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Articles 61 - 90 of 806
Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Specificity Of Interaction Of Antimicrobial Peptide With Cell Membrane, Srishhti Kumar Jha
Specificity Of Interaction Of Antimicrobial Peptide With Cell Membrane, Srishhti Kumar Jha
Pharmaceutical Sciences (MS) Theses
Antimicrobial resistance (AMR) is an increasing global health threat due to its rising incidence worldwide. Resistant microbial infections have become difficult to treat and pose serious risks to patients. In 2019, AMR was responsible for approximately 1.27 million deaths globally, with numbers continuing to rise. The World Health Organization (WHO) has highlighted the urgent need for new antibiotics with novel mechanisms of action and low toxicity to combat this issue. Antimicrobial peptides (AMPs) represent a promising solution. These peptides exhibit broad-spectrum antimicrobial activity and rapid killing kinetics, reducing the likelihood of resistance development. AMPs primarily target bacterial cell membranes. Their …
Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar
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 …
Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang
Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang
Pharmacy Faculty Articles and Research
Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and …
Small Current, Big Potential: Bridging Mechanistic Insight Of The Sk Channel With Translational Promise, Yang Zheng, Miao Zhang, Nipavan Chiamvimonvat
Small Current, Big Potential: Bridging Mechanistic Insight Of The Sk Channel With Translational Promise, Yang Zheng, Miao Zhang, Nipavan Chiamvimonvat
Pharmacy Faculty Articles and Research
"Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, with a lifetime risk of approximately 1 in 4 for adults aged 40 years and above. Despite advances in clinical management, AF remains a major public health concern. Its burden extends beyond symptoms; it quadruples the risk of heart failure and increases the likelihood of stroke fivefold – strokes that are often more severe and fatal than those unrelated to AF. In the United States alone, AF-associated healthcare costs exceed $26 billion annually, and the cost is projected to grow as the population ages (Ko et al., 2025). Regarding current treatments, …
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
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 …
Pharmacogenetic Exploration Of Burenorphine And Related Metabolites In Umbilical Cord Blood, Amelia Monfared, Derek E. Murrell, Darshan S. Shah, Melissa Hoang, Stacy D. Brown, Sam Harirforoosh
Pharmacogenetic Exploration Of Burenorphine And Related Metabolites In Umbilical Cord Blood, Amelia Monfared, Derek E. Murrell, Darshan S. Shah, Melissa Hoang, Stacy D. Brown, Sam Harirforoosh
Pharmacy Faculty Articles and Research
The goal of this study was to explore associations between single-nucleotide polymorphisms (SNPs) and umbilical cord blood concentrations of buprenorphine and its metabolites following maternal administration. This is a sub-study of a prospective observational cohort investigation which included pregnant women receiving buprenorphine for opioid use disorder during pregnancy. Following delivery, umbilical cord blood samples were collected and genotyped using a pharmacogenetic panel. The drug and metabolite concentrations were analyzed through liquid chromatography-mass spectrometry, and genetic association analysis was completed using PLINK software. The included neonates (n = 14) had a mean birth weight of 3.00 ± 0.39 kg and were …
Cilia In The Brain Display Region-Dependent Oscillations Of Length And Orientation, Roudabeh Vakil Monfared, Sherif Abdelkarim, Pieter Derdeyn, Kiki Chen, Hanting Wu, Kenneth Leong, Tiffany Chang, Justine Lee, Sara Versales, Surya M. Nauli, Kevin Beier, Pierre Baldi, Amal Alachkar
Cilia In The Brain Display Region-Dependent Oscillations Of Length And Orientation, Roudabeh Vakil Monfared, Sherif Abdelkarim, Pieter Derdeyn, Kiki Chen, Hanting Wu, Kenneth Leong, Tiffany Chang, Justine Lee, Sara Versales, Surya M. Nauli, Kevin Beier, Pierre Baldi, Amal Alachkar
Pharmacy Faculty Articles and Research
In this study, we conducted high-throughput spatiotemporal analysis of primary cilia length and orientation across 22 mouse brain regions. We developed automated image analysis algorithms, which enabled us to examine over 10 million individual cilia, generating the largest spatiotemporal atlas of cilia. We found that cilia length and orientation display substantial variations across different brain regions and exhibit fluctuations over a 24-h period, with region-specific peaks during light-dark phases. Our analysis revealed unique orientation patterns of cilia, suggesting that cilia orientation within the brain is not random but follows specific patterns. Using BioCycle, we identified rhythmic fluctuations in cilia length …
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
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
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
New Onset Diabetic Retinopathy With Glucagon-Like Peptide-1 Receptor Agonists: A Case Report, Jennifer Ko, Yaseman Jahromi
Pharmacy Faculty Articles and Research
Background
Diabetic retinopathy (DR) is a leading cause of acquired vision loss in middle-aged adults. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used in the management of type 2 diabetes (T2D). Emerging evidence has suggested a possible link between GLP-1 RAs and the acceleration of DR. However, the evidence on the association between GLP-1RA therapies and risk for DR has been mixed, and there is limited guidance on how to manage new onset or worsening DR for patients taking GLP-1RA therapy. The objective of this case report is to describe the clinical decision-making involved in the management of a patient …Utilizing Pharmacogenomics To Improve Students' Self-Perception On The Interprofessional Competencies Of Roles And Responsibilities, And Teams And Teamwork, Amanda Brown, Moom R. Roosan, Robert Goldsteen, Scott D. Ochs, Reza Taheri
Utilizing Pharmacogenomics To Improve Students' Self-Perception On The Interprofessional Competencies Of Roles And Responsibilities, And Teams And Teamwork, Amanda Brown, Moom R. Roosan, Robert Goldsteen, Scott D. Ochs, Reza Taheri
Pharmacy Faculty Articles and Research
Introduction
Pharmacogenomics (PGx) is an emerging discipline with the potential to revolutionize personalized medicine, but its successful implementation requires interprofessional collaboration. To address this need, a virtual interprofessional education (IPE) session was designed for student pharmacists and medical students to engage in a case-based learning experience.
Objective
The primary objective was to develop and implement an IPE activity focused on a patient case requiring PGx-guided dual antiplatelet therapy and to assess students' perceptions of two Interprofessional Education Collaborative (IPEC) Version 3 Core Competencies. A secondary objective was to identify key lessons from the session.
Methods
Pharmacist and physician faculty collaboratively …
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
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
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 …
Multidrug Resistance: Are We Still Afraid Of The Big Bad Wolf, Abdulelah Alhazza, Adenike Oyegbesan, Emira Bousoik, Hamidreza Montazeri Aliabadi
Multidrug Resistance: Are We Still Afraid Of The Big Bad Wolf, Abdulelah Alhazza, Adenike Oyegbesan, Emira Bousoik, Hamidreza Montazeri Aliabadi
Pharmacy Faculty Articles and Research
After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a …
Engineering Lipid–Polymer Nanoparticles For Sirna Delivery To Cancer Cells, Arthur Manda, Abdulelah Alhazza, Hasan Uludağ, Hamidreza Montazeri Aliabadi
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
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). …
Bridging Oral And Systemic Health: Exploring Pathogenesis, Biomarkers, And Diagnostic Innovations In Periodontal Disease, Max Foroughi, Mahmoud Torabinejad, Nikola Angelov, David M. Ojcius, Keykavous Parang, Marcus Ravnan, Jerika Lam
Bridging Oral And Systemic Health: Exploring Pathogenesis, Biomarkers, And Diagnostic Innovations In Periodontal Disease, Max Foroughi, Mahmoud Torabinejad, Nikola Angelov, David M. Ojcius, Keykavous Parang, Marcus Ravnan, Jerika Lam
Pharmacy Faculty Articles and Research
Purpose
This narrative review explores the multifaceted links between periodontal diseases (gingivitis and periodontitis) and systemic health conditions, including cardiovascular disease, diabetes, adverse pregnancy outcomes, Alzheimer’s disease, cancers, rheumatoid arthritis, and respiratory infections. It aims to synthesize evidence on how local oral infections exert systemic effects and evaluate the potential of diagnostic technologies to monitor these interactions.
Methods
This narrative review synthesizes current scientific literature on periodontal disease pathogenesis, focusing on key pathogens (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum) and their roles in driving local and systemic inflammation via virulence factors and microbial dysbiosis. It examines biomarker-based diagnostic approaches …
An Exploratory Pharmacogenetic Pilot Study Of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate And Tenofovir Disoproxil Fumarate, Derek E. Murrell, Benjamin C. Kennard, Maria E. Bertoni, David B. Cluck, Jonathan P. Moorman, Stacy D. Brown, Keshang Wang, Michelle M. Duffourc, Sam Harirforoosh
An Exploratory Pharmacogenetic Pilot Study Of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate And Tenofovir Disoproxil Fumarate, Derek E. Murrell, Benjamin C. Kennard, Maria E. Bertoni, David B. Cluck, Jonathan P. Moorman, Stacy D. Brown, Keshang Wang, Michelle M. Duffourc, Sam Harirforoosh
Pharmacy Faculty Articles and Research
Background and Objectives
The nucleoside reverse transcriptase inhibitors tenofovir alafenamide fumarate and tenofovir disoproxil fumarate are frequently employed in treating human immunodeficiency virus. Further, each form of tenofovir requires laboratory monitoring to determine efficacy and tolerability among patients. This study sought to investigate the relationship, if any, of single nucleotide polymorphisms (SNPs) and selected clinical parameters.
Methods
The study population, predominantly Caucasian males with a median age of 53.0 years [interquartile range 46.0–59.0], was assayed for genetic variations using an iPLEX ADME PGx Pro v1.0 Panel.
Results
Although several SNP relationships were found with both forms of tenofovir, many of …
Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang
Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang
Pharmacy Faculty Articles and Research
Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …
Integrative Computational Modeling Of Distinct Binding Mechanisms For Broadly Neutralizing Antibodies Targeting Sars-Cov-2 Spike Omicron Variants: Balance Of Evolutionary And Dynamic Adaptability In Shaping Molecular Determinants Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Integrative Computational Modeling Of Distinct Binding Mechanisms For Broadly Neutralizing Antibodies Targeting Sars-Cov-2 Spike Omicron Variants: Balance Of Evolutionary And Dynamic Adaptability In Shaping Molecular Determinants Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
In this study, we conducted a comprehensive analysis of the interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and four neutralizing antibodies—S309, S304, CYFN1006, and VIR-7229. Using integrative computational modeling that combined all-atom molecular dynamics (MD) simulations, mutational scanning, and MM-GBSA binding free energy calculations, we elucidated the structural, energetic, and dynamic determinants of antibody binding. Our findings reveal distinct dynamic binding mechanisms and evolutionary adaptation driving the broad neutralization effect of these antibodies. We show that S309 targets conserved residues near the ACE2 interface, leveraging synergistic van der Waals and electrostatic interactions, while S304 focuses on …
Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli
Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli
Pharmacy Faculty Articles and Research
Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in …
Probing Binding And Allosteric Mechanisms Of The Kras Interactions With Monobodies And Affimer Proteins : Ensemble-Based Mutational Profiling And Thermodynamic Analysis Of Binding Energetics And Allostery Reveal Diversity Of Functional Hotspots And Cryptic Pockets Linked By Conserved Communication Network, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Guang Hu, Gennady M. Verkhivker
Probing Binding And Allosteric Mechanisms Of The Kras Interactions With Monobodies And Affimer Proteins : Ensemble-Based Mutational Profiling And Thermodynamic Analysis Of Binding Energetics And Allostery Reveal Diversity Of Functional Hotspots And Cryptic Pockets Linked By Conserved Communication Network, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Guang Hu, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
KRAS, a historically "undruggable" oncogenic driver, has eluded targeted therapies due to its lack of accessible binding pockets in its active state. This study investigates the conformational dynamics, binding mechanisms, and allosteric communication networks of KRAS in complexes with monobodies (12D1, 12D5) and affimer proteins (K6, K3, K69) to characterize the binding and allosteric mechanisms and hotspots of KRAS binding. Through molecular dynamics simulations, mutational scanning, binding free energy analysis and network-based analyses, we identified conserved allosteric hotspots that serve as critical nodes for long-range communication in KRAS. Key residues in β-strand 4 (F78, L80, F82), α-helix 3 (I93, H95, …
Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli
Application Of Bioactive Materials Primary Cilia As A Novel Delivery Vehicle, Ayan K. Barui, Farideh Amirrad, Vansh Goel, Sharareh Ohadi, Rajasekharreddy Pala, Ashraf M. Mohieldin, Andromeda M. Nauli, Surya M. Nauli
Pharmacy Faculty Articles and Research
Primary cilia are hair-like structured cell organelles functioning as cellular antennae with chemosensory and mechanosensory roles. Dysfunction of cilia results in ciliopathies, including renovascular diseases (polycystic kidneys, hypertension, aneurysm), mental impedances (Alzheimer's disease, Parkinson's disease, dementia), metabolic diseases (obesity, developmental skeleton defects), blindness, and so on. With a diameter of 150 nm, cilia can be cleaved, released and circulated in the body as injury biomarkers. We here assessed the potential use of isolated cilia as a novel delivery vehicle. Cilia were isolated from renal epithelial cells, and a specific-targeting chemotherapeutic was designed on the cilia. The data show a remarkable …
The Legacy Of William M. Pardridge (1947–2024) On The Science And Fields Concerned With The Physiology Of The Blood-Brain Barrier And The Transport Of Drugs To The Brain, Ruben J. Boado, Ulrich Bickel, Rachita K. Sumbria
The Legacy Of William M. Pardridge (1947–2024) On The Science And Fields Concerned With The Physiology Of The Blood-Brain Barrier And The Transport Of Drugs To The Brain, Ruben J. Boado, Ulrich Bickel, Rachita K. Sumbria
Pharmacy Faculty Articles and Research
This article highlights the scientific achievements and professional career of William M. Pardridge, who passed away on 18th of June 2024. He was born in 1947 in Bethesda, Maryland, USA. William, known affectionately as Bill, was one of the most influential researchers in the blood-brain barrier (BBB) field. Bill’s research contributions to the field spun over 6 decades at the University of California, Los Angeles, and it was focused on the molecular physiology of the BBB, including the carrier-mediated transport of nutrients and small molecule drugs, the receptor-mediated transport of peptides and molecular Trojan horses, gene therapy of the brain …
Functional Characterization Of The C-Terminal Cholinesterase-Like (Chel) Domain Of The Thyroid Hormone Precursor Protein, Berenice Morales-Rodriguez
Functional Characterization Of The C-Terminal Cholinesterase-Like (Chel) Domain Of The Thyroid Hormone Precursor Protein, Berenice Morales-Rodriguez
Pharmaceutical Sciences (MS) Theses
Vertebrate life is unsustainable without thyroid hormones. The only known precursor for thyroid hormone synthesis is thyroglobulin (Tg), composed of upstream regions I-II-III and a C-terminal cholinesterase-like (ChEL) domain, which bears 47% similarity to acetylcholinesterase (AChE). Mutations in Tg cause congenital hypothyroidism, the most common congenital endocrinopathy affecting 1 in 2,000-4,000 newborns, with a varying degree of phenotypic manifestations. Tg protein, regulated by TSH, is secreted to the lumen of thyroid follicles, where thyroxine (T4) is formed primarily at the N-terminus, and triiodothyronine (T3) is formed primarily in the ChEL domain. Previous in vitro studies indicated …
Design And Structural Basis Of Selective 1,4-Dihydropyridine Inhibitors Of The Calcium-Activated Potassium Channel KCa3.1, Seow Theng Ong, Young-Woo Nam, Joshua A. Nasburg, Alena Ramanishka, Xuan Rui Ng, Zhong Zhuang, Stephanie Shee Min Goay, Hai M. Nguyen, Latika Singh, Vikrant Singh, Alicia Rivera, M. Elaine Eyster, Yang Xu, Seth L. Alper, Heike Wulff, Miao Zhang, K. George Chandy
Design And Structural Basis Of Selective 1,4-Dihydropyridine Inhibitors Of The Calcium-Activated Potassium Channel KCa3.1, Seow Theng Ong, Young-Woo Nam, Joshua A. Nasburg, Alena Ramanishka, Xuan Rui Ng, Zhong Zhuang, Stephanie Shee Min Goay, Hai M. Nguyen, Latika Singh, Vikrant Singh, Alicia Rivera, M. Elaine Eyster, Yang Xu, Seth L. Alper, Heike Wulff, Miao Zhang, K. George Chandy
Pharmacy Faculty Articles and Research
The 1,4-dihydropyridines, drugs with well-established bioavailability and toxicity profiles, have proven efficacy in treating human hypertension, peripheral vascular disorders, and coronary artery disease. Every 1,4-dihydropyridine in clinical use blocks L-type voltage-gated calcium channels. We now report our development, using selective optimization of a side activity (SOSA), of a class of 1,4-dihydropyridines that selectively and potently inhibit the intermediate-conductance calcium-activated K+ channel KCa3.1, a validated therapeutic target for diseases affecting many organ systems. One of these 1,4-dihydropyridines, DHP-103, blocked KCa3.1 with an IC50 of 6 nM and exhibited exquisite selectivity over calcium channels and a panel of …
Molecular Insights Into Antibiofilm Inhibitors Of Streptococcus Mutans Glucosyltransferases Through In Silico Approaches, Lubna Atta, Ali Raza Siddiqui, Mamona Mushtaq, Sajida Munsif, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq
Molecular Insights Into Antibiofilm Inhibitors Of Streptococcus Mutans Glucosyltransferases Through In Silico Approaches, Lubna Atta, Ali Raza Siddiqui, Mamona Mushtaq, Sajida Munsif, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq
Pharmacy Faculty Articles and Research
Streptococcus mutans, a primary cariogenic bacterium, plays a central role in dental caries, one of the most widespread chronic diseases globally. Glucosyltransferases (GTFs) are key virulence factors in this process, as they synthesize extracellular polysaccharides that contribute to biofilm formation and pathogenicity. Targeting GTFs has emerged as a promising strategy for preventing dental caries, with previous studies demonstrating its potential efficacy. This study builds on our prior work by providing detailed molecular insights into the binding modes of previously identified GTF inhibitors. Using computational tools, including density functional theory, molecular docking, and molecular dynamics simulations, we examined the binding …
Enhancing Holistic Patient Care Of Black Individuals Diagnosed With Hiv And Comorbid Chronic Conditions, Marc Fleming, Saharnaz Nejdat, Jon C. Schommer, Crystal K. Hodge
Enhancing Holistic Patient Care Of Black Individuals Diagnosed With Hiv And Comorbid Chronic Conditions, Marc Fleming, Saharnaz Nejdat, Jon C. Schommer, Crystal K. Hodge
Pharmacy Faculty Articles and Research
Background
Pharmacists can play a crucial role in delivering the holistic care model. Research suggests that HIV-positive African American patients particularly benefit from this approach compared to other communities. Typically, pharmacists in community pharmacy settings are limited in their access to a patient's medical record, preventing holistic care delivery.
Objectives
This study addressed the impact of access to medical records on a holistic patient care approach among pharmacists engaged in medication therapy management.
Methods
This was a sub-analysis of a randomized controlled trial of the impact of community pharmacist access to medical records during MTM for African Americans diagnosed with …
Cryo-Em Structures Of The Small-Conductance Ca2+-Activated KCa2.2 Channel, Young-Woo Nam, Dohyun Im, Ana Santa Cruz Garcia, Marios L. Tringides, Hai Minh Nguyen, Yan Liu, Razan Orfali, Alena Ramanishka, Grigore Pintilie, Chih-Chia Su, Meng Cui, Diomedes E. Logothetis, Edward W. Yu, Heike Wulff, K. George Chandy, Miao Zhang
Cryo-Em Structures Of The Small-Conductance Ca2+-Activated KCa2.2 Channel, Young-Woo Nam, Dohyun Im, Ana Santa Cruz Garcia, Marios L. Tringides, Hai Minh Nguyen, Yan Liu, Razan Orfali, Alena Ramanishka, Grigore Pintilie, Chih-Chia Su, Meng Cui, Diomedes E. Logothetis, Edward W. Yu, Heike Wulff, K. George Chandy, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (KCa2.1-KCa2.3) channels modulate neuronal and cardiac excitability. We report cryo-electron microscopy structures of the KCa2.2 channel in complex with calmodulin and Ca2+, alone or bound to two small molecule inhibitors, at 3.18, 3.50, 2.99 and 2.97 angstrom resolution, respectively. Extracellular S3-S4 loops in β-hairpin configuration form an outer canopy over the pore with an aromatic box at the canopy’s center. Each S3-S4 β-hairpin is tethered to the selectivity filter in the neighboring subunit by inter-subunit hydrogen bonds. This hydrogen bond network flips the aromatic residue (Tyr362) in …
The Effects Of Cyclic Peptide [R4w4] In Combination With First-Line Therapy On The Survival Of Mycobacterium Avium, Melissa Kelley, Kayvan Sasaninia, Ali Badaoui, Ira Glassman, Arbi Abnousian, Nadia Rai, Rakesh K. Tiwari, Vishwanath Venketaraman
The Effects Of Cyclic Peptide [R4w4] In Combination With First-Line Therapy On The Survival Of Mycobacterium Avium, Melissa Kelley, Kayvan Sasaninia, Ali Badaoui, Ira Glassman, Arbi Abnousian, Nadia Rai, Rakesh K. Tiwari, Vishwanath Venketaraman
Pharmacy Faculty Articles and Research
Background: Mycobacterium avium (M. avium) is a nontuberculous mycobacterium (NTM) that can cause pulmonary and extrapulmonary infections mostly in immunocompromised individuals, such as those with HIV and diabetes. Traditionally, rifampicin (RIF) and azithromycin (AZ) have been used for a 12-month duration as first-line antibiotics against M. avium. Due to the increased multidrug resistance, novel ways, such as enhancement of macrophages response, are needed to provide adequate immune response required to clear M. avium infection.
Methods and findings: In this study, we aim to study the effects of using THP-1 cells, which are monocyte-like cells, to induce a …