Chemicals and Drugs Commons^™

Production And Characterization Of A Phage Endolysin With Putative Antimicrobial Activity Against Cutibacterium Acnes, Kathryn M. Collins

EWU Masters Thesis Collection

Acne vulgaris (acne) is the eighth most common skin disorder worldwide. Because of the heterogeneous pathology of acne and the increasing antibiotic resistance of the causal agent (Cutibacterium acnes), novel therapeutics need to be developed to treat acne. One option is endolysins, highly conserved enzymes from bacteriophages that disrupt the bacterial cell wall. Endolysins retain bactericidal and bacteriostatic activity when applied to bacteria in vitro and are safe for topical application. We hypothesize that the endolysin (ENDL) from the P100.1 C. acnes bacteriophage will exhibit bacteriostatic activity against C. acnes in vitro. This study aims to bioinformatically characterize the P100.1 …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …

Impact Of Converging Sociocultural And Substance-Related Trends On Us Autism Rates: Combined Geospatiotemporal And Causal Inferential Analysis, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Whilst cannabis is known to be toxic to brain development, it is unknown if it is driving rising US autism rates (ASMR). A longitudinal epidemiological study was conducted using national autism census data from the US Department of Education Individuals with Disabilities Act (IDEA) 1991–2011 and nationally representative drug exposure (cigarettes, alcohol, analgesic, and cocaine abuse, and cannabis use monthly, daily, and in pregnancy) datasets from National Survey of Drug Use and Health and US Census (income and ethnicity) and CDC Wonder population and birth data. Analysis was conducted in R. 266,950 were autistic of a population of 40,119,464 8-year-olds …

The Path To U.S. National Registration Of A Toxic Bait For The Control Of The Small Indian Mongoose, Carmen C. Antaky, Steven C. Hess, Emily W. Ruell, Israel L. Leinbach, Shane R. Siers, Robert T. Sugihara

Human–Wildlife Interactions

The small Indian mongoose (Urva auropunctata [syn. Herpestes auropunctatus]; mongoose) is a highly invasive species in its introduced range that negatively impacts ecosystems. Mongooses depredate native species, serve as a vector of disease posing a risk to human health, and cause sanitation issues in food processing facilities and public areas. Introduced for biocontrol in the late 1800s in Hawaiʻi and the Caribbean, mongooses currently have well-established populations across multiple islands in both island archipelagos and have invaded numerous other locations throughout the world. The concern of accidental introduction to mongoose-free islands, the difficulty in species detection, and the …

Sugar-Sweetened Beverages Intake, Abdominal Obesity, And Inflammation Among Us Adults Without And With Prediabetes—An Nhanes Study, Wei Ting Lin, Yu Hsiang Kao, Mirandy S. Li, Ting Luo, Hui Yi Lin, Chien Hung Lee, David W. Seal, Chih Yang Hu, Lei Shih Chen, Tung-Sung Tseng

School of Public Health Faculty Publications

Excessive sugar-sweetened beverages (SSB) consumption and abdominal obesity have been independently linked to numerous disorders, including diabetes and elevated C-reactive protein (CRP). This study aimed to explore the association between SSB intake, abdominal obesity, and inflammation in normal and prediabetic adults. Sugar intake from SSBs was calculated from 24-h dietary recalls and further classified into non-, medium-, and high-intake. The status of non- and prediabetes was identified based on hemoglobin A1c level. All analyses were performed under a survey module with appropriate sampling weights to control for the complex survey design. A total of 5250 eligible adults without diabetes were …

Structure-Based Rational Design Of Small Α-Helical Peptides With Broad-Spectrum Activity Against Multidrug-Resistant Pathogens, Sandeep Lohan, Anastasia G. Konshina, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of small (7–12 mer) amphipathic cationic peptides were designed and synthesized to create short helical peptides with broad-range bactericidal activity and selectivity toward the bacterial cells. The analysis identified a lead 12-mer peptide 8b with broad-spectrum activity against Gram-positive (MIC = 3.1–6.2 μg/mL) and Gram-negative (MIC = 6.2–12.5 μg/mL) bacteria and selectivity toward prokaryotic versus eukaryotic cells (HC50 = 280 μg/mL, >75% cell viability at 150 μg/mL). The rapid membranolytic action of 8b was demonstrated by a calcein dye leakage assay and confirmed using scanning electron microscopy. According to circular dichroism and NMR spectroscopy, the peptides have an …

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies, Mukul Singal, Sanjana Kalvehalli Kashinath, S. Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed

Advances in Clinical Medical Research and Healthcare Delivery

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies.

We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies.

A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive …

Machine Learning And Protein Allostery, Sian Xiao, Gennady M. Verkhivker, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fundamental biological importance and complexity of allosterically regulated proteins stem from their central role in signal transduction and cellular processes. Recently, machine-learning approaches have been developed and actively deployed to facilitate theoretical and experimental studies of protein dynamics and allosteric mechanisms. In this review, we survey recent developments in applications of machine-learning methods for studies of allosteric mechanisms, prediction of allosteric effects and allostery-related physicochemical properties, and allosteric protein engineering. We also review the applications of machine-learning strategies for characterization of allosteric mechanisms and drug design targeting SARS-CoV-2. Continuous development and task-specific adaptation of machine-learning methods for protein allosteric …

Data Driven Classification Of Opioid Patients Using Machine Learning - An Investigation, Saddam Al Amin, Md Saddam Hossain Mukta, Md Sezan Mahmud Saikat, Md Ismail Hossain, Md Adnanul Islam, Mohiuddin Ahmed, Sami Azam

Research outputs 2022 to 2026

The opioid crisis has led to an increased number of drug overdoses in recent years. Several approaches have been established to predict opioid prescription by health practitioners. However, due to the complex nature of the problem, the accuracy of such methods is not yet satisfactory. Dependable and reliable classification of opioid dependent patients from well-grounded data sources is essential. Majority of the previous studies do not focus on the users’ mental health association for opioid intake classification. These studies do not also employ the latest deep learning based techniques such as attention and knowledge distillation mechanism to find better insights. …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Nurse-Led Education On Oral Chemotherapy Medications, Carmen Lucia Glick Alonso

Master's Projects and Capstones

Problem: Breast cancer is one of the leading causes of cancer death among women in the United States. Annually, around 264,000 breast cancer cases are diagnosed in women and 2,400 in men (Centers for Disease Control and Prevention, 2022). According to the American Cancer Society, the risk of a woman in the United States being diagnosed with breast cancer in their life is around 13% (2022).

Context: Along with a cancer diagnosis comes the need to introduce patient education about new oral chemotherapy treatments. As a treatment team member, the oncology nurse plays a vital role in this …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

Prophylactic Intravenous Prehydration With Sodium Bicarbonate Or Sodium Chloride In The Prevention Of Contrast Induced Acute Kidney Injury, Briana Lockett, Caroline Dong

Physician Assistant Capstones, 2020-current

Introduction: Iodinated contrast media is a crucial component in the diagnostic work up of many life-threatening illnesses. However, it has been reported to cause acute kidney injury after administration, especially in patients with pre-existing renal disease. Several prophylactic treatments have been studied in hopes of minimizing these adverse events. The current standard of care in this patient population is prophylactic intravenous volume administration with either sodium chloride or sodium bicarbonate. Objective: The goal of this literature review is to determine if prophylactic intravenous volume administration with either saline or sodium bicarbonate prior to contrast administration decreases the incidence of contrast …

The Use Of Autologous Prp Gel For The Treatment Of Diabetic Foot Ulcers, Erin Klein, Dominic E. Paoletti

Physician Assistant Capstones, 2020-current

The purpose of this systematic literature review is to examine the efficacy of platelet rich-plasma (PRP) gel as a therapy for diabetic foot ulcers (DFUs). Infections in patients with diabetes, especially diabetic foot ulcers, are challenging to treat due to neurovascular compromise. Searches were done in PubMed utilizing the terms “diabetic foot ulcer”, “platelet rich plasma” and “autologous”. In PubMed, the following limits and terms were used: randomized control trial (RCTs), sample size greater than 30 participants, foot ulcers, and English. A meta-analysis revealed three studies meeting inclusion/exclusion criteria: Li et al, Gude et al, and Ahmed et al. The …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Polymeric Chloroquine In Metastatic Pancreatic Cancer Therapy, Rubayat Islam Khan

Theses & Dissertations

Hydroxychloroquine (HCQ) is an established drug that has been used for the treatment of multiple diseases, including malaria, rheumatoid arthritis, and lupus erythematosus. Several recently published studies have highlighted its beneficial use in various types of cancers, and a plethora of clinical trials are currently evaluating its use in cancer therapies, wherein some of the results look promising. The preclinical studies to date suggest HCQ can work effectively in conjunction with traditional cancer treatments, as it has been shown to sensitize tumor cells to a wide range of chemotherapeutic agents. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has …

Targeted Therpeutics For Prostate Cancer, Behind The Scenes Of Psma & Cysteine Protease Trapping Mechanism, Alireza Basiri

Theses & Dissertations

In an attempt to increase the residence time of PSMA-targeted theranostics inside the prostate cancer cells and tumors, we designed and prepared a CPTA-PSMATA resembling PSMA-617 by adding a well-known cysteine protease inhibitor (E-64) to the conjugate. Lysosomal proteases, including cysteine, serine, and aspartic families of hydrolytic enzymes, are expressed in high concentrations in the lysosomes and are responsible for the catabolism of proteins inside the cell [165, 278]. We proposed that after successful internalization of the PSMA-targeted conjugates into the cells, they will be conveyed to the endolysosomes. In these endolysosomal compartments, the E-64 moiety will covalently bind to …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …