Medicine and Health Sciences Commons^™

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …

Aptamer-Based Voltammetric Biosensing For The Detection Of Codeine And Fentanyl In Sweat And Saliva, Rosa Lashantez Cromartie

FIU Electronic Theses and Dissertations

Despite the many governmental and medicinal restrictions created to combat the opioid epidemic in the United States, opioid abuse and overdose rates continue to rise. The development of an aptamer-based voltammetric sensor and biosensor is described in this dissertation. The aim was to develop a low-cost, sensitive, and specific aptamer-based sensor for on-site, label-free determination of codeine and fentanyl in biological fluids. To do this, the surfaces of screen-printed carbon electrodes (SPCE) were modified with gold nanoparticles (AuNPs), followed by the addition of single-stranded DNA aptamers. These were covalently bound to the electrode surface. Operations of the sensors were collected …

Type I Topoisomerases As Potential Targets For Therapeutics, Ahmed Seddek

FIU Electronic Theses and Dissertations

DNA topoisomerases are universal enzymes that control the topological features of DNA in all forms of life. This study aims to find potential inhibitors of some of the DNA topoisomerases in bacteria and humans that can be developed into potential therapeutics.

The first aim of this study is to find potential inhibitors of bacterial topoisomerase I that can be developed into antibiotics. There is an urgent need to develop novel antibiotics to overcome the world-wide health crisis of antimicrobial resistance. Virtual screening and biochemical assays were combined to screen thousands of compounds for potential inhibitors of bacterial topoisomerase I. NSC76027 …

The Role Of Inositol Polyphosphate-4-Phosphatase Type Ii B (Inpp4b) In Obese Models And Endocrine Cancers, Manqi Zhang

FIU Electronic Theses and Dissertations

INPP4B is a dual-specificity phosphatase and a tumor suppressor in prostate and breast cancers. Progression of the prostate and breast cancers depends on the androgen receptor (AR) or estrogen receptor alpha (ERα) signaling, respectively. In this work we demonstrated that INPP4B reprograms ERα transcriptional activity in breast cancer. INPP4B maintains expression and protein levels of progesterone receptor (PR), an ERα direct target gene required for mammary gland development. Consistently we demonstrated that Inpp4b knockout severely impairs lateral branching in the mammary gland of maturing virgin females. In advanced prostate cancer, activation and transcriptional reprogramming of AR frequently coincides with the …

Topoisomerase And Tyrosyl-Dna-Phosphodiesterase Ratio As An Indicator For The Response Of Glioblastoma Cancer To Topoisomerase Targeting Anticancer Drugs, Wenjie Wang

FIU Electronic Theses and Dissertations

Glioblastoma (GBM) patients have an estimated survival of ~15 months, with the standard of care (surgery, radiation, and chemotherapy) that has only modestly enhanced patient survival. Identifying biomarkers representing vulnerabilities in GBM biology may allow for the selection of effective and safe chemotherapy options. Irinotecan (IRT), a genotoxic compound currently in clinical trials for GBM, targets topoisomerase I (TOP1) by forming an irreversible ternary DNA-TOP1 cleavage complex (TOP1cc) and leads to apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that rescues TOP1cc and reduces the effectiveness of IRT. In the current study, we evaluate the value of the …

Mycobacterium Tuberculosis Inhibitors: Action And Resistance, Pamela K. Garcia-Moreno

FIU Electronic Theses and Dissertations

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, has been a global health problem for years. The emergence of drug resistance in this organism generates the necessity of exploring novel targets and developing new drugs. Topoisomerases are enzymes found in all kingdoms of life responsible for overcoming the topological barriers encountered during essential cellular processes. The genomes of mycobacteria encode only one type IA topoisomerase (MtopI), which has been validated as a novel TB drug target. The goal of this study is to obtain new information on the mechanism and resistance of endogenous and synthetic inhibitors of MtopI.

Rv1495 is …

Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang

FIU Electronic Theses and Dissertations

DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, …

Enzyme Catalyzed And Ultrasound Assisted Transformation Of Selected Pollutants, Yi Tan

FIU Electronic Theses and Dissertations

The widespread use of synthetic drugs and as feed additives has resulted in the release of large amounts of biologically active chemicals into the environment. Exposure to environmentally relevant concentrations of chemicals can have severe effects on human health. Therefore, effective degradation of these synthetic, biologically active compounds is of paramount importance.

Diphenhydramine (DPH) has been selected as a target compound for ultrasound remediation. The results demonstrated that ultrasound-induced degradation has potential applications in managing aqueous media contaminated with DPH.

Atorvastatin and roxarsone have been selected as representative substrates for chloroperoxidase (CPO) catalyzed transformation of pollutants. These studies demonstrate atorvastatin …

The Degradation Of Pharmaceutical Pollutants In Wastewater Catalyzed By Chloroperoxidase And The Construction Of Chloroperoxidase H105r Mutant, Qinghao He

FIU Electronic Theses and Dissertations

Trace amounts of pharmaceuticals have been detected in water, from nanograms per liter to micrograms per liter, and have a negatively effect in the aquatic environment and an increased potential risk of drug poisoning for human and animals. In order to address the problem, drug degradation catalyzed by chloroperoxidase (CPO) has been investigated. CPO is a heme-containing glycoprotein secreted by the fungus, Caldariomyces fumago, it catalyzes two major types of oxidations, two one-electron oxidations as catalyzed by most peroxidases and two-electron oxidations which are rare for conventional peroxidases.

Five common drugs from a variety of classes which were persistent in …

Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, Khoa Ngoc Pham

FIU Electronic Theses and Dissertations

Downstream regulatory element antagonist modulator (DREAM) is involved in various interactions with targets both inside and outside of the nucleus. In the cytoplasm, DREAM interacts with the C-terminal fragments of presenilins to facilitate the production of β-amyloid plaques in Alzheimer’s disease. In the nucleus, Ca²⁺ free DREAM directly binds to specific downstream regulatory elements of prodynorphin/c-fos gene to repress the gene transcription in pain modulation. These interactions are regulated by Ca²⁺ and/or Mg²⁺ association at the EF-hands in DREAM. Therefore, understanding the conformational dynamics and stability associated with Ca²⁺ and/or Mg²⁺ binding to DREAM …

Extraction, Purification And Partial Characterization Of A Carotenoid Binding Protein (Cbp) From The Epidermis Of The Monarch Butterfly Larvae (Danaus Plexippus), Nan Fang

FIU Electronic Theses and Dissertations

This dissertation describes the purification and partial characterization of CBP from the epidermis of the monarch butterfly larvae (Danaus plexippus). A yellow protein-carotenoid complex was extracted from the yellow pigmented epidermal tissue from monarch butterfly larvae by homogenization. Additional steps in the purification process included differential precipitation with ammonium sulfate, cation and anion chromatography, and lastly size exclusion chromatography. Polyacrylamide gel electrophoresis demonstrates that a single protein was isolated (M-LBP) having a ~60 kDa molecular weight, the value has subsequently been confirmed by HR-tandem MS. Lutein is the sole carotenoid bound by M-LBP with a stoichiometry of the …

Conjugated Polymer-Based Biomaterials Through Controlled Self-Assembly, Megan Twomey

FIU Electronic Theses and Dissertations

Synthetic polymeric materials have gained significant use as biological materials (biomaterials) in biomedical and pharmaceutical applications. As a result, a demand for well-defined polymers with tunable properties has emerged. The synthetic versatility of polymeric biomaterials allows the opportunity to understand the structure-property relationship of materials and their cellular interactions. A novel class of polymeric biomaterials are conjugated polymers (CPs), which possess desirable physicochemical and excellent photophysical properties, including inherent fluorescence. The synthetic versatility of CPs allows easy modification of the conjugated backbone to tune emission and side chain structures to adjust biocompatibility through increased water solubility, controlled biodegradability, and incorporation …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel

FIU Electronic Theses and Dissertations

The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.

Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. …