Chemicals and Drugs Commons^™

Rationale And Design Of The Restore Trial: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Trial To Evaluate The Effect Of Shenfu Injection On Myocardial Injury In Stemi Patients After Primary Pci, Xiao Wang, Ruifeng Guo, Yingying Guo, Qian Guo, Yan Yan, Wei Gong, Wen Zheng, Hui Wang, Lei Xu, Hui Ai, Bin Que, Xiaoyan Yan, Xin-Liang Ma, Shaoping Nie

Department of Emergency Medicine Faculty Papers

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).

METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

The Effects Of Vitamin B1 Analog, Benfotiamine, On The Prevention Of Non-Small Cell Lung Cancer, Emely Fernandez, Hannah Christensen, Kota A. Ramana

Annual Research Symposium

No abstract provided.

Carvacrol Regulates Endotoxin -Induced Arachidonic Acid Metabolism., Aliea M. Jalali, Spencer Norton

Annual Research Symposium

Plant-derived essential oil prevents endotoxin-induced inflammatory response

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

Practice Of Building Biomedical Innovation Highland In The United States And Its Enlightenment To China, Xiaoling Ma

Bulletin of Chinese Academy of Sciences (Chinese Version)

The modern pharmaceutical industry began with the large-scale production of chemical drugs. With the radical innovation of basic sciences, such as life science, biomedicine has become the focus of the pharmaceutical industry, with broad prospects. Since World War II, the U.S. government, enterprises and scientific community have cultivated the biomedical industry and scientific foundation, created an environment for innovation, established an effective life science innovation system, and gradually become the innovation highland of biomedicine in the world. Building a biomedical innovation highland is an important part of China to become the world science center. China can learn from U.S. experience …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Saliva As A Diagnostic Tool To Measure Polycyclic Aromatic Hydrocarbon Exposure In Dental Patients Exposed To Intimate Partner Violence (Ipv), Aramandla Ramesh, Leslie R. Halpern, Janet H. Southerland, Samuel E. Adunyah, Pandu R. Gangula

School of Dentistry Faculty Publications

Background: Social habits such as tobacco use, alcohol consumption, and chemically contaminated diet contribute to poor oral health. Intimate Partner Violence (IPV) is a global public health epidemic which can exacerbate the prevalence of health conditions affecting a victim's lifespan. This study investigates using saliva as a biomarker for detecting levels of benzo(a)pyrene [B(a)P]; a toxicant present in cigarette smoke and barbecued meat in a population of IPV + female patients. Methods: A cross-sectional IRB-approved study utilized 63 female participants (37 African Americans [AA], and 26 non-African Americans [NAA]), who provided consent for the study. Participants submitted samples of saliva, …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When …

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Challenging Breast Cancer Through Novel Sulfonamide–Pyridine Hybrids: Design, Synthesis, Carbonic Anhydrase Ix Inhibition And Induction Of Apoptosis., Amira Khalil, Nashwa H. Zaher, Reham Mm Elhazek, Ahmed E. Gouda, Marwa G. Elgazzar

Pharmacy

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide–pyridine hybrids (2–12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC50 of compound 7 against carbonic anhydrase IX was 253 ± 12 nM using dorzolamide HCl as control. Conclusion: …

Increasing Substance Safety Concentrating On The Fentanyl Epidemic, Rachael A. Geesaman

CAFE Symposium 2023

An action plan designed to combat the fentanyl epidemic, I plan to educate others on the dangers of fentanyl by sharing and debunking common misconceptions and research online in a digestible format. To do so, I plan to create a website and Instagram account that has a global outreach to educate others and alleviate the stigma around substance use and death by fentanyl poisoning. Furthermore, the project is to spread awareness of current efforts and resources in specific areas in South Central PA, such as Adams County, Franklin, and Cumberland Counties.

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Formulation Of Encapsulated Nanoparticles Of Leek Extract As Antimicrobial And Anticancer Agent, Rawan Hassan Mohamed Elghanam

Theses and Dissertations

Leek extract (LEK) has broad therapeutic activity. However, plant extract use has many drawbacks, which could be resolved using nanocarriers. The purpose of this research work was to prepare chitosan nanoparticles (CS NPs) encapsulating LEK and investigate their antioxidant, antimicrobial, and anticancer activity. Gas chromatography-mass spectroscopy was used to determine the LEK components. The CS-LEK NPs were produced by tripolyphosphate (TPP) crosslinking with chitosan (CS) the ionic gelation methodology. The particle size was 331 nm, zeta potential (ZP) was 28.9 mv, polydispersity index (PDI) was 0.4, encapsulation efficiency (EE) was 65.6%, and loading capacity (LC) was 28.8 % of the …

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

Patterns Of Cannabis- And Substance-Related Congenital General Anomalies In Europe: A Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction:

Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred.

Methods:

CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank. Results: CARs were higher in countries with increasing daily use overall (p = 9.99 × 10⁻¹⁴, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 × 10⁻¹⁵, mEV = 3.04). In …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

January / February 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the January & February 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Synthesis Of Fluoroorganics And Applications Of Novel Fluorinated Building Blocks, Wei Wei

Dissertations, Theses, and Capstone Projects

Diastereoselectivity of fluorination of a carbanion alpha to a sulfone in enantiomerically pure N-Boc protected (R)- and (S)-2,2-dimethyl-4-((arylsulfonyl)methyl)oxazolidines has been studied. Fluorination proceeded with good to excellent diastereoselectivity, which was base-dependent and was highest with lithium diisopropylamide (LDA). Diastereoselectivity also depended on the aryl moiety of the aryl sulfone and was highest with benzothiazole-derived sulfones. Under basic conditions, epimerization at the C–F stereogenic center alpha to the sulfone has been achieved for the first time and proceeded with good to excellent diastereoselectivity, which was highest in the case of a benzothiazole sulfone and with a lithium base. …

