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Influence Of Glucose And Lactic Acid On Macrophage Transition In Pancreatic Tumors, Anyssa A. Rodriguez Dec 2022

Influence Of Glucose And Lactic Acid On Macrophage Transition In Pancreatic Tumors, Anyssa A. Rodriguez

Theses and Dissertations

Pancreatic cancer is the seventh leading cause of cancer-related mortality worldwide. According to the American Cancer Society, it is the eleventh most common cancer diagnosed in both men and women in the United States. Pancreatic ductal adenocarcinoma (PDAC) comprises 90% of all pancreatic malignancies and is associated with poor clinical outcome because of late diagnosis and resistance to therapy. In addition, studies show that the tumor microenvironment has become an emerging interest in cancer research due to its complex components and unique characteristics that aid in cancer initiation, maintenance, and progression. Accumulating evidence signifies that tumor associated macrophages (TAMs) play …


Effects Of Roundup Exposure On Redox Status, Cellular Apoptosis, And Antioxidant And Osmoregulatory Enzyme Expressions In Goldfish (Carassius Auratus), Md Imran Noor Dec 2022

Effects Of Roundup Exposure On Redox Status, Cellular Apoptosis, And Antioxidant And Osmoregulatory Enzyme Expressions In Goldfish (Carassius Auratus), Md Imran Noor

Theses and Dissertations

Intense anthropogenic activities of industrialized nations dramatically increase environmental pollution. This study focused on the effects of Roundup, a glyphosate-based herbicide, exposure (low- and high-dose: 0.5 and 5 mg/L for 2 weeks) on dinitrophenyl protein (DNP), nitrotyrosine protein (NTP), superoxidase dismutase (SOD), catalase (CAT), Na+ /K+ - ATPase (NKA), and renin expressions, and cellular apoptosis in the gills and kidneys of goldfish. Histopathological analysis showed widespread tissue damage in both gills and kidneys. Immunohistochemical analysis provided insights into the expression of molecular biomarkers in tissues. Fish exposed to Roundup exhibited a significant (P<0.05) upregulation in DNP, NTP, SOD, and CAT expressions, and apoptotic nuclei in both tissues. Additionally, exposure to Roundup significantly increased renin expression in kidneys and decreased NKA expression in gills. Overall, our results suggest that exposure to Roundup induces oxidative/nitrative stress and cellular apoptosis and alters osmoregulatory and antioxidant systems which may lead to impaired physiological functions in goldfish.


Cucurbitacin B: A Potential Natural Agent For Targeting Tumor Immune Cell Population, Emmanuel Anning Jul 2022

Cucurbitacin B: A Potential Natural Agent For Targeting Tumor Immune Cell Population, Emmanuel Anning

Theses and Dissertations

Immune checkpoint blockade (PD1, PDL-1 and CTLA-4) immunotherapies have emerged as the breakthrough in cancer treatment. However, some malignancies show marginal response. One factor that influences the efficacy of immunotherapy is the development of immunosuppressive tumor microenvironment (TME), caused by infiltration of myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAM) into the tumor, facilitating metastatic tumor growth and immunotherapy resistance. We have identified Cucurbitacin B (Cuc. B), a potent small molecule that targets TAM and MDSCs and inhibits Stat3, CSF-1R, and PI3Kγ signaling axis at lower doses compared to the pharmacological inhibitor of PI3Kγ (IPI-549). IL-4 polarization of …


Targeting Ribosome Biogenesis For Pancreatic Cancer Treatment, Carlos Perez Iii Jul 2022

Targeting Ribosome Biogenesis For Pancreatic Cancer Treatment, Carlos Perez Iii

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related death in the United States. Currently, PanCa is one of the recalcitrant cancers that has very limited therapeutic options available for its treatment. The current standard care of PanCa is gemcitabine (GEM) alone or in combination with FOLFIRINOX, nab-paclitaxel, erlotinib, or 5-FU PanCa, which often show poor response. Therefore, new treatment strategies are required for the prevention and treatment of cancer. Ribosome biogenesis process is dysregulated in most of the cancer types of results in production of more ribosomes and synthesis of oncoproteins which lead to the induction, progression, …


Targeting Mutated Kras And Galectin-1 In Pancreatic Cancer, Ana Izavelle Martinez Bulnes Jul 2022

Targeting Mutated Kras And Galectin-1 In Pancreatic Cancer, Ana Izavelle Martinez Bulnes

Theses and Dissertations

The poor patient survival rate in pancreatic ductal adenocarcinoma (PDAC) remains a challenge. KRAS activating point mutation on codon-12 is found in 70–95 percent of PDAC patients, and no progress in inhibiting KRAS has been obtained thus far. KRASG12D is a transcription factor that controls cell proliferation, differentiation, and apoptosis. Recent preliminary and published research indicates that Galectin-1 (Gal-1) levels are high in both PDAC and stromal cells, which modulates tumor microenvironment and metastasis. As a result, we created a new combination treatment for PDAC that targets both proliferation and metastasis in PDAC by targeting mutant KRASG12D and Gal-1. This …


Screening For Potential Therapeutic Targets Of Yb-1 Protein Using A Bioinformatics Approach, Omar Muneer Karkoutly Jul 2022

Screening For Potential Therapeutic Targets Of Yb-1 Protein Using A Bioinformatics Approach, Omar Muneer Karkoutly

Theses and Dissertations

Treatment options for cancer are becoming much more limited due to the robust characteristics of cancer that allows them to rapidly develop drug resistance. This may be a result of cancer cells’ ability to switch between differentiated and undifferentiated states (plasticity). Diagnostic measurement and detection of cancer and its progression is essential for developing successful treatments. Specific cancer targets whose expressions are highly associated with increased incidence, risk, and spread of cancer therefore become perfect targets for therapeutic intervention. One such novel target that is still being studied is the Y-box binding protein 1 (YB-1), which …


Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah Jul 2022

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …


The Apoe Ε4 Allele Association With Cholesterol Related Phenotypes In The Mexican American Population, Stephanie Lozano Jul 2022

The Apoe Ε4 Allele Association With Cholesterol Related Phenotypes In The Mexican American Population, Stephanie Lozano

Theses and Dissertations

Diseases linked to high cholesterol have been well studied and several diseases-associated candidate genes have been suggested. Among these, the apolipoprotein E gene (APOE) gene associated with lipid metabolism and lipid-related traits was reported in the non-Hispanic population. There are three types of alleles APOE ε2, ε3, and ε4. The APOE ε4 allele has been identified as a biomarker for Alzheimer’s disease (AD) and cardiovascular disease (CVD). In recent years, there have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Mexican American population. Therefore, the aim of this study is to investigate …


Zinc-Mediated Regulatory Function Of Psd-95 On Nmdar At Post-Synapses, Luis F. Acosta May 2022

Zinc-Mediated Regulatory Function Of Psd-95 On Nmdar At Post-Synapses, Luis F. Acosta

Theses and Dissertations

Postsynaptic density-95 (PSD-95) is a membrane-associated guanylate kinase that mediates localization of receptors in the excitatory postsynaptic density. It has been reported that PSD-95 mediates postsynaptic localization of NMDA receptors and anchors postsynaptic AMPAR receptors mainly through its postsynaptic membrane targeting by its N-terminal palmitoylation. Recent studies have shown that Ca2+/calmodulin blocks palmitoylation of PSD-95 by binding at the N-terminus of PSD-95, which promotes dissociation of PSD-95 from the postsynaptic membrane and causes loss of surface AMPARs in cultured neurons. Another metal ion zinc is found in various areas of the brain. As an endogenous neuromodulator, zinc plays a role …


Targeting Protein Synthesis In Clostridioides Difficile To Develop Antimicrobial Candidate, Elvira L. Alanis May 2022

Targeting Protein Synthesis In Clostridioides Difficile To Develop Antimicrobial Candidate, Elvira L. Alanis

Theses and Dissertations

Clostridioides difficile is a gram positive, spore forming, obligate anaerobic bacterium that causes Clostridioides difficile infection (CDI) which can result in pseudomembranous colitis and toxic megacolon. In the case of this research a focus on Protein synthesis is made since it is an essential metabolic process and is a validated target for antibiotics. Protein synthesis begins with Initiation which includes the three translation initiation factors. Through the NMR chemical shift assignments, the IF1 structure was determined, and it was found to be composed of a short α helix and five β helixes. A peptide was designed after the short α …


Structures And Regulations Of Translation Initiation Factors In Pseudomonas Aeruginosa Protein Biosynthesis To Develop New Potential Antimicrobial Agents, Nicolette Valdez May 2022

Structures And Regulations Of Translation Initiation Factors In Pseudomonas Aeruginosa Protein Biosynthesis To Develop New Potential Antimicrobial Agents, Nicolette Valdez

Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative, multidrug resistant bacterium that has been recognized as the prominent cause of nosocomial infections. Untreated acute and chronic infections associated with P. aeruginosa can develop into other diseases such as pneumonia, otitis externa, and osteomyelitis. P. aeruginosa infections commonly affect immunocompromised individuals such as cystic fibrosis, cancer, and burn patients. The misuse and overuse of antibiotics has contributed to the increased antibiotic resistance in P. aeruginosa and thus has led to an unmet need for discovery of novel antibiotic candidates. Protein biosynthesis is an essential metabolic process occurring in all bacteria and a validated target …


Nanostructured Materials For Biomedical Applications, Silverio Lopez May 2022

Nanostructured Materials For Biomedical Applications, Silverio Lopez

Theses and Dissertations

Nanotechnology has been used in an increasing number of applications in biochemistry and molecular biology. Compared to bulk materials, nanoscale materials offer a variety of advantages in applications due to an increased surface-to-volume ratio of the reactants. The unique properties of nanostructured materials and their properties such as stability, reactivity, magnetic response, pressure discharge performance and biocompatibility depend on particle size and shape. This work focuses on a nanoenergetic material composed of Aluminum (Al), Copper II oxide (CuO), and Iodine (I) pentoxide (I2O5), and the biomedical application of nanoscale dextran-coated magnetite (Fe3O4), which was produced using microfluidics to tune particle …


Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa May 2022

Assessing The Effects Of Levonorgestrel (Lng) On Neural Differentiation In The Developing Hypothalamus Using The Zebrafish (Danio Rerio) As A Model, Gabriella Hinojosa

Theses and Dissertations

Neurogenesis is a critical component of fetal neurodevelopment consisting of: migration, proliferation and differentiation. Health concerns from anxiety to reproductive issues have been linked to alterations of neurogenesis processes. Endocrine disrupting chemicals (EDCs) can mimic hormones vital to this process, potentially adversely affecting the susceptible fetal brain. One EDC, Levonorgestrel (LNG), is a testosterone-like progestin used in birth control methods that has a high bioavailability and long half-life. Using zebrafish embryos as a model, this lab previously discovered that an environmentally relevant LNG dose (5 ng/L) significantly increased anxiety behaviors. The hypothalamus is responsible for the development …


Exploring Dna Compaction Via Bacillus Subtilis Parb Protein By Single Molecule Investigation, Miranda L. Molina May 2022

Exploring Dna Compaction Via Bacillus Subtilis Parb Protein By Single Molecule Investigation, Miranda L. Molina

Theses and Dissertations

Faithful chromosome segregation involves ParB, a DNA-binding and compacting protein that specifically recognizes parS DNA sites near the replication origin. ParB spreads 10-20 kb from parS sites, which recruitments additional ParB molecules to neighboring DNA, forming higher-order nucleoprotein complexes. ParB is also a novel CTPase enzyme and hydrolyses CTP to self-dimerization and create a clamp that slides along DNA. To understand the roles of CTP in Bacillus subtilis ParB (BsParB), we purified wild type ParB (BsParB (WT)) and recombinant ParB (BsParB(R80A)) mutant. BsParB(R80A) was known to prevent CTP binding and not compact DNA. Proteins N- and C-terminally appended with a …