Chemicals and Drugs Commons^™

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Gz17.602, A Combination Of Three Nutraceuticals, Interacts With Carboplatin And Etoposide To Kill Neuroblastoma, Michael R. Booth

Theses and Dissertations

This study examined the efficacy of GZ17.602, a combination of Harmine, Isovanillin, and Curcumin as a therapeutic for MYCN-amplified Neuroblastoma, both alone and in combination with standard of care chemotherapeutics. This was done due to the low survival rate associated with these neuroblastomas, the large degree of morbidity associated with current treatments, previous experiments in the Dent lab having shown 602 as effective for killing cancers of other types, and the current lack of understanding of the biology of GZ17.602 in solid pediatric cancers. Due to the GZ17.602 components being present at different concentrations in tumors than those administered, the …

The Myopia Epidemic: Integrating Genetic, Environmental, And Epigenetic Pathways To Define A Critical Window For Intervention, Pranavika Balaji

UROP Posters

Myopia, or nearsightedness, has increased rapidly worldwide and is now a major public health concern caused by both genetic and environmental factors. Current understanding shows that too much near work, limited time spent outdoors, and prolonged screen use contribute to abnormal eye growth in individuals who may already have a genetic predisposition. At the molecular level, epigenetic changes and shifts in DNA activity, often influenced by environmental conditions, affect the signaling pathways that regulate eye development and may help explain why myopia is increasingly common among children. This paper synthesizes recent environmental, genetic, and epigenetic research to explain how these …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk, Yasir A. Alshehry, Matthew S. Halquist Phd, Sandro R.P. Da Rocha Phd

Graduate Research Posters

Background

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance …

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 …

A Model Of Oocyte Population Dynamics For Fish Oogenesis, Louis Fostier, Frédérique Clément, Romain Yvinec, Violette Thermes

Biology and Medicine Through Mathematics Conference

No abstract provided.

Fentanyl And Methamphetamine Mixture Interactions On Drug Choice In Male And Female Sprague Dawley Rats, Voisava Bokciu, Nick Heslep, Allison Ortiz, Matthew L. Banks Phd

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

Improving Medication-Enhanced Psychotherapy Options For Ptsd: The Potential Of Oxytocin As A Treatment For Hypervigilance In Women With A History Of Childhood Sexual Abuse And Related Ptsd, Elianna Bavuso

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Childhood sexual abuse (CSA) is a notable public health concern, affecting a significant proportion of girls in high-income countries. A considerable number of CSA survivors develop Post-Traumatic Stress Disorder (PTSD) by adolescence, which is often considered to be a lifelong disorder with severe emotional and social consequences. Women with CSA-related PTSD display hypervigilance, which is characterized by significantly increased fear network activity and poor top-down control over the amygdala. This meta-analysis examines the potential of intranasal oxytocin (OT) as a treatment for hypervigilance symptoms in women with CSA-related PTSD. The evidence reviewed suggests that intranasal oxytocin can help normalize the …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Revealing The Elusive Mechanism Of Action Of The Lipid Chaperone Fatty Acid Binding Protein 4, Abdul J. Castillo Ibanez

Theses and Dissertations

Fatty acid binding proteins (FABPs) are pivotal in orchestrating lipid trafficking within cells. This dissertation aims to reveal the mechanism of action of adipocyte FABP (FABP4) by meticulously detailing steps for producing uniformly isotopically labeled protein, understanding dynamics and structural changes in aqueous conditions, analyzing protein-membrane interaction with membrane mimicking models, and revealing its membrane-bound state through novel NMR structural elucidation. Chapter 1 provides an overview of FABP4's indispensable role in lipid trafficking, emphasizing its significance in maintaining cellular homeostasis and metabolic regulation. Chapter 2 delves into the optimization of FABP4 protein expression and proposes a high yield recovery and …

Continuous Flow As A Process Intensification Tool For The Preparation Of Pharmaceutically Relevant N-Heterocycles, John W. Tomlin Jr

Theses and Dissertations

Continuous flow as a process intensification tool for the preparation of pharmaceutically relevant N-heterocycles

John W. Tomlin

Thesis Defense: 17 January 2024

Committee: B. Frank Gupton, Ph.D. (Advisor), Suzanne M. Ruder, Ph.D. (Chair), Heather R. Lucas, Ph.D., James K. Ferri, Ph.D., Matthew C.T. Hartman, Ph.D.

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

© 2024 John W. Tomlin Jr All Rights Reserved

Abstract

Essential medicines must be produced in large quantities to accommodate large global demand. The preparation of these active pharmaceutical ingredients (API) must therefore strive to be both cost-effective …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

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

UROP 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 …

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

UROP 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 …

Isoprenylation Inhibition Suppresses Fcεri-Mediated Mast Cell Function And Allergic Inflammation, Aditya Kotha, Jordan M. Dailey, Aslamuzzaman Kazi, Said Sebti, John J. Ryan

UROP Posters

Allergic disease is driven by cell signaling cascades that activate immune cells. One key player is mast cells, which is activated by IgE antibodies signaling through the high affinity IgE receptor, FceRI. Therefore, targeting FceRI-mediated cascades can offer for novel treatments for allergic disease. Statins have been demonstrated to reduce the severity of asthma, a common allergic airway disease. Statins are an FDA approved class of drugs with the intended purpose of lowering blood cholesterol. We previously found that while statins inhibit mast cell function in allergic disease, these anti-inflammatory effects vary widely amongst differing mouse strains and human donors, …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Testing The Efficacy And Synergistic Components Of Sesamol And Black Rice Extract On Human Colon Cancer Cells, Sera Lim, Philip M. Gerk

UROP Posters

Purpose: Systemic treatment of colorectal cancer involves chemotherapeutic agents which elicit serious and negative side effects from the toxicity of the drug. To address this issue, we are testing dietary supplements for their efficacy against human colon cancer cell lines and also their potential synergistic effects when combined with conventional chemotherapy. Dietary supplements (specifically sesamol and black rice extract) exhibit anticancer, anti-inflammatory, and chemo-preventive properties. Meanwhile, one of the cancer resistance mechanisms is the upregulation of drug elimination mechanisms, leading to multi-drug resistance. We hypothesize that dietary compounds will act as chemo-enhancers, thus enhancing potency of the chemotherapy drug(s) on …

Assessing Drug Development Proporties Of Antithrombotic And Anti - Cancer Agents, Elsamani I. Abdelfadiel

Theses and Dissertations

The current GAG anticoagulants such as heparin, heparin derivatives, and vitamin K antagonists, such as warfarin continue to be the backbone of anticoagulant therapy. These drugs act through an indirect mechanism to convey inhibition of several coagulation enzymes. However, xv their use leads to several serious adverse effects, such as excessive bleeding risk and unpredictability of patient response. Regardless of their clinical achievement, every individual agent is accompanied by several side effects, particularly major/minor bleeding, thrombocytopenia, drug-food or drug-drug interactions, or absence of antidote. Of all these side effects, bleeding, and a lack of an effective antidote to reverse excessive …

Hydroxyapatite Toothpaste On Caries Prevention In Children, Samantha Richardson, Kelly Vaughan

Dental Hygiene Student Scholarship

Are Hydroxyapatite Toothpastes The Answer To Fluoride Free Patients?

Richardson, Samantha 1 and Vaughan, Kelly 2

Dental Hygiene Program, Virginia Commonwealth University

Abstract:

Objectives/Aims: With the rising trend to become more clean with our ingredient lists, we are facing more patients refusing fluoride treatments and fluoridated toothpastes. This trend has been prevalent in our younger generations due to parents only wanting the purest natural ingredients for their children and now declining fluoride application. The goal of this literature is to find a safe alternative toothpaste that will be just as effective as fluoride.

Methods: This review of literature has been …

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

IRBEH/Spit for Science Publications and Presentations

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 …

The Water Solubility Of Ursolic Acid Complexes At Different Choline Concentrations, Sera Lim, Renjie Zhan, Phillip M. Gerk

UROP Posters

No abstract provided.

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

UROP Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook

Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Comparison Of Free Versus Encapsulated Drugs On 3t3 Differentiation, Simon H. Friedrich, Gabriel Volpe

UROP Posters

The scope of this project was to design, synthesize and test targeted nanoparticles containing hydrophobic and hydrophilic drugs that promote browning in adipose tissue. For hydrophilic drugs the use of liposomes and their hydrophilic core is more useful than the PLGA nanoparticles which have hydrophobic cores. The inhibition of the FOXO1 pathway and modulation of autophagy in adipose tissue can promote browning of white adipose tissue, or an energy burning state where excess energy is burned as heat instead of stored in the cell. If successful, these drugs would offer an alternative treatment for obesity where changes to the patient's …

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 …

Antiviral Effects Of Metalloshielding: Differential Antiviral Activity Of Polynuclear Platinum And Cobalt Compounds, Mary Zoepfl

Theses and Dissertations

The majority of antiviral drug development has focused on virus-specific discovery targeting discrete steps in the individual life cycles. Although great strides have been made for a number of clinically relevant diseases such as human immunodeficiency virus, influenza virus, and hepatitis B, broad spectrum antivirals do not exist. Broad spectrum antivirals would offer (1) treatment for viruses without specifically-targeted antivirals, (2) treatment for viruses which have developed resistance to their available treatments, and (3) a rapidly deployable treatment option in viral epidemics. Many viruses including human cytomegalovirus (HCMV), HIV, and SARS-CoV-2. rely on heparan sulfate (HS), a highly sulfated glycosaminoglycan …

Examining The Behavioral And Phyisiolgical Effects Of D-Methamphetamine Administered Via E-Cigarette Aerosolization, Srikethan Mahavadi

Theses and Dissertations

Abstract

EXAMINING THE BEHAVIORAL AND PHYISIOLGICAL EFFECTS OF D-METHAMPHETAMINE ADMINISTERED VIA E-CIGARETTE AEROSOLIZATION

By Srikethan Mahavadi, B.S.

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

Virginia Commonwealth University, 2021

Principal Investigator: Dr. Keith Shelton, PhD., Department of Pharmacology & Toxicology

E-cigarettes have become increasing popular worldwide. They are primarily used as a means to deliver nicotine to users, but these devices may also be used to administer a wide range of other substances including psychomotor stimulants such as d-methamphetamine. Methamphetamine has been widely abused throughout the United States …

Protein Structure And Interaction: The Role Of Aromatic Residues In Protein Structure And Interactions Between Pyridoxine 5'-Phosphate Oxidase/Dopa Decarboxylase, Mohammed H. Al Mughram

Theses and Dissertations

Naturally developed proteins are capable of carrying out a wide variety of molecular functions due to their highly precise three-dimensional structures, which are determined by their genetically encoded sequences of amino acids. A thorough knowledge of protein structures and interactions at the atomic level will enable researchers to get a deep foundational understanding of the molecular interactions and enzymatic processes required for cells, resulting in more effective therapeutic interventions. This dissertation intends to use structural knowledge from solved protein structures for two distinct objectives.

In the first project, we conducted a bioinformatics structural analysis of experimental protein structures using our …