Pharmacology, Toxicology and Environmental Health Commons^™

Exosomes Released From Multiple Myeloma Cells Influence The Angiogenic Function Of Endothelial Cells By Regulating Microrna-29b, Qinmao Ye

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Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells generally caused by chromosomal abnormalities. It occurs in the bone marrow, which is the microenvironment of multiple myeloma. Exosomes (EXs) are 30-100 nm membrane-derived micro-vesicles containing various of bioactive molecules, such as microRNAs, to mediate the cell-cell interaction. Numerous studies reported that exosomes play a significant role in tumor microenvironment. Angiogenesis has the important implication in tumor exacerbation to supply nutrients to promote the progression of cancer cells through endothelial cells (ECs). Some studies demonstrated that microRNA-29b (miR-29b) can suppress tumor development and inhibit angiogenesis. Therefore, in …

Regulation Of Microvesicle Particle Release In Keratinocytes, Azeezat Afolake Awoyemi

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Microvesicle particles (MVPs) are produced from cellular membranes and are thought to mediate cell-cell communication, including in response to stressors such as UVB radiation and thermal burn injury. Previous studies have shown that stress-induced MVP release requires the platelet-activating factor (PAF) receptor in human keratinocytes and that pharmacological inhibition of acid sphingomyelinase (ASM) blocked this release. To validate a genetic role for ASM in MVP release, we used CRISPR-Cas9 gene silencing in human keratinocytes and primary fibroblasts derived from ASM-knockout mice. Though MVP release was partially blocked in ASM-deficient mouse fibroblasts, the inability to fully knockdown ASM in HaCaT cells …

Exposure To Polybrominated Diphenyl Ethers (Pbdes) In American And Canadian Workers: Biomonitoring Data From Two National Surveys, Sabrina Gravel, Jérôme Lavoué, France Labrèche

Études primaires

Polybrominated diphenyl ethers (PBDEs) are flame retardants commonly found in many household and industrial products. They can be detected in the serum of the general population, and in even higher concentrations in workers of certain industries, due to an additional occupational exposure. The purpose of this analysis is to determine background exposure levels of PBDEs in the general working population, using national surveys where working status was self-reported. Participants aged 20–65 were selected from the 2003–2004 U.S. National Health and Nutrition Examination Survey (n = 1141) and the 2007–2009 Canadian Health Measures Survey (n = 1337). Only four congeners were …

Delay Discounting And Cannabinoid Enzyme Inhibitors, Devin Andrew Galdieri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Delay discounting is a measure of impulsive choice that is correlated with maladaptive behavior and psychological disorders. Disruptions to serotonin and dopamine pathways can cause changes in delay discounting, as can lesions to the prefrontal cortex and nucleus accumbens. The endocannabinoid system modulates other neurotransmitter systems, including dopamine and serotonin pathways. Cannabinoid receptors type 1 are found in relatively high concentrations in the nucleus accumbens and the prefrontal cortex. These receptors are activated by endogenous cannabinoids, which are synthesized on demand and broken down by catabolic enzymes. The action of these enzymes can be inhibited by a class of drugs …

Effect Of Environmental Factors On The Aggregation Behavior Of Silver Nanoparticles In The Aquatic Environment, Kamelia Afshinnia

Theses and Dissertations

Understanding the environmental factors that affect the fate and effects of engineered nanoparticles (ENPs) in the environment is crucial for NP risk assessment. Silver nanoparticles (Ag NPs) readily transform in the environment, which alters their properties and subsequently their transport, fate, and toxicity. The overall aim of this dissertation was to evaluate the effects of Ag NPs physicochemical properties (e.g., size, surface charge, surface coating) and water chemistry (e.g., buffer concentration, organic ligands, natural organic matter) in controlling Ag NPs colloidal stability. This aim was achieved by systematically 1) review and rationalize many studies that investigated the aggregation kinetics of …

Application Of Polymer-Coated Magnetic Nanoparticles For Oil Separation, Seyyedali Mirshahghassemi

Theses and Dissertations

Oil spills and storm water runoffs can have serious impact on the environment with potentially major economic impacts. Given the limitation of current oil clean-up technique, the application of nanotechnology for oil remediation has been widely studied showing a promising avenue of research. This dissertation reports a cheap, facile and cost-effective nanotechnology-based oil clean-up technique that has been optimized for effectiveness and feasibility and reduced adverse environmental impacts. The synthesized polyvinylpyrrolidone (PVP)-coated magnetic nanoparticles (NPs) have been characterized using different techniques and the oil removal efficiency investigated under a wide range of environmentally relevant conditions. Based on the characterization data, …

Understanding The Impact Of Land Use On Microbial Water Quality To Support Decisions For A Future Land Use Plan, Mohammed Tawfiq Aljassim

Theses and Dissertations

May River meandering through the Town of Bluffton, South Carolina has been known for its high level of water quality. The May River is one of the major sources of shellfish harvesting in South Carolina. Due to the non-point source pollution of fecal coliform, the water quality of the May River became degraded. As a result, shellfish harvesting classification in the May River was downgraded for the first time in its history. The rapid growth of the Town has led to a change in land use, which might be related to the increased levels of fecal coliform in the stream …

Inhibition Of Aflatoxin Biosynthesis With Vibrio Gazogenes, Phani Madhuri Gummadidala

Theses and Dissertations

Aflatoxin, a mycotoxin, is one of the world’s most potent carcinogen. It contaminates major food products such as milk, grains, nuts, corn, etc., leading to greater than $ 1 billion in economic losses and when ingested causes hepatocellular carcinoma (HCC). It is the primary risk factor for 75% HCC cases in the developing world and 3% HCC cases in developed world. Most common methods used in agriculture to reduce aflatoxin contamination are expensive, time consuming and have low efficiency with limited success rates where as biological controls were proven to be most effective in inhibiting aflatoxins and aflatoxin producing fungi. …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

Targeting Monoacylglycerol Lipase For The Reversal And Prevention Of Paclitaxel-Induced Allodynia In Mice, Zachary Curry

Theses and Dissertations

Chemotherapy-induced peripheral neuropathy (CIPN) is a side-effect of chemotherapy causing pain in the hands and feet. In particular, paclitaxel causes CIPN lasting for years without effective treatment. There is a strong need for analgesics to both treat and prevent CIPN. One system containing multiple targets to treat CIPN is the endogenous cannabinoid system. This system consists of cannabinoid type 1 (CB₁) and type 2 (CB₂) receptors primarily expressed on presynaptic neurons and cells of the immune system, respectively. Inhibition of monoacylglycerol lipase (MAGL), which hydrolyzes the endogenous cannabinoid 2- arachidonoylglycerol (2-AG), with JZL184 or MJN110 produces …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

Examining The Issue Of Compliance With Personal Protective Equipment Among Wastewater Workers Across The Southeast Region Of The United States, Tamara L. Wright

College of Graduate Studies: Theses & Dissertations

Wastewater workers are exposed to different occupational hazards such as chemicals, gases, viruses, and bacteria. Personal Protective Equipment (PPE) is a significant factor that can reduce or increase the probability of an accident from hazardous exposures to chemicals and microbial contaminants. The purpose of this study was to identify wastewater worker’s beliefs and practices on wearing PPE and protections offered by PPE through the integration of the Health Belief Model (HBM). Participants were workers in the wastewater industry, which included wastewater operators, laboratory analysts, maintenance workers, wastewater collection workers, equipment operators, managers, and supervisors (n=272). The instrument was a self-administered …

Environmental Impacts On Enterococcus In Shem Creek, South Carolina, And Characterization Of Changing Land Use, Maria Elizabeth Zubizarreta

Theses and Dissertations

Zoning and land-use practices have a direct influence on hydrologic systems and can impact water resources. Linkages between change in land uses and degradation of water quality in stream and watershed environments have been well established. Shem Creek, located in Mount Pleasant, SC, has a history of fecal indicator bacteria levels that exceed the Environmental Protection Agency’s recreational water quality standards. With recent coastal population and development trends, proper management and the sustainability of beach and estuary environments are a rising public health concern. The objective of this study is to determine what climatic and water quality parameters are associated …

Linking Microbial Phylogenetic And Functional Gene Diversity To Microbial Mat Ecosystem Function Following Environmental Disturbance, Eva Christine Preisner

Theses and Dissertations

The ability of ecosystems to adapt to environmental perturbations depends on the duration and intensity of change and the overall biological diversity of the system. In this study, a microbial mat ecosystem located on San Salvador Island, the Bahamas was used as a model to examine how environmental disturbance affects microbial community resistance, their protein synthesis potential (PSP), ecosystem function as measured by biogeochemical cycling, community stability, and resilience. This ecosystem experienced a large shift in salinity (230 to 65 g kg-1) during 2011–2012 following the landfall of Hurricane Irene on San Salvador Island. High throughput sequencing and analysis of …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Design, Synthesis And Biological Evaluation Of Inhibitors Against Both Human And Mouse Microsomal Prostaglandin E2 Synthase-1 Enzymes, Kai Ding

Theses and Dissertations--Chemistry

As the principal pro-inflammatory prostanoid, prostaglandin E₂ (PGE₂) serves as mediator of pain and fever in inflammatory reactions. The biosynthesis of PGE₂ starts from arachidonic acid (AA). Cyclooxygenase (COX)-1 and/or COX-2 converts AA to prostaglandin H₂ (PGH₂), and PGE₂ synthases transform PGH₂ to PGE₂. Current mainstream approach for treating inflammation-related symptoms remains the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). As both categories shut down the biosynthesis of all downstream prostanoids, their application renders several deleterious effects including gastrointestinalulceration and cardiovascular risk. Microsomal prostaglandin …

Study Of The Mechanism Of Action For Ru(Ii) Polypyridyl Complexes As Potential Anticancer Agents, Yang Sun

Theses and Dissertations--Chemistry

Application of chemotherapeutic agents in current cancer treatment has been limited by adverse effects as poor selectivity results in systemic toxicity; most chemotherapy approaches also experience inherited or acquired drug resistance which lead to reduced treatment outcome. Research efforts have focused on the discovery of novel chemotherapies that overcome the limitations mentioned above. Ru(II) polypyridyl complexes with anti-cancer properties have been extensively studied as traditional cytotoxic agents and photodynamic therapy agents due to their photophysical and photochemical characteristics.

Most research has focused on the design of Ru(II) polypyridyl complexes that have affinities to nucleic acids as inspired by the classic …

Validated Thin-Layer Chromatography-Densitometric Method For Simultaneous Determination Of Piperine And Plumbagin In “Benjakul” Thai Polyherbal Formulation And Its Antioxidant Activities, Savita Chewchinda, Pattamapan Lomarat, Pongtip Sithisarn

The Thai Journal of Pharmaceutical Sciences

The purpose of this study was to evaluate antioxidant activity and quantitative analysis of piperine and plumbagin content in “Benjukul (BEN)” Thai polyherbal formulation by TLC densitometric method. BEN was recognized in the list of herbal medicinal...