Pharmacology, Toxicology and Environmental Health Commons^™

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 …

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 …

Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin

Department of Medicine Faculty Publications

Background: Cardiac sequelae in Hodgkin Lymphoma (HL) can manifest as involvement of the heart and pericardium. Direct cardiac involvement is rare, and myocardial infiltration is distinctly unusual.¹ When it does occur, it is often a late manifestation of lymphoma, with a median onset of 20 months after initial diagnosis, and it is usually associated with advanced-stage disease.²

Case: A 34-year-old male was diagnosed with classic HL by lymph node biopsy. During his hospitalization, the patient remained in sinus tachycardia with heart rate up to 150 with no dysrhythmias. Transthoracic echocardiogram (TTE) revealed a reduced ejection fraction (EF) of 36% concerning …

Micro/Nanoplastics And Cancer: Focus On Gastrointestinal Malignancies - A Narrative Review, Sana Rabeeah, Priyata Dutta, Ahmad Mahdi, Alejandra Vargas, Edward C. Oldfield, David A. Johnson

Department of Medicine Faculty Publications

Micro- and nanoplastics (MNPs) are plastic particles smaller than 5 mm and 1 μm, respectively, and are emerging environmental pollutants with growing implications for human health. These particles stem from either 'primary sources', such as intentionally manufactured microbeads and industrial abrasives, or 'secondary sources', where larger plastic items break down into smaller fragments over time. Human exposure primarily occurs through ingestion and inhalation, with contaminated seafood and plastic-laden food packaging representing key routes of entry. Once ingested, MNPs can cross the intestinal barrier, accumulate in gastrointestinal (GI) tissues, and trigger biological responses. Mechanistic studies reveal that MNPs induce oxidative stress, …

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. …

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 …

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. …

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 …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Evaluation Of The Dnazyme Gr5 For The Determination Of Lead Speciation In Natural Waters, Gaganprit Gill

Theses and Dissertations (Comprehensive)

This thesis explores the development and application of a DNAzyme-based biosensor designed to detect labile metal species in environmental samples. Real time and on-site monitoring of labile metal fractions would make a valuable contribution to environmental management, as these fractions are the most bioavailable and pose significant toxicity risks to aquatic organisms. Conventional methods for detecting labile metals, while effective, are often burdened by high costs, complexity, and lengthy processing times, making them less ideal for rapid and widespread environmental assessments.

The first manuscript of this thesis (chapter 2) establishes the fundamental capabilities of the Pb²⁺-specific DNAzyme GR5 …

Characterization Of Airborne Bacterial Diversity In Conventional Hen Houses, Enriched Colonies And Aviaries, And Link Between Possible Bioaerosol Sources, M.-W. St-Germain, M. Veillette, V. Létourneau, A. D. Larios Martínez, S. Godbout, M. Boulianne, C. Duchaine

Études primaires

Background

Canada’s transition toward alternative housing systems for laying hens may have an impact on bioaerosol content and concentrations in those environments. This project aimed to characterize the airborne bacterial diversity in six conventional hen houses, six enriched colonies and six aviaries. The bacterial diversity found in bioaerosols was also compared to the diversity found in feces or litter samples from each corresponding housing type to investigate similarities between possible bioaerosol sources and bioaerosols.

Results

Specific richness (S_obs) and CHAO1 indexes were higher in air samples from conventional hen houses and enriched colonies, compared to their corresponding fecal …

Phytochemical Screening And Medicinal Properties Of Caralluma Fimbriata And Moringa Oleifera, Ammara Tariq, Anum Ashfaq, Kalsoom Sughra, Ayesha Hameed

Journal of Bioresource Management

The research was intended to evaluate the medicinal properties of Caralluma fimbriata and Moringa oleifera, as these plants are well known for their therapeutic activities. Qualitative analysis of the phytochemical components of these plants was used to identify the existence of potentially useful therapeutic compounds. Antibacterial and antifungal activities of extracts were assessed and their antioxidant and anti-inflammatory properties were evaluated using the DPPH assay and the protein denaturation inhibition assay, respectively. The α-amylase and α-glucosidase inhibition tests were utilized to determine the plant extract's effectiveness as an antidiabetic agent. Phytochemical analysis showed the presence of medicinally beneficial compounds …

Potential Health Risks From Trace Elements In Four Commercially Important Fish Species From The Gulf Of Alaska And Bering Sea Excel Data Sheet, Miranda Brohman, Dimtirios Giarikos, Amy Hirons

SECLER Data

Alaskan waters support a diverse array of fish species that are critical to apex predators and substantial commercial fisheries. Archived white lateral muscle tissue for capelin, herring, walleye pollock, and Pacific cod, from 1993 to 1996 were analyzed for 15 trace elements using induced coupled plasma mass spectrometry. This analysis serves as a proxy for assessing trace element concentrations in the Gulf of Alaska and Bering Sea. The highest concentrations of eight of the 15 elements (cadmium, chromium, cobalt, iron, manganese, selenium, vanadium, and zinc) were found in fish from the central Gulf of Alaska, while capelin showed the …

Visualizing Parcel-Level Lead Risk Using An Exterior Housing-Based Index., Neal J. Wilson, Ryan Allenbrand, Elizabeth Friedman, Kevin Kennedy, Amy Roberts, Stephen Simon

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric lead poisoning remains a persistent public health problem. Children in the US spend the preponderance of their time at home; thus, housing is an important social determinant of health. Improving health outcomes derived from housing-based sources involves differentiating the risks posed by the existing housing stock. In this paper, we developed a parcel-level lead risk index (LRI) based on external housing conditions and the year of home construction. The purpose of this study was to introduce a housing-based lead risk index (LRI), developed using retrospective data, to estimate parcel-by-parcel variation in housing-based lead risk. We described how the LRI …

Advancing Continuous Manufacturing: The Role Of Process Analytical Technology In Process Development, Samuel R. Henson

Electronic Theses and Dissertations

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Using Bivalves As An Indicator For Fecal Bacteria, Kamala Chuss

Honors Scholar Theses

This project focuses on the integration of fecal bacteria from warm-blooded animals into bivalve tissue, and the utilization of bivalves as an indicator for fecal bacteria in waterways. Bivalves may give a more representative long-term average of fecal bacteria in water as compared to direct water testing. The primary objective is to create a standard operating procedure to use bacterial testing of bivalves as a proxy for bacteria concentration in the water. This method can be used in places where bivalves do not already exist by adding them to a body of water, or by collecting bivalves that already exist …

Activities Of Cellulolytic, Amylolytic, And Secondary Metabolites From Thermophilic Actinomycetes Collected From The Heated Soil Around Cisolok Geyser, Dhian Chitra Ayu Fitria Sari, Fitria Ningsih, Mazytha Kinanti Rachmania, Akira Yokota, Wellyzar Sjamsuridzal

Makara Journal of Science

This study investigated the antimicrobial activity, cellulolytic, and amylolytic abilities of eight thermophilic Actinomy-cetes isolated from the heated soil around the Cisolok geyser, West Java, Indonesia. Cellulolytic and amylolytic abili-ties were screened for on media by adding 1% (w/v) soluble starch and carboxymethylcellulose (CMC), respectively. Antimicrobial activity was screened for using the agar-plug diffusion method by cultivating strains on various growth media. Growth at various temperatures showed that six strains could grow up to 50 °C. Seven out of eight strains showed amylolytic ability at 40 °C and 45 °C, and only four strains did so at 50 °C. Screening …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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Pediatric Flecainide Pharmacogenomics: A Roadmap To Delivering Precision-Based Care To Pediatrics Arrhythmias., Ronald Palmen, Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Flecainide acetate is a Class 1c anti-arrhythmic with a potent sodium voltage gated channel blockade which is utilized for the second-line treatment of tachyarrhythmias in children and adults. Given its narrow therapeutic index, the individualization of drug therapy is of utmost importance for clinicians. Despite efforts to improve anti-arrhythmic drug therapy, there remain knowledge gaps regarding the impact of variation in the genes relevant to flecainide's disposition and response. This variability is compounded in developing children whose drug disposition and response pathways may remain immature. The purpose of this comprehensive review is to outline flecainide's disposition and response pathways while …

Acknowledgment Of Reviewers_2024

Journal of Food and Drug Analysis

No abstract provided.

Alanine Supplementation Enhancing Cordycepin Production In Cordyceps Militaris Via Upregulation Of Cns2 And Cns3 Genes Expression Levels, Wenbin Yu, Zeying Zhao, Bin Zeng, Yayi Tu, Bin He

Journal of Food and Drug Analysis

Cordycepin, a key bioactive compound produced by Cordyceps militaris, faces the challenge of low productivity forcommercial use. In this study, alanine supplementation in Cordyceps militaris boosted cordycepin production, peakingat 3 mg/g with 12 g/L concentration. Transcriptome analysis revealed 1711 differentially expressed genes, Pathwayanalysis indicates that protein processing in the endoplasmic reticulum was the most affected pathway. In addition, thetranscriptome showed that adenylosuccinate lyase is essential for the synthesis of cordycepin. The modulation of fourgenes (Cns1-4) points to a regulatory mechanism that could increase cordycepin biosynthesis, offering a strategy to overcome low productivity for commercial applications.