Pharmacology, Toxicology and Environmental Health Commons^™

The Circadian Modulating Drug Sr8278 Slows Cell Proliferation Independent Of Rev-Erbs, Ushaswini Atluri

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The small molecule compound SR8278 was initially identified as an antagonist of the REV-ERB proteins, which play an important role in regulating circadian rhythms. Furthermore, the use of SR8278 in preclinical models has been demonstrated to ameliorate a variety of different pathologies. Using RNA-seq analysis of HaCaT keratinocytes treated with SR8278, our laboratory found that SR8278 induces a down regulation of genes involved in the G1/S phase transition of the cell cycle and an up regulation of genes involved in cholesterol biosynthesis. RT-qPCR and western blot analyses confirmed that SR8278 treatment led to lower expression of several factors involved in …

The Role Of Rad51 And Its Paralogs In Dna Damage Response In Quiescent Cells Exposed To Solar Simulating Uv Radiation, Angitha Radhakrishnan Nair

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Rad51, and its five paralog proteins Rad51B, Rad51C, Rad51D, XRCC2, and XRCC3, are crucial in homologous recombination (HR) repair of DNA double-strand breaks. Prior studies have extensively shown the roles of Rad51 in the S/G2 phase, but its role in the G0/G1 phase is still unclear. Our lab focuses on studying the role of Rad51 and its paralogs in quiescent cells. RT-qPCR and western blots helped us understand the expression of Rad51 paralogs in proliferating and quiescent keratinocyte cells. Using a pharmacological inhibitor of Rad51, we found that Rad51 promotes quiescent cell survival after exposure to UV radiation. Like Rad51, …

Comparative Impact Of Canagliflozin Versus Pioglitazone On Biomarkers Of Diabetic Kidney Disease In Db/Db Mice, Siri Chandana Minikuri

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Diabetes mellitus is a leading cause of chronic kidney disease (CKD), primarily through dysregulation of the renin-angiotensin system (RAS), characterized by elevated Ang II which promotes vasoconstriction, oxidative stress, and renal fibrosis, along with increased urinary shedding of angiotensin converting enzyme 2 (ACE2), which can exacerbate the imbalance of RAS and tubular injury. Previous studies demonstrated that rosiglitazone, a PPAR-γ agonist, attenuated hyperglycemia, glycosuria, albuminuria, and decreased urinary ACE2 shedding in db/db mice, suggesting a RAS-mediated renoprotective mechanism. Building on this evidence, the current study compared the renal effects of pioglitazone (a PPAR-γ agonist) and canagliflozin (an SGLT2 inhibitor) in …

The Role Of Base Excision Repair In Dna Damage Responses In Human Keratinocytes Exposed To Solar Simulating Uv Radiation, Mobolaji Eniola Alabi

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Ultraviolet (UV) radiation from the sun is the most prominent source of exogenous UV damage to DNA. UV directly causes damage by forming UV photoproducts, including pyrimidine-pyrimidone (6-4) photoproducts ((6-4) PPs), which significantly distort the helical structure of DNA and interfere with transcription and replication processes. The only known repair process of these photoproducts in human cells is nucleotide excision repair (NER). However, a recent study reported an APE1-dependent base excision repair (BER) of a subset of UV photoproducts. The study showed that deletion or inhibition of APE1, PARP1, NTH1, XRCC1, and FEN1 led to a 2-fold increase in sensitivity …

Characterization Of Atr Kinase Function In Quiescent Keratinocytes Exposed To Solar Simulating Uv Radiation, Mohamed Sameer Cholakkathody

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This study examines the role of Ataxia Telangiectasia and Rad3-related kinase in quiescent human keratinocytes exposed to solar-simulated UV radiation (SSL). The ATR inhibitor VE-822 did not significantly affect cell viability in the absence of UV exposure, showing that ATR kinase activity is not essential for quiescent cell survival in the absence of additional genotoxic stress. After SSL exposure, ATR inhibition did not impact acute cell viability but reduced the cells’ long-term ability to proliferate. Western blot analysis demonstrated that VE-822 potently suppressed phosphorylation of ATR target proteins KAP1 and CHK2 in a dose-dependent manner after SSL exposure, confirming strong …

Screening Of Suppressor Mutants That Confer The Suc22 S239f Mutant Cells Resistance To Hydroxyurea, An Inhibitor Of Ribonucleotide Reductase, Sairam Pasam

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Ribonucleotide reductase (RNR) is a key enzyme for the biosynthesis of dNTPs for DNA replication and repair. It is composed of a large subunit, Cdc22, and a small subunit, Suc22, in the fission yeast S. pombe. We have recently reported a suc22-S239F mutation in the small subunit of RNR, causing replication stress and hypersensitivity to hydroxyurea (HU), an inhibitor of RNR. Interestingly, this mutation does not sensitize the cell to acute treatment with HU, which mainly generates replication stress, suggesting that the mechanism of HU sensitivity in the suc22-S239F mutant remains to be fully understood. To better understand the cell-killing …

Characterization Of An Unknown Mutant C3 With A High Level Of Endogenous Replication Stress In Fission Yeast, Neha Singh

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To maintain genome stability, which is essential for cell proliferation and survival, cells rely on cell cycle checkpoint pathways to deal with perturbed DNA replication or replication stress. The fission yeast Schizosaccharomyces pombe serves as a powerful model organism for studying checkpoint mechanisms because its fundamental cellular processes are highly conserved in higher eukaryotes. During a genetic screening for mutants affecting genome integrity, we identified a novel mutant called C3 that exhibits a unique phenotype. Unlike wild-type cells, where phosphorylation of the checkpoint mediator Mrc1 is typically observed only in response to exogenously induced replication stress, such as the treatment …

Characterizing The Microvesicle Particles From Keratinocytes Stimulated With Multiple Stressors, Muslima Begum

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Many types of environmental and physical stressors act upon the skin and can initiate inflammation, systemic effects, and even damage to internal organs. Recent studies have identified that these harmful events are driven by the release of subcellular microvesicle particles (MVPs), an inflammatory process promoted by the glycerophosphocholines-derived lipid mediator, Platelet-activating Factor (PAF). These harmful effects are driven by the release of MVPs, a process promoted by the inflammatory lipid mediator, PAF. We have previously demonstrated that exposure of human HaCaT keratinocyte and mouse skin to stressors such as thermal burn injury, ultraviolet B (UVB) radiation, and topical photodynamic therapy …

Heterogeneous Being: The Inhumanities And The Creative-Scientific Aesthetic, Steven L. Ogden

Electronic Theses & Dissertations (2024 - present)

Heterogeneous Being attempts to set the often-disunited aspects of the sciences and humanities in congruence and to extol and advance a hybrid creative-scientific aesthetic that moves beyond any restricted dimensions of its previously segregated fields of study. It likewise expresses the need to perpetuate that hybrid form of inquiry and representation to successfully address or convey the precarious realities of Earth’s ecological and environmental conditions. Heterogeneous Being asks readers to observe the inexhaustible proofs of our pluralized configurations with the nonhuman world, to recognize the agentic potentialities nonhuman subjects may hold both in and outside of those inhuman enmeshments, and …

Identification Of Fentanyl And Fentanyl Analogs Found In Human Urine Using Gas Chromatography-Mass Spectrometry, Adam M. Fisher

Electronic Theses & Dissertations (2024 - present)

Identification of fentanyl and its analogs in unknown samples is a frequent practice completed in forensic crime labs, as the fentanyl epidemic continues. With the continued increase in illicit drug use, crime labs are not able to keep up with the flooding of new fentanyl analogs being developed, resulting in new analogs slipping past the crime labs’ authority. This research is to start to develop a database of commonly found fentanyl analogs in New York State. Gas Chromatography-Mass Spectrometry (GC-MS) is a widely used method for the detection and identification of illicit drugs in forensic crime labs. A database that …

Évaluation Et Caractérisation De L'Exposition Aux Fumées De Soudage Et Leurs Composantes Métalliques Lors D'Activités De Soudage Au Québec, Michèle Bouchard, Jairo Buitrago-Cortes, Naïma El Majidi, Jonathan Côté, Denis Dieme, Marc Mantha, Philippe Sarazin, Capucine Ouellet, Loïc Wingert

Rapports de recherche scientifique

Problématique et objectifs :

Les fumées de soudage sont classées comme cancérogènes chez l’humain et sont associées à un risque accru de plusieurs autres effets sur la santé des soudeurs. L’objectif général de cette recherche était d’établir la nature et le niveau d’exposition aux composantes métalliques lors d'activités de soudage chez des apprentis soudeurs au Québec, en effectuant des mesures dans différentes matrices biologiques et dans l’air lors d’un suivi longitudinal.

Méthode :Cette recherche a été réalisée dans des écoles d'apprentis soudeurs de la région de Montréal, où les techniques de soudage les plus courantes sont utilisées. Elle a …

On! Original Flavor Oral Nicotine Pouch Characterization: Biorelevant In Vitro Nicotine Release Apparatus Assessment, Jason C. Funderburk, Melissa Morgan, Maria Lasaosa Garcia, Andreas S. L. Mendez, Matthew S. Halquist

Graduate Research Posters

Background: Oral nicotine pouch (ONP) use is rising. The sales of ONPs in 2019 were 126 million units, increasing to 808 million units in 2022. Understanding ONP in vitro release is critical for assessing exposure to ONP products.

Methods: The commercial brand ON! ONPs with nicotine label claims of 2, 4, and 8 mg, were evaluated in vitro for cumulative nicotine release using the bidirectional transmucosal apparatus (BTA) for 90 minutes. Nicotine quantification was performed by HPLC-PDA. For pH determination, ONP samples were prepared in water or artificial saliva (pH 6.8) with measurements for 30 minutes. BTA results were compared …

Investigating Plk1 In Pulmonary Fibrosis, Tempany Arbogast

Theses and Dissertations--Toxicology and Cancer Biology

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease, with a median survival of only 2–3 years following diagnosis. In the United States, the disease contributes to more than 40,000 deaths annually, underscoring its severe clinical burden. Alveolar type II (AT2) lung epithelial cells serve as progenitors that maintain alveolar integrity by replenishing epithelial populations and producing surfactants, while fibroblasts and myofibroblasts regulate the extracellular matrix and structural support. In pulmonary fibrosis (PF) injury to AT2 cells promotes cytokine and growth factor release, driving inflammation, fibroblast proliferation, myofibroblast accumulation, and excessive extracellular matrix deposition. Aberrant AT2 cell …

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …

Developing A Simplified Method Of Measuring Ultrafine Particulate Matter Dose Concentrations For Diesel Emissions, Nafisat Ohunene Isa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Developing a Simplified Method of Measuring Ultrafine Particulate Matter Dose

Concentrations for Diesel Emissions

Ultra-fine particulate matter (UFP), particularly from diesel emissions, poses significant health and environmental risks due to its small size and potential to penetrate deep into the respiratory system. Accurate measurement of UFP concentrations is essential for assessing exposure and mitigating health impacts. However, current methods for measuring UFP can be complex, time-consuming, and costly. This study aims to develop a simplified method for efficiently measuring UFP concentrations from diesel emissions, which will enable easier and more widespread monitoring of air quality and public health impacts. …

An Investigation Into The Effects Of Preservatives On Ss-Hydroxybutyrate Concentrations Measured By Commercial Ketone Meter And Gas Chromatography-Mass Spectrometry, Kerry F. Murr

All ETDs from UAB

Ketoacidosis occurs when fatty acids are metabolized into ketone bodies in the liver and released into the bloodstream. This condition, which can be fatal, is commonly observed in diabetics, alcoholics, and individuals who experienced starvation or hypothermia. Although the ketone ß-hydroxybutyrate (BHB) is an accepted biomarker of ketoacidosis, the effects of preservatives on BHB concentrations in postmortem blood are unaddressed. The first aim of this research was to determine whether preservatives affect ketone levels as measured by a point-of-care device. Paired preserved and unpreserved blood samples were obtained from the Jefferson County morgue: preserved samples in grey top tubes and …

Environmental Exposure To Metals In Children And Their Effects On Autism Spectrum Disorder, Oludesola Ogunesan

All ETDs from UAB

ABSTRACT As scientific understanding of environmental determinants of health advances, growing attention has turned to the role of toxic metal exposures in exacerbating neurodevelopmental outcomes, particularly in vulnerable populations such as children with autism spectrum disorder (ASD). This dissertation investigates the intersection of environmental metal exposure, biomonitoring innovation, and social factors shaping ASD severity in Alabama. Using a multidisciplinary framework, four interrelated studies explore biological, environmental, and participatory dimensions of ASD research and public health. The first study evaluates the utility of Volumetric Absorptive Microsampling (VAMS) for measuring exposure to cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), and mercury …

Exploring Environmental Health Awareness And Knowledge In 9th – 12th Grade Students: A Mixed Methods Approach, Crystal Stephens

All ETDs from UAB

EXPLORING ENVIRONMENTAL HEALTH AWARENESS AND KNOWLEDGE IN 9TH – 12TH GRADE STUDENTS: A MIXED METHODS APPROACH CRYSTAL T. STEPHENS ENVIRONMENTAL HEALTH SCIENCES ABSTRACT Safe environments provide accessibility and community protections preventing residents from exposure to contaminants or facing health risks. Unfortunately, environmental exposures such as air pollution and neighborhood-level concerns can adversely impact human health. Environmental justice communities are overburdened with increased adverse environmental exposures and subsequent health disparities. Adolescents may be more vulnerable to exposure risks and provide an opportunity to introduce environmental health education. With their power of peer association and determination, adolescents can influence the health and …

The Effects Of Salinity On The Cutaneous Microbiome And Pathogen Infection On The Pacific Tree Frog (Pseudacris Regilla) In Monterey Bay, California, Usa, Hannah Eunhae Kim

EWU Masters Thesis Collection

Global climate change and infectious diseases are considered a leading cause of amphibian population declines worldwide. Changes in precipitation and salinity have altered watershed systems and microbial communities, reducing habitat availability and physiological performances for amphibian survival. The salt refuge hypothesis, however, is a proposed explanation that higher saline environments may reduce susceptibility to pathogens such as Batrachochytrium dendrobatidis (Bd). The Moro Cojo Slough State Marine Reserve (MCSSMR) (California, USA) is known as an abundant breeding ground for endangered/threatened amphibian species. To test and expand the salt refuge hypothesis, I evaluated Bd prevalence and intensity and the cutaneous microbiome of …

Detection Of Tetrahydrozoline In Alcoholic Beverage Residue Related To Drug-Facilitated Sexual Assault Using Gc-Ms, Alyssa Simone Hampton

All ETDs from UAB

Drug-facilitated sexual assault (DFSA) is an ongoing issue that remains significant in the United States and the World. DFSA can be either proactive or opportunistic, where a victim becomes impaired and is unable to provide consent. Common drugs found in DFSA cases are ethanol and cannabis. However, alternative drugs are increasingly being used to incapacitate a victim and enable a sexual assault. These include tetrahydrozoline (THZ), commonly found in over-the-counter eye drops, such as Visine®. Minimal research surrounds THZ, in which agencies may process case samples with a general drug screen, which may only detect common drugs, while THZ goes …