Chemical Actions and Uses Commons^™

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 …

The Impact Of Obesity On The Risk Of Venous Thromboembolism In Users Of Combined Oral Contraceptives: A Comprehensive Literature Review, Adeena Javed

Rowan-Virtua Research Day

Background: Combined oral contraceptives (COCs) are a widely used method of birth control in the U.S., particularly among women aged 15–44. COCs are known to increase the risk of venous thromboembolism (VTE). Obesity, which affects over 40% of adult women in the U.S., is also a recognized independent risk factor for VTE. However, the compounded risk posed by the simultaneous presence of obesity and COC use has not been thoroughly explored.

Hypothesis: Obesity significantly elevates the risk of VTE in women using COCs, demonstrating a synergistic interaction between these two factors.

Methods: A systematic literature review was conducted using PubMed, …

Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally

Rowan-Virtua Research Day

Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD).

Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition.

Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid …

Assessing The Efficacy Of Prolonged Doxycycline Pep Use In High-Risk Populations For Sti Prevention, Lam Doan, Pearl Joslyn, Lizann Sung, Timothy Breiner, Sarah Marotta, Shikhar Rastogi

Rowan-Virtua Research Day

First recommended in October 2022, doxycycline post-exposure prophylaxis (DoxyPEP) has been increasingly used as a treatment for multiple sexually transmitted infections (STIs). To evaluate the efficacy of prolonged DoxyPEP use in high risk populations - men who have sex with men (MSM) and transgender women - for STIs, different sources addressing various aspects of DoxyPEP, its efficacy in STI prevention, and the potential consequences of its widespread use in terms of antimicrobial resistance were examined. Across 9 studies, DoxyPEP was found to decrease the incidence of bacterial STIs, specifically, syphilis, chlamydia, and gonorrhea with varying efficacy, especially for gonorrhea. Furthermore, …

Cardiovascular Effects Of Glp-1 Receptor Agonists In Non-Diabetic Adults With Obesity: A Systematic Literature Review, Mariam Abdeen

Rowan-Virtua Research Day

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with obesity. GLP-1 receptor agonists, initially developed for glycemic control in diabetes, are now approved for weight loss in non-diabetic populations. Recent clinical trials suggest these agents may also offer direct cardiovascular benefits.

Objective: This literature review aims to evaluate the cardiovascular effects of GLP-1 receptor agonists, specifically semaglutide, liraglutide, and tirzepatide, in non-diabetic adults with overweight or obesity.

Methods: A systematic search was conducted in January 2025 using PubMed as the primary database, supplemented by Google Scholar and Embase. Clinical trials were selected based on …

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 …

A Rare Case Of Diffuse Alveolar Hemorrhage In The Setting Of Iga Nephropathy, Vasculitis And Atypical Hemolytic Uremic Syndrome In A Previously Healthy Young Adult, Karl Schlicht, Nancy Kaura

Rowan-Virtua Research Day

IgA Nephropathy, also known as Berger disease, can precipitate acute renal failure in patients. IgA Nephropathy (IgAN) is deposition of protein from IgA into the renal tissue with subsequent renal dysfunction. IgA vasculitis (IgAV) is another condition where similarly the protein of IgA is deposited into the vessels. There are some cases of co-existing atypical hemolytic uremic syndrome (aHUS) with IgAN. However, rare combinations seen with all three IgAN, IgAV, and aHUS without any pre-existing conditions nor medical history. Patients that develop any one of these conditions are looking at life long changes with hemodialysis (HD) and organ transplants being …

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 …

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 …

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 …

Ibuprofen, Flurbiprofen Or Naproxen Sodium Minimally Influences Musculoskeletal Adaptations To Treadmill Exercise In Rats, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Maximus Leiss, Alexander Kolb, Julie Hughes, Marshall Naimo, Ryan Tomlinson, Jeffery Staab

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may influence musculoskeletal health. The purpose of this study was to compare the effects of three different NSAIDS: naproxen sodium, ibuprofen, flurbiprofen or a placebo on musculoskeletal adaptations in rodents with or without 6 weeks of aerobic exercise.

METHODS: Nine-week-old male Wistar rats (n = 80) were randomized to either exercise (EX) or no-exercise control (CON) conditions and treated with naproxen, ibuprofen (IBU), flurbiprofen (FLU) or placebo (PLA). For exercise, rats ran 5 days per week for 6 weeks at a 5% incline on a motorized treadmill for 30 min. Three-point bending (3 PB) and …

Penghambat Kanal Kalsium Sebagai Kontrol Glukosa Darah Pada Insulinoma: Sebuah Laporan Kasus, Nadhira Nizam, Ryan Tresna Putra, Anshari Saifuddin Hasibuan

Jurnal Penyakit Dalam Indonesia

Insulinoma is a rare neuroendocrine tumor of the pancreas arising from β-cells, leading to excessive insulin secretion and resultant hypoglycaemia. Surgical resection is the first-line treatment for insulinoma, but when surgery is not feasible, medical therapy is an important option. Calcium channel blockers (CCBs) such as verapamil can inhibit insulin release from β-cells and have been proposed as an adjunct therapy to help control blood glucose levels in insulinoma. We report a 43-year-old man who presented to the emergency department with decreased consciousness due to hypoglycaemia. His capillary blood glucose at home was 35 mg/dL, about 8 hours after his …

Glucagon-Like Peptide-1 Receptor Agonists: Exciting Avenues Beyond Weight Loss, Lalitha Sundararaman, Divakara Gouda, Anil Kumar, Sumithra Sundararaman, Basavana Goudra

Department of Anesthesiology Faculty Papers

The last two decades have proffered many remarkable choices in managing type 1 and type 2 diabetes mellitus. Leading the list are glucagon-like peptide-1 receptor agonists (GLP1RAs), the first of which, exenatide, was approved by the FDA in 2005. Two other major classes of drugs have also entered the market: dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly known as gliptins and approved in 2006, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, with the first approval occurring in 2013. These drugs have revolutionized the treatment of diabetes. Additionally, on the horizon, the once-weekly basal insulin analog insulin icodec and the once-weekly combination of insulin icodec …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Alcohol And Cannabis Use For Pain Management: Translational Findings Of Relative Risks, Benefits, And Interactions, Sumin Lee, Scott Edwards

School of Medicine Faculty Publications

Chronic pain affects over 20% of the global population and contributes to the vast burden of psychiatric illness. While effective treatments for chronic pain remain limited, both alcohol and cannabis have been used for centuries to manage pain and closely associated negative affective symptoms. However, persistent misuse of alcohol and/or cannabis in such a negative reinforcement fashion is hypothesized to increase the risk of severity of substance use disorders (SUDs). The current review describes neurobiological evidence for the analgesic efficacy of alcohol and primary cannabis constituents and how use or co-use of these substances may influence SUD risk.

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Mouse Adrenal Macrophages Are Associated With Pre- And Postsynaptic Neuronal Elements And Respond To Multiple Neuromodulators, Matthew D. Whim

School of Medicine Faculty Publications

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to …

Randomized, Placebo-Controlled Pilot Study Of Naproxen During Dental Implant Osseointegration, Hattanas Kumchai, Daniel Taub, Ryan Tomlinson

Department of Oral and Maxillofacial Surgery Faculty Papers

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed following the placement of dental implants, but the effects of these drugs on the osseointegration process are poorly understood. We designed a randomized, placebo-controlled pilot study to quantitatively assess the effect of NSAIDs during early implant osseointegration.

MATERIALS AND METHODS: Subjects receiving a maxillary dental implant were randomized to take naproxen or placebo for 7 days after the surgery. Implant osseointegration was quantified using Resonance Frequency Analysis device. Implant-Stability-Quotient (ISQ) measurement was performed at the time of surgery and at follow-up visits 1, 4, and 16 weeks after surgery. Periapical radiographs were …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Fluorine-Containing Isosteres Enable A Structure-Activity Relationship Study Of Gingerol Derivatives, Shelby Cooper, Diarta Kabashi, Marlin Yacoub, Jessica Molen, Osman Farhan, Christina Farley, Samantha Yencha, Michelle Figueiredo, Nidheesh Phadnis, Wynter Henry, Julian Harris, Frank Wilkinson, John Milligan

College of Life Sciences Faculty Papers

A series of fluorinated and non-fluorinated [6]-gingerol, [6]-paradol, [6]-shogaol and ferulate derivatives were synthesized. Testing these analogs in anti-proliferation assays with MCF-7, A549, HCT-116 and HEK-293 cell lines provided insight into the structural features that contribute to the anti-proliferative activity of naturally occurring ginger constituents. In particular, the use of both vinyl and alkyl trifluoromethyl isosteres allowed us to evaluate the structure-activity impact of the enone motif found in shogaols. Our results indicate that enone-containing derivatives have a higher potency, suggesting the conjugated enone motif characteristic of shogaols may be primarily responsible for the anti-cancer activity of the broader natural …

Management Of Hip Fracture Patients On Direct Oral Anticoagulants: A Survey Of Orthopaedic Trauma Surgeons, Systematic Review, And Meta-Analysis, Clay Spitler, Robert Rutz, Nigel Blackwood, Meghan Wally, Joseph Johnson, Peter Krause, Jaimo Ahn, Zuhair Mohammed, Mark Mcclure, Rebecca Billings, Ziqing Yu, Matthew Yeager

School of Medicine Faculty Publications

OBJECTIVES: This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices. DATA SOURCES: A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications. STUDY SELECTION: Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an "if-reported" basis, …

Beyond Checkpoint Inhibitors: The Three Generations Of Immunotherapy, John Schaub, Shou-Ching Tang

School of Medicine Faculty Publications

Anti-tumor immunotherapy was rediscovered and rejuvenated in the last two decades with the discovery of CTLA-4, PD-1 and PD-L1 and the roles in inhibiting immune function and tumor evasion of anti-tumor immune response. Following the approval of the first checkpoint inhibitor ipilimumab against CTLA-4 in melanoma in 2011, there has been a rapid development of tumor immunotherapy. Furthermore, additional positive and negative molecules among the T-cell regulatory systems have been identified that that function to fine tune the stimulatory or inhibitory immune cells and modulate their functions (checkpoint modulators). Many strategies are being explored to target macrophages, NK-cells, cytotoxic T-cells, …

Residual Traditional Risk In Non-Traditional Atherosclerotic Diseases, Federico Biscetti, Giorgia Polito, Maria Margherita Rando, Maria Anna Nicolazzi, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and …

Nutritional, Phytochemical, And Antimicrobial Properties Of Carica Papaya Leaves: Implications For Health Benefits And Food Applications, Rajni Choudhary, Ravinder Kaushik, Ansab Akhtar, Suvendu Manna, Jyoti Sharma, Aarti Bains

School of Medicine Faculty Publications

BACKGROUND: Papaya leaves (PLs) are known for their therapeutic benefits and traditional use in treating inflammation, infections, and various health conditions. Rich in bioactive compounds, PLs are studied for their potential applications in functional foods. This study analyzed their nutritional, phytochemical, structural, thermal, and antimicrobial properties to evaluate their role as a health-promoting ingredient. METHODS: Phytochemicals were quantified spectrophotometrically and identified via GC-MS. Antioxidant activity was assessed using DPPH and FRAP assays. Mineral content was determined using ICP-OES. Structural and thermal properties were evaluated using FTIR, XRD, and calorimetry, and antimicrobial activity was tested via the agar well diffusion method. …

A Non-Toxic Analgesic Elicits Cell-Specific Genomic And Epigenomic Modulation By Targeting The Pag Brain Region, Hernan A. Bazan, Brian L. Giles, Surjyadipta Bhattacharjee, Scott Edwards, Nicolas G. Bazan

School of Medicine Faculty Publications

Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP's limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, from the periaqueductal gray (PAG) midbrain region, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund's adjuvant (CFA)-induced inflammatory pain …

Chronic Administration Of A Cannabis-Derived Mixture At An Antihyperalgesic Dose Does Not Significantly Enhance Hepatotoxicity Or The Development Of Metabolic Dysfunction-Associated Steatohepatitis In Male Mice, Kim B. Pedersen, Tomislav Jelesijevic, Tamara M. Morris, Sarah M. Melton, Ashley S. Henderson, John F. Glenn, Gregory J. Davenport, Martin J.J. Ronis, Peter J. Winsauer

School of Medicine Faculty Publications

Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic …

Myrtillin As A Promising Immunomodulator: Molecular Modeling And Pharmacokinetic Evaluation, Adolat Manakbayeva, Timur Kerimov, I D. Ershov, E. I. Anarkulova, Pavel Alexyuk, Y Moldakhanov, Ahdrey P. Bogoyavlenskiy, Vyacheslav Dushenkov

Publications and Research

Myrtillin, an anthocyanin found in blueberry fruits, is known for its antioxidant and potentially immunomodulatory properties. In this study, molecular docking was used to evaluate its interactions with a wide panel of immune-related proteins, including pro-inflammatory cytokines (TNF-α, IL-6, IL-17), antiinflammatory mediators (IL-4, IL-10), and signaling pathway proteins (1NFK, p52/RelB). The in silico results were supported by interaction analysis, and an ADMET analysis was conducted to assess the pharmacokinetic and toxicological profile. The findings confirm the promise of Myrtillin as a natural modulator of inflammatory responses.

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …