Chemicals and Drugs Commons^™

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

Glutathione-Responsive Tannic Acid-Assisted Fret Nanomedicine For Cancer Therapy, Partha Laskar, Anupam Dhasmana, Sudhir Kotnala, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications and Presentations

In cancer combination therapy, a multimodal delivery vector is used to improve the bioavailability of multiple anti-cancer hydrophobic drugs. Further, targeted delivery of therapeutics along with simultaneous monitoring of the drug release at the tumor site without normal organ toxicity is an emerging and effective strategy for cancer treatment. However, the lack of a smart nano-delivery system limits the application of this therapeutic strategy. To overcome this issue, a PEGylated dual drug, conjugated amphiphilic polymer (CPT-S-S-PEG-CUR), has been successfully synthesized by conjugating two hydrophobic fluorescent anti-cancer drugs, curcumin (CUR) and camptothecin (CPT), through an ester and a redox-sensitive disulfide (-S-S-) …

From Deep Mutational Mapping Of Allosteric Protein Landscapes To Deep Learning Of Allostery And Hidden Allosteric Sites: Zooming In On “Allosteric Intersection” Of Biochemical And Big Data Approaches, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The recent advances in artificial intelligence (AI) and machine learning have driven the design of new expert systems and automated workflows that are able to model complex chemical and biological phenomena. In recent years, machine learning approaches have been developed and actively deployed to facilitate computational and experimental studies of protein dynamics and allosteric mechanisms. In this review, we discuss in detail new developments along two major directions of allosteric research through the lens of data-intensive biochemical approaches and AI-based computational methods. Despite considerable progress in applications of AI methods for protein structure and dynamics studies, the intersection between allosteric …

Splenic Asssessment Of The Toxicological Effects Of Dietary Consumption Of Pfbs (Perfluorobutane Sulfonic Acid), Janelene Sanders

Honors College Theses

Perfluoroalkyl and polyfluoroalkyl substances (PFAs) are synthetic chemicals that can pose adverse health effects such as kidney cancer, thyroid disease, pregnancy complications and liver damage due to human exposure in food and drinking water. In this study, the class of PFAs that will be investigated is Perfluorobutane sulfonic acid (PFBS), which is commonly found in the environment and consumer products such as wastewater, dust, and floor cleaners, and consists of 4 carbon chain bonded with fluorine and a sulfonic acid functional group. To accomplish study goals, PFBS, a shorter carbon chain length was ingested by Sprague Dawley rats. Serum LDH …

Augmenting Project Echo For Opioid Use Disorder With Data-Informed Quality Improvement, Owen B. Murray, Marcy A. Doyle, Bethany M. Mcleman, Lisa A. Marsch, Elizabeth C. Saunders, Katherine Cox, Delitha Watts, Jeanne Ryer

Faculty Publications

Background

National opioid-related overdose fatalities totaled 650,000 from 1999 to 2021. Some of the highest rates occurred in New Hampshire, where 40% of the population lives rurally. Medications for opioid use disorder (MOUD; methadone, buprenorphine, and naltrexone) have demonstrated effectiveness in reducing opioid overdose and mortality. Methadone access barriers disproportionally impact rural areas and naltrexone uptake has been limited. Buprenorphine availability has increased and relaxed regulations reduces barriers in general medical settings common in rural areas. Barriers to prescribing buprenorphine include lack of confidence, inadequate training, and lack of access to experts. To address these barriers, learning collaboratives have trained …

Case Series: Continued Remission Of Ptsd Symptoms After Discontinuation Of Prazosin, Christie Richardson, Jonathan Yuh, Jing Su, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. …

Enhancement Of Deep Learning Protein Structure Prediction, Ruoming Shen

Modeling, Simulation and Visualization Student Capstone Conference

Protein modeling is a rapidly expanding field with valuable applications in the pharmaceutical industry. Accurate protein structure prediction facilitates drug design, as extensive knowledge about the atomic structure of a given protein enables scientists to target that protein in the human body. However, protein structure identification in certain types of protein images remains challenging, with medium resolution cryogenic electron microscopy (cryo-EM) protein density maps particularly difficult to analyze. Recent advancements in computational methods, namely deep learning, have improved protein modeling. To maximize its accuracy, a deep learning model requires copious amounts of up-to-date training data.

This project explores DeepSSETracer, a …

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

The Application Of Continuous Stationary Phase Gradients To High-Performance Liquid Chromatography And Its Potential To Improve Pharmacological Research, Hannah Klose

Senior Honors Theses

The separation of mixtures into different components is integral to experimentation and analysis in a multitude of fields. Chromatography is one of the most popular, well-developed, and well-studied methods used to examine the makeup of a mixture. Thus, the improvement of chromatographic procedures directly benefits research across many scientific disciplines. The application of a continuous stationary phase gradient to High-Performance Liquid Chromatography (HPLC) methods has been proposed to improve the separation of complex mixtures that are difficult to achieve with existing separation techniques. By incorporating a gradient stationary phase, analysts will create a more selective mode of separation to improve …

Contrast-Enhanced Cardiac Magnetic Resonance Imaging With A Manganese-Based Alternative To Gadolinium For Tissue Characterization Of Acute Myocardial Infarction, Benjamin P. Bonner, Salva R. Yurista, Jaume Coll-Font, Shi Chen, Robert A. Eder, Anna N. Foster, Khoi D. Nguyen, Peter Caravan, Eric M. Gale, Christopher Nguyen

School of Medicine Faculty Publications

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium-based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast-enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. METHODS AND RESULTS: Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed …

Moderate-Intensity Exercise Improves Mesenteric Arterial Function In Male Uc Davis Type-2 Diabetes Mellitus (Ucd-T2dm) Rats: A Shift In The Relative Importance Of Endothelium-Derived Relaxing Factors (Edrf), Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric …

Pyrazole-Sulfonamide Scaffold Featuring Dual-Tail Strategy As Apoptosis Inducers In Colon Cancer, Amira Khalil, Reham M. M. El Hazek, Nashwa H. Zaher, Hagar E. S. Emam, Marwa G. Elgazzar

Pharmacy

Dual-tail strategy has been successfully utilized in the development of novel carbonic anhydrase IX (CA IX) inhibitors. Herein we adopted this approach in the design and synthesis of a series of novel pyridine sulfonamide-pyrazole hybrid scaffold mimicking dual-tail inhibitors of CA IX. A library of 15 compounds was synthesized and assessed for their potential cytotoxic effects against colorectal cancer cells. Compounds 3, and 11 induced potential cytotoxic effects against the three cancer cell lines (HCT-116, HT-29, and SW-620) with IC₅₀s’ of 45.88, 28.27, and 16.57 uM, 25.01, 8.99, and 3.27 µM, respectively. Both compounds induced cellular apoptosis …

A Scoping Review Of Risk And Protective Factors For Negative Cannabis Use Consequences, Timothy J. Grigsby, Andrea Lopez, Larisa Albers, Christopher J. Rogers, Myriam Forster

Social & Behavioral Health Faculty Publications

Objective:

Numerous reviews have examined risk and protective factors for alcohol-related negative consequences, but no equivalent review of risk and protective factors exists for cannabis-related negative consequences (CRNCs)-a gap filled by the present study. This scoping review examined survey-based research of risk and protective factors for CRNCs such as neglecting responsibilities, blacking out, or needing more cannabis.

Methods:

Three databases (PubMed, PsycINFO, and Google Scholar) were searched for peer-reviewed manuscripts published between January 1, 1990, and December 31, 2021. A qualitative synthesis was performed using the matrix method and the results were organized using the socioecological model as a framework. …

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage

Doctoral Dissertations

RNA is poised to revolutionize medicine. By simply changing the sequence, one therapeutic can be converted into a wholly new one, with little or no change in manufacturing and formulation. While a single mRNA vaccine produced at massive scale can treat billions, the re-codability of RNA will also enable the widespread growth of personalized medicines. T7 RNA polymerase is highly efficient at the synthesis of therapeutic RNA, but is known to produce unintended RNA impurities during synthesis. These products arise from the encoded RNA rebinding the enzyme such that its 3’ end serves as a primer for extension. This leads …

Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker

Doctoral Dissertations

Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …

Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …

March / April 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the March & April 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Repurposing The Calcium Biosensor Twitch-2b: Creating Transition Metal Detection Proteins Through Fluorescent Analysis, Sarah Mateer

Honors Projects and Presentations: Undergraduate

Metal ions are key in regulating many biological functions, but their accumulation is associated with neurological diseases. Cellular metal ion concentrations are often detected through exogenous fluorescent dyes, but less invasive and more specific detection can be done using genetically encoded FRET-enabled metal-binding proteins, such as Twitch-2B. Twitch-2B and other ratiometric proteins change conformation when a calcium ion is bound to the active site, initiating an energy transfer between two fluorescent peptides that can be quantified through fluorescent spectroscopy. Previous analyses have demonstrated that wild-type calcium binding can be accurately detected via this method for concentrations from 10 uM to …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …