Medicinal and Pharmaceutical Chemistry Commons^™

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Investigation Of Warfarin–Human Serum Albumin Binding By Ultrafast Affinity Extraction Using Single- And Dual-Column Affinity Microcolumn Systems, Samiul Alim

Department of Chemistry: Dissertations, Theses, and Student Research

This dissertation examined the interaction of warfarin with human serum albumin (HSA) by using affinity chromatography, with particular emphasis on ultrafast affinity extraction (UAE) and affinity microcolumns. HSA affinity supports were prepared by immobilizing HSA onto diol-bonded silica via Schiff base chemistry and used to prepare affinity microcolumns for chromatographic studies under physiological-like conditions at pH 7.4 and 37.0 °C. UAE studies were performed to investigate the effects of residence time, flow rate, and column configuration on the measured apparent free fraction of warfarin and on the calculated apparent binding parameters. The results showed that the measured apparent free fraction …

Effects Of Normothermic Hepatic Ischemia–Reperfusion Injury On The Hepatic Disposition Of Arachidonic Acid And Its Cytochrome P450-Generated Metabolites In Rats, Vindhya Edpuganti, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose

Cytochrome P450 (P450) metabolites of arachidonic acid (AA) are potential therapeutic targets in ischemia–reperfusion (IR) injury, yet their disposition and actions in hepatic IR are unknown. Cellular AA and its P450 metabolites are primarily bound to lipid membranes, resulting in negligible free concentrations. This study investigates how hepatic IR injury impacts the disposition of free AA and its major P450 metabolites in rats.

Methods

Rats underwent 60 min of partial (70%) ischemia or sham surgery, followed by 5 min, 3 h, or 24 h of reperfusion. The effects of IR injury on free concentrations of AA and its major …

Herbularyo (Folk Healer): An Herbal Medicine Card Game, Maryjane T. Magsino, Inah Marie Q. Rivera, Armando M. Guidote, Genejane M. Adarlo

Chemistry Faculty Publications

Herbularyo, a card game teaching about herbal plants (HPs), was created and evaluated as a viable educational card game based on Tuomisto and Aksela’s criteria. A quasi-experiment was performed on 81 Grade 8 students from a private high school and 50 Grade 11 from a public high school. Independent t-test revealed that the control group (CG) and experimental group (EG) (p=0.386), and EG1 (played ≤5) and EG2 (played >5) (p=0.681) are not comparable with each other. Paired t-test showed EG performed better (p=0.001) than CG (p=0.901) whereas ANCOVA showed that playing Herbularyo improved students’ information retention (p=0.006). EG1 and EG2 …

Iron-Based Nanoparticles As Delivery Tools, Keykavous Parang, Rajesh Vadlapatla, Ajoy Koomer, Victoria Moran, Lanie Jackson, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Iron-based nanoparticles, particularly iron oxide nanostructures (IONPs), have emerged as versatile and clinically relevant platforms for drug delivery and theranostic applications. Among these, superparamagnetic iron oxide nanoparticles (SPIONs), including magnetite (Fe₃O₄) and maghemite (γ-Fe₂O₃), are the most extensively investigated due to their biocompatibility, magnetic responsiveness, and established safety profiles. Their unique superparamagnetic behavior enables external magnetic-field-guided targeting, magnetic resonance imaging (MRI) contrast enhancement, and magnetically triggered hyperthermia, enabling simultaneous diagnosis and therapy. Surface functionalization with polymers, silica, lipids, peptides, and biomolecules further improves colloidal stability, circulation time, targeting specificity, and controlled drug …

Structural Transformation Of A Hydrogel-Forming Cell Division Protein Zapb Of Multidrug Resistant Klebsiella Pneumoniae With Small Molecules, Ayesha Khan, M. Iqbal Choudhary, Sumaira Javaid, Humaira Zafar, Innokentiy Maslennikov, Atia-Tul Wahab

Pharmacy Faculty Articles and Research

Septal ring assembly protein ZapB (EMR18431.1) is involved in Z-ring formation, and nucleoid segregation during the bacterial cell division . It promotes cell division in the initial stages of the cell cycle through direct interaction with FtsZ, thus stimulating Z-ring assembly. The ZapB inhibition can make bacterial cell susceptible to primary antibiotics, and therefore considered as an important approach for adjuvent therapy against MDR bacterial infections. Hence in the current study, ZapB protein of multidrug resistant Klebsiella pneumoniae was cloned, and expressed in E. coli system. To understand its role, and to assess the mechanism of ZapB activation, the characteristic …

Patenting The Unexpected, Sean B. Seymore

Vanderbilt Law School Faculty Publications

Unexpected discoveries have transformed human existence. They’ve revolutionized science and spawned entire new fields of research. While unexpected discoveries seem inventive and worthy of patent protection, they don’t formally align with traditional patent theory. The bedrock principle that an invention begins with the conception of an idea in the inventor’s mind and ends with implementation doesn’t apply to unexpected discoveries. This misalignment is most acute for pharmaceuticals, where the discovery of new uses for old drugs has tremendous social and economic importance. Since a drug can inherently treat multiple conditions in a patient—even those unknown to the patient, doctor, or …

Cbx6-Ca9 Axis: An Epigenetic-Metabolic Vulnerability In Glioblastoma, Keykavous Parang

Pharmacy Faculty Articles and Research

Glioblastoma (GBM) remains one of the most therapeutically recalcitrant malignancies, with median survival rarely exceeding 15 months despite maximal therapy.¹ The hypoxic tumor microenvironment drives treatment resistance through epigenetic and metabolic adaptations.²

In this issue of Molecular Therapy Oncology, the study by Wang et al.³ demonstrates a novel regulatory axis between CBX6 (chromobox 6), a polycomb group protein, and CA9 (carbonic anhydrase 9), revealing how hypoxia-driven epigenetic reprogramming promotes tumor progression and identifying a mechanistically linked pathway for therapeutic intervention in GBM.

The study by Wang et al.3 advances our understanding of how the tumor microenvironment …

Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates In Oncology, Keon Niles Jafari, Charlene Chai, Shelby Kim, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake of drug conjugates via receptor-mediated endocytosis. This review delineates four clinically validated CSRs (HER2, Trop-2, Nectin-4, and SSTR2) with several FDA-approved drug conjugates. Furthermore, emerging CSRs (EGFR, DLL3, and keratin 1) that may support next-generation TDD platforms for cancer treatment are also highlighted. We discuss how CSR type, density on cancer cells, and its mechanism of endocytosis, …

Selectivity Modulation Of Small Cationic Membrane-Active Cyclic Peptides With Broad-Spectrum Activity Against Bacteria And Fungi, Sandeep Lohan, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Kaustav Das Gupta, Shakti Singh, Keykavous Parang

Pharmacy Faculty Articles and Research

To investigate how ring size and backbone flexibility influence antimicrobial potency and cytotoxicity, we synthesized a series of macrocyclic peptides of lead peptide p1 (c[Arg-Arg-arg-arg-dip-Trp-dip]) by incorporating Gly, 2-aminoethoxyacetic acid (EAA), or 2,4-diaminobutyric acid (Dab). Two optimized peptides, 6b and 10b, retained broad-spectrum activity against drug-resistant Gram-positive (MIC, 1.5–6.2 μg/mL) and Gram-negative bacteria (MIC, 4–25 μg/mL), as well as pathogenic fungi, while exhibiting enhanced selectivity for microbial cells. Their therapeutic indices (TI ∼407 and ∼394, respectively) were ∼2-fold higher than p1, indicating improved safety. Both peptides remained effective against Gram-negative pathogens beyond the reach of daptomycin, were rapidly bactericidal, and …

Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 inhibits synovial macrophage (SM) activation via xanthine oxidase (XO) and hypoxia inducible factor alpha (HIF-1α) suppression. We aimed to evaluate the contribution of PRG4-CD44 interaction to synovial homeostasis and investigate PRG4’s signaling dysfunction in synovial tissues from patients with osteoarthritis (OA). We hypothesized that CD44 mediates synovitis due to PRG4 loss and that PRG4 signaling dysfunction is associated with high-grade synovitis in OA.

Methods

Prg4^{FrtloxP/FrtloxP} are transgenic mice wherein tamoxifen (TAM) inactivates the Frt allele and creates a knockout state (Prg4^{FrtKO/FrtKO …}

Tumor Targeting With Peptide-Drug Conjugates: Showcasing Key Progress And Hurdles, Keykavous Parang, Thuy Do, Clare Dinh, Dorna Davanidavari, Max Foroughi, Troy Khong, Mahsa Moazen, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs’ small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss …

Dual Tyk2/Jak1 Inhibition By Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy For Rheumatoid Arthritis, Umar Saeed, Zahra Zahid Piracha, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background:

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and joint destruction. Targeted inhibition of intracellular signaling pathways, such as JAK-STAT, has improved RA treatment outcomes, though safety and selectivity remain as concerns. Brepocitinib, a dual TYK2/JAK1 inhibitor, has shown clinical efficacy in the management of autoimmune diseases, yet its mechanistic impact on synoviocytes remains underexplored.

Objectives:

To investigate the molecular and functional effects of brepocitinib on MH7A and RA-FLS synoviocytes, a key effector cell type in RA pathogenesis.

Methods:

MH7A and RA-FLS cells were treated with brepocitinib (0.5 µM, 1 µM, and 5 …

New Inhibitors Of Neuronal Nitric Oxide Synthase For The Treatment Of Melanoma, Amardeep Awasthi, Anika Patel, Huiying Li, Koon Mook Kang, Christine D. Hardy, Anas Ansari, Raghad Nowar, Hasan Alhaddad, Md. Emtiaz Hasan, Sun Yang, Thomas L. Poulos, Richard B. Silverman

Pharmacy Faculty Articles and Research

In 2024, an estimated 100,640 new cases of invasive melanoma were diagnosed in the U.S., with 9290 deaths. Our previous studies revealed that neuronal nitric oxide synthase (nNOS) derived nitric oxide plays a critical role in melanoma progression, making nNOS inhibition a promising strategy. High structural similarity among NOS isoforms requires careful design of nNOS inhibitors to avoid off-target effects. Our previous lead, HH044, demonstrated potent antimelanoma activity but exhibited only moderate nNOS selectivity. Here, we utilized a structure-based approach to design nNOS inhibitors that promote interactions with human nNOS-specific residue His342. Compound 9 exhibited inhibition of both human ( …

Molecular Survival Strategies Against Kidney Filtration: Implications For Therapeutic Protein Engineering, William Heaps, Anna Elise Packard, Kristina M. Mccammon, Tyler P. Green, Joseph P. Talley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60–70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity—essential considerations for the rational design of next-generation …

Direct Effects Of Capsaicin On Voltage-Dependent Calcium Channels Of Mammalian Skeletal Muscle, Dmytro Isaev, Tatiana Prytkova, Badarunnisa Mohamed, Mohamed Omar Mahgoub, Keun-Hang Susan Yang, Murat Oz

Pharmacy Faculty Articles and Research

Capsaicin, a naturally occurring polyphenol, is known to affect energy expenditure and muscle fatigue and modulate contractions in skeletal muscle. The L-type Ca²⁺ channels are known to be an important ion channel involved in the various muscle functions and the effect of capsaicin on the skeletal L-type Ca²⁺ channels is currently unknown. In this study, the effects of capsaicin and capsaicin analogs on depolarization-induced Ca²⁺ effluxes through L-type Ca²⁺ channels in transverse tubule membranes from rabbit skeletal muscle and L-type Ca²⁺ currents recorded using the whole-cell patch clamp technique in rat myotubes were examined. Capsaicin, …

Structural Basis For The Subtype-Selectivity Of KCa2.2 Channel Activators, Young-Woo Nam, Alena Ramanishka, Yang Xu, Rose Marie Haynes Yasuda, Joshua A. Nasburg, Dohyun Im, Meng Cui, K. George Chandy, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance (K_Ca2.2) and intermediate-conductance (K_Ca3.1) Ca²⁺-activated K⁺ channels are gated by a Ca²⁺-calmodulin dependent mechanism. NS309 potentiates the activity of both K_Ca2.2 and K_Ca3.1, while rimtuzalcap selectively activates K_Ca2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of NS309-bound K_Ca2.2 and K_Ca3.1, in addition to structures of rimtuzalcap-bound K_Ca2.2 and mutant K_Ca3.1_R355K. The different conformations of calmodulin and the cytoplasmic HC helices in the …

Proteome-Based Identification And Validation Of Nxpe3 In Childhood Acute Lymphoblastic Leukaemia, Najia Tabassum, Yamna Khurshid, Basir Syed, Aftab Ahmad, Sadia Muhammad, Rehan Imad, Talat Mirza

Pharmacy Faculty Articles and Research

Background: Childhood acute lymphoblastic leukaemia (cALL) tends to metastasize to central nervous system. Treatment with antileukemic agents against CNS leukaemia is an essential component for cure in ALL. Hence, it is essential to identify biomarkers for CNS infiltration. Proteomics, supported by mass spectrometry, is the platform for exploring biomarkers in various biological samples, contributing to translational research. Objectives: This study aimed to identify the plasma proteome profile of children across different risk groups of cALL. Neurexophilin and PC-esterase family, member 3 (NXPE3), was validated. The protein-protein interactions (PPI) of NXPE3 were evaluated with bioinformatics analyses. Methods: Plasma …

Formulation Development Of Topical Inserts Containing Doxycycline And Doxycycline Combined With Tenofovir Alafenamide And Elvitegravir For The Prevention Of Sexually Transmitted Infections, Vivek Agrahari, M. Melissa Peet, Jasmin Monpara, Rijo John, Sriramakamal Jonnalagadda, Pardeep K. Gupta, Meredith R. Clark, Gustavo F. Doncel

CONRAD Publications

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 …

Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …

The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

Evaluation Of Hypolipidemic And Hypoglycemic Effects Of Dillenia Indica L. On Alloxan-Induced Diabetic Rats, Md Mahfuj Alam Siddiq

Student Scholarship

Context: Dillenia indica L. a tropical fruit-bearing plant native to South and Southeast Asia, has attracted scientific interest due to its rich phytochemical composition and potential therapeutic benefits in managing diabetes, lipid disorders, and oxidative stress. Objective: The objective of this study was to investigate the potential antidiabetic and lipid-lowering properties of D. indica fruit and bark extracts in a rat model of alloxan-induced type 2 diabetes. Methods: Diabetes was induced in rats using an intraperitoneal injection of alloxan (160 mg/kg) after a 12-hour fast. The chloroform fractions of D. indica fruit and bark (200 mg/kg) were administered intraperitoneally, with …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

Editorial: Molecular Mechanisms Of Ion Channel Activation And Modulation, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

"Ion channels are integral membrane proteins that regulate the passage of ions across cell membranes, thereby shaping processes as diverse as neuronal signaling, muscle contraction, and hormone secretion. Channel activation is typically initiated by a stimulus such as voltage, ligand binding, or mechanical stress that induces conformational changes and opens the channel pore. Beyond activation, channels are subject to fine-tuned modulation by a wide range of endogenous and exogenous agents, from lipids and neurotransmitters to pharmacological drugs. Modulators can stabilize the open, closed, or inactivated states, shift ligand affinities, or alter gating kinetics. Dissecting the structural and dynamic basis of …

Clinical Pharmacokinetics, Pharmacodynamics, And Drug Interactions Of Remimazolam, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Remimazolam, an ultrashort-acting benzodiazepine, has emerged as a promising sedative agent for procedural sedation and general anesthesia. It combines the favorable properties of traditional benzodiazepines with a rapid onset and offset of action, largely due to its unique metabolism via hepatic carboxylesterases rather than cytochrome P450 enzymes. This metabolism allows for predictable pharmacokinetics, reducing the risk of prolonged sedation and drug accumulation, particularly in patients with hepatic or renal impairment. Clinically, remimazolam demonstrates non-inferiority to midazolam and propofol, with advantages including a lower incidence of hypotension and respiratory depression. Multiple randomized controlled trials have shown its efficacy in various procedural …

Peptide-Based Inorganic Nanoparticles As Efficient Intracellular Delivery Systems, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Anthony Nguyen, Vian Khoury, Keykavous Parang

Pharmacy Faculty Articles and Research

Background/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe3O4) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, …

Impact Of A Multi-Strain L. Crispatus-Based Vaginal Synbiotic On The Vaginal Microbiome: A Randomized Placebo-Controlled Trial, Jacques Ravel, Sheri Simmons, Eleni Greenwood Jaswa, Sara Gottfried, Miriam Greene, Susan Kellogg-Spadt, Dirk Gevers, Diane M. Harper

Institute of Emerging Health Professions Faculty Papers

A clinical trial of a multi-strain vaginal synbiotic (NCT05659745, registered 12/19/2022 at clinicaltrials.gov) led to an optimal vaginal microbiome dominated by L. crispatus (CST I). The synbiotic led to a significant increase in L. crispatus compared to placebo (p <  0.05), and conversion to CST I was significantly higher with the vaginal synbiotic than with placebo (90 vs 11%; p <  0.002). Mechanistically, the synbiotic reduced Gardnerella vaginalis and Candida, clinically important microbes.