Pharmacology, Toxicology and Environmental Health Commons^™

New Fluorinated Chalcone And Pyrazolines Analogues: Synthesis, Docking And Molecular Dynamic Studies As Anticancer Agents, Jasril Jasril

The Thai Journal of Pharmaceutical Sciences

Some of chalcones and pyrazolines analogues are known to have a good potency as anticancer agents. In this work, a fluorinated chalcone and two pyrazolines were successfully synthesized under microwave irradiation. Molecular docking and molecular dynamic.

Influence Of Disease-Related Knowledge And Personality Traits On Parkinson’S Patient Empowerment, Pramon Viwattanakulvanid, Tanattha Kittisopee

The Thai Journal of Pharmaceutical Sciences

Background: Parkinson’s disease (PD), a neurodegenerative disorder, has an impact on both the physical and mental functions of persons with Parkinson’s (PwP), who tend to lose their sense of empowerment, cognitive state of perceived competence and pe...

Stability Determination Of An Alternative Approach To Use Of Liquid Drug Substance As Oil Phase In Microemulsion Formulations: Methyl Salicylate, Warunee Leesajakul, Sunee Channarong, Pathamaporn Chuetee

The Thai Journal of Pharmaceutical Sciences

The objective of this study was to investigate the stability of microemulsions using methyl salicylate as oil phase in the presence and the absence of hydrophobic additives and/or drug after six-month storage at ambient temperature. The investigated addi.

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice, Rucha Fadnavis

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Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Effect Of Hyperglycemia And Thiazolidinediones On Cardiac Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In Db/Db Diabetic Mice., Rucha Fadnavis

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Type 2 diabetes mellitus is strongly associated with increased risk of cardiovascular disease. Despite availability of several antidiabetic medications, the cardiovascular outcomes remain unchanged. Activation of renin angiotensin system is one of the critical factors in development of diabetic complications. Hyperglycemia causes an increase in tissue and circulating Angiotensin II. Angiotensin converting enzyme (ACE2) and neprilysin (NEP) are angiotensin (1-7) forming enzymes. ACE2 was first cloned from heart failure patients and has cardioprotective and renoprotective properties. Combination of angiotensin receptor antagonism and NEP inhibition is a new therapeutic strategy for treatment of heart failure. The aim of this study was …

Axonal Transport, Parkin, And Α-Synuclein; Novel Therapeutic Targets To Treat Methamphetamine Neurotoxicity, Bryan Andrew Killinger

Wayne State University Dissertations

Methamphetamine (METH) is a commonly abuse psychostimulant. Exposure to chronic high doses of METH can result in neurotoxicity primarily characterized by damage to striatal dopaminergic (DAergic) axons. There are currently no therapeutic interventions for METH neurotoxicity. To some extent damage to striatal DAergic axons is reversible and DAergic axon function may return following abstinence from METH. The reversible nature of METH neurotoxicity suggests that normal striatal function could be restored following exposure to METH. However, potential targets to treat METH neurotoxicity are needed. Axonal transport is required for restoration of DAergic axon components damaged or lost following METH. Here we …

Underlying Mechanisms Of Arsenic-Induced Tumorigenesis: From Epigenetics To Malignancy, Lingzhi Li

Wayne State University Dissertations

Arsenic is a well-recognized environmental health threat with the capability of inducing a number of human diseases, including cancer. The aim of this dissertation is to unveil the mechanisms underlying the carcinogenic activities of environmental arsenic. The biological functions of arsenic had been studied for decades. However, there are still many questions that remain to be fully answered, such as whether and how arsenic contributes to the epigenetic regulations and migration or metastasis control of the cancer cells. In this regard, we focused our attention on both histone modifications and miRNA regulations in the arsenic-induced malignant transformation of the cells, …

Human Kinome In Skeletal Muscle Insulin Resistance, Yue Qi

Wayne State University Dissertations

Protein kinases play fundamental roles in regulation of biological processes and functions, such as insulin signaling and glucose metabolism. Dysregulation of protein kinases may cause impaired cell signaling and human diseases, such as metabolic syndrome and type 2 diabetes (T2D). Skeletal muscle is the main site responsible for insulin-stimulated glucose disposal, and insulin resistance in skeletal muscle is one of the key features of the pathogenesis of T2D. Therefore, malfunction of protein kinases and their interaction proteins may contribute to the molecular mechanism of insulin resistance in human skeletal muscle. However, no large scale profiling study has been reported to …

G-Quadruplexes As Molecular Targets For Transcriptional Control, Rhianna Kyelle Morgan

Electronic Theses and Dissertations

DNA G-quadruplexes (G4s) have gained interest in modern drug discovery efforts. The majority of G4 research, including the mass of this research, heavily focuses on cancer therapeutic development, as G4s are more pronounced in oncogenic promoters compared to the rest of the genome, our efforts extend towards neuroprotection as well. In particular, this work covers G4s in the promoters of MYC, VEGF, kRAS, and Bcl-2. MYC and VEGF harbor the two most well described promoter G4s to date, and their stabilization cultivates transcriptional silencing. Downregulation of MYC reduces cell growth and alters cell energetics; it is promising for a variety …

Thermal Burn Injury Induced Microvesicle Particle Release, Katherine Erin Fahy

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Microvesicle particles (MVP) are found to be important for cellular communication because they contain many bioactive proteins, lipids, cytokines, and nucleic acids. We have previously found that ultraviolet B radiation (UVB) and a Platelet-activating factor agonist (CPAF) can stimulate the release of MVP in keratinocytes. We hypothesized that there may also be an increase in MVP released after thermal burn and that could be involved in pathogenesis of the systemic effects found in some patients. In this thesis various keratinocyte cell lines, mice and human ex vivo skin were used as model systems to test our hypotheses. It was determined …

Extracellular Microvesicles As A Novel Biomarker For Wound Healing, Walid Omran Mari

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Introduction: Wound healing is a sophisticated dynamic process that involves complex coordination among a variety of resident cells in a suitable extracellular environment. Chronic wounds are defined as wounds that fail to heal within a period of 3 months. Negative pressure wound therapy (NPWT) is a closed suction drainage system is used to enable mass transport of fluid from the body as an adjunct to surgical procedures. (Oasis-ultra) is a triple layer extracellular matrix containing different types of glycosaminoglycans (GAGs) like heparin sulfate, hyaluronic acid and chondroitin sulfate. In addition, it has adhesion molecule such as fibronectin and laminin along …

Altered Gut Microbiome In A Mouse Model Of Gulf War Illness Causes Neuroinflammation And Intestinal Injury Via Leaky Gut And Tlr4 Activation, Firas Alhasson, Suvarthi Das, Ratanesh K. Seth, Diptadip Dattaroy, Varun Chandrashekaran, Caitlin N. Ryan, Luisa S. Chan, Traci Testerman, James Burch, Lorne J. Hofseth, Ronnie Horner, Mitzi Nagarkatti, Prakash Nagarkatti, Stephen M. Lasley, Saurabh Chatterjee

Faculty Publications

Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease …

Atp-Sensitive Inwardly Rectifying Potassium Channel Modulators Alter Cardiac Function In Honey Bees, Scott T. O'Neal, Daniel R. Swale, Jeffrey R. Bloomquist, Troy D. Anderson

Department of Entomology: Faculty Publications

ATP-sensitive inwardly rectifying potassium (KATP) channels couple cellular metabolism to the membrane potential of the cell and play an important role in a variety of tissue types, including the insect dorsal vessel, making them a subject of interest not only for understanding invertebrate physiology, but also as a potential target for novel insecticides. Most of what is known about these ion channels is the result of work performed in mammalian systems, with insect studies being limited to only a few species and physiological systems. The goal of this study was to investigate the role that K_ATP channels play in …

The International Scientific Association For Probiotics And Prebiotics (Isapp) Consensus Statement On The Definition And Scope Of Prebiotics, Glenn R. Gibson, Robert W. Hutkins, Mary Ellen Sanders, Susan L. Prescott, Raylene A. Reimer, Seppo J. Salminen, Karen Scott, Catherine Stanton, Kelly S. Swanson, Patrice D. Cani, Kristin Verbeke, Gregor Reid

Department of Food Science and Technology: Faculty Publications

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective …

Three Dimensional Homology Modeling Of Organic Cation Transporter 3 To Identify Structural Elements Mediating Transporter-Substrate Interactions, Hebing Liu

Theses and Dissertations

Organic cation transporters (OCTs) play a pivotal role in the absorption, tissue distribution, and excretion of a diverse array of substances, and currently the nature of the biochemical interactions between substrate and OCTs are unknown. Therefore, identifying which amino acid residues are critical for OCT-substrate interactions is of central importance to understanding and predicting interactions between drugs and OCTs. A three-dimensional (3-D) homology model of human OCT3 was generated using the crystal structure of a high affinity phosphate transporter from Piriformospora indica (PiPT) as template, and putative binding pocket for the prototypical hOCT3 ligand 1-methyl-4-phenylpyridinium (MPP⁺) was identified …

Ethanol Reversal Of Oxycodone Tolerances, Joanna C. Jacob

Theses and Dissertations

Oxycodone is a semi-synthetic opioid originally developed as a safer alternative to morphine. It is commonly prescribed for its pain-relieving effects, but has recently been implicated as a major underlying cause of the current opioid epidemic due to its clinical limitations that include tolerance, dependence and a high abuse liability. Simultaneous consumption of opioids and ethanol has been shown to increase the risk of overdose and death from opioids in opioid-tolerant individuals. We hypothesized that ethanol reversed opioid tolerance and previous studies showed that ethanol reversed morphine tolerance. This dissertation investigated whether ethanol reversed tolerance to other opioids in mice, …

Mercury Bioaccumulation In Three Popular Subsistence And Recreational Estuarine Fishes From Southeastern U.S.A., Taylor Cannon

Theses and Dissertations

A rising concern in recent years has occurred over the presence of methylmercury in seafood, particularly fishes, and its impact on human health. However, fish also provide many health benefits, including improved cardiovascular health and neurodevelopment. Because fishes are the main source of methylmercury exposure to humans, and are such an integral part of the human diet, understanding the risks versus the benefits of fish consumption is imperative in allowing the public to make healthy, educated choices. One way that state and federal governments attempt to do this is through issuing fish consumption advisories. Unfortunately, these advisories do not always …

Prenatal Methylmercury Exposure Through Rice Consumption In Rural China, Chuan Hong

Theses and Dissertations

Background: Methylmercury is one of the most toxic forms of mercury, which severely afflicts the developing fetus. Methylmercury exposure occurs not only through fish consumption but also through rice consumption. However, rice does not contain the same beneficial micronutrients that fish/shellfish has. Therefore, prenatal methylmercury exposure through maternal rice consumption may potentially increase adverse health effects on the developing fetus.

Objectives: The purpose of this dissertation was to investigate the magnitude of prenatal methylmercury exposure through rice consumption and the relationship between maternal mercury biomarkers and birth outcomes.

Methods: A total of 398 pregnant women were recruited at parturition in …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

A Study Of Hepatic Purinergic Receptor X7 Molecular Mechanisms In Ectopic Intestinal Inflammation In Environmental Nafld, Varun Chandrashekaran

Theses and Dissertations

Due to the increased consumption of unhealthy foods rich in sugar and fat along with a highly sedentary lifestyle the prevalence of obesity has steadily increased in the United States and the rest of the world. In America about one third of the adult population is obese putting them at a greater risk for diseases such as cancer, cardio-vascular disorders, inflammation and metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD). NAFLD can be classified into two major categories non-alcoholic fatty liver (NAFL) and non-alcoholic steato-hepatitis depending on the extent of damage which ranges from simple fat accumulation …