Pharmacology, Toxicology and Environmental Health Commons^™

Phytochemicals, Acute Toxicity And Genotoxicity Of Chewing Sticks From Zanthoxylum Zanthoxyloides Root And Distemonanthus Benthamianus Stem, Chinwe S. Alaribe, Akolade R. Oladipupo, Anjola T. Adebesin, Omolayomi Kaska, Emuejevoke T. Toye

Bulletin of Faculty of Pharmacy Cairo University

Dental caries has been reported to touch almost half of the world’s population, making it one of the most prevalent disease conditions in the world. Studies have shown that chewing sticks could be useful in cleaning of teeth and could offer protection against dental conditions, including caries. Given the increasing usage of chewing sticks and their unstandardized nature, in this study we investigated the acute toxicity, genotoxic effects on liver and kidney, and phytochemical constituents of chewing sticks from Zanthoxylum zanthoxyloides root and Distemonanthus benthamianus stem, widely used in West Africa. Chemical tests showed the presence of saponins, alkaloids, flavonoids, …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Electrospray Deposition Of Polyvinylidene Fluoride (Pvdf) Microparticles: Impact Of Solvents And Flow Rate, Akinwunmi Joaquim, Omari Paul, Michael Ibezim, Dewayne Johnson, April Falconer, Ying Wu, Frances Williams, Richard Mu

TIGER Institute Faculty Research

Polymeric microparticles have been shown to have great impacts in the area of drug delivery, biosensing, and tissue engineering. Electrospray technology, which provides a simple yet effective technique in the creation of microparticles, was utilized in this work. In addition, altering the electrospray experimental parameters such as applied voltage, flow rate, collector distance, solvents, and the polymer-solvent mixtures can result in differences in the size and morphology of the produced microparticles. The effects of the flow rate at (0.15, 0.3, 0.45, 0.6, 0.8, and 1 mL/h) and N, N-Dimethylformamide (DMF)/acetone solvent ratios (20:80, 40:60, 60:40, 80:20, 100:0 v/v) in the …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

An Investigation Into Use Of Natural Mistletoe Extracts And Their Formulations As Potential Anti-Cancer Treatments In Human Carcinomas, Rebecca Healy, Anne M. Friel

SURE Journal: Science Undergraduate Research Experience Journal

Cancer is a prevalent disease that is responsible for around 10 million deaths a year. Cases and deaths will continue to rise daily if nothing is done to find the most effective treatment. Mistletoe is an evergreen, semi-parasitic plant that grows on trees. This plant contains a number of biologically active compounds that contribute to its anti-cancer properties e.g., lectins. Mistletoe is obtained from nature and has been shown to be safe, potent, and effective in treating cancer. Herein we review the biological effects of mistletoe on cancer cells, formulations that can be used in cancer treatment and discuss the …

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and …

Corrigendum To “The Impact Of The Rare Disease And Orphan Drug Act In Taiwan” [J Food Drug Anal 29 (2021) 717-725]

Journal of Food and Drug Analysis

No abstract provided.

The Study Of Distribution Of Ingested Terbinafine On Skin With Ambient Ionization Tandem Mass Spectrometry, Yi-Tzu Cho, Hung Su, Ching-Ying Wu, Jingyueh Jeng, Chi-Wei Lee, Deng‐Chyang Wu, Tiao-Lai Huang, Jentaie Shiea

Journal of Food and Drug Analysis

We aim to develop an efficient and non-invasive strategy for monitoring of drugs and their metabolites via human skin. Probe sampling was combined with thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) to characterize trace terbinafine, which was secreted on patient’s skin after ingesting terbinafine tablets. The terbinafine ion signals were directly detected in the samples collected from different skin regions and the signals were monitored for 8 weeks. The detection and location of terbinafine via the skin suggest that the methods are useful in rapidly and noninvasively collecting the molecular information of the ingested drug on skin for pharmacokinetic studies.

Chemiluminescence Of Lucigenin-Tetracycline And Itsapplication For Sensitive Determination Of Procyanidin, Shuai Quan, Kaixiang Ji, Fangshuo Liu, Tesfaye Hailemariam Barkae, Mohamed Ibrahim Halawa, Saima Hanif, Baohua Lou, Jianping Li, Guobao Xu

Journal of Food and Drug Analysis

Tetracycline was reported to trigger intense lucigenin chemiluminescence (CL). Based on its significant quenching to lucigenin-tetracycline CL, procyanidin was detected. The mechanism of the lucigenin-tetracycline CL and its quenching by procyanidin were proposed. Under the optimum conditions, the calibration curve is linear in the range of 10-1000 nM for procyanidin with a detection limit of 4.4 nM. The RSD for nine replicate determinations of procyanidin was less than 1.7%. Moreover, this method was satisfactorily applied to the determination of procyanidin in human urine samples and health food capsule of grape seed.

Quantitation Of Mycophenolic Acid And Metabolites By Uplc-Ms/Ms In Renal Transplant Patients, Yun-Fen Huang, Ya-Ching Huang, Hsiao-Chen Ning, Chia-Ni Lin

Journal of Food and Drug Analysis

Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), specific inhibitors of lymphocyte proliferation, are commonly used as adjuvant therapy with calcineurin inhibitor agents after kidney transplantation. After administration, MMF and EC-MPS are hydrolyzed to mycophenolic acid (MPA), the active form of the drug, which must be monitored due to its narrow therapeutic window, drug–drug interactions, and large intra-and inter-individual pharmacokinetic variability despite a fixed dose. Monitoring plasma MPA level is recommended to maintain the drug within the therapeutic window, optimize its efficacy, and minimize side effects. This study aims to develop a method for quantifying MPA and its major metabolites …

Camphorataimide B Suppresses The Metastasis Of Human Colorectal Cancer Cell By Inhibiting Smad/Fak/Akt Axis And Promoting Degradation Of Snail/Bmp4 Complex, Chi-Chou Huang, Chia-Hung Hung, Yi-Ju Lee, Tsui-Hwa Tseng, Yean-Jang Lee, Shao-Hsuan Kao, Chau-Jong Wang

Journal of Food and Drug Analysis

Camphorataimide B (CamB) has anticancer activities against several tumors. Here, we aimed to investigate the mechanism(s) by which CamB inhibits metastasis of colorectal cancer (CRC) cells. Low-dose CamB did not affect the cell viability and cell cycle progression of CRC cells, but significantly inhibited the metastatic potentials of CRC cells. Mechanically, CamB reduced the protein and mRNA expression of BMP4, and inhibited Smad and FAK/Src/Akt signaling. CamB also decreased Snail levels by promoting its degradation via proteasome and thereafter reduced Snail-mediated BMP4 transcription. Moreover, CamB considerably inhibited the in vivo metastasis of DLD-1 cells in xenograft mice.

Orally Delivered Perilla (Perilla Frutescens) Leaf Extract Effectively Inhibits Sars-Cov-2 Infection In A Syrian Hamster Model, Yuan-Fan Chin, Wen-Fan Tang, Yu-Hsiu Chang, Tein-Yao Chang, Wen-Chin Lin, Chia-Yi Lin, Chuen-Mi Yang, Hsueh-Ling Wu, Ping-Cheng Li, Jun-Ren Sun, Shu-Chen Hsu, Chia-Ying Lee, Hsuan-Ying Lu, Jia-Yu Chang, Jia-Rong Jheng, Cheng Cheung Chen, Jyh-Hwa Kau, Chih-Heng Huang, Cheng-Hsun Chiu, Yi-Jen Hung, Hui-Ping Tsai, Jim-Tong Horng

Journal of Food and Drug Analysis

On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3−4 …

Assessing The Fate Of Fatty Acid Esters Of Hydroxy Fatty Acids, Diglycerides And Monoacetyldiacylglycerides In Grilled Ruminant Meats Marinated With Unfiltered Beer-Based Marinades, Charles F. Manful, Thu H. Pham, Evan Wheeler, Muhammad Nadeem, Oludoyin A. Adigun, Nicole Walsh, Raymond H. Thomas

Journal of Food and Drug Analysis

Ruminant meats contain functional lipids including fatty acid esters of hydroxy fatty acids (FAHFA), diglycerides (DG), monoacetyldiglycerides (MAcDG) and medium chain triglycerides (McTG) whose consumption in the normal diet can confer benefits for consumer health. However, very little is known concerning how meat processing techniques such as marination and grilling affect the quantity and quality of these functional lipids in ruminant meats. We used ultra high-performance liquid chromatography coupled to high resolution accurate mass tandem mass spectrometry (UHPLC-HRAM-MS/MS) to show how grilling following marination with either India or Wheat ale unfiltered beer-based marinades affected the quantity and quality of these …

Exosomal Proteomics In Kidney Disease: From Technical Approaches To Clinical Applications, Ageng Brahmadhi, Yung-Kun Chuang, San-Yuan Wang, Chih-Chin Kao, I-Lin Tsai

Journal of Food and Drug Analysis

Exosomes are small extracellular vesicles (sEVs) secreted from cells and have a general diameter ranging from 30~150 nm. It was reported that exosomes have essential roles in intercellular communication and can be targeted as biomarkers of disease or as therapeutic agents. Among the different techniques used for exosome investigation, the mass spectrometry-based proteomics approach has accelerated the unraveling of the molecular composition of exosomes and has contributed to improved knowledge of molecular processes in various diseases. In this review, we focused on proteomics-based studies of exosomes and clinical applications in kidney diseases. A general introduction of exosomes, isolation and characterization …

Differential Scanning Calorimetry For Authentication Of Edible Fats And Oils - What Can We Learn From The Past To Face The Current Challenges?, Mahbuba Islam, Liliana Bełkowska, Piotr Konieczny, Emilia Fornal, Jolanta Tomaszewska-Gras

Journal of Food and Drug Analysis

Fats and oils authentication has become an important issue recently, due to the growing interest in consumption of cold-pressed oils. Therefore, it is becoming more and more difficult to maintain official control over the growing assortment of new cold-pressed oils. Authenticity of plant oils is also an important issue for religious or cultural reasons.This review article focuses on the application of differential scanning calorimetry (DSC) in the field of assessing authenticity of various fats and oils (e.g. olive oil, palm oil, confectionery fats, butter). Extra virgin olive oil (EVOO) is the most comprehensively tested oil by means of the DSC …

Trends And Applications Of Food Protein-Origin Hydrolysates And Bioactive Peptides, Yi-Hsieng Samuel Wu, Yi-Chen Chen

Journal of Food and Drug Analysis

It was reported that protein hydrolysates or derived peptides have more functionalities than their parent protein. Most functional protein hydrolysates or peptides are identified from various food products, including plant, fish, and land-animal protein sources. Within a few decades, the application of food protein-origin functional hydrolysates or peptides could be divided into two main categories according to their applied intentions: 1) preservatives and bioactive packing materials; 2) nutraceutical ingredients. According to the literature, the applications of food protein-origin functional hydrolysates or peptides on food preservative and nutraceutical ingredients have attracted much attention. However, the approach method should be changed. Multi-activities, …

A Bioaffinity Self-Assembling Gel For Localized Delivery Of Immunotherapeutics, Ngoc Pham

Electronic Theses and Dissertations

Renal cell carcinoma (RCC) is a type of cancer in which malignant cells develop in the kidney tubules. Immune checkpoint inhibitors (ICI), including anti-PD-1 antibodies (aPD1), as monotherapies or in combination settings have advanced to the front-line treatment for patients diagnosed with RCC. Systemic infusion of ICI may render subtherapeutic concentrations in the lesions and increase risks of immune-related adverse events. To overcome these limitations, locoregional drug delivery has gained substantial interests as a modality in immuno-oncology. However, conventional intratumoral injections may be ineffective because the high interstitial fluid pressure in tumors resists drug retention and results in rapid local …

Hyperbranched Polyester-Based Drug Delivery System For The Optical Imaging And Treatment Of Cancer, Truptiben Patel

Electronic Theses & Dissertations

Hyperbranched polymers are well known to be a promising new class of drug delivery system for biomedical application. In this research, a novel hyperbranched polyester polymer was synthesized by following melt polymerization technique utilizing our proprietary A₂B monomer, triethylene glycol and diethylenetriaminepentaacetic acid (DTPA). This polymerization process was catalyzed by p-toluene sulfonic acid and was monitored by analyzing the polymer sample in regular time intervals. The final polymer was purified using the solvent precipitation method and characterized using MALDI-TOF, NMR, and GPC, DSC, TGA, FT-IR. The solvent diffusion method was used to formulate polymeric nanoparticle and doxorubicin drug …

Polymeric Nanocarriers For Delivery Of Small Molecules Inhibiting Tubulin Polymerization For The Treatment Of Pancreatic Cancer And Lung Metastatic Melanoma, Rajan Sharma Bhattarai

Theses & Dissertations

The aim of this thesis is to develop delivery systems for the novel small molecules which inhibit tubulin polymerization. One of the small molecules was modified to lipid conjugate to increase the lipophilicity of the molecules which in turn drastically improved the drug loading in amphiphilic polymeric system. The second molecule was conjugated to the amphiphilic polymeric backbone with pH sensitive Schiff’s linker for the tumor site specific delivery in lung metastatic melanoma model.

Chapter 1 discusses the tumor microenvironment for the solid tumor especially focusing on Pancreatic Ductal Adenocarcinoma (PDAC). Further the drug delivery system currently researched for addressing …

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

The Racial Divide: A Follow Up Study On Racial Disparity Amongst Covid-19 Survivors In An Urban Community, Christopher Millet, Emily Racoosin, Spandana Narvaneni, George Horani, Sherif Roman, Alisa Farokhian, Arslan Chaudhry, Sohail Chaudhry, Yezin Shamoon, Humberto Jimenez, Patrick Michael, Jin Suh

Journal of Community Hospital Internal Medicine Perspectives

Background Studies have shown that COVID-19 has had a disproportionate effect on minority groups in both the clinical and social settings in America. We conducted a follow up study on patients previously diagnosed with COVID-19 one year ago in an urban community in New Jersey. The purpose of the study was to evaluate the socioeconomic impact of COVID-19 as well as assess for receptiveness towards COVID-19 vaccination amongst various ethnic groups.

Methods This was a prospective cohort study consisting of patients who had recovered from COVID-19 one year prior. The patients included in the study had a confirmed COVID-19 diagnosis …

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

University Scholar Projects

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. My thesis focuses on identifying inhibitors capable of disrupting the Rev7/Rev3 TLS PPI. This study …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

Honors Scholar Theses

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. Our current work in this area is focusing on inhibitors capable of disrupting the Rev7/Rev3 …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

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

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

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, …

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 …