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- All Subjects: Vitamin D
- Member of: Theses and Dissertations
- Resource Type: Text
Description
Vitamin D, Klotho, and FOXO3 have all been linked to have anti-aging and anti-cancerous effects as separate pathways. Specifically, mice with knockout Klotho in their genes have displayed signs of premature aging, humans who are vitamin D deficient have been shown to develop cardiovascular disease and cognitive impairments, and those who have displayed overexpression of FOXO3 have shown to have a longer lifespan. Here we took each pathway and attempted to formulate a feedback mechanism loop linking all three separate pathways. We propose that vitamin D levels modulate klotho activity, including the expression of the s-klotho and m-klotho isoforms. Moreover, the anti-oxidation transcription factor FOXO3 is also thought to participate in crosstalk with VDR signaling. Through the connection between 1,25D and Klotho, we probed at their interactions with FOXO3 signaling in kidney and colon cells, and proposed that vitamin D and klotho may reduce oxidative stress and suppress the onset of epithelial cancers through it effects on FOXO3. Results showed a strong support for the cooperation between FOXO3 and 1,25D to stimulate both superoxide dismutase (a FOXO3 response element) and XDR3/ROC (vitamin D response elements). This cooperation was mostly seen in embryonic kidney cells (HEK293) and not in the colon cancer cells (HCT116), which has led to the conclusion that vitamin D and FOXO3 cooperation mainly occurs in kidney tissue and/or in tissue that is not yet been overtaken by cancer. Differences in the Klotho isoforms were seen when measuring FOXO3 and vitamin D activity, but experiments manipulating other components will need to be conducted to further understand the function of Klotho in maintaining reactive oxygenated species levels.
ContributorsSandoval, Ruby (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd R. (Committee member) / Heck, Michael (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Vitamin D, a bioactive lipid and essential nutrient, is obtained by humans through either endogenous synthesis in response to UV light exposure or via nutritional intake. Once activated to its hormonal form, vitamin D binds to and activates the nuclear vitamin D receptor (VDR). Activation of VDR is known to modulate gene transcription in vitamin D target tissues such as kidney, colon, and bone; however, less is known about the ability of VDR to respond to "nutritional modulators". One such potential VDR modulator is resveratrol, a plant-derived polyphenol and potent antioxidant nutrient that also functions as a chemopreventative. Resveratrol is known to activate sirtuin-1, a deacetylase enzyme with potential anti-aging properties. This study explores the potential for resveratrol, an anticancer nutraceutical, to upregulate VDR activity through its effector protein, sirtuin-1. Furthermore, due to its putative interactions with several intracellular signaling pathways, klotho has been proposed as an anti-aging protein and tumor suppressor gene, while the Wnt/β-catenin signaling pathway drives enhanced cellular proliferation leading to numerous types of cancers, especially colorectal neoplasia. Thus, the ability of klotho to cooperate with vitamin D to inhibit oncogenic β-catenin signaling was also analyzed. The experiments and resultant data presented in this thesis explore the potential role of VDR as a physiologically relevant nutritional sensor in human cells. This novel study reveals the importance of nutrient modulation of the VDR system by vitamin D and resveratrol and how this might represent a molecular mechanism that is responsible for the putative anti-cancer actions of vitamin D. Furthermore, this study enhances our understanding of how vitamin D/VDR and resveratrol interact with klotho and how this interaction affects β-catenin signaling to mitigate oncogenic growth and differentiation. This works demonstrates that the vitamin D hormone serves as a likely chemopreventive agent for various types of cancers through control of anti-oxidation and cellular proliferation pathways via its nuclear receptor. Our results also indicate the potential for resveratrol, an anticancer nutraceutical, to upregulate VDR activity through SIRT1. Furthermore, the novel data presented in this work illustrate that klotho, an anti-aging protein, cooperates with vitamin D to synergistically inhibit oncogenic β-catenin signaling. Ultimately, this study enhances our understating of the molecular pathways that underpin nutritional chemoprevention, and how modulation of these pathways via dietary intervention may lead to advances in public health strategies to eventually curb carcinogenesis.
ContributorsKhan, Zainab (Author) / Jurutka, Peter (Thesis director) / Hackney Price, Jennifer (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Women and people of color are some of the most underrepresented groups in the STEM field (science, technology, engineering, and mathematics). The purpose of this study was to uncover the barriers that undergraduate Hispanic women, as well as other women of color, face while pursuing an education in a STEM-related major at Arizona State University (ASU). In-depth interviews were conducted with 13 adult participants to dig deeper into the experiences of each woman and analyze how race and class overlap in each of the women's experiences. The concept of intersectionality was used to highlight various barriers such as perceptions of working versus middle-class students, the experience of being a first-generation college student, diversity campus-wide and in the classroom, effects of stereotyping, and impacts of mentorships. All women, no matter their gender, race, or socioeconomic status, faced struggles with stereotyping, marginalization, and isolation. Women in STEM majors at ASU performed better when provided with positive mentorships and grew aspirations to become a professional in the STEM field when encouraged and guided by someone who helped them build their scientific identities. Working-class women suffered from severe stress related to finances, family support, employment, and stereotyping. Reforming the culture of STEM fields in higher education will allow women to achieve success, further build their scientific identities, and increase the rate of women graduating with STEM degrees.
