The Dubr/Mir-210-5p/Retsat Axis In Cholesterol-Associated Steatohepatitis: Clinical Signatures And Molecular Mechanisms, Hana Mahmoud Abdelzaher

Theses and Dissertations

Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driven steatohepatitis, its underlying molecular mechanisms remain poorly understood. This study investigates a novel regulatory axis involving DPPA2 Upstream Binding RNA (DUBR), miR-210-5p, and retinol saturase (RETSAT). 170 patient samples revealed progressive axis dysregulation in disease states, with RETSAT emerging as a highly accurate diagnostic marker (AUC=1.000). Using novel in vitro models of MASH and CASH, we demonstrated that miR-210-5p modulation significantly affects lipid accumulation and cellular phenotype, with …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Nanoformulations Of Essential Oils Extracted From Pistacia Lentiscus And Boswellia Sacra And Investigation Of Their Anticancer, Antimicrobial, And Antioxidant Activities., Obaydah Abd Alkader Alabrahim

Theses and Dissertations

Essential oils (EOs) obtained from natural sources have shown promising biological and therapeutical properties such as anticancer, antimicrobial, and antioxidant activities, attributing to their high content of a variety of bioactive components. However, EOs’ therapeutic properties are limited by their low stability, poor bioavailability, high volatility, and low targeting ability. Therefore, the encapsulation and nanoformulation of EOs can maximize their therapeutical efficiency and physicochemical properties while overcoming their undesirable side effects and drawbacks. EOs extracted from the resins of Pistacia Lentiscus var. Chia (P.oil) and Boswellia Sacra (B.oil) are two promising EOs that have shown great therapeutic potential. P.oil was …

Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam

Theses and Dissertations

Lack of standard guidelines for optimal needle insertion during high-dose-rate (HDR) intracavitary-interstitial (IC-IS) brachytherapy of the cervix means a sophisticated and technical skillset of inserting needles next to IC applicators must be developed to enhance plan quality. This study sought to evaluate the performance of two separate direction modulated brachytherapy (DMBT) tandem applicators used in conjunction with one set of novel DMBT ovoids, to effectively obviate the need for IS needles.

A cohort of 32 retrospective clinical HDR brachytherapy plans was re-planned with Varian’s BrachyVision^® treatment planning system, using VEGO^® inverse optimization algorithm, with dose heterogeneity accounted for …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Copper Sulfide Manganese Nanoparticles For Multimodality Imaging And Therapy, Ali S. Gawi Ermi

Theses and Dissertations

Abstract

COPPER SULFIDE MANGANESE NANOPARTICLES FOR MULTIMODALITY IMAGING AND THERAPY

By Ali S. Gawi Ermi, MSc

Inorganic nanoparticles (NPs) are compatible with metal-based multi-modality molecular imaging and targeted therapy. Copper sulfide nanoparticles (CuS NPs) are attractive photoacoustic and photothermal agents and are amenable to incorporation of radionuclides and paramagnetic elements to facilitate image-guided therapy. The aim of this work is to develop manganese (Mn)- doped CuS NP, intrinsically radiolabeled with radionuclides such as (Zirconium-89 (⁸⁹Zr), Copper-64/67 (^64/67Cu) and Manganese-52/55 (^52/55Mn)). This novel approach combines Photoacoustic (PA), Positron emission tomography (PET), Single-photon emission computed tomography …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

A Deep Learning U-Net For Detecting And Segmenting Liver Tumors, Vidhya Cardozo

Theses and Dissertations

Visualization of liver tumors on simulation CT scans is challenging even with contrast-enhancement, due to the sensitivity of the contrast enhancement to the timing of the CT acquisition. Image registration to magnetic resonance imaging (MRI) can be helpful for delineation, but differences in patient position, liver shape and volume, and the lack of anatomical landmarks between the two image sets makes the task difficult. This study develops a U-Net based neural network for automated liver and tumor segmentation for purposes of radiotherapy treatment planning. Non-contrast simulation based abdominal CT axial scans of 52 patients with primary liver tumors were utilized. …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …