Medical Sciences Commons^™

Phytochemical And In-Vitro Cytotoxic Analyses Of Flavonoid Species Isolated From Chromolaena Leivensis, Luke A. Bryant

Electronic Theses and Dissertations

As a leading cause of death worldwide, cancer and its treatments remain a primary source of interest among researchers. Modern studies are looking into bioselective cytotoxicity to create new chemotherapies that do not have the same harsh side effects as those we use today. Natural product research has a promising future for the development of such treatments. Specifically, polar flavonoids may be the key to a bioselective treatment. Such flavonoid species are native to plants, often within flower petals or within the body. A natural antioxidant, they are designed not to harm healthy cells. This study focuses on the plant …

Characterization Of Catechol-Type Siderophore(S) From P. Mosselii Cfml 90-83, Kemper R. Rasnake

Electronic Theses and Dissertations

Iron is essential for many biological processes, where it is used as a cofactor. Even though it is abundant in the Earth’s crust, it is in an insoluble form unavailable to microorganisms in the soil. To overcome this, bacteria produce siderophores, which are secondary metabolites that have a high affinity for iron. This allows bacterial cells to obtain insoluble iron that is essential for survival. Pseudomonas mosselii, a Gram negative bacterium, was isolated from soil. It was selected for further analysis as it was found to produce siderophore(s) under iron-limited conditions, which have not been characterized previously. Therefore, we aimed …

Feasibility Of Assessing Dietary Patterns And Anxiety In College Students: A Pilot Study Using Nutrition Questionnaires, Gad-7, And Asq, Kylie Ford

Electronic Theses and Dissertations

Anxiety is highly prevalent among college students representing a significant public health concern. Research indicates that dietary patterns may influence mental health outcomes; however, the practicality of collecting comprehensive dietary and psychological data in college populations remains unclear. This pilot study assessed the feasibility of evaluating dietary patterns and anxiety using self-report instruments. Participants completed the Nutrition and Eating Habit questionnaire, the Generalized Anxiety Disorder-7 (GAD-7), and the Anxiety Sensitivity Questionnaire (ASQ). Although twenty-one students were recruited, survey completion rates were low, with only seven participants completing the nutrition questionnaire necessary to calculate the Dietary Inflammatory Index (DII). Descriptive analyses …

Synthesis And Evaluation Of Novel Mt5-Mmp Inhibitors For Treatment Of Alzheimer’S Disease, Nicholas Borges

Electronic Theses and Dissertations

Alzheimer’s Disease (AD) is a common neurodegenerative disease that is characterized by the accumulation of amyloid beta (Aβ) plaques and presence of neurofibrillary tangles (NFT) in the brain. Aβ oligomers are directly toxic to CNS synapses and can induce tau protein hyperphosphorylation, that causes NFT buildup. For these reasons, Aβ has been investigated as a therapeutic target, yet very few clinical trials have yielded effective drugs for AD treatment until now. Recently, the MT5-MMPmediated η-secretase pathway, which generates synaptotoxic Aη from amyloid precursor protein, has been reported (Wang et al 2024, Wilem et al 2015). Thus, pharmacologic inhibition of MT5-MMP …

Avaren-Fc's Effects On Lymphoma Cells., Jacob Hahn

Electronic Theses and Dissertations

This thesis investigates the therapeutic potential of Avaren-Fc (AvFc), a novel lectin fusion protein that integrates the Fc region of human IgG1 with the engineered lectin Avaren, specifically targeting lymphoma. The study delineates the in vitro binding capabilities of Avaren-Fc with a human B-cell lymphoma cell line, a canine B-cell lymphoma cell line, healthy canine peripheral blood mononuclear cells (PBMCs), and healthy human PBMCs. AvFc was shown to exhibit significant binding to human lymphoma cells. Furthermore, the direct cytotoxicity of Avaren-Fc against canine lymphoma cells, canine lymphoma cells and healthy canine PBMCs was assessed. It was found that there is …

Mechanisms Of Correlated Neuronal Activity In The Globus Pallidus, Hamza Albawaliz

