Chemicals and Drugs Commons^™

Safety Evaluation Of Epicertin, An Oral Biotherapeutic Candidate For Treating Ulcerative Colitis: A 28-Day Repeated Dose Toxicity Study., Jimmy Fernando Cifuentes Jimenez

Electronic Theses and Dissertations

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic, relapsing inflammation of the colon and rectum with limited treatment options. Among them, immunosuppressive agents have a high rate of adverse side effects and do not cure the disease. EPICERTIN (EPT), a recombinant variant of the cholera toxin B subunit (CTB) with a C-terminal hexapeptide extension consisting of a KDEL endoplasmic reticulum (ER) retention motif, is a promising oral biotherapeutic candidate for the treatment of UC. EPT has demonstrated mucosal healing activity in mouse models of colitis and human colonic explants. EPT's mechanism of action involves binding to GM1 …

Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos

School of Graduate Studies Faculty Publications

Leukemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) known for its specificity toward Ras homolog family member A (RhoA). LARG plays a crucial regulatory role in various cellular processes such as migration, proliferation, invasion, and metastasis by facilitating the exchange of GDP to GTP on RhoA. Phosphorylation of LARG at S1288 by ribosomal S6 kinase 2 (RSK2) promotes RhoA activation. However, the precise mechanism remains unclear. Here, we demonstrate the essential role and mechanism by which S1288 phosphorylation facilitates LARG-mediated invasiveness in response to epidermal growth factor (EGF). Upon EGF stimulation, RSK2 phosphorylates LARG at S1288, thereby promoting …

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

Decomposition Processes And Insect Indicators In Forensic Investigations, Eli Taylor

University Honors Theses

Insects play an essential biological and ecological role in human life, and their predictable relationship with decomposing remains has positioned them as a cornerstone of modern forensic science. Since the early 20th century, forensic entomology has provided critical evidence for estimating the postmortem interval (PMI), relying on patterns of colonization, species succession, and insect developmental timelines. Accurate PMI estimations are vital to medicolegal investigations, influencing the interpretation of biological evidence, guiding resource allocation, and informing determinations of cause and manner of death. However, insect activity is profoundly shaped by environmental and ecological variables, including temperature, humidity, seasonal shifts, and geographic …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy Grossman, Zhen Zhao

Student Papers, Posters & Projects

BACKGROUND: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

PATIENTS/MATERIALS AND METHODS: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Protrack3d: A Comprehensive Tool For Segmentation And Tracking Of Proteins With Split And Fusion, Ramu Gautam, Yang Jiao, Yasong Pang, Mo Weng, Mei Yang

Electrical & Computer Engineering Faculty Research

Background: Quantitatively tracking subcellular protein puncta over time is critical for understanding protein functions and related cellular processes, as many proteins assemble into discrete protein puncta when performing functions. Monitoring these protein puncta over an extended period enables the quantitation of their dynamic behaviors, such as repositioning, remodeling, and inter-object interactions such as fusion and split. These characteristics are essential for deciphering the underlying regulatory mechanisms of protein function. However, tracking protein puncta is challenging due to these clusters undergoing rapid and complex temporal changes.

Results: To address these challenges, a comprehensive tool ‘ProTrack3D’ is developed. It implements a multi-stage …

Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

Guide For Selecting Experimental Models To Study Dietary Fat Absorption, Andromeda M. Nauli, Ann Phan, Karen Mai, Kathleen Tran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, …

High Phosphorus Intake: The Role Of Phosphorus And Health Outcomes Through The Lens Of High Phosphorus Additive Intake, Taigen M. Mayes

Senior Honors Theses

Phosphorus is a commonly consumed mineral in the traditional human diet and plays an essential role in human physiological functions. With the use of phosphate additives, high phosphate intake has become increasingly prevalent in recent years. Phosphate is regulated in the body by a homeostasis mechanism. A disruption to the homeostasis has a link to various pathologies such as bone health, cardiovascular disease, cancers, and kidney issues. Various studies have investigated the role of phosphate and its effects on human function. Bone health, cardiovascular disease, cancer, premature aging, dementia, and kidney disease are linked with high phosphorus intake.

Semaglutide Use Before Single-Level Lumbar Fusion Associated With Fewer Readmissions And 90-Day Costs, Mitchell K. Ng, Paul G. Mastrokostas, Ariel N. Rodriguez, Abigail Razi, Leonidas E. Mastrokostas, Ahmed K. Emara, Brian T. Ford, Jacquelyn J. Xu, Jonathan Dalton, Rajkishen Narayanan, Christopher K. Kepler, Alan S. Hilibrand, Alex R. Vaccaro, Jad Bou Monsef, Afshin E. Razi

Rothman Institute Papers

CONTEXT: Semaglutide, a glucagon-like protein-1 receptor agonist used in diabetes and obesity management, has demonstrated perioperative benefits in other surgical populations. However, its role in spine surgery remains unclear.

AIMS: This study aims to evaluate whether patients undergoing single-level lumbar fusion demonstrate: (1) fewer medical complications; (2) surgical complications; and (3) healthcare utilization as measured by readmissions and costs.

SETTINGS AND DESIGN: A retrospective cohort study using a national claims database from 2010 to 2021.

SUBJECTS AND METHODS: Patients with diabetes mellitus undergoing single‑level lumbar fusion were identified and matched 1:5 using propensity scores based on age, sex, body mass …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al

School of Medicine Faculty Publications

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥ 7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams

School of Medicine Faculty Publications

Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …

Citronellol Reduces Sepsis-Induced Renal Inflammation Via Ap-1/Nf-Κb/Tnf-Α Pathway, Huda Rashid Atiyah, Sarmed H. Kathem, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sepsis is characterized by the over-production of pro-inflammatory cytokines. Cecal ligation and puncture (CLP) is a well-accepted model for recreating sepsis-induced renal injury in mice. The current study investigates how citronellol, a naturally occurring substance with a variety of biological characteristics, can prevent acute kidney inflammation brought on by CLP. In the CLP mouse model, citronellol was administered orally at doses of 50 and 100 mg/kg. Serum levels of creatinine and urea were used as markers of renal function, and the Murine Sepsis Score (MSS) was used to assess the severity of sepsis. According to our findings, CLP caused a …

Estrogen And Obesity Synergistically Suppress Protein S Via Hif1Α, Enhancing Thrombosis Potential, Mohammad A. Mohammad, Narender Kumar, Sonali Ghosh, Ashley L. Paysse, Claudia Leonardi, Vijaya Pilli, Ma Lorena Duhaylungsod, Eric Lazartigues, Diana Polania-Villanueva, Sadaf Nouman, Logan A. Barrios, Rima Chattopadhyay, Rafika Yasmin, Alaina Guilbeau, Manoj Kumar, Tina H. Nguyen, Jovanny Zabaleta, Li Li, Luis Del Valle M.D., Mallory T. Barbier, Samarpan Majumder, Laurent O. Mosnier, Samarpan Majumder

School of Graduate Studies Faculty Publications

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality, with risk heightened in premenopausal women with obesity or use estrogen-based oral contraceptives. When both risk factors are present, the thrombosis risk increases substantially. Protein S (PS), an essential anticoagulant cofactor, is downregulated by both estrogen and obesity, but the molecular basis for this suppression remains poorly defined. We investigated the effect of estrogen and obesity on PS expression using plasma samples from 157 women stratified by BMI and contraceptive use, alongside 40 mice categorized as lean or obese with or without estrogen pellet treatment. The levels of PS …

Intercellular Signaling And Synaptic Deconstruction Uncovered By Single-Cell And Spatial Transcriptomics In An Ad Tauopathy Model, Jeff X. Ji, Brian L. Giles, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Alasdair P. Masson, Sonia Do Carmo, A Claudio Cuello, Nicolas G. Bazan

School of Medicine Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this …

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

Rabies Virus-Vectored Lyme Disease Vaccine Provides Long-Term Protection Against Tick-Transmitted Borrelia Burgdorferi, Shantel Rios, Bibek Bhattachan, Christoph Wirblich, Anisha Chandwani, Kruthi Vavilikolanu, Jacob F. Myers, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. …

Targeted Injection Therapies For Temporomandibular Joint Disorders: A Comparative Review Of Hyaluronic Acid And Botox Techniques, Timothy Alexander, Marissa Siegel, Noah Schnoor, Elizabeth A. Starns

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: This study aimed to evaluate the effectiveness of different injection therapies for temporomandibular joint disorders (TMD) and answer the research question: how do botulinum toxin (onabotulinumtoxinA, Botox) and hyaluronic acid (HA) injections affect symptoms of temporomandibular joint disorder (TMD)? Methods: An electronic search of three databases was performed using the search terms “Treatment of TMD or TMJ” and one of the following: 1) “Hyaluronic Acid Injection” or 2) “Intramuscular Botox Injection”. Based on studies done with human patients, the effects of both hyaluronic acid and Botox injections as treatments for TMD were observed and analyzed. Inclusion criteria were: full …

Environmental Modulation Of Jak3-Mediated Immune Dysregulation In Alopecia Areata, Rylee Davis

Sustainability Conference

Alopecia areata (AA) is an autoimmune disorder characterized by non-scarring hair loss resulting from T-cell–driven destruction of hair follicles. Central to this process is the dysregulation of Janus kinase 3 (JAK3), a non-receptor tyrosine kinase selectively expressed in hematopoietic cells that mediates γc cytokine receptor signaling. Aberrant JAK3 activity disrupts follicular immune privilege and amplifies pro-inflammatory cytokine cascades, sustaining a chronic autoimmune state. While genetic susceptibility contributes to JAK3 overactivation, converging evidence highlights a pivotal role for environmental exposures in modulating its expression and signaling dynamics. In this framework, we focus on urban air pollutants like particularly fine particulate matter, …