Medicine and Health Sciences Commons^™

Cdk8 And Cdk19: Positive Regulators Of Signal-Induced Transcription And Negative Regulators Of Mediator Complex Proteins, Mengqian Chen, Jing Li, Li Zhang, Lili Wang, Chen Cheng, Hao Ji, Serena Altilia, Xiaokai Ding, Guoshuai Cai, Diego Altomare, Michael Shtutman, Stephanie D. Byrum, Samuel G. Mackintosh, Alexey Feoktistov, Nataliya Soshnikova, Vladislav A. Mogila, Victor Tatarskiy, Maksim Erokhin, Darya Chetverina, Angga Prawira, Yi Ni, Stephan Urban, Campbell Mcinnes, Eugenia Broude, Igor Roninson

Faculty Publications

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small …

Overcoming Resistance Mechanisms To Cdk4/6 Inhibitor Treatment Using Cdk6-Selective Protac, Sarah Truong

Theses & Dissertations

Hormone receptor-positive (HR+) breast cancer (BC) constitutes approximately 75% of all breast cancer patients. These tumors rely on hormones, estrogen and progesterone, for their proliferation. The interaction between the hormones and their respective receptors enhances cyclin D expression, which results in the persistent activation of CDK4 and CDK6. The CDK4/6-cyclin D complex engages in a phosphorylation cascade that ultimately allows the cells to proceed past the G1/S checkpoint of the cell cycle. Inhibition of CDK4/6 has been shown to trigger cell cycle arrest, inhibit tumor growth, and induce apoptosis. Currently, there are three FDA-approved CDK4/6 inhibitors (CDK4/6i). A limitation of …

Quality Control Of 11 Cannabinoids By Ultraperformance Liquid Chromatography Coupled With Mass Spectrometry (Uplc-Ms/Ms), Ashraf Duzan, Desiree Reinken, Mufeed M Basti

HPD Articles

OBJECTIVE: Cannabinoid extraction from

METHODS: In this study, we developed rapid, sensitive, selective, accurate, and validated liquid chromatography-tandem mass spectrometry for the quantification of cannabinoids. The methods are for determining 11 cannabinoids in cannabis (hemp) extracted in oil form, and we investigated the accuracy of the labeling and thermal stability regarding the cannabinoids on 17 oil cannabis samples.

RESULTS: In the UPLC chromatogram, we see a good resolution and there is no matrix effect and the accuracy were 98.2% to 102.6%, and the precision was 0.52%-8.18%. The linearity of the calibration curves in methanol was with a regression

CONCLUSION: The …

Prep And Intimate Partner Violence Among Gay, Bisexual, And Other Men Who Have Sex With Men: A Scoping Review Of The Literature, Swarnali Goswami Ph.D., Joanne Canedo Pharm.D., Cynthia Siddique B.S., Erin Holmes Pharm.D., Ph.D., Marie Barnard Ph.D.

Faculty and Student Publications

Intimate Partner Violence (IPV) continues to be a serious public health concern, impacting nearly affecting diverse communities worldwide. Approximately one in three men experience sexual violence, physical violence, or stalking by an intimate partner in their lifetime.1 Men who have sex with men (MSM) are a particularly vulnerable population, facing unique challenges in the context of both IPV and HIV prevention. MSM experience disproportionately high rates of IPV and remain at an elevated risk of HIV transmission, making them a critical target group for research and intervention efforts.2,3 In recent decades, significant strides have been made in advancing the understanding …

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

Systematic Product And Process Design Of Versatile Perfluorocarbon Nanoemulsions For Elimination Of Hypoxia And Reactive Oxygen Species, Eric Lambert

Electronic Theses and Dissertations

According to a 2022 report, organs destined for transplantation are discarded 15% of the time for various reasons (Israni et al. 2022). This highlights a critical need in transplant practices. Transplant donor tissues are in need of essential nutrients, including molecular oxygen, to maintain integrity during preservation. A current trend in preservation is to perfuse the ex vivo tissue graft with nutrient-rich aqueous perfusate on a closed circuit. This practice, known as machine perfusion (MP) is limited by the absence of an oxygen-carrying component in the perfusate. Additionally, injuries to the recipient are sustained on reperfusion of the transplanted …

Evaluation Of Antimicrobial Stewardship For The Treatment Of Urinary Tract Infections After Pharmacist-Led Provider Education At The Center For Family Medicine, Kaylee Ayers, Faith E. Bader, Karly Blaalid, Tominee Sorenson, Sara Smith, Jennifer Ball

Pharmacy and Allied Health Professions Student Research Publications and Projects

Purpose: Urinary tract infections are a common outpatient infection, and proper antibiotic treatment is important for better patient outcomes, reducing healthcare costs, and reducing bacterial resistance. Specifically at the Center for Family Medicine (CFM), resident physicians may lack experience in prescribing proper antibiotic treatments based on patient factors for UTIs. The purpose of this study is to assess the appropriate use of antibiotics before and after a provider education pertaining to guideline recommended therapy for UTIs. The education included classifications of UTIs, first line and second line antibiotic therapy for acute uncomplicated UTIs, and first line therapy based on renal …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil

Pharmaceutical Sciences (PhD) Dissertations

Background: Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the traditional medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein-ligand complex interactions through docking studies. Also, evaluate nsLTP1 in vitro cytotoxic …

Bioinspired Polymers: Transformative Applications In Biomedicine And Regenerative Medicine., Hossein Omidian, Renae L. Wilson, Niloofar Babanejad

HPD Articles

Bioinspired polymers have emerged as a promising field in biomaterials research, offering innovative solutions for various applications in biomedical engineering. This manuscript provides an overview of the advancements and potential of bioinspired polymers in tissue engineering, regenerative medicine, and biomedicine. The manuscript discusses their role in enhancing mechanical properties, mimicking the extracellular matrix, incorporating hydrophobic particles for self-healing abilities, and improving stability. Additionally, it explores their applications in antibacterial properties, optical and sensing applications, cancer therapy, and wound healing. The manuscript emphasizes the significance of bioinspired polymers in expanding biomedical applications, addressing healthcare challenges, and improving outcomes. By highlighting these …

Authorizations, Prices, And Labeling Differences Of Therapeutic Biologics Marketed In The United States And Saudi Arabia, Turki Altowairgi

Pharmaceutical Sciences (PhD) Dissertations

BACKGROUND: Since 1982, Saudi Arabia (SA) and the United States (US) have seen an increase in therapeutic biologics authorization. However, each country has regulatory regulations governing the approval of these cutting-edge drugs. The high cost of biologics financially burdens healthcare systems and delays patient access to these treatments. Sometimes a company selling the same medications in various countries will have conflicting information on drug labels.

OBJECTIVES: This study compared the characteristics of therapeutic biologics authorization by the Saudi Food and Drug Authority (SFDA) and Food and Drug Administration (FDA) as of December 31, 2021. The study also compared the US …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank S Rai

Pharmaceutical Sciences (MS) Theses

The delivery of nucleic acid therapeutics across various cell membranes has always been one of the major challenges. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) have been promising for siRNA delivery. Therefore, to enhance siRNA delivery and efficient silencing of the STAT3 gene, herein, we hypothesized to use of fatty acylation with oleyl chain to our newly designed cell-penetrating peptide (WRH) to evaluate their silencing efficiency in breast and ovarian cancer cells. Therefore, the oleyl conjugated (WRH)_n (n=1-4) peptides were synthesized using Fmoc/tBu solid-phase peptide chemistry, followed by purification using Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC), …

Pharmacy Newsletter : August 2023, Pharmacy Department, Aga Khan University

Department of Pharmacy Archives

• Therapeutic Drug Monitoring of Digoxin – What You Need to Know?
• Composition of Common Poisons/Household Items
• Dexamethasone Induced Psychosis
• TOX TOK! Cement Ingestion
• Thromboprophylaxis in Critical Care Patients
• AKUH – Adverse Drug Reactions Reporting Trend – Q1 2023
• AKUH - Antimicrobial Stewardship Program Report - Q1 & Q2 2023
• AKUH - Pharmacists’ Intervention Statistics - Q1 2023
• Clinical Pharmacists in Multidisciplinary Rounds - Dashboard - Q1 2023

July / August 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the July & August 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Exploring The Experiences Of Underrepresented Students Pursuing Health-Related Graduate Or Professional Programs, Alison Williams

Electronic Theses and Dissertations

For many years graduate and professional education programs for the health professions have sought to increase the diversity of their student body to include students from a wider variety of backgrounds. Increasing the diversity of healthcare providers is an essential component of addressing inequities in healthcare. However, despite initiatives to increase racial and ethnic diversity in the health professions, these professions remain largely White and female. Previous researchers have sought to identify the reasons that racial and ethnic minorities are underrepresented in healthcare, and the barriers to persistence and success. Little research exists explaining why men are underrepresented in the …

Prorelaxant E-Type Prostanoid Receptors Functionally Partition To Different Procontractile Receptors In Airway Smooth Muscle, Ajay P. Nayak, Elham Javed, Dominic R. Villaba, Yinna Wang, Henry P. Morelli, Sushrut D. Shah, Nicholas Kim, Rennolds S. Ostrom, Reynold A. Pannettieri Jr., Steven S. An, Dale D. Tang, Raymond B. Penn

Pharmacy Faculty Articles and Research

Prostaglandin E2 imparts diverse physiological effects on multiple airway cells through its actions on four distinct E-type prostanoid (EP) receptor subtypes (EP1–EP4). Gs-coupled EP2 and EP4 receptors are expressed on airway smooth muscle (ASM), yet their capacity to regulate the ASM contractile state remains subject to debate. We used EP2 and EP4 subtype-specific agonists (ONO-259 and ONO-329, respectively) in cell- and tissue-based models of human ASM contraction—magnetic twisting cytometry (MTC), and precision-cut lung slices (PCLSs), respectively—to study the EP2 and EP4 regulation of ASM contraction and signaling under conditions of histamine or methacholine (MCh) stimulation. ONO-329 was superior (<0.05) to ONO-259 in relaxing MCh-contracted PCLSs (log half maximal effective concentration [logEC50]: 4.9 × 10−7 vs. 2.2 × 10−6; maximal bronchodilation ± SE, 35 ± 2% vs. 15 ± 2%). However, ONO-259 and ONO-329 were similarly efficacious in relaxing histamine-contracted PCLSs. Similar differential effects were observed in MTC studies. Signaling analyses revealed only modest differences in ONO-329– and ONO-259–induced phosphorylation of the protein kinase A substrates VASP and HSP20, with concomitant stimulation with MCh or histamine. Conversely, ONO-259 failed to inhibit MCh-induced phosphorylation of the regulatory myosin light chain (pMLC20) and the F-actin/G-actin ratio (F/G-actin ratio) while effectively inhibiting their induction by histamine. ONO-329 was effective in reversing induced pMLC20 and the F/G-actin ratio with both MCh and histamine. Thus, the contractile-agonist–dependent differential effects are not explained by changes in the global levels of phosphorylated protein kinase A substrates but are reflected in the regulation of pMLC20 (cross-bridge cycling) and F/G-actin ratio (actin cytoskeleton integrity, force transmission), implicating a role for compartmentalized signaling involving muscarinic, histamine, and EP receptor subtypes.

Comments Re: Workshop On Transforming Discoveries Into Products: Maximizing Nih’S Levers To Catalyze Technology Transfer, Fred D. Ledley M.D., Edward Zhou Pharm. D, Paula Chaves Da Silva, Ph. D.

CISI Publication

We are pleased to offer written comments to this workshop focused on “… making federally funded inventions more accessible to the public… .” These comments are informed by recent research from the Center for Integration of Science and Industry at Bentley University that has:

• Quantified the scope of NIH funding for basic or applied research, clinical development, or patents associated with drugs approved by the FDA 2010-2019. This work identified $187 billion in NIH-funded research directly related to these drugs (applied research – 17%) or their biological targets (basic research – 83%), representing a (discounted) investment comparable to reported levels …

Enhancing Therapeutic Efficacy Of Curcumin: Advances In Delivery Systems And Clinical Applications., Hossein Omidian, Renae L. Wilson, Sumana Dey Chowdhury

HPD Articles

Curcumin, a potent active compound found in turmeric and Curcuma xanthorrhiza oil, possesses a wide range of therapeutic properties, including antibacterial, anti-inflammatory, antioxidant, and wound healing activities. However, its clinical effectiveness is hindered by its low bioavailability and rapid elimination from the body. To overcome these limitations, researchers have explored innovative delivery systems for curcumin. Some promising approaches include solid lipid nanoparticles, nanomicelle gels, and transdermal formulations for topical drug delivery. In the field of dentistry, curcumin gels have shown effectiveness against oral disorders and periodontal diseases. Moreover, Pickering emulsions and floating in situ gelling systems have been developed to …

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

An Analysis Of Patterns Of Distribution Of Buprenorphine In The United States Using Arcos, Medicaid, And Medicare Databases, Zhi-Shan Hsu, Justina A. Warnick, Tice R. Harkins, Briana E. Sylvester, Neal K. Bharati, Letausjua B. Eley, Stephanie D. Nichols, Kenneth Mccall, Brian J. Piper

Pharmacy Faculty Scholarship

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil, Saud O. Alshammari, Bushra Siraj, Bishoy El-Aarag, Shamshad Zarina, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein–ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic …

Juvenile Nasopharyngeal Angiofibroma - A Case Report, Dr Godha Keesara Reddy Dr, Dr Anupama Chandrappa Dr, Dr Deepak K S

Radiology Teaching Files

15 year old male who presented with a 6 month history of nasal obstruction and recurrent nasal bleeding. He had had about ten episodes of epistaxis in the 3 months. Examination revealed that vital signs were essentially within normal limits.The nasal cavity revealed fresh blood in the right nasal cavity but the bleeding site could not be visualized. An impression of epistaxis secondary rhinosinusitis was made.

Spending On Phased Clinical Development Of Approved Drugs By The Us National Institutes Of Health Compared With Industry, Edward W. Zhou, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The launch of the Advanced Research Projects Agency for Health to advance new cures and address public concern regarding drug prices has raised questions about the roles of government and industry in drug development.

This cross-sectional study examined NIH funding for published research reporting the results of phased clinical trials of drugs approved between 2010 and 2019 and compared the findings with reported industry spending estimates. Data analysis was performed between May 2021 and August 2022 using PubMed data from January 1999 through October 2021 and NIH Research Portfolio Online Reporting Tools Expenditures and Results data from January 1999 through …

Proteoglycan 4 (Prg4)/Lubricin And The Extracellular Matrix In Gout, Khaled A. Elsaid, Gregory D. Jay, Ru Liu-Bryan, Robert Terkeltaub

Pharmacy Faculty Articles and Research

Proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes, released into synovial fluid, and adsorbed on cartilage and synovial surfaces. PRG4′s roles include cartilage boundary lubrication, synovial homeostasis, immunomodulation, and suppression of inflammation. Gouty arthritis is mediated by monosodium urate (MSU) crystal phagocytosis by synovial macrophages, with NLRP3 inflammasome activation and IL-1β release. The phagocytic receptor CD44 mediates MSU crystal uptake by macrophages. By binding CD44, PRG4 limits MSU crystal uptake and downstream inflammation. PRG4/CD44 signaling is transduced by protein phosphatase 2A, which inhibits NF-κB, decreases xanthine oxidoreductase (XOR), urate production, and ROS-mediated IL-1β …

The Effect Of Heat Treatment And Chemical Treatment On Natural Fibre To The Durability Of Wood Plastic Composites – A Review, Nuratiqah Asyiqin Mohd Nasharudin, Nur Fatihah Sulaiman, Nurul Aziemah Mohammad, Wan Nor Raihan Wan Jaafar, Falah Abu Dr., Siti Norasmah Surip

Journal of Materials Exploration and Findings

The application of WPC is not only limited to indoor applications but has been extended to exterior applications where properties of WPC could compromise during service life. WPC was derived from wood fiber of various sizes to reinforce polymers. Wood fiber has the advantage of a cheaper price, being abundantly available, and ease of processing, however, the critical factor is its hydrophilic nature, where moisture absorption is likely to occur. Thus, treatments for reducing the hydrophilicity of wood fibers are applied. By treatment of wood fiber, the surface impurities were removed, leaving the roughened surface of fibers, thus providing a …

High-Performing Conductive Hydrogels For Wearable Applications., Hossein Omidian, Sumana Dey Chowdhury

HPD Articles

Conductive hydrogels have gained significant attention for their extensive applications in healthcare monitoring, wearable sensors, electronic devices, soft robotics, energy storage, and human-machine interfaces. To address the limitations of conductive hydrogels, researchers are focused on enhancing properties such as sensitivity, mechanical strength, electrical performance at low temperatures, stability, antibacterial properties, and conductivity. Composite materials, including nanoparticles, nanowires, polymers, and ionic liquids, are incorporated to improve the conductivity and mechanical strength. Biocompatibility and biosafety are emphasized for safe integration with biological tissues. Conductive hydrogels exhibit unique properties such as stretchability, self-healing, wet adhesion, anti-freezing, transparency, UV-shielding, and adjustable mechanical properties, making …

Navigating The Path To Safe Compounding In Health Systems, Thomas Pile, Craig Kimble, Alberto Coustasse

Management Faculty Research

Across the country health systems are facing increasing drug shortages that are forcing pharmacists to rely far more heavily on compounding to meet the needs of patients. Additionally, several high-profile compounding incidents have helped highlight the importance of ensuring best practices are followed during sterile and nonsterile compounding to support patient safety and high-quality care. Specifically, in 2022, 160 drug shortages were reported in pharmacies. From January 1, 2023, to March 31, 2023, 47 drug shortages were reported, 55% of which were for injectables. In response, compounding has increasingly become a solution to bridge that gap.

Phad 690: Data Management & Statistical Software, Sujith Ramachandran Ph.D., Yinan Huang, Ms, Ph.D.

GMAS Course Syllabi

No abstract provided.

Sharksrx Newsletter Summer 2023, Nova Southeastern University

NSU Sharks Rx

No abstract provided.

Effect Of Nanoparticle Weight On The Cellular Uptake And Drug Delivery Potential Of Plga Nanoparticles, Prabhat Kattel, Shoukath Sulthana, JiřÍ Trousil, Dinesh Shrestha, David Pearson, Santosh Aryal

Pharmacy Faculty Publications and Presentations

Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(L-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight …

Mechanisms Of Theta Burst Transcranial Ultrasound Induced Plasticity In The Human Motor Cortex, Yazan Shamli Oghli, Talyta Grippe, Tarun Arora, Tasnuva Hoque, Ghazaleh Darmani, Robert Chen

Department of Medicine Faculty Papers

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear.

OBJECTIVE: We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS.

METHODS: Fourteen …