Chemicals and Drugs Commons^™

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

The Impact Of Biomaterial Characteristics On Macrophage Phenotypes In Tissue Engineering: A Review, Julian Jackson, Hani Samarah, William Palmer, Zachary Kaplan, Marianna Nicodem, Parvesh Kumar, Spenser Short, Kelly Bridgham, Larry Harshyne, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Macrophages are highly plastic cells central to pathogen removal, tissue regeneration, and inflammation, making them key targets in biomaterial design for improved clinical outcomes. Foreign body responses (FBRs) to implanted biomaterials often involve excessive macrophage-mediated inflammation, leading to fibrotic encapsulation, infection, and implant failure. Advances in tissue engineering demonstrate that macrophage polarization - the transition from pro-inflammatory M1 to anti-inflammatory M2 phenotypes - can be influenced by biomaterial properties to mitigate these responses and enhance regeneration. This review synthesizes the relationship between biomaterial properties, such as surface chemistry, structure, and stiffness, and their ability to modulate macrophage behavior. Key innovations, …

A Mean Field Theory For Pulse-Coupled Neural Oscillators Based On The Spike Time Response Curve, Carmen C. Canavier

School of Medicine Faculty Publications

A mean field method for pulse-coupled oscillators with delays used a self-connected oscillator to represent a synchronous cluster of N - 1 oscillators and a single oscillator assumed to be perturbed from the cluster. A periodic train of biexponential conductance input was divided into a tonic and a phasic component representing the mean field input. A single cycle of the phasic conductance from the cluster was applied to the single oscillator embedded in the tonic component at different phases to measure the change in the cycle length in which the perturbation was initiated, that is, the first-order phase response curve …

Determining The Bioaccumulation Of Minor Cannabinoids In Zebrafish Larvae, Kamdyn A. Holt

Honors Theses

Due to the increasing prevalence of cannabis product availability and usage in the modern United States, particularly among pregnant individuals, evaluating the bioaccumulation of minor cannabinoids to further understand the adverse effects of cannabinoids during early development is critical. This study quantitated the uptake of eight minor cannabinoids ((∆8-tetrahydrocannabinol (∆8-THC), ∆9-THC, ∆10-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and hexahydrocannabinol (HHC)) in zebrafish larvae following water-borne 2 µM exposures from 6 to 96 hours post fertilization (hpf). Larvae were homogenized at 96 hpf and analyzed using a gas chromatography- mass spectrometry (GC-MS) method developed in this study. Bioconcentration …

Fluorescent Labeling And Size-Dependent Uptake Of Mesoporous Silica Nanoparticles In Ovarian Cancer Tumor Spheroids, Kimberly R. Berardis

Honors Scholar Theses

Ovarian cancer is the most lethal gynecologic malignancy, with most patients presenting at an advanced stage. While surgical debulking improves survival, nonresectable tumors (<1 cm) contribute significantly to morbidity and remain difficult to treat. Nanocarrier-based drug delivery systems offer an innovative approach to targeted therapy and palliation. In vivo models have demonstrated that intraperitoneally delivered mesoporous silica nanoparticles (MSNs) preferentially accumulate in tumors with low systemic exposure, enabling targeted chemo- and radiotherapy.

MSNs are particularly suited for radiotherapeutic delivery, as their strong interactions with tumor extracellular matrices drive selective uptake. Additionally, they exhibit excellent stability under neutron flux, allowing for loading with stable isotopes and irradiation immediately prior to administration. High radionuclide retention after dilution further minimizes systemic exposure and toxicity.

A key …

Optimization Of Reaction Conditions For Synthesizing Kasa-Targeting Drug Candidates For Tuberculosis Treatment, Megan A. Baxter

Research and Creativity Symposium

Tuberculosis (TB) remains a global health challenge, with increasing drug resistance pressing for the development of novel treatments. KasA, a key enzyme in mycobacterial fatty acid biosynthesis, is a promising drug target for TB treatment. This research focuses on the design and synthesis of potential KasA inhibitors, specifically optimizing reaction conditions to efficiently produce 1-methyl-6-aminoindazole. This molecule is an intermediate in the synthesis of drugs targeting TB. Characterization of synthesized compounds is performed using NMR, mass spectrometry, and gas chromatography to confirm structure and purity. The first step involved optimizing the solvent and base for the methylation of nitroindazole. We …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Lateral Flow Immunoassay Test Strips And Vibrational Spectroscopy For Mobile Detection Of Fentanyl, Sophia Rau

D.U.Quark

There is an increasing number of opioid-related crime scenes, resulting in more evidence that must be tested in a forensic laboratory. New fentanyl analogs are constantly being created, posing significant challenges for drug identification. This increase in drug-related crime and new substances cannot be effectively managed using current forensic technologies. There is a need for on-scene substance testing of unknown substances to improve the speed of testing of collected evidence and for the safety of responders. This review evaluates the impacts of fentanyl test strips, infrared absorption spectrometers, and surface-enhanced Raman scattering spectrometers as portable forensic instruments. The development and …

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …

The Analysis Of Reference Standard Storage Failures Through The Use Of Ibuprofen, Hope Vonder Brink

Honors Projects

Reference standards are commonly used in drug chemistry. They are used to calibrate the instruments and serve as a known point of reference for analysts’ ability to compare unknowns. Drugs can degrade over time or through environmental factors, causing contaminants to be present. In the event of environmental degradation while in storage, such as the exposure to high heat, it would be beneficial to have a database of known breakdown products in common drug reference standards for analysts’ reference. Using ibuprofen as an exemplar drug, this study attempted to identify the thermal breakdown products of ibuprofen and introduce the proposed …

Editorial: Women In Science: Allergy Research, Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

Dosage-Dependent, Carboplatin And Ng52 Show Synergistic Effect On Inhibiting Cell Proliferation In Breast Cancer Cell Line, Ben Couture, Ryan Zhuge

Biology Presentations

BT-549 (Breast Cancer), a highly invasive epithelial breast cancer cell line, was used to investigate the effects of two drugs: NG52, a selective kinase inhibitor and Carboplatin, a platinum-based DNA-alkylating agent. Using cell counting assays and calculating IC50 values, we examined their combined impact on cell proliferation. Results revealed both an antagonistic and synergistic effect dependent on concentration. Where the individual agents inhibited cell proliferation less effectively than expected. These findings show the complexity of drug interactions and provide insights into optimizing therapeutic strategies for highly invasive cancer types.

5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …

Effects Of Hyperglycemia In Cognition And Sex, Erin E. Mcdonald

Senior Honors Theses

An empirical study tested the effects of Type 1 Diabetes (T1D) on cognitive function in a hyperglycemic mouse model. Strong correlations between mental illnesses, such as major depressive disorder, neuropathologies like Alzheimer’s disease, and diabetes suggest comorbid pathology. Considering the prevalence of both T1D and cognitive decline within the general population, the findings were relevant and aimed to identify early signs of cognitive decline in diabetic patients. Behavioral tests and immunohistochemical staining were utilized to determine the cognitive function of the mice, revealing decline or deterioration caused by hyperglycemia. Data gathered from the hyperglycemic or control mice were analyzed based …

Unveiling The Potential Of Urolithin A In Cancer Therapy: Mechanistic Insights To Future Perspectives Of Nanomedicine, Vinita Karumuru, Anupam Dhasmana, Narsimha Mamidi, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Cancer remains a leading global health challenge, with high mortality rates persisting despite significant advancements in therapeutic interventions. Major obstacles, including systemic toxicity, therapy resistance, metastasis, and relapses, emphasize the urgent need for safer, more effective, and readily accessible treatment strategies. Among emerging alternatives, natural bioactive compounds have gained considerable attention because of their diverse therapeutic potential and lower toxicity profiles. Urolithin A (UA), a metabolite derived from ellagic acid through gut microbiota metabolism, has emerged as a compelling anticancer agent. UA has multiple mechanisms of action, including the regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor …

Partnering With Social Media Influencers To Promote Hpv Vaccination In Diverse Communities, Amy Leader, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Preethi Selvan, Kayla Madden, Joshua Banks, Angela Sustaita-Ruiz

Department of Medical Oncology Faculty Papers

BACKGROUND: While human papillomavirus (HPV) vaccination is one of the most effective ways to prevent HPV-related cancers, many children and adolescents remain unvaccinated. Resistance often stems from parental vaccine hesitancy and mistrust of the health care system, both of which may be higher in communities of color. Partnering with social media influencers may be an effective method for disseminating health messages. We tested the impact of HPV social media posts developed by influencers on outcomes of knowledge, attitudes, and intentions to vaccinate.

METHODS: Ten social media influencers who identified as African American or Hispanic created posts about the HPV vaccine. …

The Impact Of An Iron-Rich Diet On Fatigue In Menstruating Women With Non-Anemic Iron Deficiency, Meagan Seraydar, Lauren Latimer, Sam Miragliatto

Department of Nutrition Student Projects

Fatigue without diagnosed anemia is prevalent in menstruating women, with iron deficiency being a potential contributor. While iron supplementation is a standard intervention, dietary sources of iron may offer a sustainable alternative. This study aims to assess the impact of an iron-rich diet on fatigue levels in menstruating women. A 12-week randomized controlled trial (RCT) will be conducted, assigning participants to either an iron-rich diet group or a control group following their usual diet without specific iron recommendations. Fatigue will be measured using the Fatigue Severity Scale (FSS) at baseline, six weeks, and twelve weeks, alongside iron status biomarkers, including …

The Effects Of Stress On Injury And Sickness Rates Of Middle-Distance And Distance D3 Athletes, Hailey D. Smith Ms.

Student Scholar Showcase

A runner intentionally stresses their body to experience an adaptation, however, issues occur when the body does not have time to recover. Male athletes (n = 14) on the University of Lynchburg’s distance and middle-distance team participated in this study. For 6 weeks, heart rate variability (HRV4training app), resting heart rate, perceived stress, and cortisol levels were assessed as indicators of recovery and stress. It was anticipated that indicators of physical stress such as higher resting heart rates and higher cortisol levels, would correspond with greater perceived stress and higher occurrence of injury and sickness. Cortisol (n = 2, p …

Canadian Adolescent And Young Athletes Knowledge Of Pain-Relieving Medications, Jackie Vandertuin, Dalya Abdulla, Stephanie Lowther

Internet Journal of Allied Health Sciences and Practice

Purpose: Adolescent knowledge of pain-relieving medications (PRM) and opioids is scant, particularly from a Canadian perspective. Research indicates that athletes will often resort to PRM and opioids to manage their pain, but it is unknown whether athletes are fully informed as to its use and misuse including adverse events that may occur. The purpose of this study is to understand what elite level male athletes know about use, contraindications, and recommendations of pain-relieving medications; particularly opioids to manage their pain. Methods: Using a qualitative, grounded theory approach, we interviewed male athletes to understand their level of knowledge regarding pain-relieving medications, …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

The Placebo Effect For Opioid Abuse, Carly Longenecker

D.U.Quark

No abstract provided.

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Association Between High Triglyceride-Glucose Index And Macce In Hypertriglyceridemia Patients Undergoing Percutaneous Coronary Intervention, Yichuan Wang, Yanfeng Lu, Shanshan Gao, Zhong Zhong, Jasmine Bao, Bo Liu, Ruihan Fan, Ning Guo

SKMC Student Presentations and Publications

BACKGROUND: With a focus on metabolism-related cardiovascular diseases, the triglyceride-glucose (TyG) index has been used as a surrogate marker of insulin resistance in the prognosis of coronary heart disease. However, the prognostic role of the TyG index in patients with elevated triglycerides, still requires further research. This study aimed to investigate the association between the TyG index and Major Adverse Cardiac and Cerebrovascular Events (MACCE) in patients with hypertriglyceridemia undergoing drug-eluting stent percutaneous coronary intervention (DES-PCI).

METHODS: Out of 2250 patients, 813 with hypertriglyceridemia who underwent DES-PCI were retrospectively analyzed. MACCE was regarded as the primary endpoint. Kaplan-Meier (KM) curves …

A New Paliperidone Palmitate Formulation: How Is It Different And Where Does It Fit In Our Array Of Choices For Long-Acting Formulations Of Risperidone And Paliperidone?, Justin Faden, Leslie Citrome

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Long-acting injectable (LAI) antipsychotics have been shown to enhance treatment adherence and outcomes in individuals with schizophrenia, schizoaffective disorder, and bipolar disorder. In recent years, the U.S. Food and Drug Administration (FDA) has approved several LAIs with differing amenities of care, such as mode of administration, duration of oral medication supplementation, dosing frequency, needle gauge and size, and injection volume, amongst others. Additionally, several LAIs are distinct formulations of risperidone and paliperidone, making it difficult to distinguish between formulations, and many providers are unfamiliar with these newer agents. In 2024, a once-monthly LAI formulation of paliperidone palmitate, manufactured by Luye …

Hdac5 Enzymatic Activity Regulates Scn4b Expression To Control Relapse-Like Cocaine Seeking, Daniel J. Wood

MUSC Theses and Dissertations

Substance Use Disorder (SUD) is a relapsing disorder characterized by repeated seeking and use of psychoactive substances despite negative consequences to the individual. Epigenetic changes within the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) are thought to underly the lasting propensity to relapse in SUD. The epigenetic enzyme histone deacetylase 5 (HDAC5) in NAc MSNs limits the formation of reward-cue associations in rodent models of drug seeking, but not sucrose seeking, leading to decreased relapse-like behavior. However, whether HDAC5 reduces drug seeking behavior through its own deacetylase activity or through the recruitment of co-repressors is unknown. Furthermore, these …

Caveolin-1: An Ambiguous Entity In Breast Cancer, Naveen Chintalaramulu, Dhirendra Pratap Singh, Biplov Sapkota, Dayanidhi Raman, Suresh Alahari, Joseph Francis

School of Medicine Faculty Publications

Breast cancer (BC) is the most frequently diagnosed cancer in women and the second leading cause of death from cancer among women. Metastasis is the major cause of BC-associated mortality. Accumulating evidence implicates Caveolin-1 (Cav-1), a structural protein of plasma membrane caveolae, in BC metastasis. Cav-1 exhibits a dual role, as both a tumor suppressor and promoter depending on the cellular context and BC subtype. This review highlights the role of Cav-1 in modulating glycolytic metabolism, tumor-stromal interactions, apoptosis, and senescence. Additionally, stromal Cav-1's expression is identified as a potential prognostic marker, offering insights into its contrasting roles in tumor …

Implications Of Glyphosate-Based Herbicides On The Female Reproductive System And Reproductive Outcomes, Alexandra Stone, Olivia G. Camp Ms, David Bai Md, Awoniyi Awonuga, Husam M. Abu-Soud

Medical Student Research Symposium

Background

Glyphosate-based herbicides (GBHs) are the most widely used herbicides in the United States, accounting for 19% of estimated global use. Although the Environmental Protection Agency has reaffirmed that the active ingredient glyphosate (GLY) is safe for humans, recent studies on exposure have suggested an association with cancer, metabolic disorders, endocrine disruption and infertility, and Alzheimer’s and Parkinson’s disease. Recently, we have shown that GLY exposure deteriorates metaphase II oocyte quality through zinc deficiency, ROS accumulation, and chromosome disruption. In this work, we review the mechanisms of GLY toxicity in the female reproductive tract and discuss the potential clinical implications …

The Effects Of Diluted Fungicide On Western Tiger Salamander (Ambystoma Mavortium) Health, Sage Veomett

Honors Program: Senior Projects (Public)

The Western Tiger Salamander (Ambystoma mavortium) is a species of salamander that is native to Nebraska. The Western Tiger Salamander population has been in decline, specifically in Southeast Nebraska (Ferraro, 2016). The purpose of this study was to determine whether low levels of Azoxystrobin fungicide deposited in the soil are harmful to the Western Tiger Salamander. In this study, soil in tanks containing pairs of Western Tiger Salamanders was treated with levels of Azoxystrobin 0.5x under the recommended label amount for usage. Fifteen salamanders in total were used. Four tanks of salamander pairs were treated with the Azoxystrobin …

Profit Over Patients: Examining The Influence Of Pharmaceutical Companies On Mental Health Medication Prescriptions, Allison Beltramini

Honors Projects in Biological and Biomedical Sciences

This paper explores the relationship pharmaceutical companies have with the overprescription of mental health medication, highlighting unethical marketing practices and their impact on prescription patterns. Previous literature addresses unethical pharmaceutical company marketing strategies, relationships within the field, and cost differences. This study includes qualitative insights from professionals in the field. Interviews conducted collected information that showed the prevalence of mental health illnesses, how treatments are prescribed, and the extent of pharmaceutical influence. Initial findings suggest a significant push for medication as it is the most common treatment method for mental health illnesses. This study highlights pharmaceutical companies' profit-driven motives and …