Other Pharmacy and Pharmaceutical Sciences Commons^™

Brain Microvascular Endothelial Cells Possess A Second Cilium That Arises From The Daughter Centriole, Karthikeyan Thirugnanam, Ankan Gupta, Francisco Nunez, Shubhangi Prabhudesai, Amy Y. Pan, Surya M. Nauli, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Primary cilia from the brain microvascular endothelial cells (ECs) are specialized cell-surface organelles involved in mediating sensory perception, cell signaling, and vascular stability. Immunofluorescence (IF) analysis of human primary brain microvascular ECs reveals two cilia per cell. To confirm the in vitro observation of the two-cilia phenotype in human primary brain ECs, ECs isolated from mouse brain were cultured and stained for cilium. Indeed, brain ECs from a ciliopathic mouse (polycystic kidney disease or Pkd2−/−) also possess more than one cilium. Primary cilium emerges from the mother centriole. Centriole analysis by IF suggests that in brain ECs, markers …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

Untargeted Metabolomics Analysis On Kidney Tissues From Mice Reveals Potential Hypoxia Biomarkers, Muhammad Imran Sajid, Francisco J. Nunez, Farideh Amirrad, Moom Rahman Roosan, Tom Vojtko, Scott Mcculloch, Amal Alachkar, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic …

Addressing The Crisis: Leveraging The United Nations Sustainable Development Goals To Prepare Student Leaders To Tackle The Opioid Epidemic, Sharon Xavioer, Laressa Bethishou, Madeline Dintzner, Reza Taheri, Jelena Lewis

Pharmacy Faculty Articles and Research

The United States faces several ongoing public health issues including the opioid epidemic. This article describes a new model aimed at providing a framework that incorporates the United Nations (UN) Sustainable Development Goals (SDGs) to develop pharmacy student leaders through education, experiences, and development of critical skills. This holistic approach can serve as an example methodology to equip future leaders across public health domains to tackle many of the critical problems we face today.

Improving Pharmacist-Led Pediatric Patient Education On Oral Chemotherapy At Home, Anika Patel, Christopher M. Nguyen, Kristin Willins, Elsabella Y. Wang, Grace Magedman, Sun Yang

Pharmacy Faculty Articles and Research

Oral chemotherapy (OC) has been increasingly used in pediatric patients diagnosed with cancer, which is primarily managed in the outpatient setting. Different from adults, pediatric patients face unique challenges in administering these hazardous medications at home. Because of the complexity of pediatric pharmaceutical care and the hazardous nature of chemotherapy agents, comprehensive patient education is imperative to mitigate the potential safety risks associated with OC administration at home. Pharmacists play a vital role in patient education and medication consultations. However, the lack of practice guidelines and limited resources supporting OC counseling are noted. Additional barriers include insufficient knowledge and training …

Perbedaan Kadar Insulin-Like Growth Factor-1 Dan Tumor Necrosis Factor-Α Serum Pada Berbagai Derajat Sarkopenia Pasien Lanjut Usia: Studi Potong Lintang, Auliangi Tamayo, Roza Mulyana, Rose Dinda Martini

Jurnal Penyakit Dalam Indonesia

Introduction. Sarcopenia is a phenomenon of progressive decline in muscle function that occurs due to the aging process. Insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-α (TNF-α) have an important role in the occurrence of sarcopenia as a positive and negative regulator of muscle mass. Research shows differences in IGF-1 and TNF-α levels between sarcopenia and non-sarcopenia groups, but research on differences in severity of sarcopenia remains unclear. The purpose of this study was to determine the difference in levels of IGF-1 and TNF-α in various degrees of sarcopenia in elderly patients.

Methods. This was an analytical observational …

Stress-Induced Changes In Carf Expression Determine Growth Arrest, Apoptosis, Or Malignant Transformation In Cultured Human Cells: Molecular Evidence And Its Application, Mallika Khurana, Rajkumar Singh Kalra, Anupama Chaudhary, Amr Omar, Xiaoshuai Li, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background: CARF (Collaborator of ARF)/CDKN2AIP is an essential protein, first cloned as a binding partner of ARF. It was subsequently shown to interact with p53, HDM2 proteins and regulate growth arrest and apoptosis by its multimodal mechanism of action. Over-expression of CARF caused senescence like growth arrest of cells, its knock-down triggered apoptosis. Intriguingly, malignantly transformed cells showed high level of CARF expression. Based on these findings, we hypothesized that level of CARF expression may be a key determinant of cell proliferation fates; where an increase in its levels causes growth arrest/senescence, but beyond a threshold it activates carcinogenesis.

Methods: …

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …

Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia

Research Symposium

Epithelial Growth Factor (EGF) is the primary source in regeneration and stimulation of essential fibroblasts cells commonly found in epithelium. Studies have shown that snake venom components are becoming a growing factor in treating illnesses such as cancer, muscular dystrophy, chronic pain, blood pressure, blood clotting, etc. EGF in human cells contains a promising quaternary structure that can bind to snake venom metalloproteinases, proposing a means of activating biochemical responses through protein-protein interactions to regulate unwanted cellular functions. This supports promising research in achieving a greater understanding of regulation along cellular pathways through ligands, increasing the likelihood of targeting unwanted …

Assessing Perspectives Of A Global Health Area Of Concentration Within The Pharmd Curriculum, Jennifer Ko, Lauren Jonkman, Vidya Balakrishna Sharma, Emily Liu, Sharon E. Connor

Pharmacy Faculty Articles and Research

Introduction

While global health education in pharmacy expands, limited research has described the outcome of completing a global health area of concentration on career decisions, perceptions on cultural sensitivity, health disparity awareness, and global health competencies among pharmacists and students.

Methods

This mixed methods study enrolled 21 graduates and 17 student pharmacists who participated in a global health concentration at one school of pharmacy in the United States. Data sources included graduate interviews and surveys, student pharmacist focus groups, and global health competency self-assessments.

Results

Five themes emerged among graduates: (1) skills were applicable to diverse settings, (2) early exposure …

Murine Models Of Graft Versus Host Disease (Gvhd): Focus On Ocular Gvhd, Philipp Steven, Victor L. Perez, Ajay Sharma

Pharmacy Faculty Articles and Research

Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms …

A Causal Inference Study: The Impact Of The Combined Administration Of Donepezil And Memantine On Decreasing Hospital And Emergency Department Visits Of Alzheimer’S Disease Patients, Ehsan Yaghmaei, Albert Pierce, Hongxia Lu, Yesha M. Patel, Louis Ehwerhemuepha, Ahmad Rezaie, Seyed Ahmad Sajjadi, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Alzheimer’s disease is the most common type of dementia that currently affects over 6.5 million people in the U.S. Currently there is no cure and the existing drug therapies attempt to delay the mental decline and improve cognitive abilities. Two of the most commonly prescribed such drugs are Donepezil and Memantine. We formally tested and confirmed the presence of a beneficial drug-drug interaction of Donepezil and Memantine using a causal inference analysis. We applied doubly robust estimators to one of the largest and high-quality medical databases to estimate the effect of two commonly prescribed Alzheimer’s disease (AD) medications, Donepezil and …

Folate Conjugated Nanomedicines For Selective Inhibition Of Mtor Signaling In Polycystic Kidneys At Clinically Relevant Doses, Rajasekharreddy Pala, Ayan K. Barui, Ashraf M. Mohieldin, Jing Zhou, Surya M. Nauli

Pharmacy Faculty Articles and Research

Although rapamycin is a very effective drug for rodents with polycystic kidney disease (PKD), it is not encouraging in the clinical trials due to the suboptimal dosages compelled by the off-target side effects. We here report the generation, characterization, specificity, functionality, pharmacokinetic, pharmacodynamic and toxicology profiles of novel polycystic kidney-specific-targeting nanoparticles (NPs). We formulated folate-conjugated PLGA-PEG NPs, which can be loaded with multiple drugs, including rapamycin (an mTOR inhibitor) and antioxidant 4-hydroxy-TEMPO (a nephroprotective agent). The NPs increased the efficacy, potency and tolerability of rapamycin resulting in an increased survival rate and improved kidney function by decreasing side effects and …

Optimization Of Lubrication And Compression Process Parameters Of Vitamin C Film-Coated Caplets, Ernestine Arianditha Pranasti, Ratna Annisa Utami, Yuda Prasetya Nugraha

Pharmaceutical Sciences and Research

Tablet production is a very intricate process influenced by numerous process variables or parameters. This study aimed to identify the critical processing variables that affect Critical Quality Attributes (CQAs) of vitamin C film-coated caplets utilizing a statistical experimental design. A two-level complete factorial design with two central points was used to examine the process parameters that posed the greatest risk to CQAs. The process variables investigated included mesh size and duration for the lubrication process, as well as speed and main thickness for compression. Statistical results showed that mesh number, lubrication time, and their interaction significantly affect flow rate, Hausner …

Solid Lipid Nanoparticles (Sln): Formulation And Fabrication, Gabriella F. Punu, Yahdiana Harahap, Qonita Kurnia Anjani, Pietradewi Hartrianti, Ryan F. Donnelly, Delly Ramadon

Pharmaceutical Sciences and Research

Solid lipid nanoparticles (SLN) have emerged as a novel drug delivery system and have been utilized for delivering various kinds of drugs since the 1990s. These particles may consist of multiple solid lipids, including glycerides, waxes, and fatty acids, and can be stabilized by a wide range of surfactants. SLN have garnered significant attention from researchers due to its innovative and versatile nature. Moreover, such delivery system has numerous advantages over traditional colloidal carriers, such as liposomes, polymeric nanoparticles, and emulsions. Several research groups have been developing SLN formulations and fabrication techniques based on their intended purpose, and this research …

Optimization Of 3,4-Dimethoxychalcone And Rutin Containing Gel With Simplex Lattice Design And In Vitro-In Vivo Test As A Sunscreen, Hana Anisa Fatimi, Abdul Karim Zulkarnain, Marlyn Dian Laksitorini

Pharmaceutical Sciences and Research

3,4-Dimethoxychalcone and rutin, a flavonoid that contains chromophore groups, can absorb UV light and thus can be developed as a sunscreen. The objective of this study was to determine the optimum formula of 3,4-dimethoxychalcone and rutin containing gel, evaluate its physical stability, and activity of 3,4-dimethoxychalcone and rutin gel as a sunscreen through in vitro and in vivo tests. HPMC, CMC-Na, and methylcellulose were formulated into a gel base to obtain good adhesion and a clear appearance gel. Simplex Lattice Design (SLD) with Design Expert software version 10 was utilized to determine the optimum gel formulation. UVA-PF protection, photostability with …

Evaluation Of Anti-Vegf And Pan-Retinal Photocoagulation Laser Therapies In Proliferative Diabetic Retinopathy Patients: A Systematic Review, Senyum Indrakila, Namira Putri Imani, Aiman Hilmi Asaduddin, Muzakiya Lailatul Karima, Lygia Angelica Widjaja

Pharmaceutical Sciences and Research

Diabetic retinopathy is a complication of diabetes that is one of the top five causes of blindness in those over 50. The standard treatment is pan-retinal photocoagulation, which is effective but has established side effects. Anti-vascular endothelial growth factor (anti-VEGF) therapy becomes an alternative to avoid the side effects caused by laser therapy. This systematic review aims to know the effectiveness of anti-VEGF therapy compared to the pan-retinal photocoagulation laser therapy in patients with proliferative diabetic retinopathy. This review was carried out using a systematic review checklist on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The articles reviewed …

Individual And Combined Effect Of Eudragit® Rs 100 And Eudragit® Rl 100 On Sustained Release Characteristics Of Ropinirole Hcl-Loaded Microparticles, Aamir Hayyat, Nabeel Siddique

Pharmaceutical Sciences and Research

Ropinirole HCl is a non-ergoline dopamine agonist which is recommended for the treatment of both Parkinson’s disease and Restless Legs Syndrome (RLS). Its half-life is about 6 hours and it is metabolized in the liver primarily by CYP1A2. Its metabolites are water-soluble and rapidly excreted from the body in urine. However, its oral bioavailability is low. Therefore, this current project aimed to produce and evaluate sustained release ropinirole microparticles coated with Eudragit^® RS 100 and RL 100 by varying polymer types and concentrations. Ropinirole microparticles were prepared by oil in oil emulsion solvent evaporation technique. Emulsifier concentration was constantly …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Effects Of Transition From Closed-Book To Open-Book Assessment On Students’ Scores In A Pharmacokinetics Course, Reza Mehvar, Richard Beuttler

Pharmacy Faculty Articles and Research

Closed-book summative assessment of student learning, common in pharmacy education, is challenging to administer in a remote setting due to the need for costly and intrusive monitoring technology. Therefore, open-book assessments without monitoring have been considered an alternative in remote settings. The present study investigated the effects of the transition from in-person closed-book to remote open-book format on the students’ scores in different assessment categories in a Pharmacokinetics course. The students’ performances in the transition cohort (Transition, n = 96) during the in-person and remote periods were compared with those of an in-person cohort (Control, n = 85) during the …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil

Pharmaceutical Sciences (PhD) Dissertations

Background: Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the traditional medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein-ligand complex interactions through docking studies. Also, evaluate nsLTP1 in vitro cytotoxic …

Authorizations, Prices, And Labeling Differences Of Therapeutic Biologics Marketed In The United States And Saudi Arabia, Turki Altowairgi

Pharmaceutical Sciences (PhD) Dissertations

BACKGROUND: Since 1982, Saudi Arabia (SA) and the United States (US) have seen an increase in therapeutic biologics authorization. However, each country has regulatory regulations governing the approval of these cutting-edge drugs. The high cost of biologics financially burdens healthcare systems and delays patient access to these treatments. Sometimes a company selling the same medications in various countries will have conflicting information on drug labels.

OBJECTIVES: This study compared the characteristics of therapeutic biologics authorization by the Saudi Food and Drug Authority (SFDA) and Food and Drug Administration (FDA) as of December 31, 2021. The study also compared the US …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank S Rai

Pharmaceutical Sciences (MS) Theses

The delivery of nucleic acid therapeutics across various cell membranes has always been one of the major challenges. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) have been promising for siRNA delivery. Therefore, to enhance siRNA delivery and efficient silencing of the STAT3 gene, herein, we hypothesized to use of fatty acylation with oleyl chain to our newly designed cell-penetrating peptide (WRH) to evaluate their silencing efficiency in breast and ovarian cancer cells. Therefore, the oleyl conjugated (WRH)_n (n=1-4) peptides were synthesized using Fmoc/tBu solid-phase peptide chemistry, followed by purification using Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC), …

Prorelaxant E-Type Prostanoid Receptors Functionally Partition To Different Procontractile Receptors In Airway Smooth Muscle, Ajay P. Nayak, Elham Javed, Dominic R. Villaba, Yinna Wang, Henry P. Morelli, Sushrut D. Shah, Nicholas Kim, Rennolds S. Ostrom, Reynold A. Pannettieri Jr., Steven S. An, Dale D. Tang, Raymond B. Penn

Pharmacy Faculty Articles and Research

Prostaglandin E2 imparts diverse physiological effects on multiple airway cells through its actions on four distinct E-type prostanoid (EP) receptor subtypes (EP1–EP4). Gs-coupled EP2 and EP4 receptors are expressed on airway smooth muscle (ASM), yet their capacity to regulate the ASM contractile state remains subject to debate. We used EP2 and EP4 subtype-specific agonists (ONO-259 and ONO-329, respectively) in cell- and tissue-based models of human ASM contraction—magnetic twisting cytometry (MTC), and precision-cut lung slices (PCLSs), respectively—to study the EP2 and EP4 regulation of ASM contraction and signaling under conditions of histamine or methacholine (MCh) stimulation. ONO-329 was superior (<0.05) to ONO-259 in relaxing MCh-contracted PCLSs (log half maximal effective concentration [logEC50]: 4.9 × 10−7 vs. 2.2 × 10−6; maximal bronchodilation ± SE, 35 ± 2% vs. 15 ± 2%). However, ONO-259 and ONO-329 were similarly efficacious in relaxing histamine-contracted PCLSs. Similar differential effects were observed in MTC studies. Signaling analyses revealed only modest differences in ONO-329– and ONO-259–induced phosphorylation of the protein kinase A substrates VASP and HSP20, with concomitant stimulation with MCh or histamine. Conversely, ONO-259 failed to inhibit MCh-induced phosphorylation of the regulatory myosin light chain (pMLC20) and the F-actin/G-actin ratio (F/G-actin ratio) while effectively inhibiting their induction by histamine. ONO-329 was effective in reversing induced pMLC20 and the F/G-actin ratio with both MCh and histamine. Thus, the contractile-agonist–dependent differential effects are not explained by changes in the global levels of phosphorylated protein kinase A substrates but are reflected in the regulation of pMLC20 (cross-bridge cycling) and F/G-actin ratio (actin cytoskeleton integrity, force transmission), implicating a role for compartmentalized signaling involving muscarinic, histamine, and EP receptor subtypes.

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil, Saud O. Alshammari, Bushra Siraj, Bishoy El-Aarag, Shamshad Zarina, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein–ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic …

Proteoglycan 4 (Prg4)/Lubricin And The Extracellular Matrix In Gout, Khaled A. Elsaid, Gregory D. Jay, Ru Liu-Bryan, Robert Terkeltaub

Pharmacy Faculty Articles and Research

Proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes, released into synovial fluid, and adsorbed on cartilage and synovial surfaces. PRG4′s roles include cartilage boundary lubrication, synovial homeostasis, immunomodulation, and suppression of inflammation. Gouty arthritis is mediated by monosodium urate (MSU) crystal phagocytosis by synovial macrophages, with NLRP3 inflammasome activation and IL-1β release. The phagocytic receptor CD44 mediates MSU crystal uptake by macrophages. By binding CD44, PRG4 limits MSU crystal uptake and downstream inflammation. PRG4/CD44 signaling is transduced by protein phosphatase 2A, which inhibits NF-κB, decreases xanthine oxidoreductase (XOR), urate production, and ROS-mediated IL-1β …

Mechanisms Of Theta Burst Transcranial Ultrasound Induced Plasticity In The Human Motor Cortex, Yazan Shamli Oghli, Talyta Grippe, Tarun Arora, Tasnuva Hoque, Ghazaleh Darmani, Robert Chen

Department of Medicine Faculty Papers

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear.

OBJECTIVE: We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS.

METHODS: Fourteen …

Sirna Drug Delivery Across The Blood–Brain Barrier In Alzheimer's Disease, Muhammad Imran Sajid, Fahad Sultan Sheikh, Faiza Anis, Nourina Nasim, Rachita K. Sumbria, Surya M. Nauli, Rakesh K. Tiwari

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed. We comprehensively report the latest advances in AD pathophysiology, druggable targets, ongoing clinical trials, and the siRNA-based approaches across the blood–brain barrier for addressing …