Chemicals and Drugs Commons^™

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. …

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 …

Synthesis Of Bis-Thioacid Derivatives Of Diarylethene And Their Photochromic Properties, Pramod Aryal, Jonathan Bietsch, Gowri Sankar Grandhi, Richard Chen, Surya B. Adhikari, Ephraiem S. Sarabamoun, Joshua J. Choi, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Diarylethenes (DAEs) are an important class of photoswitchable compounds that typically undergo reversible photochemical conversions between the open and closed cyclized forms upon treatment with UV light or visible light. In this study, we introduced thioacid functional groups to several photochromic dithienylethene (DTE) derivatives and established a method that can be used to prepare these photoswitchable thioacids. Four thioacid-functionalized diarylethene derivatives were synthesized through the activation of carboxylic acids with N-hydroxysuccinimide, followed by reactions with sodium hydrosulfide with yields over 90%. These derivatives exhibited reversible photoswitching and photochromic properties upon treatment with ultraviolet (UV) and visible lights. The thioacid groups …

Quantification Of Antiretroviral Drug Emtricitabine In Human Plasma By Surface Enhanced Raman Spectroscopy, Marguerite R. Butler, Terry A. Jacot, Sucharita M. Dutta, Gustavo F. Doncel, John B. Cooper

Chemistry & Biochemistry Faculty Publications

In this study, reproducible label-free detection and quantification of the antiretroviral drug emtricitabine (FTC) down to 78 ng/mL in human plasma by surface enhanced Raman spectroscopy (SERS) is presented. A novel plasma sample pretreatment method using silver nitrate and silver colloidal nanoparticles (Ag CNPs) was used to prepare the plasma samples for analysis. The pretreated plasma samples were evaporated to dryness on an aluminum surface and a computer-controlled Raman scanning system was used to collect spatially resolved SERS spectra of the entire surface. Calibration curves of commercial human plasma samples containing FTC in a concentration range of 5000 to 78 …

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 …

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. …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Polarizable Amoeba Force Field Predicts Thin And Dense Hydration Layer Around Monosaccharides, Luke A. Newman, Mackenzie G. Patton, Breyanna A. Rodriguez, Ethan W. Summer, Valerie Vaissier Welbourn

Chemistry & Biochemistry Faculty Publications

Polarizable force fields crucially enhance the modeling of macromolecules in polar media. Here, we present new parameters to model six common monosaccharides with the polarizable AMOEBA force field. These parameters yield a thinner, but denser, hydration layer than that previously reported. This denser hydration layer results in eliminating non-physical aggregation of glucose in water-an issue that has plagued molecular dynamics simulations of carbohydrates for decades.

Reducing Short-Chain Pfas Levels In California Water Supplies, Manu Prabandham

Pomona Senior Theses

This thesis proposes twelve specific policies based on precedents set by prior regulation of persistent organic pollutants (such as PCBs), the costs and benefits of short-chain PFAS, technologies available to remove and destroy short-chain PFAS, and the roles and limitations of California’s regulatory institutions. The twelve policies are chosen to be politically and financially feasible, effective at removing short-chain PFAS from water supplies, and equitable towards lower-income and minority Californians, who suffer the most from the consequences of PFAS and other environmental pollutants. The new definitions, education campaigns, studies, taxes, bans, standards, testing, and filtration systems proposed are intended to …

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 …

Cumulative Distribution Function And Spatially Resolved Surface-Enhanced Raman Spectroscopy For The Quantitative Analysis Of Emtricitabine, Jana Hrncirova, Marguerite R. Butler, Sucharita Dutta, Meredith R. Clark, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) has exceptional analytical sensitivity and selectivity. However, SERS irreproducibility presents an obstacle when using it for precise quantitative measurements. In this study, colloidal nanoparticles evaporated to dryness are used as a SERS active surface for the detection of the HIV drug emtricitabine (FTC; trade name Emtriva). Despite the irreproducibility of the SERS resulting from the stochastic process of evaporation, using a SERS scanning instrument, the SERS enhancement factors of spatially resolved spectra have a well-defined distribution of signals for a given analyte concentration. This distribution follows a power law function ranging from weak (very abundant signals) …

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 …

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 Kinetic Modulation Of Α - Synuclein Fibrillation And Toxicity By 4-Phenylbutyric Acid, Kristos Awuah Baffour

Graduate Theses/Dissertations

ABSTRACT

The Protein misfolding and aggregation of alpha-synuclein (α-syn) into neurotoxic amyloids underlies the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). 4-Phenylbutyrate (PBA), an FDA drug approved for treating urea cycle disorders, has garnered significant attention as a potential chemical chaperone for targeting alpha-synuclein (α-syn) aggregation. Using in vitro assays, we demonstrated that PBA treatment alters the pattern of α-syn aggregation, as evidenced by reduced formation of oligomeric species and its increased susceptibility to proteolytic cleavage under the influence of PBA. Proteinase K assay, surface plasmon resonance, and Nile red studies indicate that PBA interacts with the extensive …

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 …

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 …

Observed Effects Of Physiological Melatonin Dosing On Mda-Mb-231 Breast Cancer Cell Proliferation, Wenli Wu

Williams Honors College, Honors Research Projects

This project seeks to evaluate pharmacological dosing of melatonin on the cell proliferation of MDA-MB-231 breast cancer cell line in culture, using the two solubility carriers: DMSO/water and ethanol. This experiment is a component of ongoing research at the Eaton lab which will elucidate melatonin dose-response toxicology in zebrafish and a possible breast cancer xenograft model for novel treatment therapies.

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 …