Chemicals and Drugs Commons^™

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …

A New Approach For Discriminating Spatially Acquired Sers Spectra Using Antiretroviral Drug Emtricitabine As A Test Sample, Jana Hrncirova, Marguerite R. Butler, Meredith R. Clark, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

In this study, an antiretroviral drug emtricitabine (also known as FTC or Emtriva) was detected and quantified down to 40 ng/ml by using surface-enhanced Raman spectroscopy (SERS). Its aqueous standards were tested with two types of silver nanoparticles (colloidal and dendritic) using a specially developed aluminum well plate. The SERS spectra were acquired using a Raman scanning device with 30-mu m spatial resolution. The spectral data were analyzed using a new approach for the discrimination of the spatially acquired spectra based on the Quality index (Qi). After the Qi is calculated, the spectral data are sorted based on the Qi. …

Association Of Maternal Prenatal Copper Concentration With Gestational Duration And Preterm Birth: A Multicountry Meta-Analysis Author Links Open Overlay Panel., Nagendra Monangi, Huan Xu, Yue-Mei Fan, Rasheeda Khanam, Waqasuddin Khan, Saikat Deb, Jesmin Pervin, Joan Price, Lovejeet Kaur, R. Ochieng

Paediatrics and Child Health, East Africa

Background: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB).

Objectives: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations.

Methods: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using …

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila Kunuthuru

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

Elucidating The Role Of Fatty Acid Synthase In Apc-Driven Colorectal Cancer, Courtney O. Kelson

Theses and Dissertations--Toxicology and Cancer Biology

Globally, colorectal cancer (CRC) is the second leading cause of cancer related deaths. Currently, there is a growing incidence rate for individuals aged 20-49 years. Genetic and environmental factors contribute to the risk of this cancer. Early detection of CRC allows for the most effective treatment option in which surgical resection of the primary tumor occurs along with adjuvant chemotherapy. This therapeutic approach contributes to 5-year survival rate of 91%. However, surgical procedures and chemotherapy struggles against metastatic and relapsed CRC resulting in 5-year survival rate of 14%. Inefficacious treatments for relapsed and metastatic diseases emphasizes the need for more …

The Education Prescription: Exploring The Potential Of Patient Education To Reduce Mental Health Issues In Hormonal Contraceptive Users, Maria Abraham

Nursing | Senior Theses

The many birth control options available impact a woman’s life, as hormonal contraceptives are commonly used but often misunderstood. These contraceptives, which contain progestin only, or estrogen and progestin combined, can come in various forms such as pills, implants, IUDs, injections, the vaginal ring, and skin patches. They offer benefits such as reduced menstrual cramps and ectopic pregnancy risk. However, they may lead to adverse side effects which can include increased blood pressure, nausea, headaches, breakthrough bleeding, and a higher risk of blood clots, with research indicating a potential link between oral contraceptive use and a decline in the user’s …

Receptor-Targeted Next-Generation Probiotics Ameliorate Mammalian Colitis, Nicholas L. F. Gallina, Vignesh Nathan, Akshay Krishnakumar, Dongqi Liu, Rishi Drolia, Nicole Irrizary Tardi, Yang Fu, Manalee Samadar, Shivendra Tenguria, Alvin Cai, Ruth Eunice Centeno-Martinez, Timothy A. Johnson, Abigail Cox, Lavanya Reddivari, Bruce Applegate, Xingjian Bai, Luping Xu, Deepti Tanjore, Ramesh Vemulapalli, Rahim Rahimi, Arun K. Bhunia

Biological Sciences Faculty Publications

Introduction: a loss of intestinal barrier function, inflammation, and an elevated expression of epithelial heat shock protein 60 (Hsp60) are features of an inflamed bowel. Probiotics have been used to alleviate colitis-induced pathologies, but offer poor adhesion and adaptation to the diseased gut. We hypothesize that enhancing probiotic adhesion in the inflamed bowel may ameliorate such pathologies. Listeria adhesion protein (LAP; 94-kDa acetaldehyde alcohol dehydrogenase) aids Listeria attachment to the epithelial cells by interacting with the mammalian receptor Hsp60. Bioengineered Lactobacillus casei probiotics (BLPs) expressing LAP showed strong interaction with epithelial Hsp60, a high immunomodulatory response, and sustained epithelial barrier …

The Impact Of Aging And Storage Conditions On The Performance Of Universal Adhesives: A Systematic Review, Maryam Ghamgosar, Mehrsima Ghavami-Lahiji, Sanaz Mihandoust, Enayatollah Homaie Rad, Hassan Salehipour Masooleh, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Objective: This systematic review evaluated how different storage times and conditions affect universal adhesives' bond strength and degree of conversion (DC).

Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar databases for articles published from January 1st, 2000, until May 15th, 2022. The researchers comprehensively evaluated the articles using a multi-step process to identify articles relevant to the topic of interest. Quality assessment was performed through the ROBDEMAT tool. Due to the high heterogeneity in the preliminary data, performing a meta-analysis was not feasible.

Results: A total of 3169 records were obtained, and after …

A Novel Non-Rodent Animal Model Of Hydrochloric Acid-Induced Acute And Chronic Lung Injury, Pavel A. Solopov, Ruben Manuel Luciano Biancatelli, Tierney Day, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Hydrochloric acid is one of the most prevalent and hazardous chemicals. Accidental spills occur in industrial plants or during transportation. Exposure to HCl can induce severe health impairment, including acute and chronic pulmonary diseases. We have previously described the molecular, structural, and functional aspects of the development of chronic lung injury and pulmonary fibrosis caused by intratracheal instillation of HCl in mice. Although mouse models of human disease have many advantages, rodents are evolutionary far from human and exhibit significant anatomical and physiological differences. Genetic and anatomic similarities between rabbits and humans are significantly higher. Rabbit models of HCl-induced lung …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

Harnessing Antagonistic Pleiotropy: Tolc-Dependent Coliphages Can Drive Reduced Antibiotic Resistance In E. Coli, Cooper Mckenna

CMC Senior Theses

The rise of multidrug-resistant (MDR) bacterial pathogens has been a growing concern in healthcare around the world, and bacteriophage (phage) therapy is a promising method to combat MDR infections. One defense mechanism of E. coli against antibiotics is the TolC-AcrAB efflux pump. At the same time, some phages use TolC as a surface receptor to infect the cell. This puts TolC at a crossroads in which it is beneficial to the bacteria to protect against antibiotics but harmful by allowing phage infection, creating the potential for evolutionary trade-offs. Previous research has identified only three TolC-dependent phages and shown phage-resistant E. …

Fat-Free Mass Is Positively Associated With Urine Specific Gravity In Athletes And Active Adults: A Quantitative Review, Patrick B. Wilson, Ian P. Winter

Exercise Science Faculty Publications

Background: Urine specific gravity (USG) is a commonly used assessment method to estimate the prevalence of hypohydration, typically based on a common threshold of ≥ 1.020. Some research has shown that USG can vary based on body size and composition, but the evidence to date is limited. This review examined whether an association between fat-free mass (FFM), a component of body composition, and USG could be detected among published articles that have reported these variables in athletes and physically active individuals.

Methods: By searching Google Scholar, the authors identified a large number of published articles (n = 161) reporting anthropometrics …

Impact Of Oxytocin And Tetrahydrocannabinol On Signs Of Fear In The Rat, Jair E. Alvarez Jr.

EWU Masters Thesis Collection

BACKGROUND: Oxytocin (OXT) has been used as a post-treatment for post-traumatic stress disorder (PTSD). Previous research suggests that pre-treatment of intranasal OXT attenuates signs of fear in rats; however, the impact of intraperitoneal (i.p) OXT pre-treatment on signs of fear in rats is unknown. We also explored the effects of delta-9 (psychoactive component of cannabidiol) and delta-8 (delta-9 isomer) THC pre-treatment on attenuating signs of fear in the rat. METHODS: For each experiment, male Sprague-Dawley rats were divided into 5 groups, (n=8 per group); 1.) controls (vehicle and no foot shock), 2.) shock (vehicle and foot shock), 3.) low dose …

Glutamate Optimization As A Treatment For Depression: A Clinical Guideline, Luisa Angeles Collins Villares

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Based on the use of drugs to treat hypertension and tuberculosis for depression, the monoamine hypothesis led to the development of antidepressants in 1952. Serotonin was recognized as a deficiency associated with depression in 1967. As a fine-tuning orchestration of neurotransmitters and neuromodulators, the glutamate system became known using Spravato in 2019 and Auvelity in 2022. In this pilot study, mental health experts rated the importance of 24 science-based recommendations to optimize glutamatergic therapy in depression for a proposed guideline on a Likert scale from zero to four. The results were analyzed using a non-parametric predictive modeling method called Chi-Square …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

The Unequal Distribution Of Social Risk For Black Men Across The Life-Span. A Novel Framework., Waleed Y. Sami

Adultspan Journal

This conceptual overview offers a comprehensive overview of systemic pathways that negatively impact the mental health of Black Men throughout their lives. Our argument highlights the importance for counselors and mental health professionals to utilize a thorough social risk assessment that considers these pathways in order to effectively address the mental health needs of Black Men while fostering positive working relationships. This overview strongly advocates for the use of context and structural determinants when evaluating mental health symptoms. Without an appropriate understanding of social risk and determinants, counselors may inadvertently perpetuate disparities by decontextualizing symptomology, and reproducing racist discourse.

Design, Synthesis, And Anti-Mcf-7 Activity Of New Thieno[2,3-D]Pyrimidinone Derivatives As Potential Breast Cancer Treatment, Bassem H. Naguib, Amgad Albohy, Mostafa A. Abdelaziz, Hanan H. Kadry

Pharmacy

Breast cancer is one of the top leading causes of death and the most aggressive type of cancer in women. Resistance to chemotherapy is one of the challenges associated with the development of strategies for the treatment of breast cancer. One way to overcome this issue is to design new agents that target breast cancer cell lines such as MCF-7. In this study, a new series of S-alkylated thieno[2,3-d]pyrimidin-4-ones bearing carboxamide or ketonic scaffolds was synthesized and screened for their cytotoxicity against MCF-7 breast cell lines. Among synthesized candidates, 6d exhibited more potent cytotoxicity against MCF-7 cell lines with IC50 …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

Hybridization Kinetics Of Four-Way Junctions Localized On A Dna Scaffold, Katherine N. Taylor

Honors Undergraduate Theses

DNA computing is an ever-growing field with scientists trying to design structures that optimize logic gate communication to develop fast, biologically compatible, computational structures. We hypothesize that by using the principles of DNA computing, it is possible to design a DNA tile capable of studying localized DNA hybridization that can differentiate between oligonucleotides of different structural conformations. This includes synthetically manipulating DNA into a nanostructure that can perform Boolean logic functions to calculate the different rates of hybridization. To test our hypothesis, we designed a DNA Tile that incorporated a 4WJ using YES logic. Linear and hairpin single-stranded (ss) DNA …

The Impact Of Prenatal Paternal Cigarette Smoke On Male Urogenital Disorders: A Systematic Review, Raphaelia V. Mcdonald

Honors Undergraduate Theses

Urogenital disorders, including cryptorchidism, hypospadias, and reduced semen quality, represent significant congenital and developmental challenges in male reproductive health. While maternal smoking during pregnancy is a well-established risk factor, emerging evidence indicates that paternal smoking may also have adverse effects on male offspring’s reproductive development. This systematic review assessed the impact of paternal cigarette smoke exposure before and during pregnancy on the incidence of various urogenital disorders.

By synthesizing data from five critical studies, we found that paternal smoking was associated with a 3.8-fold increased risk of cryptorchidism and hypospadias, a 1.26-fold reduction in semen quality, and potential epigenetic changes …

Chemical Synthesis And Biological Application Of Sensitive Rna, Alexander T. Apostle

Dissertations, Master's Theses and Master's Reports

In the field of epigenetics - the dynamic collection of chemical modifications that overlay DNA/RNA - there is increasing interest in the potential for therapeutic and research-based utilization of the epitranscriptomics: those epigenetic modifications specific to RNA. Epitranscriptomics can give us a new approach to understanding and treating RNA viruses, like SARS-CoV-2. Given viruses are often found modified by human epitranscriptomic machinery, understanding how these modifications can modulate virulence is of high interest. We have shown that the N1-methyladensoine modification causes RNA synthesis termination in the SARS-CoV-2 replication complex, and thus may explain the differences in symptoms observed in individuals. …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

Continuous, Platform Purification Of Viral Products Using Aqueous Two-Phase Extraction, Natalie M. Nold

Dissertations, Master's Theses and Master's Reports

Cell and gene therapies, a ground-breaking class of drugs that can heal genetic diseases and cure cancer, often have treatment costs over $1 million. Most cell and gene therapies are delivered using virus-based delivery vectors, which are incredibly expensive to manufacture. Liquid chromatography is the favored method of viral vector purification since it is easily scalable and can be functionalized to purify by biospecificity, charge, hydrophobicity, or size. However, chromatography-based purification processes are highly expensive and usually only recover 20-50% of the viral vectors. There is currently no platform purification strategy for viral vectors due to differences in their surface …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Understanding The Effects Of Hormone Treatments On The Transgender Singer: A Pedagogical Study And Voice Studio Guide, Erin M. Hannon

Theses and Dissertations--Music

Transitioning from one gender to another can be an arduous and emotionally charged experience, accompanied by many physical and mental transformations. The journey of self-discovery and vocal explorations is both unique and deeply personal. Modifications that emerge in an individual's vocal characteristics have a profound influence on their capacity to communicate and express themselves.

Transgender vocal students and professional singers must navigate the delicate balance between their vocal and gender identities while considering the possible risks of Gender Affirming Hormone Therapy. Though these therapies may significantly alter one's appearance and overall well-being, they are also capable of causing notable declines …

Spiral Wave Teleportation And Multiplex Network Synchronization In Light Sensitive Belousov-Zhabotinsky Systems, Shannyn Alicia Tyler

Graduate Theses, Dissertations, and Problem Reports (ETD)

We experimentally and computationally investigate dynamical behaviors in excitable and oscillatory media using light sensitive Belousov-Zhabotinsky (BZ) systems. These systems are not in a state of thermodynamic equilibrium, and have been proven to show various interesting phenomena including spatiotemporal patterns, self-organization, and chaos. We utilize the BZ reaction, a nonlinear chemical reaction, known for its relaxation-type oscillations, to explore the dynamics of these systems.

We examine spiral wave teleportation in an excitable media as an effective alternate defibrillation method. Spiral waves have emerged as a key phenomenon associated with the initiation and persistence of cardiac arrhythmias. Using a light sensitive …

Evaluating Outcomes Post-Adoption Of Reck Solution For Total Shoulder Arthroplasties: A Retrospective Quality Analysis, Benjamin Levi Tillis

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Evaluating Outcomes Post-adoption of RECK Solution for Total Shoulder Arthroplasties: A Retrospective Quality Analysis

Benjamin Tillis

Introduction: Local infiltration analgesia (LIA) has become an integral part of postoperative pain relief for West Virginia University (WVU) Medicine’s total joint arthroplasty procedures. However, not all LIAs are the same. Liposomal bupivacaine has a unique mechanism of delivery which could potentially lead to longer lasting effects. Ropivacaine, epinephrine, clonidine, and ketorolac (RECK) solution offers a multimodal approach to enhancing the duration of effect for the LIA. In 2022, WVU Medicine switched from liposomal bupivacaine to the RECK solution for total joint …

Flexible Fitting Of Alphafold2-Predicted Models To Cryo-Em Density Maps Using Elastic Network Models: A Methodological Affirmation, Maytha Alshammari, Jing He, Willy Wriggers

Computer Science Faculty Publications

Motivation: This study investigates the flexible refinement of AlphaFold2 models against corresponding cryo-electron microscopy (cryo-EM) maps using normal modes derived from elastic network models (ENMs) as basis functions for displacement. AlphaFold2 generally predicts highly accurate structures, but 18 of the 137 models of isolated chains exhibit a TM-score below 0.80. We achieved a significant improvement in four of these deviating structures and used them to systematically optimize the parameters of the ENM motion model.

Results: We successfully refined four AlphaFold2 models with notable discrepancies: lipid-preserved respiratory supercomplex (TM-score increased from 0.52 to 0.69), flagellar L-ring protein (TM-score increased from 0.53 …

Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis

Scripps Senior Theses

4-10% of women who use hormonal oral contraceptives (HOCs) discontinue use after experiencing symptoms of anxiety, irritability, and depression in the first 3 months of administration. Previous studies have acknowledged a relationship between HOCs and emotional dysregulation but have not identified mechanisms by which HOCs have this effect. As a result, effective treatment options for HOC-induced mood disorders are lacking. Current theories implicate combined-HOCs, particularly those containing ethinyl estradiol and levonorgestrel (EE-LNG), in reducing neuroactive steroid levels. Specifically, HOC users show decreases in allopregnanolone, a positive allosteric modulator associated with neuronal inhibition and emotional regulation. The objective of this study …