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Articles 661 - 690 of 5048

Full-Text Articles in Chemicals and Drugs

Examining The Role Of Corticosteroids In The Management Of Acute Interstitial Pneumonia: A Systematic Review., Carlos Valladares, Aalia Narvel, Bianna Koutsenko, Alexa Simonetti, Fatima Mossolem, Alexis Chow, Samrat Gollapudi, Usmaan Al-Shehab, Nicholas Averell, Katherine Chiapaikeo-Poco, Adam Kaplan Apr 2025

Examining The Role Of Corticosteroids In The Management Of Acute Interstitial Pneumonia: A Systematic Review., Carlos Valladares, Aalia Narvel, Bianna Koutsenko, Alexa Simonetti, Fatima Mossolem, Alexis Chow, Samrat Gollapudi, Usmaan Al-Shehab, Nicholas Averell, Katherine Chiapaikeo-Poco, Adam Kaplan

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Acute interstitial pneumonia (AIP), also known as Hamman-Rich syndrome, is a rapidly progressive interstitial lung disease. In addition to being challenging to diagnose, AIP is also difficult to treat. The mortality rate of AIP is greater than 70% due to the disease's rapid progression. Furthermore, survivors are likely to develop chronic interstitial lung disease as a sequela. Treatment primarily focuses on supportive care, which consists of oxygenation through mechanical ventilation, administration of broad-spectrum antibiotics, and the use of corticosteroids. Although the use of steroids as empiric treatment is controversial and results on its mortality benefit are variable, some studies …


Analyzing Social Media Trends In Cosmeceuticals: Insights From Google Trends And Tiktok Analytics, E. Correia, Jenna Mandel, Stephanie R. Jackson Cullison Apr 2025

Analyzing Social Media Trends In Cosmeceuticals: Insights From Google Trends And Tiktok Analytics, E. Correia, Jenna Mandel, Stephanie R. Jackson Cullison

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Social media usage has surged, particularly since the COVID-19 pandemic. Dermatology invokes intense interest on social media, and cosmeceuticals are among the most trending topics, offering a unique space for dermatologists to share their expertise. By using tools like Google Trends and TikTok viewership, we aim to capture cosmeceutical trends to guide dermatologists' educational efforts.

METHODS: A Google Trends search from January 2004 to December 2023 was performed on retinol, bakuchiol, salicylic acid, glycolic acid, azelaic acid, hydroquinone, niacinamide, vitamin C serum, and hyaluronic acid. Trend lines were created for each term, and yearly percent differences in relative search …


Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden Apr 2025

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. …


The Impact Of Employer-Provided Drug/Alcohol Education On Marijuana And Alcohol Use In Young Adults., Sonia Cerrillo, Naomi Ramirez Apr 2025

The Impact Of Employer-Provided Drug/Alcohol Education On Marijuana And Alcohol Use In Young Adults., Sonia Cerrillo, Naomi Ramirez

Posters - 2025

According to the American Society of Addiction Medicine, addiction is a treatable, chronic medical disease involving complex interactions among brain circuits, genetics, the environment, and an individual’s life experiences (1). People with addiction use substances or engage in behaviors that become compulsive and often continue despite harmful consequences. The most common addictions in the United States are alcohol and marijuana (2). In the U.S., 59.277 million people twelve and older have used illegal drugs or misused prescription drugs. Out of the 138.522 million Americans who overdrink alcohol, 28.32 million have an alcohol use disorder (3).

Since alcohol and drug abuse …


Spectroscopic And Electrochemical Properties Of Ugi Adducts Of Isatin, Callah Preti, Erick Y. Morales Orrante Apr 2025

Spectroscopic And Electrochemical Properties Of Ugi Adducts Of Isatin, Callah Preti, Erick Y. Morales Orrante

Posters - 2025

• β-lactams are essential structural components of many antibiotics and widely studied due to their biological importance and synthetic versatility.

• The Ugi reaction is a multicomponent reaction involving: • Aldehyde, primary amine, carboxylic acid, and isocyanide.

• Rapidly generates α-acetamido carboxamide derivatives (Ugi adducts). • The study focuses on the synthesis and characterization of two oxindole-based β-lactam derivatives:

• 1-Benzyl-N-(tert-butyl)-2-oxo-3-(2-oxoazetidin-1-yl)indoline-3- carboxamide (4a).

• N-(tert-Butyl)-2-oxo-3-(2-oxoazetidin-1-yl)indoline-3- carboxamide (4d).

• Characterization methods included IR Spectroscopy, UV-Visible Spectroscopy, and X-Ray Crystallography.

• Future work will investigate metal complexation to enhance β-lactam stability, alter electronic properties, and improve biological activity


Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon Apr 2025

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …


Proposed Evaluation Of Nonpharmacological Treatments And Therapies For Paclitaxel Based Chemotherapy-Induced Peripheral Neuropathy (Cipn), Mackenzie Lesczcynski Apr 2025

Proposed Evaluation Of Nonpharmacological Treatments And Therapies For Paclitaxel Based Chemotherapy-Induced Peripheral Neuropathy (Cipn), Mackenzie Lesczcynski

D.U.Quark

Chemotherapy-induced Peripheral Neuropathy (CIPN) is a common complication in breast cancer patients receiving Paclitaxel, a chemotherapeutic agent (1). CIPN symptoms range from numbness to extreme pain and sensitivity in bodily extremities, forcing chemotherapy to be halted (2). The mechanism of this side effect is not well understood and there is no standard pharmacological treatment available to improve effects. Nonpharmacological treatments have been attempted on small patient cohorts, but there are no conclusive findings (3). Due to this, we believe that a comprehensive murine model must be developed in order to assess nonpharmacological treatment efficacy and potential molecular targets for pharmacological …


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 Apr 2025

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 …


April 2025, Swosu Rural Health Center Apr 2025

April 2025, Swosu Rural Health Center

RURAL ROCKS

This is the April 2025 issue of Rural Rocks from the SWOSU College of Pharmacy.


A Preliminary Analysis Of Transaminitis Observed In Oxandrolone Versus Testosterone Therapy In Major Burn Injury, Alexandra Dewitt, Athena Hoppe, Anastasiya Ivanko, Victoria Miles Apr 2025

A Preliminary Analysis Of Transaminitis Observed In Oxandrolone Versus Testosterone Therapy In Major Burn Injury, Alexandra Dewitt, Athena Hoppe, Anastasiya Ivanko, Victoria Miles

School of Medicine Faculty Publications

57th Annual Meeting of the American Burn Association, ABA 2025, April 8 - 11, 2025, Phoenix, AZ


Efficacy Of Glucagon-Like Peptide-1 Receptor Agonists For Prevention Of Stroke Among Patients With And Without Diabetes: A Meta-Analysis With The Select And Flow Trails, Asmita Gera, Fakhar Latif, Vamsikalayan Borra, Sidra Naz, Vivek Mittal, Fathima Shehnaz Ayoobkhan, Tushar Kumar, Zarghoona Wajid, Novonil Deb, Tanisha Prasad Apr 2025

Efficacy Of Glucagon-Like Peptide-1 Receptor Agonists For Prevention Of Stroke Among Patients With And Without Diabetes: A Meta-Analysis With The Select And Flow Trails, Asmita Gera, Fakhar Latif, Vamsikalayan Borra, Sidra Naz, Vivek Mittal, Fathima Shehnaz Ayoobkhan, Tushar Kumar, Zarghoona Wajid, Novonil Deb, Tanisha Prasad

School of Medicine Publications

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established among diabetic and non diabetic patients.

Objective

We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with and without Diabetes.

Methods

We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until 15th July 2024, without any language restrictions. Odds ratios (OR) and 95 % …


Relevance Of Cellular Homeostasis-Related Gene Expression Signatures In Distinct Molecular Subtypes Of Breast Cancer, Sharda P. Singh, Chathurika S. Dhanasekara, Michael W. Melkus, Chhanda Bose, Sonia Y. Khan, Flavia Sardela De Miranda, Maria F. Mahecha, Prrishti J. Gukhool, Sahil S. Tonk, Se-Ran Jun Apr 2025

Relevance Of Cellular Homeostasis-Related Gene Expression Signatures In Distinct Molecular Subtypes Of Breast Cancer, Sharda P. Singh, Chathurika S. Dhanasekara, Michael W. Melkus, Chhanda Bose, Sonia Y. Khan, Flavia Sardela De Miranda, Maria F. Mahecha, Prrishti J. Gukhool, Sahil S. Tonk, Se-Ran Jun

School of Medicine Publications

Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I-III breast cancer patients across 90 institutions in the …


Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay Apr 2025

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 Mar 2025

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 …


Penghambat Kanal Kalsium Sebagai Kontrol Glukosa Darah Pada Insulinoma: Sebuah Laporan Kasus, Nadhira Nizam, Ryan Tresna Putra, Anshari Saifuddin Hasibuan Mar 2025

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 …


Real-World Impact Of Latanoprostene Bunod Ophthalmic Solution 0.024% In Glaucoma Therapy: A Narrative Review, W. Daniel Stamer, Thomas Chiu, Da-Wen Lu, Tsing Hong Wang, Prin Rojanapongpun, Ngamkae Ruangvaravate, Youn Hye Jo, Marlene R. Moster, Murray Fingeret, Nora Lee Cothran, Jessica Steen, Ian B. Gaddie, Ömür Uçakhan-Gündüz, Wesam S. Shalaby, Cindy M. L. Hutnik Mar 2025

Real-World Impact Of Latanoprostene Bunod Ophthalmic Solution 0.024% In Glaucoma Therapy: A Narrative Review, W. Daniel Stamer, Thomas Chiu, Da-Wen Lu, Tsing Hong Wang, Prin Rojanapongpun, Ngamkae Ruangvaravate, Youn Hye Jo, Marlene R. Moster, Murray Fingeret, Nora Lee Cothran, Jessica Steen, Ian B. Gaddie, Ömür Uçakhan-Gündüz, Wesam S. Shalaby, Cindy M. L. Hutnik

Wills Eye Hospital Papers

Latanoprostene bunod ophthalmic solution (LBN) 0.024% is a topical nitric oxide (NO)-donating prostaglandin F2α (PGF2α) analog first approved in November 2017 for reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG). This narrative review describes the unique mechanism of action of LBN and summarizes available real-world data. Upon instillation, LBN is metabolized into latanoprost acid and butanediol mononitrate, which is further reduced to NO and an inactive metabolite. Latanoprost acid increases aqueous humor outflow primarily through the uveoscleral (unconventional) pathway, whereas NO increases outflow through the trabecular (conventional) pathway. Eight studies were identified: 2 …


Thyrotoxic Periodic Paralysis: Acute Paralysis As The Initial Presentation Of Graves' Disease Triggering A Stroke Alert, Osadebamwen Osaghae, Hafiza Qadeer, Sapna Sharma, Vinita Singh Mar 2025

Thyrotoxic Periodic Paralysis: Acute Paralysis As The Initial Presentation Of Graves' Disease Triggering A Stroke Alert, Osadebamwen Osaghae, Hafiza Qadeer, Sapna Sharma, Vinita Singh

Tower Health Research Day

No abstract provided.


Ocular Surface Glycocalyx In Health And Disease, Rafael Martínez-Carrasco, Ajay Sharma Mar 2025

Ocular Surface Glycocalyx In Health And Disease, Rafael Martínez-Carrasco, Ajay Sharma

Pharmacy Faculty Articles and Research

The glycocalyx is a dynamic carbohydrate-enriched structure that forms a dense coating on the surface of animal cells, including those at the ocular surface. It plays a critical role in maintaining cellular functions and it has a significant influence in disease processes. At the ocular surface, glycoproteins such as mucins are essential for hydration, lubrication, and barrier protection. Proteoglycans and glycolipids contribute to cell signaling, and mediate interactions with pathogens. Alterations in the glycocalyx are implicated in a spectrum of ocular conditions, including dry eye disease, ocular allergies, infections, and systemic diseases such as Graft-versus-host disease (GVHD) and diabetes mellitus. …


Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman Mar 2025

Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman

Honors Program: Senior Projects (Public)

The reduction potential of flavin bound to Sinorhizobium meliloti proline utilization A (SmPutA) is beneficial in providing vital information on enzyme activity and the active site environment. Flavin is crucial in biological metabolism such as aerobic respiration and other important processes like oxygen activation that are catalyzed by flavin-dependent enzymes. (4). In this study, we seek to determine whether the redox potential of SmPutA-bound flavin can be used to characterize potential long-distance communication and analyze the possibilities of inactivation reversibility. SmPutA is a large bifunctional enzyme that catalyzes the overall oxidation of proline to glutamate via two catalytic domains (1). …


Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold Mar 2025

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …


Characterization Of Novel Arrhythmogenic Patterns Arising Secondary To Heterogeneous Expression And Activation Of Nav1.8, Zhong-He Zhang, Hector Barajas-Martinez, Hong-Yi Duan, Guo-Hua Fan, Hong Jiang, Charles Antzelevitch, Hao Xia, Dan Hu Mar 2025

Characterization Of Novel Arrhythmogenic Patterns Arising Secondary To Heterogeneous Expression And Activation Of Nav1.8, Zhong-He Zhang, Hector Barajas-Martinez, Hong-Yi Duan, Guo-Hua Fan, Hong Jiang, Charles Antzelevitch, Hao Xia, Dan Hu

Department of Medicine Faculty Papers

Background: Previous studies suggested that SCN10A/Nav1.8 may influence cardiac electrophysiology and the susceptibility to cardiac arrhythmias. Notably, the expression of SCN10A is not uniform, showing variable expression in each cardiac chamber. The present study aims to explore the functional significance of Nav1.8 expression among different cell types present in the ventricular myocardium.

Methods: The effect of the specific Nav1.8 blocker, A-803467, on action potential was recorded from epicardial, mid-myocardial (M cells) and Purkinje tissue slices isolated from the canine left ventricle using standard microelectrode techniques and on late sodium current from Purkinje cells using patch-clamp techniques.

Results: A-803467 treatment …


The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner Mar 2025

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …


Small Molecule B-Raf Inhibitors As Anti-Cancer Therapeutics: Advances In Discovery, Development, And Mechanistic Insights, Yamile Abuchard Anaya, Ricardo Pequeno Bracho, Subhash Chauhan, Manish K. Tripathi, Debasish Bandyopadhyay Mar 2025

Small Molecule B-Raf Inhibitors As Anti-Cancer Therapeutics: Advances In Discovery, Development, And Mechanistic Insights, Yamile Abuchard Anaya, Ricardo Pequeno Bracho, Subhash Chauhan, Manish K. Tripathi, Debasish Bandyopadhyay

School of Medicine Publications

B-RAF is a serine/threonine kinase that plays a crucial role in the MAPK signaling pathway, regulating cell proliferation and survival. Mutations in B-RAF, particularly V600E, are associated with several malignancies, including melanoma, colorectal cancer, and non-small cell lung cancer, making it a key therapeutic target. The development of B-RAF inhibitors, such as Vemurafenib, Dabrafenib, and second-generation inhibitors like Encorafenib, has led to significant advancements in targeted cancer therapy. However, acquired resistance, driven by MAPK pathway reactivation, RAF dimerization, and alternative signaling pathways, remains a major challenge. This review explores the molecular mechanisms of B-RAF inhibitors, their therapeutic efficacy, and resistance …


Glucagon-Like Peptide-1 Receptor Agonists: Exciting Avenues Beyond Weight Loss, Lalitha Sundararaman, Divakara Gouda, Anil Kumar, Sumithra Sundararaman, Basavana Goudra Mar 2025

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 …


Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John Mar 2025

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …


Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky Mar 2025

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …


Screening For Penicillin G Acylase (Pga)-Producing Bacteria And Gene Cloning Using Degenerate Oligonucleotide Primed-Pcr, Masdalifah Masdalifah, Sri Rezeki Wulandari, Gabriela Christy Sabbathini, Maria Ulfah, Dini Achnafani, Ahmad Wibisana, Feronika Heppy Sriherfyna, Is Helianti, Niknik Nurhayati Mar 2025

Screening For Penicillin G Acylase (Pga)-Producing Bacteria And Gene Cloning Using Degenerate Oligonucleotide Primed-Pcr, Masdalifah Masdalifah, Sri Rezeki Wulandari, Gabriela Christy Sabbathini, Maria Ulfah, Dini Achnafani, Ahmad Wibisana, Feronika Heppy Sriherfyna, Is Helianti, Niknik Nurhayati

Makara Journal of Science

The growing concern over antibiotic resistance has driven global efforts to explore innovative solutions, including the use of Penicillin G acylase (PGA) to produce semisynthetic β-lactam antibiotics. This study screened four potential in-tracellular PGA-producing bacteria: Alcaligenes faecalis InaCC B444 (AfPGA), Kluyvera cryocrescens InaCC B850 (KcPGA), Providencia rettgeri InaCC B25 (Pr25PGA), and P. rettgeri InaCC B466 (Pr466PGA). Penicillin G Acylase encoding genes (pgas) were isolated from them using a Degenerate Oligonucleotide Primed-PCR (DOP-PCR) approach and sequenced. Microbiological assays confirmed all tested crude extracts to exhibit inhibitory effects. Penicillin G was used for evaluating hydrolytic activity and 6-Amino Penicillanic Acid (6-APA) coupled …


A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink Mar 2025

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …


Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato Mar 2025

Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato

Kimmel Cancer Center Faculty Papers

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …


Exploring Cucurbitacin D'S Protective Mechanism Against Benzo[A]Pyrene-Induced Liver Injury Through Nrf2 Activation, Shabnam Malik, Mohammed Sikander, Anyssa Rodriguiez, Daniel Zubieta, Debanhi Esparaza, Fathi T. Halaweish, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan Mar 2025

Exploring Cucurbitacin D'S Protective Mechanism Against Benzo[A]Pyrene-Induced Liver Injury Through Nrf2 Activation, Shabnam Malik, Mohammed Sikander, Anyssa Rodriguiez, Daniel Zubieta, Debanhi Esparaza, Fathi T. Halaweish, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Background: Numerous studies have established a strong association between hepatocellular carcinoma (HCC) and various co-morbidity factors, including smoking. Tobacco smoke is a significant source of benzo[a]pyrene, a highly carcinogenic compound known to cause liver damage. Cucurbitacin, a triterpene with diverse biological activities, exhibits antioxidant, antiinflammatory, and anticancer effects. However, its hepatoprotective properties have not been thoroughly investigated. In this study, we aimed to evaluate the hepatoprotective effects of cucurbitacin D, a novel analog of cucurbitacin, against liver injury induced by benzo[a]pyrene in human HepG2 cells.

Method: To investigate the hepatoprotective effect of cucurbitacin D against benzo[a]pyreneinduced liver damage, proliferation, clonogenicity, …