Engineered Plga Nanofibers For Drug Delivery, Andrew Mancuso

Dissertations, Theses, and Capstone Projects

Poly-lactic-co-glycolic acid (PLGA) polymers are rapidly gaining momentum as a platform for next-generation drug delivery systems due to their ease and low cost of synthesis, favorable biocompatibility and biodegradability, and lack of toxicity. In particular, the application of drug-loaded PLGA nanofibers directly to a target tissue may represent a promising alternative to traditional routes of drug administration (e.g., oral, injectable) as they offer the potential to greatly improve bioavailability, increase efficacy, and reduce off-target toxicity. Furthermore, the use of such a system may potentially allow for greater flexibility in clinical drug development, by enabling the use of compounds which have …

Brivaracetam To Treat Partial Onset Seizures In Adults., Dustin Latimer, David Le, Evan P. Falgoust, Patrick Ingraffia, Alaa Abd-Elsayed, Elyse M. Cornett, Rupin Singh, Joohee Choi, Giustino Varrassi, Adam M. Kaye, Alan D. Kaye, Latha Ganti

School of Pharmacy Faculty Articles

PURPOSE OF REVIEW: Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials.

RECENT FINDINGS: Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory …

Suvorexant, A Novel Dual Orexin Receptor Antagonist, For The Management Of Insomnia., Andrew H. Han, Carolin R. Burroughs, Evan P. Falgoust, Jamal Hasoon, Grace Hunt, Juyeon Kakazu, Tim Lee, Adam M. Kaye, Alan D. Kaye, Latha Ganti

School of Pharmacy Faculty Articles

PURPOSE OF REVIEW: The present investigation is a comprehensive review regarding the use of Suvorexant for insomnia treatment. It covers the background, pathophysiology, and significance of addressing insomnia, the pharmaceutical details of Suvorexant, and its safety, efficacy, and implications in treating insomnia. We further discuss Suvorexant's role in targeting insomnia with other comorbidities.

RECENT FINDINGS: Insomnia refers to poor quality and/or quantity of sleep. While there are many existing treatments such as benzodiazepines, melatonin agonists, TCAs, and atypical antipsychotics used to target various receptors involved in normal induction and maintenance of sleep, Suvorexant is an antagonist that specifically targets orexin …

Review Of Interventional Therapies For Refractory Pediatric Migraine., Jacquelin Peck, Justin Zeien, Megha Patel, Elyse M. Cornett, Amnon A. Berger, Jamal Hasoon, Hisham Kassem, Jai Won Jung, Giovanni F. Ramírez, Paola Fugueroa, Neil R. Singhal, Jaehong Song, Adam M. Kaye, Alan D. Kaye, Sarang S. Koushik, Natalie H. Strand, Latha Ganti

School of Pharmacy Faculty Articles

This is a review of the latest and seminal evidence in pediatric migraine. It covers the etiology and pathophysiology known today, and then will review treatment options, efficacy and safety, quality of data and indications. Though migraine is usually regarded as an infliction in adults, it is not uncommon in the pediatric population and affects up to 8% of children. Children may experience migraine differently than adults, and present not only with headache but also frequent gastrointestinal symptoms. They are frequently shorter in duration than in adults. Traditional migraine treatment in adults is less effective in children. In this population, …

Molecular Characteristics Of Periodontal Health: Collagens: Defining The Healthy Human Gingival Collagen Transcriptome, Christina Zachariadou, Thomas Hart, Deborah Hooper, Angelo Mariotti

School of Dentistry Faculty Publications

Background: Defining periodontal health has been an ambitious and complex goal. The numerous and varied definitions of what constitutes periodontal health have resulted in a collection of subjective and unreliable clinical findings to diagnose and classify periodontal health and disease. The aim of this study was to fundamentally delineate the molecular characteristics of healthy periodontal tissues in men and women as they age, using the most abundant connective tissue component: Collagens. Methods: Healthy gingival biopsies were separated into “young” (aged 18–35 years, five men/five women) and “old” (≥60 years, five men/four women) age groups depending on biological sex. RNA was …

Dietary Strawberries Improve Serum Metabolites Of Cardiometabolic Risks In Adults With Features Of The Metabolic Syndrome In A Randomized Controlled Crossover Trial, Arpita Basu, Kenneth Izuora, Andrew Hooyman, Hal R. Scofield, Jeffrey L. Ebersole

Physical Therapy Faculty Articles and Research

Dietary strawberries have been shown to improve cardiometabolic risks in multiple clinical trials. However, no studies have reported effects on serum metabolomic profiles that may identify the target pathways affected by strawberries as underlying mechanisms. We conducted a 14-week randomized, controlled crossover study in which participants with features of metabolic syndrome were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, 1 serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were …

Potential Of Biduri Fiber (Calotropis Gigantea) As Material For Oil Spill Absorbent, Anne Sukmawati, Wulan Septiani

Journal of Materials Exploration and Findings

Biduri fiber (Calotropis gigantea) is a natural hollow fiber with hydrophobic and oleophilic properties potentially used as oil spilled sorbent from seawater. This study aims to determine the absorption capacity and efficiency of the Biduri fiber and membrane to fuel oil. Measurement of oil absorption to seawater was carried out at various fiber weights (0.5-1.5 g), fiber composition (50-95%), contact time (10-90 minutes), temperature (30 and 50°C), and compared with commercial products. The results showed that the fiber weight variation of 0.5-1.5 g has an average absorption efficiency of 96.67%, and the highest absorption was obtained in a weight of …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …