Pharmacology, Toxicology and Environmental Health Commons^™

Chemical Composition, Mineral Profile, Anti-Bacterial, And Wound Healing Properties Of Snail Slime Of Helix Aspersa Müller, Marouane Aouji, Amine Rkhaila, Bouchra Bouhaddioui, Malak Zirari, Hala Harifi, Youness Taboz, Lalla Aicha Lrhorfi, Rachid Bengueddour

BioMedicine

Mucus is a substance made by snails that serves a variety of purposes and is increasingly employed in the medical and cosmetic industries. It includes bioactive compounds with a range of biological characteristics that could be useful in the treatment of particular issues. This study assessed the wound-healing efficiency, antibacterial activity, chemical and mineral composition of Helix aspersa Müller slime. Inductively Coupled Argon Plasma Atomic Emission Spectrometry (ICP-OES) was used for mineral analysis, while Gas chromatography coupled to mass spectrometry (GC-MS) analysis was used for chemical characterization. The findings showed that the H. aspersa Müller slime had inhibitory activity on …

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 …

An Insight Into The Physicochemical, Drug-Likeness, Pharmacokinetics And Toxicity Profile Of Kigelia Africana (Lam) Bioactive Compounds, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Marili Funmilayo Zubair, Oluwagbemiga Tayo Amusan, Fatimah Ronke Abdulkadri, Bashir Lawal, Lateefat Bello Abdulfatah, Olubunmi Atolani

Al-Bahir

Kigelia africana plant is multipurpose plant whose therapeutic potential has been thoroughly investigated. The physicochemical, solubilities, ADMET, pharmacological, and drug-like properties of this plant have not been reported in details. This study makes use of the information that is currently known on the chemical make-up of the plant to forecast its overall toxicity as well as the potential for the phytochemicals it contains to be employed in medication discovery. The study also employed free web servers for the lipophilicity, water solubility, drug-likness, bioavailability score, medicinal chemistry and toxicological profiling of the compounds of K. africana. Artemether, a known antimalaria …

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 …

Relationship Between Plasma Fluoride Levels, Glutathione Peroxidase Activity, Hemoglobin, And Abortion In Rural And Urban Pregnant Women From Settat (Morocco), Lalla Asmaa Katir Masnaoui, Abdellatif Rahim, Habiba Bouchab, Bouchra El Amiri, Boubker Nasser, Essamadi Abdel Khalid

Makara Journal of Health Research

Background: This study aimed to investigate the relationship between plasma fluoride and hemoglobin levels, glutathione peroxidase (GPx) activity, and abortion among rural and urban pregnant women from Settat province (Morocco).

Methods: Blood samples were collected from rural pregnant women who had not undergone abortion (N = 224), rural pregnant women who had an abortion (N = 38), urban pregnant women who had not undergone abortion (N = 163), and urban pregnant women who had an abortion (N = 14).

Results: The highest (p < 0.01) plasma fluoride levels and the lowest (p < 0.01) GPx activity were observed in rural pregnant women. In all participants, plasma fluoride levels were significantly higher (p < 0.001), and the GPx activity was significantly (p < 0.001) lower in pregnant women who had an abortion compared with those who did not undergo such process. No significant difference was observed between the hemoglobin levels of all participants. Furthermore, abortion was positively correlated with plasma fluoride levels (p < 0.001) and negatively correlated with GPx activity (p < 0.001) in rural participants.

Conclusions: Rural pregnant women had higher plasma …

Pharmacological And Pharmacokinetic Studies Of A KCa2.2 Positive Allosteric Modulator, Mohammad Asikur Rahman

Pharmaceutical Sciences (PhD) Dissertations

Small-conductance Ca²⁺-activated potassium channels (K_Ca2.x) family is widely expressed in neurons, the heart, and endothelial cells. K_Ca2.x channels are named small conductance Ca²⁺-activated potassium channels due to their comparatively low single-channel conductance and are activated solely by rises in intracellular Ca²⁺. The family has three subtypes: K_Ca2.1, K_Ca2.2, and K_Ca2.3, encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. K_Ca2.x channels regulate neuronal excitability and responsiveness to synaptic input patterns. Small-conductance Ca²⁺-activated potassium channels subtype 2 (K_Ca2.2, …

Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Biphasic, non-sigmoidal dose-response relationships are frequently observed in biochemistry and pharmacology, but they are not always analyzed with appropriate statistical methods. Here, we examine curve fitting methods for “hormetic” dose-response relationships where low and high doses of an effector produce opposite responses. We provide the full dataset used for modeling, and we provide the code for analyzing the dataset in SAS using two established mathematical models of hormesis, the Brain-Cousens model and the Cedergreen model. We show how to obtain and interpret curve parameters such as the ED50 that arise from modeling, and we discuss how curve parameters might change …

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, …

Linking The Metabolic And Ecological Fate Of Caribbean Ciguatoxins And Related Neurotoxins In Reef Herbivores, Jessica K. Gwinn

Graduate Theses and Dissertations (2019 - present)

Ciguatera poisoning (CP) is one of the most prominent seafood-borne illnesses worldwide, affecting between 25,000–500,000 people annually. Ciguatera is caused by the ingestion of seafood contaminated with algal-derived ciguatoxins (CTX), the precursors of which are produced by benthic and toxigenic dinoflagellates in the genera Gambierdiscus and Fukuyoa. These compounds enter marine food webs through herbivory and are subsequently transferred to higher trophic levels, undergoing complex metabolic biotransformations, which produce structurally related CTX derivatives. Consumption of CTX induces a variety of severe neurological, gastrointestinal, and/or cardiovascular symptoms beginning within hours and lasting for weeks to months following exposure. Despite the impact …

Migratory Material: Epigenetics & Weaving At The Us-Mexico Border, Valerie Navarrete

Masters Theses

Discourse often sutures the body shut, disallowing representations of identity to outgrow sociopolitical interests. This issue may originate from borders, but also from the unnamable pathology that generational colonial trauma transmits to the mind, body, and environment. Without a direct form of translatability, this thesis proposes a new materialism that deviates from any object-oriented ontology. Untethered and intra-active, epigenetics and weaving represent objects that transform typical ways of knowing and seeing. Their sensitivity to the environment, in addition to their mobility across generations of time, broaden the spatiotemporal loci of the body and its embodiment. Proposing new materials that expand …

Early Life Δ9-Tetrahydrocannabinol Exposure Of F0 Zebrafish Causes Hyperactivity In F1 Offspring, Jenna Cripe

Honors Theses

As cannabis increases in its accessibility, potency, and acceptance across the United States, investigation into the multigenerational effects of Δ9-tetrahydrocannabinol (THC) exposure during key stages of development is critical. The aim of this study was to evaluate whether there would be behavioral impacts in the F1 offspring following a dose-response of THC exposure (0.08, 0.4, or 1 µM) during development in the F0 generation. Zebrafish (Danio rerio) were utilized in this study. Behaviors (locomotive activity and anxiety-like behavior) in the F1 generation were evaluated at 120 hours post-fertilization (hpf) with the larval photometer response (LPR) assay, and at 3, 11, …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …

Nanoparticle Conjugated Photosensitizer For Targeted Photodynamic Inactivation Of Cancer Cells, Symone D. Crowder

Honors College Theses

Photodynamic therapy (PDT) is considered to be a potential replacement for traditional methods of chemotherapy. It includes the administration of photosensitizing agents (PS), which generate reactive oxygen species (ROS) upon excitation at a specific wavelength. With new outlooks and techniques, cancer research is advancing each day. It has allowed the progress of several theranostic drug delivery systems (DDS) exploring the area of nanomedicine.2 In the present work, a Rhodamine derivative, Rhodamine 6G (R6G) was used as the PS. In general, rhodamine compounds undergo cytotoxic reactions on photoexcitation by electron transfer reactions with folic acid within cells, making them a favorable …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Esterase Mediated Insecticide Resistance In The Southern House Mosquito, Culex Quinquefasciatus, Vivek Pokhrel

LSU Doctoral Dissertations

Much is known about the development of insecticide resistance associated with targeted application against insect populations. However, off-target selection by applications of insecticides in agricultural and residential sites also impacts development of insecticide resistance and is understudied. Similarly, the impact of selecting one life stage of mosquitoes on the insecticide susceptibility of different life stages is largely unknown. The first part of this study shows that susceptibility to chlorantraniliprole, which is applied in rice and sugarcane fields in LA, decreased (5.7 to12-fold) in populations of Culex quinquefasciatus collected from near these fields compared to a reference field strain. In addition, …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

Neuropilin-2 In Advanced Prostate Cancer And Its Targeting With Novel Small Molecule Inhibitors, Ridwan Islam

Theses & Dissertations

Despite the development of new therapies, clinical management of advanced metastatic castrationresistant prostate cancer (mCRPC) still remains challenging owing to the emergence of therapy resistance. Resistance to the therapies is driven by both AR and non-AR pathways. Non-AR pathway is characterized by a lineage switch that leads to the development of neuroendocrine-like (NE-like) prostate cancer (PCa), which has a fulminant clinical course due to the lack of effective treatment strategy. Therefore, novel molecular targets need to be identified to develop effective therapeutic regimen to improve the outcomes in advanced PCa patients including NE-like PCa. Recent investigation on advanced PCa patients …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system ^12-14. Our …

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 …

Floating Treatment Wetlands For Brackish Waters: Plant Selection And Nutrient Uptake Potential., Andrea Landaverde

All Theses

Brackish water bodies in coastal regions provide critical ecosystem services that support human and environmental health. Anthropogenic activities such as agricultural and industrial activities, construction, urban settlements, and tourism contribute to increased inputs of nitrogen (N) and phosphorus (P) in brackish coastal ecosystems. Excess nutrients can lead to impaired water quality and affect marine organisms. Floating treatment wetlands (FTWs) are a vegetated-base technology used to remove contaminants from water column, that has been mainly studied and applied in freshwater systems. Application of FTWs in brackish systems requires further investigation, as high salinity in brackish waters could result in toxicity to …

Hyper Stable Variants Of Fgf-1-Fgf-2 Dimer, Madison Shields Mcclanahan

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast Growth Factors (FGFs), including FGF-1 and FGF-2, are proteins that play a crucial role in cell proliferation, cell differentiation, cell migration, and tissue repair. FGF-1 and FGF-2 are useful in accelerating the healing process in the human body; however, these proteins are naturally thermally unstable, resulting in a relatively low half-life in vivo. 1,8 In efforts to improve the stability of this protein, FGF-1 and FGF-2 proteins are engineered by combining the amino acid sequences of the two proteins to form a heterodimer and obtain novel properties. These two FGF variants are chosen for their specific wound healing capabilities. …

The Various Nervous System Drugs Commonly Used For Treatment And The Disparities In Availability Of These Drugs In Minority Groups, Iman Haurami

Honors Scholars Collaborative Projects

The nervous system is a complex network in our body that is responsible for actions, reflexes, and even sensations. With the brain being part of the CNS, many common nervous system disorders are due to a defect in the central nervous system and the functions of this organ. These disorders include mental health problems, degenerative diseases, seizures, infections, and other possible genetic diseases. Many of these diseases are common in society and constantly researched. Even though these diseases are common, treatment accessibility and effects on people of minority groups are overlooked compared to the focus on majority groups. For drug …

Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow

Honors Theses

Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …

Investigating The Efficacy Of Tazemetosttat For In Vitro Treatment Of Human Triple Negative Breast Cancer Cells, Harshita Indukuri

Honors Scholars Collaborative Projects

Cancer is a formidable, genetic disease that affects many people, either directly or indirectly. Breast cancer is the most commonly diagnosed cancer worldwide (31). Triple-negative breast cancer (TNBC) is a type of breast cancer that has a higher lethality compared to other breast cancers and has a poor prognosis due to its highly invasive nature and limited treatment options. Finding safe, effective, and accessible treatment for TNBC is integral to treating TNBC patients. Tazemetostat is an EZH2-inhibitor that has recently been approved for use in epithelioid sarcoma (23). EZH2 is an overexpressed protein in many cancers, including TNBC (11). However, …