Chemicals and Drugs Commons^™

Ensemble-Based Binding Free Energy Profiling And Network Analysis Of The Kras Interactions With Darpin Proteins Targeting Distinct Binding Sites: Revealing Molecular Determinants And Universal Architecture Of Regulatory Hotspots And Allosteric Binding, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allostery remain poorly understood. In this study, we employ microsecond molecular dynamics simulations, mutational scanning, and binding free energy calculations together with dynamic network modeling to dissect how engineered DARPin proteins K27, K55, K13, and K19 engage KRAS through diverse molecular mechanisms ranging from effector mimicry to conformational restriction and allosteric modulation. Mutational scanning across all four DARPin systems identifies a core set of evolutionarily constrained residues …

Cross-Sectional Analysis Of Wound-Associated Soluble Factors In Early, Established, And Chronic Wounds Of Recessive Dystrophic Epidermolysis Bullosa Patients, Vitali Alexeev, Leonie Huitema, Taylor Phillips, Paras Patel, Mauricio Garza, Franziska Ringpfeil, Julio Salas-Alanis, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds represent the primary health-related burden for hereditary recessive dystrophic epidermolysis bullosa (RDEB) patients. Contribution of wound-associated soluble constituents to wound progression remains not well defined.

OBJECTIVE: To conduct cross-sectional analysis of cytokine, chemokine, and growth factor in exudates from RDEB wounds and define changes associated with wound progression.

METHODS: Concentrations of selected cytokines, chemokines, and growth factors were evaluated by multiplex ELISA in eight blister fluids and 66 exudates from early, established, and chronic RDEB and five chronic venous ulcers (VU). A cross-sectional analysis was performed.

RESULTS: Our data demonstrated that proinflammatory CXCL8 and IL-1β tend …

Advances In Molecular Imaging Of Vegfrs: Innovations In Imaging And Therapeutics, Hanieh Karimi, Sarah Lee, Wenqi Xu, Sigrid A. Langhans, David K. Johnson, Erik Stauff, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful …

Refine: A Database Of Linked Clinical Data And Genomic Biomarkers In Renal Cell Carcinoma Patients Receiving Immunotherapy-Based Treatment Regimens, Jeffrey Zhong, Albert Jang, Bashar Abuqayas, Arnab Basu, David Benjamin, Vineel Bhatlapenumarthi, Mehmet Asim Bilen, Dhvani Buch, Mark Chang, Erica Chin, Sourat Darabi, Nagendra Dhanikonda, Pooja Ghatalia, Claud Grigg, Abby Grier, Tanya Jindal, Joannah Jung, Deepak Kilari, Hamsa Kumar, Suzanna Lee, Brittany Neelands, Chinmayi Pandya, Jeff Pawalek, Jaimee Staggers, Ahmet Yildirim, Yousef Zakharia, Kevin Zarrabi, Michael Zimmerman, George Sledge, David Spetzler, Andrew Elliott, Rana Mckay, Pedro Barata

Department of Medical Oncology Faculty Papers

The REnal cancer consortium for Focused Investigation of Novel biomarkers and Expression (REFINE) consortium represents an important initiative in integrating clinical data with molecular sequencing in patients with advanced renal cell carcinoma (RCC) treated with immunotherapy-based approaches. By leveraging real-world evidence and genomic analysis, this consortium aims to explore putative predictive biomarkers with the potential to inform personalized treatment strategies. Findings from the REFINE database may further contribute to our understanding of disease courses of immunotherapy-based approaches for various molecular subtypes of RCC, associations of race and ethnicity with RCC treatment and outcomes with representation of patient populations underrepresented in …

Molecular Insights Into The Role Of Estrogen Receptor Beta In Ecdysterone Mediated Anabolic Activity, Syeda Sumayya Tariq, Madiha Sardar, Muhammad Shafiq, Hendrick Heinz, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Ecdysterone, often dubbed a “natural steroid,” has garnered significant attention among athletes for its reputed growth-promoting and anabolic properties. Unlike synthetic anabolic steroids, which are classified as controlled substances, ecdysteroids remain largely unregulated in many countries and are widely marketed as dietary supplements. Notably, ecdysterone has been included in the World Anti-Doping Agency (WADA) monitoring program, highlighting its potential impact on athletic performance and raising questions about its regulation. Emerging evidence indicates that, unlike traditional anabolic steroids that act primarily via the Androgen Receptor (AR), ecdysterone’s anabolic effects may be mediated through Estrogen Receptors (ERs), particularly Estrogen Receptor beta (ERβ). …

June 2025, Swosu Rural Health Center

RURAL ROCKS

• PBM Reform Takes Off in 2025
• Tirzepatide as Compared with Semaglutide for the Treatment of Obesity | New England Journal of Medicine
• Know the ABCs of Diabetic Skin Care
• Updated Recommendations for Pneumococcal Vaccination

Opioid Use Patterns After Nonsurgical Management Of Distal Radius Fractures: A Call For Opioid Stewardship, Sina Ramtin, Sara Khan, Vijay Chhabra, Wali Pirzada, Mohammad Khak, Asif M. Ilyas

Rothman Institute Papers

PURPOSE: While most opioid research focuses on postoperative use, limited data exist on prescribing patterns in nonsurgical management of common injuries such as distal radius fractures (DRFs). This study aimed to assess opioid prescribing trends and identify factors linked to prolonged use in nonsurgically treated DRFs.

METHODS: A retrospective cohort study of 591 patients aged 18-50 with nonsurgically managed DRFs between 2018 and 2024 was conducted. Opioid use was classified as prior opioid use (POU), fracture-related opioid use (FxOU), or delayed opioid use (DOU). Prescription data were obtained from the Prescription Drug Monitoring Program and analyzed for morphine milligram equivalents, …

Antiarrhythmic Drug Use In Atrial Fibrillation Among Different European Countries – As Determined By A Physician Survey, Espen Fengsrud, Carina Blomström-Lundqvist, A. John Camm, Andreas Goette, Peter R. Kowey, Jose L. Merino, Jonathan P. Piccini, Sanjeev Saksena, James A. Reiffel, Giuseppe Boriani

Department of Medicine Faculty Papers

BACKGROUND: There is limited knowledge of physicians' antiarrhythmic drug (AAD) treatment practices for patients with atrial fibrillation and adherence to guidelines in European countries.

METHODS: An online survey (n = 321) of cardiologists, cardiac electrophysiologists and interventional electrophysiologists was conducted in Germany (DE; n = 83), Italy (IT; n = 95), Sweden (SE; n = 60) and the United Kingdom (UK; n = 83) including 96 questions on treatment practices.

RESULTS: ESC guidelines were the most important non-patient factor influencing treatment practice (55-72 %). However, while amiodarone was frequently (88-93 %) used in heart failure with reduced left ventricular ejection …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Molecular Biomarkers Of Glioma, Punsasi Rajakaruna, Stella A. Rios, Hana Elnahas, Ashley Villanueva, David Uribe, Sophia Leslie, Walaa A. Abbas, Larissa Barroso, Stephanie Oyervides, Michael W. Persans, Wendy Innis-Whitehouse, Megan E. Keniry

School of Integrative Biological & Chemical Sciences Faculty Publications

In this review, we discuss how mutations in glioma are associated with prognosis and treatment efficacy. A fascinating characteristic of glioma and all cancers is that while common growth and developmental pathways are altered, the characteristic mutations are distinct depending on the specific type of tumor with concomitant prognoses. Next-generation sequencing, precision medicine, and artificial intelligence are boosting the employment of molecular biomarkers in cancer diagnosis and treatment. Understanding the biological underpinnings of distinct mutations on critical signaling pathways is crucial for developing novel therapies for glioma.

An Exploratory Pharmacogenetic Pilot Study Of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate And Tenofovir Disoproxil Fumarate, Derek E. Murrell, Benjamin C. Kennard, Maria E. Bertoni, David B. Cluck, Jonathan P. Moorman, Stacy D. Brown, Keshang Wang, Michelle M. Duffourc, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Background and Objectives

The nucleoside reverse transcriptase inhibitors tenofovir alafenamide fumarate and tenofovir disoproxil fumarate are frequently employed in treating human immunodeficiency virus. Further, each form of tenofovir requires laboratory monitoring to determine efficacy and tolerability among patients. This study sought to investigate the relationship, if any, of single nucleotide polymorphisms (SNPs) and selected clinical parameters.

Methods

The study population, predominantly Caucasian males with a median age of 53.0 years [interquartile range 46.0–59.0], was assayed for genetic variations using an iPLEX ADME PGx Pro v1.0 Panel.

Results

Although several SNP relationships were found with both forms of tenofovir, many of …

Cenobamate Use In Pregnancy: A Case Report, Tiara Paul, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

Elv-N34, Rvd6-Isomer, Or Npd1 Halt Replication Of Sars-Cov-2 Omicron Ba.5 Virus In Human Lung And Nasal Cells, Jorgelina M. Calandria, Haydee E. Bazan, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Nicholas J. Maness, Nicolas G. Bazan

School of Medicine Faculty Publications

Current vaccines rely on the sequence of Spike (S) protein to induce immunity against the severe acute respiratory coronavirus-2 (SARS-CoV-2) virus. Because of the high mutation rate of the viral S protein, new mutant strains are developed to generate new infectivity profiles. Bioactive lipid mediators (LMs) derived from docosahexaenoic acid (DHA) are synthesized on demand to sustain homeostasis. The purpose of this study was to determine the action of selected LMs in the viral replication of SARS-CoV-2 Omicron BA.5 variant in human lung and nasal epithelial cells. Cells from healthy donors were infected with Omicron BA.5 for one hour and …

Integrative Computational Modeling Of Distinct Binding Mechanisms For Broadly Neutralizing Antibodies Targeting Sars-Cov-2 Spike Omicron Variants: Balance Of Evolutionary And Dynamic Adaptability In Shaping Molecular Determinants Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we conducted a comprehensive analysis of the interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and four neutralizing antibodies—S309, S304, CYFN1006, and VIR-7229. Using integrative computational modeling that combined all-atom molecular dynamics (MD) simulations, mutational scanning, and MM-GBSA binding free energy calculations, we elucidated the structural, energetic, and dynamic determinants of antibody binding. Our findings reveal distinct dynamic binding mechanisms and evolutionary adaptation driving the broad neutralization effect of these antibodies. We show that S309 targets conserved residues near the ACE2 interface, leveraging synergistic van der Waals and electrostatic interactions, while S304 focuses on …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

The Effect Of Nonsteroidal Anti-Inflammatory Drugs On Union Rates Following Operative Repair Of Distal Radius Fractures, Michael Chang, Alexis Kasper, Juliet Chung, Justin Wright, Margaret Pennington, Asif M. Ilyas

Student Papers, Posters & Projects

Purpose

Methods

Methylprednisolone After Shoulder Arthroplasty Leads To Decreased Opioid Prescriptions Without An Increased Risk Of Infection: A Matched Cohort Analysis, Tej Joshi, Tuckerman Jones, Akhil Katakam, Daniella Ogilvie, Amanda Azer, Sefy Paulose, Balazs Galdi

Jefferson Hospital Staff Papers and Presentations

Background

Methods

Fear And Oxytocin: Effects Of Intraperitoneal Pretreatment In Rats, Daniel Yeromenko, Kelsie German, Eros Fuentes, Jenna Meade, Ben Bustos

2025 Symposium

INTRODUCTION: Oxytocin is a neuropeptide widely known for its role in social bonding and emotional regulation. Recent studies have suggested its involvement in modulating fear, stress, and anxiety responses, potentially offering therapeutic applications for trauma-related disorders such as PTSD. This study investigated whether pretreatment with oxytocin reduces behavioral and physiological fear responses in male and female Sprague-Dawley rats using a classical fear conditioning model. METHODS : Twenty-four Sprague-Dawley rats (12 males, 12 females) were assigned to one of four groups: control (no shock, no oxytocin), shock only, shock + low-dose oxytocin (0.5 mg/kg), and shock + high-dose oxytocin (1.0 mg/kg). …

Preparation And In-Vitro Evaluation Of Dompridone Oral Thin Film, Fatima Mohammed Hussein Wais

Maaen Journal for Medical Sciences

The aim of the current study was to formulate and evaluatedompridone nanoparticles and loaded in oral fast dissolve film, for enhance the solubility of poor water soluble dompridone by nanoparticles and fasten the action by prepared as oral thin film and also to improve patient compliance. Domperidone is the recommended medication for nausea and vomiting brought on by viral infections, chemotherapy, migraines, and food poisoning.Domperidonenanoparticles were made using two type of polymers (hydroxypropyl methylcellulose HPMC-K15 and methylcellulose MC-A4C) in a range of ratios (1:1, 1:2, and 1:3) drug:polymer ratio by solvent antisolvent technique. In nanoparticle formulation, HPMC-K15 and MC-A4C were …

Spravato® Fda-Approved As Monotherapy For Adults With Treatment-Resistant Depression, Rileigh Rahrig, Kennedy Kosikowski, Haylee Whyde, Kiley Devoll, Allie Honigford, Macy Davis, Joshua Honaker, Samantha Mccord, Manoranjan D'Souza

Pharmacy and Wellness Review

Treatment-resistant depression (TRD) is a challenging and possibly life-threatening condition that affects millions of people worldwide. Patients with major depressive disorder (MDD) are diagnosed with TRD once they have tried and failed to respond to two antidepressant treatments at the maximum dose for a full trial of six to eight weeks. Most traditional antidepressant therapies work by increasing the levels of monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine in the brain. These medications have a delayed onset of action, ranging from two to eight weeks, and often fail to relieve depressive symptoms in a patient with TRD. Therefore, targeting …