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Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow 2022 University of Mississippi

Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow

Honors Theses

Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …


The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez 2022 University of Southern Maine

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …


Investigating The Efficacy Of Tazemetosttat For In Vitro Treatment Of Human Triple Negative Breast Cancer Cells, Harshita Indukuri 2022 Belmont University

Investigating The Efficacy Of Tazemetosttat For In Vitro Treatment Of Human Triple Negative Breast Cancer Cells, Harshita Indukuri

Honors Scholars Collaborative Projects

Cancer is a formidable, genetic disease that affects many people, either directly or indirectly. Breast cancer is the most commonly diagnosed cancer worldwide (31). Triple-negative breast cancer (TNBC) is a type of breast cancer that has a higher lethality compared to other breast cancers and has a poor prognosis due to its highly invasive nature and limited treatment options. Finding safe, effective, and accessible treatment for TNBC is integral to treating TNBC patients. Tazemetostat is an EZH2-inhibitor that has recently been approved for use in epithelioid sarcoma (23). EZH2 is an overexpressed protein in many cancers, including TNBC (11). However, …


Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson 2022 Liberty University

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …


Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari 2022 University of Nebraska-Lincoln

Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Influenza A virus of the swine (IAV-S) is an economically important swine pathogen that has the potential to spread to humans, thus posing an ongoing public health concern due to its zoonotic potential. Hemagglutinin (HA), the most abundant viral envelope protein, is known to be the key protective antigen. Anti-HA antibodies alone, have been shown to prevent IAV infection. In this study we evaluated the feasibility of a recombinant tri segmented Pichinde virus (PICV) as a viral vector to deliver IAV-S hemagglutinin antigen in pigs. Four groups of weaned pigs (T01-04) were immunized twice with PBS, rPICV-GFP as a vector …


Sex Differences In Lateral Hypothalamic Extracellular Glucose Concentrations During Cumulative Dosing Of Methamphetamine In Rats, Joshua A. Jolton 2022 University of Nebraska-Lincoln

Sex Differences In Lateral Hypothalamic Extracellular Glucose Concentrations During Cumulative Dosing Of Methamphetamine In Rats, Joshua A. Jolton

Honors Program: Senior Projects (Public)

The present study experimentally investigated sex differences in lateral hypothalamic glucose concentrations following cumulative dosing of methamphetamine. Male (n=17) and female (n=11) rats were surgically implanted with enzyme-based glucose biosensors in the lateral hypothalamus. Rats then received a saline injection followed by four methamphetamine doses (0.025 mg/kg, 0.05 mg/kg, 0.1 mg/kg, and 0.2 mg/kg) spaced 55 minutes apart. We found that while there was a general decrease in glucose baseline throughout the study for both sexes, the magnitude of the decrease was significantly greater in females compared to males. On a rapid timescale, fixed sex effects existed at the lower …


The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen 2022 College of Saint Benedict/Saint John's University

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …


Attempted Synthesis & Antibacterial Properties Of Apt-6k Against Ndm-1 K. Pneumoniae, Alec Bofetiado 2022 Andrews Universty

Attempted Synthesis & Antibacterial Properties Of Apt-6k Against Ndm-1 K. Pneumoniae, Alec Bofetiado

Honors Theses

NDM-1 K. pneumoniae is a highly resistant bacterial organism that is capable of causing debilitating nosocomial infections in immunocompromised patients. Only "last-resort" antibiotics--such as colistin--work against this organism. Therefore, new antibiotics are needed to help fight against these types of infections. APT-6K is a novel compound that was demonstrated to be effective against MRSA with nanomolar concentrations in a prior study. Novel methods of APT-6K synthesis and its testing for antibiotic effects against NDM-1 K. pneumoniae were attempted in this research. APT-6K synthesis was unsuccessful. Commercially-prepared APT-6K also did not demonstrate growth inhibition against NDM-1 K. pneumoniae nor against a …


Targeting The Side-Chain Convergence Of Α-Helical Hot Spots To Design Small-Molecule Mimetics Disrupting Protein-Protein Interaction, Zhen Wang 2022 University of South Florida

Targeting The Side-Chain Convergence Of Α-Helical Hot Spots To Design Small-Molecule Mimetics Disrupting Protein-Protein Interaction, Zhen Wang

USF Tampa Graduate Theses and Dissertations

α-Helix accounts for the largest class of protein secondary structures and plays a key role in mediating protein-protein interactions (PPIs). Small-molecule α-helix mimetics mimic the structural features of α-helical hot spots and offer a powerful tool to unravel complex signaling networks and mitigate aberrant PPIs. In this dissertation, the side-chain conformational convergence of α-helical hot spots was disclosed, and insights into the side-chain convergence were exploited to instruct the design of small-molecule α-helix mimetics. The first chapter of this dissertation provides an overview of the characteristics of α-helical hot spots and current strategies to design small-molecule α-helix mimetics. In chapter …


Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger 2022 Roseman University of Health Sciences

Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger

Annual Research Symposium

The small molecule ketamine has generated much interest due to its rapid antidepressant effects. Despite having a rapid onset, ketamine has poor bioavailability, short duration of action, toxicities with long-term use, and a high potential for abuse. The molecule MI-4 (RO 25-6981) has also been shown to have both a rapid and sustained antidepressant effect. Most of the research into the mechanism of the rapid onset of MI-4 and ketamine has focused on their interaction with the NMDA receptor in addition to some monoamine transporters. Some recent publications have shown a significant role of AMPA receptors in the ketamine antidepressant …


Response To A Water Bolus In Long Term Oral Contraceptive Users, Whitley C. Atkins, Brendon P. McDermott, Abigail T. Colburn, Stavros A. Kavouras 2022 University of Arkansas, Fayetteville

Response To A Water Bolus In Long Term Oral Contraceptive Users, Whitley C. Atkins, Brendon P. Mcdermott, Abigail T. Colburn, Stavros A. Kavouras

Health, Human Performance and Recreation Faculty Publications and Presentations

The purpose of our study was to determine the responses to an acute water bolus in long-term oral contraception (OCP) users. Seventeen female volunteers (27 ± 5 y, 64.1 ± 13.7 kg, 39.6 ± 5.9 kg/LBM) provided consent and enrolled in our study. All were long-term OCP users and participated in two trials, one during the active pill (High Hormone, HH) dose of their prescribed OCP and one during the sham pill (Low Hormone, LH) dose. Participants reported to the laboratory euhydrated, were fed breakfast, remained seated for 60 min and were provided a bolus of room temperature water in …


Antimicrobial Activity Of Zinc Oxide Nanoparticles Compared To Silver Nanoparticles Administered Towards Methicillin-Resistant Staphylococcus Aureus Biofilms, Kevin Núño 2022 University of South Florida

Antimicrobial Activity Of Zinc Oxide Nanoparticles Compared To Silver Nanoparticles Administered Towards Methicillin-Resistant Staphylococcus Aureus Biofilms, Kevin Núño

USF Tampa Graduate Theses and Dissertations

Zinc oxide nanoparticles (ZnO NPs), silver nanoparticles (AgNPs), and chitosan nanoparticles have strong antibacterial activity as a broad-spectrum antibiotic against multi-drug resistant (MDR) bacteria. MDR bacteria have a mechanism that increases antibiotic resistance through biofilm formations. MDR methicillin-resistant Staphylococcus aureus BAA-1720 was chosen for an in vitro assessment to calculate the biofilm reduction rate and the median effective dose (ED50) by performing biofilm quantification. Dynamic light scattering was chosen to determine the physiochemical characteristics of ZnO NPs, silver nanoparticles (AgNPs), and chitosan NPs. Transmission electron microscopy was conducted to verify each treatment’s physiochemical characteristics. Antimicrobial susceptibility testing of broad-spectrum and …


The Use Of Atmospheric-Pressure Chemical Ionization For Pesticide Analysis Using Liquid Chromatography Mass Spectrometry, Pei-Ting Jiang, Kuan-Lu Wu, Hsueh-Ting Wang, Sung-Fang Chen 2022 Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan

The Use Of Atmospheric-Pressure Chemical Ionization For Pesticide Analysis Using Liquid Chromatography Mass Spectrometry, Pei-Ting Jiang, Kuan-Lu Wu, Hsueh-Ting Wang, Sung-Fang Chen

Journal of Food and Drug Analysis

Based on the regulations of the Ministry of Health and Welfare (MOHW) of Taiwan in 2017, an analysis of 373 pesticides in food was conducted using the MOHW official method. The analyses involved the use of either liquid chromatography mass spectrometry (LC-MS) with electrospray ionization (ESI) or gas chromatography mass spectrometry (GC-MS) with electron ionization (EI). In this study, the applicability of detecting pesticides using atmospheric pressure chemical ionization (APCI) was investigated and evaluated. The pesticides were separated using an aqueous solution of ammonium formate with methanol as the mobile phase, and ionization efficiency was compared between APCI, ESI, and …


A Substructure-Based Screening Approach To Uncover N-Nitrosamines In Drug Substances, Yu-Ting Kao, Shu-Fen Wang, Meng-Hsiu Wu, Shwu-Huey Her, Yi-Hsuan Yang, Chung-Hsien Lee, Hsiao-Feng Lee, An-Rong Lee, Li-Chien Chang, Li-Heng Pao 2022 School of Pharmacy, National Defense Medical Center, Taipei City, Taiwan, Republic of China

A Substructure-Based Screening Approach To Uncover N-Nitrosamines In Drug Substances, Yu-Ting Kao, Shu-Fen Wang, Meng-Hsiu Wu, Shwu-Huey Her, Yi-Hsuan Yang, Chung-Hsien Lee, Hsiao-Feng Lee, An-Rong Lee, Li-Chien Chang, Li-Heng Pao

Journal of Food and Drug Analysis

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug …


Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah 2022 Infectious Diseases, Mayo Clinic, Jacksonville, Florida, USA

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Journal of Food and Drug Analysis

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1,622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …


Effect Of Repeated Shengmai-San Administration On Nifedipine Pharmacokinetics And The Risk/Benefit Under Co-Treatment, Hong-Jaan Wang, Elise Chia-Hui Tan, Tzu-Yi Chiang, Wei-Ching Chen, Chien-Chang Shen, Yune-Fang Ueng 2022 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan

Effect Of Repeated Shengmai-San Administration On Nifedipine Pharmacokinetics And The Risk/Benefit Under Co-Treatment, Hong-Jaan Wang, Elise Chia-Hui Tan, Tzu-Yi Chiang, Wei-Ching Chen, Chien-Chang Shen, Yune-Fang Ueng

Journal of Food and Drug Analysis

Herbal interactions with nifedipine/felodipine through cytochrome P450 (CYP) 3A inhibition is significant in humans. Shengmai-San (SMS), a three-herbal formula of Chinese medicine, is commonly prescribed in Asia populations for cardiovascular disorders. This study aimed to elucidate the impact of SMS on nifedipine/felodipine treatment by the findings from rat pharmacokinetic study of nifedipine to the retrospective cohort study of patients with hypertension. The 3-week SMS treatment increased the systemic exposure to nifedipine by nearly two-fold and decreased nifedipine clearance by 39% in rats. Among the ingredients of SMS component herbs, schisandrin B, schisantherin A, and methylophiopogonanone A, inhibited the nifedipine oxidation …


Evaluation Of Opioid Consumption Trends For Pain In Taiwan And Comparison With Neighboring Asian Countries, Jhi-Joung Wang, Shu-Fang Teng, Yu-Roo Chu, Chin-Chen Chu, Chung-Han Ho, Li-Ling Chu 2022 Chi Mei Medical Center, Tainan, Taiwan

Evaluation Of Opioid Consumption Trends For Pain In Taiwan And Comparison With Neighboring Asian Countries, Jhi-Joung Wang, Shu-Fang Teng, Yu-Roo Chu, Chin-Chen Chu, Chung-Han Ho, Li-Ling Chu

Journal of Food and Drug Analysis

Opioids are effective analgesics for pain relief, however, inappropriate use may cause risks. The aims of the study were to evaluate trends of opioid consumption for pain management in Taiwan and compare them among neighboring Asian countries. Opioid consumption data, including fentanyl, morphine, oxycodone, hydromorphone, codeine, and pethidine, were collected from the Controlled Drugs Management Information System of Taiwan Food and Drug Administration from 2008 to 2018. Data of different continents and neighboring Asian countries were retrieved from the WHO website. The major findings include: (1) In Taiwan, the total annual opioid consumption has gradually increased from 2008 to 2018, …


A Three-Step Stacking Capillary Electrophoresis Of Field-Amplified Sample Injection, Sweeping, And Micellar Collapse For Determination Of Dabigatran And Its Active Metabolite In Human Plasma, Cheng-Wei Cheng, Wen-Han Feng, Wei-Hua Tang, Hwang-Shang Kou, Chun-Chi Wang, Shou-Mei Wu 2022 College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

A Three-Step Stacking Capillary Electrophoresis Of Field-Amplified Sample Injection, Sweeping, And Micellar Collapse For Determination Of Dabigatran And Its Active Metabolite In Human Plasma, Cheng-Wei Cheng, Wen-Han Feng, Wei-Hua Tang, Hwang-Shang Kou, Chun-Chi Wang, Shou-Mei Wu

Journal of Food and Drug Analysis

A three-step stacking capillary electrophoresis (CE) composed of field-amplified sample injection, sweeping, and analyte focusing by micellar collapse (FASI-sweeping-AFMC) was developed to determine dabigatran (D) and its major active metabolite, dabigatran acyl-beta-d-glucuronide (DAG), in human plasma. After optimization and validation, this novel approach was further applied to monitor 5 real samples, and the 25.2 to 186.8 ng mL-1 D could be observed among those. Based on these results, the novel CE stacking strategy was successfully applied for the analysis of D and DAG in human plasma and could be served as a tool for clinical assays.


The Antihyperlipidemic Equivalent Combinatorial Components From Peel Of Citrus Reticulata ‘Chachi’, Ping-Ting Xiao, Yu-Jia Kuang, Shi-Yu Liu, Zhi-Shen Xie, Jin-Hua Hao, E-Hu Liu 2022 State Key Laboratory of Natural Medicines, China Pharmaceutical University

The Antihyperlipidemic Equivalent Combinatorial Components From Peel Of Citrus Reticulata ‘Chachi’, Ping-Ting Xiao, Yu-Jia Kuang, Shi-Yu Liu, Zhi-Shen Xie, Jin-Hua Hao, E-Hu Liu

Journal of Food and Drug Analysis

Since the combinatorial components responsible for the antihyperlipidemic activity of Citrus reticulata‘Chachi’ (CRC) peels remains unclear, we herein developed a bioactive equivalence oriented feedback screening method to discover the bioactive equivalent combinatorial components (BECCs) from CRC peels. Using palmitic acid (PA)- stimulated hepatocyte model, a combination of five polymethoxyflavones (PMFs) including tangeretin, sinensetin, nobiletin, 5,7,8,4′-tetramethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone was identified to be responsible for the antihyperlipidemic effect of CRC peels. Via evaluation of combination effect by combination index (CI), these 5 PMFs were found to take effect via a synergistic mode. Our data indicated that the antihyperlipidemic mechanism of PMF …


Food Glycomics: Dealing With Unexpected Degradation Of Oligosaccharides During Sample Preparation And Analysis, Yu-Ping Huang, Randall C. Robinson, Daniela Barile 2022 Department of Food Science and Technology, University of California-Davis, Davis, CA, USA

Food Glycomics: Dealing With Unexpected Degradation Of Oligosaccharides During Sample Preparation And Analysis, Yu-Ping Huang, Randall C. Robinson, Daniela Barile

Journal of Food and Drug Analysis

This study reveals that unexpected degradation of food oligosaccharides can occur during conventional glycomics workflows, including sample preparation and analysis by liquid chromatography-mass spectrometry (LC-MS). With the present investigation, we aim to alert the scientific community of the susceptibility of specific glycosidic linkages to degradation induced by heat and acid. Key standard oligosaccharides representing the major types found in foods (3’-sialyllactose and 6’-sialyl-N-acetyllactosamine for milk, raffinose and stachyose for legumes) were selected as model systems and underwent each of the following treatments independently: (1) labeled with the derivatizing agent 1-aminopyrene-3,6,8-trisulfonic (APTS) (followed by analysis with a capillary electrophoresis system coupled …


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