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Articles 1 - 30 of 56
Full-Text Articles in Life Sciences
Study Of The Effects Of Chronic Cadmium Exposure On The Pathogenesis Of Pulmonary Arterial Hypertension., Dakotah Dominique Cathey
Study Of The Effects Of Chronic Cadmium Exposure On The Pathogenesis Of Pulmonary Arterial Hypertension., Dakotah Dominique Cathey
Electronic Theses and Dissertations
We reported pulmonary artery hypertension (PAH) patients had elevated levels of Cd in both blood and urine, therefore, this study tested whether Cd directly induces PAH or facilitates PAH pathogenesis in mouse models. C57/6J mice were initially exposed to drinking water with or without 5ppm Cd for 8 weeks. Then, half the mice in both control and Cd groups were given SU5416 and hypoxia (SuHx) for 4 weeks to induce PAH, resulting in 4 subgroups: Control, Cd, PAH, and Cd+PAH. Diastolic and systolic functions of the left and right ventricles (LV, RV) were examined with echocardiography before and after PAH. …
The Impact Of Environmental Pollutants On Alcohol-Associated Liver Disease Pathogenesis., Tyler Charles Gripshover
The Impact Of Environmental Pollutants On Alcohol-Associated Liver Disease Pathogenesis., Tyler Charles Gripshover
Electronic Theses and Dissertations
Steatotic liver disease is brought upon by differing etiologies and its global prevalence is expected to keep increasing over the next several decades. Particularly, alcohol-associated liver disease (ALD) manifests from excessive alcohol consumption where the liver retains lipids and progresses with metabolic dysfunction. Previous studies have demonstrated that environmental pollutants, polychlorinated biphenyls (PCBs) promote metabolic dysfunction associated steatotic liver disease (MASLD), in diet-induced obesity models. However, it is unknown if environmental pollutants may also promote ALD pathogenesis. Thus, this dissertation focuses on characterizing the effects of PCB126 in a rodent ALD model followed by multiple ‘Omics approaches to identify mechanisms …
Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee
Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee
Electronic Theses and Dissertations
We are facing an aging crisis, with 20% of the U.S. population projected to be geriatric (65+) by 2030 and live another 40+ years. Age-related diseases accompany a growing geriatric population, emphasizing the need to understand their etiology. Environmental pollutants compound this crisis by: 1) geriatrics are more susceptible, exacerbating age-related diseases and comorbidities, and 2) they accelerate biological aging, inducing age-related diseases at younger ages. We address this crisis using a ‘toxic aging coin’ approach; heads examines how age impacts toxicity, tails examines how chemicals accelerate aging. This thesis applies the heads side for Cr(VI)-induced neurotoxicity across ages. We …
Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri
Epitranscriptomic Regulation In Breast Cancer And Pcb-Induced Liver Disease., Belinda Petri
Electronic Theses and Dissertations
Post-transcriptional RNA modifications including N6-methyladenosine (m6A) regulate mRNA stability, splicing, and translation. My research examined m6A in two disease models: breast cancer (BCa) and non-alcoholic fatty liver disease (NAFLD). Acquired resistance to endocrine therapies (ET) develops in approximately 20% of BCa patients with estrogen receptor α positive (ER+) tumors following treatment. The mechanisms by which tumor cells evade ET are not completely understood. Using a cell line model, we investigated the role of an m6A reader protein, HNRNPA2B1 (A2B1) that is upregulated in ET-resistant ER+ BCa cells. Stable overexpression of A2B1 in ET-sensitive MCF-7 cells (MCF-7-A2B1), results in ET resistance, …
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
The Role Of E-Liquid Constituents In E-Cigarette-Induced Cardiac Arrhythmia And Autonomic Imbalance., Cory Kucera
Electronic Theses and Dissertations
Introduction. Accumulating evidence indicates that exposure to electronic cigarettes (e-cigs) promotes sympathetic dominance and electrophysiologic instability in the heart, potentially culminating in arrhythmogenesis. E-liquids contain various formulations of nicotine and flavorings, but the effects of specific e-liquid constituents and their concentrations on e-cig-induced autonomic imbalance and electrical dysfunction are unresolved. To that end, we tested the hypothesis that e-cigs modify cardiac autonomic balance and ventricular arrhythmogenesis in mice dependent on e-liquid constituent type and concentration. Methods. Using a crossover design and a serial exposure regimen, ECG-telemetered male C57BL/6J mice underwent whole-body exposure to e-cig aerosols generated from e-liquids containing different …
Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy For Alcohol-Associated Liver Disease., Jeffrey Warner
Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy For Alcohol-Associated Liver Disease., Jeffrey Warner
Electronic Theses and Dissertations
Introduction Alcohol-associated liver disease (ALD) is a common chronic liver disease and healthcare burden, and a spectrum of pathologies ranging from steatosis to steatohepatitis, fibrosis, and alcohol-associated hepatitis (AH). Despite its prevalence, there are limited effective therapeutic options for the treatment of ALD/AH. Previous evidence suggested that inhibition of soluble epoxide hydrolase (sEH), a lipid metabolism enzyme which degrades beneficial metabolites of dietary polyunsaturated fatty acids, may be a beneficial strategy. The central hypothesis of the current dissertation is that sEH inhibition will ameliorate alcohol-associated liver injury and inflammation in mouse models of ALD. Methods To determine the efficacy of …
Investigation Of Human N-Acetyltransferases (Nat1 And Nat2) Genetic Polymorphisms In Susceptibility To Aromatic Amine And Alkylaniline Genotoxicity., Mariam Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT1 and NAT2 genotypes. We hypothesize that different NATs alleles will impact levels of N-acetylation, HPRT mutations, DNA damage and oxidative stress induced by carcinogens. NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and NAT1*4, NAT1*14B, NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of benzidine, β-naphthylamine (BNA), and 4, 4’-methylene bis (2-chloroaniline) (MOCA) as aromatic amines and 3,4-dimethylaniline (3,4-DMA) as one of alkylanilines and their associated toxicity. Our …
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
The Effect Of Volatile Organic Compounds On Endothelial Function And Atherogenesis., Samantha Mcfall
Electronic Theses and Dissertations
Volatile organic compounds (VOCs) are a group of pervasive air pollutants that are released into the atmosphere from both anthropogenic and environmental sources. Recent epidemiological studies suggest that exposure to various VOCs is associated with an increased risk of cardiovascular disease. However, the relationship between VOCs and cardiovascular disease is not well-studied. Using animal models and three select VOCs, benzene, xylene, and trichloroethylene, we studied the effects of VOCs on endothelial injury and benzene-induced atherogenesis. We found that exposure to benzene and xylene increased circulating endothelial microparticles, depleted progenitor cells, and increased platelet activation. Following the exposure to the representative …
Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun
Application Of Cannabidol To Ocular Pharmacokinetics And Pharmacodynamics., Alyssa Laun
Electronic Theses and Dissertations
Cannabidiol (CBD) is the most abundant non-psychotropic cannabinoid constituent of Cannabis sativa. CBD is potentially therapeutic for the eye through antioxidant, anti-inflammatory, and neuroprotective effects. However, the effect of CBD on intraocular pressure (IOP)- the major risk factor for glaucoma- is controversial and large variability exists in the literature. IOP is regulated through aqueous humor (AH) dynamics in trabecular meshwork (TM) tissues. Measurement of CBD in AH and correlation with effects on IOP would clarify what concentrations mediate changes to IOP. Therefore, the overall goal of this dissertation is to measure CBD in ocular tissues and correlate concentrations with …
The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt
The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt
Electronic Theses and Dissertations
Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Cannabinoids And Retinal Fibrotic Disorders., Lucy June Sloan
Electronic Theses and Dissertations
Retinal fibrosis is detrimental to vision. Retinal pigment epithelial (RPE) cells contribute to several retinal fibrotic diseases. Upon exposure to TGF-β, a key fibrotic cytokine, RPE cells trans-differentiate to myofibroblasts marked by the integration of α-SMA fibers into F-actin stress fibers, which confer strong contractility. Myofibroblasts produce and contract the collagen-rich fibrotic scar and disrupt retinal architecture. In this study, we investigated the in vitro effects of the putative endocannabinoid compound N-oleoyl dopamine (OLDA) on TGF-β2 induced porcine RPE cell contraction and α-SMA expression. Using an in vitro collagen matrix contraction assay, we found that OLDA inhibited TGF-β2 induced contraction …
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Particulate Hexavalent Chromium Inhibits Homologous Recombination Repair By Targeting Rad51 Paralogs In Human Lung Fibroblasts., Aggie R. Williams
Electronic Theses and Dissertations
Hexavalent Chromium [Cr(VI)] is a known human lung carcinogen and general health hazard. The mechanism of carcinogenesis remains poorly understood, but chromosome instability (CIN) is the major theory in its carcinogenic mechanism. Homologous recombination (HR) repair is a DNA repair pathway that prevents CIN by repairing DNA double-strand breaks. RAD51, a key mediator protein of HR repair, along with the RAD51 paralogs (RAD51B, C, D, XRCC2, and 3) are required for HR repair. During HR, RAD51 loads and forms a helical nucleoprotein filament structure to promote DNA strand exchange and stimulate pairing activity of DNA. Cr(VI) exposures have been shown …
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Characterizing The Role Of Macrophages In Cisplatin-Induced Kidney Injury And Progression To Chronic Kidney Disease., Sophia M. Sears
Electronic Theses and Dissertations
Cisplatin is a commonly used chemotherapeutic for treatment of many solid-organ cancers. Unfortunately, 30% of patients treated with cisplatin develop acute kidney injury (AKI), and even patients who do not develop AKI are at risk for long term declines in kidney function and development of chronic kidney disease (CKD). While traditional rodent toxicity studies have utilized a single, lethal dose of cisplatin, new models of cisplatin-induced kidney injury have revealed that repeated, low doses of cisplatin lead to development of kidney fibrosis. This model can be used to examine AKI-to-CKD transition processes. C57BL/6 mice are one of the most used …
The Role Of Sphingolipids In Aki And The Progression To Ckd: Potential Therapuetic Targets., Nicholas A. Hoffman
The Role Of Sphingolipids In Aki And The Progression To Ckd: Potential Therapuetic Targets., Nicholas A. Hoffman
Electronic Theses and Dissertations
Acute Kidney Injury (AKI) is most simply defined as a rapid decline in kidney function over a period of hours to days. There is currently a lack of effective treatment options for patients with AKI, highlighting the need to identify new therapeutic targets. Sphingolipids play a number of roles in different models of AKI, suggesting they could be promising future targets for treating kidney injury. Specifically, sphingosine-1-phosphate (S1P) and its receptors (S1PRs) have been implicated in numerous inflammatory disorders and models of AKI. The purpose of this review is to better characterize the role of S1P receptors in models of …
Translating Particulate Hexavalent Chomium-Induced Chromosome Instability, Loss Of Homologous Recombination Repair And Targeting Of Rad51 From Human Lung Fibroblasts To Human Bronchial Epithelial Cells., Idoia Meaza Isusi
Electronic Theses and Dissertations
Particulate hexavalent chromium [Cr(VI)] is a well-established human lung carcinogen. RAD51, a key protein in homologous recombination repair pathway, is inhibited after prolonged exposure to Cr(VI), leading to an increase in chromosome instability after prolonged exposures in human lung fibroblasts. chromosome instability is the proposed driver of Cr(VI) carcinogenesis. Since tumors from chromate workers develop from epithelial cells, we sought to translate these findings from human bronchial fibroblasts to human bronchial epithelial cells. We hypothesized Cr(VI) inhibits RAD51 after prolonged exposure leading to an increase in chromosome instability in human bronchial epithelial cells (BEP2D). We characterized the cytotoxicity and measured …
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Investigating The Effects Of Perfluorooctanoic Sulfonate (Pfos) And Ethanol On Fatty Liver Disease Using A Modified Niaaa Model., Tyler Charles Gripshover
Electronic Theses and Dissertations
Perfluoroalkyl Substances (PFAS) are a family of man-made, surfactant-like compounds that are a major environmental contaminant. A multitude of studies have indicated that PFAS are able to induce fatty liver disease and modulate lipid metabolism. However, the distinct mechanism of PFAS influence on the liver and metabolism disruption remains to be elucidated. On the other hand, it is well documented that alcohol consumption has various adverse health impacts including fatty liver disease and subsequent progression to more adverse liver states. To date, there are no published studies on whether PFAS and alcohol can jointly exacerbate fatty liver progression or interact …
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Assessing The Role Of Chronic Arsenite Exposure In Disrupting The Egfr Signaling Axis., Christine Kim
Electronic Theses and Dissertations
Chronic arsenic exposure is a risk factor for the development of pulmonary diseases, including lung cancer, but the exact mechanism is not yet fully understood. Many previous studies have relied on acute arsenic exposure (i.e. 1-10 uM arsenic for 24 hours) to study arsenic toxicological effects. However, acute exposure does not reflect the levels or duration of arsenic associated with environmental exposure, or drinking of contaminated well water. This dissertation differentiates the effects of acute versus chronic arsenic exposures on the EGFR signaling axis and suggests possible mechanisms for chronic arsenic-induced pulmonary diseases. The EGFR is a receptor tyrosine kinase …
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil
Electronic Theses and Dissertations
Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …
Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle
Volatile Organic Compound Exposure And Cardiometabolic Syndrome Risk In A Nationally Representative Cohort., Stacey Lane Konkle
Electronic Theses and Dissertations
BACKGROUND: The relative importance of environmental exposures such as volatile organic compounds (VOCs) is one of the paramount public health priorities of our time, yet is presently unstudied. VOCs are ubiquitous in the environment and have been associated with numerous adverse health effects, including a number of cardiovascular and metabolic effects that are components of Cardiometabolic Syndrome (CMS). OBJECTIVES: To examine the relationship between CMS and individual-level exposures to VOCs, measured as urinary metabolites of VOCs (UM-VOCs), in a nationally representative sample. METHODS: Associations between urinary biomarkers of exposure to 19 parent VOCs and CMS were assessed using the National …
The Role Of Slc7a11 In Controlling Extracellular And Intracellular Redox Environments Of Lung Fibroblasts - Potential Targets For Intervention In Aging And Idiopathic Pulmonary Fibrosis., Yuxuan Zheng
Electronic Theses and Dissertations
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (Eh) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular Eh(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system Xc-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 …
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Dual Role Of Antimicrobial Peptide Cathelicidin In Alcohol-Associated Liver Disease., Fengyuan Li
Electronic Theses and Dissertations
Patients with alcohol-associated liver disease (ALD) have high morbidity and mortality in its severe forms. One of the major features in different forms of ALD is the altered gut microbiota. Antimicrobial peptides (AMPs) play a crucial role in maintaining gut microbiota homeostasis. LL-37 (known as CRAMP in mouse) is the sole member of the human cathelicidin family and has piqued great research interest for its dual role in modulating microbiota and the immune response in metabolic diseases. Inflammasome activation is an important component of the liver pathophysiology in ALD and requires two signals for its full activation to induce the …
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Tobacco Product-Derived Aldehydes: Effects On Circulating Angiogenic Cells & Implications For Cardiovascular Disease., Jordan B. Lynch
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. …
The Cardiovascular Effects Of Tobacco Product-Derived Aldehydes: Contribution Of Transient Receptor Potential Ankyrin-1., Lexiao Jin
Electronic Theses and Dissertations
Cardiovascular diseases (CVD) are the leading cause of death in most countries and are significant health and financial burden worldwide. Smoking contributes to more than 480,000 premature deaths annually -- accounting for one of every five deaths in the United States each year. Numerous studies have shown that smoking increases the risk of factors including endothelial dysfunction, thrombosis, and atherosclerosis, which may lead to an incidence of myocardial infarction, coronary artery disease, and stroke. Electronic cigarettes (e-cigarettes) are a new kind of tobacco product, and some studies show that e-cigarettes also could induce CVD since both e-cigarettes and conventional tobacco …
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Tobacco-Derived Aldehydes: Platelet Activation, Thrombosis, And The Role Of Trpa1., Andre Dwayne Richardson
Electronic Theses and Dissertations
Cigarette smoking is the single largest risk factor for cardiovascular disease (CVD) pathophysiology. Numerous researchers have shown potential associations between aldehydes in tobacco-derived aerosols from mainstream cigarette smoke (MCS) or electronic cigarettes (e-cigs) and their cardiotoxicity by damaging blood vessel endothelium. The severity of exposure to these toxicants can furthermore lead to adverse cardiovascular outcomes such as myocardial infarctions, stroke, coronary and peripheral artery disease, or atherosclerosis due to blood clots, a pro-thrombotic event. However, the mechanisms by which levels of harmful and potentially harmful constituents (HPHCs) such as aldehydes induce thrombosis are not well-known. Of specific interest, evidence has …
Therapeutic Potential Of Withaferin A Against Non-Small Cell Lung Cancer., Al Hassan Kyakulaga
Therapeutic Potential Of Withaferin A Against Non-Small Cell Lung Cancer., Al Hassan Kyakulaga
Electronic Theses and Dissertations
Lung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, chemoresistance and metastasis remain a major therapeutic challenge. Withaferin A (WFA), a plant-derived compound has recently emerged as a promising antitumor agent. In the present study, we explored the therapeutic potential of WFA against advanced NSCLC. Briefly, WFA was evaluated for its efficacy, toxicity and pharmacokinetic properties against advanced NSCLC using in vitro and in vivo models. Two human NSCLC cell lines, H1299 and A549 were used in cell culture to determine the anticancer properties of WFA. Repeat dose …
Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears
Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears
Electronic Theses and Dissertations
Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout …
Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent
Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent
Electronic Theses and Dissertations
This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC50 values. Furthermore, AvFc recognizes a number of cell …
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Development Of Bar-Peptide Nanoparticles And Electrospun Fibers For The Prevention And Treatment Of Oral Biofilms., Mohamed Yehia Mahmoud
Electronic Theses and Dissertations
Background: Periodontal diseases are globally prevalent inflammatory disorders that affect ~47% of U.S adults. Porphyromonas gingivalis (Pg) has been identified as a “keystone” pathogen that disrupts host-microbe homeostasis and contributes to the initiation and progression of periodontitis. Pg associates with oral streptococci in supragingival plaque and this interaction represents a potential target for therapeutic intervention. Previously our group developed a peptide (designated BAR), that potently inhibits Pg/Streptococcus gordonii (Sg) adherence in vitro and Pg virulence in a murine model of periodontitis. While efficacious, BAR (SspB Adherence Region) provided transient inhibition and required higher concentrations of BAR to disrupt established …
Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt
Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt
Electronic Theses and Dissertations
Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 …