Chemicals and Drugs Commons^™

Inhibition Of Glutathione Peroxidase, Tosin Masha, Carol Chrestensen, Daniela Tapu, Meleye Mel, Madison Jaames

Symposium of Student Scholars

Glutathione peroxidase (GPx) is an intracellular antioxidant enzyme that mediates the amount of hydrogen peroxide present in cells. Through this activity, GPx aids in the regulation of cellular processes that use hydrogen peroxide, including growth and proliferation. It may be desirable to inhibit GPx in certain diseased states, e.g. cancer, where GPx is over expressed. The Tapu lab is making N-heterocyclic compounds that have shown efficiency inhibiting thioredoxin reductase, which is another selenocysteine containing enzyme. Our aim is to test similar compounds to see if they have the ability to inhibit GPx. In order to test these compounds, we have …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

Preparation Of Meta-Nitrobenzoylhydrazone Ferrocenoylacetone And Synthesis On Its Basis, Zilola Abduraxmonovna Sulaymonova, Bako Bafayevich Umarov Doctor Chemical Science, Professor

Chemical Technology, Control and Management

β-diketone-ferrocenoylacetone was obtained by Claisen condensation. Meta-nitrobenzoylhydrazone of ferrocenoylacetone (H₂L) was synthesized by the interaction of meta-nitrobenzoic acid hydrazide with ferrocenoylacetone. On its basis, complexes with copper(II) and nickel(II) ions were synthesized. The obtained compounds were characterized by the methods of elemental analysis, IR-, ¹H NMR andelectronic spectroscopy. The research results showed that H₂L in solution exists in the form of a tautomeric mixture: hydrazone, α-hydroxyazine, and cyclic 5-hydroxypyrazoline forms. According to the results of IR and ¹H NMR spectra, the complexes were assigned a planar-square structure, and in them the doubly deprotonated …

No Ordinary Proteins: Adsorption And Molecular Orientation Of Monoclonal Antibodies, Ankit D. Kanthe, Andrew Ilott, Mary Krause, Songyan Zheng, Jinjiang Li, Wei Bu, Mrinal K. Bera, Binhua Lin, Charles Maldarelli, Raymond S. Tu

Publications and Research

The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. …

Does Epa Cause A Decrease In Inflammation Of Bend.3 Cells Through Ffar4?, Clay J. Weidenhamer

Masters Theses

Atherosclerosis is an inflammatory disease initiated by low and oscillatory shear stress on the endothelium. The inflammatory process recruits leukocytes to the vessel wall by expression of the adhesion molecule VCAM-1. Activation of the NF-κB inflammatory signaling pathway is responsible for the increase in VCM-1 expression. Omega 3 FAs, such as EPA, reduce the risk of atherosclerosis by decreasing this inflammatory response. The pathway by which omega 3 FAs is proposed to inhibit inflammation includes activating FFAR4 to decrease NF-κB activation thereby reducing expression of adhesion molecules. We hypothesized that treatment of endothelial cells with 30 μM EPA would decrease …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Development Of Once-A-Year Injectable Formulation Of Cabotegravir For Prevention And Treatment Of Hiv Infection, Tanmay Abhay Kulkarni

Theses & Dissertations

Long-acting cabotegravir (CAB) extends antiretroviral drug (ARV) dosing to monthly for maintenance of human immunodeficiency virus type one (HIV-1) suppression and to every other month for prevention of viral transmission. However, injection dose volumes, site reactions, and clinical oversights that are required remain obstacles towards broad usage. To meet these needs, surfactant coated hydrophobic and lipophilic CAB prodrugs were created with controlled prodrug dissolution, hydrolysis and drug tissue penetration. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18, and 22 added carbon chains were synthesized then nanoformulated as NMCAB, NM2CAB, and NM3CAB. These nanocrystal formulations were tested …

Small Molecule Inhibitors Of Inflammatory Caspases-1, -4, And -5, Christopher D. Ahlers

DePaul Discoveries

Inflammatory caspases-1, -4, and -5 play critical roles in mediating the innate immune response to pathogen- and damage-associated molecular patterns. Caspase-1 produces the cytokine interleukin-1β (IL-1β), while caspases-4 and -5 activate the NOD-like receptor protein 3 inflammasome via the non-canonical pathway. Overactivation of these enzymes is associated with an increased risk for inflammatory diseases such as lupus, psoriasis, and rheumatoid arthritis. Small molecule inhibitors (SMIs) have been developed to attenuate the production of IL-1β, but unfavorable bioavailability and toxicity have provided an insurmountable barrier in clinical trials. This work is concerned with delivering an overview of current progress in the …

Quantifying Phosphatidylethanol From Blood Samples, James V. Defrancesco, Majid Afshar

Chemistry: Faculty Publications and Other Works

Disclosed herein is a method for quantifying phosphatidylethanol (“ PEth ”), direct ethanol biomarker, from a blood sample using gas chromatography mass spectrometry. The method disclosed herein is useful for diagnosing acute and chronic alcohol abuse.

Dose Adjustment Of Antidiabetic Medications In Chronic Kidney Disease, Matthew Salvatore Snyder, Joshua Fogel, Svetlana Pyatigorskaya, Sofia Rubinstein

Publications and Research

Purpose: The purpose of this study is to identify whether Internal Medicine house-staff (IMHS) have awareness and knowledge about the correct dosage of antidiabetic medications for patients with chronic kidney disease (CKD), as dosing errors result in adverse patient outcomes for those with diabetes mellitus (DM) and CKD.

Methods: There were 353 IMHS surveyed to evaluate incorrect level of awareness of medication dose adjustment in patients with CKD (ILA) and incorrect level of knowledge of glomerular filtration rate level for medication adjustment (ILK-GFR) for Glipizide, Pioglitazone, and Sitagliptin.

Results: Lack of awareness and knowledge was high, with the highest for …

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma

Chemistry Theses and Dissertations

In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Modulation Of Antibacterial Activity And Cytotoxicity In Amphipathic Cyclic Peptide [R4w4] Using Histidine Substitution, Ryan Stueber

Pharmaceutical Sciences (MS) Theses

Antibiotics have been the gold standard frontline defense against bacterial infections for decades. At the same time, these infecting bacteria have continued to evolve to resist developed antibiotics in an almost endless cycle. As such, we aim to take an alternative approach utilizing antimicrobial peptides (AMPs) as a means to end this cycle. [R4W4] is among known AMPs that demonstrated antimicrobial activity against methicillin-resistant staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 2.67 μg/mL. This peptide had notably effective antimicrobial activity, especially relative to linear (R4W4). However, it displayed a concerning level of cytotoxicity; eliciting a human embryonic …

Targeting Plasma Membrane Phosphatidylserine Content To Inhibit Oncogenic Kras Function, Walaa E. Kattan

Dissertations and Theses (Open Access)

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We therefore investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidylinositol-4-phosphate (PI4P) synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion …

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

Graduate Theses/Dissertations

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

July / August 2021, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy.

Exploration Of Patient Variables And Characteristics Best Suited For Medical Marijuana Treatment For Anxiety And Depressive Disorders, Corey Gazoo

Dissertations

Individuals with posttraumatic stress, anxiety and depressive disorders are currently being prescribed medical marijuana as a treatment in many states across the United States. However, marijuana is still considered a schedule one narcotic by the Drug Enforcement Administration and federal government, which provides several barriers and challenges to conduct research such as approval from the U.S. Food and Drug Administration and following guidelines from the National Institute on Drug Abuse issued by the DEA. Additionally, individuals prescribed medical marijuana for mental health disorders are not always thoroughly instructed on the type of medical marijuana, the dosage, and how frequently to …

Milk Exosomes: Nature's Abundant Nanoplatform For Theranostic Applications, Benilde Adriano, Nycol Cotto, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

School of Medicine Publications

Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the …