Chemicals and Drugs Commons^™

Design And Investigation Of Small Molecule Drugs For Potential Treatment Of Cns Disorders, Flaviviral Infections, And Cancers, Viktoriya Mashinson

Theses & Dissertations

Chapter 1 discusses the development of antagonists against the dopamine 4 receptor (D4R) that is expressed in the motor, associative, and limbic subdivisions of the basal ganglia network and is involved in Parkinson’s disease (PD). Levodopa is the firstline drug for the management of PD symptoms but its long-term use often leads to development of levodopa-induced dyskinesia (LID). D4R antagonists have been shown to decrease the abnormal involuntary movement scores in mouse models of LID. Chapter 1 outlines the development and optimization of selective D4R antagonists for potential treatment of LID. During the investigation of our D4R antagonists we discovered …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight …

Proteoglycan 4 (Lubricin) And Regulation Of Xanthine Oxidase In Synovial Macrophage As A Mechanism Of Controlling Synovitis, Khaled A. Elsaid, Ling X. Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Tannin A. Schmidt, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Synovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis. Proteoglycan 4 (PRG4) is a mucinous glycoprotein that fulfills lubricating and homeostatic roles in the joint. The aim of this work is to study the role of PRG4 in modulating synovitis in the context of SM homeostasis and assess the contribution of xanthine oxidase (XO)-hypoxia inducible factor alpha (HIF-1a) axis to this regulation.

Methods

We used Prg4FrtloxP/FrtloxP …

The Revised Cdc Chronic Pain Guidelines And Payer Opioid Analgesic Policies In Michigan, Victoria Tutag Lehr, Cynthia L. Arfken

Michigan Journal of Public Health

Abstract

The 2016 publication of A Guideline for Prescribing Opioids for Chronic Pain by the Centers for Disease Control and Prevention motivated commercial and Medicaid payers to restrict their opioid prescribing policies including the imposition of hard limits on opioid daily dosages and duration. One result of these policies was an increase in abrupt opioid discontinuation and rapid tapering events for patients receiving long-term opioid therapy. Responding to this misapplication of the 2016 guideline, the 2022 revised guidelines emphasized individualized opioid therapy and exclusion of certain chronic diseases. However, it is not known if the payers changed their policies to …

Investigating The Expression Of C-Myc And Birc5 In Trail And Pbox-15 Treated Metastatic Prostate Cancer Cells, Corinne Kai Leng Chew, Hannah O'Toole, Daniela M. Zisterer, Seema M. Nathwani, Jade K. Pollock

SURE Journal: Science Undergraduate Research Experience Journal

Purpose Metastatic prostate cancer is associated with poor survival rate and limited treatment options. Overexpression of c-Myc and BIRC5 has been reported in prostate cancer cells which contribute to the development of the tumour environment. The specific tumour receptor mechanism of the death ligand TRAIL (tumour necrosis factor related apoptosis inducing ligand) has attracted remarkable therapeutic interest. However, many cancer cells are resistant to TRAIL monotherapy. A novel microtubule-targeting agent, PBOX-15 is known to exhibit anti-tumour activity in cancer cell lines including those with multi-drug resistance. Previous studies demonstrated that PBOX-15 is capable in sensitising cancer cells to TRAIL-mediated cell …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Investigation Into The Effect Of Aspartame On The Expression Of P53 And Bax In Mouse Stomach Tissue, Angelique Cheryl, Aoife Mac Cooey

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The recent reclassification of aspartame as a Group 2B hazard by the International Agency for Research on Cancer, along with studies suggesting links to cancer, has raised concerns and prompted further investigation. Evidence suggests that aspartame exposure may alter p53 and BAX gene expression, affecting apoptosis in cancer cells. This study aims to examine how aspartame exposure affects p53 and BAX gene expression in normal mouse stomach tissue, shedding light on cellular stress and apoptosis mechanisms.

Methods: Mice were sacrificed, and stomach tissue was excised and divided into control and treatment groups. RNA extraction was carried out in the …

Total Organic Carbon Analysis Of Residual Contaminants In Bioreactor Equipment: A Cleaning Verification Study Using Surface Swabbing, Ciara E. Fitzpatrick, James J. Roche

SURE Journal: Science Undergraduate Research Experience Journal

Contamination is a major issue in the biopharmaceutical industry. Bioreactors must be meticulously cleaned to remove residual impurities and avoid cross-contamination. Cleaning validation is necessary to ensure residual contaminants are reduced to the lowest acceptable limits. Bacterial cells represent the paramount challenge in manufacturing equipment cleaning because they are composed of insoluble organic contaminants. Total organic carbon (TOC) analysis is a fast, highly sensitive, and inexpensive analytical technique commonly used to evaluate the approximate level of organic contamination.

A study was conducted to assess the effectiveness of cleaning procedures in the removal of contaminants from bioreactor equipment by measuring the …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Effects Of Modification In Limonene And Geraniol On The Properties Of Thermal Cured Polyurethane Films, Sauravkumar Rajeshbhai Patel

Electronic Theses & Dissertations

The increasing demand for green materials has inspired in-depth research into biobased polymers; among these polymers, polyurethanes stand out because of their widest range of applications: coatings, adhesives, and biomedical devices. The subject of this paper is the preparation of bio-based polyurethane films based on the polyols synthesized from renewable feedstocks such as limonene, geraniol, and soybean oil. Limonene and geraniol were chemically modified from natural sources such as citrus fruits and essential oils to high-functionality polyols. Characterization of such polyols showed that geraniol had the highest hydroxyl (OH) value and thus geraniol-based polyurethane films were highly influencing in reactivity …

Cftr Modulator Therapy In The Treatment Of Cystic Fibrosis As Compared To Placebo, Rebecca L. Doody, Harrison James Hall

Physician Assistant Capstones, 2020-current

Objective: To assess the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor combinations in the improvement of lung function in patients aged 12 and older with Cystic Fibrosis. Design: Systematic Literature Review Methods: A search was performed in PubMed using the search terms “CFTR modulators in Cystic Fibrosis.” Further parameters set were: published in the last 10 years, Randomized Control Trials, and trials that include participants under 18. Articles were excluded if they did not compare to placebo or had a primary endpoint measurement of FEV₁. Results: The Taylor-Cousar et al study showed …

A Conjugate Of An Egfr-Binding Peptide And Doxorubicin Shows Selective Toxicity To Triple-Negative Breast Cancer Cells, Phi-Phung Than, Shih-Jing Yao, Emad Althagafi, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell migration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin (Dox) retains selectivity for TNBC cells and exhibits significant toxicity comparable …

The 2024 Nobel Prize In Physiology Or Medicine: Microrna Takes Center Stage, George A. Calin, Florent Hubé, Michael R. Ladomery, Nicholas Delihas, Manuela Ferracin, Laura Poliseno, Luca Agnelli, Suresh K. Alahari, Ai-Ming Yu, Xiao-Bo Zhong

School of Medicine Faculty Publications

The Non-coding Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering a previously unknown layer of gene control in eukaryotes [...].

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

The Role And Therapeutic Possibilities Of Pelp1 In Hepatocellular Carcinoma (Hcc) Cells, Marian Hernandez Fernandez

Honors Program Theses and Research Projects

Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer mortality in the USA and ranks as the fourth leading cause of cancer-related deaths worldwide. Moreover, advanced HCC has a bleak prognosis, with a median survival rate of approximately 10 months. Latinos in South Texas exhibit the greatest incidence of liver cancer nationwide. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is an oncogene associated with the advancement of several cancers; however, its function in hepatocellular carcinoma (HCC) remains unclear. Analysis of publicly accessible cancer databases revealed elevated expression of PELP1 oncogene in HCC relative to the control group. …

Induction Of Tier 2 Hiv-Neutralizing Iga Antibodies In Rhesus Macaques Vaccinated With Bg505.664 Sosip, Justin C. Smith, Prabhu S. Arunachalam, Traci H. Legere, Lisa A. Cavacini, Eric Hunter, Bali Pulendran, Rama R. Amara, Pamela A. Kozlowski

School of Graduate Studies Faculty Publications

BACKGROUND: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. METHODS: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is …

Lipid Discovery Enabled By Sequence Statistics And Machine Learning, Priya M. Christensen, Jonathan Martin, Aparna Uppuluri, Luke R. Joyce, Yahan Wei, Ziqiang Guan, Faruck Morcos, Kelli L. Palmer

School of Podiatric Medicine Publications

Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified that Streptococcus agalactiae MprF synthesizes lysyl-phosphatidylglycerol (Lys-PG) from anionic PG, and a novel cationic lipid, lysyl-glucosyldiacylglycerol (Lys-Glc-DAG), from neutral glycolipid Glc-DAG. This unexpected result prompted us to investigate whether Lys-Glc-DAG occurs in other MprF-containing bacteria, and whether other novel MprF products exist. Here, we studied protein sequence features determining MprF substrate specificity. First, pairwise analyses identified several streptococcal MprFs synthesizing LysGlc-DAG. Second, a restricted Boltzmann machine-guided approach led us to discover an …

Smart Sequential Spectrophotometric Analysis Of Fluconazole And Its Two Toxic Official Impurities Having Superimposed Spectra; Greenness, Whiteness, Blueness Assessment And In Silico Toxicity Profiling, Ekram Hany Mohamed, Christine Magued Elmaraghy, Mai Saeed

Pharmacy

Owing to the health hazards of impurities presence in active pharmaceutical ingredients, even in minute amount. A smart green sustainable spectrophotometric method was developed for simultaneous determination of Fluconazole (FLU) along with its official impurities B and C. The novel sequential dual amplitude difference (SDAD) technique succeeded in resolving the severe overlapping between the three compounds and restoring their respective mother spectrum. According to international Council of Harmonization (ICH) guidelines, the developed method is accurate, precise, and selective with linearity range (50–500 µg/mL) for FLU, (0.5–6 µg/mL) for impurity B and (0.05–0.6) for impurity C. The method was successfully applied …