Electronic Theses and Dissertations

This thesis investigates the mechanisms of correlated neuronal activity in the globus pallidus externus (GPe), a key structure in the basal ganglia. Neuronal activity in the GPe is reportedly decorrelated in healthy subjects but can become highly correlated in Parkinson’s disease. However, high-density neuronal recordings in the GPe of healthy rats reveal a surprising degree of correlated activity. This raises the question of whether intrinsic properties or network connectivity alone can account for such patterns. To explore this, a computational model was developed in which GPe neurons are represented as coupled phase oscillators influenced by experimentally derived phase-response curves and …

Immunopathogenic Crosstalk Between Cancer And The Kidney: A Central Role For Macrophages As Potential Mediators., Dana Hammouri

Electronic Theses and Dissertations

Cisplatin remains a mainstay in the treatment of solid tumors, yet its therapeutic efficacy is frequently compromised by dose-limiting nephrotoxicity. Approximately 30% of patients receiving cisplatin develop acute kidney injury (AKI), which increases the risk of chronic kidney disease (CKD), a leading cause of morbidity and mortality. Despite extensive preclinical efforts, no FDA-approved therapy currently exists to prevent or treat cisplatin-induced nephrotoxicity (CIN). This in part is due to the reliance of preclinical studies on non-cancer animal models that fail to capture the complex physiological alterations associated with malignancy. To address this limitation, we developed a clinically relevant model in …

Intestinal Stromal Cells Play A Critical Role In Protection Mediated By Male Microbiota-Derived Metabolites And Androgens Against Disease In Lupus-Prone Mice., Jing Ma

Electronic Theses and Dissertations

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving broad immune dysregulation. Despite decades of research, most lupus treatments still have limited effectiveness and can cause serious side effects. Both genetic and environmental factors contribute to lupus susceptibility, and a better understanding of how environmental factors influence disease could guide future therapeutic strategies. SLE shows a strong female predominance. Growing evidence implicates the gut microbiota and sex hormones as key environmental contributors to some autoimmune diseases, including lupus. The gut microbiota can influence host immune function, and interestingly, recent studies have revealed sex-bias in microbiota composition and function. Moreover, …

Role Of Cardiac Ketone Body Metabolism In Myocardial Perfusion And Exercise Performance., Kara R. Gouwens

Electronic Theses and Dissertations

Cardiorespiratory fitness, a crucial determinant of overall health and a strong predictor of all-cause mortality, is largely dependent on the capacity of the cardiovascular system to deliver oxygen and nutrients. The heart, as the central pump, requires a continuous and adaptable oxygen supply, particularly during increased workload such as occurs with exercise. Impaired myocardial blood flow (MBF) in response to increased demand can lead to ischemia, limiting exercise capacity and potentially causing severe cardiac events. Interestingly, changes in myocardial metabolism and cardiac work correlate with changes in MBF. Therefore, understanding the regulation of MBF, especially the link between local cardiac …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

Advancing Research On Retinitis Pigmentosa: An Investigation Of Natural History, Visual System Plasticity, And Mutation-Independent Treatment., Cecilia A. Attaway

Electronic Theses and Dissertations

Retinitis Pigmentosa (RP) is an inherited retinal disease characterized by rod and then cone photoreceptor degeneration. ~25% of cases are caused by a genetic mutation that results in autosomal dominant RP (adRP). There has been a lack of exploration of the progression of degeneration in adRP models. In Chapter Two, I examined visual acuity (VA) changes, retinal structure, and function from early to late-stage disease in a murine P23H Rho ‘knock-in’ mouse model (Rho^P23H/+), the most common form of adRP in North America. To establish a natural history, I evaluated behavioral VA, using the visual water task, …

Cns-Specific Hiv Reservoir Characterization In Humans: Advancing Our Understanding Through Novel Genomics Methods., Ghazal Sadri

Electronic Theses and Dissertations

The persistence of the human immunodeficiency virus (HIV) reservoir despite years of suppressive antiretroviral therapy (ART) represents the principal obstacle to achieving a functional cure. Because the intact, replication-competent portion of the reservoir drives viral rebound after treatment interruption, HIV cure strategies must specifically identify and target cells harboring these proviruses. Conventional reservoir‐characterization techniques typically require separate assays to capture integration sites, assess proviral integrity, and quantify clonal proliferation and they rely on short‐read sequencing. These limitations hinder our ability to understand how integration landscapes, the integrity of the HIV genome, and cell‐division dynamics intersect to maintain viral persistence in …

