Chemicals and Drugs Commons^™

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 …

Addition Of Prg4 To Optimize The Anti‑Adhesive Properties Of Tissue Barrier Sepraflm®, Ava J. Marks, Khaled A. Elsaid, Ling X. Zhang, Timmy Lin, Janette Baird, Tannin A. Schmidt, Gregory D. Jay

Pharmacy Faculty Articles and Research

Purpose

Postsurgical adhesion remains a significant clinical challenge. Seprafilm^® is widely used as a barrier to reduce adhesion formation, however its efficacy may be inconsistent. Recombinant human proteoglycan-4 (rhPRG4), a surface-active, anti-inflammatory glycoprotein found in synovial fluid inhibits cell and protein adhesion. This study investigated whether coating Seprafilm with rhPRG4 could enhance its anti-adhesive potential.

Methods

Macrophages (J774), human fibroblast-like synoviocytes (HFLS), and melanoma (A375) cells were cultured on tissue culture wells treated with rhPRG4 or bovine submaxillary mucin (BSM) to determine optimal seeding density. Seprafilm sheets were coated with rhPRG4 or BSM (0.78–200 µg/mL). Cell adhesion was quantified …

Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado

Pharmacy Faculty Articles and Research

Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer’s disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood–brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed …

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 …

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 …

Microbiome-Responsive Hydrogels: From Biological Cues To Smart Biomaterials, Rajesh Vadlapatla, Amir Nasrolahi Shirazi, Ajoy Koomer, Judy Weng, Matthew Ernest Ghilarducci, Alai Qudus, Keykavous Parang

Pharmacy Faculty Articles and Research

Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect the dynamic, disease-relevant complexity of native tissue microenvironments. Microbe-colonized tissues display distinctive biochemical features driven, shaped by microbial metabolism, including localized pH gradients, short-chain fatty acid production, secretion of quorum-sensing molecules, biofilm formation, and expression of specialized enzymes. These endogenous, spatiotemporally regulated signals are closely linked to host physiology and pathology but remain underutilized in hydrogel …

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 …

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, …

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 …

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. …

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 …

Guide For Selecting Experimental Models To Study Dietary Fat Absorption, Andromeda M. Nauli, Ann Phan, Karen Mai, Kathleen Tran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, …

Citronellol Reduces Sepsis-Induced Renal Inflammation Via Ap-1/Nf-Κb/Tnf-Α Pathway, Huda Rashid Atiyah, Sarmed H. Kathem, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sepsis is characterized by the over-production of pro-inflammatory cytokines. Cecal ligation and puncture (CLP) is a well-accepted model for recreating sepsis-induced renal injury in mice. The current study investigates how citronellol, a naturally occurring substance with a variety of biological characteristics, can prevent acute kidney inflammation brought on by CLP. In the CLP mouse model, citronellol was administered orally at doses of 50 and 100 mg/kg. Serum levels of creatinine and urea were used as markers of renal function, and the Murine Sepsis Score (MSS) was used to assess the severity of sepsis. According to our findings, CLP caused a …

Additive Effects Of N-Acetylcysteine And [R4W4] Combination Treatment On Mycobacterium Avium, Kayvan Sasaninia, Iffat Hasnin Era, Nezam Newman, Jesse Melendez, Wajiha Akif, Eashan Sharma, Omid Nikjeh, Ira Glassman, Cristián Jiménez, Navya Sharma, Ama Xu, Maria Lambros, Miou Zhou, Rakesh Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R₄W₄] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R₄W₄] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of …

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …

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 …

Air Pollution And Diseases: Signaling, G Protein-Coupled And Toll Like Receptors, Isabella Cattani-Cavalieri, Katrina F. Ostrom, Jordyn Margolis, Rennolds S. Ostrom, Martina Schmidt

Pharmacy Faculty Articles and Research

Air pollution is a significant public health issue that impacts lung health, particularly in vulnerable populations such as children, the elderly, and individuals with pre-existing respiratory conditions. Both natural and anthropogenic sources of air pollution give rise to a variety of toxic compounds, including particulate matter (PM), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAHs). Exposure to these pollutants is strongly associated with the development and exacerbation of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Notably, early life exposure to pollutants such as …

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, …

Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar

Pharmacy Faculty Articles and Research

Alterations in drug transporters in acute liver failure and chronic liver diseases, such as cirrhosis, have been reviewed before. However, there is a lack of comprehensive reviews on how liver surgery, including transplantation and partial hepatectomy, affects drug transporters. Because ischemia–reperfusion (IR) injury is a hallmark of liver transplantation and most other surgical procedures of the liver, this review focuses on the effects of IR injury, in addition to liver resection, on the expression and function of transporters in the liver and remote organs. Most of the reported studies in this area are carried out in animal models of liver …

A Genetically-Engineered Thyroid Gland Built For Selective Triiodothyronine Secretion, Cintia E. Citterio, Berenice Morales-Rodriguez, Xiao-Hui Liao, Catherine Vu, Rachel Nguyen, Jessie Tsai, Jennifer Le, Ibrahim Metawea, Ming Liu, David P. Olson, Samuel Refetoff, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG …

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …

Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the …

New Onset Diabetic Retinopathy With Glucagon-Like Peptide-1 Receptor Agonists: A Case Report, Jennifer Ko, Yaseman Jahromi

Pharmacy Faculty Articles and Research

Background

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …

Impact Of Stereochemical Replacement On Activity And Selectivity Of Membrane-Active Antibacterial And Antifungal Cyclic Peptides, Sandeep Lohan, Anastasia G. Konshina, Eman H. M. Mohammed, Naiera M. Helmy, Srishhti K. Jha, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we report a library of 7-mer macrocyclic peptides designed by systematically replacing one, multiple, or all L-amino acids with their D-isomers in our previously identified hit compounds. Lead peptides, 15c and 16c, showed broad-spectrum activity against bacteria (Gram-positive minimum inhibitory activity (MIC 1.5–6.2 µg/mL and Gram-negative MIC 6.2–25 µg/mL) and fungi (MIC = 3.1–25 µg/mL). Additionally, peptides 15c and 16c showed rapid kill kinetics and biofilm degradation potential against both bacteria and fungi, while resistance development was not observed. The antimicrobial effect of these macrocyclic peptides was attributed to their membranolytic action, which was confirmed by calcein dye …

Engineering Lipid–Polymer Nanoparticles For Sirna Delivery To Cancer Cells, Arthur Manda, Abdulelah Alhazza, Hasan Uludağ, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Background: RNA interference (RNAi) is a powerful tool that can target many proteins without the expensive and time-consuming drug development studies. However, due to the challenges in delivering RNA molecules, the potential impact of RNAi approaches is yet to be fully realized in clinical settings. Lipid nanoparticles (LNPs) have been the most successful delivery system for nucleic acids, but targeted delivery to a solid tumor still eludes the developed LNPs. We hypothesized that specially designed low-molecular-weight PEIs can partially or completely replace the ionizable lipids for more accommodating vehicles due to the structural flexibility offered by polymers, which could …

Molecular Insights Into The Role Of Estrogen Receptor Beta In Ecdysterone Mediated Anabolic Activity, Syeda Sumayya Tariq, Madiha Sardar, Muhammad Shafiq, Hendrick Heinz, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Ecdysterone, often dubbed a “natural steroid,” has garnered significant attention among athletes for its reputed growth-promoting and anabolic properties. Unlike synthetic anabolic steroids, which are classified as controlled substances, ecdysteroids remain largely unregulated in many countries and are widely marketed as dietary supplements. Notably, ecdysterone has been included in the World Anti-Doping Agency (WADA) monitoring program, highlighting its potential impact on athletic performance and raising questions about its regulation. Emerging evidence indicates that, unlike traditional anabolic steroids that act primarily via the Androgen Receptor (AR), ecdysterone’s anabolic effects may be mediated through Estrogen Receptors (ERs), particularly Estrogen Receptor beta (ERβ). …