Medicine and Health Sciences Commons^™

Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin

Open Access Theses & Dissertations

Apoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating …

Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (Viannia) Braziliensis, Eileni Rodriguez Gil

Open Access Theses & Dissertations

Protozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentially diagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of these methods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi …

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano

Open Access Theses & Dissertations

Despite notable progress in lipid nanoparticle (LNP)-mediated gene delivery, achieving selective transfection of specific cell types, such as cancer cells, remains a significant hurdle, hindering the advancement of innovative gene therapies. In this study, we engineered an LNP formulation encapsulating plasmid DNA (pDNA) encoding the monomeric Green Lantern (mGL) fluorescent reporter protein. The DT7 peptide ligand targeting human transferrin receptor 1 (hTfR1) was also conjugated to the LNP surface for targeted delivery to hTfR1-expressing cells. Optimization of LNP composition yielded favorable particle diameter, ζ-potential, yield, and pDNA encapsulation efficiency. Evaluation of transfection selectivity using a panel of two engineered cell …

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

A Novel Neuroinvasive Infection Modality For Francisella Tularensis Elicits Neuroinflammation Resulting In Cellular Damage, Mireya Griselle Ramos-Muniz

Open Access Theses & Dissertations

Francisella tularensis (Ft.) is a gram-negative coccobacillus bacterium that causes the zoonotic disease tularemia in humans. Ft. causes the most severe, often fatal, form of the disease through inhalation. However, Ft. is most commonly transmitted through direct contact with infected animal carcasses such as rodents and rabbits, consumption of contaminated food or water, or through arthropod bites, particularly ticks. Due to its extremely low infectious dose, high mortality rate, and potential use as a biological warfare agent, Ft. is classified by the CDC as a "Tier 1 select agent". Ft. infection triggers an overactive inflammatory response, termed a "cytokine storm", …

Acute Effects Of Neuromuscular Electrical Stimulation On Blood Glucose And Energy Metabolism In Overweight/Obese Population, Ali Mossayebi

Open Access Theses & Dissertations

Background: In the perspective of preventing cardiovascular disease and promoting health, weight control and physical activity are the main concerns. Electrical stimulation (ES) is an alternate strategy to induce muscle contraction, using electrical impulses. However, effectiveness of ES induced muscle contraction to improve energy expenditure and glucose metabolism is not well examined.Purpose: To determine the acute effect of ES on whole body energy expenditure and body glucose metabolism in sedentary overweight or obese population Methods: Sedentary overweight/obese participants (n=8; age: 37.25 ± 6.09 years; BMI= 37.57 ± 2.43 kg/m2) were included in this study. All participants received bilateral quadriceps ES …

Autoantibody Against Tumor-Associated Antigens As Diagnostic Biomarkers In Hispanic Patients With Hepatocellular Carcinoma, Yangcheng Ma

Open Access Theses & Dissertations

Liver cancer is one of the most prevalent malignancies, in which hepatocellular carcinoma (HCC) takes up more than 80% of liver cancer cases. Early diagnosis and treatment are practical approaches to impede HCC progression. Identifying and classifying autoantibodies against tumor-associated antigens (TAAs) have long been interested in cancer diagnosis, especially for HCC. Circulating anti-TAA autoantibodies amplify the antigen expression and are more stable in blood, guaranteeing anti-TAA autoantibodies as valid diagnostic biomarkers in clinical application. Nonetheless, very few studies had focused on the Hispanic HCC group, which might retain distinct etiological risk factors compared to other ethnicities. The high incidence …

Regulation Of C-C Chemokine Receptor 7 (Ccr7) Ligand-Mediated Internalization And Chemotaxis By G Protein-Coupled Receptor Kinase Family 4 (Grk-4, 5, 6) In Human Pediatric T-Cell Acute Lymphoblastic Leukemia (T-All), Eduardo Elias Chaib

Open Access Theses & Dissertations

Background and Significance: The Hispanic population is disproportionally affected by T-ALL (T-cell acute lymphoblastic leukemia) when compared to other races in the US. C-C Chemokine Receptor 7 (CCR7) in T-ALL is used during disease progression, and may lead to migration of cancerous cells into the Central Nervous System (CNS) of patients. Goals and Objectives: This project aims to find relevant rates and risk factors for T-ALL for the Hispanic population in the US/Mexico border region. The other aim is to assess the effect of the G protein-coupled Receptor Kinase 4 (GRK-4) family proteins on migration and receptor internalization through CCR7 …

Targeting Delivery Of Bcl-2 Family Protein Inhibitor Has The Potential To Treat Cancer And Fibrosis, Mohammad Nurul Huda

Open Access Theses & Dissertations

Apoptosis is a naturally occurring cell death mechanism to remove the selective cell population. B-cell leukemia/lymphoma-2 (BCL-2) family protein plays a critical role in activating the upstream apoptosis signaling pathway, primarily the intrinsic apoptosis pathway. The BCL-2 family consists of both pro-and anti-apoptotic proteins, which are structurally and functionally similar, containing up to four BCL-2 homologies (BH) motifs (BH1-4). Defecting apoptosis along this signaling pathway can lead to various events, including malignant cell transformation, tumor metastasis, tissue fibrosis, and drug resistance. In fibrosis, the aberrant apoptosis signaling also activates multiple effector proteins and growth factors, such as TGF-β, CTGF, and …

Examination Of The Association Between C - Reactive Protein(Crp) And Covid-19 Infection Severity And Length Of Hospitalization, Abdulahi Aremu Ayanwale

Open Access Theses & Dissertations

Chronic stress can lead to many systemic complications and low-grade systemic inflammation including increased levels of inflammatory cytokines, such as C-reactive protein (CRP). CRP is a marker of systemic inflammation and is associated with depression and perceived stress. Elevations can result in ineffective immune responses, thereby increasing the risk of complications and mortality from infections. Recent evidence suggests that uncontrolled inflammatory responses associated with COVID 19 are a major determinant of disease severity.  The COVID 19 is transmitted from one person to another through droplets from coughing, sneezing, talking, touching droplets on surfaces and contamination by hand-to-mouth routes. The mechanism …

Impact Of Xenobiotics On Neuronal Outcomes, Gabriela Henriquez

Open Access Theses & Dissertations

Neurodegenerative diseases are a common affliction of the Central Nervous System. They are caused by age, genetics, and environmental factors. Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are well-known among the host of neurodegenerative disorders, with Alzheimer's disease and Parkinson's disease being the leading pathologies across this canvas. It is known that the pathogenesis of neurodegenerative diseases is multifactorial due to the involvement of genetic mutations, radical-induced protein damage, abnormal aggregation of misfolded proteins, and the formation of amyloid deposits. The amyloid proteins in neurodegenerative disease include Tau and Amyloid (Aβ) in Alzheimer's disease and α-Synuclein in …

The Role Of Calcium Ions In Signaling And Regulation Of Efflux Pump Genes In Staphylococcus Aureus, Amy Rebecca Nava

Open Access Theses & Dissertations

Calcium ions (Ca2+) play an important role in eukaryote cell signaling and regulation of physiological functions. Although evidence of a similar role for Ca2+ in prokaryotes has been difficult to demonstrate, there is mounting evidence that Ca2+ acts as a cell regulator in bacteria. The purpose of this study was to investigate Ca2+ signaling and the effect of Ca2+ on gene expression of various multidrug resistant (MDR) efflux pumps and their regulator MgrA in Staphylococcus aureus and clinically isolated MRSA. We hypothesized that the presence of Ca2+ increased gene expression of multidrug resistance pumps, LmrS, NorA, and the regulator, MgrA. …

Determination Of Perceived Calorie Content Of Common Foods, Sarah Leticia Ruiz

Open Access Theses & Dissertations

Currently, dietary weight-loss interventions focus on recommended caloric intake aimed at creating an energy deficit through the use of calorie-based education. This approach assumes individuals can accurately estimate caloric content of foods and beverages, yet little is known about the validity of such assumptions. This study assessed the accuracy of perceptions of calorie content for individual food items and mixed meals and determined its association with education level, nutrition background, body composition, fruit and vegetable intake, and the domains of eating (emotional eating, uncontrolled eating, and cognitive restraint). A cross-sectional survey assessed calorie perceptions using both visual food displays and …

Suppression Of Inflammation Of Cytokine Following Induced Francisella Tularensis Infection, Nicole Renee Setzu

Open Access Theses & Dissertations

Francisella tularensis is intracellular bacteria which is the causative agent of the disease Tularemia. Highly virulent in both humans and animals, it takes only as few as 10 microorganisms to cause a lethal infection. The bacteria can enter via direct or indirect routes causing the activations of the host innate inflammatory response to ensue. The bacteria invade host dendritic cells and neutrophils but predominately macrophages. This causes a mass inflammatory response resulting in the cytokine storm. Activation of Natural Killer T (NKT) cells has been shown to suppress inflammation in in vivo studies. Development and optimization of an in vitro …

The Effect Of Waterpipe/Hookah On Platelet Function And The Impact Of Inhibition Of Gβγ Subunits On Hemostasis And Thrombogenesis, Ahmed Alarabi

Open Access Theses & Dissertations

Abstract (Hookah)

Cardiovascular diseases (CVD’s) is a major public health problem. Among CVD’s risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of CVD’s mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipe/hookah has been rising, mainly due to the perception that they are “less harmful” than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. We employed a waterpipe whole-body exposure protocol that mimics real‐life human …

The Associations Between Socioeconomic Status And Childhood And Adult Psychosocial Experiences Among Men Living In El Paso, Texas, Sophia Marie Ornelas

Open Access Theses & Dissertations

BACKGROUND: Substantial evidence indicates that low levels of Socioeconomic Status (SES) can have adverse psychosocial health implications in early childhood that can persist into adulthood. While there is extensive research about this relationship very little is known about the relationship between SES characteristics and adult psychosocial burden among Hispanic men. OBJECTIVE: This research aims to explore the associations between SES characteristics and childhood adverse experiences, adult perceived stress burden, and depressive symptoms among Hispanic men living in El Paso, Texas. METHODS: This research used data from a cross-sectional study of 100 adult men residing in El Paso, Texas in 2018. …

Association Of A Repetitive Manual Task On Inflammatory Biomarker Expression, Heart Rate Variability And Rating Of Perceived Exertion, Daniel Conde

Open Access Theses & Dissertations

The National Institute for Occupational Safety and Health (NIOSH) defines work related musculoskeletal disorders (WMSDs) as a group of disorders involving muscles, tendons, and nerves. The WMSDs symptoms are considered the most common occupational disease, causing limitations in daily activities. Even though there is an association between repetitive manual tasks involving short work cycles, force demanding tasks, and the development of WMSDs, the specific cause of the physiological changes over a long period of time is a cause of debate. The study of mechanisms underlying the physiological changes is essential for the early detection, diagnosis, and appropriate management of WMSDs.

Identification Of A Novel Single Amino Acid Substitution (V666g) Of Jak1 From A Patient With Acute Lymphoblastic Leukemia Impairs Jak3 Mediated Il-2 Signaling, Alice Hernandez Grant

Open Access Theses & Dissertations

The Janus kinase (JAK) family, notably JAK1, JAK2 and JAK3 are recognized as oncogenic drivers in high risk Acute Lymphoblastic Leukemia (ALL). The bulk of activating JAK mutations are thought to occur within functional hot-spots across Janus Homology (JH) domains. The most frequently mutated regions is the JH2 pseudo-kinase, which provides a negative regulatory role to the adjacent catalytically active JH1 kinase domain. Despite the prevalence of JAK activating mutations and a need for new therapeutic inhibitors, there is a lack of understanding in the allosteric regulation of JAK kinases. Here we sought to identify mutations involved in driving ALL …

Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini

Open Access Theses & Dissertations

Chagas disease (ChD) is a neglected tropical disease (NTD) caused by the protozoan parasite, Trypanosoma cruzi. It is transmitted by the insect-vector triatomine (popular known as kissing bug), blood transfusion, organ transplantation, congenitally, and contaminated foods and juices. T. cruzi has evolved several strategies to invade the host cells, including the release extracellular vesicles (EVs), which assist pathogen survival and its replication within the host. T. cruzi is covered with highly glycosylated surface molecules such as glycoproteins and glycolipids, which are shown to be involved in the interaction with host immune cells. These molecules are highly immunogenic and reactive with …

Expression And Functional Sialome Of Triatomines, Insect Vectors Of Chagas Disease, Maria Tays Mendes

Open Access Theses & Dissertations

Triatomines are blood-sucking arthropods that transmit Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD). Triatomines use bioactive molecules in the saliva for successful blood feeding and to evade the hemostatic and immune defense system of the hosts. Knowing the saliva composition could be useful for a better understanding which and how insect-derived molecules might influence host-parasite interactions. Previous studies have shown that some saliva-derived proteins and lipids can modulate the host immune system and increase T. cruzi infection. We hypothesize that the triatomine saliva contains a great diversity of lipids and proteins that can modulate the mammalian host immune …

Molecular And Functional Characterization Of Α-Galactosyl Epitopes In Trypanosoma Cruzi, Uriel Ortega Rodriguez

Open Access Theses & Dissertations

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates …

The Effects Of A 6-Week Controlled Whole-Body Vibration Training Program In Reducing Falls Risk Among Healthy Older Adults, Fabricio Saucedo Jr.

Open Access Theses & Dissertations

Falling is the second leading cause of accidental or injury-related death in the aging population worldwide and a leading cause of serious injury. Whole-body vibration (WBV) training has been implemented as a way to improve functional performance among the elderly and reduce the falls risk. The purposes of this study were: 1) examine to what extent a six-week course of WBV training reduced falls risk and improved fall outcomes in response to slips, and 2) examine whether the benefits of WBV training could be retained at least 2 months after the completion of the entire training session. A total of …

The Effectiveness Of The Natural Ear On Adults Ability To Accurately Match Pitch, Kendra Nicole Rosales

Open Access Theses & Dissertations

Background: Many theories, such as oral motor, perceptual, and sensorimotor deficits, have been posited to explain inaccurate pitch matching abilities. The current study identifies with the sensorimotor deficit theory and found it to be the most plausible explanation for inaccurate singing abilities. The Natural Ear (NE) program was designed to process voice productions in real-time and filter out the discordant harmonics, allowing a person to hear only their F0.

Purpose: The purpose of this study was to examine the effectiveness of the Natural Ear program in increasing pitch matching accuracy in singers.

Methods: A total of 50 participants were included …

The Role Of P62/Imp2 In Hepatocellular Carcinoma Progression, Mengtao Xing

Open Access Theses & Dissertations

The family of insulin- like growth factor 2 mRNA binding proteins (IMPs) contains three members: IMP1, p62/IMP2 and IMP3. All these proteins are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, p62/IMP2 were found overexpressed in various cancers but its function in carcinogenesis remains to be investigated. Our previous studies found that p62/IMP2 was not only overexpressed in hepatocellular carcinoma (HCC) tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low …

Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna

Open Access Theses & Dissertations

Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …

Serosurvey For Evidence Of Dengue And West Nile Virus Human Infections In El Paso, Texas, Veronica Suarez

Open Access Theses & Dissertations

Dengue viruses (DENV), including the 4 serotypes are the cause of dengue fever and dengue hemorrhagic fever. The viruses are transmitted by Aedes aegypti mosquitoes in urban communities in tropical, sub-tropical, and temperate regions and are the cause of the highest rate of infection and death of all known Flaviviruses. DENV are endemic in United States (US) -Mexico (MX) border communities in the Rio Grande Valley and suspected of being endemic in Ciudad Juarez, a sister city to El Paso, TX. To determine if DENV were endemic in the El Paso community, cord-blood samples from mothers were tested for antibody …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Platelet Biology And Thrombosis: Juul E-Cigarette Exposure And 5ht2a Receptor Drug Discovery, Jean Emmanuel Montes Ramirez

Open Access Theses & Dissertations

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Differences In The M1 And M2 Macrophage Subtypes Between The Sexes Determine Susceptibility To Francisella Tularensis Infection, Michelle Arlene Sanchez

Open Access Theses & Dissertations

Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host's own inflammatory response initiated by the macrophage's response to infection.

Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more …

Does A Family History Of Type 2 Diabetes Affect Exercise Induced Improvements In Insulin Sensitivity, Metabolic Flexibility, And Myokine Expression In Mexican-American Males?, Manuel Amador

Open Access Theses & Dissertations

A family history of diabetes (FH+) is considered a risk factor for the development of insulin resistance and type 2 diabetes. However, it is not known whether exercise induced improvement in insulin sensitivity (IS) and metabolic flexibility (MF) are impacted by a FH+. Purpose: To determine if a FH+ limits exercise induced improvements in Insulin sensitivity, MF, body composition, and strength following an 8-week combined aerobic and resistance training intervention compared to those without a family history of diabetes (FH-). Methods: 19 (FH- n=9, age 21.89 ± 0.60 years, BMI 27.51 ± 1.68 kg/m2; FH+ n=10, age 23.41 ± 0.86 …