Other Pharmacy and Pharmaceutical Sciences Commons^™

Harnessing Exosomes As A Platform For Drug Delivery In Breast Cancer: A Systematic Review For In Vivo And In Vitro Studies, Abdulwahab Teflischi Gharavi, Saeed Irian, Azadeh Niknejad, Keykavous Parang, Mona Salimi

Pharmacy Faculty Articles and Research

Breast cancer remains a significant global health concern, emphasizing the critical need for effective treatment strategies, especially targeted therapies. This systematic review summarizes the findings from in vitro and in vivo studies regarding the therapeutic potential of exosomes as drug delivery platforms in the field of breast cancer treatment. A comprehensive search was conducted across bibliographic datasets, including Web of Science, PubMed, and Scopus, using relevant queries from several related published articles and the Medical Subject Headings Database. Then, all morphological, biomechanical, histopathological, and cellular-molecular outcomes were systematically collected. A total of 30 studies were identified based on the Preferred …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Real-Time Camp Dynamics In Live Cells Using The Fluorescent Camp Difference Detector In Situ, Isabella Cattani-Cavalieri, Jordyn Margolis, Camelia Anicolaesei, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

cAMP Difference Detector In Situ (cADDis) is a novel biosensor that allows for the continuous measurement of cAMP levels in living cells. The biosensor is created from a circularly permuted fluorescent protein linked to the hinge region of Epac2. This creates a single fluorophore biosensor that displays either increased or decreased fluorescence upon binding of cAMP. The biosensor exists in red and green upward versions, as well as green downward versions, and several red and green versions targeted to subcellular locations. To illustrate the effectiveness of the biosensor, the green downward version, which decreases in fluorescence upon cAMP binding, was …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

Limonene Exerts Anti-Inflammatory Effect On Lps-Induced Jejunal Injury In Mice By Inhibiting Nf-Κb/Ap-1 Pathway, Sarmed H. Kathem, Yasameen Sh. Nasrawi, Shihab H. Mutlag, Surya M. Nauli

Pharmacy Faculty Articles and Research

The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Tiny But Mighty, An Exploration Of Microbes And Plants As Sources Of Small Novel Bioactive Compounds Against Invasive Mycoses., Hannah Mai Peacock, James Anthony O'Connor

SURE Journal: Science Undergraduate Research Experience Journal

Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier.

In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity.

Metabolites of S.epidermidis, and extracts …

Paper-Based Ratiometric Sensor Array For Pathogenic Bacterial Species Identification, Aayushi Laliwala

Theses & Dissertations

Bacterial infections are the leading cause of mortality worldwide due to the lack of accurate diagnosis of the pathogens causing infections. Currently, microbiological and molecular techniques are used to identify pathogenic bacteria. However, these techniques have limitations as they are time-consuming, cost-inefficient, and require trained personnel. Therefore, timely and precise identification of pathogenic bacteria is crucial for public safety. Our lab previously synthesized a fluorescent sensor array (3-hydroxyflavone derivatives) encapsulated in hyaluronic acid-based nanoparticles to identify bacterial species and recognize their Gram status. Though promising, this technique was relatively time-consuming and required high sample and volumes.

To overcome these limitations, …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Development And Validation Of An Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K_Ca2.2/K_Ca2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently developed positive allosteric modulator of K_Ca2.2/K_Ca2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar …

The Opioid Epidemic: How Genetics Play A Role In Addiction And Treatment, Kirsten Houston

Honors College Theses

The opioid epidemic is an issue within the pharmaceutical industry in the United States of America due to prescription and non-prescription substances being made available to the population. Opioids include chemical substances that affect the body and brain through opioid receptors, including the mu, kappa, and delta receptors. These substances are derived and synthesized from the poppy plant. Multiple causes have been linked to opioid abuse disorder, including but not limited to employment, income, housing, nutrition, mental health disorders, and genetics. By gathering information from previous literature, genetics may be the main cause of narcotic analgesic tolerance and abuse. Specific …

Creation Of Tatde Rlnps For The Excision Of Integrated Hiv-1 Proviral Dna, Mahmudul Hasan

Theses & Dissertations

The persistence of integrated human immunodeficiency virus type 1 (HIV-1) proviral DNA despite combination antiretroviral therapy (ART) is the principal challenge to eliminating HIV-1 infection. This is made ever more complex based on the high viral mutation rates, diversity and resistance profiles. Taken together, these factors present principal obstacles towards any means to eliminate the virus from its infective human host. To address these factors, we have developed and validated a TatDE rLNP RNA delivery system. The system utilizes Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) guide RNAs (gRNAs) to target multiple exons of an integrated proviral HIV-1 (tat_{1-2 …}

Antibody-Drug Conjugates For Multiple Myeloma: Just The Beginning, Or The Beginning Of The End?, Upasana Ray, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved …