Pharmacology Commons^™

A Deep Dive Into The Orchard Of Health: Exploring The Anti-Cancer And Anti-Aging Potential Of Apple Polyphenols, Li-Ching Chen, Han-Sheng Chang, Yuan-Soon Ho

Journal of Food and Drug Analysis

Apples, a ubiquitous and beloved fruit, harbor a treasure trove of bioactive compounds, with apple polyphenols (APs) taking center stage. This review delves into the latest scientific advancements illuminating the anti-cancer and anti-aging properties of APs. We dissect the intricate mechanisms by which APs combat cancer initiation, progression, and metastasis, highlighting their prowess in inducing apoptosis, inhibiting angiogenesis, and modulating cell signaling pathways. Furthermore, we explore the multifaceted ways APs combat aging, including their potent antioxidant and anti-inflammatory actions, DNA protective effects, and ability to modulate cellular processes like autophagy and metabolism. This comprehensive review underscores the therapeutic promise of …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Adiporon, Adiponectin Receptor Agonist, Exhibits Antiproliferative And Apoptotic Effects In Ht29 And Hct116 Colon Cancer Cells, Arwa Fairaq, Ashraf N. Abdalla, Alanood S. Algarni, Yosra Alhindi

Saudi Toxicology Journal

AdipoRon is the first synthetic analog of endogenous adiponectin, which is an adipose tissue derived hormone. As it is characterized with pharmacological properties like adiponectin through binding and activating AdipoR1 and AdipoR2 receptors this makes it a target for therapeutic treatments for a multitude of disorders. In this study AdipoRon effect on HT29 and HCT116 colon cancer cells were investigated. Cytotoxic activity of AdipoRon was observed, with a significant inhibition rate in HT29 and HCT116 cells. Moreover, there was a significant decrease in the number of HCT116 colonies by clonogenicity test. In addition, cell migration assay showed significant decrease in …

Awareness Of Aspirin’S Dual Role As An Anti-Cancer Agent And Anti- Thrombotic Agent And Its Association With Medication Adherence To Low-Dose Aspirin: A Cross-Sectional Study, Hadhyah N. Alabdali, Sarah S. Al- Harbi, Layan Z. Sharalahi, Yosra Z. Alhindi

Saudi Toxicology Journal

Background: Aspirin is known to be an effective antithrombotic agent. Multiple studies have been studying its effect on cancer as colorectal cancer. Aim: This study aimed to measure the Awareness of Aspirin's Dual Function as an Anti-Cancer Agent and Anti-Thrombotic among Residents of the Makkah region in the Kingdom of Saudi Arabia. Methods: A cross-sectional study was conducted involving 490 participants from the Makkah region. Data collection was achieved through a self-reported online questionnaire and distributed via social media platforms from period of November 2024 until January 2025. Results: Over 340 of the participants in this research have bachelor's degrees. …

Could Psilocin Rescue Chronic, Stress-Accelerated, Transcriptional Aging In Brain?, Danny R. Craig, Eric M. Blalock

Journal of Pharmacology & Nutritional Sciences

Brain aging (BA) processes are complex, often affect multiple systems, and frequently lead to cognitive decline and increased susceptibility to insults. BA appears to be a primary risk for the development of many prominent neurodegenerative pathologies. The US Census Bureau predicts that the aging population (65+) will represent a greater proportion of the US population than children (under 18) by 2034, dramatically increasing the burden on health-care infrastructure.¹⁷ Several mechanisms of stress driven, aging-related neurologic dysfunction have been advanced in the past 50 years and include: Stress hormone exposure and glucocorticoid cascade;^{7, 16} calcium ion dyshomeostasis;⁸ allostatic …

Putting The Substance In Substantial Evidence: An Evidence-Based Approach To Flexible Drug Regulation, Emanuel Krebs, Tania M. Bubela, Melanie Mcphail, Christopher Mccabe, Dean A. Regier

Office of the Provost

For new drugs or indications, substantial evidence of clinical effectiveness is required for market authorization. In most jurisdictions, substantial evidence is not explicitly defined. Health regulators exercise discretion and are increasingly tolerant of earlier or less mature evidence. To align with flexible evidentiary standards, we argue for the adoption of a principle and, context-based approach to the evidence threshold. Our approach aims to balance the potential benefits and harms of accelerated authorization, low therapeutic value, and safety, based on a value of information (VoI) framework. In our VoI framework, substantial evidence exists when the expected net health value of further …

Antiseizure Medications And Their Differing Effects On Cardiovascular Risk, Aleena Abbasi, Bassil Abbasi, Scott Mintzer, Carla Lopinto-Khoury

Department of Neurology Faculty Papers

This review discusses the differing effects of enzyme-inducing and non-inducing antiseizure medications on cardiovascular risk and their implications for the management strategies of epilepsy patients. Traditional risk markers, including low density lipoprotein, high density lipoprotein and triglycerides, can be altered by both enzyme induction and inhibition. Other markers of vascular risk, including c-reactive protein, non-high-density lipoprotein and homocysteine, are affected by antiseizure medications, although adults and children may have different responses. The overall atherosclerotic risk picture is more complex due to indirect effects such as neuroendocrine function and the metabolic syndrome. Large scale data shows an evolving understanding of cardiovascular …

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), …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale

Annual Research Symposium

No abstract provided.

Pharmacogenomics Implications Of Tamoxifen In Breast Cancer Treatment: Clinical Relevance And Future Directions, Khalda E. M. Elhaj, Mahmoud M. E. Mudawi, Hamad A. Albagir A. Ali, Kamal A.A. Mohammed

Saudi Toxicology Journal

Tamoxifen is a cornerstone therapy for estrogen receptor-positive (ER+) breast cancer, improving survival and reducing recurrence. Its efficacy and toxicity, however, vary due to genetic polymorphisms influencing metabolism and transport. Key genes, such as CYP2D6, CYP3A4, and ATP-binding cassette transporters (ABCB1, ABCC2), are crucial in forming and distributing active metabolites like endoxifen. This review explores tamoxifen pharmacogenetics through an analysis of literature from PubMed, Scopus, Google Scholar, and PharmaGKB. Genetic variations like CYP2D6*10 in Asians and CYP2D6*17/29 in Africans impact therapeutic outcomes. Barriers to personalized tamoxifen therapy include inconsistent guidelines, limited access to genetic testing, and underrepresentation of ethnic groups …

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 …

Improving The Safety Of N,N-Dimethylacetamide As A Potential Treatment For Preterm Birth Using A Vaginal Nanoformulation, Asad Mir

Theses and Dissertations

With no available treatment for preterm birth, the field of reproductive medicine has been repurposing small molecule candidates into vaginal nanoformulations as potential treatments for the condition. The commercial solvent N,N-Dimethylacetamide (DMA) has previously been shown to delay and prevent inflammation-induced preterm birth in a mouse model. A vaginal nanoformulation of DMA loaded into a self-nanoemulsifying drug delivery system (SNEEDS) was studied to see if it can also be efficacious. A side by-side histological comparison was done in the more pertinent tissues of the reproductive tract between the traditional formulation of DMA given intraperitoneally (IP) and the vaginal nanoformulation of …

Gene Ontology Enrichment Reveals Pufa-Responsive Functional Themes In The Nucleus Accumbens Of Female Dba/2j Mice, Eman Mahjoub, Jennifer Wolstenholme Ph.D.

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

Validating A Genetic Knockout Of Ninein In A Mouse Model, Jessikah M. Buys, E R. Gnatowski, L Vermuri, A Safeer, L Holmes, M. F. Miles

IRBEH/Spit for Science Publications and Presentations

Ninein (Nin) is a microtubule associated protein that has been previously characterized by the Miles Lab for regulating the anxiety-reducing (anxiolytic) effects of alcohol, which is thought to contribute to development of Alcohol Use Disorder (AUD). Previous studies in the lab have investigated the role of Nin deletion on anxiety and ethanol-related behaviors in a conditional knockout model. The following set of studies seek to validate this genetic model. The model was validated using three main methods: immunofluorescence, qRT-PCR, and gel electrophoresis. In PCR studies, Ninein was significantly reduced in cre-expressing animals compared to controls. Gel Electrophoresis confirmed this reduction …

Effects Of Psychedelics On Acute Nicotine Pharmacological Responses, Aleny Oros, Belle Buzzi, Julian Vaughn, Burhan Buttar, Javier Gonzalez-Maeso, M Imad Damaj

IRBEH/Spit for Science Publications and Presentations

Smoking is a major risk factor for illnesses, such as cancers, cardiovascular diseases and respiratory conditions. In smoking, nicotine activates nicotinic acetylcholine receptors in the brain region. Prolonged use of nicotine will desensitize these specific receptors and cause nicotine dependence, resulting in smokers to experience withdrawal symptoms, such as anhedonia, depression, stress, and craving, leading to relapse.2 As the rate cigarette smoking has declined over the years, it is not significantly entitled by the tremendous increase rate of e-cigarette use. In a previous study being published, life-time use of psychedelics is associated with lower nicotine dependence.1

Psychedelics, specifically psilocybin, which …

Developing Stiripentol Analogs As Potential Ldh Inhibitors For The Treatment Of Glioblastoma, Anshika Y. Jain

Theses and Dissertations

Glioblastoma multiforme (GBM) is a highly proliferative brain tumor that has a 5-year survival rate of ~7 %. Temozolomide (TMZ) is the current standard of care therapeutic for GBM. However, 50% of patients develop resistance to TMZ. Therefore, further investigation for new GBM therapeutics is necessary to overcome this issue of drug resistance. GBM patients are known to overexpress lactate dehydrogenase (LDH), which is inversely correlated with their survival. This key glycolytic enzyme catalyzes the interconversion of pyruvate and lactate and plays an important role in cancer proliferation and invasion. Therefore, we aimed to inhibit LDH for developing therapeutics for …

Metformin In Overcoming Enzalutamide Resistance In Castration-Resistant Prostate Cancer, Kendall Simpson, Derek B. Allison, Daheng He, Jinpeng Liu, Chi Wang, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance. This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential antitumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of enzalutamide-resistant CRPC. We first …

Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart

Theses and Dissertations

Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …