Biological Factors Commons^™

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Comparative Metabolism Of Aflatoxin B1 In Two Quail Genera Coturnix Japonica And Callipepla Californica, Sean Moody

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B₁ (AFB₁). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB₁ in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB₁, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

MSU Graduate Theses

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root

Undergraduate Honors Theses

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid …

The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou

Electronic Theses and Dissertations

The goal of this study is to investigate the effects of wild blueberry fractions (Anthocyanins and Phenolic acids) on vascular function and physiology. More specifically the potential effects of the above fractions and their combination in physiological concentrations on endothelial cell migration, angiogenesis, gene expression and proteins synthesis of markers related to the above processes. The objectives are to study whether anthocyanins, phenolic acids and their combinations (ACNs:PAs) affect: a) cell proliferation, b) speed of endothelial cell migration, c) angiogenesis, d) gene expression of genes critical for cell migration and angiogenesis such as RAC1, RHOA, AKT1, eNOS and VEGF and …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke

Dissertations, Master's Theses and Master's Reports

Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate’s role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative …

Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll

Theses & Dissertations

Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis, …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Traveling With Stowaways: The Human Microbiome And Travel, Alisha N. Hughes

Global Honors Theses

The human microbiome is a research field that is fairly new and thus, not yet fully understood. However, past research has revealed that the human host and the microorganisms interact with each other. To comprehend how influential the connection between host and its stowaways is, the following text will first offer general information on the human microbiome, before moving on to a pilot case study proposal. With the use of similar case studies, this proposal aims to investigate how the human microbiome changes when the host travels and analyzes the changes and their affects on the individual’s health. The paper’s …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

The Relationship Between Vitamin D Status Of Adult Women And Diet, Sun Exposure, Skin Reflectance, Body Composition, And Insulin Sensitivity, Marisa M. Mcadler

Master's Theses

As the prevalence of vitamin D deficiency continues to grow, mounting evidence supporting its link with chronic disease strengthens suggesting vitamin D’s candidacy in the prevention and treatment of multiple disease states and their complications. Dietary guidelines, however, do not take sun exposure into account. The present study sought to explore the impact of sun exposure on vitamin D status (serum 25(OH)D), and identify other significant determinants of serum levels which may have the greatest effects on overall health. Participants (n = 34) were pre-menopausal women aged 18 to 50 years (mean age 39 ± 6 years), who had their …

The Morbidity & Mortality Of Prevalent Heart Failure, Jennifer Kwon

Loma Linda University Electronic Theses, Dissertations & Projects

The first study population included 292 unselected consecutive patients from the LLUMC heart failure clinic who were enrolled in the study from January to July 2006 and were followed up through the end of December 2010. The treatment policy at the clinic was to uptitrate dosages of beta-adrenergic blockade (β-blockers), angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) to the most tolerable levels in order to reach target dosages, as recommended by the Heart Failure Society of America (HFSA). Patients were classified into systolic heart failure (ejection fraction (EF) < 40%) or diastolic heart failure (EF≥40%). All dosages of β-blockers, ACEi and ARB were extracted through chart reviews and were used as the main predictors of the patients' survival. Results from analyses showed that reaching target dosages of β-blockers and ACEi/ARB may increase survival when compared to not reaching target among the systolic HF population (HR_{β_biockers}= 0.64, 95% CI 0.26-1.56 and HR_ACEi/ARB=0.50, …

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Characterization Of Host-Bacteria Interactions Contributing To Group B Streptococcus Colonization, Jennifer Marie Smith

Theses, Dissertations and Capstones

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number …