Healthcare Utilization Patterns, Associated Factors, And Readmission Rates Among Children With Sickle Cell Disease., Daniya Mohammed Sabrah

Electronic Theses and Dissertations

Sickle Cell Disease (SCD) is common in Saudi Arabia, with a prevalence rate of 2.3%. It is an expensive disease to manage due to the extensive utilization of healthcare resources, including hospital readmissions, extended hospital stays, and frequent emergency department visits, which cost approximately $395 million annually in U.S. dollars. The primary objective of this study was to conduct a systematic literature review of healthcare utilization and cost of patients with SCD, following the PICO framework and PRISMA guidelines. The second aim utilized count models, including the negative binomial and Poisson, to identify factors associated with emergency, inpatient, and outpatient …

Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman

Electronic Theses and Dissertations

Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.

A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …

Impact Of Human Immunoglobulin Genetic Variants On The Expressed Antibody Repertoire., Eric Engelbrecht

Electronic Theses and Dissertations

B cells produce immunoglobulins (IGs; antibodies), which are critical protein components of the immune system. Human IGs are composed of two pairs of identical ‘heavy’ chains and ‘light’ kappa or lambda chains, encoded by genes located at three loci in the genome: the IG heavy chain locus (IGH, chromosome 14), and the IG lambda (IGL, chromosome 22) and kappa (IGK, chromosome 2) loci. Each locus spans ~920-100 kilobase pairs (Kbp) of DNA and harbors families of gene segments that are somatically rearranged during B cell development. The IG loci collectively harbor >180 functional genes, many of which are part of …

Plasma Resuscitation Attenuates Hemorrhage-Induced Glomerular Barrier Damage And Dysfunction., William Byron Risinger

Electronic Theses and Dissertations

Introduction: Acute renal dysfunction following traumatic injury and hemorrhagic shock carries significant morbidity and mortality. Despite an extensive understanding of renal tubule damage after injury, less is known regarding early alterations to the glomerular filtration barrier following hemorrhagic shock and resuscitation. Previously, our lab and others have demonstrated improved hepatic and intestinal microcirculatory parameters when resuscitation strategies incorporate fresh frozen plasma. In addition to improving end-organ perfusion, plasma reconstitutes the endothelial glycocalyx, an essential regulator of vascular permeability and microcirculatory function. However, the impact of plasma resuscitation on the glomerular glycocalyx and barrier following hemorrhage remains unknown. We hypothesized …

Regulation And Mechanisms Of Ocular Dominance Plasticity At Cellular Resolution., Thomas Christopher Brown

Electronic Theses and Dissertations

Sensory systems throughout the brain require experience to aid in proper wiring during development. While forming, many sensory systems have periods of heightened sensitivity where alterations in the quality of experience can have a profound impact on cortical responses throughout life. These periods of heightened sensitivity have been coined critical periods. In the visual system of mice a critical period for ocular dominance has been well studied and defined between postnatal days nineteen and thirty-six. During this critical period, altering visual experience by suturing one eye closed called monocular deprivation (MD) shifts responses in cortex towards the non-deprived eye. Similar …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Cannabis Exposure During Pregnancy And Neural Mechanisms Of Parenting: Assessing Neural Responses To Infant Cues And Parenting Outcomes, Shannon Powers

Electronic Theses and Dissertations

As legalization of cannabis and cannabinoids spreads in the United States, access and use of cannabis during the prenatal period has increased. There is limited knowledge on the effects of prenatal cannabis use on the parental brain. One way to identify potential effects of cannabis on parenting is through studying parenting brain functions and behavior. Cannabis use disorder (CUD) has been shown to be associated with lower positive parenting and lower sensitivity to infants, but it is unclear by what mechanisms. The following two studies address this gap in knowledge by examining the association between cannabis use during the prenatal …

