Chemicals and Drugs Commons^™

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage

Theses & Dissertations

Ovarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.^1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.

YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a …

Menthalactone From Mentha Piperita L., A Monocot-Selective Bioherbicide, Adam Soltani

Honors Theses

The challenge of managing invasive weed species continues to affect the agricultural industry, presenting ecological, economic, and agronomic hurdles that lead to over 100 billion USD in annual crop losses globally. One such concern is the management of Agrostis stolonifera L., commonly known as creeping bentgrass, particularly due to its ability to form hybrids. This scenario underscores the urgent need for innovative, effective, and environmentally sustainable herbicides, steering the focus toward natural substances as potential candidates. We report here a promising natural lactone, commonly known as menthalactone, which is derived from Mentha piperita L. Its phytotoxic activity was assessed against …

Impaired Dnajb2 Response To Heat Shock In Fibroblasts From A Neuropathy Patient With Dnajb2/Hsj1 Mutation: Cystamine As A Potential Therapeutic Intervention, Raj K. Pradhan, Nikolas G. Kinney, Brigid K. Jensen, Hristelina Ilieva

Farber Institute for Neuroscience Faculty Papers

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase …

Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (Acan^CreERT2; Sirt6^fl/fl). Histological studies showed a degenerative phenotype in knockout mice …

Effects Of Novel Dopamine D4 Receptor-Targeted Compounds On Locomotor Activity And Anxiety-Like Behavior In Male And Female Sprague Dawley Rats, Samantha Alyse Walkow, Noah A. Ivak, Daniel Chandler, John Tkaczynski, Thomas M. Keck, Comfort A. Boateng, Eleni Papadopoulos, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was …

Investigating Fatty Acid Influence On West Nile Virus In Mosquitoes And Birds, Hayley Moree

Honors Program: Senior Projects (Public)

Vector-borne diseases, including Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), pose considerable global health threats, accounting for over 400 million infections and more than 700,000 deaths annually. Many vector-borne diseases are within the Flaviviridae family. Despite this, effective treatments have not been found for some flaviviruses. Flaviviruses exploit host cellular machinery to facilitate their replication and survival, reprogramming metabolic pathways, including lipid metabolism. Lipids play essential roles in the viral life cycle, providing structural components for the viral envelope, enabling membrane rearrangements for replication complexes, and supplying energy resources necessary for particle assembly.

Targeting lipid metabolism …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …

Effects Of The Non-Stimulant Norepinephrine Reuptake Inhibitor, Atomoxetine, On Cognitive Flexibility In Healthy Adult Long-Evans Rats, Noah A. Ivak, Samantha Walkow, Christopher Knapp, Eleni Papadopoulos, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua Research Day

Executive function is the control of multiple higher order cognitive processes that include attention, working memory, and cognitive flexibility. Cognitive flexibility is the ability to shift behavioral strategies

in response to changing environmental demands and task complexity. This cognitive modality is often impaired in many neuropsychiatric disorders like attention deficit hyperactivity disorder (ADHD). Deficits in cognitive flexibility are associated with dysregulation of the catecholamines, norepinephrine (NE) and dopamine (DA) within the prefrontal cortex (PFC). Atomoxetine (ATX), a non-stimulant NE reuptake inhibitor, elevates levels of NE and DA in the PFC by inhibiting the norepinephrine transporter (NET). ATX is used to …

Antiproliferative Effects Of Salvia On Breast Cancers., Allison C. Portaro

College of Arts & Sciences Senior Theses

Breast cancer is the most common cancer diagnosed in female adults, with 2.3 million new cases worldwide in 2020. Plants have been used in traditional medicine and are a potential source of pharmaceuticals. One example is the large Lamiaceae (mint) family. The Salvia genus, commonly known as the sages, is the largest genus in Lamiaceae with almost 900 known species. Salvia lyrata (lyre-leaved sage) has a history of Native American medicinal use to treat cancers and other ailments resulting in this plant being referred to as ‘cancer weed.’ Extracts were produced from the leaves of S. lyrata, S. lyrata …

Acetylcholine Release In The Dorsal Lateral Straitum During Social Approach Task, Taylor Good, Oyku Dinckol, Noah Wenger, Jake Caselli, Munir Gunes Kutlu

Rowan-Virtua Research Day

Nicotine Decreases ACh Release in the DS leading to a Serenic Effect during Social Approach Task

Acetylcholine (ACh) regulates attention, learning, and stress responses (Benarroch E. E., 2012). The dorsal striatum (DS), essential for stimulus-response learning, is also linked to anxiety and compulsivity (Casado-Sainz et al., 2021). We used behavioral pharmacology and in vivo fiber photometry to study ACh responses during social approach tasks in the dorsal striatum. Male and female C57BL/6J mice underwent stereotaxic surgeries to inject a fluorescent ACh sensor (ACh.Sn.Fr) and implant fiber optic cannulas in the DS. Using in vivo fiber photometry, we tracked ACh release …

Investigating The Effects Of Prenatal E-Cigarette Exposure On Postnatal Liver Histology, Emma Mcclellan

College of Arts & Sciences Senior Theses

The electronic cigarette (e-cigarette) entered the American market in the mid-2000s and quickly became popular. This product poses a significant threat to youth with 1.63 million students reporting use in 2024. Adverse health effects to different organs are well known. The liver is less studied, and despite its role in detoxification of e-cigarette chemicals, is a target of injury. Unlike the known effects of cigarettes and nicotine on the liver from adult or prenatal exposure, effects of prenatal exposure to e-cigarettes on liver remain to be defined. The current study investigated the effects of prenatal exposure of e-cigarettes on liver …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Mechanistic Investigation Of Ring-Opening Polymerization Of Polycaprolactone Using Tin(Ii) Catalysts: Ligand Effects And Biomedical Applications, Eva-Larue M. Barber

Honors Scholar Theses

This research explores the mechanistic aspects of ring-opening polymerization (ROP) of ε-caprolactone (CL) to produce polycaprolactone (PCL), a biodegradable polymer widely used in biomedical applications. The study investigates how light exposure and catalyst concentration influence polymerization efficiency, using tin(II) 2-ethylhexanoate [Sn(Oct)₂] as the catalyst in a non-polar toluene solvent at 90 °C. Reactions were conducted under either ambient light or black light bulb (BLB) illumination, with monomer-to-catalyst ratios of 1:1 and 200:1.

Proton nuclear magnetic resonance (¹H NMR) spectroscopy was used to analyze conversion efficiency by tracking the disappearance of monomer signals and appearance of characteristic PCL peaks. Results revealed …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

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 …

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 …

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 …

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 …

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 …

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 …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay

School of Medicine Publications

Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease’s impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying …

Antituberculosis Potential Of Borrelidin Derivatives: An In Silico Molecular Docking And Molecular Dynamic Approach, Teni Ernawati, Donny Ramadhan, Faris Hermawan, Sasmito Wulyoadi, Bambang Marwoto, Ahmad Wibisana, Bambang Srijanto

The Thai Journal of Pharmaceutical Sciences

Background: The present tuberculosis (TB) treatment requires a significant time commitment, often lasting from 6 months to 2 years, with strict daily adherence. Non-compliance leads to drug resistance and suboptimal outcomes. Present research indicates that borrelidin shows potential activity against Mycobacterium tuberculosis, including strains that are resistant to first-line medications. Borrelidin has shown remarkable activity against M. tuberculosis H37Rv, with a minimum inhibitory concentration value of 3.12 μg/mL. Therefore, investigating the inhibition activity of borrelidin derivatives was essential for finding new anti-TB candidates. Objectives: This study aims to investigate the effects of 31 borrelidin derivative compounds …