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The Role Of Transcription Factor Nrf2 In The Toxicity Of Perfluorooctane Sulfonate (Pfos) And Perfluorooctanoic Acid (Pfoa) In Vitro And In Vivo In Wild-Type And Nrf2 Deficient C57bl/6 Mice, Saif A. Alharthy

Theses and Dissertations

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of compounds known as perfluoroalkyl substances (PFAS). This study aimed to determine the protective role of Nrf2 against the toxicity of these agents. Nrf2-/- and wild-type astrocytes from C57BL/6 mice were exposed to PFOS (75-600µM) and PFOA (400-1000µM) for 24 hours. Lactate dehydrogenase (LDH) and Neutral Red (NR) uptake assays showed cytotoxicity being significantly greater in nrf2-/- than in the wild-type astrocytes. Concentrations of 600µM PFOS and 800µM PFOA showed significant increases in reactive oxygen species, lipid peroxidation, and TUNEL positive cells in both cells types with significantly …

Self-Emulsified Nanoemulsion As Permeation Enhancer And Its Application For Intranasal Delivery Of Insulin, Kanyaphat Bunchongprasert

Theses and Dissertations

This study aimed to investigate the permeation enhancing property and safety of self-emulsified nanoemulsion (SEN) and use these findings to enhance insulin absorption through the nasal route.

The first part of the project was to identify the factors affecting cytotoxicity and permeation enhancement of SEN on Madin-Darby Canine Kidney (MDCK) cells, a widely used paracellular model. Twenty-six fatty acid esters (FAEs) commonly used in SEN were investigated. Among the FAEs (mono-, di-, and triesters), fatty acid monoesters (FAME) are the main excipient causing cytotoxicity and opening tight junction. The cytotoxicity of FAME in SEN was reduced with the presence of …

Particle Shape Engineering For Improved Drug Delivery To Peripheral Lungs By Non-Invasive Route, Snehal Shukla

Theses and Dissertations

Inhalation of therapeutics has been gaining importance owing to immense advantages offered by pulmonary route and have attracted significant advancements in the pharmaceutical field. However, pulmonary drug delivery has been challenging because of the complexity of the respiratory tract and the existing defense mechanism. The pulmonary drug delivery has experienced advances in approaches and strategies to combat the existing challenges by tailoring the physicochemical properties of the delivery carriers and enabling both localized as well as systemic delivery. Pulmonary drug delivery is governed by several biophysical parameters of the delivery carriers such as particle size, shape, density, charge, and surface …

Development Of Nanoliposomes For The Treatment Of Braf V600e Mutated Parent And Vemurafenib-Resistant Melanoma, Yige Fu

Theses and Dissertations

Melanoma is one of the most aggressive and deadliest types of skin cancer. Currently, off-target toxicities and the rapid resistance development of metastatic melanoma mainly restrict the efficiency of the treatments. This thesis presents efforts towards developing liposomes to address current problems of BRAF-mutant metastatic melanoma.

EphA2-Receptor Targeted PEGylated Nanoliposomes for the Treatment of BRAF V600E Mutated Parent and Resistant Melanoma

In order to address off-target toxicities of the targeted therapy of MEK inhibitor trametinib (TMB), we developed a physically stable EphrinA1-mimicking peptide (YSA) anchored TMB-loaded PEGylated nanoliposomes (YTPLs). The YTPLs were evaluated in BRAFV600E-mutated parent cell lines (A375 and …

Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain

Theses and Dissertations

Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …

Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan

Theses and Dissertations

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, …

Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez

Theses and Dissertations

Ferroptosis is a non-apoptotic regulated form of cell death driven by the toxic accumulation of lipid peroxides and the presence of iron. The mechanism by which ferroptosis operates requires further investigation; here I will discuss the findings regarding the role of ferroptosis in different cellular models as well as the genes that may be involved with either promoting or hindering the ferroptotic pathway. NSC-34 is a hybrid cell line of neuroblastoma and primary spinal cord cells that can be differentiated into a motor neuron-like state allowing the characterization of ferroptosis in two distinct cellular conditions. Additionally, iNIL cells are a …

The Ion Channel Trpm7 Regulates Zinc Depletion-Induced Mdmx Degradation, Herui Wang

Theses and Dissertations

Zinc deficiency has been linked to human diseases including cancer. p53, a zinc-containing transcription factor, is the most frequently mutated tumor suppressor protein in human cancer. MDM2 and MDMX are zinc- containing proteins and crucial negative regulators of p53, which have been found to be amplified or overexpressed in various cancers. To investigate the effects of zinc depletion on the p53 signaling pathway, we have used ion chelators TPEN and bispicen as well as zinc-deficient medium to treat cells. We report here that zinc depletion results in MDMX degradation in a ubiquitination-independent and 20S proteasome-dependent manner. Restoration of zinc recovers …

Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen

Theses and Dissertations

Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …

Exploring Efficacy Of An Anti-Malarial Nanomedicine In Non-Small Cell Lung Cancer Treatment, Vineela Parvathaneni

Theses and Dissertations

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes and formulation parameters so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded …

Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi

Theses and Dissertations

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …

International Baccalaureate Primary Years Teachers´ Perceptions On Educating Students With Dyslexia, Jennifer Preschern

Theses and Dissertations

Global organizations, such as the United Nations, have increasingly focused on ensuring that students with special needs are receiving high quality education. With schools in over 158 countries worldwide, the International Baccalaureate (IB) system provides an ideal forum to investigate if students with dyslexia globally are receiving adequate instruction. Yet, there is a general lack of research investigating IB schools, specifically for students with learning differences such as dyslexia. Providing a curriculum framework for students ages three to 12, the Primary Years Program (PYP) forms the foundation of the IB system. This quantitative research study used online survey methods to …

Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot

Theses and Dissertations

Metabolic reprogramming is one of the important features of cancers, and there has been growing interest in targeting metabolic proteins to treat cancer. Glycogen is a polymer of glucose and serves as its storage unit in cells. Glycogen can provide energy to cells during the situations of high energy demand. A number of tumors are known to contain high levels of glycogen than their normal tissue counterparts. The liver plays an essential role in maintaining glucose homeostasis in the body via storing it into glycogen. The significance of glycogen metabolism in patients suffering from hepatocellular carcinoma (HCC) has not been …

A Phenomenological Study: Understanding Inner City African American Adolescent Exposures To Literacy, Lupita-Marial T. Matadi

Theses and Dissertations

Underrepresented children of color living in poverty have become over-represented as unsuccessful literacy students. Within the last 20 years, new instructional practices have been developed to help practitioners better meet the needs of children often unintentionally neglected by traditional instruction. The purpose of this study was to identify the relationship inner city African American adolescents have with literacy. This topic explored home-based literacy exposure, the role engagement with the Eurocentric literary canon has on English class performance, and the relationship students have with

literacy in and out of school. Areas considered were the influence of family, home-based literacy exposure, and …

Proactive Interventions For Collegiate Success: Using Response To Intervention With College Students Of Science, Technology, Engineering, Mathematics, And Psychology, Jenna Cook

Theses and Dissertations

College student attrition can cause a multitude of issues for students and universities. When a student leaves a program, the student may have to take additional credits and thus spend more on tuition, and the program may lose funding due to reduced enrollment. At a small private university in New Jersey, science, technology, engineering, mathematics and psychology (STEM) students were more likely than non-STEM students to change degree programs and be deemed at risk of failing. The purpose of this study was to determine whether a targeted response to intervention program that used academic coaching positively affected retention and persistence …

Evolution And Flower Shape From The Hawaiian Lobelioids To The Campanulaceae, Jingjing Tong

Theses and Dissertations

Campanulaceae, with roughly 2,400 species, is divided into five subfamilies, in part, by differences in their floral orientation and symmetry, with broad transitions between radial and bilateral floral symmetry. The Hawaiian lobelioids in the Campanulaceae is the largest endemic clade of Hawaiian angiosperms, and they have long been viewed as one of the most spectacular examples of an adaptive radiation in plants. In the first part of our study, we focus on Clermontia, which is one of the largest genera of Hawaiian lobelioids, employing variable low-copy nuclear gene sequences to determine their phylogenetic relationships. We use intron regions from four …

Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang

Theses and Dissertations

ATP-binding cassette (ABC) transporters are responsible for the efflux of structurally distinct endo- and xenobiotics energized by ATP hydrolysis. MRP7/ABCC10 belongs to the 10th member of subfamily C and responsible for mediating MDR against a series of chemotherapeutic drugs such as taxanes, epothilones, Vinca alkaloids, anthracyclines and epipodophyllotoxins. Establishment of new in silico and in vitro models for MRP7 substrates/inhibitors prediction Considering the limited knowledge of MRP7, we established a homology model based on bovine MRP1 cryo-EM models. The final model was used for protein global motion analysis and docking analysis. Before docking, potential drug binding pockets were identified and …

Changes In Youth Executive Function During Trauma-Focused Cognitive Behavioral Therapy: Associations With Ptsd Symptom Severity, Amy Hyoeun Lee

Theses and Dissertations

Youth with maltreatment and/or interpersonal trauma histories often demonstrate significant executive function difficulties, which may negatively affect self-regulation and represent a transdiagnostic risk factor for trauma-related psychopathology and impaired functioning across domains. Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an evidence-based treatment for posttraumatic stress disorder (PTSD) symptoms and other mental health sequelae among maltreated youth; however, the potential impact of impact of TF-CBT on youth executive function difficulties has not been examined despite emerging evidence that executive function may be related to PTSD symptom severity among trauma-exposed youth. The current study sought to evaluate caregiver-reported executive function as a treatment …

Return To Play And Class For Concussed College Athletes Predicted From Post-Concussion Symptom Domains, Jazmin Nicole Mogavero

Theses and Dissertations

Each year approximately 1.6 to 3.8 million people suffer a sports-related traumatic brain injury (Langlois, Rutland-Brown, & Wald, 2006). Concussions, a common form of mild traumatic brain injury, account for 75% of total brain injuries in the United States (Faul, Xu, Wald, & Coronado, 2010). In sports, concussions account for 1 of every 10 injuries (Marar, McIlvain, Fields, & Comstock, 2012). Overall, concussion symptoms typically remit within one to four weeks from injury (McCrea, 2007); however, conflict exists surrounding the duration of time that would be safe for a concussed student-athlete to return to functioning, both to sport and to …

Qbd Approach For Development Of Ivermectin-Loaded Gastro Retentive Sustained Release Tablets As Mass Drug Administration For Malaria Transmission Control, Zhangjie Xi

Theses and Dissertations

Malaria is a life-threatening disease with a high prevalence worldwide. Mass drug administration (MDA) of ivermectin have been shown to prevent the transmission of malaria. The objective of this investigation is to develop ivermectin-loaded gastro retentive sustained release tablets (GRSRTs), which have the potential to avoid not only frequent administration of MDA but also fluctuation of ivermectin in systemic circulation. Based on the outcomes from screening various materials to be the suitable matrix forming polymer and bio-adhesive polymer mixture of GRSRTs, HPMC K100M, Carbopol 934p and sodium alginate:chitosan (1:1) were selected as formulation variables. Eight formulations of ivermectin-loaded GRSRTs were …

Double-Coated Biodegradable Poly (Butyl Cyanoacrylate) Nanoparticulate Delivery Systems For Brain Targeting Of Doxorubicin Via Oral Administration, Neeraj Kaushal

Theses and Dissertations

Primary brain cancer cells grow within the brain or cancer cells can metastasis from different site of the body into brain. The major hurdle in the treatment of brain cancer is the presence of blood-brain barrier (BBB). Additionally, acquired multidrug-resistant (MDR) impedes the success of long-term chemotherapy. Therefore, the objective of this investigation is to evaluate the brain targeting potential of orally administered poly(butyl cyanoacrylate) nanoparticulate delivery systems (PBCA-NPDS), double-coated with Tween 80 and polyethylene glycol (PEG) 20000 for brain delivery of doxorubicin, that does not cross the BBB by itself. And, evaluate the MDR reversal potential of PBCA-NPDS. Doxorubicin-loaded …

Up-Regulation Of Fibroblast Growth Factor (Fgf) 21 Via Ap-1 Activation Attenuates Cisplatin-Induced Hepatotoxicity, Yue Zhang

Theses and Dissertations

Fibroblast growth factor (Fgf in rodents and FGF in human) 21 plays important roles in the maintenance of sugar, lipid and energy homeostasis. Fgf/FGF21 can be up-regulated via activation of peroxisome proliferator-activated receptors (PPARs), aryl hydrocarbon receptor (AhR), glucocorticoid receptor (GR), and activating transcription factor (ATF) 4. Recent studies also demonstrated that Fgf/FGF21 plays cytoprotective roles against chemical-induced toxicities, such as of dioxins, acetaminophen, and alcohols. Cisplatin (cis-diamminedichloroplatinum, CDDP) is a widely used chemotherapeutic drug. However, numerous adverse effects have been noted during CDDP therapy, which largely limit its clinical applications. This study was designed to determine the regulation of …

Resting-State Cerebral Perfusion Patterns: An Exploratory Factor Analysis Of Single-Photon Emission Computed Tomography Clinical Data, Scott Harcourt

Theses and Dissertations

Resting-state (RS) networks (neural regions demonstrating a temporal correlation when a person is not engaged in deliberate activity) are a new topic in neuroscience and neuropsychology, not gaining significant traction in the literature until 2005. Few studies have used single-photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) to analyze RS. The omission is critical because SPECT RS networks have a different structure and statistical representation than functional magnetic resonance imaging (fMRI) RS networks. Moreover, recent fMRI research has explored RS differences in persons with psychopathology but have not studied brain-behavior assessment with the potential of application of neuropsychological …

Assembly And Function Of The Polycystin Receptor-Ion Channel Complexes And The Otop1 Proton Channel, Bin Li

Theses and Dissertations

Polycystin complexes, or TRPP/PKD complexes, made of transient receptor potential channel polycystin subfamily proteins (TRPP) and polycystic kidney disease (PKD) proteins, play key roles in coupling extracellular stimuli with intracellular Ca2+ signals. For example, the TRPP2/PKD1 complex has a crucial function in renal physiology, with mutations in either protein causing autosomal dominant polycystic kidney disease (ADPKD). In contrast, the TRPP3/PKD1L3 complex responds to low pH and plays a potential role in sour taste. It has been previously shown that the protein partners interact via association of the C-terminal or transmembrane segments, with consequences for the assembly, surface expression, and function …

An Examination Of The Impacts Of Childhood Trauma On Healthy Intimate Relationships In College-Aged African Americans, Broquelynn D. Shepard

Theses and Dissertations

For African Americans, the dynamics of relationships are rooted in childhood experiences of unconditional love, restraint, and respect. These experiences help individuals form their understanding of how relationships function. Experiencing healthy relationships has an enduring impact on social development and interpersonal relationships. However, regarding studies on childhood trauma and intimate relationships, there is insufficient literature that includes African American samples as the primary foci of the research. Due to gaps in extant literature, the present study aims to explore whether experiences of healthy intimate relationship in African Americans are associated with childhood trauma (neglect, emotional, sexual, and physical abuse). Using …

Ndikimi I Sulmeve Kibernetike Në Sektorin Bankar Dhe Shëndetësor Gjatë Vitit 2020, Triflona Tolaj

Theses and Dissertations

- Punimi im i temës së diplomës është një hulumtim shkencor rreth sulmeve kibernetike dhe ndikimit të tyre në dy sektorët më të rrezikuar, sektorin bankar dhe atë shëndetësor. Tema është përzgjedhur e tillë pasi që çdo ditë përballemi me risi të reja në fushën e teknologjisë. Kjo gjë ka ndikuar edhe në rritjen e sulmeve kibernetike, e numri i tyre është shtuar edhe më shumë gjatë periudhës së po këtij viti, pandemisë së koronavirusit. Në kapitujt e parë të projektit është shtjelluar fillimisht koncepti i sigurisë kibernetike dhe masat që duhet të merren për mbrojtjen ndaj sulmeve të mundshme, …

Kujdesi Infermieror Te Pacientët Me Artrit Reumatoid, Valbona Zeqiraj

Theses and Dissertations

Artriti reumatoid është një çrregullim inflamator, sistemik,kronik i cili kryesisht prek nyjet që janë të veshura me synovium. Karakterizohet tipikisht nga një përfshirje simetrike,herë pas here deformuar, poliartriti periferik. Për shkak se është një sëmundje sistemike, mundet gjithashtu ndikojnë në të gjithë trupin, duke përfshirë zemrën, mushkëritë dhe sytë.

Shkaku AR nuk njihet plotësisht. Ka të ngjarë që individët e ndjeshëm gjenetikisht të ekspozohen ndaj një antigjeni të panjohurduke rezultuar në vetë-stimulim të sistemit imunitar (autoimuniteti).

Përgjigja imune reagon në mënyrë të kryqëzuar me indin pritës (membranën synoviale) duke rezultuar në pezmatim të membranës sinoviale (sinovit).Kjo krijon hipertrofi sinoviale.

Ky …

Kanceri I Gjirit Dhe Mundësitë E Sotshme Diagnostikuese, Medina Ilijazi

Theses and Dissertations

Kanceri i gjirit është një tumor që zhvillohet nga qelizat e vetë gjirit. Kanceri i gjirit është rritja jashtë kontrollit dhe përhapja e qelizave jo normale të indit të gjirit. Metoda kryesore moderne për zbulimin e kancerit të gjirit është mamografia, e cila në mënyrë të besueshme zbulon nga 80% në 96% të tumoreve të gjirit, më të mëdha se 10 mm në diametër. Mamografia kryhet çdo vit si masë profilaktike për të gjitha gratë mbi moshën 40 vjet. Qellimi baze i ketij hulumtimi eshte analizimi i detajizuar i procedurave të hershme diagnostikuese bashkëkohore në kuadër te zbulimit te hershem …

Opioid System's Involvement In Ketamine's Antidepressant-Like Effects, Fan Zhang

Theses and Dissertations

Depression is one of the most debilitating disorders in the world. The currently available medications typically have a 2-4 week delay in their therapeutic effects and are ineffective for about 40% of patients. In 2000, a subanesthetic dose (0.5 mg/kg i.e.) of the dissociative anesthetic ketamine was reported to have both rapid and robust antidepressant effects in in treatment-resistant depressed patients. However, the mechanisms responsible for ketamine’s antidepressant effects remain unclear. In 2018, a clinical study reported that pretreatment with the nonselective opioid antagonist naltrexone attenuated the rapid antidepressant effect of ketamine in depressed patients. The current study investigated the …

Role Of P53 Deficient Clonogenic Endothelial Cells In The Pathogenesis Of Pulmonary Hypertension, Aneel Roy Bhagwani

Theses and Dissertations

Pulmonary Artery Hypertension (PAH) is a progressive disorder of the small vessels of the pulmonary vasculature. It is characterized by occlusive vascular remodeling leading to right heart failure and ultimately death. PAH pathogenesis involves a multifactorial etiology leading to formation of occlusive lesions in small (preacinary) pulmonary arteries. These lesions contain hyper-proliferative, apoptosis resistant endothelial cells (ECs), smooth muscle cells and fibroblasts. ECs play a major role in the development of PAH. These ECs in vascular lesions are primitive and express progenitor cell markers, including CD117 (c-kit).

We have isolated clonally expanded, c-kit+ ECs from the lungs of Green Fluorescent …