Macrophage Polarization And Colorectal Cancer Immune Checkpoint Protein Expression., Anne Macleod

Electronic Theses and Dissertations

The majority of patients with colorectal cancer do not respond to treatment with immunotherapy. Immunotherapy requires the expression of cell surface immune checkpoint proteins (e.g. PDL1) to exert its effect. Most (>85%) of colorectal cancers do not express these proteins and this contributes in part to the poor prognosis and survival in patients with advanced disease. The patients in which immunotherapy is a potential treatment option, are a genetic subtype known as mismatch repair deficient, and have demonstrated an excellent response to anti-PD-1/PDL1 immunotherapy. A key feature of mismatch repair deficient (MMRd) cancers is their immune cell rich tumor …

Perinatal Buprenorphine Effects On Offspring Growth, Opioid Withdrawal, And Brain Morphology In Rats, Parker Barnes

Electronic Theses and Dissertations

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant …

Validation Of A Novel Heritable Rodent Model Of Drug Abuse Vulnerability In Psychosis And Investigation Of Therapeutic Targets, Loren D. Peeters

Electronic Theses and Dissertations

Schizophrenia is a severe neuropsychiatric disorder of largely unknown etiology that is often accompanied by high rates of cigarette smoking, reduced quit success, and high relapse rates. Dysregulated dopamine signaling and aberrant synaptic plasticity in the mesocorticolimbic pathway are implicated in the pathophysiology of schizophrenia and conferred substance abuse disorder and relapse vulnerability. Genetic factors are presumed to play a significant role in the development of schizophrenia, with a 40-50% concordance rate for monozygotic twins, although genetic markers are inconsistent. As such, epigenetic factors have instead been implicated. Specifically, there is strong evidence to suggest DNA methylation at several candidate …

Control Of Muscle Activation In The Lower Limbs During Leg Cycling After A Motor Complete Spinal Cord Injury., Jae Fish

Electronic Theses and Dissertations

Spinal cord injury (SCI) affects the central nervous system (CNS) causing muscle paralysis and autonomic dysfunctions throughout the body. Muscle activation after SCI is essential to facilitate functional recovery and may be produced via remaining input from supraspinal centers, the central pattern generators (CPG), or muscle stretch reflex responses. In this study, assisted leg cycling is evaluated as a tool to identify the neural structure control of muscle activation after motor complete SCI. Eight individuals with a complete or sensory incomplete SCI between C2 and T5 participated in the study. Participants completed leg cycling trials with and without supraspinal intention …

Optimization Of Vagus Nerve Stimulation (Vns) And The Use Of Cervical Vns As A Treatment For Heart Failure With Reduced Ejection Fraction, Misty Owens

Electronic Theses and Dissertations

Vagus nerve stimulation (VNS) is a promising neuromodulatory therapy under investigation for a range of disorders, including heart failure, gastric dysmotility, and migraine. Two primary forms of VNS are currently investigated: cervical VNS (cVNS), involving surgically implantation to activate vagal afferents in the cervical branch in the neck and transcutaneous auricular VNS (taVNS) which subcutaneously stimulates the auricular branch in the outer ear. The nucleus of the solitary tract (NTS) serves as a relay-station receiving 90% of vagal afferents, enabling connections with higher-order brain regions and other brainstem nuclei like the spinal trigeminal nucleus (Sp5) and locus coeruleus (LC), facilitating …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …

Investigating The Role Of Maternal Adiposity On Human Breast Milk And Preterm Infant Stool Short Chain Fatty Acid And Microbiome Profiles, Kristy L. Thomas

Electronic Theses and Dissertations

Preterm birth is the number one cause of death in neonates, accounting for 35% of neonatal mortality. The preterm birth rate in the U.S. in 2021 was 10.5%, disproportionally affected by race and ethnicity. Obese women have an increased risk of preterm pregnancy, and if delivered before 37 weeks of gestation, the offspring have higher rates of complications that extend from the neonatal period into life-long metabolic and immune adverse outcomes. In the early months after delivery, preterm infants have higher rates of adverse health outcomes than term infants, including infections, extrauterine growth restrictions, respiratory, metabolic, and neurological complications, necrotizing …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …