minerals, particularly copper, zinc and manganese, play a role in ensuring optimal immune function. To examine the effects of diets containing different levels and sources of trace minerals on the inflammatory response, Cobb 500 broilers were fed four experimental diets containing 5 mg/kg Cu and 45 mg/kg of Zn and Mn or 10 mg/kg Cu and 90 mg/kg Zn and Mn in either the sulfate or hydroxychloride form. When the broilers were 5 weeks of age, 16 μg of lipopolysaccharide (LPS) was injected into the pulp of growing feathers (GF; 16 GF per chicken; 1 μg LPS per GF). …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

MSU Graduate Theses

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Effects Of A 12-Week Vigorous Interval Training Intervention On Pro-Inflammatory Markers In Post-Operative Bariatric And Obese Participants, Brittany Rood

Masters Theses, 2010-2019

Increase prevalence of cardiovascular and other chronic diseases linked to inflammation has led to research on pro-inflammatory cytokines, like tumor necrosis factor - alpha (TNF-α) and lipoprotein-associated phospholipase A₂ (Lp-PLA₂), in attempt to define the relationship between chronic disease, inflammation, and obesity. PURPOSE: Examine the effect of twelve weeks of vigorous intensity interval training on pro-inflammatory markers in post-operative bariatric and obese participants. METHODS: 9 post-operative bariatric individuals [1 man, 8 women; Body mass index (BMI) = 34.23 ± 2.54 kg/m²], 12 obese individuals [5 men, 7 women; BMI=35.77 ± 1.67 kg/m^{2 …}

The Effects Of Indirubin Derivative E804 On Inflammatory Profiles In Glioblastoma Multiforme Cell Lines And Subsequent Crosstalk Effect On Tumor Associated Thp-1 Macrophages, Micaela Ro Scobie

All Dissertations

Glioblastoma Multiforme (GBM) is a highly invasive brain tumor that affects approximately 18,000 people annually in the USA alone yet remains without curative treatment. Median survival with treatment is 14 months, with most treatments only prolonging life for several months while causing severe adverse side effects. There is a need for new therapeutic modalities. Herein I explore two small molecules that show promise in modulating inflammatory signaling in an in vitro GBM model. Indirubins E804 (indirubin-3’-(2,3 dihydroxypropyl)-oximether) and 7BIO (7-Bromoindirubin-3’-oxime) are synthetic derivatives of natural indirubin. Natural indirubin is a bisindole alkaloid derived from tryptophan precursors and is an agonist …

Examining The Relationship Between Yoga Participation And Health. You Down, Dog?, Bethany Forseth Hanson

Theses and Dissertations

The prevalence of debilitating chronic diseases, such as cardiovascular disease (CVD) and Alzheimer’s disease, are increasing in the United States. Inflammation, mitochondrial dysfunction, stress and depression are common pathologies associated with these chronic diseases. Many individuals engage in yoga because they believe it will improve their health. However, research examining the impact of yoga on markers of health associated with chronic diseases is limited and often reports conflicting results. Therefore, the purpose of this dissertation is to examine the relationship between yoga and inflammation, protein content of oxidative phosphorylation complexes, stress and depression, which may support the use of lifestyle …

Baseline And Stress-Induced Cognitive Control Deficits And Pro-Inflammatory Cytokines In Currently, Remitted, And Never Depressed Individuals, Katerina Rnic

Electronic Thesis and Dissertation Repository

Background: Cognitive theories posit that cognitive control deficits promote depression by reducing ability to self-regulate under stress. When activated by stress and accessible to working memory, negative cognitive content and structure (i.e., schemas), may interfere with cognitive control abilities, resulting in even greater declines in executive functioning. Moreover, burgeoning evidence indicates that social stress upregulates inflammation, resulting in a pro-inflammatory phenotype that drives depression pathogenesis. However, cognitive mechanisms underlying this process are not well understood. An objective of this study was to examine depression-related deficits in cognitive control and their association with poor self-regulation. Another purpose was to evaluate the …

Comorbid Metabolic Syndrome And Prodromal Alzheimer's Disease In A Rat Model, Nadezda Ivanova

Electronic Thesis and Dissertation Repository

Metabolic syndrome (MetS), the development of which is associated with high-caloric Western diet intake, represents a risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and appears to contribute to AD progression when MetS and AD are comorbid. The interaction between AD and MetS might be through white matter inflammation, since white matter abnormalities and inflammation are important early events in the etiopathogenesis of both diseases. In these investigations, the effect of a high-caloric diet (HCD), to induce metabolic disturbances, on white matter neuroinflammation and cognitive function was investigated in a transgenic (TG) rat model of prodromal AD …

Diet, Inflammation, Gut Microbiome, And Mental Health, Ashley R. Polokowski

Dissertations, Theses, and Capstone Projects

Omega-3 fatty acids (ω-3 FAs) are an essential fatty acid necessary for healthy development in mammals. They possess anti-inflammatory properties and have more recently been shown to impact gut microbiota, both factors hypothesized to be associated with depression and anxiety. Thus, empirical efforts have begun to examine the benefit of ω-3 FAs as a treatment option for various psychological disorders. Although there is evidence that ω-3 FAs have favorable outcomes on depressive symptoms, the relationship between ω-3 FAs and anxiety and the pathways by which ω-3 FAs produce beneficial health effects are poorly understood. Both inflammation and the gut microbiome …

Scaffold Design Considerations For Soft Tissue Regeneration, Madeleine M. Di Gregorio

Electronic Thesis and Dissertation Repository

Tissue engineering has emerged as a promising strategy for the replacement of degenerating or damaged tissues in vivo. Also known as regenerative medicine, integral to this therapeutic strategy is biomimetic scaffolds and the biomaterial structural components used to form them. In this study, three different biomaterial scaffolds for tissue engineering applications were fabricated: three-dimensional reverse embedded collagen scaffolds, polymer fusion printed polycaprolactone (PCL) scaffolds, and electrospun gelatin scaffolds. Three-dimensional collagen and PCL scaffolds promoted human adipose-derived stem/stromal cell (ASC) spreading, proliferation, and fibronectin deposition in vitro. Secondly, this study investigated the efficacy of exogenous galectin-3 delivery as a …

Monocyte Mri Relaxation Rates Are Regulated By Extracellular Iron And Hepcidin, Praveen S.B Dassanayake

Electronic Thesis and Dissertation Repository

Monocytes are an important immune cell type in chronic inflammatory conditions like atherosclerosis and heart failure. The increase in number of monocytes released to the peripheral blood circulation, the differentiation of monocytes to macrophages, and the presence of different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury may provide markers for monitoring inflammation. In particular, changes in monocyte iron metabolism during an inflammatory response may increase the possibility of tracking these immune cells non-invasively using magnetic resonance imaging (MRI). When secretion of the polypeptide hormone hepcidin is stimulated during inflammation, it binds the iron export protein ferroportin (FPN) …

An Assessment Of Bsa Protein Hydrogel Biocompatibility In The Vertebrate Intestinal Tract, Ryan Joseph Garde

Theses and Dissertations

The fields of biomedicine and pharmacology have a mission to design methods to treat disease while minimizing adverse side effects using novel drug delivery systems. In developing new therapeutic systems, it is crucial to test that drug delivery systems target pathological cells and tissue and is non-toxic in healthy tissue. One promising method for targeted drug delivery is the use of hydrogels as carriers. Here, we studied the effects of bovine serum albumin (BSA) hydrogel consumption to assess the potential for hydrogel use in treating intestinal disease via oral administration. We investigated intestinal architecture and cell populations following hydrogel treatments …

Brain-Specific And Systemic Inflammatory Response Following Repetitive Concussive Impact In A Mouse Model, So Young Eo

Electronic Thesis and Dissertation Repository

Concussion is the most common form of mild traumatic brain injury (mTBI). TBI resolution is modulated by neuroinflammation, which is augmented by the infiltration of innate immune cells from the circulation. Peripheral, myeloid immune cells not only invade neural tissues but other organs as well causing local inflammation and tissue damage, known as systemic inflammatory response syndrome. Here, I assessed the temporal and anatomical nature of the neural and systemic cellular inflammatory response to repetitive, mTBI in a 3-hit mouse model of concussion. The results showed significant microglial activity, accumulation of peripheral myeloid cells and prominent axonal damage post-injury. The …

Gouty Arthritis, Erin Dutt

Nursing Student Class Projects (Formerly MSN)

Gout is an arthritic condition that can lead to destruction of the affected joints. Often the main complaint is severe pain of the big toe but could affect other joints. Due to the frequency of this condition, the family nurse practitioner (FNP) could easily encounter it in family practice. What causes the joint destruction is the deposit monosodium urate crystals (MSU) along a joint due to hyperuricemia. Not only can gout cause permanent joint damage, it also increases the risk for kidney damage. Treatment will be aimed at managing acute attacks and lowering serum uric acid (SUA) levels. Controlling modifiable …

Macrophages And Associated Inflammation Differentially Impact Obesity, Colorectal Cancer And Obesity-Enhanced Colorectal Cancer, Jackie Bader

Theses and Dissertations

Colorectal Cancer (CRC) is the third-most common malignancy for men or women, with chronic inflammation considered as a primary risk factor. Obesity is also considered a chronic inflammatory disease and is associated with increased CRC incidence. Further, obesity and CRC occur in men and women differently with the highest incidence of either disease found in men, suggesting that female sex hormones may play a protective role in inflammatory diseases. Macrophages can promote inflammation and are a driving force in obesity-associated metabolic dysfunction. Conversely, macrophages also contribute to pro-tumoral responses including, proliferation, angiogenesis and tissue remodeling. This heterogeneity of macrophage behavior …

Role Of Epigenome And Microbiome In Endocannabinoid-Mediated Regulation Of Inflammation During Diet-Induced Obesity, Kathryn Miranda

Theses and Dissertations

Obesity is an inflammatory disease involving accumulation of adipose tissue, gut microbiota dysbiosis, and over-activation of the endocannabinoid system (ECS). Mechanisms involved in ECS regulation of obesity-induced inflammation are not well understood. Presented here are three chapters involving microRNA (miR) regulation of inflammatory adipose tissue macrophages (ATM) during high-fat diet (HFD)-induced obesity and cannabinoid receptor-mediated regulation of gut microbiota dysbiosis.

ATMs are innate immune cells that drive chronic low-grade inflammation during obesity. Polarization between pro-(M1) and anti-(M2-like) inflammatory phenotypes influence insulin sensitivity and energy expenditure; however, the mechanisms involved are unclear. In study one, we characterized miRs involved in ATM …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

The Effect Of Emdogain Periodontal Regenerative Material On Inflammation In Periodontal Maintenance Patients, Jessica M. Gradoville

Theses & Dissertations

The purpose of this double-blinded, randomized, controlled clinical trial was to determine if local application of enamel matrix protein derivative (Emdogain:EMD), combined with minimally-invasive papilla reflection is effective in reducing inflammation in periodontal pockets in patients on periodontal maintenance therapy (PMT).Fifty patients diagnosed with advanced chronic periodontitis presenting with a 6-9mm interproximal probing depth were included in the trial. Experimental (EMD; n=24) and control (saline, n=26) therapies were randomly allocated. Roots were treated with mini-flaps and root planing assisted with endoscope evaluation before EMD or saline application. Inflammation was assessed by bleeding on probing (BOP) at baseline, 6-, and 12-months …

The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …

Effects Of A 28-Day Carbohydrate-Restricted Diet On Metabolic And Performance Markers In Professional Firefighters, Hunter Scott Waldman

Theses and Dissertations

Cardiovascular disease is the leading cause of death in firefighters (FF) around the nation. Recent observational studies have emerged suggesting that FF consume calorically dense foods, high in sugar and fat, but low in nutritional value which can exacerbate heart diseases and impair performance. The potential to improve cardiometabolic and performance measurements when following a carbohydrate (CHO) restricted diet (CRD) has gained interest in the literature. To date, only one study has employed a nutrition intervention in FF, yet its’ focus was on nutrient dense foods and antioxidant supplements. Therefore, the purpose of this study was to examine the cardiometabolic …

Does Acute Preprandial Exercise Modify Postprandial Inflammation After A High Fat Meal In Young And Older Adults?, William Wisseman

Masters Theses, 2010-2019

A single high-fat meal (HFM) can increase systemic inflammation (postprandial inflammation; PPI) and may be attenuated by recent exercise. However, the effect of preprandial exercise on PPI in older adults (OA) is not clear. Purpose: To determine if preprandial exercise attenuates PPI in YA and OA. Methods: 12 YA (23.3±3.9 years n= 5 M/7 F) and 12 OA (67.7±6 years, n= 8 M/4 F) completed two HFM challenges in a randomized order. During HFM alone, participants abstained from exercise 48 hours prior to the HFM session (except for the exercise session) and adhered to a 12 hour overnight …

Relationships Among Optimism, Inflammation, And Stroke Recovery, Yun-Ju Lai

Dissertations & Theses (Open Access)

Objective: Post-stroke inflammation is detrimental to the brain and results in an unfavorable recovery. Optimism has been associated with lower inflammation and better health outcomes among people with medical conditions, but no studies have assessed this association in the stroke population. The overall goals were to examine the relationships among optimism, stroke severity, physical disability, and inflammation during hospitalization and evaluate the relationships among optimism, inflammation, and stroke recovery over the three-month post-stroke period.

Methods: This study was a secondary analysis of data collected from the BioRepository of Neurological Diseases biobank. Outcomes included optimism, stroke severity, physical recovery, and inflammatory …

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 …

A Review Of Osteoarthritis, Madelin Brooke Session

Undergraduate Honors Capstone Projects

Osteoarthritis is a degenerative joint disease which plagues many older animals and humans. It is a disease that is characterized by the degeneration of joint cartilage, inflammation, as well as chronic pain and stiffness that results from this disorder. Unfortunately, most of the treatments for this painful and chronic disease mostly involve pain management and temporary relief strategies. These strategies usually include pain medication, non-steroidal anti-inflammatory drugs, injectable lubricants, as well as surgical techniques. However, because these treatments are just temporary fixes meant for pain management and to improve quality of life they must continue throughout the remainder of the …

Effect Of Physical Stimuli On Angiogenic Factor Expression In Retinal Pigment Epithelial Cells, Farhad Farjood

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Age-related macular degeneration (AMD) is a major cause of blindness in adults. Abnormal growth of blood vessels in the eye during the course of AMD causes damage to the retina, resulting in irreversible blindness. The goal of this research was to determine whether physical pressure on retinal cells can contribute to the increased blood vessel formation. To replicate the tears in the cell layers, a micropatterning method was used as a means of detaching cells from each other. Two new devices were also developed to mimic slow and fast increases in mechanical pressure on cell layers of the eye. After …

Volumetric Muscle Loss: The Role Of Physical Activity And Autologous Repair On Force Recovery And Signaling Pathways, Richard Perry

Graduate Theses and Dissertations

Volumetric muscle loss affects both military and civilian persons. The hallmark of this injury is incomplete muscle regeneration, excessive fibrosis, and chronic inflammatory signaling resulting in permanent functional loss. Since permanent functional loss drastically reduces quality of life, many studies have been conducted to improve force recovery. Current scientific literature considers a repair strategy of either devitalized scaffolds infused with growth factors or viable tissue plus activating factors to be the more promising interventions for optimal force recovery. PURPOSE The purpose of this study is to incorporate autologous repair and physical activity and observe the effects of muscle force recovery …