Diseases Commons^™

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

Mechanical Characterization And Modeling Of Rat Myocardia Under The Influence Of Epirubicin, Abdallah Mahmoud Alkhaiyat

Theses and Dissertations

Cancer remains a predominant health challenge that is responsible for a significant portion of global morbidity and mortality. Epirubicin (EPI), a chemotherapeutic anti-cancer drug, has shown remarkable efficacy in combating various malignancies. However, it is known to have undesirable side effects on the heart, collectively referred to as cardiotoxicity. This research investigates the adverse effects of chemotherapy on cardiac contractility through an in vitro examination of the mechanics of healthy and infarcted animal heart tissues. Electrically stimulated slices of rat ventricular tissue were tested using an isometric force measurement tissue bath. The tissue slices were subjected to uniaxial stretching, allowing …

Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal

Theses and Dissertations

Background: Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic abnormalities associated with elevated cardiometabolic risk. While diagnosis is based on well-established five clinical criteria, these may overlook early or atypical metabolic alterations. Large-scale metabolomic profiling offers an opportunity to identify biochemical signatures of MetS beyond diagnostic bias and to evaluate their relative importance across different presentations of the syndrome.

Methods: Data from 117,147 UK Biobank participants were analyzed in a cross-sectional design. High-throughput NMR quantified 75 circulating metabolites, for. Univariate analyses, MetS subtype stratification, and elastic net models with SHAP interpretation were applied to assess feature …

What’S Sleep Got To Do With It? A Mixed Methods Exploration Of The Feasibility, Acceptability, And Initial Outcomes Of Group Cbt For Insomnia In Parkinson’S Disease, Claire M. Williams

Theses and Dissertations

Parkinson’s disease is a progressive neurodegenerative disease that is commonly associated with sleep disturbances, affecting up to 80 percent of individuals with Parkinson’s. Effective and accessible treatments for sleep problems in Parkinson’s disease remain limited. Cognitive Behavioral Therapy for Insomnia (CBTi) is a well-established, non-pharmacological treatment for insomnia but has been minimally studied in Parkinson’s populations. This study evaluated the feasibility, acceptability, and preliminary outcomes of a group-based CBTi intervention adapted for individuals with Parkinson’s disease. Participants engaged in a six-week group intervention that incorporated Parkinson’s-specific adaptations. Preliminary findings indicated that the adapted group CBTi intervention was generally feasible and …

Novel Piperidone And Bispidine Derivatives: A New Approach In Cancer Therapy, Lereen Khaled Youssry

Theses and Dissertations

Cancer remains the second leading cause of death worldwide. As a result, scientists have been trying to find novel therapeutic approaches that target specific metabolic pathways selective to tumor cells. In this study, two novel piperidone and bispidine derivatives, organic molecules that target polyamine metabolism, were synthesized, and their potential cytotoxic, antioxidant and anti-inflammatory effects were investigated. Polyamines are naturally occurring metabolites that were reported to be in excess at cancer cells and were accounted for tumor proliferation, invasion and metastasis. Accordingly, the novel piperidone and bispidine derivatives were expected to disrupt tumor growth and progression via up-regulation of key …

Mir-125a-3p And Its Targets: Promising Biomarkers For Ovarian, Liver, And Breast Cancers, Offering A Beacon Of Hope For More Effective Diagnosis And Treatment Strategies, Eman Kamaleldien Anwer

Theses and Dissertations

Cancer is a worldwide health problem with various genetic and epigenetic alterations, resulting in disease heterogeneity. Effective diagnostic, therapeutic, and monitoring markers have been determined recently; however, new diagnostic, prognostic, and therapeutic markers are needed. MicroRNAs (miRNA), short non-coding RNAs, have a highlighted role in cancer progression, migration, and programmed cell death. Our study aims to investigate the significance of miR-125a-3p and its downstream targets in breast (BRCA), hepatocellular (HCC), and ovarian (OVCA) malignancies and their possibility as diagnostic biomarkers and targets for therapeutic agents. Bioinformatics and online tools were used to determine the miRNA-predicted downstream targets, analyze GEO datasets, …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Caspases Protect Against Hyperglycemia Induced Necroptosis-Like Cell Death In Brain Endothelial Cells, Aleena S. Mathew

Theses and Dissertations

Acute diabetes characterized by high spikes in blood glucose levels in association with severe hyperglycemia can lead to an increased risk of ischemic stroke in the brain. To better understand high blood glucose levels, hyperglycemia, in the brain we explored its effects on endothelial cells. Endothelial cells line the inner walls of blood vessels and are directly impacted in hyperglycemia. Brain endothelial cells are a major component of the blood brain barrier (BBB) which tightly regulates the brain’s microenvironment. The type of cell death such as apoptosis, caspase dependent, or necroptosis, caspase independent, can exacerbate diabetes associated complications. There is …

The Diseased Extracellular Matrix In Chronic Obstructive Pulmonary Disease Modeling, Leigh-Ann M. Antczak

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the world, with an increasing prevalence as the world’s population ages. In the distal regions of the lungs, COPD is characterized by progressive emphysema due to an imbalance of proteases that continuously degrade essential extracellular matrix (ECM) proteins within the alveolar walls, causing fatal tissue impairment. This dissertation examines the unique properties of this diseased lung ECM in two parts: (1) As a key constituent in inflammatory signaling that leads to increased inflammation and progression of COPD, and (2) as a tool in three-dimensional (3D) in …

Opioid Tolerance And Withdrawal In The Mouse Colon, James Fune

Theses and Dissertations

Constipation is a major clinical obstacle associated with opioids, prompting patients to discontinue treatment due to pain, discomfort, and psychosocial stressors. Moreover, chronic users become tolerant to the analgesic effects of opioids, but not to their constipating effects. Upon cessation of long-term treatment, serious diarrhea–among other somatic signs of withdrawal–may ensue. These symptoms become a driving factor for relapse, causing patients to restart opioid treatment. In this study, we aim to understand mechanisms that contribute to opioid tolerance and withdrawal in the colon. Previous findings suggest that constipation occurs partly due to the colon’s lack of tolerance to opioids’ inhibitory …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Role Of Customized Visual And Multifactorial Interventions In Preventing Falls Among Individuals With Visual Impairment In South India, Ramya S

Theses and Dissertations

Falls are the second leading cause of unintentional injuries and extensively studied among the elderly. Hence, intervention studies for falls prevention are restricted to the elderly with or without visual impairment (VI). Even among studies with VI, strategies for treatable VI are widely explored. Hence this study aimed to understand falls and interventions that may reduce falls in all the age groups especially among those with untreatable VI.

This mixed methods study included identification of subjects aged ≥ 18 years with VI from clinical records of Medical Research Foundation, Chennai and details of previous history of falls were enquired over …

Deciphering The Microbial Fingerprint Of Covid-19: A Multi-Layered Exploration Of The Oral And Gut Microbiome Dysbiosis, Iman Mostafa Sultan

Theses and Dissertations

The impact of SARS-CoV-2 infection on the human microbiome remains a dynamic and intricate puzzle. This study delves deeper into this mystery by revisiting the oral and gut microbial compositions of 53 COVID-19 patients before and after viral clearance, alongside comparisons to 76 healthy individuals. Through a comparative lens, we have emploed two distinct differential abundance methods – DeSeq2 and ANCOM – while drawing upon the thorough SILVA database encompassing the full-length 16S rRNA gene. The analysis underscores the crucial role of a diverse methodological choir in microbiome research. In certain instances, the congruence between DeSeq2 and ANCOM may exhibit …

Effect Of Plumbagin On Chemo-Resistant Metastatic Retinoblastoma, John J. Soto

Theses and Dissertations

Retinoblastoma, which is an ocular malignancy, usually results in poor prognoses in pediatric patients worldwide. Retinoblastoma in some events, can develop metastatic phenotypes which can lead to secondary tumor formation, furthering deleterious patient outcomes. It is of paramount importance to identify and research potent novel compounds that can be used to increase the likelihood of remission. Plumbagin (PLB) is a plant-derived, neuroprotective agent, which exhibits significant anticancer activities during in vitro study. PLB has been shown to have a high therapeutic efficacy against chemoresistant sublines as well as their normal counterparts. We attempted to show that the chemoresistant ABCC1 could …

Effect Of Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Loss In Lung Adenocarcinoma (Luad), Marilyn G. Vallejo Alvarez

Theses and Dissertations

Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer in the United States and is a major cause of cancer-related mortality. Patients with LUAD experience severe pulmonary symptoms and often progress to metastatic disease. Our previous work has shown that LUAD cells downregulate lung cell identity programs across cancer progression such as genes involved in the maintenance of epithelial barrier integrity. For example, CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a water and bicarbonate channel, is expressed in normal alveolar type 2 (AT2) cells and is downregulated in cells that give rise to LUAD. Although the loss …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Pricks And Pills, Anna A. Charles

Theses and Dissertations

"Pricks and Pills" is a collection of audio pieces designed for an online platform where individuals with diabetes can listen to and find emotional support from others who share their experiences. This audio project provides an intimate look into the lives of people navigating the challenges of diabetes. Through heartfelt interviews with individuals and their families, the podcast highlights their journeys, showcasing both their struggles and triumphs.

Can Mirna Be The Missing Link Between Parkinson’S Disease And Pesticides?, Fatma Gobba

Theses and Dissertations

Parkinson’s disease (PD) is a common neurodegenerative condition that leads to significant morbidity and a decline in the quality of life. It develops as a consequence of the loss of dopaminergic neurons in the substantia nigra pars compacta. Nevertheless, the development of PD is influenced by environmental factors, and the intricate nature of these relationships is further complicated by a multitude of factors, including the genetic backgrounds that are specific to populations and variations in environmental exposures, such as pesticides. Pesticides, consisting of a diverse family of chemicals commonly used in both agricultural and household settings to protect crops against …

Impairment Of The Glial Phagolysosomal System Drives Prion-Like Propagation Of Huntington’S Disease, Graham Davis

Theses and Dissertations

The ability of glia to tightly regulate neuronal health and homeostasis in the CNS is conserved across species. Yet, despite the ability to degrade protein aggregates, glia are vulnerable to the accumulation of neurotoxic amyloid aggregates during neurodegenerative disease progress, and even exacerbate their spread. A developing narrative highlights glia as a double-edged sword in neurodegenerative diseases: initially capable of dynamically responding to amyloid aggregate-ladened dying neurons but also capable of inducing chronic inflammation and creating seeding-competent amyloid oligomers. Thus, uncovering the mechanisms that allow glia to control aggregate deposition while preventing the neurotoxic effects and seed generation is vital …

Exploring Drivers Of Sex-Based Disparities In Relapsing Multiple Sclerosis, Stephanie K. Buxhoeveden

Theses and Dissertations

Females are three times more susceptible to relapsing multiple sclerosis (MS) and males typically have more severe disease, but the molecular underpinnings of these sex-based disease disparities are unknown and represent a critical knowledge gap.Subject Population: Blood samples from a demographically homogenous group of treatment naïve males and females with relapsing-MS and healthy controls. Research Design: Cross-sectional combinatorial omics pilot study. Instruments: Whole transcriptomic analysis with messenger RNA (mRNA) expression profiling using next generation sequencing (RNA-seq) and micro-RNA (miRNA) expression using NanoString technology. Aim 1) Identify and compare the actively expressed mRNAs in the transcriptome of males and …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

Cardiometabolic Genomics And Pharmacogenomics In Filipino Americans: A Cross-Sectional Study, Khalifa Y. Alrajeh

Theses and Dissertations

Background: Heart disease remains a leading cause of death in the country, with significant ethnic disparities. Filipino Americans (FAs), the third-largest Asian subgroup in U.S., face an elevated burden of dyslipidemia, a primary modifiable risk factor for heart disease. Objectives: This community-based study addresses critical knowledge gaps by characterizing the cardiometabolic and genetic factors contributing to dyslipidemia among FAs and implications for personalized cardiovascular drug therapies, particularly statin pharmacogenomics (PGx). Methods: We characterized dyslipidemia prevalence in FAs and major ethnic subgroups using nationally representative NHANES data. We examined associations between uric acid (UA) levels and lipid profiles, …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

Chronobiology Of Meal Timing In Early-Stage Hypertension: Effects On Renal And Vascular Function, Natalie J. Bohmke

Theses and Dissertations

Introduction: Previous research determined that a Western-style meal acts as a stressor to the kidney and contributed to impaired blood pressure and vascular function. Despite an understanding of acute postprandial physiology in humans, studies have not investigated the impact of the time of day of meal consumption on physiology. Methods: Ten participants with elevated or stage-one hypertension underwent a randomized crossover trial with a controlled feeding intervention of a Western-style meal in the morning or the evening. Participants completed a run-in day to standardize diet followed by the experimental day. On day 2, participants completed ambulatory blood pressure, core temperature, …

Established Colonization Of Sneathia Vaginalis In A Mouse Model, Kailyn E. Turcios-Gonzalez

Theses and Dissertations

Sneathia vaginalis (Sv) is a gram-negative anaerobic bacterium associated with adverse reproductive outcomes. Sv can traverse the fetal membrane and damage epithelial cells in vitro by producing a pore-forming cytotoxin, cytopathogenic toxin A (CptA). To further understand the transition of Sv from normal flora to a pathogen, an animal in vivo model needs to be created to observe the preliminary ascending infection before we begin to study the effects on pregnancy. Experimentation was conducted to optimize mouse breed, bacteria administration methods, and other variables that arise when working in vivo. The C57BL/6 mouse strain displayed the most consistent …

Nanoformulations Of Essential Oils Extracted From Pistacia Lentiscus And Boswellia Sacra And Investigation Of Their Anticancer, Antimicrobial, And Antioxidant Activities., Obaydah Abd Alkader Alabrahim

Theses and Dissertations

Essential oils (EOs) obtained from natural sources have shown promising biological and therapeutical properties such as anticancer, antimicrobial, and antioxidant activities, attributing to their high content of a variety of bioactive components. However, EOs’ therapeutic properties are limited by their low stability, poor bioavailability, high volatility, and low targeting ability. Therefore, the encapsulation and nanoformulation of EOs can maximize their therapeutical efficiency and physicochemical properties while overcoming their undesirable side effects and drawbacks. EOs extracted from the resins of Pistacia Lentiscus var. Chia (P.oil) and Boswellia Sacra (B.oil) are two promising EOs that have shown great therapeutic potential. P.oil was …

Metabolic Adaptation Of Staphylococcus Aureus Pathogenesis And Therapeutic Approach In Diabetic Foot Ulcers., Carol L. Baker

Theses and Dissertations

37.3 million Americans (11.2% of the US population) currently have Type 2 diabetes mellitus (T2DM) with over 1.5 million new cases being diagnosed each year. The multifactorial etiology of the patient having neuropathy, overweight/obesity, foot deformities, ischemia, and infection leads to a condition called diabetic foot ulcer (DFU). One in six patients with a DFU will require amputation with infected DFUs have a 155-fold increased risk of amputation. Staphylococcus aureus is the most common bacteria isolated from severe DFU infections that require amputation. Interestingly, diabetics are more heavily colonized with S. aureus compared to non-diabetics suggesting a unique advantageous adaptation …

Evaluation Of The Virulence Potential Of Avian Pathogenic Escherichia Coli Isolated From Broiler Breeders With Colibacillosis In Mississippi, Jiddu Joseph

Theses and Dissertations

Avian pathogenic Escherichia coli (APEC) is a bacterium that is responsible for colibacillosis in birds. However, information about broiler breeder APEC isolates is limited, but the data is critical due to the transfer of this bacteria down the production pyramid to progenies resulting in high mortality. Therefore, we evaluated the phenotypic virulence characteristics of 28 isolates using embryo lethality and day-old chick challenge assays. Also, the in vitro adhesion and invasion potential of selected nine isolates were identified. Results showed more than 1/3^rd of the isolates were highly virulent and the virulence increased as the number of virulence-associated genes …

Adherence To A Gluten-Free Diet And Depression, And Nutrient Distribution In Participants With Celiac Disease, Mohammad K. Shushari

Theses and Dissertations

Celiac disease (CD), an autoimmune disorder affecting millions of Americans, poses significant obstacles leading to a normal life. With no known cure, adherence to a strict glutenfree diet (GFD) is essential. However, the cost and limited availability of gluten-free alternatives can burden individuals with CD. Additionally, factors such as socioeconomic status, nutrient deficiencies, and the nature of the disease may contribute to mental health issues. This study aimed to investigate the influence of adherence to a GFD on depression in CD patients. The prevalence of depression among individuals with CD from diverse backgrounds was examined, along with the analysis of …