ContributorsValdivia, Lilianna Alina (Author) / Kim, Linda (Thesis director) / Camacho, Erika (Committee member) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The diagnosis of irritable bowel syndrome (IBS) is currently based on symptomatic criteria that exclude other conditions affecting the gastrointestinal tract, such as celiac disease, food allergies, and infections. The absence of appropriate diagnostic and therapeutic approaches for IBS places a significant burden on the patient and the health care system due to direct and indirect costs of care. Limitations associated with the application of symptomatic criteria include inappropriate use and/or intrinsic limitations such as the population to which these criteria are applied. The lack of biomarkers specific for IBS, non-specific abdominal symptoms, and considerable variability in the disease course creates additional uncertainty during diagnosis. This project involved screening tissue samples from patients with verified IBS to identify gene expression-based biomarkers associated with IBS. Through validation of microarray gene chip data on the tissue samples using PCR, it was determined that a number of genes within the diseased IBS patient tissue samples were differentially expressed in comparison to the healthy subjects. These findings could potentially lead to the diagnosis of IBS on the basis of a genetic "fingerprint".
ContributorsHockley, Maryam (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd (Committee member) / Zhang, Lin (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2013-12
Description
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that afflicts more than 20% of the population in the United States. Symptoms include mild to severe abdominal discomfort accompanied by a change in stool character and form ranging from constipation to diarrhea. Additionally, IBS is associated with secondary effects including depression, anxiety, poor quality of life, insomnia and sexual dysfunction. Despite the known association of secondary effects, patients are often tested for potential illnesses that share similar pathological symptoms. This process can be costly and protracted and yet not deliver a completely accurate diagnosis. The aim of this research is to identify gene expression-based biological signatures and unique biomarkers for the detection of IBS. Through the use of quantitative polymerase chain reaction (qPCR), comparison of pooled samples of non-IBS patient-derived RNA were used to identify differentially expressed genes in patients with IBS. Data obtained from preliminary DNA microarray analysis demonstrated a degree of success in differentiating between IBS and asymptomatic patients. Additional comprehensive DNA microarray analyses have led to the identification of a series of 858 differentially expressed genes, including genes associated with serotonin metabolism, which may characterize the IBS pathological state. The microarray results were screened using a combination of gene ontological analysis and qPCR. Real-time PCR revealed repressed levels of tryptophan hydroxylase (TPH1), an enzyme involved in the rate- limiting step in serotonin biosynthesis, in IBS patients relative to controls. Lower concentrations of serum 25(OH)D were also observed among the IBS cohort relative to asymptomatic patients, especially among IBS-D subtype. Vitamin D was shown to modulate differentially expressed genes in IBS patients, suggesting that IBS pathophysiology may involve vitamin D insufficiency and/or an irregularity in serotonin metabolism. Additional qPCR analysis of 32 differentially expressed genes in IBS patients identified 7 putative genetic biomarkers proposed for a potential IBS diagnostic panel. Based on the quality of these results, we may be able to develop, test, and market a diagnostic kit for IBS.
ContributorsGrozic, Aleksandra (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd (Committee member) / Foxx-Orenstein, Amy (Committee member) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Child abuse is a hard topic to talk about, and even harder to diagnose without proper training. Though there is a list of general characteristics that child abuse victim's exhibit, it could be difficult to diagnose because everyone reacts to maltreatment differently. Teachers are required by law to report any case where they believe a child is in an abusive environment. Unfortunately, teachers are given the tools to report the abuse, but they lack the knowledge of what to look for. The results are two fold; one is there is an overflow of false reporting, and two, the children who do not having obvious symptoms go unnoticed. This project aims to bridge the gap between these two extremes. It will lower the frequency of false reporting while increasing the chance that a child in need will be helped. The best way to achieve this is through education. The purpose of the study is to create an informational manual for teachers at the kindergarten and elementary level on how to identify child abuse and neglect victims. It will outline the behavioral and physical symptoms of physical abuse, sexual abuse, emotional abuse, and neglect. It will also highlight the importance of realizing that not all maltreatment victims react the same to abuse. It will then follow into advice on how to approach the situation and what questions to ask. The primary form of research was primary observation by volunteering at the Mesa Child Crisis Center (with IRB approval). Interviews were conducted with Child Crisis Center workers, child behavioral psychologists, and Special Victims Unit detectives. The goal of this research is to help teachers better identify children that are at risk of abuse
eglect, and to understand the theory behind their behavior. In the end, teachers will be more informed on the topic so they can better help their students and create a safe environment for them, and be more confident in reporting.
eglect, and to understand the theory behind their behavior. In the end, teachers will be more informed on the topic so they can better help their students and create a safe environment for them, and be more confident in reporting.
ContributorsBaker, Karen Colette (Author) / Kobojek, Kimberly (Thesis director) / Broberg, Gregory (Committee member) / Kelley, Michael (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.
ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
Description
Vitamin D3 (cholecalciferol) is an essential micronutrient that plays a key role in developmental growth and lifespan in mammals. However, few studies have shown how vitamin D3 plays its vital functions in arthropods. Here, we examined the effects of full (13.3 IU/mL) and half dose (6.65 IU/mL) vitamin D3 on the growth and lifespan of Drosophila melanogaster. Vitamin B12 is another micronutrient that shows decreases absorption in elderly patients and might be linked to symptoms associated with aging rather than lifespan, but again, the effects of vitamin B12 supplementation in arthropods is poorly characterized. Results showed that both full and half doses of vitamin D3 and B12 do not significantly alter the timing of pupariation or adult eclosion. Similarly, the mortality rate of adult D. melanogaster exposed to vitamin B12 or higher doses of vitamin D3 was not significantly decreased or increased. However, a low dose of vitamin D3 did significantly lower the mortality rate of D. melanogaster. The genetic composition of Drosophila for vitamin B12 and D metabolism showed similarities in humans. However, there are no biological evidences if these genes are functional thus, this may explain the results of this study.
ContributorsRebonza, Edzel May Suico (Author) / Hackney Price, Jennifer (Thesis director) / Jurutka, Peter (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05