Diseases Commons^™

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 …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) Infection By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4⁺ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

Evaluation Of Spliceai For Improved Genetic Variant Classification In Inherited Ophthalmic Disease Genes, Melissa Reeves

Theses and Dissertations

ABSTRACT

EVALUATION OF SPLICEAI FOR IMPROVED GENETIC VARIANT CLASSIFICATION IN INHERITED OPHTHALMIC DISEASE GENES

By Melissa Jean Reeves, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2023

Major Director: Melissa Jamerson, PhD, MLS(ASCP)

Associate Professor, Department of Medical Laboratory Sciences

Inherited ophthalmic diseases impact individuals around the globe. Inherited retinal diseases (IRDs) are the leading cause of blindness in individuals aged 15 to 45. The personal, social, and economic impact of vision loss is profound. Due to individual differences, symptoms can be variable, and …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter

Biology and Medicine Through Mathematics Conference

No abstract provided.

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay

Theses and Dissertations

The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …

Molecular Basis Of Cross-Sensitization In Colonic Inflammation-Induced Somatic Hypersensitivity, Parshva K. Mehta

Theses and Dissertations

A major portion of pain experienced by patients with an Irritable Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) can be attributed to visceral hypersensitivity. Visceral stimuli transmitted through primary afferent neurons in the dorsal root ganglia (DRG) induce a nociceptive response. Notably, a subset of patients has also experienced the development of somatic pain, such as leg pain, after diagnosis of a bowel disorder. The aim of this investigation is to ascertain which biochemical mediators are involved in the development of such viscerosomatic cross-sensitization. Initially, the Von Frey Test was used to find behavioral evidence of somatic referred pain; …

Ectopic Pregnancy In A Woman With T9 Ais A Paraplegia Secondary To High-Grade Spinal Cord Pilocytic Astrocytoma, Elisabeth K. Acker

Graduate Medical Education (GME) Resident and Fellow Research Day Posters

Ectopic pregnancy in a woman with T9 AIS A (motor complete, sensory complete) paraplegia secondary to a high-grade spinal cord pilocytic astrocytoma

Background

In the United States, 20,000 women of childbearing age have a spinal cord injury (SCI). While SCI induces transient amenorrhea immediately after injury, women generally have normal reproductive function after SCI, and their fertility is unimpaired. Medications that commonly manage complications of SCI should be avoided or discontinued during pregnancy. Complications inherent to SCI, including urologic issues, are often exacerbated during pregnancy.

Methods

This is a case report on a female Veteran who initially presented to the …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

The Effects Of An Inflammasome Inhibitor Olt1177 On The Development Of Ischemic Heart Failure, Joseph S. Aliaga

Theses and Dissertations

Thesis Abstract

THE EFFECTS OF AN INFLAMMASOME INHIBITOR OLT1177 ON THE DEVELOPMENT OF ISCHEMIC HEART FAILURE

By Joseph S. Aliaga, BS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2020

Background: Evidence suggests that prolonged and enhanced pro-inflammatory signaling, modulated by the NLRP3 inflammasome, plays a crucial role in the pathophysiology of several different types of cardiovascular diseases such as acute myocardial infarction (AMI), adverse ventricular remodeling, and heart failure (HF). Consequently, we hypothesize that attenuating the enhanced inflammatory response using a pharmacological NLRP3 …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey

Undergraduate Research Posters

The aim of this study is to observe cell proliferation, cell viability, apoptosis, and autophagy on acute myeloid leukemia (AML) cell lines, NB4 and U937, with the drug repurposing of mefloquine (MQ). Methods such as the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and trypan blue staining have shown a decrease in live cells with high concentrations of mefloquine. Using their average perspective IC50 values of MQ concentration, Western blotting was applied by means of apoptosis and autophagy markers to determine if the induction of apoptosis and inhibition of autophagy was present in MQ-treated AML cells. The experiment will be continued with more …

Usefulness Of The Captia Syphilis Igg Eia Test Method And Reverse Algorithm For Detection Of Syphilis Infection In A Public Health Setting, Patricia Armour

Theses and Dissertations

Syphilis, a systemic sexually transmitted disease, is on the rise in the US, with infection rates the highest recorded since 1994 according to the CDC. Useful laboratory testing is an important diagnostic tool for determining individual syphilis infection and preventing community-wide disease spread.

The purpose of this study was to determine the usefulness of a specific automated treponemal test method, the Captia^TM Syphilis IgG EIA, and the syphilis reverse algorithm interpretation for detecting syphilis infection among patients seeking care in a public health clinic. The study employed a retrospective, nonexperimental descriptive correlational design with data collected between 2012-2013 from …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Researching The History Of Hiv/Aids: An Interview With Christopher Ewing, Emily Furlich

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

Uncertainty Of 1-D Fluid Models In Patients With Pulmonary Hypertension, Mitchel J. Colebank

Biology and Medicine Through Mathematics Conference

No abstract provided.

Commonly Used H1 And H2 Histamine Receptor (Hr) Blockers Decrease Cholangiocarcinoma Xenograft Tumor Growth, Angiogenesis And Emt, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Walker Karstens, Steven Smith, Heather Francis

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Regulation Of Biliary Progenitor Cell Proliferation By Hedgehog Signaling In In Vivo And Ex Vivo Organoid Models, Nataliya Razumilava M.D., Junya Shiota M.D., Ramon Ocadiz-Ruiz Ph.D., Nureen Hanisah Mohamad Zaki, Kais Zakharia M.D., Michael Mathew Hayes, Juanita Lynn Merchant M.D., Ph.D.

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Short And Long Chain Free Fatty Acids Differentially Regulate Glucagon-Like Peptide-1 And Peptide Yy Transcript Levels In Enteroendocrine Cells (Stc-1), Colin M. Catherman

Theses and Dissertations

The regulation of glucagon-like peptide-1 and peptide YY hormone levels are regulated based on different influential factors, but primarily levels are dependent upon ingested food content. As meals today become more fat-enriched, there is greater requirement for evaluation of these hormones that regulate insulin and satiety levels within the body. We have shown that the gene expression transcript production of glucagon-like peptide-1 and peptide YY are modulated by different concentrations, and times of short-chain fatty acids and long-chain fatty acids. Although the peptide hormone levels have the influential physiological role on effector tissue, the regulation of these hormones begins at …

Reverse Engineering A Kinetic Model Of A Dopaminergic Neuron To Apoptosis, Johnathan Morris

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.