Pharmacology, Toxicology and Environmental Health Commons^™

Marigold-Silver Nanoparticles (Agnps) Complex: Characterization, Therapeutic Potential, And Future Approaches For Lung Injury Via Antioxidant And Anti-Inflammatory Effects, Navdeep Kaur

USF Tampa Graduate Theses and Dissertations

Chronic respiratory diseases (CRDs) and other lung conditions are a key cause of the problems facing global health, as they greatly increase morbidity, death, and the financial burden. In order to achieve the third Sustainable Development Goal of the United Nations, which is to reduce premature mortality from non-communicable illnesses by one-third by 2030, updated epidemiological statistics are crucial for directing prevention, control, and treatment measures. One of the major reasons of illness and death globally is chronic obstructive pulmonary disease (COPD). Lung damage and the emergence of CRDs, such as asthma, emphysema, COPD, and other respiratory disorders, are largely …

Formulation And Characterization Of Albumin Nanoparticles For Nsclc Photochemotherapy, Faisal Mohammad Shamim Khan

USF Tampa Graduate Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) is the most common type of lung cancer and is a leading cause of worldwide cancer-related death, which is a strong motivation to develop more efficacious approaches to its treatment. This thesis outlines the construction of folate-targeted bovine serum albumin (FA-BSA) nanoparticles co-loading Chlorin e6 (Ce6), a photodynamic therapy photosensitizer, and Evofosfamide (EVO), a hypoxia-activated prodrug, to enable synergistic photochemotherapy. The 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is a water-soluble carbodiimide coupling reagent and used for amide bonds between carboxylic acid and amines. FA-BSA nanoparticles were prepared through a desolvation approach and stabilized through crosslinking by the carbodiimide reagent …

Untangling The Roles Of Pulmonary Vagal Afferent Subsets With Inhaled Irritants, Teresa Darcey

USF Tampa Graduate Theses and Dissertations

The sensory nerves in the airways directly regulate critical defenses and indirectly regulate vital gas exchange. Airway function is largely controlled by the autonomic nervous system, and our understanding of its sensory regulation is directly connected to our ability to treat respiratory and cardiovascular pathologies. Airway sensory afferents are heterogeneous with respect to their electrophysiological properties, peptidergic capacity, and stimuli sensitivity, which at least in part dictate some of their various functions. There is evidence that embryological origin impacts reflex function: activation of the neural crest-derived population of sensory afferents has been shown to evoke the cough reflex whereas activation …

Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response In Aged And Young Tbi Mouse Models, Salma S. Abdelmaboud

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and …

Utilization Of Bixin-Loaded Polycaprolactone Nanoparticles To Ameliorate E-Cigarette-Induced Damage To Human Bronchial Epithelial Cells, Sophia R. Claymore

USF Tampa Graduate Theses and Dissertations

Electronic cigarettes (e-cigs) have increased in popularity and usage over the last few decades. E-cigs are generally composed of a liquid containing nicotine flavoring chemicals, a battery, a vaporization chamber, and a coil that heats the liquid upon inhalation of the mouthpiece. E-cigs were initially introduced as a healthy alternative to cigarette smoking. However, recent research has demonstrated that e-cigs elicit comparable cytotoxic and dangerous effects to conventional cigarettes. Bixin has been introduced in recent research as a candidate for therapeutic applications due to its innate anticancer, antioxidative, and anti-inflammatory characteristics. Nanoparticles (NPs) have emerged over the past few decades …

Evaluating The Protective Role Of Epo-R76e In Oxidative Stress-Induced Cell Death In Retinal Pigment Epithelium, Jemima Alam

USF Tampa Graduate Theses and Dissertations

Age-Related Macular Degeneration (AMD) causes dysfunction and loss of Retinal pigment epithelium (RPE). The degeneration and death of RPE cells causes irreversible visual impairment. Oxidative stress is a widely accepted triggering factor for RPE dysfunction. A hormone called Erythropoietin (EPO) is responsible to facilitate the erythropoiesis process, prevents progenitor cells from apoptosis and protects photoreceptors downregulating retinal degeneration. In this study, we aim to elucidate the role of EPO in downregulating oxidative stress in RPE. It is hypothesized that EPO will have a positive impact on suppressing oxidative stress and ferroptosis-mediated RPE degeneration due to its vital role in apoptosis …

Analysis Of Adverse Events Associated With Sglt2 Inhibitors And Molecular Mechanisms Using Faers Database And Transcriptome Data, Rahinatu Bawah Ali

USF Tampa Graduate Theses and Dissertations

In this thesis, we explored the differential effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal health, utilizing both clinical data and molecular insights. Focusing on three commonly prescribed SGLT2 inhibitors—Dapagliflozin, Canagliflozin, and Empagliflozin—we employed the Food and Drug Administration Adverse Event Reporting System (FAERS) database to assess adverse events, including myocardial infarction, cardiac failure, tachycardia, acute kidney injury (AKI), renal failure, urinary tract infections, and fungal infections. This analysis was complemented by transcriptomic data from kidney cell lines treated with these drugs, processed through NCBI’s GEO2R and Limma programs, to reveal the gene expression profiles linked to these …

Advancing Text Summarization And Classification: Deep Insights From Transformer-Based Statistical Learning, Kun Bu

USF Tampa Graduate Theses and Dissertations

Artificial Intelligence (AI) is a part of human's daily life nowadays. Machine Learning (ML) as one aspect from AI has been rapidly developing during the past two decades, especially from the statistical learning approaches, which emphasized the use of probability and statistics to model data, such as Support Vector Machines (SVMs) for classification and regression tasks to the ensemble learning techniques, such as Random Forest, Gradient Boosting Machine (GBM), and stacking. Ensemble learning has evolved into a pivotal concept in contemporary machine learning, empowering practitioners to amalgamate multiple models to enhance generalization, accuracy, and robustness. As the field of machine …

Elucidation Of Molecular Mechanisms Underlying Novel Multi-Targeted Therapy Strategies For, Qianqian Hu

USF Tampa Graduate Theses and Dissertations

EML4-ALK fusion non-small cell lung cancer (NSCLC) represents a distinct subset of lung cancers that possesses unique molecular and clinical features, paving the way for targeted therapeutic interventions. Despite the promise of ALK-directed therapies, challenges such as metastasis at the time of diagnosis and treatment resistance persist, necessitating deeper research into the underlying mechanisms and potential solutions. In the context of these challenges, our study embarked on two specific objectives. The first goal, elucidated in Chapter 2, revolved around brain metastasis, an event critically facilitated by cell migration. Here, we assessed the anti-migratory activities of several clinical ALK inhibitors in …

Neuroendocrine Regulation Of Chemokine Receptor-Mediated Leukocyte Migration Via Heteromeric G Protein-Coupled Receptor Complexes, Garrett Enten

USF Tampa Graduate Theses and Dissertations

Neuroendocrine regulation of the innate immune system is a well-documentedphenomenon. The underlying mechanisms, however, are not well understood. Here we show that at least 20 members of the human chemokine receptor (CR) family heteromerize with one or more members of the α1-adrenergic receptor (AR) family and that all CRs, apart from CXCR1, heteromerize with arginine vasopressin receptor 1A (AVPR1A) in recombinant systems. These heteromeric complexes are detectable in human monocytes and the monocytic leukemia cell line THP-1. Though currently technical limitations prevent the direct visualization of endogenously expressed higher-order hetero-oligomeric receptor complexes, we provide evidence through functional analysis and proximity-based …

Developing A Point-Of-Care Detection Kit For Parkinson’S Disease Using Gold Nanoparticle-Based Lateral Flow Assay, Ali Aljassabi

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and the fastest-growing neurodegenerative disorder in the world. The major issue with PD is that it takes several years of biological changes until the patient starts to experience physiological symptoms that could affect their daily lives. The major hallmark of PD is the appearance of Lewy body inclusions in the neuron’s cytoplasm, which is rich in a protein called α-Synuclein (α-Syn). Several studies have shown that the levels of α-Syn in blood increase because the excess α-Syn is released from neurons into the bloodstream through extracellular vesicles. …

Utilization Of Detonation Nanodiamonds: Nanocarrier For Gene Therapy In Non-Small Cell Lung Cancer, Allan E. Gutierrez

USF Tampa Graduate Theses and Dissertations

Lung cancer is one of the most prevalent and high mortality cancers in the world. Two different categories of lung cancer are non-small cell lung cancer which makes up 85% of cases, and small cell lung cancer which makes up the remaining 15% of cases. A significant risk factor that can lead to lung cancer is cigarette smoking (CS) however non-smoking cases i.e., secondhand CS, exposure to certain toxins and family history are on the rise. Both the main types of lung cancer have different system of stages, different ranges of treatment, and consequently low survival rates. Unfortunately, detection and …

Pamam- Cyclodextrin Conjugate Upregulates Brain-Derived Neurotropic Factor In Arpe-19 Cells, Gopika Ashokan

USF Tampa Graduate Theses and Dissertations

Background: Traumatic Brain Injury (TBI) is a major contributor to death and disability due to motorvehicle accidents, sports, physical abuse, and battlefield injuries. The primary insult to the brain leads to inflammation, vascular dysfunction, and oxidative stress in the brain as well as in the eye. This leads to loss of Retinal Ganglion Cells (RGCs) and downregulation of Brain derived Neurotopic Factor (BDNF). BDNF is a neurotrophic factor that binds to Tropomyosin Receptor Kinase B (TrkB) receptor to promote cell growth, survival, and differentiation. Current treatment strategies do not promote neuronal regeneration. Therefore, novel treatments are needed to restore vision …

Effect Of Hyperoxia On Cardiac Pathophysiology In Female Guinea Pig Hearts, Chayapatou Chayawatto

USF Tampa Graduate Theses and Dissertations

Hyperoxia is widely implemented in critical care and ICU patients. The administration of a high concentration of inspired oxygen to the lung can unknowingly cause hyperoxia and thereby damaging the lungs and heart due to oxidative stress. Technically, hyperoxia occurs when the patient receives PaO2 > 200 mmHg. Major research focused on hyperoxia-induced lung injury, but nothing is known on its effect on heart. Our lab is the pioneer in understanding the effect of hyperoxia on cardiovascular remodeling using mice model. Previous results show that mice under 72 hours of hyperoxia present severe cardiac pathophysiology. This research uses Guinea pigs, which …

Association Between Use Of Remdesivir And Bradycardia, Gibret Umeukeje

USF Tampa Graduate Theses and Dissertations

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see …

Screening Pathological Protein Specific Antibodies As Biomarker Discovery Tools For Neurodegenerative Disease, Yitong Li

USF Tampa Graduate Theses and Dissertations

With the increase in the average life span, the incidence of neurodegenerative diseases also increases, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common types of neurological disorders. AD and PD share the same pathogenic mechanism that involves a class of proteins called beta-amyloid (Aβ), which, under the induction of some factors, changes from its natural monomeric state to the oligomers containing β-sheet, which is neurotoxic and thus leads to cell damage or apoptosis. This study focused on the selection of antibodies used as biomarkers for AD and PD. The selection of antibodies was based …

Targeting The Side-Chain Convergence Of Α-Helical Hot Spots To Design Small-Molecule Mimetics Disrupting Protein-Protein Interaction, Zhen Wang

USF Tampa Graduate Theses and Dissertations

α-Helix accounts for the largest class of protein secondary structures and plays a key role in mediating protein-protein interactions (PPIs). Small-molecule α-helix mimetics mimic the structural features of α-helical hot spots and offer a powerful tool to unravel complex signaling networks and mitigate aberrant PPIs. In this dissertation, the side-chain conformational convergence of α-helical hot spots was disclosed, and insights into the side-chain convergence were exploited to instruct the design of small-molecule α-helix mimetics. The first chapter of this dissertation provides an overview of the characteristics of α-helical hot spots and current strategies to design small-molecule α-helix mimetics. In chapter …

Antimicrobial Activity Of Zinc Oxide Nanoparticles Compared To Silver Nanoparticles Administered Towards Methicillin-Resistant Staphylococcus Aureus Biofilms, Kevin Núño

USF Tampa Graduate Theses and Dissertations

Zinc oxide nanoparticles (ZnO NPs), silver nanoparticles (AgNPs), and chitosan nanoparticles have strong antibacterial activity as a broad-spectrum antibiotic against multi-drug resistant (MDR) bacteria. MDR bacteria have a mechanism that increases antibiotic resistance through biofilm formations. MDR methicillin-resistant Staphylococcus aureus BAA-1720 was chosen for an in vitro assessment to calculate the biofilm reduction rate and the median effective dose (ED50) by performing biofilm quantification. Dynamic light scattering was chosen to determine the physiochemical characteristics of ZnO NPs, silver nanoparticles (AgNPs), and chitosan NPs. Transmission electron microscopy was conducted to verify each treatment’s physiochemical characteristics. Antimicrobial susceptibility testing of broad-spectrum and …

Effects Of Acid Hydrolyzed Chitosan Derivatives On Mhv Infection, Krishna Sharma

USF Tampa Graduate Theses and Dissertations

Coronaviruses have recently been under significant scrutiny due to the ongoing covid-19 pandemic that began in Wuhan, China, and subsequently spread to the rest of the world. Chitosan is a common chemical from crustaceans that has several desirable properties due to being biodegradable, non-toxic, and, most importantly, cheap. It also exhibits anti-viral properties, which is the focus of these experiments. We tested the toxicity of the chitosan on cell lines to see how much chitosan the cells can tolerate. We hydrolyzed the chitosan in acid, and the chitosan fibrils added cell lines to see if the anti-viral properties increased in …

Effects Of Exogenous Ketone Therapy On Performance, Cardiorespiration, And Seizure Genesis During Exposure To Hbo2 In The Sprague Dawley Rat, Nicole M. Stavitzski

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is used for clinical HBO2 therapy and in undersea and aerospace medicine. HBO2 is a humanmade extreme environment and protracted exposures can cause several adverse physiological effects on the body. For example, HBO2 increases the partial pressure of oxygen (PO2) in the body leading to redox stress. Redox stress is, in part, a cause of oxygen toxicity that manifests as seizures in its most severe form (central nervous system oxygen toxicity, CNS-OT). This dissertation focuses on strategies to be employed specifically for the warfighter breathing HBO2. Currently, the only way to prevent CNS-OT is to lower the …

Application Of Gold Nanoshells For Photothermal Therapy In Lung Cancer Cells, Yva K. Luc

USF Tampa Graduate Theses and Dissertations

Lung cancer is the leading cause of cancer deaths in the world. For the year 2020, it was estimated 1.8 million deaths were due to lung cancer alone, making it more lethal than breast cancer and prostate cancer combined. For the year 2021, it is estimated 235,760 new cases of lung cancer and 50% will lead to death. The primary cause of lung cancer is due to cigarette smoking, which accounts for 80% of all lung cancer deaths. Lung cancer screening relies on only different methods, biopsy, bronchoscopy, ultrasound, chest x-ray film, and sputum cytology. These techniques are used to …

Quercetin Loaded Nanoparticles For The Treatment Of Dry Eye Disease, Bassma Sami Nashaat Hamed Eltanameli

USF Tampa Graduate Theses and Dissertations

Dry eye disease (DED) is a common condition that affects the eye's anterior surface due to tear deficiency or excessive evaporation. The lack of tears leads to dryness and initiation of an inflammatory response which can irritate the eye and interfere with daily activities. Current treatment depends mainly on artificial tears eye drops which offer temporary relief and require repetitive administration due to frequent blinking. Prescription medications are also available but need around three months to relieve dry eye symptoms. Quercetin is a flavonoid that has an anti-inflammatory and antioxidant effect. However, it suffers from low water solubility and low …

Evaluating Daily Systemic Betaine Delivery In Alleviating Dry-Amd Pathophysiology, Dawin Khiev

USF Tampa Graduate Theses and Dissertations

MnSod (Sod2) deletion in the retinal pigment epithelium (RPE) of Sod2flox/floxVMD2-cre mice leads to oxidative stress-induced apoptosis of the RPE and photoreceptor cells that show salient features of dry-AMD. The purpose of this study was to investigate the potential antioxidant effect of betaine in protecting retinal health in Sod2flox/floxVMD2-cre mice. Betaine low dose (50mg/Kg Body Weight) and high dose (500mg/kg Body Weight, n=9) were administered intraperitoneally to 8-weeks old male and female Sod2flox/floxVMD2-cre mice daily for four months, while the control group (Sod2flox/floxVMD2-cre mice; n=9) received saline. We used spectral-domain optical coherence tomography (SD-OCT), retinal outer nuclear layer (ONL) thickness …

Mitigation Strategies For Central Nervous System Oxygen Toxicity In Rodents: Ketone Metabolic Therapy And Mitochondrial Antioxidant Therapy, Christopher Manuel Hinojo

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is a frequently encountered condition in undersea medicine and hyperbaric oxygen therapy (HBOT). The risk of CNS oxygen toxicity (CNS-OT) seizures limits its use in hyperbaric medicine and limits bottom time for diving operations. In this study, we sought to understand the role of reactive oxygen species (ROS) in two mitigation strategies for CNS-OT; ketone metabolic therapy (KMT), which is known to delay onset of CNS-OT seizures, and mitochondria targeted antioxidant therapy (MitoTAT), which has never been tested under HBO2 conditions. We specifically focused on superoxide anions, one of the early reduction products of molecular oxygen, and …

The Effects Of Agrochemical Pesticide Applications On Target And Off-Target Species In Aquatic Ecosystems, Bryan K. Delius

USF Tampa Graduate Theses and Dissertations

The increase in the global human population is driving agricultural expansion, which increases the likelihood and degree by which agrochemicals impact aquatic systems. It is projected that by 2100 the global human population will exceed 11 billion, and to feed the increased human population, the necessary increase in agricultural infrastructure is estimated to double irrigation, nearly triple fertilizer applications, and increase pesticide applications by tenfold. It stands to reason that wetlands impacts from agriculture are also likely to increase as the industry expands its operation to meet the globally growing demand for food.

Wetlands are highly productive habitats that not …

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …

Hyperoxia-Induced Cardiac Pathophysiology In Guinea Pig Hearts, Zain Ul Abidin

USF Tampa Graduate Theses and Dissertations

Hyperoxia, is regularly introduced to critically ill patients in ICU. Nevertheless, recent studies have shown the negative effects of this treatment on patients in critical care, including increased rates of lung and cardiac injury and thereby high in-hospital mortality. Large part of the literature related to hyperoxia was majorly focused on lung injury, with no or minimal investigations on cardiac injury. Our lab is the first to investigate the effect of hyperoxia on cardiac pathophysiology in mice and showed that mice exposed to hyperoxia for 3 days demonstrated brady-arrhythmia, cardiac hypertrophy, QTc prolongation along with other electrical remodeling and functional …

Investigating The Novel Role Of Dextromethorphan In Mitigating Oxidative Stress Induced Changes In Retinal Pigment Epithelial Cells (Rpe), Zeinab A. Mohamed

USF Tampa Graduate Theses and Dissertations

Oxidative stress contributes to the degeneration of retinal pigment epithelial (RPE) cells and photoreceptors that lead to the dry form of age-related macular degeneration. Activation of N-Methyl-D-aspartate (NMDA) receptors contributes to the increase of free radicals that induce oxidative stress-induced changes. Our study investigates if Dextromethorphan, an NMDA receptor antagonist, reverses oxidative stress-induced changes in RPE. We used Paraquat and H2O2 as oxidative stress-inducing agents to induce oxidative damage in human ARPE-19 cells. To illustrate the change in cell viability and measure the apoptosis of ARPE-19 cells from oxidative damage, we performed MTT assay and Annexin V-DAPI flow cytometry analysis. …

Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, Ryan Martin

USF Tampa Graduate Theses and Dissertations

Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), …

Glutathione-S-Transferase Mu 1 (Gstm1) Gene Augmentation Attenuated Oxidative Stress Induced Changes In Retinal Pigment Epithelium Cells (Rpe), Riddhi Sandeep Vichare

USF Tampa Graduate Theses and Dissertations

Purpose: Loss of Retinal Pigment Epithelial (RPE) cells and photoreceptors leads to Age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly worldwide. Oxidative stress-mediated damage is one of the factors that impair the survival of RPE and photoreceptors in dry-AMD. We sought to determine the role of human Glutathione S-Transferase Mu-1 (GSTM1) in protecting RPE cells from oxidative stress-induced changes.

Method: We cloned human GSTM1 cDNA with P2A tag into a lenti-plasmid vector and later made a lentivector to express GSTM1. After that, we infected human retinal pigment epithelial cells (ARPE-19), screened stable ARPE-19 cells …